Intravenous Iloprost in Subjects With Symptomatic Raynaud... | NCT04040322

NCT04040322

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.

Eligibility Module

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

Contacts/Locations Module

Name	Affiliation	Role
Wade Benton, Pharm D	Eicos Sciences, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Arthritis & Rheumatology Research, PLLC		Phoenix	Arizona	85032	United States
Mayo Clinic - Scottsdale

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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. Placebo IV infusion: 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 18, 2020	Apr 23, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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. Placebo IV infusion: 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.
BG001	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. Iloprost Injection, for intravenous use: 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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00052.0± 10.92 BG00152.4± 13.59 BG00252.2± 12.31

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00086 BG00188 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00010 BG00112 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0012 BG002

Phosphodiesterase-5 (PDE5) Inhibitors at Screening

Count of Participants

Participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00037 BG00140 BG002

Weekly frequency of symptomatic RP attacks at baseline

Mean

Standard Deviation

Weekly frequency of RP attacks

Title

Denominators

Categories

Title	Measurements
	BG00028.63± 18.113 BG00132.49± 26.393 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

The Intention-To-Treat (ITT) Population was defined as all randomized patients who initiated (received) study drug infusion.

Posted

Least Squares Mean

95% Confidence Interval

Number of RP attacks per week

From baseline (Day 10 to Day 25 of screening period) to the end ofthe efficacy follow-up (Day 8 to Day 21).

ID	Title	Description
OG000	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. Placebo IV infusion: 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.
OG001	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. Iloprost Injection, for intravenous use: 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.

Units	Counts
Participants	OG00097 OG00199

Title

Denominators

Categories

Title	Measurements
	OG000-11.47(-13.69 to -9.25) OG001-12.73(-14.92 to -10.55)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.4210	Threshold for statistical significance was p < 0.05	Least squares mean difference in change	-1.26			2-Sided	95	-4.34	1.82					Superiority

Secondary

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.

The ITT-To-Treat (ITT) population, defined as all randomized patients who initiated (received) study drug infusion.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).

ID	Title	Description
OG000	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. Placebo IV infusion: 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.

Secondary

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.

Posted

Least Squares Mean

95% Confidence Interval

Minutes

From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).

ID	Title	Description
OG000	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. Placebo IV infusion: 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.
OG001	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. Iloprost Injection, for intravenous use: 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.

Secondary

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.

Posted

Count of Participants

Participants

From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).

ID	Title	Description
OG000	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. Placebo IV infusion: 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.
OG001	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. Iloprost Injection, for intravenous use: 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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. Placebo IV infusion: 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.	0	97	0	97	78	97
EG001	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. Iloprost Injection, for intravenous use: 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.	0	99	1	99	99	99

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hand fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 events0 affected97 at risk EG0011 events1 affected99 at risk
Limb traumatic amputation	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment		EG0000 events0 affected97 at risk EG0011 events1 affected99 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG00082 events38 affected97 at risk EG001271 events85 affected99 at risk
Dizziness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG00014 events10 affected97 at risk EG00116 events10 affected99 at risk
Head discomfort	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG00011 events5 affected97 at risk EG0015 events2 affected99 at risk
Paraesthesia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0008 events5 affected97 at risk EG0011 events1 affected99 at risk
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG00030 events15 affected97 at risk EG001104 events57 affected99 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0005 events5 affected97 at risk EG00132 events24 affected99 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0009 events9 affected97 at risk EG00120 events13 affected99 at risk
Fatigue	General disorders	MedDRA 22.0	Systematic Assessment	EG00011 events9 affected97 at risk EG00121 events15 affected99 at risk
Infusion site pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0006 events6 affected97 at risk EG00118 events15 affected99 at risk
Infusion site erythema	General disorders	MedDRA 22.0	Systematic Assessment	EG0004 events4 affected97 at risk EG0015 events5 affected99 at risk
Asthenia	General disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected97 at risk EG0015 events5 affected99 at risk
Infusion site extravasation	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0016 events6 affected99 at risk
Chills	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0017 events5 affected99 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0007 events4 affected97 at risk EG00158 events27 affected99 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0004 events4 affected97 at risk EG00111 events6 affected99 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0005 events5 affected97 at risk EG0019 events4 affected99 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG00022 events12 affected97 at risk EG00116 events11 affected99 at risk
Flushing	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG00021 events7 affected97 at risk EG00148 events28 affected99 at risk
Palpitations	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0008 events5 affected97 at risk EG0010 events0 affected99 at risk

First MCP Posted Date

ID	Term
D012595	Scleroderma, Systemic
D011928	Raynaud Disease

Ancestor Terms

ID	Term
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D012871	Skin Diseases
D000090122	Livedoid Vasculopathy
D013927	Thrombosis
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D016491	Peripheral Vascular Diseases
D017445	Skin Diseases, Vascular

ID	Term
D016285	Iloprost

Ancestor Terms

ID	Term
D011465	Prostaglandins, Synthetic
D011453	Prostaglandins
D015777	Eicosanoids
D005231	Fatty Acids, Unsaturated
D005227	Fatty Acids
D008055	Lipids
D012898	Autacoids
D018836	Inflammation Mediators
D001685	Biological Factors

Units	Counts
Participants	OG00097 OG00199