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

Keio University

Status and phase: Unknown; Phase 4

Conditions: Rheumatoid Arthritis

Treatments: Drug: Adalimumab; Drug: Methotrexate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03505008

D2E7-C000-401

Details and patient eligibility

About

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.

Full description

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

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 3 patient groups

MTX-Monotherapy Group

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

ADA/MTX-Maximum Tolerated Dose Group

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

Drug: Adalimumab

ADA/MTX-Reduced Dose Group

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

Drug: Adalimumab