A Multicenter, Double-Blind, Randomized, Parallel-Arm Study to Determine the Effect of Methotrexate Dose on Clinical Outcome and Ultrasonographic Signs in Subjects With Moderately to Severely Active Rheumatoid Arthritis Treated With Adalimumab (MUSICA)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 309
- 试验地点
- 49
- 主要终点
- Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at Week 24
研究概览
简要总结
This study will investigate the efficacy of both low and high doses of methotrexate (MTX) in combination with open-label adalimumab (ADA) in patients who have had an inadequate response to high dose of MTX. The study will also evaluate the pharmacokinetics and safety of the two regimens of MTX in combination with ADA in participants with rheumatoid arthritis (RA).
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 subjects with moderately to severely active rheumatoid arthritis
- •Subjects must have a DAS28(CRP) (Disease Activity Score using C-Reactive Protein) greater than or equal to 3.2 at baseline (there is no minimum CRP score required to qualify)
- •Subjects must have at least 5/68 tender joints plus 5/66 swollen joints assessed at screening or baseline
- •Subject must treated with and MTX (methotrexate) dose (oral and/or injectable) of 15 mg or more per week (no upper limit on dose) for at least 12 weeks prior to screening
- •Subject is either biologic-naïve or has only one prior biologic disease-modifying antirheumatic drug (i.e. abatacept, anakinra, certolizumab, etanercept, golimumab, infliximab, or tocilizumab)
排除标准
- •Previous exposure to adalimumab (Humira), rituximab (Rituxan), natalizumab (Tysabri), efalizumab (Raptiva)
- •Subject has been treated with intra-articular or parenteral administration of corticosteroids within 4 weeks of screening
- •Subject has diagnosis or history of gout or pseudogout
- •Subject has undergone joint surgery within 12 weeks of screening (at joints to be assessed by ultrasound)
- •Subject has history of chronic arthritis diagnosed before age 16 years
研究组 & 干预措施
Adalimumab + Low Dose Methotrexate
Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, low dose methotrexate (7.5 mg orally once weekly).
干预措施: Adalimumab (Biological)
Adalimumab + Low Dose Methotrexate
Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, low dose methotrexate (7.5 mg orally once weekly).
干预措施: Methotrexate (Drug)
Adalimumab + High Dose Methotrexate
Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, high dose methotrexate (20 mg orally once weekly).
干预措施: Adalimumab (Biological)
Adalimumab + High Dose Methotrexate
Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, high dose methotrexate (20 mg orally once weekly).
干预措施: Methotrexate (Drug)
结局指标
主要结局
Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at Week 24
时间窗: Week 24
The DAS28(CRP) score includes 28 tender joint counts, 28 swollen joint counts, C-reactive protein, and participant's global assessment of disease activity. Scores on the DAS28(CRP) range from 0 to 10. A DAS28(CRP) score ≥ 5.1 indicates high disease activity, and a DAS28(CRP) score \< 2.6 indicates clinical remission. Least squares means and 95% CI were from 2-way ANCOVA model with effects for baseline DAS28(CRP) value, treatment group, and prior methotrexate dose group.
次要结局
- Percentage of Participants With American College of Rheumatology 50% (ACR50) Criteria Response at Week 24(Baseline, 24 weeks)
- Percentage of Participants With American College of Rheumatology 70% (ACR70) Criteria Response at Week 24(Baseline, 24 weeks)
- Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) ≤ -0.22 at Week 24(Baseline, 24 weeks)
- Percent Change From Baseline in Medical Outcomes Study Version II (MOS) Sleep Problem Index 9 at Week 24(Baseline, 24 weeks)
- Percentage of Participants With Power Doppler Ultrasound (PD U/S) Score for Synovial Vascularity Improvement by 30% at Week 24(Baseline, 24 weeks)