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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03505008
• Other study ID #: D2E7-C000-401
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: April 18, 2018
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2021
• Source: Keio University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: June 30, 2022
• Est. primary completion date: May 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Route of Administration: Oral
• Adalimumab
Route of Administration: Subcutaneous

Locations

Country	Name	City	State
Japan	Fujita Health University Hospital	Aichi
Japan	Chiba University Hospital	Chiba
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kawasaki Municipal Hospital	Kanagawa
Japan	Tokai University Hospital	Kanagawa
Japan	Tohoku University Hospital	Miyagi
Japan	Nagoya University Hospital	Nagoya
Japan	Seirei Hamamatsu General Hospital	Shizuoka
Japan	Keio University Hospital	Tokyo
Japan	National Hospital Organization Tokyo Medical Center	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Japan	Toho University Ohashi Medical Center	Tokyo
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Seoul Metropolitan Government Seoul National University Boramae Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Taiwan	Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital	Taoyuan

Sponsors (2)

Lead Sponsor	Collaborator
Keio University	Eisai Co., Ltd.

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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