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

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ClinicalTrials.gov Identifier: NCT03505008
Recruitment Status : Recruiting
First Posted : April 20, 2018
Last Update Posted : January 23, 2019
Sponsor:
Collaborator:
Eisai Co., Ltd.
Information provided by (Responsible Party):
Yuko Kaneko, Keio University

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Methotrexate Drug: Adalimumab Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MIRACLE (Methotrexate Inadequate Response Patient With Rheumatoid Arthritis Treated by Adalimumab in Combination With Low-dose Methotrexate) Study
Actual Study Start Date : April 18, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: MTX

Drug: Adalimumab
Route of Administration: Subcutaneous
Other Name: 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 Name: MTX

Drug: Adalimumab
Route of Administration: Subcutaneous
Other Name: ADA




Primary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03505008


Contacts
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Contact: Hiroya Tamai, MD +81-3-5363-3786 h.tamai@keio.jp

Locations
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Japan
Keio University Recruiting
Tokyo, Japan
Contact: Hiroya Tamai, MD    +81-3-5363-3786    h.tamai@keio.jp   
Sponsors and Collaborators
Keio University
Eisai Co., Ltd.
Investigators
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Principal Investigator: Yuko Kaneko, MD, PhD Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine

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Responsible Party: Yuko Kaneko, Study Principal Investigator, Keio University
ClinicalTrials.gov Identifier: NCT03505008     History of Changes
Other Study ID Numbers: D2E7-C000-401
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yuko Kaneko, Keio University:
Methotrexate
Adalimumab
Autoimmune Disease
Connective Tissue Diseases
Rheumatic Disease
Rheumatoid Arthritis

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents