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

October 17, 2024 updated by: Helga Lechner-Radner, Medical University of Vienna

An International, Multicentre, Interventional, Randomised, Assessor-blinded Trial to MAXimise the METHotrexate Therapy Potential in Patients with Active Rheumatoid Arthritis

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 by sufficient dose and route optimisation. Furthermore, individual factors effecting the treatment response are unknown. Thus, we aim to evaluate the "maximised methotrexate therapy" before switching to biologic or targeted synthetic drugs.

The MethMax trial is a prospective, randomised, assessor-blinded, parallel-group, low-intervention trial, including 182 patients across 7 European countries. Patients with active rheumatoid arthritis, naïve to biologic or targeted synthetic antirheumatic drugs, who have been on a stable oral methotrexate therapy for the past 3 months will be randomised in 1:1 ratio to either 25mg oral or 25mg subcutaneous methotrexate weekly. In both arms, a short glucocorticoid therapy will be prescribed at baseline visit. The active study duration for each patient is 24 weeks. After inclusion, study visits take place at baseline, weeks 4, 8, 12, 16 and 24. The clinical efficacy and safety parameters will be obtained at each visit. At predefined timepoints, further patient reported outcomes, exploratory biomarkers like sweat and blood metabolites, as well as medication adherence will be assessed. Written consent will be obtained for all participants. The study has received regulatory approval via the Clinical Trials Information System and has recently started recruitment at the first centre.

The anticipated results will suggest whether the subcutaneous administration of 25mg methotrexate weekly is superior to oral methotrexate 25mg and lower doses in each route respectively. The outcomes include clinical disease activity, methotrexate metabolism analyses and medication adherence. The gained knowledge could lead to individual therapy optimisation and new therapy recommendations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
182

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: methotrexate 25mg s.c.
methotrexate 25mg s.c. weekly dose
Drug: Methotrexate
comparison between oral and subcutaneous methotrexate dosis of 25mg
Active Comparator: methotrexate 25mg p.o.
methotrexate 25mg p.o. weekly dose
Drug: Methotrexate
comparison between oral and subcutaneous methotrexate dosis of 25mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
CDAI remission (≤2.8) at week 24
Time Frame: 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).
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
CDAI low disease activity (≤10) at week 24
Time Frame: 24 weeks
To assess the proportion of patients in CDAI low disease activity (≤10) at week 24
24 weeks
CDAI remission (≤2.8) at week 12
Time Frame: 12 weeks
To assess the proportion of patients in CDAI remission (≤2.8) at week 12
12 weeks
CDAI low disease activity (≤10) at week 12
Time Frame: 12 weeks
To assess the proportion of patients in CDAI low disease activity (≤10) at week 12
12 weeks
ACR20% response at week 24
Time Frame: 24 weeks
To assess the proportion of patients achieving an ACR20% response at week 24
24 weeks
ACR20% response at week 12
Time Frame: 12 weeks
To assess the proportion of patients achieving an ACR20% response at week 12
12 weeks
ACR50% response at week 24
Time Frame: 24 weeks
To assess the proportion of patients achieving an ACR50% response at week 24
24 weeks
ACR50% response at week 12
Time Frame: 12 weeks
To assess the proportion of patients achieving an ACR50% response at week 12
12 weeks
ACR70% response at week 24
Time Frame: 24 weeks
To assess the proportion of patients achieving an ACR70% response at week 24
24 weeks
ACR70% response at week 12
Time Frame: 12 weeks
To assess the proportion of patients achieving an ACR70% response at week 12
12 weeks
Patient reported outcomes on NRS
Time Frame: 24 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
24 weeks
Patient reported outcomes on NRS
Time Frame: 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
12 weeks
Quality of Life questionnaires
Time Frame: 24 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
24 weeks
Quality of Life questionnaires
Time Frame: 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
12 weeks
Joint count and inflammatory markers
Time Frame: 24 weeks
Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 24
24 weeks
Joint count and inflammatory markers
Time Frame: 12 weeks
Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 12
12 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
MTX-PGs levels and CDAI response
Time Frame: week 12 and 24
Association of MTX-PGs levels and CDAI response at week 12 and week 24
week 12 and 24
Therapeutic drug monitoring (MTX metabolites, TTV)
Time Frame: week 12 and 24
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
week 12 and 24
Finger sweat analysis
Time Frame: week 12 and 24
Association of MTX-metabolites and inflammatory markers in finger sweat analysis and CDAI at week 12 and week 24
week 12 and 24
Cumulative glucocorticoid dose
Time Frame: 24 weeks
Difference in cumulative glucocorticoid (GC) dose between treatment arms
24 weeks
Treatment adherence
Time Frame: 24 weeks
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)
24 weeks
Safety profile
Time Frame: 24 weeks
Differences in safety profile according to number of adverse events and organ systems (haematologic, hepatic, gastrointestinal, infections)
24 weeks
Trajectories of disease activity
Time Frame: 24 weeks
Trajectories of disease activity in the two groups over all visits, and its relation to predictors
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Vienna

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Karolinska Institutet
Queen Mary University of London
Leiden University Medical Center
Diakonhjemmet Hospital AS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 12, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 18, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MethMax Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

upon reasonable request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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