Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)
- Conditions
- Raynaud's Phenomenon Secondary to Systemic Sclerosis
- Interventions
- Drug: Placebo IV infusion
- Registration Number
- NCT04040322
- Lead Sponsor
- Eicos Sciences, Inc.
- Brief Summary
This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of iloprost on the frequency of and relief from symptomatic digital ischemic episodes in subjects with systemic sclerosis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 198
- Male or female subjects must be greater than or equal to 18 years of age.
- Subjects must have a diagnosis of Systemic Sclerosis as defined by the 2013 American College of Rheumatology criteria/EULAR criteria
- Subjects must have a diagnosis or history of Raynaud's Phenomenon, self-reported or reported by a physician, with at least a 2-phase color change in finger(s) of pallor, cyanosis, and/or reactive hyperemia in response to cold exposure or emotion
- Subjects must have a minimum of 10 symptomatic Raynaud's Phenomenon attacks, documented in the electronic patient-reported outcomes (ePRO) diary, occurring over at least 3 separate days of the 3- to 5-day eligibility period
- Subjects must complete a minimum of 80% of the daily ePRO diary entry during the baseline period
- Female subjects of childbearing potential and male subjects must agree to use contraception for the duration of the study.
- Subjects must be willing and able to comply with the study requirements and give informed consent for participation in the study
- Female subjects who are pregnant or breastfeeding
- Subjects with systolic blood pressure <85 mmHg
- Subjects with an estimated glomerular filtration rate <15 mL/min/1.73 m2
- Subjects with an alanine aminotransferase and/or aspartate aminotransferase value >3 × the upper limit of normal at screening
- Subjects who have a digital ulcer infection within 30 days of screening
- Subjects with a history of cervical or digital sympathectomy, or botulism toxin injections in their hands [for RP or digital ulcers] within 90 days of screening. Subjects should not have a planned botulism toxin or sympathectomy during their participation in the study.
- Subjects with gangrene or digital amputation within 6 months of screening
- Subjects with current intractable diarrhea or vomiting
- Subjects with a risk of clinically significant bleeding events, including those with coagulation or platelet disorders at screening
- Subjects with a history of major trauma or hemorrhage within 30 days of screening.
- Subjects with clinically significant chronic intermittent bleeding, such as active gastric antral vascular ectasia or active peptic ulcer disease, within 60 days of screening
- Subjects who have had any cerebrovascular events (eg, transient ischemic attack or stroke) within 6 months of screening
- Subjects with a history of myocardial infarction or unstable angina within 6 months of screening. Subjects should not have a planned coronary procedure during their participation in the study
- Subjects with acute or chronic congestive heart failure (New York Heart Association Class III [moderate] or Class IV [severe]) at screening
- Subjects with a history of more than mild restrictive or congestive cardiomyopathy uncontrolled by medication or implanted device
- Subjects with a history of life-threatening cardiac arrhythmias
- Subjects with a history of hemodynamically significant aortic or mitral valve disease
- Subjects with a history of known pulmonary hypertension, pulmonary arterial hypertension, or pulmonary veno-occlusive disease
- Subjects with a history of significant restrictive lung disease, defined as forced vital capacity <45% predicted and diffusing capacity of the lungs for carbon monoxide <40% predicted (uncorrected for hemoglobin)
- Subjects with scleroderma renal crisis within 6 months of screening
- Subjects with a concomitant life-threatening disease with a life expectancy <12 months
- Subjects who have a clinically significant disorder that, in the opinion of the Investigator, could contraindicate the administration of study drug, affect compliance, interfere with study evaluations, or confound the interpretation of study results
- Subjects who have taken or are currently taking any parenteral, inhaled, or oral prostacyclin or prostacyclin receptor agonists (eg, epoprostenol, treprostinil, iloprost, and selexipag) within 8 weeks of screening
- Subjects who have initiated or had a dose change of any of the following within 2 weeks of screening: oral, topical, or intravenous (IV) vasodilators (eg, calcium channel blockers, phosphodiesterase-5 (PDE5) inhibitors [eg, sildenafil, tadalafil, or vardenafil], nitrates, and fluoxetine)
- Subjects with any history of acetaminophen intolerability (eg, allergic reaction to acetaminophen)
- Subjects with any malignancy that requires treatment during the study period, that has required treatment within 1 year of screening (including excision of skin cancer) or that is currently not in remission
- Subjects who have used any investigational medication or device for any indication within 30 days or 5 half-lives (whichever is longer)
- Subjects who have participated in ES-201 or ES-301 studies and were randomized and treated with study drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Iloprost Injection, for intravenous use Iloprost Injection, for intravenous use Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo Placebo IV infusion Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min.
- Primary Outcome Measures
Name Time Method Frequency of symptomatic RP attacks Day 6 - Day 21 will be compared to baseline The primary efficacy parameter is the change in the weekly frequency of symptomatic RP attacks from baseline
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (30)
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of California, Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Arizona Arthritis & Rheumatology Research, PLLC
🇺🇸Phoenix, Arizona, United States
University of Arizona - Arthritis Research Center
🇺🇸Tucson, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Georgetown University Medical Center - Department of Rheumatology
🇺🇸Washington, District of Columbia, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
West Michigan Rheumatology PLLC
🇺🇸Grand Rapids, Michigan, United States
University of Minnesota Maple Grove
🇺🇸Minneapolis, Minnesota, United States
Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
University of Cincinnati - Scleroderma Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
The University of Toledo Medical Center (UTMC) - Ruppert Health Center
🇺🇸Toledo, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics
🇺🇸Houston, Texas, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Mayo Clinic - Scottsdale
🇺🇸Scottsdale, Arizona, United States