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

Sponsor

Cumberland Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02682511

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Scleroderma, Diffuse Scleroderma, Systemic Scleroderma, Limited Sclerosis, Progressive Systemic Skin Diseases Connective Tissue Diseases Pathologic Processes Autoimmune Diseases	Drug: Oral Ifetroban Drug: Oral Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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)
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.

Other Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

SSc-PAH Criteria:

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
Stable oral therapy for PAH for at least 30 days (monotherapy or combination)
New York Heart Association (NYHA) Class I-III Heart Failure

Exclusion Criteria:

Have a diagnosis of systemic sclerosis sine scleroderma;
Be less than 18 years of age or greater than or equal to 80 years of age;
Be pregnant, nursing, or planning to become pregnant;
Current or planned treatment with prostanoid therapy;
Current or planned treatment with pirfenidone;
Use of rituximab in the last 3 months;
Use of mycophenolic acid (Myfortic, CellCept) at a stable dose for less than 3 months;
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;
Significant kidney disease, defined as Glomerular Filtration Rate (GFR) < 60 ml/min;
Have moderate or severe hepatic impairment;
Contraindication to MRI (e.g., implanted magnetic material, claustrophobia);
Known hypersensitivity to gadolinium;
Any cause of pulmonary hypertension other than World Health Organization (WHO) Group I associated with SSc;
Use of aspirin > 81 mg per day in the last two weeks;
Use of warfarin, heparin or other anticoagulants in the last 30 days;
Recent (within 6 weeks) myocardial infarction or persistent atrial arrhythmias;
Have a history of allergy or hypersensitivity to ifetroban;
Have taken investigational drugs within 30 days before study treatment administration;
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;
Be otherwise unsuitable for the study, in the opinion of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Universtity of Arizona Arthrtis Center	Tucson	Arizona	United States	85724
2	UCLA	Los Angeles	California	United States	90095-1670
3	New Life Medical Research Center, Inc.	Hialeah	Florida	United States	33012
4	Cleveland Clinic - Florida	Weston	Florida	United States	33331
5	Johns Hopkins University	Baltimore	Maryland	United States	21224
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Boston University School of Medicine	Boston	Massachusetts	United States	02118
8	Hospital for Special Surgery	New York	New York	United States	10021
9	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
10	Medical University of South Carolina	Charleston	South Carolina	United States	29403
11	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37203
12	Baylor Research Institute	Dallas	Texas	United States	75204-651
13	Benaraoya Research Institute at Virginia Mason	Seattle	Washington	United States	98101
14	KDH - Kokilaben Dhirubhai Ambani Hospital	Mumbai	Maharashtra	India	400053
15	B. J. Government Medical College	Pune	Maharashtra	India	411001
16	PGIMER	Chandigarh		India	160012