Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04084678




Registration number
NCT04084678
Ethics application status
Date submitted
6/09/2019
Date registered
10/09/2019
Date last updated
24/10/2023

Titles & IDs
Public title
A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Ralinepag to Evaluate Safety and Effects on Exercise Capacity Assessed by CPET in Subjects With WHO Group 1 Pulmonary Hypertension Who Recently Initiated Therapy
Secondary ID [1] 0 0
ROR-PH-302
Universal Trial Number (UTN)
Trial acronym
CAPACITY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PAH 0 0
Pulmonary Hypertension 0 0
Hypertension 0 0
Connective Tissue Disease 0 0
Familial Primary Pulmonary Hypertension 0 0
Vascular Diseases 0 0
Cardiovascular Diseases 0 0
Hypertension, Pulmonary 0 0
Lung Diseases 0 0
Respiratory Tract Disease 0 0
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ralinepag
Treatment: Drugs - Placebo

Experimental: Ralinepag - Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the individual maximum tolerated dose (maximum dose of 1400 mcg)

Placebo comparator: Placebo - Matching placebo tablets (oral)


Treatment: Drugs: Ralinepag
Oral ralinepag

Treatment: Drugs: Placebo
Matching oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in peak VO2 assessed by CPET
Timepoint [1] 0 0
Baseline to Week 28
Secondary outcome [1] 0 0
Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
Timepoint [1] 0 0
Baseline to Week 28
Secondary outcome [2] 0 0
Change from Baseline in Minute Ventilation (VE)/Carbon Dioxide output (VCO2) slope
Timepoint [2] 0 0
Baseline to Week 28
Secondary outcome [3] 0 0
Change from Baseline in health-related quality of life measured by the Short Form Health Survey (SF-36) Scores
Timepoint [3] 0 0
Baseline to Week 28
Secondary outcome [4] 0 0
Time to First All-cause Non-elective Hospitalization
Timepoint [4] 0 0
Baseline to Week 28

Eligibility
Key inclusion criteria
1. Signed informed consent form.
2. At least 18 years of age.
3. Primary diagnosis of PAH.
4. Has had a diagnostic RHC performed at or within 3 years before Screening (or at Screening if one is not available) that is consistent with the diagnosis of PAH.
5. Has World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) II to III symptoms
6. Must be on a stable dose of PAH-specific oral therapy, defined as no change in dose or regimen for at least 90 days prior to randomization. Allowable PAH-specific therapy is an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator. Subjects may be on a stable dose of either a PDE5-I or a sGC stimulator, not both.
7. Has a 6-minute walk distance (6MWD) of =150 meters at Screening.
8. Has a peak VO2 of =9 to <18 mL/min/kg during the Screening CPET, as assessed by the CPET core laboratory.
9. If the subject is taking concomitant medications that may affect the clinical manifestations of PAH, the subject must be on a stable dose for at least 30 days prior to randomization. The exception is that the dose of diuretics must be stable for at least the 10 days prior to randomization.
10. Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the Week 28 Visit/28-day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the final dose of study drug. Eligible male subjects must agree not to participate in sperm donation for 90 days after the final dose of study drug. Women who are surgically sterile or postmenopausal are not considered to be of childbearing potential. If of childbearing potential, female partners of male study participants should agree to utilize medically acceptable methods of contraception for the duration of study participation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. For subjects with known human immunodeficiency virus-associated PAH, a cluster of differentiation 4 T-cell count <200/mm3 at Screening.
2. Has 3 or more left ventricular disease/dysfunction risk factors.
3. Symptomatic coronary artery disease and/or myocardial infarction within past 6 months.
4. Current symptomatic aortic or mitral valve disease.
5. Has evidence of more than mild lung disease on pulmonary function tests performed within 1 year prior to, or during, Screening.
6. Has evidence of thromboembolic disease as determined by ventilation-perfusion lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
7. Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
8. Requires use of supplemental oxygen during CPET.
9. Respiratory exchange ratio <1.0 at Screening CPET as determined by the CPET core laboratory.
10. Acute non-cardiac disorder that may affect exercise performance or be aggravated by exercise (eg, infection, renal failure, thyrotoxicosis).
11. Male subjects with a QTcF >450 msec and female subjects with a QTcF >470 msec on electrocardiogram (ECG) recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval >110 msec, will be excluded if QTcF is >500 msec for both males and females.
12. Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis, or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
13. Confirmed active infection with hepatitis B virus or hepatitis C virus.
14. Subjects with alanine aminotransferase or aspartate aminotransferase =3 times the upper limit of normal or total bilirubin =2 times the upper limit of normal at Screening.
15. Chronic renal insufficiency as defined by an estimated glomerular filtration rate using the Modification of Diet in Renal Disease Study equation of <30 mL/min/1.73 m2 or requiring dialysis at Screening.
16. Hemoglobin concentration <9 g/dL at Screening.
17. Subjects treated with an intravenous, subcutaneous, inhaled, or oral prostacyclin pathway agent (eg, epoprostenol, treprostinil, iloprost, beraprost, or selexipag) for PAH within 90 days of randomization (use in vasoreactive testing is permitted). Subject is not eligible if previous prostacyclin therapy was stopped for a safety or tolerability issue related to systemic prostacyclin adverse effects.
18. Subject has pulmonary veno-occlusive disease.
19. Malignancy diagnosed and/or treated within 3 years of Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
20. Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine, or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. Subjects will not be excluded due to a positive drug screen caused by prescribed medications.
21. Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
22. Prior participation in any study of ralinepag or another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, if the subject can fulfill all other entry criteria and comply with all study procedures.
23. Any reason that, in the opinion of the Investigator, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis (eg, right-to-left shunt detected during CPET) or impair study participation or cooperation.
24. Known hypersensitivity to ralinepag or any of the excipients.
25. Life expectancy <12 months based on the Investigator's opinion.
26. Women who are pregnant, lactating, or breast-feeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/04/2023
Sample size
Target
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Macquarie University - North Ryde
Recruitment hospital [2] 0 0
Westmead Hospital, Dept Respiratory and Sleep Medicine - Westmead
Recruitment hospital [3] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2109 - North Ryde
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4032 - Chermside
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Wisconsin
Country [5] 0 0
Argentina
State/province [5] 0 0
Ciudad Autónoma de Bs. As.
Country [6] 0 0
Argentina
State/province [6] 0 0
Corrientes
Country [7] 0 0
Austria
State/province [7] 0 0
Linz
Country [8] 0 0
Austria
State/province [8] 0 0
Vienna
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussels
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Brazil
State/province [11] 0 0
MG
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Brazil
State/province [13] 0 0
Porto Alegre
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Germany
State/province [16] 0 0
Baden-Wurttemberg
Country [17] 0 0
Germany
State/province [17] 0 0
Sachsen
Country [18] 0 0
Italy
State/province [18] 0 0
Milano
Country [19] 0 0
Italy
State/province [19] 0 0
Rome
Country [20] 0 0
Poland
State/province [20] 0 0
Bialystok
Country [21] 0 0
Poland
State/province [21] 0 0
Otwock
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
United Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04084678