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A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Mavrilimumab 10 mg

Mavrilimumab 30 mg

Mavrilimumab 50 mg

Mavrilimumab 100 mg

Placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Mavrilimumab, CAM-3001

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18 through 80 years (20 to 75 years in Japan)
Written consent
Diagnosis of adult onset Rheumatoid Arthritis (RA) of at least 3 months duration as defined by the 1987 American College of Rheumatology (ACR) classification criteria (Arnett et al, 1988)
Treatment with methotrexate at a stable and tolerated doses
Positive anti-cyclic citrullinated peptide (CCP) immuno-globulin G antibodies (more than [>] 5 international unit per milliliter [IU/mL]) and/or rheumatoid factor (RF >14 IU/mL) at screening
Received more than or equal to (>=) 5 milligram (mg) per week folic acid as a single or divided dose during the study.

Exclusion Criteria:

A rheumatic autoimmune disease other than RA
A history of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder
Subjects at a high risk of infection
Subjects (male and female) of reproductive potential who are not willing to use contraception from screening through the end date of the trial
History of methotrexate or any drug-induced lung fibrosis or pneumonitis.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

Mavrilimumab 10 mg

Mavrilimumab 30 mg

Mavrilimumab 50 mg

Mavrilimumab 100 mg

Placebo

Arm Description

Mavrilimumab (CAM-3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per Liter [mg/L]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (<) 3.2 = low disease activity, greater than or equal to (>=) 3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85.

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. DAS28 (CRP) response at Day 85 for the European and Japanese regions were reported.

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85.

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline >1.2 with baseline DAS28 (CRP) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (CRP) >=3.2 to less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (CRP) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (CRP) >5.1.

Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline >1.2 with baseline DAS28 (CRP) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (CRP) >=3.2 to =< 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (CRP) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (CRP) >5.1. DAS28 (CRP) response by EULAR category at Day 85 for the European and Japanese regions were reported.

Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

DAS28 (ESR) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline >1.2 with baseline DAS28 (ESR) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (ESR) >=3.2 to =< 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (ESR) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (ESR) >5.1.

Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up Day 169 that were absent before treatment or that worsened relative to pretreatment state.

Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported.

Number of Participants With Abnormal Electrocardiogram (ECG) Results

12-lead ECG was recorded and corrected QT (QTc) interval was measured with the participant in a rested supine position for at least 10 minutes. Any ECG abnormality deemed clinically significant as per investigator's discretion were reported.

Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide.

Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% for the European and Japanese regions were reported.

Change From Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide.

Dyspnea Score at Day 85

Change From Baseline in Dyspnea Score at Day 85

Categorized Dyspnea Score at Day 85

Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The modified BORG dyspnea scale was categorized as - no/slight (0 to 2), moderate (3 and 4), severe (5 and 6) and very severe breathlessness (7 and above).

Oxygen Saturation Level at Day 85

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

Oxygen Saturation Level at Day 85 by Region

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. Oxygen saturation for the European and Japanese regions were reported.

Change From Baseline in Oxygen Saturation Level at Day 85

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, reticulocytes, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration); serum chemistry (creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma glutamyl transferase, CRP, ESR, albumin, total cholesterol, triglycerides, rheumatoid factor and anti-cyclic citrullinated peptide antibodies); urinalysis (albumin, glucose, protein, blood, nitrite).

Secondary Outcome Measures

Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. Time to response for DAS28 (CRP) and DAS28 (ESR) by region were reported. Time to remission for DAS28 (CRP) and DAS28 (ESR) by region were not analyzed because time to remission for the overall study population could not be achieved.

Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. Expected duration of response (DOR) was calculated as response rate (in percentage) multiplied by mean DOR (in days) by using Weibull Model. Duration of DAS28 (CRP) and DAS28 (ESR) remission were not analyzed because very few participants achieved remission in the overall study population.

Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

ACR20, ACR50, and ACR70, were defined as greater than or equal to (>=) 20 percent (%),>=50%, or >=70% improvement, respectively, in: swollen joint count and tender joint count and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).

Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Data for the European and Japanese regions were reported.

Number of Participants Who Achieved ACR Categorical Responses

ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. ACR responses were categorized as "No response", "ACR20 but not ACR50", "ACR50 but not ACR70", and "ACR70".

Continuous ACR (ACRn) Score

ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement.

Continuous ACR (ACRn) Score by Region

Swollen and Tender Joint Count

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1. Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1.

Swollen and Tender Joint Count by Region

Physician Global Assessment of Disease Activity Score

Physician Global Assessment of Arthritis was measured on a 0 to 10 centimeter (cm) Visual Analogue Scale (VAS), where 0 cm = very good and 10 cm = very bad.

Physician Global Assessment of Disease Activity Score by Region

Physician Global Assessment of Arthritis was measured on a 0 to 10 cm VAS, where 0 cm = very good and 10 cm = very bad. Data for European and Japanese regions were reported.

Patient Global Assessment of Disease Activity Score

Participants responded to a question, "Considering all the ways your arthritis affects you, how are you feeling today?" by using a 0 - 100 millimeter (mm) VAS, where 0 = very well and 100 = very poorly.

Patient Global Assessment of Disease Activity Score by Region

Participants responded to a question, "Considering all the ways your arthritis affects you, how are you feeling today?" by using a 0 - 100 mm VAS, where 0 = very well and 100 = very poorly. Data for European and Japanese regions were reported.

Patient Pain Assessment Score

Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.

Patient Pain Assessment Score by Region

Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain. Data for European and Japanese regions were reported.

Health Assessments Questionnaire-Disability Index (HAQ-DI) Score

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Health Assessments Questionnaire-Disability Index (HAQ-DI) Score by Region

Health Assessments Questionnaire (HAQ) Pain Score

Participants were asked to assess the severity of pain in the past week on a 100 VAS with 0 being no pain and 100 being severe pain.

Health Assessments Questionnaire (HAQ) Pain Score by Region

Participants were asked to assess the severity of pain in the past week on a 100 VAS with 0 being no pain and 100 being severe pain. Data for European and Japanese regions were reported.

Serum Concentration of C-Reactive Protein (CRP)

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Serum Concentration of C-Reactive Protein (CRP) by Region

Serum Concentration of Erythrocyte Sedimentation Rate (ESR)

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube.

Serum Concentration of Erythrocyte Sedimentation Rate (ESR) by Region

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Data for European and Japanese regions were reported.

Serum Concentration of Rheumatoid Factor (RF)

Serum Concentration of Anti-Citrullinated-Peptide-Antibody (ACPA)

Number of Participants Who Had Additional Medications

Additional medication included concomitant medication (medication used for purposes other than managing rheumatoid arthritis [RA]) and RA medication (for managing RA). Number of participants who used concomitant medication and RA medication was reported by anatomical therapeutic chemical (ATC) classification system.

Number of Participants With Change in Methotrexate (MTX) and Corticosteroid (CST) Dose

Participants received MTX at stable and tolerated dose during baseline were categorized as "low dose (<12.5 mg per week [mg/wk])", "medium dose (>=12.5 - <20 mg/wk)", and "high dose (>=20 mg/wk)". Participants received oral CST at stable dose during baseline were categorized as "low dose (<5 mg/day)", and "high dose (>=5 mg/day)". Change in MTX and CST dose from baseline between Day 1-85 and Day 86-169 were categorized as follows: 'Increased', 'no change' and 'decreased'. Participants were counted once with dose increases counted first, followed by no change and then dose decreases.

Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After First Dose by Region

Data for European and Japanese regions were reported.

Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After First Dose by Region

Data for European and Japanese regions were reported.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After First Dose by Region

Data for European and Japanese regions were reported.

Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After Last Dose by Region

Data for European and Japanese regions were reported.

Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After Last Dose by Region

Data for European and Japanese regions were reported.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After Last Dose by Region

Data for European and Japanese regions were reported.

Terminal Phase Elimination Half-Life (t1/2) for Mavrilimumab After Last Dose by Region

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Data for European and Japanese regions were reported.

Accumulation Ratio for Mavrilimumab After Last Dose by Region

Accumulation ratio was calculated as ratio of AUCtau after last dose and AUCtau after first dose. Data for European and Japanese regions were reported.

Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit

ADA detection measured by using electrochemiluminescence assays.

Full Information

NCT ID

NCT01050998

First Posted

January 15, 2010

Last Updated

March 23, 2018

Sponsor

MedImmune LLC

Collaborators

MedImmune Ltd

1. Study Identification

Unique Protocol Identification Number

NCT01050998

Brief Title

A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis

Official Title

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Efficacy and Safety of CAM-3001 in Subjects With Rheumatoid Arthritis

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

January 5, 2010 (Actual)

Primary Completion Date

June 9, 2011 (Actual)

Study Completion Date

July 27, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedImmune LLC

Collaborators

MedImmune Ltd

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objectives of this study is to assess the safety, tolerability and efficacy of multiple doses of the mavrilimumab (CAM-3001) administered subcutaneously in subjects with moderately active Rheumatoid Arthritis (RA).

Detailed Description

This is a Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of multiple doses of the mavrilimumab (CAM-3001) (10 milligram [mg], 30 mg, 50 mg, and 100 mg) administered subcutaneously in adult subjects with moderately active RA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis, Mavrilimumab, CAM-3001

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

516 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mavrilimumab 10 mg

Arm Type

Experimental

Arm Description

Mavrilimumab (CAM-3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm Title

Mavrilimumab 30 mg

Arm Type

Experimental

Arm Description

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm Title

Mavrilimumab 50 mg

Arm Type

Experimental

Arm Description

Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm Title

Mavrilimumab 100 mg

Arm Type

Experimental

Arm Description

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Intervention Type

Biological

Intervention Name(s)

Mavrilimumab 10 mg

Other Intervention Name(s)

CAM-3001

Intervention Description

Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks.

Intervention Type

Biological

Intervention Name(s)

Mavrilimumab 30 mg

Other Intervention Name(s)

CAM-3001

Intervention Description

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks.

Intervention Type

Biological

Intervention Name(s)

Mavrilimumab 50 mg

Other Intervention Name(s)

CAM-3001

Intervention Description

Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks.

Intervention Type

Biological

Intervention Name(s)

Mavrilimumab 100 mg

Other Intervention Name(s)

CAM-3001

Intervention Description

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks.

Primary Outcome Measure Information:

Title

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Description

DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline >1.2 with baseline DAS28 (CRP) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (CRP) >=3.2 to =< 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (CRP) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (CRP) >5.1. DAS28 (CRP) response by EULAR category at Day 85 for the European and Japanese regions were reported.

Time Frame

Day 85

Title

Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Description

Time Frame

Day 85

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Description

Time Frame

Baseline up to Day 169 (follow-up)

Title

Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

Description

Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported.

Time Frame

Baseline up to Day 169 (follow-up)

Title

Number of Participants With Abnormal Electrocardiogram (ECG) Results

Description

Time Frame

Baseline up to Day 169 (follow-up)

Title

Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Description

Time Frame

Day 85

Title

Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

Description

Time Frame

Day 85

Title

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Description

Time Frame

Baseline and Day 85

Title

Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Description

DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide.

Time Frame

Day 85

Title

Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

Description

DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% for the European and Japanese regions were reported.

Time Frame

Day 85

Title

Change From Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Description

DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide.

Time Frame

Baseline and Day 85

Title

Dyspnea Score at Day 85

Description

Time Frame

Day 85

Title

Change From Baseline in Dyspnea Score at Day 85

Description

Time Frame

Baseline and Day 85

Title

Categorized Dyspnea Score at Day 85

Description

Time Frame

Day 85

Title

Oxygen Saturation Level at Day 85

Description

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

Time Frame

Day 85

Title

Oxygen Saturation Level at Day 85 by Region

Description

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. Oxygen saturation for the European and Japanese regions were reported.

Time Frame

Day 85

Title

Change From Baseline in Oxygen Saturation Level at Day 85

Description

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

Time Frame

Baseline and Day 85

Title

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

Description

Time Frame

Baseline up to Day 169 (follow-up)

Secondary Outcome Measure Information:

Title

Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

Description

Time Frame

Baseline and Day 85

Title

Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

Description

Time Frame

Baseline and Day 85

Title

Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

Description

Time Frame

Day 85

Title

Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

Description

Time Frame

Baseline up to Day 169 (follow-up)

Title

Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

Description

Time Frame

Baseline up to Day 169 (follow-up)

Title

Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

Description

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. Expected duration of response (DOR) was calculated as response rate (in percentage) multiplied by mean DOR (in days) by using Weibull Model. Duration of DAS28 (CRP) and DAS28 (ESR) remission were not analyzed because very few participants achieved remission in the overall study population.

Time Frame

Baseline up to Day 169

Title

Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

Description

Time Frame

Day 85

Title

Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

Description

Time Frame

Day 85

Title

Number of Participants Who Achieved ACR Categorical Responses

Description

ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. ACR responses were categorized as "No response", "ACR20 but not ACR50", "ACR50 but not ACR70", and "ACR70".

Time Frame

Day 85

Title

Continuous ACR (ACRn) Score

Description

Time Frame

Day 85

Title

Continuous ACR (ACRn) Score by Region

Description

Time Frame

Day 85

Title

Swollen and Tender Joint Count

Description

Time Frame

Day 85

Title

Swollen and Tender Joint Count by Region

Description

Time Frame

Day 85

Title

Physician Global Assessment of Disease Activity Score

Description

Physician Global Assessment of Arthritis was measured on a 0 to 10 centimeter (cm) Visual Analogue Scale (VAS), where 0 cm = very good and 10 cm = very bad.

Time Frame

Day 85

Title

Physician Global Assessment of Disease Activity Score by Region

Description

Physician Global Assessment of Arthritis was measured on a 0 to 10 cm VAS, where 0 cm = very good and 10 cm = very bad. Data for European and Japanese regions were reported.

Time Frame

Day 85

Title

Patient Global Assessment of Disease Activity Score

Description

Time Frame

Day 85

Title

Patient Global Assessment of Disease Activity Score by Region

Description

Time Frame

Day 85

Title

Patient Pain Assessment Score

Description

Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.

Time Frame

Day 85

Title

Patient Pain Assessment Score by Region

Description

Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain. Data for European and Japanese regions were reported.

Time Frame

Day 85

Title

Health Assessments Questionnaire-Disability Index (HAQ-DI) Score

Description

Time Frame

Day 85

Title

Health Assessments Questionnaire-Disability Index (HAQ-DI) Score by Region

Description

Time Frame

Day 85

Title

Health Assessments Questionnaire (HAQ) Pain Score

Description

Participants were asked to assess the severity of pain in the past week on a 100 VAS with 0 being no pain and 100 being severe pain.

Time Frame

Day 85

Title

Health Assessments Questionnaire (HAQ) Pain Score by Region

Description

Participants were asked to assess the severity of pain in the past week on a 100 VAS with 0 being no pain and 100 being severe pain. Data for European and Japanese regions were reported.

Time Frame

Day 85

Title

Serum Concentration of C-Reactive Protein (CRP)

Description

Time Frame

Day 85

Title

Serum Concentration of C-Reactive Protein (CRP) by Region

Description

Time Frame

Day 85

Title

Serum Concentration of Erythrocyte Sedimentation Rate (ESR)

Description

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube.

Time Frame

Day 85

Title

Serum Concentration of Erythrocyte Sedimentation Rate (ESR) by Region

Description

Time Frame

Day 85

Title

Serum Concentration of Rheumatoid Factor (RF)

Time Frame

Day 85

Title

Serum Concentration of Anti-Citrullinated-Peptide-Antibody (ACPA)

Time Frame

Day 85

Title

Number of Participants Who Had Additional Medications

Description

Time Frame

Baseline up to Day 169

Title

Number of Participants With Change in Methotrexate (MTX) and Corticosteroid (CST) Dose

Description

Time Frame

Baseline, Day 1 to 85, Day 86 to 169

Title

Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After First Dose by Region

Description

Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After First Dose by Region

Description

Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After First Dose by Region

Description

Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After Last Dose by Region

Description

Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After Last Dose by Region

Description

Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After Last Dose by Region

Description

Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Terminal Phase Elimination Half-Life (t1/2) for Mavrilimumab After Last Dose by Region

Description

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Accumulation Ratio for Mavrilimumab After Last Dose by Region

Description

Accumulation ratio was calculated as ratio of AUCtau after last dose and AUCtau after first dose. Data for European and Japanese regions were reported.

Time Frame

Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169

Title

Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit

Description

ADA detection measured by using electrochemiluminescence assays.

Time Frame

Day 1 up to Day 169

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 through 80 years (20 to 75 years in Japan) Written consent Diagnosis of adult onset Rheumatoid Arthritis (RA) of at least 3 months duration as defined by the 1987 American College of Rheumatology (ACR) classification criteria (Arnett et al, 1988) Treatment with methotrexate at a stable and tolerated doses Positive anti-cyclic citrullinated peptide (CCP) immuno-globulin G antibodies (more than [>] 5 international unit per milliliter [IU/mL]) and/or rheumatoid factor (RF >14 IU/mL) at screening Received more than or equal to (>=) 5 milligram (mg) per week folic acid as a single or divided dose during the study. Exclusion Criteria: A rheumatic autoimmune disease other than RA A history of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder Subjects at a high risk of infection Subjects (male and female) of reproductive potential who are not willing to use contraception from screening through the end date of the trial History of methotrexate or any drug-induced lung fibrosis or pneumonitis.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marius Albulescu

Organizational Affiliation

MedImmune Ltd

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Plovdiv

Country

Bulgaria

Facility Name

Research Site

City

Sofia

Country

Bulgaria

Facility Name

Research Site

City

Varna

Country

Bulgaria

Facility Name

Research Site

City

Bruntal

Country

Czechia

Facility Name

Research Site

City

Ostrava - Trebovice

Country

Czechia

Facility Name

Research Site

City

Praha 2

Country

Czechia

Facility Name

Research Site

City

Praha 4 - Nusle

Country

Czechia

Facility Name

Research Site

City

Praha 4

Country

Czechia

Facility Name

Research Site

City

Uherske Hradiste

Country

Czechia

Facility Name

Research Site

City

Zlin

Country

Czechia

Facility Name

Research Site

City

Tallinn

Country

Estonia

Facility Name

Research Site

City

Budapest

Country

Hungary

Facility Name

Research Site

City

Sopron

Country

Hungary

Facility Name

Research Site

City

Zalaegerszeg

Country

Hungary

Facility Name

Research Site

City

Chiba-shi

Country

Japan

Facility Name

Research Site

City

Chiyoda-ku

Country

Japan

Facility Name

Research Site

City

Fukui-shi

Country

Japan

Facility Name

Research Site

City

Fukuoka-shi

Country

Japan

Facility Name

Research Site

City

Goshogawara-shi

Country

Japan

Facility Name

Research Site

City

Hamamatsu-shi

Country

Japan

Facility Name

Research Site

City

Iizuka-shi

Country

Japan

Facility Name

Research Site

City

Kagoshima-shi

Country

Japan

Facility Name

Research Site

City

Kasama-shi

Country

Japan

Facility Name

Research Site

City

Kitakyushu-shi

Country

Japan

Facility Name

Research Site

City

Nagano-Shi

Country

Japan

Facility Name

Research Site

City

Nagoya-shi

Country

Japan

Facility Name

Research Site

City

Okayama-shi

Country

Japan

Facility Name

Research Site

City

Omura-shi

Country

Japan

Facility Name

Research Site

City

Sagamihara-shi

Country

Japan

Facility Name

Research Site

City

Sasebo-shi

Country

Japan

Facility Name

Research Site

City

Shinjuku-ku

Country

Japan

Facility Name

Research Site

City

Liepaja

Country

Latvia

Facility Name

Research Site

City

Riga

Country

Latvia

Facility Name

Research Site

City

Valmiera

Country

Latvia

Facility Name

Research Site

City

Klaipeda

Country

Lithuania

Facility Name

Research Site

City

Vilnius

Country

Lithuania

Facility Name

Research Site

City

Bialystok

Country

Poland

Facility Name

Research Site

City

Bydgoszcz

Country

Poland

Facility Name

Research Site

City

Katowice

Country

Poland

Facility Name

Research Site

City

Legnica

Country

Poland

Facility Name

Research Site

City

Lublin

Country

Poland

Facility Name

Research Site

City

Poznan

Country

Poland

Facility Name

Research Site

City

Torun

Country

Poland

Facility Name

Research Site

City

Warszawa

Country

Poland

Facility Name

Research Site

City

Bucuresti

Country

Romania

Facility Name

Research Site

City

Ploiesti

Country

Romania

Facility Name

Research Site

City

Targu Mures

Country

Romania

Facility Name

Research Site

City

Barnaul

Country

Russian Federation

Facility Name

Research Site

City

Kazan

Country

Russian Federation

Facility Name

Research Site

City

Kemerovo

Country

Russian Federation

Facility Name

Research Site

City

Novosibirsk

Country

Russian Federation

Facility Name

Research Site

City

St. Petersburg

Country

Russian Federation

Facility Name

Research Site

City

Yaroslavl

Country

Russian Federation

Facility Name

Research Site

City

Donetsk

Country

Ukraine

Facility Name

Research Site

City

Kiev

Country

Ukraine

Facility Name

Research Site

City

Kyiv

Country

Ukraine

12. IPD Sharing Statement

Citations:

PubMed Identifier

23234647

Citation

Burmester GR, Weinblatt ME, McInnes IB, Porter D, Barbarash O, Vatutin M, Szombati I, Esfandiari E, Sleeman MA, Kane CD, Cavet G, Wang B, Godwood A, Magrini F; EARTH Study Group. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis. 2013 Sep 1;72(9):1445-52. doi: 10.1136/annrheumdis-2012-202450. Epub 2012 Dec 12.

Results Reference

background

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=29&filename=CAM-3001_CP-219_Redacted_4Mar13.pdf

Description

CAM-3001_CP-219_Redacted_4Mar13

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis

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A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis

Rheumatoid Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial