Diffuse Cutaneous Systemic SclerosisPhase 2NCT07287670
EncompaSSc: Evaluation of MTX-474 in Participants With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
A Phase 2 study testing MTX-474 in people with Diffuse Cutaneous Systemic Sclerosis, run by Mediar Therapeutics at 58 sites in 10 countries.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Cutaneous Systemic Sclerosis
- What is being tested?
- MTX-474
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 58 sitesin 10 countries
- Study dates
- 16 Apr 2026to Dec 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
- 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
- Other agents:
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- 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
- Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- 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
- 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
- Major surgery within 8 weeks prior to Screening or planned surgery during study period
- Unable to routinely access veins for blood draws and IV infusions
- 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
- History of myocardial infarction, angina or congestive heart failure
Trial locations and contacts
58 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
58 sites in 10 countries
United States23 sites, 23 recruiting
- Recruiting
Stryde Research - DFW
Allen, Texas, 75013
Moraima Avalos, 617-802-6568, patients@stryderesearch.com
John Lavery
- Recruiting
University of Colorado Center for Lungs/Breathing/Scleroderma Clinic
Aurora, Colorado, 80045
Chong Pedrick, 617-802-6568, CHONG.PEDRICK@CUANSCHUTZ.EDU
Melissa Griffith
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21205
Gwen Leatherman, 617 802 6568, gleathe1@jh.edu
Laura Hummers
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Joyce Shen, 617-802-6568, jshen0@bwh.harvard.edu
Avery LaChance
- Recruiting
Boston Medical Center
Boston, Massachusetts, 02118
Kimberly Finch, 617 802 6568, kimtobin@bu.edu
Andreea Bujor
- Recruiting
NYU Langone Health
Brooklyn, New York, 11201
Debra London, 617-802-6568, Debra.London@nyulangone.org
David Goddard
- Recruiting
Clinical Research of West Florida
Clearwater, Florida, 33765
Amber Tipker, 617 802 6568, atipker@crwf.com
Rodney Daniel
- Not yet recruiting
EncompaSSc site in Cleveland, OH
Cleveland, Ohio, 44195
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Recruiting
Baylor Scott & White Research Institute
Dallas, Texas, 75246
Felicia Padilla, 617-802-6568, felicia.padilla@bswhealth.org
Susan Mathai
- Not yet recruiting
EncompaSSc site in Houston, TX
Houston, Texas, 77030
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Kansas City, KS
Kansas City, Kansas, 66103
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in La Jolla, CA
La Jolla, California, 92037
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Loma Linda, CA
Loma Linda, California, 92350
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Recruiting
University of California Los Angeles Scleroderma Center
Los Angeles, California, 90095
Nahal Ghanoongooi, 617-802-6568, nghanoongooi@mednet.ucla.edu
Elizabeth Volkmann
- Not yet recruiting
EncompaSSc site in Minneapolis, MN
Minneapolis, Minnesota, 55455
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Recruiting
NewportNativeMD, Inc.
Newport Beach, California, 92663
Jennifer Gonzolez, 617 802 6568, jennifer@newportnativemd.com
Ryan Klein
- Recruiting
The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Tiffany Moore, 405-271-3480, OSCTR@ouhsc.edu
Aikaterini Thanou
- Not yet recruiting
EncompaSSc site in Palo Alto, CA
Palo Alto, California, 94304
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Philadelphia, PA
Philadelphia, Pennsylvania, 19107
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Phoenix, AZ
Phoenix, Arizona, 85054
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15219
UPMC, 617-802-6568, kal128@pitt.edu
Christina Padilla
- Recruiting
Sarasota Arthritis Center
Sarasota, Florida, 34239
Research Department, 1-941-365-0770 ext:1052, research@arthritiscenters.net
Jesse Boodoo
- Recruiting
Clinical Research of West Florida
Tampa, Florida, 33606
Michelle Villela, 617 802 6568, mvillela@crwf.com
John Carter
France6 sites, 6 recruiting
- Not yet recruiting
EncompaSSc site in La Tronche, France
La Tronche, 38700
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Montpellier, France
Montpellier, 34090
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Paris, France
Paris, 75014
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Strasbourg, France
Strasbourg, 67000
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Toulouse, France
Toulouse, 31059
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Vandœuvre-lès-Nancy, France
Vandœuvre-lès-Nancy, 54500
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Italy6 sites, 6 recruiting
- Not yet recruiting
EncompaSSc site in Ancona, Italy
Ancona, 60126
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Catania, Italy
Catania, 95123
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Genoa, Italy
Genoa, 16132
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Milan, Italy
Milan, 20122
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Modena, Italy
Modena, 41124
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Roma, Italy
Roma, 00128
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Spain5 sites, 5 recruiting
- Not yet recruiting
EncompaSSc site in Barcelona, Spain
Barcelona, 08003
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Barcelona, Spain
Barcelona, 08025
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Córdoba, Spain
Córdoba, 14004
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Malaga, Spain
Málaga, 29004
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Valencia, Spain
Valencia, 46026
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Poland4 sites, 4 recruiting
- Not yet recruiting
EncompaSSc site in Bydgoszcz, Poland
Bydgoszcz, 85-168
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Nowa Sól, Poland
Nowa Sól, 67-100
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Warszawa, Poland
Warsaw, 00-874
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Warszawa, Poland
Warsaw, 02-507
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Romania4 sites, 4 recruiting
- Not yet recruiting
EncompaSSc site in Brasov, Romania
Brasov, 500283
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Bucharest, Romania
Bucharest, 030463
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Bucharest, Romania
Bucharest, 041303
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Timişoara, Romania
Timișoara, 300133
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
United Kingdom4 sites, 4 recruiting
- Not yet recruiting
EncompaSSc site in Walsgrave Coventry, UK
Coventry, CV2 2DX
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
- Recruiting
Royal Liverpool University Hospital
Liverpool, L7 8XP
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Marina Anderson
- Not yet recruiting
EncompaSSc site in London, UK
London, SW8 3RN
EncompaSSc contact, 617 802 6568, EncompaSSc@mediartx.com
- Not yet recruiting
EncompaSSc site in Westcliff-on-Sea, UK
Westcliff-on-Sea, SS0 0RY
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Australia3 sites, 3 recruiting
- Recruiting
Austin Health
Heidelberg, Victoria, 3084
Rheumatology Department, 617-802-6568, rheumatology@austin.org.au
Jessica Leung
- Recruiting
Griffith University (Clinical Trial Unit)
Southport, Queensland, 4222
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Gerald Tracey
- Recruiting
Veracity Clinical Research
Woolloongabba, Queensland, 4102
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Lynda Spelman
New Zealand2 sites, 2 recruiting
- Recruiting
Aotearoa Clinical Trials
Auckland, 2025
Research Department, 617-802-6568, info@aotearoatrials.nz
Mark Sapsford
- Recruiting
Waikato Hospital
Hamilton, 3204
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
Kamal Solanki
Netherlands1 site, 1 recruiting
- Not yet recruiting
EncompaSSc site in Groningen, Netherlands
Groningen, 9713 GZ
EncompaSSc contact, 617-802-6568, EncompaSSc@mediartx.com
About this study
Official title: 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)
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)
Read the detailed description
Participants with dcSSc who meet the study's inclusion and exclusion criteria will be randomly assigned in a 3:2 ratio to receive MTX-474 or a matching placebo by intravenous (IV) infusion. Concomitant use of one of the approved dcSSc therapies (immunosuppressive therapy, systemic glucocorticoids or other antifibrotic agents) is permitted under certain criteria. Participants randomized to the MTX-474 arm of the study will receive an IV infusion every 4 weeks, beginning at Day 0 and ending at Week 20. The End of Treatment Visit will occur at Week 24, and a Safety Follow-Up Visit will occur at Week 28, 8 weeks after the final infusion. mRSS assessments will occur at Screening, Baseline, and at all subsequent treatment visits up to and including Week 24. Spirometry will be performed at screening and Weeks 12. HRCT will be performed at screening and week 24. DLCO will be performed at Screening. Skin biopsies will be performed at Baseline and Week 12. Participants will have blood drawn for safety assessment and to assess Ephrin receptor levels at Screening, Baseline and every 4 weeks until Week 28. Blood will be drawn for serum PK analyses relative to the first and last doses of MTX-474.
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Being tested
- MTX-474, Placebo
- Keywords
- MTX-474-S201, MTX-474, Diffuse Cutaneous Systemic Sclerosis, dcSSc participants, dcSSc, Adult, mRSS, EncompaSSc, monoclonal antibody, EphrinB2
- Medical subject headings
- Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTX-474Biological
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).
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| MTX-474 | Experimental | MTX-474 Receives: Biological: MTX-474 |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Baseline to week 24
Secondary outcomes (8)
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 (%)
Measured: 12 weeks
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 (%)
Measured: Baseline through end of study (week 28)
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 (%)
Measured: 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)
Incidence, seriousness, and severity of TEAEs and TRAEs as determined by investigator assessment.
Unit of measure: Participants (%)
Measured: Baseline through end of study (week 28)
Serum concentration of MTX-474 at sparse PK time points
Serum MTX-474 concentrations collected at predefined sparse PK time points to support population pharmacokinetic (popPK) analysis Unit of Measure: ng/mL
Measured: Baseline to week 28
Clearance (CL) of MTX-474
Clearance of MTX-474 calculated from serial PK sampling using noncompartmental analysis Unit of Measure: L/hour
Measured: Baseline to week 28
Terminal elimination half-life (t½) of MTX-474
Terminal elimination half-life of MTX-474 derived from serial PK sampling. Unit of Measure: Hours
Measured: Baseline to week 28
Area under the plasma concentration-time curve (AUC) of MTX-474
AUC of MTX-474 calculated from serial PK sampling using noncompartmental analysis.
Unit of Measure: ng·h/mL
Measured: Baseline to week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2025
- Study start16 Apr 2026
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Cutaneous Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mediar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07287670
- Sponsor's protocol ID
- MTX-474-S201
- Other IDs
- 2025-523288-39, 2025
- Status last verified
- Oct 2026
- First submitted
- 18 Nov 2025
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No