A Randomised, Double Dummy Controlled, Parallel Group Study of the Efficacy and Safety of MabThera (Rituximab) Alone or in Combination With Either Cyclophosphamide or Methotrexate, in Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 161
- 主要终点
- Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
研究概览
简要总结
WA16291 is a Phase IIa "proof-of-concept" study. The primary objective of this study is to determine the safety and efficacy of rituximab (a B cell depleting chimeric monoclonal antibody) used either as monotherapy or in combination with methotrexate or cyclophosphamide in participants with rheumatoid arthritis who have failed prior Disease Modifying Anti-Rheumatic Drug (DMARD) therapy and currently have an inadequate clinical response to methotrexate.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with moderate to severe rheumatoid arthritis (RA) who have previously failed 1-5 DMARDS who currently have partial clinical response to treatment with methotrexate
- •Using methotrexate as a single DMARD for at least 16 weeks, of which the last 4 weeks prior to baseline on a stable oral dose greater than or equal to (>=) 10 milligrams per week (mg/week)
- •>=21 years of age
- •Swollen Joint Count (SJC) and Tender Joint Count (TJC) >= 8 (out of 66 and 68 joints respectively)
- •At least 2 of the following parameters at Baseline: C- Reactive Protein >= 15 mg/dL; Erythrocyte Sedimentation Rate >= 30 millimeters per hour (mm/hr); Morning stiffness >45 minutes
- •Rheumatoid factor titer >=20 International units per milliliter (IU/mL)
- •Corticosteroid (less than or equal to [=<] 12.5 milligrams per deciliter [mg/d] prednisone or equivalent) or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are permitted if stable for at least 4 weeks prior to baseline
排除标准
- •American Rheumatism Association (ARA) Class IV RA disease
- •Concurrent treatment with any DMARD (apart from randomized treatment) or anti-TNF-alpha therapy
- •Active infection or history of recurrent significant infection
- •Prior history of cancer including solid tumors and hematologic malignancies (except basal carcinoma of the skin that have been excised and cured)
- •Evidence of serious uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders
- •Bone/joint surgery within 6 weeks prior to screening
- •Rheumatic Autoimmune disease other than RA
- •Active rheumatoid vasculitis
- •Prior history of gout
- •Chronic fatigue syndrome
研究组 & 干预措施
Group A: Methotrexate
Participants will receive methotrexate at dosage >=10 milligrams per week (mg/week) orally as determined by the investigator. They also receive placebo infusion on days 1 and 15 in place of rituximab and on Days 3 and 17 in place of cyclophosphamide.
干预措施: Methotrexate (Drug)
Group A: Methotrexate
Participants will receive methotrexate at dosage >=10 milligrams per week (mg/week) orally as determined by the investigator. They also receive placebo infusion on days 1 and 15 in place of rituximab and on Days 3 and 17 in place of cyclophosphamide.
干预措施: Placebo Cyclophosphamide (Other)
Group A: Methotrexate
Participants will receive methotrexate at dosage >=10 milligrams per week (mg/week) orally as determined by the investigator. They also receive placebo infusion on days 1 and 15 in place of rituximab and on Days 3 and 17 in place of cyclophosphamide.
干预措施: Placebo Rituximab (Other)
Group B: Rituximab Monotherapy
Participants will receive 1 g intravenous infusions of rituximab on Days 1 and 15. They also receive Weekly placebo orally instead of methotrexate and placebo infusion in place of cyclophosphamide on Days 3 and 17.
干预措施: Placebo Cyclophosphamide (Other)
Group B: Rituximab Monotherapy
Participants will receive 1 g intravenous infusions of rituximab on Days 1 and 15. They also receive Weekly placebo orally instead of methotrexate and placebo infusion in place of cyclophosphamide on Days 3 and 17.
干预措施: Placebo Methotrexate (Other)
Group B: Rituximab Monotherapy
Participants will receive 1 g intravenous infusions of rituximab on Days 1 and 15. They also receive Weekly placebo orally instead of methotrexate and placebo infusion in place of cyclophosphamide on Days 3 and 17.
干预措施: Rituximab (Drug)
Group C: Rituximab and Cyclophosphamide
Participants will receive 1g IV infusion of rituximab on Days 1 and 15 and 750 mg infusion of Cyclophosphamide on Days 3 and 17. They also receive weekly oral placebo in place of methotrexate.
干预措施: Cyclophosphamide (Drug)
Group C: Rituximab and Cyclophosphamide
Participants will receive 1g IV infusion of rituximab on Days 1 and 15 and 750 mg infusion of Cyclophosphamide on Days 3 and 17. They also receive weekly oral placebo in place of methotrexate.
干预措施: Placebo Methotrexate (Other)
Group C: Rituximab and Cyclophosphamide
Participants will receive 1g IV infusion of rituximab on Days 1 and 15 and 750 mg infusion of Cyclophosphamide on Days 3 and 17. They also receive weekly oral placebo in place of methotrexate.
干预措施: Rituximab (Drug)
Group D: Methotrexate and Rituximab
Participants will receive >=10 mg/week methotrexate orally along with 2 times 1 gram (g) rituximab IV infusions on Days 1 and 15. Participants will also receive placebo infusions on Days 3 and 17 in place of cyclophosphamide.
干预措施: Methotrexate (Drug)
Group D: Methotrexate and Rituximab
Participants will receive >=10 mg/week methotrexate orally along with 2 times 1 gram (g) rituximab IV infusions on Days 1 and 15. Participants will also receive placebo infusions on Days 3 and 17 in place of cyclophosphamide.
干预措施: Placebo Cyclophosphamide (Other)
Group D: Methotrexate and Rituximab
Participants will receive >=10 mg/week methotrexate orally along with 2 times 1 gram (g) rituximab IV infusions on Days 1 and 15. Participants will also receive placebo infusions on Days 3 and 17 in place of cyclophosphamide.
干预措施: Rituximab (Drug)
结局指标
主要结局
Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
时间窗: Week 24
次要结局
- Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)(Baseline up to Week 24)
- Mean change in Rheumatoid factor levels at 24 weeks(Baseline and Week 24)
- AUC of the mean Disease Activity Scores (DAS)(Baseline up to Week 24)
- Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores(Baseline, Weeks 12, 16, 20 and 24)
- Percentage of participants who withdrew due to insufficient therapeutic response(Up to 24 Weeks)
- Change from Baseline in the Tender Joint Count(Baseline, Weeks 12, 16, 20 and 24)
- Change from Baseline in C-Reactive Protein (CRP) Levels(Baseline, Weeks 12, 16, 20 and 24)
- Change from Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline, Weeks 12, 16, 20 and 24)
- Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24(Week 24)
- Change from Baseline in the Swollen Joint Count(Baseline, Weeks 12, 16, 20 and 24)
- Change from Baseline in participant's global assessment of disease activity using a Visual Analog Scale (VAS)(Baseline, Weeks 8, 12, 16, 20 and 24)
- Change from Baseline in physician's global assessment of disease activity using VAS(Baseline, Weeks 8, 12, 16, 20 and 24)
- Change from Baseline in participant's pain measured by VAS(Baseline, Weeks 12, 16, 20 and 24)