Ralinepag for Pulmonary Arterial Hypertension

(CAPACITY Trial)

No longer recruiting at 40 trial locations

Overseen By United Therapeutics Global Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: United Therapeutics

Must be taking: Endothelin antagonists, PDE5 inhibitors

Must not be taking: Prostacyclin agents

Disqualifiers: Coronary artery disease, Lung disease, Liver disease, Renal insufficiency, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a new treatment, ralinepag, can improve exercise capacity in people with pulmonary arterial hypertension (PAH). Researchers aim to determine if ralinepag helps participants breathe better and exercise more effectively after 28 weeks of treatment. Participants will receive either ralinepag or a placebo (a pill with no active medicine) to compare results. Individuals diagnosed with PAH, experiencing symptoms that affect daily activities, and already on stable PAH medication might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current PAH-specific oral therapy for at least 90 days before joining. If you're taking other medications that might affect PAH, those doses should be stable for at least 30 days before starting, except for diuretics, which need to be stable for 10 days.

Is there any evidence suggesting that ralinepag is likely to be safe for humans?

Research has shown that ralinepag is generally safe for people. In earlier studies, the most common side effects included headaches, nausea, and jaw pain, none of which were serious. No deaths or major health issues occurred. Some participants also experienced diarrhea and flushing, a warm and red feeling in the skin. These effects are typical for this type of medication. While these side effects might be uncomfortable, they are usually not dangerous. Overall, evidence suggests that ralinepag is safe to try, but clinical trial participants should be aware of these possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary hypertension (PH), which typically include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs, Ralinepag offers a novel approach. Ralinepag is unique because it is a once-daily, extended-release oral medication that acts as a selective prostacyclin receptor agonist, which might improve exercise capacity in patients. This mechanism allows it to potentially provide more sustained and targeted effects compared to existing therapies, which is why researchers are keenly interested in its potential benefits.

What evidence suggests that ralinepag might be an effective treatment for exercise capacity?

Research has shown that ralinepag, which participants in this trial may receive, might help treat pulmonary arterial hypertension (PAH). An earlier study found that people with PAH experienced a 29.8% reduction in the resistance of blood flow in their lungs, suggesting improved heart and lung function. Ralinepag helps open blood vessels and lower pressure in the lungs, which can enhance exercise capacity and support heart health. Another study found ralinepag safe and effective for long-term use. These findings suggest that ralinepag could help people with PAH exercise more easily and manage their symptoms better. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

Inclusion Criteria

You have provided a signed consent form.

You are displaying WHO/NYHA FC II to III symptoms.

You have a peak VO2 between 9 and 18 mL/min/kg, as determined by the CPET core laboratory.

Exclusion Criteria

For subjects with known human immunodeficiency virus-associated PAH, a cluster of differentiation 4 T-cell count <200/mm3 at Screening.

Has evidence of more than mild lung disease on pulmonary function tests performed within 1 year prior to, or during, Screening.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ralinepag or placebo for 28 weeks to evaluate effects on exercise capacity

28 weeks

Visits at Baseline, Weeks 4, 8, 12, 16, 20, 24, and 28

Follow-up

Participants are monitored for survival status every 6 months if they discontinue or do not enter the open-label extension

6 months

Open-label extension (optional)

Participants may opt into continuation of ralinepag treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ralinepag

How Is the Trial Designed?

Group I: Ralinepag Experimental Treatment 1 Intervention

Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the individual maximum tolerated dose (maximum dose of 1400 mcg)

Group II: Placebo Placebo Group 1 Intervention

Matching placebo tablets (oral)

Who Is Running the Clinical Trial?

United Therapeutics

Lead Sponsor

Trials

112

Recruited

14,500+

Dr. Martine Rothblatt

United Therapeutics

Chief Executive Officer since 1996

PhD in Medical Ethics from the Royal London College of Medicine and Dentistry, JD and MBA from UCLA

Dr. Michael Benkowitz

United Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

A systematic review of 108 adverse drug event (ADE) reporting systems revealed 1782 unique data fields, highlighting significant variability in how ADEs are reported, which complicates data comparison and aggregation across different systems.

Despite consistent reporting concepts, the lack of standardized terminology and the use of multiple drug and disease dictionaries hinder effective drug safety monitoring, suggesting a need for a common standardized dataset to improve ADE reporting and surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug event reporting systems: a systematic review. Bailey, C., Peddie, D., Wickham, ME., et al.[2021]

The over-reporting of serious adverse events (SAEs) during clinical trials can obscure true safety signals and burden sponsors, investigators, and FDA reviewers, potentially endangering patient safety.

A working group from LUNGevity Foundation suggests that 'anticipated' SAEs related to lung cancer should not be reported individually to the FDA, but rather analyzed in aggregate, which could streamline reporting and improve safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing Uninformative IND Safety Reports: A List of Serious Adverse Events anticipated to Occur in Patients with Lung Cancer. Bonomi, P., Stuccio, N., Delgra, CJ., et al.[2021]

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

A new standardized strategy for reporting adverse events (AEs) and serious adverse events (SAEs) in substance use disorder (SUD) clinical trials was developed, which aims to reduce the reporting burden while maintaining safety monitoring.

In a review of 17 SUD trials involving 6737 participants, the new strategy showed a significant reduction in irrelevant safety event reporting, leading to a more consistent safety assessment system tailored to the risks associated with specific trial interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for safety reporting in substance abuse trials. Lindblad, R., Campanella, M., Styers, D., et al.[2013]

Citations

1. ir.unither.com ir.unither.com/press-releases/2025/06-23-2025-120029259

United Therapeutics Corporation Concludes Enrollment of ... A previous phase 2 study of ralinepag in 61 PAH participants met its primary endpoint, showing a 29.8% reduction (p=0.03) in median pulmonary ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38198043/

Ralinepag Phase II Open-Label Extension Study in ... This clinical study of 45 patients investigated whether ralinepag was safe and effective for long-term use to treat people with pulmonary arterial hypertension.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2950133425000655

Safety and pharmacokinetics of ralinepag, a novel oral ... Ralinepag is an oral, potent, highly selective prostacyclin receptor agonist and is in development for pulmonary arterial hypertension.

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT03626688

Ralinepag to Improve Treatment Outcomes in PAH Patients Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03626688

NCT03626688 | A Study Evaluating the Efficacy and Safety ... Study ROR-PH-301, ADVANCE OUTCOMES, is designed to assess the efficacy and safety of ralinepag when added to pulmonary arterial hypertension (PAH) standard ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7238799/

Safety, tolerability, and pharmacokinetics of the selective ... Dose-limiting side effects may include headache, flushing, diarrhea, nausea, and jaw pain. Parenteral modes of administration for this drug class include ...

7. publications.ersnet.org publications.ersnet.org/content/erj/54/4/1901030

Efficacy and safety of ralinepag, a novel oral IP agonist, in ... For patients treated with ralinepag, the most common adverse events reported during the study were headache (n=31, 78%), nausea (n=20, 50%) and diarrhoea (n=19, ...

8. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/30009m.pdf

Safety Data Sheet Information on toxicological effects. · Acute toxicity: · Primary irritant effect: · on the skin: Irritant to skin and mucous membranes. · on ...