A Phase 2 interventional study of MTX-474 and Placebo in Diffuse Cutaneous Systemic Sclerosis, sponsored by Mediar Therapeutics. Recruiting at 58 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-05.
Sponsored by Mediar Therapeutics · Phase 2, Interventional, and Treatment
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)
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.
310 studies on the registry are indexed under Scleroderma, Diffuse; 76 are open to participants now.
This study's planned enrollment of 85 is above the median of 38 across 227 interventional studies indexed under Scleroderma, Diffuse.
Browse Scleroderma, Diffuse studies →Mediar Therapeutics is the lead sponsor of 6 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participant is either:
Exclusion Criteria:
Participant is currently on therapy, systemic or other antifibrotic agents detailed as follows:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MTX-474
Biological: MTX-474
Placebo
Other: Placebo
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).
Placebo
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)
Time frame: Baseline to week 24
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 (%)
Time frame: 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 (%)
Time frame: 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 (%)
Time frame: 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 (%)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline to week 28
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 (%)
Time frame: Baseline to week 24
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)
Time frame: Baseline to week 24
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)
Time frame: Baseline to week 24
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 (%)
Time frame: Baseline to week 24
Change from baseline in quantitative interstitial lung disease (QILD) score by high-resolution computed tomography (HRCT)
Mean change from baseline to week 24 in the QILD score by high resolution computed tomography scan (HRCT) in each arm Unit of Measure: Units on QILD score (0-100 scale; higher score = greater fibrosis)
Time frame: Baseline to week 24
Change from Baseline in free EphrinB2 levels
Median change from baseline to Week 24 in serum free EphrinB2 levels in each treatment arm. Unit of Measure: pg/mL
Time frame: Baseline to week 24
Change from baseline in forced vital capacity (FVC) by EphrinB2 levels
Mean change from baseline to Week 24 in FVC, analyzed by baseline EphrinB2 levels, in the subset of participants with interstitial lung disease (ILD). Unit of Measure: Percent predicted (%)
Time frame: Baseline to week 24
Proportion of participants achieving rACR-CRISS response by EphrinB2 levels
Proportion of participants achieving a response on the revised ACR Composite Response Index in Systemic Sclerosis (rACR-CRISS), stratified by baseline EphrinB2 levels. Unit of Measure: Participants (%)
Time frame: Up to 24 weeks
To assess the presence, titer and impact of antidrug antibodies (ADA) against MTX-474
Samples will be collected from baseline until Week 28 to assess the rate at which antibodies develop to the study drug Unit of Measure: Titer units
Time frame: Baseline to week 28
Change from baseline in expression of total and phosphorylated EphB2, EphB3, and EphB4 receptors in skin
Mean change from baseline to Week 12 in total and phosphorylated EphB2, EphB3, and EphB4 receptor expression in skin biopsy samples. Unit of Measure: Relative expression units (fold change from baseline)
Time frame: Baseline to Week 12
Change from baseline in transcriptomic profile
Change from baseline to Week 12 in global transcriptomic profile via bulk RNA sequencing analysis of skin biopsies in each arm. Unit of Measure: Differential gene expression (log₂ fold change)
Time frame: Baseline to Week 12
Change from baseline in serum biomarkers of organ involvement
Change from baseline to Weeks 12 and 24 in serum levels biomarkers, including but not limited to, ProC3 and IL-6 associated with organ involvement Unit of Measure: ng/mL (or unit per biomarker)
Time frame: Baseline to weeks 12 and 24
Change from baseline in fatigue symptoms (FACIT-Fatigue score)
Mean change from baseline to Week 24 in fatigue symptoms as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Unit of Measure: Units on FACIT-Fatigue scale (range 0-52; higher score = less fatigue)
Time frame: Baseline to week 24
Change from baseline in gastrointestinal (GI) symptoms (UCLA SCTC GIT 2.0 score)
Mean change from baseline to Week 24 in GI symptom burden assessed by the UCLA SCTC GIT 2.0 questionnaire. Unit of Measure: Units on UCLA SCTC GIT 2.0 total score (range 0-3; higher score = worse symptoms)
Time frame: Baseline to week 24
Change from baseline in anxiety and depression symptoms (HADS)
Mean change from baseline to Week 24 in symptoms of anxiety and depression measured by the HADS instrument. Unit of Measure: Units on Hospital Anxiety and Depression Scale (HADS total and subscale scores; range 0-21 per subscale; higher score = worse symptoms)
Time frame: Baseline to week 24
Change from baseline in HAQ-DI
Mean change from Baseline in functional disability as assessed by HAQ-DI. Unit of measure: Score (0-3 scale)
Time frame: Baseline to week 24
Plan to share: No
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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