EncompaSSc: Evaluation of MTX-474 in Participants With Diffuse Cutaneous Systemic Sclerosis (dcSSc)

NCT07287670 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MTX-474-S2012025-523288-39
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Diffuse Cutaneous Systemic Sclerosis

Keywords

MTX-474-S201; MTX-474; Diffuse Cutaneous Systemic Sclerosis; dcSSc participants; dcSSc; Adult; mRSS; EncompaSSc; monoclonal antibody; EphrinB2

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Modified Rodnan Skin Score (mRSS)

  Mean change from baseline to week 24 in the modified Rodnan Skin Score, a clinician-assessed measure of skin thickness across 17 body areas. Unit of measure: Score (range 0-51)

  Baseline to week 24

Secondary Outcomes (8)

• Proportion of participants with a gene signature response in skin biopsy

  12 weeks

• Number of participants with clinically significant findings on physical examination, vital signs, and clinical laboratory tests

  Baseline through end of study (week 28)

• Number of participants with dose interruptions or treatment discontinuations due to adverse events

  Baseline through end of study (week 28)

• Safety and tolerability of MTX-474 in participants with dcSSc: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs)

  Baseline through end of study (week 28)

• Serum concentration of MTX-474 at sparse PK time points

  Baseline to week 28

Other Outcomes (16)

• Proportion of participants with a response on the revised American College of Rheumatology Composite Response Index in Systemic Sclerosis (rACR-CRISS)

  Baseline to week 24

• Change from baseline in Physician Global Assessment (PhGA) of disease status

  Baseline to week 24

• Change from baseline in Patient Global Assessment (PtGA) of disease status

  Baseline to week 24

Study Arms (2)

MTX-474

EXPERIMENTAL

MTX-474

Biological: MTX-474

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

MTX-474 BIOLOGICAL

Dosage level: 4 mg/kg Unit dose strength: 50mg/ml MTX-474 is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds the human EphrinB2 with high specificity and high affinity. MTX-474 is being developed as a therapy for patients with systemic sclerosis (SSc).

MTX-474

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of diffuse cutaneous systemic sclerosis, classified according to 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR)
• Participant is either:
• Within 2 years of their first non-Raynaud's symptom and their mRSS is \>7; OR
• \>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
• \>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 pp10
• 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.
• 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

You may not qualify if:

• Concomitantly have another serious medical illness, which, in the opinion of the Investigator, would interfere with the participant's ability to complete the study
• Participant is currently on immunosuppressive therapy, systemic glucocorticoids or other antifibrotic agents detailed as follows:
• 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)
• 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
• 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)
• Current use of PAH medication (endothelin receptor antagonists, prostacyclin analogues, soluble guanylate cyclase stimulators) excluding calcium channel blockers and phosphodiesterase-5 inhibitors
• Pregnant or currently breastfeeding
• Aspartate transaminase (AST) or alanine transaminase (ALT) \>2.0 upper limit of normal
• Creatinine clearance \<45mL/min
• History of myocardial infarction, angina or congestive heart failure
• International normalized ratio \>2 or partial thromboplastin time \>1.5 × upper limit of normal

Sponsors & Collaborators

• Mediar Therapeutics: lead

Study Sites (5)

EncompaSSc site in Newport Beach, CA 92663

Newport Beach, California, 92663, United States

RECRUITING

EncompaSSc site in Clearwater, FL 33765

Clearwater, Florida, 33765, United States

RECRUITING

EncompaSSc site in Tampa, FL

Tampa, Florida, 33606, United States

RECRUITING

EncompaSSc site in Baltimore, MD

Baltimore, Maryland, 21224, United States

RECRUITING

EncompaSSc site in Boston, MA

Boston, Massachusetts, 02118, United States

RECRUITING

MeSH Terms

Conditions

Scleroderma, Diffuse

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Central Study Contacts

Jeffrey Bornstein, MD

CONTACT

(617) 936-0960; jeffrey@mediartx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 17, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)