A Phase 3 interventional study of Ralinepag and Placebo in PAH, Pulmonary Hypertension and Pulmonary Arterial Hypertension, sponsored by United Therapeutics. Completed at 209 sites in 33 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-16.
Sponsored by United Therapeutics · Phase 3, Interventional, and Treatment
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.
Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable. The primary endpoint is the time (in days) from randomization to the first adjudicated protocol-defined clinical worsening event. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC) in a blinded fashion. Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on treatment at the conclusion of the study who have completed the Week 28 Visit (after the target number of confirmed events is achieved) will have the option to enroll in an open-label extension (OLE) study. Subjects who do not choose to participate in the OLE study will discontinue study drug and should remain in the study for long-term follow-up of survival status and will receive standard of care PAH treatment, at the discretion of the treating physician.
1,105 studies on the registry are indexed under Hypertension, Pulmonary; 234 are open to participants now.
This study's enrollment of 687 is above the median of 35 across 649 interventional studies indexed under Hypertension, Pulmonary.
Browse Hypertension, Pulmonary studies →United Therapeutics is the lead sponsor of 81 studies on the registry; 6 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 14 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose.
Drug: Ralinepag
Matching placebo tablets (oral)
Drug: Placebo
Active
Also known as: APD811
Placebo
Time from randomization to the first adjudicated protocol-defined clinical worsening event
Clinical worsening events are defined as death, nonelective hospital admission for worsening PAH (further defined in clinical study protocol), initiation of parenteral or inhaled prostacyclin pathway agent for treatment of worsening PAH, disease progression (further defined in clinical study protocol), or unsatisfactory long-term clinical response (further defined in clinical study protocol).
Time frame: The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years
Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)
NT-proBNP was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.
Time frame: Baseline to Week 28
Change from Baseline in 6-minute walk distance (6MWD)
6MWD was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.
Time frame: Baseline to Week 28
Change from Baseline in WHO/New York Heart Association (NYHA) Functional Class
The severity of PAH was graded according to the functional status of the subject and assessed at every visit.
Time frame: Baseline to Week 28
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
Data from NT-proBNP, 6MWD, and WHO/NYHA functional class assessment were compiled as a composite endpoint at visits through Week 28.
Time frame: Baseline to Week 28
Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score
Data from NT-proBNP, 6MWD, WHO/NYHA functional class, systolic blood pressure, heart rate, and estimated glomerular filtration rate values collected at visits through Week 28 were used to calculate the composite REVEAL risk score.
Time frame: Baseline to Week 28
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%.
Data from 6MWD, WHO/NYHA functional class assessment, and NT-proBNP were compiled as a composite endpoint at visits through Week 28.
Time frame: Baseline to Week 28
Change from Baseline in health-related quality of life as measured by patient-reported outcomes.
Quality of life was assessed using patient-reported outcomes at Baseline (prior to starting study drug) and Week 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.
Time frame: Baseline to Week 28
Time to first all-cause nonelective hospitalization
All nonelective hopsitalizations during the study period were collected.
Time frame: 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).
Time to all-cause mortality
All deaths during the study period were collected.
Time frame: 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).
Change from Baseline in heart rate recovery (HRR) following completion of the 6MWT
HRR was measured at Baseline (prior to starting study drug) and Week 4, 8, 12, and 16, then every 12 weeks thereafter including the End of Study/Early Termination Visit.
Time frame: Baseline to Week 28
Safety and tolerability of ralinepag in subjects with PAH
Safety and tolerability were assessed by adverse events.
Time frame: Baseline to Week 28
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