Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab (TCZ) With or Without Methotrexate (MTX) and Possible Addition of Other Disease-modifying Anti-rheumatic Drugs (DMARDs) in Patients...
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 556
- 主要终点
- Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24
研究概览
简要总结
This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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;
- •moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) > 4.4);
- •inadequate response to methotrexate;
- •on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.
排除标准
- •prior treatment with a biologic;
- •Rheumatoid arthritis (RA) functional class IV;
- •known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
- •evidence of active malignant disease.
研究组 & 干预措施
Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.
干预措施: methotrexate (Drug)
Tocilizumab + Placebo
Tocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab + Placebo
Tocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.
干预措施: placebo (Drug)
结局指标
主要结局
Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24
时间窗: Week 24
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
次要结局
- Change From Baseline in Swollen Joint Count(Baseline, Weeks 24, 52)
- Change From Baseline in the Health Assessment Questionnaire Disability Index(Baseline, Weeks 24, 52)
- Change From Baseline in Academic Medical Center (AMC) Linear Disability Scale (ALDS)(Baseline, Weeks 104)
- Percentage of Participants With American College of Rheumatology (ACR20) Response(Baseline, Weeks 24, 52, 104)
- Percentage of Participants With ACR90 Response(Baseline, Weeks 24, 52, 104)
- Change From Baseline in Tender Joint Count(Baseline, Weeks 24, 52)
- Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (VAS)(Baseline, Weeks 24, 52)
- Change From Baseline in Patient Global Assessment of Pain (VAS)(Baseline, Weeks 24, 52)
- Percentage of Participants Who Withdrew Due to Safety Reasons(Up to 3 years)
- Area Under the Curve (AUC) From Baseline to Week 52 for ACR Response(Baseline to Week 52)
- Percentage of Participants With ACR50 Response(Baseline, Weeks 24, 52, 104)
- Percentage of Participants With ACR70 Response(Baseline, Weeks 24, 52, 104)
- Time to First ACR20 Response(104 Weeks)
- Time to First ACR90 Response(104 Weeks)
- Change From Baseline in C-Reactive Protein (CRP)(Baseline, Weeks 24, 52)
- Time to First ACR50 Response(104 Weeks)
- Time to First ACR70 Response(104 Weeks)
- Percentage of Participants With Disease Activity Score 28 (DAS28) Remission(Week 52)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline, Weeks 24, 52)
- Area Under Curve (AUC) DAS28(Baseline to Week 24)
- Change From Baseline in DAS28 Score(Baseline, Weeks 24, 52)
- Percentage of Participants With Good or Moderate European League (EULAR) DAS28 Responses(Baseline, 24, 52)
- Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale (VAS)(Baseline, Weeks 24, 52)
- Change From Baseline in Total Genant Modified Sharp Scores (GSS)(Baseline, Weeks 24, 52, 104)
- Change From Baseline in Erosion Score(Baseline, Weeks 24, 52, 104)
- Time to Tocilizumab Remission(104 Weeks)
- Time to Drug-Free Remission(104 Weeks)
- Time to Flare After Tocilizumab Remission(104 Weeks)
- Percentage of Participants With DAS28 Low Disease Activity (LDAS)(Weeks 24, 52)
- Change From Baseline in Joint Space Narrowing Score(Baseline, Weeks 24, 52, 104)
- Percentage of Participants Discontinuing Tocilizumab Due to Remission(Weeks 52, 104)
- Change From Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL)(Baseline, Weeks 24, 52, 104)
- Percentage of Participants Who Withdrew Due to Lack of Sufficient Therapeutic Response(Up to 3 years)
- Area Under the Curve (AUC) From Baseline to Week 24 for ACR Response(Baseline to Week 24)
- Time to Restart of Treatment After Discontinuation/Remission(104 Weeks)