MethMax Trial: MAXimising the METHotrexate Therapy Potential in Patients with Active Rheumatoid Arthritis

Phase 4

Recruiting

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Methotrexate

• Registration Number: NCT06649136
• Lead Sponsor: Medical University of Vienna

Brief Summary

The MethMax trial is a prospective, international, multicentre, randomised, assessor-blinded, parallel-group, low intervention study. Patients with active rheumatoid arthritis treated with oral methotrexate up to 25mg weekly will be randomised in 50:50 fashion to receive 25mg oral vs subcutaneous methotrexate for the period of 24 weeks. In regular visits, pa...

Detailed Description

Methotrexate is recommended as the first-line therapy in patients with rheumatoid arthritis. However, a significant proportion of patients does not achieve disease remission with methotrexate monotherapy, which can be attributed to multiple reasons. We hypothesize, that the efficacy limitations of this well-known medication can be, to some extent, overcome b...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2024-08-12
• Status Verified: 2024-10
• Study First Submitted: 2024-10-15
• Study First Submitted QC: 2024-10-17
• Last Update Submitted: 2024-10-17
• Study First Posted: 2024-10-18
• Last Update Posted: 2024-10-18
• Primary Completion: 2026-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 182

Inclusion Criteria

1. Men and women, ≥ 18 years of age, capable of understanding and signing an informed consent (including sufficient literacy and proficiency in the local language) and following the study procedures
2. Patients with rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria
3. Ongoing conventional therapy with oral methotrexate (between ≥10mg and 25mg weekly) for ≥3 months with stable dosing, and clinical and laboratory tolerance of this treatment for at least 12 weeks
4. CDAI > 2.8 + at least 1 clinically swollen joint (on 28-Joint count)
5. Willingness to increase methotrexate dosing and change the route of administration according to study procedures

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Exclusion Criteria

1. Inflammatory rheumatic diseases other than RA
2. Ongoing or previous therapy with any biological DiseaseModifying Anti-Rheumatic Drug (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) or conventional synthetic DMARDs (csDMARDs) other than methotrexate and hydroxychloroquine
3. Use of GC unless on stable oral dose ≤10mg for at least 4 weeks prior to study inclusion
4. Patients using NSAIDs, unless taken at a stable dose for ≥2 weeks prior to study inclusion
5. Intraarticular GC treatment in the last 8 weeks
6. Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator
7. Elevated liver enzymes (aspartate transaminase (ASAT) and/or alanine transaminase (ALAT)), and/or alkaline phosphatase (AP), and/or gamma-glutamyl transferase (GGT) above 2x the upper limit normal (ULN)
8. Reduced kidney function (glomerular filtration rate (GFR)<60)
9. Haematologic abnormalities (grade 2 or 3: anaemia, leukopenia, thrombocytopenia)
10. Stomatitis under the treatment with MTX
11. Known history of recurrent/serious infections in the previous two months (such as, but not limited to, hepatitis, pneumonia, or pyelonephritis)
12. A positive HBsAg and/or HCV test at screening visit
13. Ongoing or recurring opportunistic infections (e.g., herpes zoster, cytomegalovirus, pneumocystis, aspergillosis, histoplasmosis, or mycobacteria) as judged by the investigator
14. Women of childbearing potential without the use of adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) and willing to continue this precaution for the duration of the study until 6 months after receiving the last medication
15. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease, as judged by the investigator
16. Being unable or unwilling to undergo multiple venepunctures because of poor tolerability or lack of sufficient venous access
17. Being unwilling or unable to perform s.c injections
18. Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening)
19. Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion
20. History of alcohol or substance abuse within the preceding 6 months
21. Any medical or psychological condition that, judged by the investigator, would interfere with safe completion of the trial
22. Immunisation with a live/attenuated vaccine within 12 weeks prior to baseline or potential need to receive a live vaccine during the course of the study
23. Active participation in any other interventional study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
methotrexate 25mg s.c.	Methotrexate	methotrexate 25mg s.c. weekly dose
methotrexate 25mg p.o.	Methotrexate	methotrexate 25mg p.o. weekly dose

Primary Outcome Measures

Name	Time	Method
CDAI remission (≤2.8) at week 24	24 weeks	The primary endpoint is the achievement of remission defined as the CDAI ≤2.8 assessed 24 weeks after randomisation comparing patients with dose/route optimization (≥10mg MTX oral weekly switched to 25mg MTX subcutaneously weekly) and oral dose optimization (≥10mg MTX oral weekly switched to 25mg MTX oral weekly).

Secondary Outcome Measures

Name	Time	Method
CDAI low disease activity (≤10) at week 24	24 weeks	To assess the proportion of patients in CDAI low disease activity (≤10) at week 24
CDAI remission (≤2.8) at week 12	12 weeks	To assess the proportion of patients in CDAI remission (≤2.8) at week 12
CDAI low disease activity (≤10) at week 12	12 weeks	To assess the proportion of patients in CDAI low disease activity (≤10) at week 12
ACR20% response at week 24	24 weeks	To assess the proportion of patients achieving an ACR20% response at week 24
ACR20% response at week 12	12 weeks	To assess the proportion of patients achieving an ACR20% response at week 12
ACR50% response at week 24	24 weeks	To assess the proportion of patients achieving an ACR50% response at week 24
ACR50% response at week 12	12 weeks	To assess the proportion of patients achieving an ACR50% response at week 12
ACR70% response at week 24	24 weeks	To assess the proportion of patients achieving an ACR70% response at week 24
ACR70% response at week 12	12 weeks	To assess the proportion of patients achieving an ACR70% response at week 12
Patient reported outcomes on NRS	12 weeks	Difference in change (absolute and relative) of patient reported outcomes on numeric response scale (NRS), including pain, patient global assessment, and joint stiffness between the treatment groups between baseline and week 24
Quality of Life questionnaires	12 weeks	Difference in change (absolute and relative) of patient reported outcomes measured by questionnaires: 1. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F); 2. the 36-Item Short Form Survey version 1 (SF36v1); 3. The Health Assessment Questionnaire Disability Index (HAQ-DI) between the treatment groups between baseline and week 12
Joint count and inflammatory markers	12 weeks	Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 12

Trial Locations

Locations (1)

Medical University of Vienna; 🇦🇹 Vienna, Austria