Clinical trial NCT05623592: Methotrexate as Remission Maintenance Therapy After Remission-Induction With Tocilizumab and Glucocorticoids in Giant Cell Arteritis
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Giant Cell Arteritis
Keywords: Giant cell arteritis
Methotrexate
Tocilizumab
Glucocorticoids
Remission maintenance
Vasculitis
Rheumatic disease
Ultrasound
Lead sponsor: University of Bonn
Sponsor class: OTHER
First posted: 2022-11-21
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time to relapse during the 12 months treatment period
timeFrame: 12 months
Secondary outcomes:
measure: Cumulative prednisone doses at months 6, 12 and 18
timeFrame: 18 months
measure: Number of relapses per patient during the 12 months treatment period
timeFrame: 12 months
measure: Time to first, second and third relapse after randomization
timeFrame: 18 months
measure: Percentage of patients with a relapse at month 6 and 18 after discontinuation of Tocilizumab
timeFrame: 18 months
measure: Health-related quality of life: Short Form-36
timeFrame: 18 months
measure: Self-reported fatigue : FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue Scale)
timeFrame: 18 months
measure: Patient Global Assessment of disease activity (PGA)
timeFrame: 18 months
measure: Patient Assessment of pain
timeFrame: 18 months
measure: Investigator reported Evaluator Global Assessment of disease activity (EGA)
timeFrame: 18 months
measure: Occurrence of symptoms and signs related to Giant cell arteritis
timeFrame: 18 months
measure: Number of vasculitic vessels and change of intima-media-values of temporal and axillary arteries
timeFrame: 18 months
measure: Prevalence of aortitis at baseline and month 12 and 18 in MRI
timeFrame: 18 months
measure: Proportion of subjects with increased Erythrocyte Sedimentation Rate (>20mm/h) and C-Reactive Protein levels (> 10mg/L)
timeFrame: 18 months
measure: Occurrence of adverse events and serious adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Medical Clinic and Polyclinic III Internal medicine Oncology, Hematology University Hospital Bonn, Rheumatology and Clinical Immunology
Study officials:
affiliation: University Hospital of Bonn
name: Valentin S. Schäfer, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: