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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mediar Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-06-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Mediar Therapeutics

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacogenetic, Pharmacokinetic, Efficacy, Safety

To assess the change from Baseline on skin thickening

Secondary objectives 3

1. To assess the safety and tolerability of MTX-474 in participants with dcSSc
2. To assess the effect of MTX-474 on dcSSc gene expression signature
3. To assess the pharmacokinetics (PK) of MTX-474 in participants with dcSSc

Conditions and MedDRA coding

Diffuse Cutaneous Systemic Sclerosis (dcSSc)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Diagnosis of diffuse cutaneous systemic sclerosis, classified according to 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria
2. 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.
3. Participant is ≥18 years of age at time of signing the ICF.
4. Able to understand the study and provide a signed, written ICF
5. Able to read and understand the language of the ICF and other study-related materials
6. Forced vital capacity (FVCpp) of ≥45
7. Have diffusing capacity of the lungs for carbon monoxide (DLCO) of ≥30 percent predicted at Screening
8. Willing and able to complete all protocol-required study visits and procedures
9. Participants of childbearing potential must have a negative serum pregnancy test at Screening.
10. 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

Exclusion criteria 20

1. Concomitantly have another serious medical illness, which, in the opinion of the Investigator, would interfere with the participant’s ability to complete the study
2. History of myocardial infarction, angina or congestive heart failure
3. 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.
4. Previous or planned hematopoietic stem cell or solid organ transplantation
5. Previous treatment with chimeric antigen receptor (CAR)-T/CAR-NK therapy
6. Clinically significant PAH as determined by the Investigator at, or prior to first day of dosing (Baseline)
7. Current use of PAH medication (endothelin receptor antagonists, prostacyclin analogues, soluble guanylate cyclase stimulators) excluding calcium channel blockers and phosphodiesterase-5 inhibitors
8. Pregnant or currently breastfeeding
9. Aspartate transaminase (AST) or alanine transaminase (ALT) >2.0 upper limit of normal
10. Creatinine clearance <45mL/min
11. International normalized ratio >2 or partial thromboplastin time >1.5 × upper limit of normal
12. Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
13. History of clinically significant thrombotic event within 12 months prior to Screening
14. Positive anticentromere antibody
15. Systemic sclerosis renal crisis within 12 months prior to Screening
16. 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
17. Known malignancy or history of malignancy within 5 years of Screening other than non-melanoma skin cancer and in situ cervical cancer
18. Major surgery within 8 weeks prior to Screening or planned surgery during study period
19. Unable to routinely access veins for blood draws and IV infusions
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from Baseline to Week 24 on the modified Rodnan skin score (mRSS) in each study arm.

Secondary endpoints 4

1. Incidence, seriousness, and severity of AEs, TEAEs, SAEs, and treatment-related adverse events (TRAEs)
2. Clinically significant findings on physical examination, vital signs, and clinical laboratory tests.
3. Proportion of participants in each arm with a gene signature response on skin biopsy at Week 12.
4. Sparse and serial PK profiles after MTX-474 administration to participants will be evaluated by population PK, based on drug concentrations in serum over time. For a subset of participants with serial PK sampling, noncompartmental PK parameters (CL, t1/2, and AUCs) will be reported.

Investigational products

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

Test 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mediar Therapeutics Inc.

Sponsor organisation

Mediar Therapeutics Inc.

Address

20 Overland Street Suite 520

City

Boston

Postcode

02215-3336

Country

United States

Scientific contact point

Organisation

Mediar Therapeutics Inc.

Contact name

Mediar Clinical Study Information

Public contact point

Organisation

Mediar Therapeutics Inc.

Contact name

Mediar Clinical Study Information

Third parties 11

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 13 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