A Randomized, Double-blind, Placebo-controlled Study to Assess Efficacy of Tocilizumab+Non-biological DMARD in Reducing Synovitis as Measured by MRI at 12 Weeks After Initiation of Treatment in Patients With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Non-biological DMARDs
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 54
- 主要终点
- Percent Change From Baseline to Week 12 in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score
研究概览
简要总结
This randomized, double-blind, placebo-controlled study will use Magnetic Resonance Imaging (MRI) to assess the efficacy of tocilizumab plus non-biological DMARD in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to non-biological DMARDS. Patients will be randomized to receive either intravenous tocilizumab at 8mg/kg (minimal dose 480mg, maximum dose 800mg) or placebo every 4 weeks, in addition to their stable dose of non-biological DMARD. Anticipated time on study treatment is 24 weeks, and target sample size is <100.
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 —（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 rheumatoid arthritis of >/=6 months duration
- •synovitis (swollen and tender joint) in the wrist of the dominant hand
- •non-biologic DMARDs at stable dose for >/=12 weeks prior to baseline
- •oral corticosteroids at stable dose for at least 25 out of 28 days prior to baseline
排除标准
- •rheumatic autoimmune disease other than RA
- •history of or current inflammatory joint disease other than RA
- •functional class IV (ACR classification)
- •intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
- •previous treatment with a biologic agent for RA
研究组 & 干预措施
1
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
1
干预措施: non-biological DMARDs (Drug)
2
干预措施: placebo (Drug)
2
干预措施: non-biological DMARDs (Drug)
结局指标
主要结局
Percent Change From Baseline to Week 12 in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score
时间窗: Week 12
Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th metacarpophalangeal (MCP) were assessed for synovitis via magnetic resonance imaging (MRI) and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.
次要结局
- Change From Baseline to Week 12 in 17 Hydroxy Progesterone (17OHP)(Week 12)
- Percent Change From Baseline to Week 12 in OMERACT RAMRIS Score(Week 12)
- Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Score(Week 12)
- Percent Change From Baseline to Week 24 in OMERACT RAMRIS Score(Week 24)
- Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Score(Week 24)
- Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score(Week 12)
- Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score(Week 24)
- Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score(Week 12)
- Absolute Change From Baseline to Week 12 in DCE-MRI EER Wrist Score(Week 12)
- Change From Baseline to Week 24 in Patient Global Assessment of Pain(Week 24)
- Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score(Week 12)
- Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score(Week 24)
- Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score(Week 24)
- Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score(Week 12)
- Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score(Week 12)
- Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score(Week 24)
- Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score(Week 24)
- Percent Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score(Week 12)
- Absolute Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score(Week 12)
- Percent Change From Baseline to Week 24 in DCE-MRI EER Global Score(Week 24)
- Absolute Change From Baseline to Week 24 in DCE-MRI EER Global Score(Week 24)
- Percent Change From Baseline to Week 12 in DCE-MRI EER MCP Score(Week 12)
- Absolute Change From Baseline to Week 12 in DCE-MRI EER MCP Score(Week 12)
- Change From Baseline to Week 12 in Patient Global Assessment of Pain(Week 12)
- Percent Change From Baseline to Week 24 in DCE-MRI EER MCP Score(Week 24)
- Change From Baseline to Week 24 in Serum Cortisol(Week 24)
- Absolute Change From Baseline to Week 24 in DCE-MRI EER MCP Score(Week 24)
- Percent Change From Baseline to Week 12 in DCE-MRI EER Wrist Score(Week 12)
- Change From Baseline to Week 12 in Plasma Adrenocorticotrophic Hormone (ACTH)(Week 12)
- Change From Baseline to Week 24 in Plasma ACTH(Week 24)
- Percent Change From Baseline to Week 24 in DCE-MRI EER Wrist Score(Week 24)
- Absolute Change From Baseline to Week 24 in DCE-MRI EER Wrist Score(Week 24)
- Disease Activity Score Based on 28-Joint Count (DAS28)(Baseline, Weeks 12 and 24)
- Change From Baseline to Week 12 in DAS28 Global Score(Week 12)
- Change From Baseline to Week 24 in DAS28 Global Score(Week 24)
- Tender and Swollen Joint Counts(Weeks 12 and 24)
- Change From Baseline to Week 12 in TJC(Week 12)
- Change From Baseline to Week 24 in TJC(Week 24)
- Change From Baseline to Week 12 in SJC(Week 12)
- Change From Baseline to Week 24 in SJC(Week 24)
- Change From Baseline to Week 12 in Patient Global Assessment of Disease Activity(Week 12)
- Change From Baseline to Week 24 in Patient Global Assessment of Disease Activity(Week 24)
- Patient Global Assessment of Pain(Baseline, Weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline to Week 12 in Serum Androstenedione(Week 12)
- Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores(Baseline, Weeks 12 and 24)
- Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR)(Week 12)
- Change From Baseline to Week 24 in ESR(Week 24)
- Change From Baseline to Week 12 in C-Reactive Protein (CRP)(Week 12)
- Change From Baseline to Week 24 in CRP(Week 24)
- Change From Baseline to Week 12 in Serum Cortisol(Week 12)
- Change From Baseline to Week 24 in Serum Androstenedione(Week 24)
- Change From Baseline to Week 24 in 17OHP(Week 24)
- Change From Baseline to Week 12 in Serum Dehydroepiandrosterone (DHEA)(Week 12)
- Change From Baseline to Week 24 in Serum DHEA(Week 24)
- Change From Baseline to Week 12 in Neuropeptide Y(Week 12)
- Change From Baseline to Week 24 in Neuropeptide Y(Week 24)