Clinical trial NCT03505008: Evaluation of the Optimal MTX Dose as an Add-on Therapy to Adalimumab for RA Patients in Japan, South Korea and Taiwan
Official title: MIRACLE (Methotrexate Inadequate Response Patient With Rheumatoid Arthritis Treated by Adalimumab in Combination With Low-dose Methotrexate) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate
Adalimumab
Autoimmune Disease
Connective Tissue Diseases
Rheumatic Disease
Rheumatoid Arthritis
Lead sponsor: Keio University
Sponsor class: OTHER
Collaborators: name: Eisai Co., Ltd.
First posted: 2018-04-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Patients aged ≥18 years (≥20 years in Taiwan) at the time of informed consent
2. Patients who meet the 1987 revised ACR criteria or 2010 ACR/EULAR criteria
3. Patients who have RA within 2 years from initial diagnosis to informed consent
4. Patients who were previously untreated with MTX, JAK inhibitor, or bDMARDs
5. Patients who have disease activity of SDAI \>11 at screening
6. 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
7. 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.
8. 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.)
9. Virile male who can use appropriate contraceptive during the study
10. 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:

1. 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
2. Patients who have serious infections such as sepsis
3. Patients who have active tuberculosis
4. Patients who have a history or current complication of demyelinating disease such as multiple sclerosis
5. Patients who have congestive heart failure
6. Pregnant female, or female who intend to conceive during the study period
7. Patients who have bone marrow depression and whom investigator considered ineligible
8. Patients who have chronic liver disease and whom investigator considered ineligible, and who is positive for HBs antigen
9. Patients who have nephropathy and whom investigator considered ineligible
10. Lactating female
11. Patients who have pleural effusion or ascites
12. Patients with a known hypersensitivity to MTX or ADA
13. Patients otherwise whom principal investigator/sub-investigator considered medically ineligible to participate in the study

Primary outcomes:
measure: Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS
timeFrame: Week 48
Secondary outcomes:
measure: Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in PPS
timeFrame: Week 48
measure: American College of Rheumatology (ACR) 20 Response Rate at Week 48
timeFrame: Week 48
measure: American College of Rheumatology (ACR) 50 Response Rate at Week 48
timeFrame: Week 48
measure: American College of Rheumatology (ACR) 70 Response Rate at Week 48
timeFrame: Week 48
measure: Health Assessment Questionnaire - Disability Index ≤0.5 at Week 48
timeFrame: Week 48
measure: Change in Modified Total Sharp Score ≤ 0.5 at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kanagawa
country: Japan
facility: Kawasaki Municipal Hospital
city: Kanagawa
country: Japan
facility: Tokai University Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Shizuoka
country: Japan
facility: Seirei Hamamatsu General Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo Medical Center
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo
country: Japan
facility: Toho University Ohashi Medical Center
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine
name: Yuko Kaneko, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: