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 (MTXinGCA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rheinische Friedrich Wilhelms Universität Bonn

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

23 Nov 2022 → 2 Oct 2025

Decision date (initial)

2022-08-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess efficacy of metex® on sustained remission of GCA

Secondary objectives 9

1. 1. To assess the need for rescue therapy with prednisone
2. 2. To assess the number of flares/relapse during maintenance therapy with metex®
3. 3. To evaluate the impact of metex® maintenance therapy on patient reported outcomes
4. 4. To evaluate the impact of metex® maintenance therapy on investigator reported outcomes
5. 5. To assess impact of metex® maintenance thera-py on the visual symptoms and other ischemic complications related to GCA
6. 6. To assess the vasculitic involvement and change of intima-media-values of temporal and axillary arteries in patients with/without flares
7. 7. Influence of study treatment on patients with aortitis in MRI of the aorta
8. 8. To analyse the influence of study treatment on local and systemic inflammation
9. 9. To evaluate the safety of methotrexate

Conditions and MedDRA coding

Giant cell arteritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Subjects male or female, aged ≥18 years
2. 2. Written informed consent of the capable subject for voluntary participation in the study.
3. 3. Diagnosis of GCA as confirmed by the investigator fulfilment (also in retro-spect) of the proposed extended 1990 classification criteria for GCA.
4. 4. Previous treatment with glucocorticoids and tocilizumab for new or relapsing GCA
5. 5. 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.
6. 6. Total tocilizumab therapy should have been at least 6 months before inclusion.
7. 7. Patients should be in stable remission (defined as the absence of signs or symptoms of GCA and normal CRP <1mg/dl), off glucocorticoids for at least 1 months at screening.
8. 8. Willing and able to inject methotrexate or placebo subcutaneously at randomization
9. 9. Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential)

Exclusion criteria 8

1. 1. Severe renal (glomerular filtration rate <30/min) failure
2. 2. Conditions other than GCA requiring continuous or intermittent treatment with oral or parenteral Glucocorticoids (GCs) unless the last exposure to GCs was >1 months before screening
3. 3. Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
4. 4. Current treatment with any other conventional, biologic or targeted synthet-ic DMARD except tocilizumab
5. 5. Elevation of transaminases above three times the norm
6. 6. 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.
7. 7. Pregnant or breast feeding women
8. 8. Contraindications for therapy with metex®, as indicated in the summary of product characteristics

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to relapse during the 12 months treatment period

Secondary endpoints 9

1. 1. Cumulative prednisone doses at months 6, 12 and 18
2. 2. Number of flares per patient during the 12 months treatment period, Time to first, second and third relapse after randomization, Percentage of patients with a relapse at month 6 and 18 after discontinuation of tocilizumab
3. 3. Patient reported outcomes including SF-36, FACIT-Fatigue, Patient Global Assessment of Disease Activity (PGA), Patient assessment of pain
4. 4. Investigator reported outcomes including Eval-uator Global Assessment of disease activity (EGA)
5. 5. Occurrence of symptoms and signs related to GCA
6. 6. Number of vasculitic vessels and change of intima-media-values during the study
7. 7. Prevelance of aortitis at baseline and month 12 and 18
8. 8. Proportion of subjects with increased ESR (>20mm/h) and CRP levels (> 10mg/L) at every visit
9. 9. Occurrence of adverse events and serious adverse events, incidence of glucocorticoid-related adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rheinische Friedrich Wilhelms Universität Bonn

Sponsor organisation

Rheinische Friedrich Wilhelms Universität Bonn

Address

Venusberg-Campus 1, Venusberg Venusberg

City

Bonn

Postcode

53127

Country

Germany

Scientific contact point

Organisation

Rheinische Friedrich Wilhelms Universität Bonn

Contact name

PD Dr. med. Valentin S. Schäfer

Public contact point

Organisation

Rheinische Friedrich Wilhelms Universität Bonn

Contact name

PD Dr. med. Valentin S. Schäfer

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Application history

1 submissions — initial application plus substantial / non-substantial modifications