An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (Cp-690,550) On Magnetic Resonance Imaging Endpoints, In Methotrexate Naive Subjects With Early Active Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 109
- 试验地点
- 38
- 主要终点
- Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis
研究概览
简要总结
Evaluation of efficacy and safety of tofacitinib (CP-690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment.
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 with moderate to severe early rheumatoid arthritis (< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.
排除标准
- •Pregnant or lactating patients;
- •Patients with renal or hepatic impairment or other severe or progressing disease;
- •Patients with contraindication to magnetic resonance imaging with gadolinium contrast.
研究组 & 干预措施
Tofacitinib (CP 690,550) 10 mg BID plus MTX
干预措施: Tasocitinib plus Methotrexate (Drug)
Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX
干预措施: Tofacitinib plus placebo methotrexate (Drug)
Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk
干预措施: Placebo tofacitinib plus Methotrexate (Drug)
结局指标
主要结局
Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis
时间窗: Month 3
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. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.
Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema
时间窗: Month 6
Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.
次要结局
- Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response(Months 1, 2, 3, 6, 9, and 12)
- Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement)(Months 1, 2, 3, 6, 9, and 12)
- Percentage of Participants With DAS28-4 (ESR) ≤3.2(Months 1, 2, 3, 6, 9, and 12)
- Percentage of Participants With DAS28-4 (ESR) <2.6(Months 1, 2, 3, 6, 9, and 12)
- Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions(Months 1, 3, 6, and 12)
- Modified Total Sharp Score (mTSS) at Months 6 and 12(Months 6 and 12)
- Percentage of Participants With an ACR 50% Improvement (ACR50) Response(Months 1, 2, 3, 6, 9, and 12)
- Percentage of Participants With DAS28-3 (CRP) Score ≤3.2(Months 1, 2, 3, 6, 9, and 12)
- Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis(Months 1, 6, and 12)
- Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP(Months 1, 3, and 12)
- Change From Baseline to Months 6 and 12 in JSN Scores(Months 6 and 12)
- Erosion Scores at Months 6 and 12(Months 6 and 12)
- Percentage of Participants With an ACR 70% Improvement (ACR70) Response(Months 1, 2, 3, 6, 9, and 12)
- Change From Baseline to Months 6 and 12 in mTSS(Months 6 and 12)
- Joint Space Narrowing (JSN) Scores at Months 6 and 12(Months 6 and 12)
- Change From Baseline to Months 6 and 12 in Erosion Score(Months 6 and 12)
- Change From Baseline in DAS28-3 (CRP)(Months 1, 2, 3, 6, 9, and 12)
- Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP])(Baseline and Months 1, 2, 3, 6, 9, and 12)
- Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement)(Months 1, 2, 3, 6, 9, and 12)
- Percentage of Participants With DAS28-3 (CRP) Score <2.6(Months 1, 2, 3, 6, 9, and 12)
- Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR])(Baseline and Months 1, 2, 3, 6, 9, and 12)
- Change From Baseline in DAS28-4 (ESR)(Months 1, 2, 3, 6, 9, and 12)