A Randomized, Double-Blind, Parallel-Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab Given As a Single Infusion or Dual Infusion Compared With Placebo in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Genentech, Inc.
- Enrollment
- 314
- Primary Endpoint
- Percentage of Participants With American College of Rheumatology (ACR) 20 Response
Study Overview
Brief Summary
This study will evaluate the efficacy and safety of ocrelizumab, compared to placebo, in patients with active rheumatoid arthritis who have an inadequate response to methotrexate therapy. Patients will be randomized 2:2:1 to receive 1) infusions of ocrelizumab 200mg iv on Days 1 and 15, 2) infusions of ocrelizumab 400mg iv on Day 1 and placebo iv on Day 15, or 3) infusions of placebo iv on Days 1 and 15. At the end of the placebo-controlled treatment period at 24 weeks, patients in groups 1 and 3 will be re-randomized to receive either a single infusion of 400mg iv ocrelizumab or 2 infusions of 200mg iv ocrelizumab, and group 2 will receive a second single infusion of 400mg iv ocrelizumab. All patients will receive a stable dose of concomitant methotrexate (7.5-25mg/week) throughout the study. The anticipated time on study treatment is 1-2 years. Target number of patients to be enrolled in this trial is 300.
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
Participants received matching placebo:
- on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate)
- on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)
Intervention: Methotrexate (Drug)
Placebo
Participants received matching placebo:
- on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate)
- on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)
Intervention: Placebo (Drug)
Ocrelizumab 400mg
Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.
Intervention: Methotrexate (Drug)
Ocrelizumab 400mg
Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.
Intervention: Ocrelizumab (Drug)
Ocrelizumab 200mg
Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.
Intervention: Methotrexate (Drug)
Ocrelizumab 200mg
Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.
Intervention: Ocrelizumab (Drug)
Ocrelizumab 200mg/ Ocrelizumab 200mg
Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Methotrexate (Drug)
Ocrelizumab 200mg/ Ocrelizumab 200mg
Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Ocrelizumab (Drug)
Ocrelizumab 200mg/ Ocrelizumab 400mg
Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Methotrexate (Drug)
Ocrelizumab 200mg/ Ocrelizumab 400mg
Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Ocrelizumab (Drug)
Ocrelizumab 400mg/ Ocrelizumab 400mg
Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Methotrexate (Drug)
Ocrelizumab 400mg/ Ocrelizumab 400mg
Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Ocrelizumab (Drug)
Placebo/ Ocrelizumab 200mg
Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Methotrexate (Drug)
Placebo/ Ocrelizumab 200mg
Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Ocrelizumab (Drug)
Placebo/ Ocrelizumab 200mg
Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Placebo (Drug)
Placebo/ Ocrelizumab 400mg
Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Methotrexate (Drug)
Placebo/ Ocrelizumab 400mg
Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Ocrelizumab (Drug)
Placebo/ Ocrelizumab 400mg
Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With American College of Rheumatology (ACR) 20 Response
Time Frame: Week 24
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
- Change in SF-36 Subscale and Summary Scores From Baseline(Week 24)
- Percentage of Participants Achieving an ACR50 Response(Week 48)
- Change From Baseline in the Individual Parameters of the ACR Core Set: Erythrocyte Sedimentation Rate (ESR)(Week 24)
- Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score(Week 24)
- Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)(Week 24)
- Change in DAS28 From Baseline(Week 24)
- European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders)(Week 24)
- Percentage of Participants Achieving an ACR70 Response(Week 48)
- Change From Baseline in the Individual Parameters of the ACR Core Set(Week 24)
- Change From Baseline in the Individual Parameters of the ACR Core Set: C-Reactive Protein (CRP) Concentration(Week 24)
- Change in FACIT-F Fatigue Assessment From Baseline(Baseline, Weeks 4, 12, and 24)
- Percentage of Participants Achieving an ACR20 Response(Week 48)
- Percentage of Participants Achieving DAS28 Remission (DAS28 < 2.6)(Week 48)
- Cmax: Maximum Observed Serum Concentration of Ocrelizumab Following First Infusion(Week 24, 48)
- Csecond: Maximum Observed Serum Concentration of Ocrelizumab Following Second Infusion(Day 15 of Cycles 1 and 2)