A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 755
- 主要终点
- Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
研究概览
简要总结
This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Rituximab (0.5 g x 2) + Methotrexate
Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: folate (Drug)
Rituximab (0.5 g x 2) + Methotrexate
Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: methotrexate (Drug)
Rituximab (0.5 g x 2) + Methotrexate
Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: methylprednisolone (Drug)
Rituximab (0.5 g x 2) + Methotrexate
Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: rituximab (Drug)
Rituximab (1.0 g x 2) + Methotrexate
Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: folate (Drug)
Rituximab (1.0 g x 2) + Methotrexate
Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: methotrexate (Drug)
Rituximab (1.0 g x 2) + Methotrexate
Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: methylprednisolone (Drug)
Rituximab (1.0 g x 2) + Methotrexate
Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
干预措施: rituximab (Drug)
Placebo + Methotrexate
Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8.
From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.
干预措施: folate (Drug)
Placebo + Methotrexate
Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8.
From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.
干预措施: methotrexate (Drug)
Placebo + Methotrexate
Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8.
From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.
干预措施: methylprednisolone (Drug)
Placebo + Methotrexate
Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8.
From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.
干预措施: placebo (Drug)
结局指标
主要结局
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
时间窗: Baseline and week 52
Rate of progression in structural joint damage (PJD) by change in Total Modified Sharp Score (TMSS) from screening to Week 52 in the modified intent-to-treat (MITT) population. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.
次要结局
- Change From Baseline in Modified Sharp Erosion Score at Week 52(Baseline and week 52)
- Percentage of Patients Without Radiographic Progression at Week 52(Baseline, Week 52)
- Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52(Baseline, Week 52)
- Change From Baseline in the Modified Total Sharp Score at Week 24(Baseline, Week 24)
- Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52(Baseline, Week 52)
- Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52(Baseline, Week 52)
- Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52(Baseline, Week 52)
- Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52(Baseline, Week 52)
- Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52(Baseline, Week 52)
- Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52(Baseline and week 52)
- Percentage of Participants With DAS28-ESR Remission at Week 52(Week 52)
- Change From Baseline in the Total Erosion Score at Week 24(Baseline, Week 24)
- Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24(Baseline, Week 24)
- Percentage of Participants Without Radiographic Progression at Week 24(Baseline, Week 24)
- Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52(Week 52)
- Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52(Baseline, Week 52)
- The Percentage of Participants With Major Clinical Response at Week 52(Week 52)
- Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52(Week 52)
- Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52(Baseline, Week 52)
- Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104(Baseline, Weeks 52, Week 104)
- Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52(Baseline, Week 52)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52(Baseline, Week 52)
- Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104(Baseline, Week 52, Week 104)
- Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52(Baseline, Week 52)
- Change From Baseline in the Modified Total Sharp Score at Week 104(Baseline, Week 104)
- Change From Baseline in the Total Erosion Score at Week 104(Baseline, Week 104)
- Percentage of Participants Without Radiographic Progression at Week 104(Baseline, Week 104)
- Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104(Week 104)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104(Baseline, Week 104)