Oral Ifetroban for Scleroderma

Recruiting in Palo Alto (17 mi)

+11 other locations

Overseen by Evan Brittain, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Cumberland Pharmaceuticals

Must be taking: Oral PAH therapy

Must not be taking: Prostanoids, Pirfenidone, Rituximab, others

Disqualifiers: Pregnancy, Lung disease, Kidney disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing ifetroban, an oral medication, in patients with severe forms of systemic sclerosis. The goal is to see if it can reduce inflammation and improve blood flow, potentially helping to manage their condition better.

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

The trial requires that you have been on stable oral therapy for pulmonary arterial hypertension (PAH) for at least 30 days. However, you cannot participate if you are currently or planning to use certain medications like prostanoid therapy, pirfenidone, or high-dose corticosteroids, among others. Please review the exclusion criteria carefully to see if any apply to your current medications.

How is the drug Ifetroban unique in treating scleroderma?

Ifetroban is unique in treating scleroderma because it is administered orally, unlike some other treatments that require injections or more complex administration. It is also being explored as a novel option, as there are limited standard treatments specifically targeting scleroderma. ^{1 2 3 4 5}

Research Team

Evan Brittain, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults under 80 with diffuse cutaneous systemic sclerosis (dcSSc) within 7 years of their first symptom or SSc-associated pulmonary arterial hypertension, confirmed by cardiac catheterization. They must be on stable oral PAH therapy and have NYHA Class I-III Heart Failure. Exclusions include recent heart issues, certain drug treatments, severe lung or kidney disease, MRI contraindications, hypersensitivity to ifetroban or gadolinium.

Inclusion Criteria

I was diagnosed with diffuse cutaneous systemic sclerosis within the last 7 years.

I have scleroderma-related pulmonary arterial hypertension, am on stable oral treatment for it, and have mild to moderate heart failure.

Exclusion Criteria

Contraindication to MRI (e.g., implanted magnetic material, claustrophobia)

I have not used rituximab in the last 3 months.

I have been taking mycophenolic acid at the same dose for less than 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral ifetroban or placebo daily for 12 months

52 weeks

Baseline, 12, 26, 39, and 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ifetroban (Thromboxane A2 Receptor Antagonist)
• Oral Placebo (Drug)

Trial Overview The study tests the safety and effectiveness of an oral medication called Ifetroban compared to a placebo in patients with dcSSc or SSc-PAH. It's a phase 2 trial where participants are randomly assigned to either the treatment group receiving Ifetroban or a control group getting a placebo without knowing which one they're taking.

Participant Groups

Group I: Patients with dcSSc Experimental Treatment 2 Interventions

Patients with dcSSc will be randomized to receive either oral ifetroban or oral placebo daily for 365 days

Group II: Patients with SSc-PAH Experimental Treatment 2 Interventions

Patients with SSc-PAH will be randomized to receive either oral ifetroban or oral placebo daily for 365 days

Who Is Running the Clinical Trial?

Cumberland Pharmaceuticals

Lead Sponsor

Trials

63

Recruited

9,400+

A.J. Kazimi

Cumberland Pharmaceuticals

Chief Executive Officer since 1999

B.S. from the University of Notre Dame, MBA from Vanderbilt University Owen Graduate School of Management

Ines Macias-Perez

Cumberland Pharmaceuticals

Chief Medical Officer

Ph.D. in Cancer Biology from Vanderbilt University

Findings from Research

A 48-week study involving 146 patients with scleroderma found that aminobenzoate potassium (KPAB) did not significantly improve skin mobility or thickening compared to a placebo, indicating it may not be effective for this condition.

While KPAB was generally well tolerated, with a compliance rate of over 75%, some patients experienced adverse drug reactions, primarily gastrointestinal issues and headaches, leading to withdrawals from the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of aminobenzoate potassium and placebo in the treatment of scleroderma. Clegg, DO., Reading, JC., Mayes, MD., et al.[2013]

In a 24-week randomized trial involving 29 patients with systemic sclerosis, those treated with low-dose methotrexate (MTX) showed a significantly higher favorable response rate (53%) compared to the placebo group (10%), indicating its potential efficacy in treating this condition.

After an additional 24 weeks of treatment, 68% of patients who received MTX from the start demonstrated significant improvements in skin score, general well-being, and other health measures, suggesting that MTX can lead to meaningful clinical benefits for patients with active systemic sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. van den Hoogen, FH., Boerbooms, AM., Swaak, AJ., et al.[2022]

Scleroderma is a complex disease that primarily affects connective tissues and blood vessels, leading to symptoms like Raynaud's phenomenon, skin hardening, and gastrointestinal issues, with progressive complications such as pulmonary fibrosis.

Recent therapeutic trials have shown that treatments like penicillamine, certain vasodilators, and cyclofenil can provide good short-term clinical results with minimal serious side effects, particularly in influencing connective tissue and collagen metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scleroderma (progressive systemic sclerosis, PSS); pathophysiological, clinical and pharmacological aspects of the syndrome. Herbai, G.[2013]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Comparison of aminobenzoate potassium and placebo in the treatment of scleroderma. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. [2022]

3. Hungary pubmed.ncbi.nlm.nih.gov

Scleroderma (progressive systemic sclerosis, PSS); pathophysiological, clinical and pharmacological aspects of the syndrome. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Successful combined medical and surgical treatment of a lower extremity sclerodermal ulcer. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of Bosentan in treatment of refractory sclerodermic bone prominences skin ulcers. [2018]