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

Giant Cell Arteritis Clinical Trial

— MTXinGCA  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy of Methotrexate as Remission Maintenance Therapy After Remission-Induction Therapy With Tocilizumab and Glucocorticoids in Subjects With Giant Cell Arteritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05623592
• Other study ID #: MED3-201802
• Secondary ID: EU-CT No: 2022-5
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 23, 2022
• Est. completion date: November 2025

Study information

• Verified date: April 2024
• Source: University of Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

Drug:
• Methotrexate
17,5/15/10 mg Methotrexate subcutaneously
• Sodium chloride
Sodium chloride subcutaneously

Locations

Country	Name	City	State
Germany	Medical Clinic and Polyclinic III Internal medicine Oncology, Hematology University Hospital Bonn, Rheumatology and Clinical Immunology	Bonn

Sponsors (1)

Lead Sponsor	Collaborator
University of Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to relapse during the 12 months treatment period		12 months
Secondary	Cumulative prednisone doses at months 6, 12 and 18		18 months
Secondary	Number of relapses per patient during the 12 months treatment period		12 months
Secondary	Time to first, second and third relapse after randomization		18 months
Secondary	Percentage of patients with a relapse at month 6 and 18 after discontinuation of Tocilizumab		18 months
Secondary	Health-related quality of life: Short Form-36	The possible score ranges from 0 to 100 points, where 0 points represent the greatest possible health limitation, while 100 points represent no health limitation at all	18 months
Secondary	Self-reported fatigue : FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue Scale)	The possible score ranges from 0 to 52 points. The higher this value, the better the quality of life.	18 months
Secondary	Patient Global Assessment of disease activity (PGA)	The possible score ranges from 0 to 100 points, where 0 points represent the lowest disease activity and 100 the highest.	18 months
Secondary	Patient Assessment of pain	The possible score ranges from 0 to 100 points, where 0 points represent the least pain intensity and 100 the most pain intensity	18 months
Secondary	Investigator reported Evaluator Global Assessment of disease activity (EGA)	The possible score ranges from 0 to 100 points, where 0 points represent the lowest disease activity and 100 the highest.	18 months
Secondary	Occurrence of symptoms and signs related to Giant cell arteritis		18 months
Secondary	Number of vasculitic vessels and change of intima-media-values of temporal and axillary arteries		18 months
Secondary	Prevalence of aortitis at baseline and month 12 and 18 in MRI		18 months
Secondary	Proportion of subjects with increased Erythrocyte Sedimentation Rate (>20mm/h) and C-Reactive Protein levels (> 10mg/L)		18 months
Secondary	Occurrence of adverse events and serious adverse events		12 months