Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension

Phase 2

Recruiting

• Conditions: Scleroderma, Diffuse; Scleroderma, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Scleroderma, Limited; Sclerosis, Progressive Systemic; Skin Diseases; Pathologic Processes
• Interventions: Drug: Oral Ifetroban; Drug: Oral Placebo

• Registration Number: NCT02682511
• Lead Sponsor: Cumberland Pharmaceuticals

Brief Summary

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 diffuse cutaneous systemic SSc (dcSSc) or SSc-associated pulmonary arterial hypertension (SSc-PAH).

Detailed Description

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 participants with dcSSc will be randomized to receive either oral ifetroban daily or matching placebo. Study participants will be treated for 12 months, followed by a 30-day follow-up period. The study will test whether ifetroban is safe and statistically superior to placebo in reducing the effects of their disease at month 12 and explore the ability of ifetroban to prevent or reverse progression in patients with early disease duration and reverse established disease in patients with longer disease duration.

Study Timeline

• Study First Submitted: 2016-02-08
• Study First Submitted QC: 2016-02-10
• Study First Posted: 2016-02-15
• Study Start: 2017-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-06
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

Diffuse Cutaneous Criterion:

1. 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.

SSc-PAH Criteria:

1. Adults fulfilling the 2013 American College of Rheumatology/ European Union League Against Rheumatism Classification Criteria with confirmed SSc-PAH (limited or dcSSc) confirmed via previous cardiac catheterization
2. Stable oral therapy for PAH for at least 30 days (monotherapy or combination)
3. New York Heart Association (NYHA) Class I-III Heart Failure

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Exclusion Criteria

1. Have a diagnosis of systemic sclerosis sine scleroderma;
2. Be less than 18 years of age or greater than or equal to 80 years of age;
3. Be pregnant, nursing, or planning to become pregnant;
4. Current or planned treatment with prostanoid therapy;
5. Current or planned treatment with pirfenidone;
6. Use of rituximab in the last 3 months;
7. Use of mycophenolic acid (Myfortic, CellCept) at a stable dose for less than 3 months;
8. Current or planned corticosteroid therapy greater than 15mg per day of prednisone or prednisone equivalent;
9. Significant lung disease, defined as FVC < 50% predicted or DLCO <40% predicted;
10. Significant kidney disease, defined as Glomerular Filtration Rate (GFR) < 60 ml/min;
11. Have moderate or severe hepatic impairment;
12. Contraindication to MRI (e.g., implanted magnetic material, claustrophobia);
13. Known hypersensitivity to gadolinium;
14. Any cause of pulmonary hypertension other than World Health Organization (WHO) Group I associated with SSc;
15. Use of aspirin > 81 mg per day in the last two weeks;
16. Use of warfarin, heparin or other anticoagulants in the last 30 days;
17. Recent (within 6 weeks) myocardial infarction or persistent atrial arrhythmias;
18. Have a history of allergy or hypersensitivity to ifetroban;
19. Have taken investigational drugs within 30 days before study treatment administration;
20. Inability to understand the requirements of the study, inability to understand spoken English and abide by the study restrictions and to return for the required treatments and assessments;
21. Be otherwise unsuitable for the study, in the opinion of the investigator.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with dcSSc	Oral Ifetroban	Patients with dcSSc will be randomized to receive either oral ifetroban or oral placebo daily for 365 days
Patients with dcSSc	Oral Placebo	Patients with dcSSc will be randomized to receive either oral ifetroban or oral placebo daily for 365 days
Patients with SSc-PAH	Oral Placebo	Patients with SSc-PAH will be randomized to receive either oral ifetroban or oral placebo daily for 365 days
Patients with SSc-PAH	Oral Ifetroban	Patients with SSc-PAH will be randomized to receive either oral ifetroban or oral placebo daily for 365 days

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs) and Serious AEs (SAEs)	56 weeks	Safety is measured using AEs, including clinical significant changes in vital signs, laboratory test abnormalities and clinical tolerability of ifetroban.

Secondary Outcome Measures

Name	Time	Method
Change from baseline in the modified Rodnan skin score (mRSS)	Baseline, 12, 26, 39, and 52 weeks	The efficacy of treatment on skin fibrosis will be measured by changes from baseline in mRSS, a measure of skin thickness, at 52 weeks.
Change from baseline in forced vital capacity (FVC)	Baseline, 12, 26, and 52 weeks	To determine if ifetroban improves pulmonary function in subjects with diffuse cutaneous SSc or SSc-PAH compared to placebo as measured by a change from baseline FVC.
Change from baseline in diffusion capacity for carbon monoxide (DLCO)	Baseline, 12, 26, and 52 weeks	To determine if ifetroban improves pulmonary function in subjects with diffuse cutaneous SSc or SSc-PAH compared to placebo as measured by a change from baseline diffusion capacity for carbon monoxide (DLCO)

Trial Locations

Locations (17)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Boston University School of Medicine; 🇺🇸 Boston, Massachusetts, United States

KDH - Kokilaben Dhirubhai Ambani Hospital; 🇮🇳 Mumbai, Maharashtra, India

B. J. Government Medical College; 🇮🇳 Pune, Maharashtra, India

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

UCLA; 🇺🇸 Los Angeles, California, United States

PGIMER; 🇮🇳 Chandigarh, India

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Benaraoya Research Institute at Virginia Mason; 🇺🇸 Seattle, Washington, United States

The Universtity of Arizona Arthrtis Center; 🇺🇸 Tucson, Arizona, United States

New Life Medical Research Center, Inc.; 🇺🇸 Hialeah, Florida, United States

Cleveland Clinic - Florida; 🇺🇸 Weston, Florida, United States

Baylor Research Institute; 🇺🇸 Dallas, Texas, United States

Hospital for Special Surgery; 🇺🇸 New York, New York, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States