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 Who Have an Inadequate Response to at Least One Anti-TNF-α Therapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Genentech, Inc.
- Enrollment
- 836
- Locations
- 264
- Primary Endpoint
- Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses
Study Overview
Brief Summary
This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in patients with active rheumatoid arthritis who have an inadequate response to at least one anti-TNF-alpha therapy. 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 stable doses of either concomitant methotrexate (7.5-25mg/week) or leflunomide (10-20mg po daily) and may receive additional DMARDs. The treatment period is planned for 48 weeks (until primary analysis) and then participants will enter the open label phase until the drug is commercialized. 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
- •Adult patients, ≥ 18 years of age
- •Rheumatoid arthritis for at least 3 months
- •Inadequate response to previous or current treatment with at least one anti-TNF-alpha agent
- •Receiving either leflunomide or methotrexate for ≥ 12 weeks, with a stable dose for the last 4 weeks
- •Swollen joint count (SJC) ≥ 4 (66 joint count) and tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline.
- •CRP ≥ 0.6 mg/dL using a high-sensitivity assay.
- •Positive rheumatoid factor or positive anti-CCP antibody or both.
Exclusion Criteria
- •Rheumatic autoimmune disease or inflammatory joint disease, other than RA
- •Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline
Arms & Interventions
Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy
Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Leflunomide (Drug)
Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy
Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Methotrexate (Drug)
Ocrelizumab 200 mg x 2 IV + Non-Biologic DMARD Therapy
Participants will receive 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Ocrelizumab (Drug)
Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy
Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Leflunomide (Drug)
Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy
Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Methotrexate (Drug)
Ocrelizumab 500 mg x 2 IV + Non-Biologic DMARD Therapy
Participants will receive 2 IV infusions of 500 mg of ocrelizumab, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Ocrelizumab (Drug)
Placebo x 2 IV + Non-Biologic DMARD Therapy
Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Leflunomide (Drug)
Placebo x 2 IV + Non-Biologic DMARD Therapy
Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Methotrexate (Drug)
Placebo x 2 IV + Non-Biologic DMARD Therapy
Participants will receive ocrelizumab matching placebo IV in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses
Time Frame: Weeks 24 and 48
ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.
Secondary Outcomes
- Percentage of Participants Achieving an ACR70 Response(Weeks 24 and 48)
- Percentage of Participants With a Major Clinical Response(Week 48)
- Percentage of Participants With a Reduction in the HAQ-DI Score(Weeks 24 and 48)
- Percentage of Participants Achieving Disease Activity Score (DAS28) Remission(Weeks 24 and 48)
- Change in DAS28 From Baseline(Weeks 24 and 48)
- Percentage of Participants Achieving an ACR50 Response(Weeks 24 and 48)
- Percentage of Participants With EULAR Response Rates of Good/ Moderate(Weeks 24 and 48)