MethMax trial

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 21.1Level: LLTClassification code: 10003268Term: Arthritis rheumatoid Class: 10028395; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: CTIS2023-507714-27-00
• Lead Sponsor: Medical University of Vienna

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-18
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 182

Inclusion Criteria

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 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

Exclusion Criteria

Inflammatory rheumatic diseases other than RA, 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 other than TB) as judged by the investigator, Women of childbearing potential without 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 willingness 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, hematologic, 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, Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening), Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion, 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, History of alcohol or substance abuse within the preceding 6 months, Any medical or psychological condition that, judged by the investigator, would interfere with safe completion of the trial, Immunization 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, Active participation in any other interventional study, Use of GC unless on stable oral dose =10mg for at least 4 weeks prior to study inclusion, Patients using NSAIDs, unless taken at a stable dose for =2 weeks prior to study inclusion, 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), Hematologic abnormalities (Grade 2 or 3: Anaemia, Leukopenia, Thrombocytopenia)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the proportion of patients in the Clinical Disease Activity Index (CDAI) remission (=2.8) at week 24.;Secondary Objective: To assess the proportion of patients achieving CDAI low disease activity, American College of Rheumatology scores ACR20%, ACR50%, ACR70%, patient reported outcomes and inflammatory markers across different timepoints. Exploratory objectives include assessment of methotrexate-polyglutamates (MTX-PGs), sweat metabolites, treatment adherence, safety parameters and cumulative glucocorticoid dose;Primary end point(s): 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).