Back to resultsA Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis (OSCAR)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Non-Biologic DMARDs
Tocilizumab
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Participants with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
- Oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for greater than or equal to (≥]) 4 weeks prior to Baseline.
- Use of effective contraception throughout the study as defined by protocol; female participants of childbearing potential cannot be pregnant.
Exclusion Criteria:
- Presence of clinically significant medical conditions.
- History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease that might predispose to perforation.
- Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections.
- Any infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
- Clinically significant findings on laboratory tests.
- Positive hepatitis B surface antigen or hepatitis C antibody.
- Active tuberculosis requiring treatment within the previous 3 years.
- Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years.
- History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
- Neuropathies or other conditions that might interfere with pain evaluation.
- Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline.
- Rheumatic autoimmune disease other than RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted.
- Functional Class IV as defined by the ACR Classification of Functional Status in RA.
- Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16 years.
- Prior history of or current inflammatory joint disease other than RA.
- Exposure to tocilizumab (either intravenous or SC) at any time prior to Baseline.
- Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening.
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
- Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
- Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.
Sites / Locations
- ZGT Almelo; Reumatologie
- Jan Van Breemen Instituut
- Gelre Ziekenhuizen; Reumatologie
- Amphia ziekenhuis, locatie langendijk
- Albert Schweitzer Ziekenhuis ; Dordwijk
- Universitair Medisch Centrum Groningen; Department of Rheumatology
- Martini Ziekenhuis
- Kennemer Gasthuis
- Atrium Medisch Centrum
- Spaarne Ziekenhuis; Inwendige Geneeskunde
- Medisch Centrum Leeuwarden; Reumatology
- Academisch Ziekenhuis Leiden; Dept of Rheumatology
- Maastricht University Medical Centre; Rheumatology
- Erasmus Medisch Centrum; Reumatologie
- Maasstadziekenhuis; Reumatologie
- Vlietland Hospital
- Antonius Ziekenhuis Sneek; Department of Rheumatology
- Leyenburg Ziekenhuis; Internal Medecine
- St. Bronovo-Nebo
- University Medical Centre Utrecht; Reumatologie en Klinische Immunologie
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tocilizumab Alone or in Combination with Methotrexate or DMARD
Arm Description
Participants will receive a weekly SC injection of tocilizumab 162 milligrams (mg) as monotherapy or in combination with methotrexate or other non-biologic DMARDs for 24 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events
An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Adverse events included serious as well as non-serious adverse events.
Secondary Outcome Measures
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour [mm/hour]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale [VAS] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR less than (<) 2.6 implied clinical remission.
Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).
Percentage of Participants Achieving an ACR50 Response
A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
Percentage of Participants Achieving an ACR70 Response
A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
Percentage of Participants Achieving an ACR90 Response
A participant had an ACR90 response if there was at least a 90% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline >1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline >0.6 to ≤1.2 with a DAS28 score >5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity .
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal
The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI <= 2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity.
Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
Number of tender joints was determined by examining 28 joints for TJC28 and 68 joints for TJC68, 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 at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 for a TJC28 and 68 for a TJC68. A reduction in number of tender joints compared to baseline indicates improvement.
Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
Number of swollen joints was determined by examination of 28 joints for SJC28 and 66 joints for SJC66 and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 for a SJC28 and 66 for a SJC66. A reduction in number of swollen joints compared to baseline indicates improvement.
Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons
Results are reported for percentage of participants who had NSAIDs dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).
Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons
Results are reported for percentage of participants who had corticosteroid dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).
Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs
Time to discontinuation or first dose reduction of corticosteroids or NSAIDs (weeks) = (Date of the first dose reduction or end date of corticosteroids or NSAIDs treatment - date of first drug intake of this study) + 1. Time to discontinuation or first dose reduction was based on the first occurring event (corticosteroid discontinuation or corticosteroid first dose reduction or NSAIDs discontinuation or NSAIDs first dose reduction, whichever occurred first).
Percentage of Participants With Anti-Tocilizumab Antibodies
Serum Levels of Tocilizumab
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)
Patient Global Assessment of Disease Activity VAS Scores
Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.
Patient Pain VAS Scores
This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.
Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records
A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01987479
Brief Title
A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis
Acronym
OSCAR
Official Title
Multi-Center, Open Label, Single Arm Phase IIIB Study on Safety and Efficacy of Subcutaneous Tocilizumab in Monotherapy or in Combination With Methotrexate or Other Non-Biologic Disease Modifying Antirheumatic Drugs in Rheumatoid Arthritis Patients With an Inadequate Response to Non-Biologic DMARDs - OSCAR
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 30, 2014 (Actual)
Primary Completion Date
May 26, 2016 (Actual)
Study Completion Date
May 26, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This multi-center, open-label single arm Phase IIIb study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab administered as monotherapy and/or in combination with methotrexate or other non-biologic disease modifying antirheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) with an inadequate response to non-biologic DMARDs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tocilizumab Alone or in Combination with Methotrexate or DMARD
Arm Type
Experimental
Arm Description
Participants will receive a weekly SC injection of tocilizumab 162 milligrams (mg) as monotherapy or in combination with methotrexate or other non-biologic DMARDs for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Non-Biologic DMARDs
Intervention Description
Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study and is at the investigator's discretion.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra, Actemra
Intervention Description
Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Methotrexate will be administered per investigator's discretion.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Description
An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Adverse events included serious as well as non-serious adverse events.
Time Frame
Baseline up to Week 32
Secondary Outcome Measure Information:
Title
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
Description
DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour [mm/hour]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale [VAS] where 0 mm=no disease activity and 100 mm=worst disease activity). DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. Total score range: 0-10, higher score=higher disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR less than (<) 2.6 implied clinical remission.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response
Description
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Percentage of Participants Achieving an ACR50 Response
Description
A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Percentage of Participants Achieving an ACR70 Response
Description
A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Percentage of Participants Achieving an ACR90 Response
Description
A participant had an ACR90 response if there was at least a 90% improvement, ie, reduction from Baseline, in TJC and SJC (28 assessed joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR
Description
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline >1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1. Participants with change from baseline >0.6 to ≤1.2 with a DAS28 score >5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
Description
The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L). SDAI total score = 0-86. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity .
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal
Description
The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity). CDAI total score = 0-76. CDAI <= 2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
Description
Number of tender joints was determined by examining 28 joints for TJC28 and 68 joints for TJC68, 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 at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28 for a TJC28 and 68 for a TJC68. A reduction in number of tender joints compared to baseline indicates improvement.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
Description
Number of swollen joints was determined by examination of 28 joints for SJC28 and 66 joints for SJC66 and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28 for a SJC28 and 66 for a SJC66. A reduction in number of swollen joints compared to baseline indicates improvement.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
Title
Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons
Description
Results are reported for percentage of participants who had NSAIDs dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).
Time Frame
From Week 16 and before Week 20; From Week 20 and before Week 24
Title
Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons
Description
Results are reported for percentage of participants who had corticosteroid dose reductions or discontinuation by reasons for dose reductions or discontinuation (unknown reasons, safety reasons, other reasons, lack of efficacy, and discomfort).
Time Frame
From Week 16 and before Week 20; From Week 20 and before Week 24
Title
Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs
Description
Time to discontinuation or first dose reduction of corticosteroids or NSAIDs (weeks) = (Date of the first dose reduction or end date of corticosteroids or NSAIDs treatment - date of first drug intake of this study) + 1. Time to discontinuation or first dose reduction was based on the first occurring event (corticosteroid discontinuation or corticosteroid first dose reduction or NSAIDs discontinuation or NSAIDs first dose reduction, whichever occurred first).
Time Frame
Baseline up to Week 32
Title
Percentage of Participants With Anti-Tocilizumab Antibodies
Time Frame
Baseline, Weeks 12 and 24, early withdrawal (up to Week 24), follow-up visit (8 weeks after last dose of tocilizumab, up to 32 weeks)
Title
Serum Levels of Tocilizumab
Time Frame
Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)
Title
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)
Time Frame
Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)
Title
Patient Global Assessment of Disease Activity VAS Scores
Description
Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)
Title
Patient Pain VAS Scores
Description
This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)
Title
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Description
The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life. It measures the participant's ability to perform everyday tasks. The index consists of 20 questions regarding the function of the upper and lower extremities. These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week. Each question is evaluated according to the degree of severity on a 4-point scale. Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)
Title
Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records
Description
A diary card was provided to participants to record home injections. Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance. A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.
Time Frame
Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)
Title
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
Description
The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
Oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for greater than or equal to (≥]) 4 weeks prior to Baseline.
Use of effective contraception throughout the study as defined by protocol; female participants of childbearing potential cannot be pregnant.
Exclusion Criteria:
Presence of clinically significant medical conditions.
History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease that might predispose to perforation.
Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections.
Any infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
Clinically significant findings on laboratory tests.
Positive hepatitis B surface antigen or hepatitis C antibody.
Active tuberculosis requiring treatment within the previous 3 years.
Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years.
History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
Neuropathies or other conditions that might interfere with pain evaluation.
Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline.
Rheumatic autoimmune disease other than RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted.
Functional Class IV as defined by the ACR Classification of Functional Status in RA.
Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16 years.
Prior history of or current inflammatory joint disease other than RA.
Exposure to tocilizumab (either intravenous or SC) at any time prior to Baseline.
Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening.
Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
ZGT Almelo; Reumatologie
City
Almelo
ZIP/Postal Code
7609 PP
Country
Netherlands
Facility Name
Jan Van Breemen Instituut
City
Amsterdam
ZIP/Postal Code
1056 AB
Country
Netherlands
Facility Name
Gelre Ziekenhuizen; Reumatologie
City
Apeldoorn
ZIP/Postal Code
7334 DZ
Country
Netherlands
Facility Name
Amphia ziekenhuis, locatie langendijk
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
Albert Schweitzer Ziekenhuis ; Dordwijk
City
Dordrecht
ZIP/Postal Code
3318AT
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen; Department of Rheumatology
City
Groningen
ZIP/Postal Code
9700RB
Country
Netherlands
Facility Name
Martini Ziekenhuis
City
Groningen
ZIP/Postal Code
9728 MG
Country
Netherlands
Facility Name
Kennemer Gasthuis
City
Haarlem
ZIP/Postal Code
2035 RC
Country
Netherlands
Facility Name
Atrium Medisch Centrum
City
Heerlen
ZIP/Postal Code
6419 PC
Country
Netherlands
Facility Name
Spaarne Ziekenhuis; Inwendige Geneeskunde
City
Hoofddorp
ZIP/Postal Code
2134 TM
Country
Netherlands
Facility Name
Medisch Centrum Leeuwarden; Reumatology
City
Leeuwarden
ZIP/Postal Code
8934 AD
Country
Netherlands
Facility Name
Academisch Ziekenhuis Leiden; Dept of Rheumatology
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Maastricht University Medical Centre; Rheumatology
City
Maastricht
ZIP/Postal Code
6202 ZA
Country
Netherlands
Facility Name
Erasmus Medisch Centrum; Reumatologie
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Maasstadziekenhuis; Reumatologie
City
Rotterdam
ZIP/Postal Code
3079 DZ
Country
Netherlands
Facility Name
Vlietland Hospital
City
Schiedam
ZIP/Postal Code
3118 JH
Country
Netherlands
Facility Name
Antonius Ziekenhuis Sneek; Department of Rheumatology
City
Sneek
ZIP/Postal Code
8601 ZK
Country
Netherlands
Facility Name
Leyenburg Ziekenhuis; Internal Medecine
City
The Hague
ZIP/Postal Code
2545 CH
Country
Netherlands
Facility Name
St. Bronovo-Nebo
City
The Hague
ZIP/Postal Code
2597 AX
Country
Netherlands
Facility Name
University Medical Centre Utrecht; Reumatologie en Klinische Immunologie
City
Utrecht
ZIP/Postal Code
3584 GA
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
30649524
Citation
Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
Results Reference
derived
PubMed Identifier
29244149
Citation
Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443. Erratum In: Rheumatology (Oxford). 2018 Jun 1;57(6):1129.
Results Reference
derived
Learn more about this trial
A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis
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