A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Retreatment With Rituximab in Subjects With Rheumatoid Arthritis Receiving Background Methotrexate
Overview
- Phase
- Phase 3
- Intervention
- rituximab
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Genentech, Inc.
- Enrollment
- 559
- Primary Endpoint
- Retreated Subjects With an American College of Rheumatology 20% (ACR20) Response at Week 48 Relative to Baseline
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy of retreatment with rituximab in subjects with active rheumatoid arthritis (RA) who are receiving Methotrexate (MTX).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent form
- •Ability and willingness to comply with the requirements of the study protocol
- •Age 18-80 years
- •Diagnosis of RA for at least 6 months
- •Receiving treatment for RA on an outpatient basis
- •Documented moderate to severe active RA activity at screening and Day 1
- •Documented inadequate response to previous or current treatment with one or more of the following: etanercept, infliximab, and/or adalimumab because of toxicity or inadequate efficacy
- •Use of MTX 10-25 mg/wk for ≥ 12 weeks prior to Day 1 at a stable dose for ≥ 4 weeks
- •Willingness to receive oral folic acid
- •If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to Day 1
Exclusion Criteria
- •Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; Secondary Sjogren's syndrome with RA is permitted.
- •History of or current inflammatory joint disease other than RA or other systemic rheumatic disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, or overlap syndrome)
- •History of deep space/tissue infection within 52 weeks prior to Day 1
- •Diagnosis of juvenile idiopathic arthritis (JIA), juvenile rheumatoid arthritis (JRA), and/or RA before age 16
- •Functional Class IV, as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- •Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement), within 12 weeks prior to Day 1 or planned within 48 weeks after Day 1
- •Known hypersensitivity to any component of a humanized or murine monoclonal antibody
- •Receipt of any vaccination within 4 weeks prior to Day 1
- •Significant cardiac or pulmonary disease, including obstructive pulmonary disease
- •Evidence of significant uncontrolled concomitant disease, such as, but not limited to nervous system, renal, hepatic, endocrine, or gastrointestinal disorders
Arms & Interventions
Arm A: Rituximab Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
Intervention: rituximab
Arm A: Rituximab Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
Intervention: methotrexate
Arm A: Rituximab Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by re-treatment during weeks 24 -40 consisting of two additional doses of 1000 mg rituximab 14 days apart plus 10-25 mg/week methotrexate.
Intervention: folate
Arm B: Placebo Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
Intervention: placebo
Arm B: Placebo Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
Intervention: methotrexate
Arm B: Placebo Retreatment
1000 mg rituximab intravenous initial treatment on day 1 and day 15 plus 10-25 mg/week methotrexate followed by retreatment during weeks 24 -40 consisting of two doses of placebo 14 days apart plus 10-25 mg/week methotrexate.
Intervention: folate
Outcomes
Primary Outcomes
Retreated Subjects With an American College of Rheumatology 20% (ACR20) Response at Week 48 Relative to Baseline
Time Frame: 48 Weeks
ACR20 response was defined as a ≥ 20% improvement compared with baseline in both tender joint count (TJC) \[68 joints\] and swollen joint count (SJC) \[66 joints\] as well as a ≥ 20% improvement in three of five additional measurements: 1) Physician's Global Assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 2) Patient's Global Assessment of Disease Activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\]; 3) Patient's Assessment of Pain \[visual analog scale: 0=no pain to 100=unbearable pain\]; 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) erythrocyte sedimentation rate.
Secondary Outcomes
- Percentage of Retreated Subjects With a European League Against Rheumatism (EULAR) Response at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Subject's Global Assessment of Disease Activity at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Subject's Assessment of Pain at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: C-Reactive Protein at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Erythrocyte Sedimentation (ESR) at Week 48(Baseline, Week 48)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) at Week 48 in Retreated Subjects(Baseline, Week 48)
- Percentage of Retreated Subjects Achieving DAS28-ESR Low Disease at Week 48(Week 48)
- Change From Baseline in Disease Activity Score (DAS28-CRP) at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Swollen Joint Count at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Tender Joint Count at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 48(Baseline, Week 48)
- Change From Baseline in American College of Rheumatology (ACR) Core Set Component: Physician's Global Assessment of Disease Activity at Week 48(Baseline, Week 48)
- Retreated Subjects With American College of Rheumatology 50% (ACR50) Response and American College of Rheumatology 70% (ACR70) Response at Week 48 Relative to Baseline(Baseline, Week 48)
- Change From Baseline in the Disease Activity Score Using 28 Joint Counts (DAS28-ESR) at Week 48(48 weeks)
- Change From Baseline in SF-36 Health Summary Scores at Week 48 in Retreated Subjects(Baseline, Week 48)
- Percentage of Retreated Subjects Achieving DAS28-ESR Remission at Week 48(Week 48)
- Percentage of Retreated Subjects With a Change ≥ 0.22 From Baseline in HAQ-DI at Week 48(Baseline, Week 48)
- Percentage of Retreated Subjects With a Change ≥ 0.3 From Baseline in HAQ-DI at Week 48(Baseline, Week 48)
- ACRn in Retreated Subjects at Week 48(Baseline, Week 48)