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

Autoimmune Diseases Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02682511
• Other study ID #: CPI-IFE-004
• Status: Recruiting
• Phase: Phase 2
• Start date: January 2017
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Cumberland Pharmaceuticals
• Contact: Ingrid Anderson, PhD, CCRP
• Phone: 615-255-0068
• Email: ianderson[@]cumberlandpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Connective Tissue Diseases
• Pathologic Processes
• Pulmonary Arterial Hypertension
• Scleroderma, Diffuse
• Scleroderma, Limited
• Scleroderma, Localized
• Scleroderma, Systemic
• Sclerosis
• Sclerosis, Progressive Systemic
• Skin Diseases

Intervention

Drug:
• Oral Ifetroban
Subjects will be treated with oral ifetroban or placebo daily for 365 days
• Oral Placebo
Subjects will be treated with oral ifetroban or placebo daily for 365 days

Locations

Country	Name	City	State
India	PGIMER	Chandigarh
India	KDH - Kokilaben Dhirubhai Ambani Hospital	Mumbai	Maharashtra
India	B. J. Government Medical College	Pune	Maharashtra
United States	Johns Hopkins University	Baltimore	Maryland
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Baylor Research Institute	Dallas	Texas
United States	New Life Medical Research Center, Inc.	Hialeah	Florida
United States	UCLA	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Hospital for Special Surgery	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Benaraoya Research Institute at Virginia Mason	Seattle	Washington
United States	The Universtity of Arizona Arthrtis Center	Tucson	Arizona
United States	Cleveland Clinic - Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cumberland Pharmaceuticals

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in ventricular function as determined by cardiac MRI		Baseline, 26, and 52 weeks
Other	Change from baseline in ventricular function as determined by echocardiography		Baseline, 26, and 52 weeks
Other	Improve skin and peripheral vascular disease as measured by active digital ulcer count		Baseline, 12, 26, 39, and 52 weeks
Other	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
Other	Change from baseline in blood biomarkers		Baseline, 26, and 52 weeks
Other	Change from baseline in skin biomarkers		Baseline, 26, and 52 weeks
Other	Change from baseline in erythrocyte sedimentation rate		Baseline, 26, and 52 weeks
Other	Change from baseline in subject-reported health status assessed by the Scleroderma Health Assessment Questionnaire (SHAQ)		Baseline, 12, 26, 39, and 52 weeks
Other	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
Other	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
Other	Change from baseline in subject-reported outcomes as assessed by the short-form health survey (SF-36)		Baseline, 12, 26, 39, and 52 weeks
Primary	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	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
Secondary	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
Secondary	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