Evaluation of MTX-474 in Participants with Diffuse Cutaneous Systemic Sclerosis (dcSSc)

Trial details

Who runs it

Mediar Therapeutics Inc.

Trial code

EU 2025-523288-39-00

Record updated

2026. október 14.

Original description

To assess the change from Baseline on skin thickeningRead full original descriptionShow less

A Phase 2 Randomized, Double-blind, Placebo-Controlled Study to Assess the Safety and Efficacy of MTX-474 in the Treatment of Participants with Diffuse Cutaneous Systemic Sclerosis (dcSSc)

To assess the change from Baseline on skin thickening

Inclusion: Diagnosis of diffuse cutaneous systemic sclerosis, classified according to 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria; All participants with reproductive potential must agree to use and follow medically approved, highly effective methods of contraception during treatment and until 5 half-lives or 125 days after the last dose, whichever is longer; Participant is either: a. Within 2 years of their first non-Raynaud’s symptom and their mRSS is >7; OR b. >2 and ≤5 years from their first non-Raynaud’s symptom, their mRSS is between 10 and 30, they are negative for the RNA polymerase 3 autoantibody, and (1) they have never had any previous spontaneous improvement in skin thickening of ≥4 points by mRSS on exams performed by the same clinician, or (2) they were never clinically noted to have a meaningful spontaneous reduction in skin thickness if mRSS was never done; OR c. >5 and ≤10 years from their first non-Raynaud’s symptom, their mRSS is between >15 and ≤25, they are negative for the RNA polymerase 3 autoantibody, and (1) they have never had any previous spontaneous improvement in skin thickening of ≥4 points by mRSS, or (2) were never clinically noted to have a meaningful spontaneous reduction in skin thickness if mRSS was never done; Participant is ≥18 years of age at time of signing the ICF; Able to understand the study and provide a signed, written ICF; Able to read and understand the language of the ICF and other study-related materials; Forced vital capacity (FVCpp) of ≥45; Have diffusing capacity of the lungs for carbon monoxide (DLCO) of ≥30 percent predicted at Screening; Willing and able to complete all protocol-required study visits and procedures; Participants of childbearing potential must have a negative serum pregnancy test at Screening.

Exclusion: History of clinically significant thrombotic event within 12 months prior to Screening; Positive anticentromere antibody; Systemic sclerosis renal crisis within 12 months prior to Screening; Major surgery within 8 weeks prior to Screening or planned surgery during study period; Currently receiving another experimental agent or participating in another clinical trial. If a participant has recently received another experimental agent, then the last dose must have been at least 5 half-lives or 30 days (whichever is longer) prior to Screening; Participant is currently on immunosuppressive therapy, systemic glucocorticoids or other antifibrotic agents detailed as follows: a. Immunosuppresive agents: Cyclophosphamide (IV or oral if used in the 6 months prior to Screening), calcineurin inhibitors (if used in the 30 days prior to Screening), azathioprine (if used in the 30 days prior to Screening), Janus-kinase inhibitors (if used in the 30 days prior to Screening), rituximab (if used in the 6 months prior to Screening), tocilizumab (if used in the 60 days prior to Screening) or any other biologic Disease-Modifying Antirheumatic Drugs (DMARD, if used in the last 30 days or 3 half-lives prior to Screening, whichever is longer) b. Antifibrotic agents: nintedanib or pirfenidone (if used in the 30 days prior to Screening). Also, exclusionary if used within 3 months of Screening are tyrosine-kinase inhibitors with recognized anti-fibrotic activity (imatinib, nilotinib, etc.) c. Systemic glucocorticoids: equivalent doses of prednisone greater than 10 mg/day (≤10 mg/day allowed). Has received any pulse intramuscular (IM) or intravenous (IV) steroid within 1 month of Screening d. Other agents: i. mycophenolate mofetil unless on a stable dose for at least 6 months prior to Screening and there are no plans to adjust the dose during the study; ii. mycophenolic acid unless on a stable dose for at least 6 months prior to Screening and there are no plans to adjust the dose during the study; iii. hydroxychloroquine unless on a stable dose for at least 3 months prior to Screening and there are no plans to adjust the dose during the study; and iv. methotrexate unless on a stable dose for at least 3 months prior to Screening and there are no plans to adjust the dose during the study; Previous or planned hematopoietic stem cell or solid organ transplantation; Previous treatment with chimeric antigen receptor (CAR)-T/CAR-NK therapy; Clinically significant PAH as determined by the Investigator at, or prior to first day of dosing (Baseline); Concomitantly have another serious medical illness, which, in the opinion of the Investigator, would interfere with the participant’s ability to complete the study; Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; Confirmed diagnosis of overlap syndrome, systemic lupus erythematosus with anti-double strand (ds)DNA antibody, rheumatoid arthritis with anti-cyclic citrullinated peptide (anti-CCP) antibody, or systemic sclerosis mimics (eosinophilic fasciitis, scleromyxedema) at the time of inclusion in the study; Known malignancy or history of malignancy within 5 years of Screening other than non-melanoma skin cancer and in situ cervical cancer; History of myocardial infarction, angina or congestive heart failure; Creatinine clearance <45mL/min; Current use of PAH medication (endothelin receptor antagonists, prostacyclin analogues, soluble guanylate cyclase stimulators) excluding calcium channel blockers and phosphodiesterase-5 inhibitors; Aspartate transaminase (AST) or alanine transaminase (ALT) >2.0 upper limit of normal; International normalized ratio >2 or partial thromboplastin time >1.5 × upper limit of normal; Unable to routinely access veins for blood draws and IV infusions; Pregnant or currently breastfeeding.

EU CTIS 2025-523288-39-00