Pulmonary HypertensionPhase 3CAPACITYNCT04084678
Study of Ralinepag on Exercise Capacity by Cardiopulmonary Exercise Testing (CPET) in WHO Group 1 PH Subjects
A Phase 3 study testing Ralinepag in people with Pulmonary Hypertension and Pulmonary Arterial Hypertension, run by United Therapeutics at 33 sites in 12 countries.
Trial summary
Study ROR-PH-302, ADVANCE CAPACITY, was designed to evaluate the effects of ralinepag therapy on exercise capacity as assessed by change in peak oxygen consumption (VO2) derived from cardiopulmonary exercise testing (CPET) after 28 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension, Pulmonary Arterial Hypertension
- What is being tested?
- Ralinepag
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 33 sitesin 12 countries
- Study dates
- 20 Jan 2021to 12 Apr 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form.
- At least 18 years of age.
- Primary diagnosis of PAH.
- 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.
- Has World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) II to III symptoms
- 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.
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- Has a 6-minute walk distance (6MWD) of ≥150 meters at Screening.
- Has a peak VO2 of ≥9 to <18 mL/min/kg during the Screening CPET, as assessed by the CPET core laboratory.
- 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.
- 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.
Who cannot join
- For subjects with known human immunodeficiency virus-associated PAH, a cluster of differentiation 4 T-cell count <200/mm3 at Screening.
- Has 3 or more left ventricular disease/dysfunction risk factors.
- Symptomatic coronary artery disease and/or myocardial infarction within past 6 months.
- Current symptomatic aortic or mitral valve disease.
- 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.
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- Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
- Requires use of supplemental oxygen during CPET.
- Respiratory exchange ratio <1.0 at Screening CPET as determined by the CPET core laboratory.
- Acute non-cardiac disorder that may affect exercise performance or be aggravated by exercise (eg, infection, renal failure, thyrotoxicosis).
- 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.
- Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis, or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
- Confirmed active infection with hepatitis B virus or hepatitis C virus.
- 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.
- 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.
- Hemoglobin concentration <9 g/dL at Screening.
- 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.
- Subject has pulmonary veno-occlusive disease.
- 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.
- 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.
- Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
- 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.
- 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.
- Known hypersensitivity to ralinepag or any of the excipients.
- Life expectancy <12 months based on the Investigator's opinion.
- Women who are pregnant, lactating, or breast-feeding.
Trial locations and contacts
33 sites in 12 countries.
33 sites in 12 countries
United States5 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
National Jewish Health
Denver, Colorado, 80206
Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226
Tampa General Hospital/University of South Florida Center for Advanced Lung Disease and Lung Transplant
Tampa, Florida, 33606
Banner University Medical Center (University of Arizona)
Tucson, Arizona, 85724
Australia4 sites
The Prince Charles Hospital
Chermside, Queensland, 4032
Macquarie University
North Ryde, New South Wales, 2109
Westmead Hospital, Dept Respiratory and Sleep Medicine
Westmead, New South Wales, 2145
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Brazil4 sites
Hospital Madre Teresa
Belo Horizonte, Minas Gerais, 30441-070
Centro de Hipertensão Pulmonar
Porto Alegre, 90035074
Hospital Sao Paulo
São Paulo, São Paulo, 04037-002
Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo - InCor-HCFMUSP
São Paulo, São Paulo, 05403-000
Canada3 sites
Peter Lougheed Center
Calgary, Alberta, T1Y 6J4
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
London Health Science Centre- Victoria Hospital
London, Ontario, N6A 5W9
Italy3 sites
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
Centro Cardiologico Monzino, IRCCS
Milan, 20138
AOU Policlinico Umberto I
Rome, 00161
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clínic I Provincial de Barcelona
Barcelona, 08036
Hospital Universitario 12 de Octubre
Madrid, 28041
Argentina2 sites
Hospital Britanico de Buenos Aires
Ciudad Autónoma de Bs. As., 1280
Instituto de Cardiología de Corrientes
Corrientes, W3400AMZ
Austria2 sites
Ordensklinikum Linz GmbH, Elisabethinen
Linz, 4020
AKH Wien, Innere Med. II, Kardiologie
Vienna, 1090
Belgium2 sites
Erasme University Hospital - Department of Cardiology
Brussels, 1070
Gasthuisberg University Hospital - Department of Pulmonology
Leuven, 3000
Germany2 sites
Universitätsklinikum Carl Gustav Carus TU Dresden, Medizinische Klinik I, Abteilung für Pneumologie
Dresden, Saxony, 01307
Thoraxklinik-Heidelberg, Zentrum für Pulmonale Hypertonie
Heidelberg, Baden-Wurttemberg, 69126
Poland2 sites
Uniwersytecki Szpital Kliniczny w Białymstoku, Klinika Kardiologii z Oddziałem Intensywnego Nadzoru Kardiologicznego
Bialystok, 15-276
Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Oddział Kardiologiczny
Otwock, 05-400
United Kingdom1 site
Imperial college Healthcare NHS Trust
London, W12 0HS
About this study
Official 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
Study ROR-PH-302, ADVANCE CAPACITY, was designed to evaluate the effects of ralinepag therapy on exercise capacity as assessed by change in peak oxygen consumption (VO2) derived from cardiopulmonary exercise testing (CPET) after 28 weeks of treatment.
Read the detailed description
ROR-PH-302 was a 28-week multicenter, randomized, double-blind, placebo-controlled study. Subjects who met entry criteria were randomly allocated 2:1 to receive ralinepag or placebo, in addition to their PAH-specific background therapy, as applicable. The primary endpoint was change from Baseline in peak VO2 (assessed by CPET) at Week 28. All subjects who completed the study on study drug through Week 28 had the option to receive ralinepag in an open-label extension (OLE) study. Subjects who discontinued study drug prior to Week 28, as well as those who completed Week 28 on study drug but chose not to participate in the OLE study, were contacted every 6 months and at the end of the study to determine their survival status. Subjects who prematurely discontinued study drug or withdrew from the study for any reason were not eligible to enter the OLE study.
- Being tested
- Ralinepag, Placebo
- Keywords
- Prostacyclin, Connective Tissue Disease-Associated, Cardiopulmonary Exercise Capacity (CPET), IP Receptor Agonist
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RalinepagDrug
Also called APD811
Oral ralinepag
PlaceboDrug
Matching oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Ralinepag | Experimental | Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the individual maximum tolerated dose (maximum dose of 1400 mcg) Receives: Drug: Ralinepag |
| Placebo | Placebo comparator | Matching placebo tablets (oral) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Peak VO2 Assessed by CPET
Peak VO2 by CPET was measured at Baseline (prior to starting study drug) and Week 28
Measured: Baseline to Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start20 Jan 2021
- Primary completion12 Apr 2023
- Study completion12 Apr 2023
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04084678
- Sponsor's protocol ID
- ROR-PH-302
- Acronym
- CAPACITY
- Status last verified
- Jun 2026
- First submitted
- 6 Sep 2019
- Last updated
- 6 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04084678
- Acronym / sponsor ID
- CAPACITY / ROR-PH-302
- Keywords
- Prostacyclin, Connective Tissue Disease-Associated, Cardiopulmonary Exercise Capacity (CPET), IP Receptor Agonist
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 10 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 20 Jan 2021 (actual)
- Primary completion
- 12 Apr 2023 (actual)
- Study completion
- 12 Apr 2023 (actual)
- First posted
- 10 Sep 2019 (actual)
- Results
- Posted 6 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study ROR-PH-302, ADVANCE CAPACITY, was designed to evaluate the effects of ralinepag therapy on exercise capacity as assessed by change in peak oxygen consumption (VO2) derived from cardiopulmonary exercise testing (CPET) after 28 weeks of treatment.
Detailed description
ROR-PH-302 was a 28-week multicenter, randomized, double-blind, placebo-controlled study. Subjects who met entry criteria were randomly allocated 2:1 to receive ralinepag or placebo, in addition to their PAH-specific background therapy, as applicable. The primary endpoint was change from Baseline in peak VO2 (assessed by CPET) at Week 28. All subjects who completed the study on study drug through Week 28 had the option to receive ralinepag in an open-label extension (OLE) study. Subjects who discontinued study drug prior to Week 28, as well as those who completed Week 28 on study drug but chose not to participate in the OLE study, were contacted every 6 months and at the end of the study to determine their survival status. Subjects who prematurely discontinued study drug or withdrew from the study for any reason were not eligible to enter the OLE study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ralinepag | Experimental | Drug: RalinepagRalinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the individual maximum tolerated dose (maximum dose of 1400 mcg) |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo tablets (oral) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed informed consent form.
- At least 18 years of age.
- Primary diagnosis of PAH.
- 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.
- Has World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) II to III symptoms
Key exclusion criteria (26 listed)
- For subjects with known human immunodeficiency virus-associated PAH, a cluster of differentiation 4 T-cell count <200/mm3 at Screening.
- Has 3 or more left ventricular disease/dysfunction risk factors.
- Symptomatic coronary artery disease and/or myocardial infarction within past 6 months.
- Current symptomatic aortic or mitral valve disease.
- Has evidence of more than mild lung disease on pulmonary function tests performed within 1 year prior to, or during, Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RalinepagAlso: APD811Oral ralinepag | Drug | Ralinepag |
| PlaceboMatching oral tablets | Drug | Placebo |
Primary outcome
Change From Baseline in Peak VO2 Assessed by CPET
Time frame: Baseline to Week 28
Peak VO2 by CPET was measured at Baseline (prior to starting study drug) and Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
33 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ralinepag in people with Pulmonary Hypertension and Pulmonary Arterial Hypertension, run by United Therapeutics at 33 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Australia, Brazil, Canada, Italy and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Peak VO2 Assessed by CPET (time frame: Baseline to Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.