Raynaud Phenomenon Secondary to Systemic Sclerosis
Conditions
Keywords
systemic sclerosis, raynaud phenomenon
Brief summary
This is a Phase 2, multicenter, double-blind, randomized, placebo-controlled study to evaluate the effect of iloprost on the symptomatic relief of Raynaud's Phenomenon attacks in subjects with symptomatic Raynaud's Phenomenon secondary to Systemic Sclerosis.
Interventions
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 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.
Sponsors
Civi Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Subjects must have a diagnosis or history of Raynaud's Phenomenon * Subjects must have a minimum of 10 symptomatic Raynaud's Phenomenon attacks * 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 \<30 mL/min/1.73 m2 * Subjects with Child-Pugh Class B or Class C liver disease or an alanine aminotransferase and/or aspartate aminotransferase value \>3 × the upper limit of normal at screening. * Subjects with gangrene, digital ulcer infection, or requirement of cervical or digital sympathectomy * Subjects with intractable diarrhea or vomiting * Subjects with a risk of clinically significant bleeding events including those with coagulation or platelet disorders * Subjects with a history of major trauma or hemorrhage * Subjects with clinically significant chronic intermittent bleeding such as active gastric antral vascular ectasia or active peptic ulcer disease * Subjects who have had any cerebrovascular events * Subjects with a history of myocardial infarction or unstable angina within 6 months of screening * Subjects with acute or chronic congestive heart failure * Subjects with a history of life-threatening cardiac arrhythmias * Subjects with a history of hemodynamically significant aortic or mitral valve disease * Subjects with more than mild restrictive or congestive cardiomyopathy uncontrolled by medication or implanted device. * Subjects with 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 a history of cervical or digital sympathectomy * Subjects with scleroderma renal crisis * 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 * Subjects must not initiate dosing of oral, topical, or intravenous (IV) vasodilators or if currently receiving any vasodilator must have been stably medicated * Subjects with any history of acetaminophen intolerability * Subjects with any malignancy that requires treatment during the study period, that has required treatment within 1 year of screening, 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Frequency of Symptomatic RP Attacks | Day 8 - Day 21 will be compared to baseline | 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. |
Countries
United States
Participant flow
Recruitment details
The study was initiated on 07 March 2019 and completed on 06 August 2019. It was conducted in 16 sites located in the United States.
Pre-assignment details
In this study 41 participants with Systemic Sclerosis (SSc) were screened.34 participants who had at least 10 symptomatic Raynaud's phenomenon (RP) attacks on the 5-day eligibility period were randomized on to the study: 17 to the placebo arm and 17 to the Iloprost arm.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 17 |
| 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. | 17 |
| Total | 34 |
Baseline characteristics
| Characteristic | Iloprost Injection, for Intravenous Use | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 50.2 years STANDARD_DEVIATION 13.48 | 49.6 years STANDARD_DEVIATION 12.4 | 48.9 years STANDARD_DEVIATION 11.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 29 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Phosphodiesterase inhibitor at baseline No | 12 n (%) | 22 n (%) | 10 n (%) |
| Phosphodiesterase inhibitor at baseline Yes | 5 n (%) | 12 n (%) | 7 n (%) |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 28 Participants | 15 Participants |
| Sex: Female, Male Female | 17 Participants | 32 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
| Weekly frequency of symptomatic RP attacks at baseline | 37.05 no. of attacks STANDARD_DEVIATION 18.643 | 39.69 no. of attacks STANDARD_DEVIATION 24.525 | 42.32 no. of attacks STANDARD_DEVIATION 29.635 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 14 / 17 | 17 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
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.
Time frame: Day 8 - Day 21 will be compared to baseline
Population: The modified Intention-to-Treat (mITT) Population was defined as all randomized subjects who initiated infusion of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in Frequency of Symptomatic RP Attacks | -14.32 Number of RP attacks per week |
| Iloprost Injection, for Intravenous Use | Change in Frequency of Symptomatic RP Attacks | -15.09 Number of RP attacks per week |
Comparison: Treatment comparison of change versus placebo. LS mean difference in change. When a subject had no RP attacks in the past 24 hours, the frequency was considered as zero for that day.~The LS means, SEs, CIs, and p-values came from an ANCOVA model with randomized treatment group and use of phosphodiesterase inhibitors at screening (yes, no) as factors and baseline as a covariate.p-value: 0.849895% CI: [-9.04, 7.49]ANCOVA
Comparison: Change in the Weekly Frequency of Symptomatic Raynaud's Phenomenon Attacks From Baseline to the Double-Blind Endpoint Using Nonparametric Analysis - Modified Intent-to-Treat Population.~Treatment comparison of change versus placebo.p-value: 0.972995% CI: [-9.97, 9.32]Wilcoxon (Mann-Whitney)