A Randomized, Active Controlled, Double-blind, Study to Compare the Safety and Reduction in Disease Activity With the Combination of Rituximab (MabThera®)and Tocilizumab (RoActemra®) Versus Tocilizumab in Patients With Active Rheumatoid Arthritis With an Incomplete Response to Methotrexate
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 24
- 主要终点
- Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)
研究概览
简要总结
This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12.
All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the tar get sample size is <100 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients, 18-65 years of age;
- •rheumatoid arthritis, functional status I-III;
- •SJC>=4 (28 joint count) and TJC>=4 (28 joint count) at screening and baseline;
- •RF and/or anti-CCP positive;
- •may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab);
- •inadequate response to methotrexate, at a dose of 7.5-25mg weekly for at least 12 weeks, at a stable dose for past 4 weeks.
排除标准
- •rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis;
- •history of, or current, inflammatory joint disease other than rheumatoid arthritis;
- •diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16;
- •significant cardiac or pulmonary disease;
- •previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).
研究组 & 干预措施
1
干预措施: rituximab [MabThera/Rituxan] (Drug)
1
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
2
干预措施: Placebo (Drug)
2
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
结局指标
主要结局
Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)
时间窗: Week 16
The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC \[28 joints\]), Swollen Joint Count (SJC \[28 joints\]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (\*) (square root)√ TJC plus (+) (0.28 \* √ SJC + (0.70 \* ln(ESR))+(0.014 \* (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log
次要结局
- Clinical Disease Activity Index Scores(Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Simplified Disease Activity Index (SDAI) Scores(Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48)
- Change From Baseline to Week 48 in C-Reactive Protein (CRP)(Baseline and Week 48)
- Change From Baseline to Week 48 in Participant's Assessment of Pain(Baseline and Week 48)
- Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR(Week 16)
- Change From Baseline in DAS28-ESR(Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16(Week 16)
- Change From Baseline to Week 48 in SJC and TJC(Baseline and Week 48)
- Change From Baseline to Week 48 in ESR(Baseline and Week 48)
- Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ)(Baseline and Week 48)
- Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity(Baseline and Week 48)
- Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity(Baseline and Week 48)