Methotrexate for Rheumatoid arthritis

Inclusion criteria

• {"criterion_text":"- 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\n- Patients with rheumatoid arthritis (RA) according to the 2010 ACR/EULAR classification criteria\n- 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\n- CDAI > 2.8 + at least 1 clinically swollen joint (on 28-Joint count)\n- Willingness to increase methotrexate dosing and change the route of administration according to study procedures"}

Exclusion criteria

• {"criterion_text":"- Inflammatory rheumatic diseases other than RA\n- Stomatitis under the treatment with MTX\n- Known history of recurrent/serious infections in the previous two months (such as, but not limited to, Hepatitis, Pneumonia, or Pyelonephritis)\n- A positive HBsAg and/or HCV test at screening visit\n- Ongoing or recurring opportunistic infections (e.g., Herpes Zoster, Cytomegalovirus, Pneumocystis, Aspergillosis, Histoplasmosis, or Mycobacteria other than TB) as judged by the investigator\n- 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\n- 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\n- Being unable or unwilling to undergo multiple venepunctures because of poor tolerability or lack of sufficient venous access\n- Being unwilling or unable to perform s.c injections\n- Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening)\n- Women who are pregnant, nursing; or planning pregnancy during the study and 6 months after the individual study completion\n- Ongoing or previous therapy with any targeted synthetic DMARDs (tsDMARD) or biological Disease-Modifying Anti-Rheumatic Drug (bDMARD) with the exception of any TNFα inhibitor in a stable dose and interval for at least 4 months; we allow ongoing or previous therapy with a conventional synthetic DMARD (csDMARD) with a stable dose in the past 4 months.\n- History of alcohol or substance abuse within the preceding 6 months\n- Any medical or psychological condition that, judged by the investigator, would interfere with safe completion of the trial\n- 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\n- Active participation in any other interventional study\n- Use of GC unless on stable oral dose ≤10mg for at least 4 weeks prior to study inclusion\n- Patients using NSAIDs, unless taken at a stable dose for ≥2 weeks prior to study inclusion\n- Intraarticular GC treatment in the last 8 weeks\n- Patients with significant and clinically relevant MTX-drug toxicity as judged by the investigator\n- 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)\n- Reduced kidney function (glomerular filtration rate (GFR)<60mL/min/1.73m2)\n- Hematologic abnormalities (Grade 2 or 3: Anaemia, Leukopenia, Thrombocytopenia)"}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"To assess the proportion of patients in the Clinical Disease Activity Index (CDAI) remission (≤2.8) at week 24."}

Secondary endpoints

• {"endpoint_text":"- To assess the proportion of subjects in CDAI low disease activity (≤10) at week 24","definition_or_measurement_approach":"Proportion of subjects achieving CDAI ≤10 at week 24."}
• {"endpoint_text":"- To assess the proportion of subjects in CDAI remission (≤2.8) at week 12","definition_or_measurement_approach":"Proportion of subjects achieving CDAI ≤2.8 at week 12."}
• {"endpoint_text":"- To assess the proportion of subjects in CDAI low disease activity (≤10) at week 12","definition_or_measurement_approach":"Proportion of subjects achieving CDAI ≤10 at week 12."}
• {"endpoint_text":"- To assess the proportion of subjects achieving an ACR20% response at week 24","definition_or_measurement_approach":"Proportion of subjects achieving ACR20 response at week 24."}
• {"endpoint_text":"- To assess the proportion of subjects achieving an ACR20% response at week 12","definition_or_measurement_approach":"Proportion of subjects achieving ACR20 response at week 12."}
• {"endpoint_text":"- To assess the proportion of subjects achieving an ACR50% response at week 24","definition_or_measurement_approach":"Proportion of subjects achieving ACR50 response at week 24."}
• {"endpoint_text":"- To assess the proportion of subjects achieving an ACR50% response at week 12","definition_or_measurement_approach":"Proportion of subjects achieving ACR50 response at week 12."}
• {"endpoint_text":"- To assess the proportion of subjects achieving an ACR70% response at week 24","definition_or_measurement_approach":"Proportion of subjects achieving ACR70 response at week 24."}
• {"endpoint_text":"- To assess the proportion of subjects achieving an ACR70% response at week 12","definition_or_measurement_approach":"Proportion of subjects achieving ACR70 response at week 12."}
• {"endpoint_text":"- Difference in change (absolute and relative) of patient reported outcomes, including pain, patient global assessment, the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F), the 36-Item Short Form Survey version 1 (SF36v1) and the The modified Health Assessment Questionnaire (mHAQ) between the treatment groups between baseline and week 24","definition_or_measurement_approach":"Change from baseline to week 24 in specified patient-reported outcome measures (pain, patient global, FACIT-F, SF36v1, mHAQ), compared between groups."}
• {"endpoint_text":"- Difference in change (absolute and relative) of swollen joint count, tender joint count and C-reactive protein (CRP)/erythrocyte sedimentation rate (ESR) at week 24 between the treatment groups between baseline and week 24","definition_or_measurement_approach":"Change from baseline to week 24 in swollen joint count, tender joint count and CRP/ESR, compared between groups."}
• {"endpoint_text":"- Difference in change (absolute and relative) of patient reported outcomes, including pain, patient global assessment, FACIT-F, SF36v1 and mHAQ between the treatment groups between baseline and week 12","definition_or_measurement_approach":"Change from baseline to week 12 in specified patient-reported outcomes, compared between groups."}
• {"endpoint_text":"- Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 12","definition_or_measurement_approach":"Change from baseline to week 12 in swollen joint count, tender joint count and CRP/ESR."}
• {"endpoint_text":"- exploratory: To explore the association of MTX-PGs levels and CDAI response at week 12 and week 24","definition_or_measurement_approach":"Exploratory association analyses between methotrexate-polyglutamates (MTX-PGs) levels and CDAI response at weeks 12 and 24."}
• {"endpoint_text":"- exploratory: To explore the association of MTX dosage, MTX-PGs levels and torque teno virus titer as a potential marker to guide levels of immunosuppressive therapy at week 12 and week 24","definition_or_measurement_approach":"Exploratory association analyses between MTX dose, MTX-PGs, torque teno virus titer and outcomes at weeks 12 and 24."}
• {"endpoint_text":"- exploratory: Association of MTX-metabolites and inflammatory markers in finger sweat analysis and CDAI at week 12 and week 24","definition_or_measurement_approach":"Exploratory analyses of MTX-metabolites in finger sweat, inflammatory markers and CDAI at weeks 12 and 24."}
• {"endpoint_text":"- exploratory: To explore the difference in cumulative GC dose between treatment arms","definition_or_measurement_approach":"Comparison of cumulative glucocorticoid dose between treatment arms."}
• {"endpoint_text":"- exploratory: To explore the association of CDAI response and treatment adherence as measured by paper-based questionnaires, methotrexate metabolites and electronic adherence monitoring (in patients using the RheumaBuddy mobile app)","definition_or_measurement_approach":"Exploratory association between CDAI response and adherence measured via questionnaires, methotrexate metabolites and electronic monitoring (RheumaBuddy users)."}
• {"endpoint_text":"- exploratory: To explore the differences in safety profile according to number of adverse events and organ systems (haematologic, hepatic, gastrointestinal, infections)","definition_or_measurement_approach":"Comparison of safety profiles by number and organ-system categorization of adverse events between arms."}
• {"endpoint_text":"- exploratory: To explore the trajectories of disease activity in the two groups over all visits, and its relation to predictors","definition_or_measurement_approach":"Exploratory analysis of longitudinal disease activity trajectories across visits and relation to predictors."}

Austria

Earliest CTIS Part Ii Submission Date

26-03-2024

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

503

Number Of Sites

1

Number Of Participants

62

Netherlands

Earliest CTIS Part Ii Submission Date

15-03-2024

Latest Decision Or Authorization Date

06-08-2025

Processing Time Days

509

Number Of Sites

1

Number Of Participants

30

Norway

Earliest CTIS Part Ii Submission Date

21-03-2024

Latest Decision Or Authorization Date

07-08-2025

Processing Time Days

504

Number Of Sites

1

Number Of Participants

30

Sweden

Earliest CTIS Part Ii Submission Date

26-03-2024

Latest Decision Or Authorization Date

06-08-2025

Processing Time Days

498

Number Of Sites

1

Number Of Participants

30

Romania

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

442

Number Of Sites

1

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

26-06-2024

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

506

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Medical University of Vienna

Organisation Type

Educational Institution

Country Of Registered Address

Austria

Third parties

• {"country":"Austria","full_name":"Medical University Of Vienna","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Educational Institution"}