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

August 31, 2021 updated by: Yuko Kaneko, Keio University

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Methotrexate
Route of Administration: Oral
Other Names:
  • MTX
Experimental: 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.
Drug: Methotrexate
Route of Administration: Oral
Other Names:
  • MTX
Drug: Adalimumab
Route of Administration: Subcutaneous
Other Names:
  • ADA
Experimental: 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.
Drug: Methotrexate
Route of Administration: Oral
Other Names:
  • MTX
Drug: Adalimumab
Route of Administration: Subcutaneous
Other Names:
  • ADA

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Keio University

Collaborators

Eisai Co., Ltd.

Investigators

  • Principal Investigator: Yuko Kaneko, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 18, 2018

Primary Completion (Actual)

May 11, 2021

Study Completion (Anticipated)

June 30, 2022

Study Registration Dates

First Submitted

April 16, 2018

First Submitted That Met QC Criteria

April 16, 2018

First Posted (Actual)

April 20, 2018

Study Record Updates

Last Update Posted (Actual)

September 1, 2021

Last Update Submitted That Met QC Criteria

August 31, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D2E7-C000-401

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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