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

NCT05623592 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: MED3-201802EU-CT No: 2022-501058-12-00DRKS-ID: DRKS00030571
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

Keywords

Giant cell arteritis; Methotrexate; Tocilizumab; Glucocorticoids; Remission maintenance; Vasculitis; Rheumatic disease; Ultrasound

Outcome Measures

Primary Outcomes (1)

• Time to relapse during the 12 months treatment period

  12 months

Secondary Outcomes (14)

• Cumulative prednisone doses at months 6, 12 and 18

  18 months

• Number of relapses per patient during the 12 months treatment period

  12 months

• Time to first, second and third relapse after randomization

  18 months

• Percentage of patients with a relapse at month 6 and 18 after discontinuation of Tocilizumab

  18 months

• Health-related quality of life: Short Form-36

  18 months

Study Arms (2)

Methotrexate

EXPERIMENTAL

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.

Drug: Methotrexate

Placebo

PLACEBO COMPARATOR

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.

Drug: Sodium chloride

Interventions

Methotrexate DRUG

17,5/15/10 mg Methotrexate subcutaneously

Methotrexate

Sodium chloride DRUG

Sodium chloride subcutaneously

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Bonn: lead

Study Sites (1)

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

Bonn, Germany

Location

Related Publications (1)

• 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.

  PMID: 38225579 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis; Vasculitis; Rheumatic Diseases

Interventions

Methotrexate; Sodium Chloride

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Musculoskeletal Diseases; Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Valentin S. Schäfer, Dr. med.

  University Hospital of Bonn

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. MuDr.

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 21, 2022
• Study Start: November 23, 2022
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: We plan to share data, if an adequate proposal is submitted

Locations

DE (1)