A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients

Inclusion Criteria:

1. At least 18 years of age.

2. Evidence of a personally signed and dated informed consent form indicating that thesubject has been informed of all pertinent aspects of the study prior to initiationof 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 toScreening (RHC will be performed during Screening if not available) that isconsistent 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 eitheran 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 receptorblockers), must be on a stable dose for at least 30 days prior to the Baseline Visitand the dosage maintained throughout the study. The exception is that the dose ofdiuretics 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 birthcontrol throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male andfemale subjects must also agree not to participate in a conception process duringthe study and for 30 days after the last dose of IMP. Eligible male subjects mustagree 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-cellcount <200/mm3 within 90 days of Baseline.

2. Must not have 3 or more left ventricular dysfunction risk factors as defined in thestudy protocol.

3. Has evidence of more than mild lung disease on pulmonary function tests performedwithin 180 days prior to, or during Screening.

4. Has evidence of thromboembolic disease as determined by a V/Q lung scan or localstandard of care diagnostic evaluation at or after diagnosis of PAH.

5. Current diagnosis of ongoing and clinically significant sleep apnea as defined bythe Investigator.

6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450msec and female subjects with a QTcF >470 msec on ECG recorded at Screening andanalyzed by the central ECG laboratory. Subjects with evidence of intraventricularconduction delay, defined as a QRS interval greater than 110 msec, will be excludedif 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 varicealhemorrhage, 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 theupper 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 requiringdialysis 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) or activin signaling inhibitor for PAH at any time priorto Baseline (use in vasoreactive testing is permitted).

13. Subjects currently on or who were treated with an inhaled or oral prostacyclinpathway agent (iloprost, treprostinil, beraprost, or selexipag) for >6 months orwithin 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 theexception of localized non-metastatic basal cell or squamous cell carcinoma of theskin 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 atScreening, or has a recent history (6 months) of alcohol or drug abuse. A subjectwill not be excluded due to a positive drug screen caused by prescribed medications.

17. Initiation or discontinuation of a cardio-pulmonary rehabilitation program basedupon exercise within 90 days prior to Screening and/or planned during studyparticipation.

18. Prior participation in any study of ralinepag or participation in anotherinterventional clinical study with medicinal products within 30 days prior toScreening. Concurrent participation in registry or observational studies is allowed,as long as the subject can fulfill all other entry criteria and comply with allstudy procedures.

19. Any reason that, in the opinion of the Investigator or Medical Monitor, precludesthe subject from participating in the study (eg, any previous or intercurrentmedical condition) that may increase the risk associated with study participation orthat 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.