What is the mechanism of action of this treatment?

Connective Tissue Diseases (CTDs) are often treated with a variety of medications that target different aspects of the immune response and inflammation. Common treatments include corticosteroids, which reduce inflammation by suppressing the immune system; disease-modifying antirheumatic drugs (DMARDs) like methotrexate, which slow disease progression by inhibiting immune cell activity; and biologics such as TNF inhibitors, which block specific inflammatory cytokines. Thromboxane Receptor Antagonists like Ifetroban work by inhibiting thromboxane, a compound that promotes platelet aggregation and vasoconstriction, thereby potentially reducing vascular complications associated with CTDs. These treatments are crucial for CTD patients as they help manage symptoms, prevent disease progression, and improve quality of life by targeting the underlying mechanisms of inflammation and autoimmunity.

What side effects are associated with this type of intervention?

Common treatments for Connective Tissue Disease (CTD) include glucocorticoids, TNF-alpha inhibitors, and other immunosuppressive agents. Glucocorticoids can cause side effects such as increased risk of cardiovascular events, osteoporosis, weight gain, and hyperglycemia. TNF-alpha inhibitors, like etanercept, may lead to infections, injection site reactions, and rare cases of drug-induced lupus or angioedema. Thromboxane Receptor Antagonists, such as Ifetroban, are still under study, but potential side effects could include gastrointestinal issues, bleeding risks, and liver enzyme abnormalities. Patients should discuss these risks with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

FDA-approved treatments for connective tissue diseases, such as systemic sclerosis, include immunosuppressive agents like methotrexate and biologics such as tocilizumab and rituximab. Tocilizumab, an anti-interleukin-6 receptor antibody, has shown efficacy in treating skin fibrosis and interstitial lung disease in systemic sclerosis. Rituximab, a monoclonal antibody targeting CD20, has been approved in Japan for its beneficial effects on skin fibrosis and lung function in systemic sclerosis. These treatments focus on modulating the immune response and reducing inflammation, similar to the investigational approach of Ifetroban, which targets thromboxane receptors to potentially mitigate disease progression.

What other types of research exist?

Promising novel alternatives to Ifetroban for connective tissue disease patients include Janus kinase (JAK) inhibitors like tofacitinib, which have shown efficacy in treating refractory dermatomyositis. Additionally, biologics such as rituximab, which targets B-cells, have been effective in treating various inflammatory myopathies. These treatments have demonstrated potential in clinical trials and could be considered as alternatives in 2024.

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Thromboxane A2 Receptor Antagonist

Oral Ifetroban for Scleroderma

Phase 2

Recruiting

Led By Evan Brittain, MD

Research Sponsored by Cumberland Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diffuse Cutaneous Criterion: Systematic Sclerosis (SSc) as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism Classification Criteria and dcSSc within 7 years following initial diagnosis as defined by the onset of the first non-Raynaud symptom.

Be older than 18 years old

Must not have

Current or planned corticosteroid therapy greater than 15mg per day of prednisone or prednisone equivalent

Significant lung disease, defined as FVC < 50% predicted or DLCO <40% predicted

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 12, 26, 39, and 52 weeks

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects for Ifetroban aren't listed here, common ones may include digestive discomforts like nausea or diarrhea, potential liver function changes, headaches, dizziness and possible allergic reactions. The severity can vary from person to person.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am taking or will take more than 15mg of prednisone or its equivalent daily.

Select...

My lung function is significantly impaired.

Select...

My kidney function is reduced with a GFR under 60 ml/min.

Select...

I understand English and can follow the study's requirements.

Select...

I have been diagnosed with systemic sclerosis without skin thickening.

Select...

I am currently on or will start prostanoid therapy.

Select...

My liver function is significantly impaired.

Select...

I am either younger than 18 or 80 years old or older.

Select...

My pulmonary hypertension is not caused by scleroderma.

Select...

I am currently taking or will start taking pirfenidone.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 12, 26, 39, and 52 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 12, 26, 39, and 52 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 12, 26, 39, and 52 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events (AEs) and Serious AEs (SAEs)

Secondary study objectives

Change from baseline in diffusion capacity for carbon monoxide (DLCO)

Change from baseline in forced vital capacity (FVC)

Change from baseline in the modified Rodnan skin score (mRSS)

Trial Design

2Treatment groups

Experimental Treatment

Group I: Patients with dcSScExperimental Treatment2 Interventions

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

Group II: Patients with SSc-PAHExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Oral Placebo

2017

Completed Phase 4

~4590

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Connective Tissue Diseases (CTDs) are often treated with a variety of medications that target different aspects of the immune response and inflammation. Common treatments include corticosteroids, which reduce inflammation by suppressing the immune system; disease-modifying antirheumatic drugs (DMARDs) like methotrexate, which slow disease progression by inhibiting immune cell activity; and biologics such as TNF inhibitors, which block specific inflammatory cytokines. Thromboxane Receptor Antagonists like Ifetroban work by inhibiting thromboxane, a compound that promotes platelet aggregation and vasoconstriction, thereby potentially reducing vascular complications associated with CTDs. These treatments are crucial for CTD patients as they help manage symptoms, prevent disease progression, and improve quality of life by targeting the underlying mechanisms of inflammation and autoimmunity.

Skin involvement as a relevant outcome measure in clinical trials of systemic sclerosis.The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases.The BeSt story: on strategy trials in rheumatoid arthritis.