A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study Evaluating the Safety and Efficacy of Intravenous Iloprost in Subjects With Systemic Sclerosis Experiencing Symptomatic Digital Ischemic Episodes (AURORA Study)
Overview
- Phase
- Phase 3
- Intervention
- Placebo IV infusion
- Conditions
- Raynaud's Phenomenon Secondary to Systemic Sclerosis
- Sponsor
- Civi Biopharma, Inc.
- Enrollment
- 198
- Locations
- 30
- Primary Endpoint
- Change in Frequency of Symptomatic RP Attacks
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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.
Investigators
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.
Arms & Interventions
Placebo
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.
Intervention: Placebo IV infusion
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.
Intervention: Iloprost Injection, for intravenous use
Outcomes
Primary Outcomes
Change in Frequency of Symptomatic RP Attacks
Time Frame: From baseline (Day 10 to Day 25 of screening period) to the end ofthe efficacy follow-up (Day 8 to Day 21).
The primary efficacy parameter is the change in the weekly frequency of symptomatic RP attacks from baseline. The baseline weekly frequency of symptomatic RP attacks was defined as the average number of weekly symptomatic RP attacks that occurred during the 10- to 25-day baseline ePRO diary completion period. The double-blind endpoint weekly frequency of symptomatic RP attacks was defined as the average number of weekly symptomatic RP attacks that occurred during Days 8 to 21, inclusive
Secondary Outcomes
- Change in Severity of RP Attack Symptoms(From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).)
- Weekly Total Duration of Symptomatic RP Attacks.(From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).)
- Percentage of Responders(From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).)