A Randomized, Open-label, Parallel-group Study of the Reduction of Signs and Symptoms During Treatment With Tocilizumab Versus Adalimumab, Both in Combination With MTX, in Patients With Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to Treatment With Only One TNF Inhibitor
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 96
- 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 randomized, parallel-group study will assess the efficacy and safety of RoActemra/Actemra (tocilizumab) versus adalimumab, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients, already treated with MTX at stable doses, will be randomized to receive either RoActemra/Actemra 8 mg/kg intravenously (IV) every 4 weeks or adalimumab 40 mg subcutaneous (SC) every 2 weeks. All patients will receive methotrexate (10-25 mg weekly) and folate (at least 5 mg weekly). The anticipated time on study treatment is 24 weeks.
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
- •Rheumatoid arthritis of >/= 6 months duration (according to American College of Rheumatology (ACR) criteria)(according to ACR criteria)
- •Inadequate response due to inefficacy of treatment (for at least 3 months) with only one approved Tumor Necrosis Factor (TNF)-agent other than adalimumab Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study
- •On methotrexate treatment for >/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks
- •Disease Activity Score (DAS28) >3.2 at baseline
- •Oral corticosteroids (</=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs) are permitted if the dose has been stable for >/=6 weeks prior to baseline.
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
- •Rheumatic autoimmune disease other than rheumatoid arthritis
- •Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- •Functional class IV (ACR criteria)
- •History of severe allergic reaction to human, humanized or murine monoclonal antibodies
- •Known active current or history of recurrent infection (including tuberculosis)
- •Primary or secondary immunodeficiency (history of or currently active)
- •Body weight >150 kg
- •Previous treatment with any cell-depleting therapies
- •Previous treatment with tocilizumab
- •Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline.
研究组 & 干预措施
Adalimumab + Methotrexate
Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: folate (Drug)
Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: placebo to adalimumab (Drug)
Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: methotrexate (Drug)
Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: folate (Drug)
Adalimumab + Methotrexate
Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: adalimumab (Drug)
Adalimumab + Methotrexate
Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: placebo to tocilizumab (Drug)
Adalimumab + Methotrexate
Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.
干预措施: methotrexate (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 2 to 10. DAS28 Remission is defined as a DAS28 score \<2.6.
次要结局
- Change From Baseline in the Patient Global Assessment of Disease Activity VAS at Week 24(Baseline, Week 24)
- Change From Baseline in the Physician Global Assessment of Disease Activity VAS at Week 24(Baseline, Week 24)
- Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Week 24(Baseline, Week 24)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24(Baseline, Week 24)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline, Week 24)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) Score at Week 24(Baseline, Week 24)
- Change From Baseline in Quality of Life Short Form (SF-36) Score at Week 24(Baseline, Week 24)
- Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 24(Baseline, Week 24)
- Percentage of Participants With ACR50 Response at Week 24(Baseline, Week 24)
- Percentage of Participants With ACR70 Response at Week 24(Baseline, Week 24)
- Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) DAS28 Responses at Week 24(Baseline, Week 24)
- Percentage of Participants With DAS28 Low Disease Activity (LDAS) at Week 24(Week 24)
- Change From Baseline in DAS28 Score at Week 24(Baseline, Week 24)
- Change From Baseline in Swollen Joint Count (SJC) at Week 24(Baseline, Week 24)
- Change From Baseline in Tender Joint Count (TJC) at Week 24(Baseline, Week 24)
- Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS) at Week 24(Baseline, Week 24)
- Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Week 24(Baseline, Week 24)
- Change From Baseline in Hemoglobin at Week 24(Baseline, Week 24)
- Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Discontinuation Due to AEs and Deaths(32 weeks)