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

Phase 2
Active, not recruiting
Conditions
Interventions
Registration Number
NCT05623592
Lead Sponsor
University of Bonn
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-...

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
52
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)
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MethotrexateMethotrexateThe 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.
PlaceboSodium chloridePatients 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.
Primary Outcome Measures
NameTimeMethod
Time to relapse during the 12 months treatment period12 months
Secondary Outcome Measures
NameTimeMethod
Cumulative prednisone doses at months 6, 12 and 1818 months
Self-reported fatigue : FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue Scale)18 months

The possible score ranges from 0 to 52 points. The higher this value, the better the quality of life.

Number of relapses per patient during the 12 months treatment period12 months
Time to first, second and third relapse after randomization18 months
Percentage of patients with a relapse at month 6 and 18 after discontinuation of Tocilizumab18 months
Health-related quality of life: Short Form-3618 months

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

Patient Global Assessment of disease activity (PGA)18 months

The possible score ranges from 0 to 100 points, where 0 points represent the lowest disease activity and 100 the highest.

Investigator reported Evaluator Global Assessment of disease activity (EGA)18 months

The possible score ranges from 0 to 100 points, where 0 points represent the lowest disease activity and 100 the highest.

Prevalence of aortitis at baseline and month 12 and 18 in MRI18 months
Patient Assessment of pain18 months

The possible score ranges from 0 to 100 points, where 0 points represent the least pain intensity and 100 the most pain intensity

Occurrence of symptoms and signs related to Giant cell arteritis18 months
Occurrence of adverse events and serious adverse events12 months
Number of vasculitic vessels and change of intima-media-values of temporal and axillary arteries18 months
Proportion of subjects with increased Erythrocyte Sedimentation Rate (>20mm/h) and C-Reactive Protein levels (> 10mg/L)18 months

Trial Locations

Locations (1)

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

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Bonn, Germany

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