A Study of Ocrelizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA)
- Registration Number
- NCT02720120
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study is in two parts and will evaluate the safety, tolerability and efficacy of escalating single intravenous (IV) doses of ocrelizumab compared with placebo in combination with methotrexate in participants with moderate to severe RA. Part 1 is the dose-escalation study, at one of the following dose levels of ocrelizumab \[400, 1000, 1500, and 2000 milligrams (mg)\]. In Part 2, participants will be randomized to explore tolerability and efficacy of doses which have been shown to be tolerated in Part 1.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 175
Inclusion Criteria
- Moderate to severe RA for at least 6 months
- Positive serum rheumatoid factor (>/= 20 international units per milliliter)
- Current treatment with RA on an outpatient basis
- Treatment failure with one disease modifying anti-rheumatic drug (DMARD) or biologic, but have not failed more than six of these agents including methotrexate
- Current treatment with methotrexate for at least 12 weeks, at a stable dose
- Use of highly effective contraception.
Exclusion Criteria
- Rheumatic autoimmune disease or inflammatory joint disease, other than RA
- Concurrent treatment with any disease-modifying anti-rheumatic drug (DMARD) (other than methotrexate) or any anti-tumor necrosis factor (TNF) -alfa or other biologic therapy
- Treatment with any other investigational drug within 4 weeks of screening
- Previous treatment with cell-depleting therapies, IV gamma-globulin, intra-articular or parenteral corticosteroids, and receipt of live/attenuated vaccine prior to screening
- Previous treatment with rituximab or any other anti-cluster of differentiation 20 (CD20) agent
- History of severe allergic or anaphylactic reactions to humanized monoclonal antibodies
- Known active bacterial, viral or fungal infections
- History of active tuberculosis and primary or secondary immunodeficiency
- History of concomitant diseases such as cardiovascular disease, nervous system, pulmonary disease, renal, hepatic, endocrine or gastrointestinal disorders
- Pregnancy or lactation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Placebo Placebo Participants will receive single IV infusion of placebo matched to ocrelizumab. Part 1: Ocrelizumab 1000 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 1000 mg. Part 1: Ocrelizumab 1500 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 1500 mg. Part 1: Ocrelizumab 400 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg) Part 1: Ocrelizumab 2000 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 2000 mg. Part 2: Ocrelizumab 1000 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 1000 mg. Part 2: Ocrelizumab 1500 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 1500 mg. Part 2: Ocrelizumab 400 mg Ocrelizumab Participants will receive single IV infusion of ocrelizumab 400 mg.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Anti-Ocrelizumab Antibodies Baseline up to approximately 7.25 years Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs) Baseline up to approximately 7.25 years
- Secondary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Concentration AUC(0-last) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Terminal Rate Constant of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Systemic Clearance (CL) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Time to Blood B-Cell Depletion Baseline up to approximately 7.25 years Percentage of Participants achieving European League Against Rheumatism (EULAR) Response at Week 24 Week 24 Time to Maximum Observed Plasma Concentration (Tmax) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Percentage of Participants with American College of Rheumatology (ACR) 20%, 50%, and 70% (ACR20/50/70) Response at Week 24 Week 24 Disease Activity Score at Week 24 Week 24 Mean Residence Time (MRT) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Maximum Plasma Concentration (Cmax) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Terminal Elimination Half-Life (t1/2) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Steady State Volume of Distribution (Vss) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab Pre-infusion (0 hours); 30 minutes post infusion on Day 1; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 (up to Week 24), and Weeks 36, 48 (Post Week 24) Duration of Blood B-Cell Depletion Baseline up to approximately 7.25 years