MIRACLE (Methotrexate Inadequate Response Patient With Rheumatoid Arthritis Treated by Adalimumab in Combination With Low-dose Methotrexate) Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 24
- 主要终点
- Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS
研究概览
简要总结
This study will be conducted in Japan, South Korea and Taiwan to evaluate the optimal dosage of methotrexate (MTX) as an add-on therapy to adalimumab (ADA) in participants with rheumatoid arthritis (RA) who have not achieved remission by MTX monotherapy.
详细描述
The erythrocyte MTX-polyglutamates (MTX-PG) concentration will be measured to evaluate its relationship to the efficacy and safety of MTX therapy.
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
- •Patients aged ≥18 years (≥20 years in Taiwan) at the time of informed consent
- •Patients who meet the 1987 revised ACR criteria or 2010 ACR/EULAR criteria
- •Patients who have RA within 2 years from initial diagnosis to informed consent
- •Patients who were previously untreated with MTX, JAK inhibitor, or bDMARDs
- •Patients who have disease activity of SDAI >11 at screening
- •Patients who are no need for concomitant use of DMARDs other than hydroxychloroquine (only in South Korea and Taiwan) and study drugs during the study as judged by principal investigator/sub-investigator at screening
- •Patients who are no need for concomitant use of corticoid steroid equivalent to >10 mg/day prednisolone during the study as judged by principal investigator/sub-investigator at screening.
- •Female of child-bearing potential who can use appropriate contraceptive during the study, female in whom time from menopause to informed consent is ≥1 year, or female of no child-bearing potential through sterilization (bilateral tubal ligation, bilateral ovariectomy or hysterectomy, etc.)
- •Virile male who can use appropriate contraceptive during the study
- •Patients who can adequately understand this study procedures, and voluntarily consent in writing to take part in this study (consent of a legally-acceptable representative is also required for patients aged <20 years in Japan and aged <19 years in South Korea)
排除标准
- •Patients who currently have a malignant tumor, except for non-melanoma forms of skin cancer limited within epidermis, and uterine cervix cancer limited within epidermis
- •Patients who have serious infections such as sepsis
- •Patients who have active tuberculosis
- •Patients who have a history or current complication of demyelinating disease such as multiple sclerosis
- •Patients who have congestive heart failure
- •Pregnant female, or female who intend to conceive during the study period
- •Patients who have bone marrow depression and whom investigator considered ineligible
- •Patients who have chronic liver disease and whom investigator considered ineligible, and who is positive for HBs antigen
- •Patients who have nephropathy and whom investigator considered ineligible
- •Lactating female
- •Patients who have pleural effusion or ascites
- •Patients with a known hypersensitivity to MTX or ADA
- •Patients otherwise whom principal investigator/sub-investigator considered medically ineligible to participate in the study
研究组 & 干预措施
ADA/MTX-Maximum Tolerated Dose Group
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
干预措施: Methotrexate (Drug)
MTX-Monotherapy Group
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48.
干预措施: Methotrexate (Drug)
ADA/MTX-Maximum Tolerated Dose Group
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48.
干预措施: Adalimumab (Drug)
ADA/MTX-Reduced Dose Group
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
干预措施: Methotrexate (Drug)
ADA/MTX-Reduced Dose Group
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
干预措施: Adalimumab (Drug)
结局指标
主要结局
Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS
时间窗: Week 48
SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 \[none\] to 10 \[most severe\]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, \> 3.4 to 11 = low disease activity, \> 11 to 26 = moderate disease activity, and \> 26 = high disease activity.
次要结局
- Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in PPS(Week 48)
- American College of Rheumatology (ACR) 20 Response Rate at Week 48(Week 48)
- American College of Rheumatology (ACR) 50 Response Rate at Week 48(Week 48)
- American College of Rheumatology (ACR) 70 Response Rate at Week 48(Week 48)
- Health Assessment Questionnaire - Disability Index ≤0.5 at Week 48(Week 48)
- Change in Modified Total Sharp Score ≤ 0.5 at Week 48(Week 48)
研究者
Yuko Kaneko
Study Principal Investigator
Keio University