MTX-474 for Scleroderma

Overseen By Jeffrey Bornstein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mediar Therapeutics

Must not be taking: Immunosuppressants, Antifibrotics, Glucocorticoids, others

Disqualifiers: Organ transplant, PAH, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, MTX-474, for individuals with diffuse cutaneous systemic sclerosis (dcSSc), a condition that causes skin hardening and thickening. The goal is to determine if MTX-474 is safe and effective in improving symptoms compared to a placebo (a substance with no active treatment). Suitable participants have experienced non-Raynaud's symptoms of this condition for over two years without significant improvement in skin thickening. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications to join the trial. If you are on immunosuppressive therapy, systemic glucocorticoids, or antifibrotic agents, you might need to stop or adjust them before joining. Some medications like mycophenolate mofetil, mycophenolic acid, hydroxychloroquine, and methotrexate can be continued if they have been stable for a certain period.

Is there any evidence suggesting that MTX-474 is likely to be safe for humans?

Research has shown that MTX-474 is being tested for safety in humans. In an earlier study, participants took MTX-474, and researchers closely monitored them for side effects. The results indicated that MTX-474 was generally well-tolerated, with no major safety issues reported.

Experts regularly review safety during trials to manage potential risks. Since MTX-474 remains in Phase 2 trials, earlier results were promising enough to warrant further testing for more detailed safety and effectiveness information. This ongoing research aims to confirm that MTX-474 can be safely used in people with systemic sclerosis, a condition that causes the skin and other tissues to harden. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for scleroderma?

Most treatments for scleroderma focus on alleviating symptoms, such as immunosuppressants and anti-inflammatory drugs that help reduce the immune system's attack on the body. However, MTX-474 is unique because it offers a new mechanism of action, potentially targeting the underlying processes that drive scleroderma rather than just managing symptoms. Researchers are excited about MTX-474 because it might modify the disease course itself, offering hope for more effective and lasting relief for patients with this challenging condition.

What evidence suggests that MTX-474 might be an effective treatment for scleroderma?

Research has shown that MTX-474 is being developed to treat systemic sclerosis, a condition where the skin and internal organs become hard and tight. In this trial, participants will receive either MTX-474 or a placebo. Studies have found that people with systemic sclerosis often have higher levels of a protein called soluble EphrinB2. MTX-474 targets this protein, aiming to reduce the symptoms of the disease. Early results suggest that this treatment might change certain gene activities linked to the condition. Although the treatment is still under study, initial signs are promising for addressing the thickening and scarring of tissue seen in systemic sclerosis. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with diffuse cutaneous systemic sclerosis (dcSSc), diagnosed per specific criteria, within certain timeframes from their first symptoms. They must have a minimum lung function and skin available for biopsy, understand the study, and not be pregnant if of childbearing potential.

Inclusion Criteria

I have taken a pregnancy test and it was negative.

My lung function, measured by FVC, is at least 45% of the expected value.

I am willing and able to attend all required study visits and procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive MTX-474 or placebo by IV infusion every 4 weeks from Day 0 to Week 20

20 weeks

6 visits (in-person)

End of Treatment

End of Treatment Visit occurs at Week 24

4 weeks

1 visit (in-person)

Follow-up

Safety Follow-Up Visit occurs 8 weeks after the final infusion to monitor safety and effectiveness

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MTX-474

Trial Overview

The EncompaSSc trial is testing MTX-474 against a placebo in people with dcSSc. It's a Phase 2 study where participants are randomly assigned to either the drug or placebo without knowing which one they're getting to measure safety and effectiveness.

How Is the Trial Designed?

Group I: MTX-474 Experimental Treatment 1 Intervention

MTX-474

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Mediar Therapeutics

Lead Sponsor

Trials

2

Recruited

140+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07287670?term=TREATMENt

NCT07287670 | EncompaSSc: Evaluation of MTX-474 in ...

MTX-474 is being developed as a therapy for patients with systemic sclerosis (SSc). Participant Group/Arm, Placebo Comparator : Placebo. Placebo.

2.

sofinnovapartners.com

sofinnovapartners.com/news/mediar-therapeutics-announces-oversubscribed-usd76-million-series-b-financing-and-clinical-advancement-of-first-in-class-fibrosis-portfolio

Mediar Therapeutics Announces Oversubscribed $76 ...

For Mediar's MTX-474, Ph2a study in patients with SSc, and MTX-439, Ph1 studies for the treatment of CKD associated fibrosis.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06535841

NCT06535841 | A First-in-Human Safety Trial of MTX-474

Increased levels of circulating soluble EphrinB2 have been found in patients with systemic sclerosis. Participant Group/Arm, Placebo Comparator : Placebo.

4.

mediartx.com

mediartx.com/wp-content/uploads/2025/07/2025_SclerodermaResearchUK_antiEphrinB2GeneSignature.pdf

Gene Signature in Systemic Sclerosis Modulated by a ...

MTX-474-S201 Phase 2 clinical trial. dcSSc vs. healthy in human SSc. Genes and pathways that are common between human and rodent. Disease vs. control in the ...

5.

anzctr.org.au

anzctr.org.au/Trial/Registration/TrialReview.aspx?id=387800

ANZCTR - Registration

A cumulative review of safety and tolerability of MTX-474 will be conducted by the study Investigator, Medical Monitor, and Sponsor's ...

6.

amplitudevc.com

amplitudevc.com/en/news/mediar-therapeutics-announces-oversubscribed-76-million-series-b-financing-and-clinical-advancement-of-first-in-class-fibrosis-portfolio

Amplitude is a proud investor in Mediar Therapeutics

MTX-474 Global Phase 2a study Initiated in Systemic Sclerosis (SSc). MTX-463 Global Phase 2a Study in Idiopathic Pulmonary Fibrosis (IPF) ...

7.

mediartx.com

mediartx.com/wp-content/uploads/2025/06/Mediar-Doses-First-Patient-in-Phase-2.pdf

Mediar Therapeutics Doses First Patient in Phase 2

The WISPer trial is a randomized, double-blind, placebo-controlled 24-week. Phase 2 study designed to evaluate the efficacy, safety, and ...