Back to resultsStudy of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Apremilast 30 mg
Apremilast 20 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid, Arthritis
Eligibility Criteria
Inclusion Criteria:
- Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.
- Must be receiving treatment on an outpatient basis.
Must have active disease despite current methotrexate treatment as defined below:
- ≥ 6 swollen joints (66 swollen joint count) AND
≥ 6 tender joints (68 tender joint count)
-. Must meet at least one of the four lab requirements below:
- High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L
- Erythrocyte Sedimentation Rate (ESR) > 28 mm after the first 1 hour
- Positive for Rheumatoid Factor (RF)
- Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies
For participants participating in the Magnetic Resonance Imaging (MRI) assessment:
• Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.
Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.
• Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.
- Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.
Must meet the following laboratory criteria at screening:
- White blood cell count ≥ 3000/mm^3 (≥ 3.0 x 10^9/L) and < 14,000/mm^3 (< 14 x 10^9/L)
- Platelet count (≥ 100,000/μL ((≥ 100 x 10^9/L)
- Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
- Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 2 x upper limit of normal (ULN). If initial test shows Aspartate aminotransferase (AST) or alanine aminotransferase (SLT) or 2 times the upper limit of normal (ULN), one repeat test is allowed during the screening period.
- Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.
- Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
- Hemoglobin A1c ≤ 9.0%
- Negative for hepatitis B surface antigen
- Negative for hepatitis C antibody
- Males who engage in activity in which conception is possible must use protocol described barrier contraception while on Investigational Product and for at least 28 days after the last dose of Investigational Product.
- Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use protocol described contraception while on Investigational Product and for at least 28 days after taking the last dose or Investigational Product.
Exclusion Criteria:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
- Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.
- Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
- Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).
- Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.
- Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
- Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
- Previous treatment with any cell depleting therapies, including investigational agents.
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
- Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
- Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
- Pregnant women or nursing (breast feeding) mothers.
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c > 9.0%) or gastrointestinal (GI) disease.
- Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
- History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
- History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
- History of alcohol, drug or chemical abuse within the 6 months prior to screening.
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).
For Magnetic Resonance Imaging (MRI) Only:
- Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.
- Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding [eg, a metal worker, etc]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.
- Allergic or adverse reactions to gadolinium
- Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease [MDRD] formula).
Sites / Locations
- ArthroCare, Arthritis Care Research
- Arizona Research Center
- TriWest Research Associates
- Desert Medical Advances
- Stanford University Medical Center
- Med Investigations/Sierra
- Inland Rheumatology Clinical Trials, Inc.
- Denver Arthritis Clinic
- In Vivo Clinical Research
- San Marcus Research Clinic
- Advanced Pharma CR, LLC
- Jeffrey Alper, MD Research
- Suncoast Clinical Research
- Tampa Medical Group, PA
- Alastair Kennedy, MD
- LaPorte County Institute for Clinical Research, Inc.
- Associated Internal Medicine Specialists, PC
- Saint Paul Rheumatology
- Physician's East
- David R. Mandel, M.D., Inc.
- Health Research of Oklahoma
- Altoona Center for Clinical Research
- Austin Regional Clinic
- Metroplex Research Center
- Modern Research Associates
- Sun Research Institute
- Stone Oak Rheumatology
- Center for Excellence in Aging and Geriatric Health
- Arthritis Northwest, Rheumatology
- Revmatologie s.r.o.
- L.K.N. Arthrocentrum s.r.o.
- ARTMEDI UPD s.r.o.
- Revmatologicky ustav
- Revmatologicka ambulance
- Fakultni Thomayerova nemocnice s poliklinikou
- PV - MEDICAL, s.r.o.
- NZOZ Osteo-Medic s.c. Artur Racewicz, Jerzy Supronik
- NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych
- Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
- Centrum Kliniczno-Badawcze
- Centrum Leczenia Chorob Cywilizacyjnych
- Centrum Leczenia Chorob Cywilizacyjnych
- Malopolskie Centrum Medyczne (408)
- Niepubliczny Zaklad Opieki Zdrowotnej REUMED
- Prywatna Praktyka Lekarska Pawel Hrycaj
- Centrum Leczenia Chorob Cywilizacyjnych
- Hospital Universitario a Coruña
- Hospital Universitario de Canarias
- Hospital Clinico Universitario de Santiago
- Hospital Sierrallana
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Apremilast 30 mg
Apremilast 20 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
Secondary Outcome Measures
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 16
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16
The DAS28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC28)
28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's global assessment of disease activity (SGA )
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Percentage Change From Baseline in the Tender Joint Count at Week 16
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Percentage Change From Baseline in the Swollen Joint Count at Week 16
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Percentage Change From Baseline in the Subject Assessment of Pain at Week 16
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.
The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 24
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 24
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 24
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP at Week 24
The DAS28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count
28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's Global Assessment of Disease Activity.
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Percentage Change From Baseline in the Tender Joint Count at Week 24
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Percentage Change From Baseline in the Swollen Joint Count at Week 24
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Percentage Change From Baseline in the Subject Assessment of Pain at Week 24
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.
The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 52
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 52
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP at Week 52
The DAS28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC28)
28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's global assessment of disease activity (SGA).
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Percentage Change From Baseline in the Tender Joint Count at Week 52
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Percentage Change From Baseline in the Swollen Joint Count at Week 52
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Percentage Change From Baseline in the Subject Assessment of Pain at Week 52
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.
The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 52
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2
The DAS 28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC28)
28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's global assessment of disease activity (SGA ). A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2
The Individual ACR Components were defined as follows:
Tender Joint Count (out of 68 joints)
Swollen Joint Count (out of 66 joints)
Subject Assessment of Pain (0 to 100 mm VAS)
Subject Global Assessment of Disease Activity (0 to 100 mm VAS)
Physician Global Assessment of Disease Activity (0 to 100 mm VAS)
HAQ-DI Score
Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR)
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01285310
Brief Title
Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis
Official Title
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study, To Compare the Efficacy and Safety of Two Doses of Apremilast (CC-10004) in Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Study is terminated due to lack of efficacy
Study Start Date
December 9, 2010 (Actual)
Primary Completion Date
February 21, 2012 (Actual)
Study Completion Date
September 10, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether Apremilast is safe and effective in the treatment of patients with rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid, Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
237 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Apremilast 30 mg
Arm Type
Experimental
Arm Title
Apremilast 20 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Apremilast 30 mg
Other Intervention Name(s)
CC-10004
Intervention Description
30 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 30mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Intervention Type
Drug
Intervention Name(s)
Apremilast 20 mg
Intervention Description
20 mg oral Apremilast tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in the active treatment / active treatment extension phase.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral Placebo tablets administered twice daily (BID) for 24 weeks during the placebo-controlled phase followed by 20mg Apremilast tablets administered BID for up to 1.5 years in active treatment / active treatment extension phase. Participants who are nonresponders will advance early to 20 mg Apremilast BID at Week 16.
Primary Outcome Measure Information:
Title
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16
Description
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
Time Frame
Baseline and Week 16
Secondary Outcome Measure Information:
Title
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 16
Title
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24
Description
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Time Frame
Baseline and Week 24
Title
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 24
Title
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16
Description
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 16
Title
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Time Frame
Baseline and Week 16
Title
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 16
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Time Frame
Baseline and Week 16
Title
Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16
Description
The DAS28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC28)
28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's global assessment of disease activity (SGA )
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the Tender Joint Count at Week 16
Description
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the Swollen Joint Count at Week 16
Description
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the Subject Assessment of Pain at Week 16
Description
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16
Description
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16
Description
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16
Description
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time Frame
Baseline and Week 16
Title
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16
Description
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.
The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time Frame
Baseline and Week 16
Title
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16
Description
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 16
Title
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 16
Title
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16
Description
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 16
Title
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16
Description
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Time Frame
Baseline and Week 16
Title
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16
Description
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Time Frame
Baseline and Week 16
Title
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16
Description
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Time Frame
Baseline and Week 16
Title
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24
Description
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24
Description
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Time Frame
Baseline and Week 24
Title
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 24
Description
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Time Frame
Baseline and Week 24
Title
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 24
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 24
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Time Frame
Baseline and Week 24
Title
Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP at Week 24
Description
The DAS28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count
28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's Global Assessment of Disease Activity.
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the Tender Joint Count at Week 24
Description
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the Swollen Joint Count at Week 24
Description
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the Subject Assessment of Pain at Week 24
Description
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24
Description
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24
Description
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24
Description
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time Frame
Baseline and Week 24
Title
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24
Description
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.
The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time Frame
Baseline and Week 24
Title
Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24
Description
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24
Description
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24
Description
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Time Frame
Baseline and Week 24
Title
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52
Description
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
Time Frame
Baseline and Week 52
Title
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 52
Title
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52
Description
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.
Time Frame
Baseline and Week 52
Title
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 52
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Time Frame
Baseline and Week 52
Title
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 52
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22
Time Frame
Baseline and Week 52
Title
Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP at Week 52
Description
The DAS28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC28)
28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's global assessment of disease activity (SGA).
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the Tender Joint Count at Week 52
Description
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the Swollen Joint Count at Week 52
Description
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the Subject Assessment of Pain at Week 52
Description
The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52
Description
The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52
Description
The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52
Description
C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.
Time Frame
Baseline and Week 52
Title
Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
Description
The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.
The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.
Time Frame
Baseline and Week 52
Title
Change From Baseline in the FACIT-Fatigue Scale Score at Week 52
Description
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 52
Title
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
Time Frame
Baseline and Week 52
Title
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52
Description
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
Time Frame
Baseline and Week 52
Title
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52
Description
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
Time Frame
Baseline and Week 52
Title
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52
Description
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time Frame
Baseline and Week 52
Title
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 52
Description
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
Time Frame
Baseline and Week 52
Title
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2
Description
Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 20% improvement in 68 tender joint count;
≥ 20% improvement in 66 swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2
Description
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2
Description
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:
28 tender joint count (TJC),
28 swollen joint count (SJC),
Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest;
Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest.
The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:
Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2
Description
The DAS 28 measures the severity of disease at a specific time and is derived from the following variables:
28 tender joint count (TJC28)
28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;
C-reactive protein (CRP)
Subject's global assessment of disease activity (SGA ). A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2
Description
The Individual ACR Components were defined as follows:
Tender Joint Count (out of 68 joints)
Swollen Joint Count (out of 66 joints)
Subject Assessment of Pain (0 to 100 mm VAS)
Subject Global Assessment of Disease Activity (0 to 100 mm VAS)
Physician Global Assessment of Disease Activity (0 to 100 mm VAS)
HAQ-DI Score
Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR)
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2
Description
The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
A positive change from baseline score indicates an improvement.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2
Description
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2
Description
Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:
≥ 50% improvement in 68 tender joint count;
≥ 50% improvement in 66 swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2
Description
Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:
≥ 70% improvement in 68 tender joint count;
≥ 70% improvement in 66 swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2
Description
The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
Title
Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2
Description
EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.
Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2
The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.
Time Frame
Baseline and Year 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.
Must be receiving treatment on an outpatient basis.
Must have active disease despite current methotrexate treatment as defined below:
≥ 6 swollen joints (66 swollen joint count) AND
≥ 6 tender joints (68 tender joint count)
-. Must meet at least one of the four lab requirements below:
High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L
Erythrocyte Sedimentation Rate (ESR) > 28 mm after the first 1 hour
Positive for Rheumatoid Factor (RF)
Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies
For participants participating in the Magnetic Resonance Imaging (MRI) assessment:
• Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.
Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.
• Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.
Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.
Must meet the following laboratory criteria at screening:
White blood cell count ≥ 3000/mm^3 (≥ 3.0 x 10^9/L) and < 14,000/mm^3 (< 14 x 10^9/L)
Platelet count (≥ 100,000/μL ((≥ 100 x 10^9/L)
Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 2 x upper limit of normal (ULN). If initial test shows Aspartate aminotransferase (AST) or alanine aminotransferase (SLT) or 2 times the upper limit of normal (ULN), one repeat test is allowed during the screening period.
Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.
Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
Hemoglobin A1c ≤ 9.0%
Negative for hepatitis B surface antigen
Negative for hepatitis C antibody
Males who engage in activity in which conception is possible must use protocol described barrier contraception while on Investigational Product and for at least 28 days after the last dose of Investigational Product.
Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use protocol described contraception while on Investigational Product and for at least 28 days after taking the last dose or Investigational Product.
Exclusion Criteria:
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.
Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).
Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.
Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
Previous treatment with any cell depleting therapies, including investigational agents.
Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
Pregnant women or nursing (breast feeding) mothers.
Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c > 9.0%) or gastrointestinal (GI) disease.
Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
History of alcohol, drug or chemical abuse within the 6 months prior to screening.
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).
For Magnetic Resonance Imaging (MRI) Only:
Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.
Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding [eg, a metal worker, etc]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.
Allergic or adverse reactions to gadolinium
Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease [MDRD] formula).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
ArthroCare, Arthritis Care Research
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Arizona Research Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
TriWest Research Associates
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Desert Medical Advances
City
Palm Desert
State/Province
California
ZIP/Postal Code
92260
Country
United States
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Med Investigations/Sierra
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Inland Rheumatology Clinical Trials, Inc.
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Denver Arthritis Clinic
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
In Vivo Clinical Research
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
San Marcus Research Clinic
City
Miami
State/Province
Florida
ZIP/Postal Code
33015
Country
United States
Facility Name
Advanced Pharma CR, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33175
Country
United States
Facility Name
Jeffrey Alper, MD Research
City
Naples
State/Province
Florida
ZIP/Postal Code
34102
Country
United States
Facility Name
Suncoast Clinical Research
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34652
Country
United States
Facility Name
Tampa Medical Group, PA
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
Alastair Kennedy, MD
City
Vero Beach
State/Province
Florida
ZIP/Postal Code
32962
Country
United States
Facility Name
LaPorte County Institute for Clinical Research, Inc.
City
Michigan City
State/Province
Indiana
ZIP/Postal Code
46360
Country
United States
Facility Name
Associated Internal Medicine Specialists, PC
City
Battle Creek
State/Province
Michigan
ZIP/Postal Code
49015
Country
United States
Facility Name
Saint Paul Rheumatology
City
Eagan
State/Province
Minnesota
ZIP/Postal Code
55121
Country
United States
Facility Name
Physician's East
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
David R. Mandel, M.D., Inc.
City
Mayfield
State/Province
Ohio
ZIP/Postal Code
44143
Country
United States
Facility Name
Health Research of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Austin Regional Clinic
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
Facility Name
Metroplex Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Modern Research Associates
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Sun Research Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Stone Oak Rheumatology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78232
Country
United States
Facility Name
Center for Excellence in Aging and Geriatric Health
City
Williamsburg
State/Province
Virginia
ZIP/Postal Code
23185
Country
United States
Facility Name
Arthritis Northwest, Rheumatology
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Revmatologie s.r.o.
City
Brno
ZIP/Postal Code
638 00
Country
Czechia
Facility Name
L.K.N. Arthrocentrum s.r.o.
City
Hlucin
ZIP/Postal Code
748 01
Country
Czechia
Facility Name
ARTMEDI UPD s.r.o.
City
Hostivice
ZIP/Postal Code
253 01
Country
Czechia
Facility Name
Revmatologicky ustav
City
Praha
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Revmatologicka ambulance
City
Praha
ZIP/Postal Code
140 00
Country
Czechia
Facility Name
Fakultni Thomayerova nemocnice s poliklinikou
City
Praha
ZIP/Postal Code
140 59
Country
Czechia
Facility Name
PV - MEDICAL, s.r.o.
City
Zlin
ZIP/Postal Code
760 01
Country
Czechia
Facility Name
NZOZ Osteo-Medic s.c. Artur Racewicz, Jerzy Supronik
City
Bialystok
ZIP/Postal Code
15-351
Country
Poland
Facility Name
NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych
City
Bialystok
ZIP/Postal Code
15-461
Country
Poland
Facility Name
Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Centrum Kliniczno-Badawcze
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
Facility Name
Centrum Leczenia Chorob Cywilizacyjnych
City
Gdynia
ZIP/Postal Code
81-384
Country
Poland
Facility Name
Centrum Leczenia Chorob Cywilizacyjnych
City
Katowice
ZIP/Postal Code
40-478
Country
Poland
Facility Name
Malopolskie Centrum Medyczne (408)
City
Krakow
ZIP/Postal Code
30-552
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej REUMED
City
Lublin
ZIP/Postal Code
20-607
Country
Poland
Facility Name
Prywatna Praktyka Lekarska Pawel Hrycaj
City
Poznan
ZIP/Postal Code
61-397
Country
Poland
Facility Name
Centrum Leczenia Chorob Cywilizacyjnych
City
Warszawa
ZIP/Postal Code
02-777
Country
Poland
Facility Name
Hospital Universitario a Coruña
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario de Canarias
City
La Laguna
ZIP/Postal Code
38320
Country
Spain
Facility Name
Hospital Clinico Universitario de Santiago
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Sierrallana
City
Torrelavega
ZIP/Postal Code
39300
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
25779750
Citation
Genovese MC, Jarosova K, Cieslak D, Alper J, Kivitz A, Hough DR, Maes P, Pineda L, Chen M, Zaidi F. Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study. Arthritis Rheumatol. 2015 Jul;67(7):1703-10. doi: 10.1002/art.39120.
Results Reference
derived
Learn more about this trial
Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis
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