Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 2)

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, double-blind, randomized, placebo-controlled study to evaluate the effect of iloprost on the symptomatic relief of Raynaud's Phenomenon attacks in subjects with symptomatic Raynaud's Phenomenon secondary to Systemic Sclerosis.

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Pilot Study Evaluating Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis

Conditions
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Raynaud Phenomenon Secondary to Systemic Sclerosis

Intervention / Treatment
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* Drug: Placebo IV infusion
* Drug: Iloprost Injection, for intravenous use


Participation Criteria
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Eligibility Criteria
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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 Subjects must have a diagnosis or history of Raynaud's Phenomenon Subjects must have a minimum of 10 symptomatic Raynaud's Phenomenon attacks 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 <30 mL/min/1.73 m2 Subjects with Child-Pugh Class B or Class C liver disease or an alanine aminotransferase and/or aspartate aminotransferase value >3 × the upper limit of normal at screening. Subjects with gangrene, digital ulcer infection, or requirement of cervical or digital sympathectomy Subjects with intractable diarrhea or vomiting Subjects with a risk of clinically significant bleeding events including those with coagulation or platelet disorders Subjects with a history of major trauma or hemorrhage Subjects with clinically significant chronic intermittent bleeding such as active gastric antral vascular ectasia or active peptic ulcer disease Subjects who have had any cerebrovascular events Subjects with a history of myocardial infarction or unstable angina within 6 months of screening Subjects with acute or chronic congestive heart failure Subjects with a history of life-threatening cardiac arrhythmias Subjects with a history of hemodynamically significant aortic or mitral valve disease Subjects with more than mild restrictive or congestive cardiomyopathy uncontrolled by medication or implanted device. Subjects with 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 a history of cervical or digital sympathectomy Subjects with scleroderma renal crisis 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 Subjects must not initiate dosing of oral, topical, or intravenous (IV) vasodilators or if currently receiving any vasodilator must have been stably medicated Subjects with any history of acetaminophen intolerability Subjects with any malignancy that requires treatment during the study period, that has required treatment within 1 year of screening, 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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. | Drug: Placebo IV infusion<br>* Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.<br>|
| Active Comparator: Iloprost Injection, for intravenous use<br>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. | Drug: Iloprost Injection, for intravenous use<br>* Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of symptomatic RP attacks | The primary efficacy parameter is the change in the weekly frequency of symptomatic RP attacks from baseline. | Day 8 - Day 21 will be compared to baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic sclerosis, raynaud phenomenon