Clinical trial NCT04040322: Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Raynaud's Phenomenon Secondary to Systemic Sclerosis
Keywords: systemic sclerosis
raynaud's phenomenon
Lead sponsor: Civi Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-31
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Frequency of Symptomatic RP Attacks
timeFrame: From baseline (Day 10 to Day 25 of screening period) to the end ofthe efficacy follow-up (Day 8 to Day 21).
Secondary outcomes:
measure: Change in Severity of RP Attack Symptoms
timeFrame: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).
measure: Weekly Total Duration of Symptomatic RP Attacks.
timeFrame: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).
measure: Percentage of Responders
timeFrame: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Tucson
country: United States
facility: University of Arizona - Arthritis Research Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center - Department of Rheumatology
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: West Michigan Rheumatology PLLC
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Maple Grove
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati - Scleroderma Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo Medical Center (UTMC) - Ruppert Health Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Houston
country: United States
facility: University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Eicos Sciences, Inc.
name: Wade Benton, Pharm D
role: STUDY_DIRECTOR
References: