MethMax trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University of Vienna, Diakonhjemmet Sykehus AS, Academisch Ziekenhuis Leiden, Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

20 Jun 2024 → ongoing

Decision date (initial)

2024-04-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Horizon Europe, SQUEEZE project

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To assess the proportion of patients in the Clinical Disease Activity Index (CDAI) remission (≤2.8) at week 24.

Secondary objectives 1

1. 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

Conditions and MedDRA coding

Rheumatoid Arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 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 23

1. Inflammatory rheumatic diseases other than RA
2. 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.
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)<60mL/min/1.73m2)
9. Hematologic 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 other than TB) as judged by the investigator
14. 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
15. 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
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. 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
23. Active participation in any other interventional study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 20

1. To assess the proportion of subjects in CDAI low disease activity (≤10) at week 24
2. To assess the proportion of subjects in CDAI remission (≤2.8) at week 12
3. To assess the proportion of subjects in CDAI low disease activity (≤10) at week 12
4. To assess the proportion of subjects achieving an ACR20% response at week 24
5. To assess the proportion of subjects achieving an ACR20% response at week 12
6. To assess the proportion of subjects achieving an ACR50% response at week 24
7. To assess the proportion of subjects achieving an ACR50% response at week 12
8. To assess the proportion of subjects achieving an ACR70% response at week 24
9. To assess the proportion of subjects achieving an ACR70% response at week 12
10. 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
11. 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
12. 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
13. Difference in change (absolute and relative) of swollen joint count, tender joint count and CRP/ESR between baseline and week 12
14. exploratory: To explore the association of MTX-PGs levels and CDAI response at week 12 and week 24
15. 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
16. exploratory: Association of MTX-metabolites and inflammatory markers in finger sweat analysis and CDAI at week 12 and week 24
17. exploratory: To explore the difference in cumulative GC dose between treatment arms
18. 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)
19. exploratory: To explore the differences in safety profile according to number of adverse events and organ systems (haematologic, hepatic, gastrointestinal, infections)
20. exploratory: To explore the trajectories of disease activity in the two groups over all visits, and its relation to predictors

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University of Vienna

Sponsor organisation

Medical University of Vienna

Address

Waehringer Guertel 18-20, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University of Vienna

Contact name

Division of Rheumatology

Public contact point

Organisation

Medical University of Vienna

Contact name

Division of Rheumatology

Third parties 1

Diakonhjemmet Sykehus AS

Sponsor organisation

Diakonhjemmet Sykehus AS

Address

Diakonveien 12

City

Oslo

Postcode

0370

Country

Norway

Scientific contact point

Organisation

Diakonhjemmet Sykehus AS

Contact name

Clinic for rheumatology, polyclinic and research - Unit for clinical research

Public contact point

Organisation

Diakonhjemmet Sykehus AS

Contact name

Clinic for rheumatology, polyclinic and research - Unit for clinical research

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Department of Rheumatology

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Department of Rheumatology

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Aikaterini Chatzidionysiou

Public contact point

Organisation

Karolinska University Hospital

Contact name

Aikaterini Chatzidionysiou

Sponsor responsibilities

Article 77 compliance

Medical University of Vienna

Contact point sponsor

Medical University of Vienna

Article 77 implementation

Medical University of Vienna

Locations

6 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications