A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Continuing Methotrexate Treatment
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Genentech, Inc.
- Enrollment
- 1,015
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Adverse Events (AEs)
Study Overview
Brief Summary
This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in combination with methotrexate in patients with active rheumatoid arthritis who have had an inadequate response to methotrexate. Patients will be randomized to receive placebo, 200mg of intravenous ocrelizumab or 500mg of i.v. ocrelizumab on Days 1 and 15. A repeat course of i.v. treatment will be administered at Weeks 24 and 26. All patients will receive 7.5mg - 25mg/week concomitant methotrexate at a stable dose. The anticipated time on study treatment is 1-2 years. Target sample size is 1000.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Placebo × 2 IV + MTX
Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Intervention: Methotrexate (Drug)
Placebo × 2 IV + MTX
Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Intervention: Placebo (Drug)
Ocrelizumab 200 mg × 2 IV + MTX
Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.
Intervention: Methotrexate (Drug)
Ocrelizumab 200 mg × 2 IV + MTX
Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.
Intervention: ocrelizumab (Drug)
Ocrelizumab 500 mg × 2 IV + MTX
Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.
Intervention: Methotrexate (Drug)
Ocrelizumab 500 mg × 2 IV + MTX
Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.
Intervention: ocrelizumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Adverse Events (AEs)
Time Frame: From baseline up to 8.5 years
An AE was defined as any untoward medical occurrence in a subject administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. Pre-existing conditions which worsened during the study were also reported as AEs.
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
Time Frame: Week 24
ACR20 is defined as 20 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 48
Time Frame: Week 48
ACR20 is defined as 20 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).
Secondary Outcomes
- Percentage of Participants With a Major Clinical Response (ACR70 for ≥ 6 Months) at Week 48(Week 48)
- Change From Baseline in Tender Joint Count (TJC) at Weeks 24 and 48(Baseline, Weeks 24, 48)
- Percentage of Participants Achieving an ACR70 Response at Weeks 24 and 48(Weeks 24 and 48)
- Change From Baseline in C-Reactive Protein (CRP) at Weeks 24 and 48(Baseline, Week 24, 48)
- Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6) at Weeks 24 and 48(Weeks 24 and 48)
- Change From Baseline in the Erythrocyte Sedimentation Rate (ESR) at Weeks 24 and 48(Baseline, Week 24, 48)
- Percentage of Participants With a Reduction in Modified Total Sharp Score (mTSS) From Baseline at Week 48(Baseline, Week 48)
- Change From Baseline in DAS28 at Weeks 24 and 48(Weeks 24 and 48)
- Percentage of Participants Achieving an ACR50 Response at Weeks 24 and 48(Weeks 24 and 48)
- Percent Change From Baseline in Swollen Joint Count (SJC) at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in Patient's Global VAS at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in Physician's Global VAS at Weeks 24 and 48(Baseline, Week 24, 48)
- European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) at Weeks 24 and 48(Weeks 24 and 48)
- Change From Baseline in Patient's Pain Visual Analogue Scale (VAS) at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 24 and 48(Baseline, Week 24, 48)
- Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score at Weeks 24 and(Week 24, 48)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Fatigue Assessment at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in the Modified Total Sharp Score (mTSS) at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in Modified Erosion Score at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48(Baseline, Week 24, 48)
- Change From Baseline in Modified Joint Space Narrowing Score at Weeks 24 and 48(Baseline, Week 24, 48)
- Percentage of Participants Without Radiographic Progression Defined as Change in mTSS ≤ 0 at Weeks 24 and 48(Weeks 24, 48)
- Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48(Baseline, Week 24, 48)