Skip to main content
OpenTrials
Completed

NCT Number: NCT03505008

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Fujita Health University Hospital, Aichi, Japan

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

methotrexate

Drug

Route of Administration: Oral

Other names: MTX

Adalimumab

Drug

Route of Administration: Subcutaneous

Other names: ADA

Primary outcomes

  1. Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS

    Time frame: Week 48

    SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL).

    Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.

Secondary outcomes

  1. Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in PPS

    Time frame: Week 48

    SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL).

    Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.

  2. American College of Rheumatology (ACR) 20 Response Rate at Week 48

    Time frame: Week 48

    ACR 20 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 20 response will be referred to as ACR 20 response rate.

    • ≥20% improvement in the tender joint count (of the total 68 joints) compared to Week 0 of treatment
    • ≥20% improvement in the swollen joint count (of the total 66 joints) compared to Week 0 of treatment
    • ≥20% improvement in ≥3 of 5 parameters (physician- and patient-reported disease activities, patient-reported pain score, HAQ, and CRP) compared to Week 0 of treatment

  3. American College of Rheumatology (ACR) 50 Response Rate at Week 48

    Time frame: Week 48

    ACR 50 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 50 response will be referred to as ACR 50 response rate.

    • ≥50% improvement in the tender joint count (of the total 68 joints) compared to Week 0 of treatment
    • ≥50% improvement in the swollen joint count (of the total 66 joints) compared to Week 0 of treatment
    • ≥50% improvement in ≥3 of 5 parameters (physician- and patient-reported disease activities, patient-reported pain score, HAQ, and CRP) compared to Week 0 of treatment

  4. American College of Rheumatology (ACR) 70 Response Rate at Week 48

    Time frame: Week 48

    ACR 70 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 70 response will be referred to as ACR 70 response rate.

    • ≥70% improvement in the tender joint count (of the total 68 joints) compared to Week 0 of treatment
    • ≥70% improvement in the swollen joint count (of the total 66 joints) compared to Week 0 of treatment
    • ≥70% improvement in ≥3 of 5 parameters (physician- and patient-reported disease activities, patient-reported pain score, HAQ, and CRP) compared to Week 0 of treatment

  5. Health Assessment Questionnaire - Disability Index ≤0.5 at Week 48

    Time frame: Week 48

    HAQ-DI is a patient-reported questionnaire, consists of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week as: without any difficulty (0); with some difficulty (1); with much difficulty (2); unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0=no disability and 3=very severe, high-dependency disability. Normal physical function is defined by HAQ-DI score of < 0.5.

  6. Change in Modified Total Sharp Score ≤ 0.5 at Week 48

    Time frame: Week 48

    Bone erosions will be evaluated for each region from a scale of 0 (no damage) to 5 (complete collapse of the joint). The score will be 0 to 5 for each hand joint, and 0 to 10 for each foot joint. The maximum total erosion score of both hands will be 160 points, and that of both feet will be 120 points.

    Joint space narrowing will be evaluated for each region from a scale of 0 (no damage) to 4 (ankylosis or luxation). The maximum total joint space narrowing score of both hands will be 120 points, and that of both feet will be 48 points.

    Erosion scores and joint space narrowing scores were added to obtain the mTSS (range from 0 to 448).

Sponsors and collaborators

Lead sponsor

Keio University

Other

Collaborators

  • Eisai Co., Ltd.

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Apr 20, 2018
Registry last updated
Mar 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.