Raynaud's Phenomenon Secondary to Systemic SclerosisPhase 3NCT04040322
Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)
A Phase 3 study testing Iloprost Injection, for intravenous use in people with Raynaud's Phenomenon Secondary to Systemic Sclerosis, run by Civi Biopharma, Inc. at 30 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Raynaud's Phenomenon Secondary to Systemic Sclerosis
- What is being tested?
- Iloprost Injection, for intravenous use
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 198 participants
- Where
- 30 sitesUnited States
- Study dates
- 14 Oct 2019to 9 Jun 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 28Show fewer
- 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
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
United States30 sites
University of Michigan
Ann Arbor, Michigan, 48109-5422
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21224
Tufts Medical Center
Boston, Massachusetts, 02111
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
Northwestern Medical Faculty Foundation
Chicago, Illinois, 60611
University of Cincinnati - Scleroderma Center
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
West Michigan Rheumatology PLLC
Grand Rapids, Michigan, 49546
University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics
Houston, Texas, 77030
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of California, Los Angeles Medical Center
Los Angeles, California, 90059
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota Maple Grove
Minneapolis, Minnesota, 55369
Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08903
University Medical Center New Orleans
New Orleans, Louisiana, 70112
Hospital for Special Surgery
New York, New York, 10021
Columbia University Medical Center
New York, New York, 10032
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Stanford University Medical Center
Palo Alto, California, 94305
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Arizona Arthritis & Rheumatology Research, PLLC
Phoenix, Arizona, 85032
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261
University of Utah
Salt Lake City, Utah, 84132
University of California San Francisco
San Francisco, California, 94143
Mayo Clinic - Scottsdale
Scottsdale, Arizona, 85259
Virginia Mason Medical Center
Seattle, Washington, 98101
The University of Toledo Medical Center (UTMC) - Ruppert Health Center
Toledo, Ohio, 43614
University of Arizona - Arthritis Research Center
Tucson, Arizona, 85724
Georgetown University Medical Center - Department of Rheumatology
Washington D.C., District of Columbia, 20007
About this study
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)
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.
- Being tested
- Placebo IV infusion, Iloprost Injection, for intravenous use
- Keywords
- systemic sclerosis, raynaud's phenomenon
- Medical subject headings
- Scleroderma, Systemic, Raynaud Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo IV infusionDrug
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.
Iloprost Injection, for intravenous useDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo IV infusion |
| Iloprost Injection, for intravenous use | Active comparator | 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. Receives: Drug: Iloprost Injection, for intravenous use |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Frequency of Symptomatic RP Attacks
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
Measured: From baseline (Day 10 to Day 25 of screening period) to the end ofthe efficacy follow-up (Day 8 to Day 21).
Secondary outcomes (3)
Change in Severity of RP Attack Symptoms
Change in overall severity of RP attack symptoms as registered in electronic diary. It was measured using an 11-point numeric rating scale (NRS) as follows: 0 = no pain/numbness/tingling/discomfort, 1 to 3 = mild pain/numbness/tingling/discomfort, 4 to 6 = moderate pain/numbness/tingling/discomfort, and 7 to 10 = severe pain/numbness/tingling/discomfort. The severity of the symptoms (pain, numbness, discomfort or tingling) was rated by the patient in the electronic diary (ePRO). The symptom with the worst average baseline value for each patient was compared to the average severity rate of that symptom which occurred during Days 8 to 21 of the treatment period. If more than 1 symptom had the same value, the symptom used for analysis was based on the following order of rank: pain>numbness>tingling>discomfort.
Measured: 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.
The weekly duration is calculated as the average duration of a systematic RP attack times weekly frequency, as registered in electronic diary.
The baseline weekly duration was calculated as the average duration of a systematic RP attack times weekly frequency during the 10- to 25-day baseline electronic diary completion period.
The end of the efficacy follow-up weekly duration of symptomatic RP attacks is calculated as the average duration of a systematic RP attack times weekly frequency during Days 8 to 21, inclusive.
Measured: 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
The responders are defined as participants that have at least 50% reduction in weekly total duration of symptomatic RP attacks and at least 50% reduction in overall severity from baseline.
Duration of symptomatic RP attacks and severity of attacks are obtained from electronic diary.
Measured: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start14 Oct 2019
- Primary completion9 Jun 2021
- Study completion9 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Raynaud's Phenomenon Secondary to Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- Civi Biopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wade Benton, Pharm D, Study director, Eicos Sciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04040322
- Sponsor's protocol ID
- ES-301
- Status last verified
- May 2025
- First submitted
- 30 Jul 2019
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04040322
- Acronym / sponsor ID
- ES-301
- Keywords
- systemic sclerosis, raynaud's phenomenon
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 198 participants (actual)
- Lead sponsor
- Civi Biopharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 9 Jun 2021 (actual)
- Study completion
- 9 Jun 2021 (actual)
- First posted
- 31 Jul 2019 (actual)
- Results
- Posted 25 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo IV infusionSubjects 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. |
| Iloprost Injection, for intravenous use | Active comparator | Drug: Iloprost Injection, for intravenous useSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo IV infusionStudy 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. | Drug | Placebo |
| Iloprost Injection, for intravenous useStudy 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. | Drug | Iloprost Injection, for intravenous use |
Primary outcome
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
3 secondary outcomes
Change in Severity of RP Attack Symptoms
Time frame: 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.
Time frame: 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
Time frame: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wade Benton, Pharm D study director
Eicos Sciences, Inc.
30 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Iloprost Injection, for intravenous use in people with Raynaud's Phenomenon Secondary to Systemic Sclerosis, run by Civi Biopharma, Inc. at 30 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.