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

A Phase 2 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Ifetroban in Patients With Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension (SSc-PAH)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Pathologic Processes; Skin Diseases; Autoimmune Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Limited; Sclerosis, Progressive Systemic
• Intervention / Treatment: Drug: Oral Ifetroban; Drug: Oral Placebo

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 Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Chandigarh
    • Chandigarh, Chandigarh, India, 160012
      • PGIMER
  • Maharashtra
    • Mumbai, Maharashtra, India, 400053
      • KDH - Kokilaben Dhirubhai Ambani Hospital
    • Pune, Maharashtra, India, 411001
      • B. J. Government Medical College
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • The Universtity of Arizona Arthrtis Center
  • California
    • Los Angeles, California, United States, 90095-1670
      • UCLA
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic - Florida
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75204-651
      • Baylor Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with dcSSc; Patients with dcSSc will be randomized to receive either oral ifetroban or oral placebo daily for 365 days	Drug: Oral Ifetroban; Subjects will be treated with oral ifetroban or placebo daily for 365 days; Other Names: Ifetroban; Drug: Oral Placebo; Subjects will be treated with oral ifetroban or placebo daily for 365 days; Other Names: Ifetroban
Experimental: Patients with SSc-PAH; Patients with SSc-PAH will be randomized to receive either oral ifetroban or oral placebo daily for 365 days	Drug: Oral Ifetroban; Subjects will be treated with oral ifetroban or placebo daily for 365 days; Other Names: Ifetroban; Drug: Oral Placebo; Subjects will be treated with oral ifetroban or placebo daily for 365 days; Other Names: Ifetroban

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in forced vital capacity (FVC)	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.	Baseline, 12, 26, and 52 weeks
Change from baseline in diffusion capacity for carbon monoxide (DLCO)	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)	Baseline, 12, 26, and 52 weeks
Change from baseline in the modified Rodnan skin score (mRSS)	The efficacy of treatment on skin fibrosis will be measured by changes from baseline in mRSS, a measure of skin thickness, at 52 weeks.	Baseline, 12, 26, 39, and 52 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline in ventricular function as determined by cardiac MRI	Baseline, 26, and 52 weeks
Change from baseline in ventricular function as determined by echocardiography	Baseline, 26, and 52 weeks
Improve skin and peripheral vascular disease as measured by active digital ulcer count	Baseline, 12, 26, 39, and 52 weeks
Improve skin and peripheral vascular disease as measured by the subject's self-assessment of pain in digits by a visual analog scale (VAS), if active digital ulcers are present.	Baseline, 12, 26, 39, and 52 weeks
Change from baseline in blood biomarkers	Baseline, 26, and 52 weeks
Change from baseline in skin biomarkers	Baseline, 26, and 52 weeks
Change from baseline in erythrocyte sedimentation rate	Baseline, 26, and 52 weeks
Change from baseline in subject-reported health status assessed by the Scleroderma Health Assessment Questionnaire (SHAQ)	Baseline, 12, 26, 39, and 52 weeks
Change from baseline in subject health and disability measurements as assessed by the World Health Organization Disability Assessment Assessment Schedule 2.0 (WHODAS 2.0)	Baseline, 12, 26, 39, and 52 weeks
Change from baseline in subject-reported gastro-intestinal tract symptoms as assessed by the University of California, Los Angles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Tract (GIT) Questionnaire	Baseline, 12, 26, 39, and 52 weeks
Change from baseline in subject-reported outcomes as assessed by the short-form health survey (SF-36)	Baseline, 12, 26, 39, and 52 weeks

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Principal Investigator: Evan Brittain, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 8, 2016
• First Submitted That Met QC Criteria: February 10, 2016
• First Posted (Estimated): February 15, 2016

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Scleroderma; Ifetroban
• Additional Relevant MeSH Terms: Immune System Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Autoimmune Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Scleroderma, Limited; Platelet Aggregation Inhibitors; ifetroban
• Other Study ID Numbers: CPI-IFE-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No