A Randomized Placebo-Controlled, Multi-Center, Phase I/II Study of the Safety of Escalating Single Intravenous Doses of Ocrelizumab (rhuMAb 2H7, RO4964913, PRO70769) in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Stable Doses of Concomitant Methotrexate But With Unsatisfactory Clinical Response
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 175
- 主要终点
- Percentage of Participants with Anti-Ocrelizumab Antibodies
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Part 1: Ocrelizumab 1000 mg
Participants will receive single IV infusion of ocrelizumab 1000 mg.
干预措施: Ocrelizumab (Drug)
Part 1: Ocrelizumab 1500 mg
Participants will receive single IV infusion of ocrelizumab 1500 mg.
干预措施: Ocrelizumab (Drug)
Part 1: Ocrelizumab 2000 mg
Participants will receive single IV infusion of ocrelizumab 2000 mg.
干预措施: Ocrelizumab (Drug)
Part 1: Ocrelizumab 400 mg
Participants will receive single IV infusion of ocrelizumab 400 milligrams (mg)
干预措施: Ocrelizumab (Drug)
Part 1: Placebo
Participants will receive single IV infusion of placebo matched to ocrelizumab.
干预措施: Placebo (Drug)
Part 2: Ocrelizumab 1000 mg
Participants will receive single IV infusion of ocrelizumab 1000 mg.
干预措施: Ocrelizumab (Drug)
Part 2: Ocrelizumab 1500 mg
Participants will receive single IV infusion of ocrelizumab 1500 mg.
干预措施: Ocrelizumab (Drug)
Part 2: Ocrelizumab 400 mg
Participants will receive single IV infusion of ocrelizumab 400 mg.
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Percentage of Participants with Anti-Ocrelizumab Antibodies
时间窗: Baseline up to approximately 7.25 years
Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs)
时间窗: Baseline up to approximately 7.25 years
次要结局
- 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)