Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)

NCT04040322 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ES-301
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 30

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.

Conditions

Raynaud's Phenomenon Secondary to Systemic Sclerosis

Keywords

systemic sclerosis; raynaud's phenomenon

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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).

Study Arms (2)

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.

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.

Drug: Iloprost Injection, for intravenous use

Interventions

Placebo IV infusion DRUG

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.

Placebo

Iloprost Injection, for intravenous use DRUG

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 use

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Civi Biopharma, Inc.: lead

Study Sites (30)

Arizona Arthritis & Rheumatology Research, PLLC

Phoenix, Arizona, 85032, United States

Location

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of Arizona - Arthritis Research Center

Tucson, Arizona, 85724, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, Los Angeles Medical Center

Los Angeles, California, 90059, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Georgetown University Medical Center - Department of Rheumatology

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5422, United States

Location

West Michigan Rheumatology PLLC

Grand Rapids, Michigan, 49546, United States

Location

University of Minnesota Maple Grove

Minneapolis, Minnesota, 55369, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Cincinnati - Scleroderma Center

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

The University of Toledo Medical Center (UTMC) - Ruppert Health Center

Toledo, Ohio, 43614, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Scleroderma, Systemic; Raynaud Disease

Interventions

Iloprost

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Results Point of Contact

• Title: Chief Executive Officer
• Organization: CiVi Biopharma, Inc.

sj@civibio.com

301-968-2390

Study Officials

• Wade Benton, Pharm D

  Eicos Sciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: July 31, 2019
• Study Start: October 14, 2019
• Primary Completion: June 9, 2021
• Study Completion: June 9, 2021
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (30)