The PREDMETH trial: Effectiveness of methotrexate versus prednisone as first-line therapy for pulmonary sarcoidosis – A randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

19 Nov 2024 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514055-15-00

EudraCT number

2019-004148-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenomic, Therapy, Efficacy

Investigate the effectiveness and tolerability of methotrexate as firstline therapy in patients with pulmonary sarcoidosis compared with prednisone.

Secondary objectives 3

1. Examine (immunological) biomarkers of disease progression and chronicity.
2. Assess whether response to therapy can be predicted in individual patients
3. Gain more insights into the underlying disease mechanism and potential new targets

Conditions and MedDRA coding

Pulmonary sarcoidosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria (7), in case of absent histology a diagnosis of sarcoidosis can also be established in a multidisciplinary team meeting in a sarcoidosis expert center based on a highly suggestive clinical and radiological picture (18, 19)
2. Age ≥18 years
3. A pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scan conducted within three months before inclusion (determined by the treating physician and conform current guidelines)
4. A forced vital capacity (FVC) of ≤90% of predicted, or a diffusion capacity of the lung for carbon monoxide (DLCO) ≤70% of predicted, or ≥5% FVC decline/≥10% DLCO decline in the past year. For pulmonary functions tests GLI reference values are used.

Exclusion criteria 5

1. Any condition or circumstance that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures
2. Previous immunosuppressive treatment for sarcoidosis
3. Use of systemic immunosuppressive therapy within the preceding three months for another disease than sarcoidosis
4. Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study treatment or within 90 days after the last dose in the randomized study phase. For males; planning to pro-create during the study or within 90 days after the last dose of the randomized study phase.
5. Contra-indication for methotrexate or corticosteroids: • severely impaired renal function (creatinine clearance <30 ml/min) • impaired hepatic function (serum bilirubin-value >5 mg/dl or 85,5 micromole/l) • bone marrow insufficiency with severe leukopenia, thrombocytopenia, or anaemia • severe acute or chronic infections, such as tuberculosis, HIV, parasitic infections or other immunodeficiency syndromes • mouth, stomach or duodenal ulcers

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in hospital-measured Forced Vital Capacity

Secondary endpoints 1

1. Biomarkers

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof. dr. M.S. Wijsenbeek-Lourens

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Ton Boersma

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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