A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH

NCT04084678 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: ROR-PH-302
• Study Type: interventional
• Target: 10
• Locations: 11 countries
• Sites: 31

Brief Summary

Study ROR-PH-302, ADVANCE CAPACITY, is 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

Conditions

PAH; Pulmonary Hypertension; Hypertension; Connective Tissue Disease; Familial Primary Pulmonary Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Disease; Pulmonary Arterial Hypertension

Keywords

Prostacyclin; Connective Tissue Disease-Associated; Cardiopulmonary Exercise Capacity (CPET); IP Receptor Agonist

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to Week 28

Secondary Outcomes (4)

• Change from Baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP)

  Baseline to Week 28

• Change from Baseline in Minute Ventilation (VE)/Carbon Dioxide output (VCO2) slope

  Baseline to Week 28

• Change from Baseline in health-related quality of life measured by the Short Form Health Survey (SF-36) Scores

  Baseline to Week 28

• Time to First All-cause Non-elective Hospitalization

  Baseline to Week 28

Study Arms (2)

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)

Drug: Ralinepag

Placebo

PLACEBO COMPARATOR

Matching placebo tablets (oral)

Drug: Placebo

Interventions

Ralinepag DRUG

Oral ralinepag

Also known as: APD811

Ralinepag

Placebo DRUG

Matching oral tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (33)

Banner University Medical Center (University of Arizona)

Tucson, Arizona, 85724, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Tampa General Hospital/University of South Florida Center for Advanced Lung Disease and Lung Transplant

Tampa, Florida, 33606, United States

Location

Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Britanico de Buenos Aires

Ciudad Autónoma de Bs. As., 1280, Argentina

Location

Instituto de Cardiología de Corrientes

Corrientes, W3400AMZ, Argentina

Location

Macquarie University

North Ryde, New South Wales, 2109, Australia

Location

Westmead Hospital, Dept Respiratory and Sleep Medicine

Westmead, New South Wales, 2145, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Ordensklinikum Linz GmbH, Elisabethinen

Linz, 4020, Austria

Location

AKH Wien, Innere Med. II, Kardiologie

Vienna, 1090, Austria

Location

Erasme University Hospital - Department of Cardiology

Brussels, 1070, Belgium

Location

Gasthuisberg University Hospital - Department of Pulmonology

Leuven, 3000, Belgium

Location

Hospital Madre Teresa

Belo Horizonte, Minas Gerais, 30441-070, Brazil

Location

Hospital Sao Paulo

São Paulo, São Paulo, 04037-002, Brazil

Location

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo - InCor-HCFMUSP

São Paulo, São Paulo, 05403-000, Brazil

Location

Centro de Hipertensão Pulmonar

Porto Alegre, 90035074, Brazil

Location

Peter Lougheed Center

Calgary, Alberta, T1Y 6J4, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

London Health Science Centre- Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

Thoraxklinik-Heidelberg, Zentrum für Pulmonale Hypertonie

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

Universitätsklinikum Carl Gustav Carus TU Dresden, Medizinische Klinik I, Abteilung für Pneumologie

Dresden, Saxony, 01307, Germany

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Centro Cardiologico Monzino, IRCCS

Milan, 20138, Italy

Location

AOU Policlinico Umberto I

Rome, 00161, Italy

Location

Uniwersytecki Szpital Kliniczny w Białymstoku, Klinika Kardiologii z Oddziałem Intensywnego Nadzoru Kardiologicznego

Bialystok, 15-276, Poland

Location

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Oddział Kardiologiczny

Otwock, 05-400, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Imperial college Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Hypertension; Connective Tissue Diseases; Familial Primary Pulmonary Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Pulmonary Arterial Hypertension

Interventions

ralinepag

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2019
• First Posted: September 10, 2019
• Study Start: January 20, 2021
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

AU (4); BR (4); IT (3); CA (3); GB (1); BE (2); AR (2); DE (2); ES (3); PL (2); US (5)