intravenous iloprost in subjects with symptomatic raynaud's phenomenon secondary to systemic sclerosis (phase 3)

Conditions: Raynaud's Phenomenon Secondary to Systemic Sclerosis

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.


Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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

Keywords: systemic sclerosis raynaud's phenomenon