A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH

• Register: ClinicalTrials.gov
• Last refreshed on: 30 October 2023
• Main ID: NCT04084678
• Date of registration: 06/09/2019
• Prospective Registration: Yes
• Primary sponsor: United Therapeutics
• Public title: A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH CAPACITY
• 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
• Date of first enrolment: January 20, 2021
• Target sample size: 10
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT04084678
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Germany, Italy, Poland, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

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.

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lung Diseases

Hypertension, Pulmonary

Respiratory Tract Disease

Familial Primary Pulmonary Hypertension

Pulmonary Arterial Hypertension

Connective Tissue Disease

Pulmonary Hypertension

Cardiovascular Diseases

Hypertension

PAH

Vascular Diseases

Intervention(s)

Drug: Ralinepag

Drug: Placebo

Primary Outcome(s)

Change from Baseline in peak VO2 assessed by CPET [Time Frame: Baseline to Week 28]

Secondary Outcome(s)

Time to First All-cause Non-elective Hospitalization [Time Frame: Baseline to Week 28]

Change from Baseline in health-related quality of life measured by the Short Form Health Survey (SF-36) Scores [Time Frame: Baseline to Week 28]

Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) [Time Frame: Baseline to Week 28]

Change from Baseline in Minute Ventilation (VE)/Carbon Dioxide output (VCO2) slope [Time Frame: Baseline to Week 28]

Secondary ID(s)

ROR-PH-302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors