A Multicenter, Randomized, Double-Period, Double - Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Abbott
- 入组人数
- 1,032
- 试验地点
- 170
- 主要终点
- Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4
研究概览
简要总结
This study compared the safety and efficacy of combination therapy with adalimumab plus methotrexate (MTX) to that of MTX monotherapy (i.e., placebo plus MTX) in subjects with early rheumatoid arthritis (RA).
详细描述
This was a 78-week, multicenter, randomized, double-blind, double-treatment period study designed to compare the safety and efficacy of adalimumab and MTX with placebo and MTX in subjects with early RA. Subjects were randomized to receive adalimumab 40 mg every other week (eow) or placebo subcutaneous injections in combination with orally administered MTX for 26 weeks (Period 1). All subjects in all arms received open-label MTX weekly throughout the study (both Period 1 and Period 2).
At Weeks 22 and 26, subjects were assessed for achievement of low disease activity, defined as a DAS28 score below 3.2. DAS28 is a measure of RA disease activity calculated using the number of tender and swollen joints (out of a total of 28), C-reactive protein level (CRP, a blood marker of inflammation), and the patient's global assessment of disease activity (indicated by marking a 10 cm line between very good and very bad). Subjects who achieved low disease activity at Week 22 and 26 in the adalimumab arm at the end of Period 1 were randomized to receive MTX monotherapy (placebo and MTX) or combination therapy (adalimumab and MTX) in a 1:1 ratio for the duration of Period 2 (52 weeks, i.e., to Week 78 of the study). Subjects achieving low disease activity at Week 22 and 26 in the placebo arm (MTX monotherapy) at the end of Period 1 continued to receive MTX monotherapy (and placebo injections in a blinded fashion) for the duration of Period 2. Subjects failing to achieve low disease activity at Week 22 and 26 at the end of Period 1 received open-label combination therapy during Period 2 regardless of treatment assignment in Period 1.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ADA+MTX/PBO+MTX (Arm 1)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2
干预措施: adalimumab (Biological)
ADA+MTX/PBO+MTX (Arm 1)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2
干预措施: methotrexate (Drug)
ADA+MTX/PBO+MTX (Arm 1)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2
干预措施: placebo (Biological)
ADA+MTX/ADA+MTX (Arm2)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2
干预措施: adalimumab (Biological)
ADA+MTX/ADA+MTX (Arm2)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2
干预措施: methotrexate (Drug)
ADA+MTX/OL ADA+MTX (Arm 3)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2
干预措施: adalimumab (Biological)
ADA+MTX/OL ADA+MTX (Arm 3)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2
干预措施: methotrexate (Drug)
PBO+MTX/PBO+MTX (Arm 4)
Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2
干预措施: methotrexate (Drug)
PBO+MTX/PBO+MTX (Arm 4)
Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2
干预措施: placebo (Biological)
PBO+MTX/OL ADA+MTX (Arm 5)
Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.
干预措施: adalimumab (Biological)
PBO+MTX/OL ADA+MTX (Arm 5)
Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.
干预措施: methotrexate (Drug)
PBO+MTX/OL ADA+MTX (Arm 5)
Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.
干预措施: placebo (Biological)
结局指标
主要结局
Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4
时间窗: Week 78
The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
次要结局
- Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1(Week 78)
- Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78(Week 78)
- Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78(Week 78)
- Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78(Week 78)
- Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78(Week 78)
- Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78(Week 78)
- Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78(Week 78)
- Change From Baseline in DAS28 Score at Week 78(Baseline to Week 78)
- Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78(Week 78)
- Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78(Week 78)
- Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78(Week 78)
- Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78(Week 78)
- Change From Baseline in CDAI Score at Week 78(Baseline to Week 78)
- Change From Baseline in SDAI Score at Week 78(Baseline to Week 78)
- Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78(Baseline to Week 78)
- Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78(Week 78)
- Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78(Week 78)
- Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78(Week 78)