Oral Ifetroban for Scleroderma

Not currently recruiting at 12 trial locations

Overseen By Ines Macias-Perez, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 12

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a drug called ifetroban for individuals with certain types of scleroderma, a condition that causes hardening and tightening of the skin and connective tissues. The trial focuses on those with diffuse cutaneous systemic scleroderma (dcSSc) or pulmonary arterial hypertension (PAH) linked to scleroderma. Participants will take either ifetroban or a placebo (a pill with no active medicine) daily for one year. Those who have experienced scleroderma symptoms other than Raynaud's for less than seven years or have stable treatment for PAH might be suitable candidates. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

Is there any evidence suggesting that ifetroban is likely to be safe for humans?

Research shows that ifetroban is usually well-tolerated. In previous studies, patients took ifetroban without experiencing many serious side effects. Most reported side effects were mild, meaning they were not serious and could be managed easily.

Researchers are testing ifetroban for safety in people with scleroderma, a condition affecting the skin and organs. They are also studying it in people with pulmonary arterial hypertension (PAH), a type of high blood pressure in the lungs.

While this trial focuses on safety, its advanced phase suggests some previous safety evidence exists. However, it remains important to join a trial with the understanding that researchers are closely monitoring for any possible side effects. ^{1 2 3 4 5}

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

Ifetroban is unique because it specifically targets the thromboxane-prostanoid (TP) receptor, which is different from most standard treatments for scleroderma-related conditions like SSc-PAH and dcSSc. Current treatments often focus on vasodilation or immunosuppression, but ifetroban works by blocking the TP receptor involved in inflammation and fibrosis, potentially reducing these symptoms more effectively. Researchers are excited about ifetroban because this novel mechanism could offer a new way to manage the progression of scleroderma, offering hope for better outcomes in patients who don't respond well to existing therapies.

What evidence suggests that ifetroban might be an effective treatment for scleroderma?

This trial will evaluate the effectiveness of ifetroban in treating conditions such as diffuse cutaneous systemic sclerosis (dcSSc) and pulmonary arterial hypertension (SSc-PAH) linked to systemic sclerosis. Participants will be randomized to receive either oral ifetroban or an oral placebo daily for 365 days. Research suggests that ifetroban blocks a specific part of the body that contributes to inflammation and blood clotting, which are issues in these conditions. Early studies have shown promise in reducing these symptoms, although more research is needed to confirm its effectiveness. While data remains limited, the mechanism of ifetroban offers hope for those facing these challenging conditions. ^{3 4 6 7 8}

Who Is on the Research Team?

Evan Brittain, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ifetroban
• Oral Placebo

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

A combined approach of medical and surgical treatment for chronic lower extremity ulcers in patients with systemic scleroderma shows promise for effective wound closure.

Recent advancements, such as the use of calcium channel blockers and meticulous surgical care including skin grafting, have improved outcomes for healing sclerodermal skin ulcerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful combined medical and surgical treatment of a lower extremity sclerodermal ulcer. Grossman, JA., Barrall, DT., Dennison, A., et al.[2019]

In a case study of a patient with scleroderma, the endothelin receptor antagonist Bosentan was effective in treating refractory skin ulcers, leading to complete healing of the lesions.

This suggests that Bosentan could be a promising alternative treatment for managing sclerodermic skin ulcers, potentially influencing future therapeutic strategies for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Bosentan in treatment of refractory sclerodermic bone prominences skin ulcers. Richetta, AG., Mattozzi, C., Maiani, E., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02682511

NCT02682511 | Oral Ifetroban to Treat Diffuse Cutaneous ... This study is a randomized, placebo-controlled, double-blind phase 2 trial of patients with dcSSc or SSc-PAH. Twenty participants with SSc-PAH and 14 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02682511?term=AREA%5BConditionSearch%5D(%22Scleroderma,%20Limited%22)&rank=10

Study Details | Oral Ifetroban to Treat Diffuse Cutaneous ... A group of independent scientists who monitor the safety and scientific integrity of a clinical trial. The DMC can recommend to the sponsor that the trial be ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12215137/

New horizons in systemic sclerosis treatment: advances and ... Despite the significant disease burden, there is a lack of robust data confirming the efficacy of corticosteroids, TCZ or rituximab in improving ...

4. ctv.veeva.com ctv.veeva.com/study/oral-ifetroban-to-treat-diffuse-cutaneous-systemic-sclerosis-ssc-or-ssc-associated-pulmonary-arter

Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis ... The purpose of this phase 2 multicenter, randomized, double-blind, placebo-controlled, study is to assess the safety and efficacy of ifetroban ...

5. app.trialscreen.org app.trialscreen.org/trials/phase-2-scleroderma-diffuse-oral-ifetroban-to-treat-cutaneous-systemic-trial-nct02682511

Oral Ifetroban to Treat Diffuse Cutaneous Systemic ... Evaluating the Safety and Effectiveness of Ifetroban in Treating Diffuse Cutaneous Systemic Sclerosis and Pulmonary Arterial Hypertension. Check your ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02682511

NCT02682511 | Oral Ifetroban to Treat Diffuse Cutaneous ... The purpose of this phase 2 multicenter, randomized, double-blind, placebo-controlled, study is to assess the safety and efficacy of ifetroban in patients with ...

7. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/cumberland_ifetroban

Oral Ifetroban to Treat Diffuse Systemic Sclerosis or ... We also want to find out if Ifetroban is safe to take without causing too many side effects. It will take you about 1 year to complete this research study.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7125406/

Management of Pulmonary Arterial Hypertension in ... A phase 2 multicenter, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of ifetroban in patients with ...