NCT01126541已完成3 期
A Comparative Study to Assess the Effect of Retreatment With 2 Doses of MabThera on Disease Activity Score in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response or Intolerance to antiTNF-alfa Therapy.(SMART)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 224
- 主要终点
- Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104
研究概览
简要总结
This study will compare the efficacy and safety of re-treatment with 2 doses of MabThera (rituximab) in patients with active rheumatoid arthritis (RA) who have previously experienced an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapies etanercept, infliximab or adalimumab therapy. All patients will receive infusions of 1000 mg intravenous (IV) MabThera on Days 1 and 15; at Week 24 patients who have demonstrated a moderate or good response will be randomized to receive re-treatment with either 1 or 2 additional infusions of 1000 mg IV MabThera. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients >18 years of age
- •RA for >=6 months
- •Receiving outpatient treatment
- •Ongoing treatment with methotrexate for >=3 months, stable for >=1 month
- •Inadequate response or intolerance to etanercept, infliximab or adalimumab
排除标准
- •Previous treatment with MabThera
- •Concurrent treatment with any anti TNF-alfa therapy or biologic therapy
- •Previous treatment with any investigational cell-depleting therapies
研究组 & 干预措施
A
Experimental
1000 mg IV rituximab
干预措施: rituximab (Drug)
B
Experimental
2 x 1000 mg IV rituximab
干预措施: rituximab (Drug)
结局指标
主要结局
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104
时间窗: Week 104
DAS28-CRP was based on joint counts, overall participant assessment, and serum CRP levels (measured in milligrams per liter \[mg/L\]) at each visit. Joint counts included swollen joint count (SJC) and tender joint count (TJC). Total score range was 0 to 9.4; a higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and less than (\<)2.6 equals (=) remission. The AUC of all DAS28-CRP values between Day 1 and Week 104 (15 values of protocol visits) was calculated using the trapeze method (AUC between t1 and t2=(t2-t1)\*((DAS28-CRP at t1 + DAS28-CRP at t2)/2). The true visit dates were used to calculate the time between 2 DAS28-CRP evaluations. All the AUC were censored at Week 104 (linear extrapolation using the 2 last DAS28-CRP values (Weeks 96 and 104) to obtain the "true" DAS28-CRP value at the "true" Week 104).
次要结局
- DAS28-CRP During the Initial Treatment(Days 1 and 15, and Weeks 6, 12, and 24)
- DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course(Day 1, 24 weeks following each infusion up to 72 Weeks)
- Duration of DAS28-CRP Remission After Retreatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS(Week 24, 12 and 24 weeks after 1st retreatment)
- Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2)(Week 24 of the Initial Treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment)
- Time to Achieve DAS28-CRP Remission After the First Course(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Time to Achieve DAS28-CRP Remission After Retreatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Patient's Global Assessment of Pain(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- SF-12 Mental Health Composite Score(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS)(Week 24, 12 and 24 weeks after 1st retreatment)
- DAS28-CRP AUC Weighted Time(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Percentage of Participants Achieving a Response During Retreatment by EULAR Category(Week 24, 24 weeks after 1st retreatment, 24 weeks after 2nd retreatment)
- Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment(Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment)
- Physician's Global Assessment of Disease Activity(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- Participant Assessment of Fatigue(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- Total Mean Dose of Cortisone Between Week 24 and Week 104(Week 24 to Week 104)
- HAQ-DI Scores(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS(Week 24, 12 and 24 weeks after 1st retreatment)
- Time to Achieve DAS28-CRP ≤3.2 After Retreatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70)(Week 24 of the initial treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment)
- Short Form 12 (SF-12) Physical Health Composite Score(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS(Week 24, 12 and 24 weeks after 1st retreatment)
- Change From Baseline in HAQ-DI in Participants With MCII(Baseline, Week 24, 12 and 24 weeks after 1st retreatment)
- Duration of DAS28-CRP Remission After the First Course of Treatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Duration of DAS28-CRP ≤3.2 After the First Course of Treatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Duration of DAS28-CRP ≤3.2 After Retreatment(Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104)
- Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category(Day 15, Weeks 6, 12, and 24)
- Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment(Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment)
- Patient Global Assessment of Disease Activity(Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment)
- Cortisone Intake AUC (Time- and Weight-Weighted)(Day 1 (each infusion), Week 24, Week 104)
- Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS(Week 24, 12 and 24 weeks after 1st retreatment)
- Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity(Week 24, 12 and 24 weeks after 1st retreatment)
- Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII(Baseline, Week 24, 12 and 24 weeks after 1st retreatment)
- Percentage of Participants With MCII in Functioning(Week 24, 12 and 24 weeks after 1st retreatment)
- Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS(Week 24, 12 and 24 weeks after 1st retreatment)
- Percentage of Participants With MCII in Pain(Week 24, 12 and 24 weeks after 1st retreatment)
- Change From Baseline in Patient Global Assessment of Pain in Participants With MCII(Baseline, Week 24, 12 and 24 weeks after 1st retreatment)
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