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)
Diagnosis of diffuse cutaneous systemic sclerosis, classified according to 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR)
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.
Concomitantly have another serious medical illness, which, in the opinion of the Investigator, would interfere with the participant's ability to complete the study
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)
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.)
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
Parallel
MTX-474
Biological/VaccineDosage 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).
Placebo
Other interventionPlacebo
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)
Proportion of participants with a gene signature response in skin biopsy
Proportion of participants in each arm (MTX-474 and placebo) demonstrating a dcSSc gene expression signature response on skin biopsy at Week 12. Unit of Measure: Participants (%)
Number of participants with clinically significant findings on physical examination, vital signs, and clinical laboratory tests
Number of participants with clinically significant findings on physical examination, vital signs, and clinical laboratory tests Unit of Measure: Participants (%)
Number of participants with dose interruptions or treatment discontinuations due to adverse events
Number of participants with dose interruptions or treatment discontinuations due to adverse events Unit of Measure: Participants (%)
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)
Incidence, seriousness, and severity of TEAEs and TRAEs as determined by investigator assessment. Unit of measure: Participants (%)
Proportion of participants with a response on the revised American College of Rheumatology Composite Response Index in Systemic Sclerosis (rACR-CRISS)
Proportion of participants achieving rACR-CRISS composite response Unit of Measure: Participants (%)
Change from baseline in Physician Global Assessment (PhGA) of disease status
Mean change from baseline to week 24 in the physician global assessment (phGA) of disease status in each arm Unit of Measure: Units on 0-10 visual analog scale (higher score = worse disease)
Change from baseline in Patient Global Assessment (PtGA) of disease status
Mean change from baseline to week 24 in the patient global assessment (PtGA) of disease status in each arm Unit of Measure: Units on 0-10 visual analog scale (higher score = worse disease)
Change from baseline in percent predicted forced vital capacity (FVCpp)
Mean change from baseline to week 24 on percent predicted forced vital capacity (FVCpp) Unit of Measure: Percent predicted (%)
Click on the lead sponsor to view all of their trials.
