Clinical trial NCT02682511: Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Scleroderma, Diffuse
Scleroderma, Systemic
Scleroderma, Limited
Sclerosis, Progressive Systemic
Skin Diseases
Connective Tissue Diseases
Pathologic Processes
Autoimmune Diseases
Keywords: Ifetroban
Scleroderma
Systemic Sclerosis
Lead sponsor: Cumberland Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-02-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events (AEs) and Serious AEs (SAEs)
timeFrame: 56 weeks
Secondary outcomes:
measure: Change from baseline in forced vital capacity (FVC)
timeFrame: Baseline, 12, 26, and 52 weeks
measure: Change from baseline in diffusion capacity for carbon monoxide (DLCO)
timeFrame: Baseline, 12, 26, and 52 weeks
measure: Change from baseline in the modified Rodnan skin score (mRSS)
timeFrame: Baseline, 12, 26, 39, and 52 weeks
Other outcomes:
measure: Change from baseline in ventricular function as determined by cardiac MRI
timeFrame: Baseline, 26, and 52 weeks
measure: Change from baseline in ventricular function as determined by echocardiography
timeFrame: Baseline, 26, and 52 weeks
measure: Improve skin and peripheral vascular disease as measured by active digital ulcer count
timeFrame: Baseline, 12, 26, 39, and 52 weeks
measure: 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.
timeFrame: Baseline, 12, 26, 39, and 52 weeks
measure: Change from baseline in blood biomarkers
timeFrame: Baseline, 26, and 52 weeks
measure: Change from baseline in skin biomarkers
timeFrame: Baseline, 26, and 52 weeks
measure: Change from baseline in erythrocyte sedimentation rate
timeFrame: Baseline, 26, and 52 weeks
measure: Change from baseline in subject-reported health status assessed by the Scleroderma Health Assessment Questionnaire (SHAQ)
timeFrame: Baseline, 12, 26, 39, and 52 weeks
measure: 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)
timeFrame: Baseline, 12, 26, 39, and 52 weeks
measure: 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
timeFrame: Baseline, 12, 26, 39, and 52 weeks
measure: Change from baseline in subject-reported outcomes as assessed by the short-form health survey (SF-36)
timeFrame: Baseline, 12, 26, 39, and 52 weeks
Locations:
city: Tucson
country: United States
facility: The Universtity of Arizona Arthrtis Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Hialeah
country: United States
facility: New Life Medical Research Center, Inc.
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic - Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Seattle
country: United States
facility: Benaraoya Research Institute at Virginia Mason
state: Washington
city: Mumbai
country: India
facility: KDH - Kokilaben Dhirubhai Ambani Hospital
state: Maharashtra
city: Pune
country: India
facility: B. J. Government Medical College
state: Maharashtra
city: Chandigarh
country: India
facility: PGIMER
Study officials:
affiliation: Vanderbilt University Medical Center
name: Evan Brittain, MD
role: PRINCIPAL_INVESTIGATOR
References: