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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03626688




Registration number
NCT03626688
Ethics application status
Date submitted
27/07/2018
Date registered
13/08/2018
Date last updated
14/08/2024

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH
Secondary ID [1] 0 0
APD811-301
Secondary ID [2] 0 0
ROR-PH-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PAH 0 0
Pulmonary Hypertension 0 0
Pulmonary Arterial Hypertension 0 0
Hypertension 0 0
Connective Tissue Diseases 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
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 highest tolerated dose.

Placebo comparator: Placebo - Matching placebo tablets (oral)


Treatment: Drugs: Ralinepag
Active

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

Outcomes
Primary outcome [1] 0 0
Time from randomization to the first adjudicated protocol-defined clinical worsening event
Timepoint [1] 0 0
The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years
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 6-minute walk distance (6MWD)
Timepoint [2] 0 0
Baseline to Week 28
Secondary outcome [3] 0 0
Change from Baseline in WHO/New York Heart Association (NYHA) Functional Class
Timepoint [3] 0 0
Baseline to Week 28
Secondary outcome [4] 0 0
Shift and proportion of subjects who attain all 3 of the following: NT-proBNP level <300 pg/mL, 6MWD >440 meters, and WHO/NYHA Functional Class I or II
Timepoint [4] 0 0
Baseline to Week 28
Secondary outcome [5] 0 0
Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score
Timepoint [5] 0 0
Baseline to Week 28
Secondary outcome [6] 0 0
Clinical improvement as defined by the absence of clinical worsening and fulfillment of at least 2 of the 3 of the following: increase in 6MWD =10% or =30 m, improvement to or maintenance of WHO FC I or II, and decrease in NT-proBNP by at least 30%.
Timepoint [6] 0 0
Baseline to Week 28
Secondary outcome [7] 0 0
Change from Baseline in health-related quality of life as measured by patient-reported outcomes.
Timepoint [7] 0 0
Baseline to Week 28
Secondary outcome [8] 0 0
Time to first all-cause nonelective hospitalization
Timepoint [8] 0 0
The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).
Secondary outcome [9] 0 0
Time to all-cause mortality
Timepoint [9] 0 0
The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study (when the target number of adjudicated events was achieved, as defined in the study protocol).
Secondary outcome [10] 0 0
Change from Baseline in heart rate recovery (HRR) following completion of the 6MWT
Timepoint [10] 0 0
Baseline to Week 28
Secondary outcome [11] 0 0
Safety and tolerability of ralinepag in subjects with PAH
Timepoint [11] 0 0
Baseline to Week 28

Eligibility
Key inclusion criteria
1. At least 18 years of age.
2. Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
4. Primary diagnosis of symptomatic PAH.
5. Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.
6. Has WHO/ NYHA functional class II to IV symptoms.
7. If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator.
8. Has a 6MWD of =150 meters.
9. If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.
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 30-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 last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.
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 HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count <200/mm3 within 90 days of Baseline.
2. Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
3. Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
4. Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
5. Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is >500 msec for both males and females.
7. Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
8. Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
9. Subjects with alanine aminotransferase or aspartate aminotransferase =3 times the upper limit of normal (ULN) or total bilirubin =2 × ULN at Screening.
10. Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL or requiring dialysis at Screening.
11. Hemoglobin concentration <9 g/dL at Screening.
12. Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
13. Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for >6 months or within 90 days prior to Baseline.
14. Subject has pulmonary veno-occlusive disease.
15. Malignancy diagnosed and/or treated within 5 years prior to 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.
16. 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. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
17. Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
18. Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
19. Any reason that, in the opinion of the Investigator or Medical Monitor, 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 or impair study participation or cooperation.
20. Known hypersensitivity to ralinepag or any of the excipients.
21. Life expectancy <12 months based on the Investigator's opinion.
22. 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 0 0
Macquarie University - Macquarie
Recruitment hospital [5] 0 0
Westmead Hospital - Sydney
Recruitment hospital [6] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [7] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [9] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [10] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [11] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2751 - Kingswood
Recruitment postcode(s) [4] 0 0
2109 - Macquarie
Recruitment postcode(s) [5] 0 0
2145 - Sydney
Recruitment postcode(s) [6] 0 0
4032 - Chermside
Recruitment postcode(s) [7] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 0 0
7000 - Hobart
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy
Recruitment postcode(s) [10] 0 0
3004 - Melbourne
Recruitment postcode(s) [11] 0 0
6150 - Murdoch
Recruitment outside Australia
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Istanbul
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Izmir
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Ukraine
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Dnipro
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Ukraine
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Kyiv
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Ukraine
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Lviv
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United Kingdom
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Greater London
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Tyne & Wear
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United Kingdom
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London

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

Ethics approval
Ethics application status

Summary
Brief summary
Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard of care or PAH-specific background therapy in subjects with World Health Organization (WHO) Group 1 PAH.
Trial website
https://clinicaltrials.gov/study/NCT03626688
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
United Therapeutics Global Medical Information
Address 0 0
Country 0 0
Phone 0 0
919-485-8350
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03626688