A Study to Evaluate the Effectiveness and Safety of RalinEpag for Improving Treatment Outcomes in PAH Patients

Overview

About this study

The purpose of this study is to demonstrate the effect of ralinepag the time to first adjudicated clinical worsening event in subjects with pulmonary arterial hypertension (PAH).Clinical worsening event is defined as 1 of the following: death, nonelective hospital admission of <24 hours due to worsening PAH or RHF, initiation of parenteral or inhaled therapy, disease progression, or unsatisfactory long term clinical response.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 6/1/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Charles Burger, M.D.

Open for enrollment

Contact information:

Inna Dawson CCRP

Abrea.Inna@mayo.edu

More information

Publications

Publications are currently not available