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

NCT06649136 | Recruiting Phase 4

• 1 other identifier: MethMax Trial
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 1

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, patient reported outcomes, clinical disease activity, therapy adherence and diverse established and exploratory biomarkers will be assessed.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; methotrexate; therapy adherence; biomarker

Outcome Measures

Primary Outcomes (1)

• CDAI remission (≤2.8) at week 24

  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).

  24 weeks

Secondary Outcomes (15)

• CDAI low disease activity (≤10) at week 24

  24 weeks

• CDAI remission (≤2.8) at week 12

  12 weeks

• CDAI low disease activity (≤10) at week 12

  12 weeks

• ACR20% response at week 24

  24 weeks

• ACR20% response at week 12

  12 weeks

Other Outcomes (7)

• MTX-PGs levels and CDAI response

  week 12 and 24

• Therapeutic drug monitoring (MTX metabolites, TTV)

  week 12 and 24

• Finger sweat analysis

  week 12 and 24

Study Arms (2)

methotrexate 25mg s.c.

ACTIVE COMPARATOR

methotrexate 25mg s.c. weekly dose

Drug: Methotrexate

methotrexate 25mg p.o.

ACTIVE COMPARATOR

methotrexate 25mg p.o. weekly dose

Drug: Methotrexate

Interventions

Methotrexate DRUG

comparison between oral and subcutaneous methotrexate dosis of 25mg

methotrexate 25mg p.o.; methotrexate 25mg s.c.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients with rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria
• 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
• CDAI \> 2.8 + at least 1 clinically swollen joint (on 28-Joint count)
• Willingness to increase methotrexate dosing and change the route of administration according to study procedures

You may not qualify if:

• Inflammatory rheumatic diseases other than RA
• 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
• Intraarticular GC treatment in the last 8 weeks
• Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator
• 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)
• Reduced kidney function (glomerular filtration rate (GFR)\<60)
• Haematologic abnormalities (grade 2 or 3: anaemia, leukopenia, thrombocytopenia)
• Stomatitis under the treatment with MTX
• Known history of recurrent/serious infections in the previous two months (such as, but not limited to, hepatitis, pneumonia, or pyelonephritis)
• A positive HBsAg and/or HCV test at screening visit
• Ongoing or recurring opportunistic infections (e.g., herpes zoster, cytomegalovirus, pneumocystis, aspergillosis, histoplasmosis, or mycobacteria) as judged by the investigator
• 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
• 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
• Being unable or unwilling to undergo multiple venepunctures because of poor tolerability or lack of sufficient venous access
• Being unwilling or unable to perform s.c injections

Sponsors & Collaborators

• Medical University of Vienna: lead
• Leiden University Medical Center: collaborator
• Karolinska Institutet: collaborator
• Queen Mary University of London: collaborator
• Diakonhjemmet Hospital AS: collaborator

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: joint assessor blinding
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical University of Vienna

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 18, 2024
• Study Start: August 12, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)