Evaluation of the Optimal MTX Dose as an Add-on Therapy to Adalimumab for RA Patients in Japan, South Korea and Taiwan

Study Overview
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Brief Summary
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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.

Detailed Description
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The erythrocyte MTX-polyglutamates (MTX-PG) concentration will be measured to evaluate its relationship to the efficacy and safety of MTX therapy.

Official Title
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MIRACLE (Methotrexate Inadequate Response Patient With Rheumatoid Arthritis Treated by Adalimumab in Combination With Low-dose Methotrexate) Study

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MTX-Monotherapy Group<br>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. | Drug: Methotrexate<br>* Route of Administration: Oral<br>* Other names: MTX;|
| Experimental: ADA/MTX-Maximum Tolerated Dose Group<br>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. | Drug: Methotrexate<br>* Route of Administration: Oral<br>* Other names: MTX;Drug: Adalimumab<br>* Route of Administration: Subcutaneous<br>* Other names: ADA;|
| Experimental: ADA/MTX-Reduced Dose Group<br>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. | Drug: Methotrexate<br>* Route of Administration: Oral<br>* Other names: MTX;Drug: Adalimumab<br>* Route of Administration: Subcutaneous<br>* Other names: ADA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simple Disease Activity Index (SDAI) Remission Rate | SDAI Remission Rate at Week 48 in ADA/MTX-Maximum Tolerated Dose Group and ADA/MTX-Reduced Dose Group | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methotrexate, Adalimumab, Autoimmune Disease, Connective Tissue Diseases, Rheumatic Disease, Rheumatoid Arthritis