Methotrexate as Remission Maintenance Therapy After Remission-Induction With Tocilizumab and Glucocorticoids in Giant Cell Arteritis

NCT ID: NCT05623592

Last Updated: 2024-04-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-23
• Study Completion Date: 2025-11-30

Brief Summary

The standard treatment for Giant Cell arteritis (GCA) is Glucocorticoids(GC), even if GC-related adverse events are commonly occuring. Therefore, other practises for reducing relapses and cumulative GC-doses are needed. Currently, the Interleukin-6-inhibitor tocilizumab is used in combination with GC to achieve higher remission rates and lower cumulative GC-doses. The use of tocilizumab also has some disadvantages. One is the increased susceptibility to infections. On top of that, a long-term follow-up of the phase II study by Villiger et al. showed a 55% relapse-rate after discontinuation of intravenous tocilizumab after a median of five months.

Studies have also shown that methotrexate(MTX) in combination with GC was able to prevent relapses and reduce cumulative GC doses.

The aim of the study is to evaluate whether MTX is superior to placebo to prevent relapses in subjects with GCA after Remission-Induction Therapy with Glucocorticoids and Tocilizumab. Our hypothesis is that Methotrexate can maintain remission, once stable remission has been induced by GC and Tocilizumab and will prevent the occurrence of relapses.

Conditions

Giant Cell Arteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Methotrexate

The patient will be treated for 12 months weekly with methotrexate. Methotrexate will be provided at a dose of 17.5mg as a pre-filled syringe for self-injection. A dose reduction to 15 mg/week in case of intolerance, elevated liver enzymes \>3x upper limit of normal or to 10 mg/week if glomerular filtration rate \<50/min will be possible. If glomerular filtration rate \<30/min, termination of treatment.

Group Type: EXPERIMENTAL

Methotrexate

Intervention Type: DRUG

17,5/15/10 mg Methotrexate subcutaneously

Placebo

Patients receive sodium chloride as a placebo subcutaneously. It will be administered in the form of a pre-filled syringe for self-injection once a week for 12 months.

Group Type: PLACEBO_COMPARATOR

Sodium chloride

Intervention Type: DRUG

Sodium chloride subcutaneously

Interventions

Methotrexate

17,5/15/10 mg Methotrexate subcutaneously

Intervention Type: DRUG

Sodium chloride

Sodium chloride subcutaneously

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects male or female, aged ≥18 years
• Written informed consent of the capable subject for voluntary participation in the study.
• Diagnosis of GCA as confirmed by the investigator fulfilment (also in retrospect) of the proposed extended 1990 classification criteria for GCA .
• Previous treatment with glucocorticoids and tocilizumab for new or relapsing GCA
• GCA patients who have been treated with tocilizumab and in whom discontinuation of tocilizumab therapy has been decided by the treating rheumatologist, within standard treatment at the department of rheumatology are eligible.
• total tocilizumab therapy should have been at least 6 months before inclusion.
• Patients should be in stable remission (defined as the absence of signs or symptoms of GCA and normal C-Reactive Protein (<1mg/dl), off glucocorticoids for at least 1 months at screening.
• Willing and able to inject methotrexate or placebo subcutaneously at randomization
• Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential)

Exclusion Criteria

• Severe renal (glomerular filtration rate <30/min) failure
• Conditions other than GCA requiring continuous or intermittent treatment with oral or parenteral Glucocorticoids unless the last exposure to Glucocorticoids was >1 months before screening
• Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
• Current treatment with any other conventional, biologic or targeted synthetic DMARD except tocilizumab
• Elevation of transaminases above three times the norm
• Simultaneous participation in another clinical trial, or participation in a clinical trial taking an investigational product, up to 30 days prior to participation in this clinical trial.
• Pregnant or breast feeding women
• Contraindications for therapy with Methotrexate, as indicated in the summary of product characteristics

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bonn

OTHER

Sponsor Role: lead

Responsible Party

Valentin Schäfer

PD Dr. med. MuDr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Valentin S. Schäfer, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Bonn

Locations

Medical Clinic and Polyclinic III Internal medicine Oncology, Hematology University Hospital Bonn, Rheumatology and Clinical Immunology

Bonn, , Germany

Countries

Germany

References

Kreis L, Dejaco C, Schmidt WA, Nemeth R, Venhoff N, Schafer VS. The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis-study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study. Trials. 2024 Jan 15;25(1):56. doi: 10.1186/s13063-024-07905-4.

Reference Type: DERIVED

PMID: 38225579 (View on PubMed)

Other Identifiers

EU-CT No: 2022-501058-12-00

Identifier Type: OTHER

Identifier Source: secondary_id

DRKS-ID: DRKS00030571

Identifier Type: OTHER

Identifier Source: secondary_id

MED3-201802

Identifier Type: -

Identifier Source: org_study_id