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

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Ralinepag When Added to PAH Standard of Care or PAH Specific Background Therapy in Subjects With WHO Group 1 PAH

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 Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Vascular Diseases; Lung Diseases; Hypertension; Connective Tissue Diseases; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary; Pulmonary Hypertension; PAH; Respiratory Tract Disease
• Intervention / Treatment: Drug: Placebo; Drug: Ralinepag

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 687
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1039AAO
    • Sanatorio de la Trinidad Mitre
  • Caba, Argentina, 1425
    • Cardiologia Palmero
  • Ciudad Autonoma Buenos Aires, Argentina, 1280
    • Hospital Britanico de Buenos Aires
  • Ciudad Autonoma Buenos Aires, Argentina, C1093AAS
    • Fundacion Favaloro
  • Ciudad Autonoma Buenos Aires, Argentina, 1426
    • Fundación Respirar
  • Corrientes, Argentina
    • Instituto de Cardiologia de Corrientes
  • Córdoba, Argentina, X5004BAL
    • Hospital Italiano de Cordoba
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado Centro Medico de Cordoba S.A
  • Santa Fe, Argentina, 3000
    • Hospital PROVINCIAL "Dr. Jose Maria Cullen"
  • Buenos Aires
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1181ACH
      • Hospital Italiano
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Instituto de Investigaciones Clinicas Mar del Plata
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Sanatorio Parque
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Kingswood, New South Wales, Australia, 2751
      • Nepean Hospital
    • Macquarie, New South Wales, Australia, 2109
      • Macquarie University
    • Sydney, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universitat Innsbruck
  • Linz, Austria, 4020
    • Ordensklinikum Linz GmbH - Elisabethinen, Fadingerstrasse 1
  • Vienna, Austria, 1090
    • AKH Wien, Innere Med. II, Kardiologie, Währingergürtel 18-20
• Belgium
  • Brussels, Belgium, 1070
    • Cliniques universitaires de Bruxelles Hopital Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven, UZ Leuven Campus Gasthuisberg, Herestraat 49
• Brazil
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-020
      • HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30441-070
      • Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
  • R.S
    • Porto Alegre, R.S, Brazil, 90610-000
      • Hospital Sao Lucas da PUC-RS
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-074
      • Irmandade da Santa Casa de Misericordia de Porto Alegre
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618-687
      • UNESP-Faculdade de Medicina da Universidade Estadual Paulista Campus Botucatu
    • São Paulo, São Paulo, Brazil, 04037-002
      • Hospital São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Instituto do Coracao
• Bulgaria
  • Sofia, Bulgaria, 1309
    • MHAT - "National Heart Hospital" EAD, 65, Konyovitza Str.
  • Sofia, Bulgaria, 1750
    • MHAT "Sveta Anna" Sofia AD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Peter Lougheed Centre
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • LHSC - Victoria Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network-Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T1E2
      • SMBD Jewish General Hospital d/b/a Jewish General Hospital
    • Québec, Quebec, Canada, G1V 4G5
      • Institut Universitaire De Cardiologie Et De Pneumologie De Québec
• Chile
  • Santiago de Chile
    • Providencia, Santiago de Chile, Chile, 7500691
      • Instiuto Nacional del Torax
• China
  • Beijing, China, 100037
    • Fuwai Hospital, Chinese Academy of Medical Sciences
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100038
      • Beijing Shijitan Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200443
      • Shanghai Pulmonary Hospital
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Dubrava Zagreb, Avenija G.Šuška 6
  • Zagreb, Croatia, 10000
    • University Clinic for Pulmonary Diseases, Jordanovac 104
• Czechia
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze, II. interni klinika kardiologie a angiologie VFN a 1. LF UK, U nemocnice 2
• Denmark
  • Aarhus, Denmark, 8200
    • Århus Universitetshospital
  • Copenhagen, Denmark, 2100
    • Copenhagen University Hospital (Rigshospitalet)
• France
  • Besançon, France, 25030
    • CHU Besancon - Hôpital Jean Minjoz
  • Brest, France, 29609
    • CHU de Brest - Hopital de la Cavale Blanche
  • Lille, France, 59037
    • CHRU de Lille - Hôpital Cardiologique
  • Marseille, France, 13015
    • Hopital Nord - CHU Marseille
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67091
      • CHU de Strasbourg - Nouvel Hôpital Civil, Ctre de competence Hypertension Arterielle Pulmona, 1 place de l Hopital
  • Isere
    • Grenoble, Isere, France, 38048
      • CHU de Grenoble - Hôpital Albert Michallon, Clinique de Cardiologie, Boulevrad de la Chantourne
  • Meurthe Et Moselle
    • Vandœuvre-lès-Nancy, Meurthe Et Moselle, France, 54511
      • CHU Nancy - Hôpital de Brabois Adultes, Pneumologie- Oncologie Médicale, Rue du Morvan
  • Pays de la Loire Region
    • Saint-Étienne-de-Montluc, Pays de la Loire Region, France, 42005
      • CHU de Saint-Etienne - Hopital Nord, Service de Medecine vasculaire et therapeutique, 81 Avenue A. Raimond
  • Rhone
    • Bron, Rhone, France, 69677
      • CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel, Service de Pneumologie, 59 Boulevard Pinel
  • Seine Maritime
    • Rouen, Seine Maritime, France, 76031
      • CHU de Rouen - Hôpital Charles Nicolle
  • Val De Marne
    • Le Kremlin-Bicêtre, Val De Marne, France, 94275
      • Groupement Hospitalier Sud - Hôpital Bicêtre
• Germany
  • Donaueschingen, Germany, 78166
    • Schwarzwald-Baar Klinikum
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg Zentrum für Pulmonale Hypertonie
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • Universitätsmedizin Greifswald
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitaetsmedizin der Johannes-Gutenberg-Universitaet Mainz, Zentrum für Kardiologie I, Centrum für Thrombose und Hämostase (CTH), Langenbeckstrasse 1
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • Universitaetsklinikum des Saarlandes, Innere Medizin V, IMED, Kirrberger Strasse 100, Gebäude 41
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Universitätsklinikum Leipzig, Medizinische Klinik II, Pneumologie
• Greece
  • Alexandroupoli, Greece, 68100
    • University General Hospital of Alexandroupolis
  • Chaïdári, Greece, 12462
    • University General Hospital Attikon
  • Thessaloniki, Greece, 54636
    • AHEPA General Hospital of Thessaloniki, A' Cardiology Clinic, 1 St. Kyriakidi Street
  • Kallithea
    • Athens, Kallithea, Greece, 17674
      • "Onasseio" Cardiosurgery Hospital, Hemodynamic Research and Interventional Cardiology Dept., 356, Syggrou Avenue
• Hungary
  • Budapest, Hungary, 1096
    • Gottsegen György Országos Kardiovaszkuláris Intézet
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem, Szivgyogyaszati Klinika, Ifjusag u. 13.
  • Csongrád-Csanád
    • Szeged, Csongrád-Csanád, Hungary, Hungary
      • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Családorvosi Intézet és Rendelő
• Israel
  • Haifa, Israel, 3436212
    • The Lady Davis Carmel Medical Center, 7 Michal st.
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center, Kiryat Hadassah
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center, 59 Tshernichovski st.
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus, Pulmonary Institute, 39 Jabotinsky St Ground floor
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center, 6 Weizmann St.
• Italy
  • Foggia, Italy, 71100
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia, S.C. di Cardiologia, Viale Luigi Pinto, 1
  • Genova, Italy, 16132
    • IRCC Ospedale Policlinico San Martino
  • Milan, Italy, 20122
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35
  • Monza, Italy, 20900
    • Azienda Socio Sanitaria Territoriale Di Monza (Presidio San Gerardo)
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
  • Roma, Italy, 00161
    • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza, Viale del Policlinico, 155
  • PA
    • Palermo, PA, Italy, 90127
      • Istituto Mediterraneo Trapianti e Terapie a Alta Specializzazione (IRCCS-ISMETT)
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • CICUM San Miguel
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Dr. Salvador Zubiran
    • Mexico City, Mexico City, Mexico, 14080
      • Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera
  • N.L.
    • Monterrey, N.L., Mexico, 64718
      • Unidad de Investigación Clínica en Medicina, S.C.
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum, De Boelelaan 1117
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Kardiologii z Oddzialem Intensywnego Nazdoru Kardiologicznego, M. Sklodowskiej 24a
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II, Oddział Kliniczny Chorób Serca i Naczyń z Pododdziałem Intensywnego Nadzoru Kardiologicznego, Pradnicka 80
  • Otwock, Poland, 05-400
    • NZOZ Europejskie Centrum Zdrowia, ul. Borowa 14/18
  • Poznan, Poland, 61-848
    • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu, Oddzial Kardiologii - F, ul. Dluga 1/2
  • Wroclaw, Poland, 50-414
    • Premium Clinic Wrocław CM, Podwale 83/17
• Portugal
  • Almada, Portugal, 2805-267
    • Hospital Garcia de Orta, E.P.E
  • Coimbra, Portugal, 3000-075
    • Centro Hospitalar e Universitário de Coimbra, E.P.E.
  • Lisbon, Portugal, 1769-001
    • Centro Hospitalar Universitário Lisboa Norte, E.P.E. Hospital Pulido Valente
  • Porto, Portugal, 4099-001
    • Centro Hospitalar de Santo António E.P.E.
• Romania
  • Bucharest, Romania, 022328
    • Institutul de Urgenta pentru Boli Cardiovasculare "Prof. Dr. C.C. Iliescu", Sos. Fundeni nr. 258
  • Bucharest, Romania, 050159
    • Institutul de Pneumoftiziologie "Marius Nasta", Sos. Viilor nr. 90, Sector 5
  • Cluj-Napoca, Romania, 400001
    • Institutul Inimii "Niculae Stancioiu" Cluj-Napoca, Cardiologie, Str. Motilor nr. 19-21
  • Timișoara, Romania, 300310
    • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara, Str. Gheorghe Adam nr. 13
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Koste Todorovica 8
  • Belgrade, Serbia, 11080
    • Clinical Center Zemun. Clinic for internal medicine, Department of Cardiology
  • Kamenitz, Serbia, 21204
    • Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana 4
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169609
    • National Heart Centre
• South Korea
  • Gangnam-gu
    • Seoul, Gangnam-gu, South Korea, 06351
      • Samsung Medical Center
  • Jongno-gu
    • Seoul, Jongno-gu, South Korea, 03080
      • Seoul National University Hospital
  • Namdong-gu
    • Incheon, Namdong-gu, South Korea, 21565
      • Gachon University Hospital Gil Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron, Respiratory Dept., Passeig Vall d'Hebron,119-129, Neumologia
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona, C/ Villarroel, 170
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46026
    • Hospoital Universitari i Politecnic La Fe
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska Universitetssjukhuset
  • Linköping, Sweden, 58185
    • Linköping Universitetssjukhuset
  • Umeå, Sweden, 90185
    • Norrlands Universitetssjukhus, Hjärtcentrum
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06560
    • Gazi University Medical Faculty Hospital
  • Bursa, Turkey (Türkiye), 16059
    • Uludag Universitesi Tip Fakültesi, Gorukle Kampusu
  • Istanbul, Turkey (Türkiye), 34899
    • Marmara Universitesi Istanbul Pendik Egitim ve Arastirma Hastanesi
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylul Universitesi Tip Fakultesi, Mithatpasa caddesi Inciralti Balcova
  • Odunpazari
    • Eskişehir, Odunpazari, Turkey (Türkiye), 26040
      • Osmangazi Uni Medical Faculty
  • Saricam
    • Adana, Saricam, Turkey (Türkiye), 01330
      • Balcalı, Çukurova Üniversitesi Kardiyoloji ABD
  • Yenisehir
    • Mersin, Yenisehir, Turkey (Türkiye), 33343
      • Mersin Üniversitesi Tip Fakültesi Ciftlikköy Kampüsü
• Ukraine
  • Dnipro, Ukraine, 49070
    • CE Dniprop RCC&C Center of Dniprop RC Dept of Card SI DMA of MOHU, Chair of Internal Medicine 3, 28, Knyazya Volodymyra Velykogo St.
  • Kyiv, Ukraine, 03680
    • SI F.H.Yanovskyi National Institute of Phthisiology and Pulmonology of NAMSU, Clinical and Functional Dept, 10, Amosova St.
  • Lviv, Ukraine, 79010
    • Communal Noncommercial Enterprise of Lviv Regional Council Lviv Clinical Hospital, Dept of Cardiology, D.Halytskyi Lviv NMU, Ch of Internal Medicine #1, 7, Chernihivska str.
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Greater London
    • London, Greater London, United Kingdom, NW3 2QG
      • Royal Free London NHS Foundation Trust, Pond Street
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE7 7DN
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir William Leech Lung Research Centre
  • West Dunbartonshire
    • Glasgow, West Dunbartonshire, United Kingdom, G81 4DY
      • Golden Jubilee National Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • La Jolla, California, United States, 92037
      • UCSD Health Sciences
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Los Angeles, California, United States, 90024
      • Ronald Reagan UCLA Medical Center
    • Orange, California, United States, 19103
      • University of California, Irvine
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • Santa Barbara, California, United States, 93105
      • SBPA Research LLC
    • Stanford, California, United States, 94305
      • Stanford Healthcare
    • Torrance, California, United States, 90502
      • LA Biomedical Research Institute Harbor-UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Austell, Georgia, United States, 30106
      • Piedmont Healthcare Pulmonary and Critical Care Research
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Elk Grove Village, Illinois, United States, 60007
      • Ascension Alexian Brothers
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Medical Group, Inc.
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network Cancer Center North
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Research Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maine
    • South Portland, Maine, United States, 04106
      • Chest Medicine Associates
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Spectrum Health Medical Group
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10021
      • Weill-Cornell-New York Presbyterian Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati-Medical Science Building
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • INTEGRIS Baptist Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
    • Portland, Oregon, United States, 97225
      • Oregon Clinic-Pulmonary West
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • StatCare Pulmonary Consultants
  • Texas
    • Austin, Texas, United States, 78705
      • Ascension Texas Cardiovascular
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • The Methodist Hospital Research Institute
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Vermont Lung Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute
    • Roanoke, Virginia, United States, 24014
      • Carilion Clinic Pulmonary and Sleep Medicine
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin/Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 18 years of age.
2. Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of 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 to Screening (RHC will be performed during Screening if not available) that is consistent 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 either an 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 receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics 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 birth control throughout the entire study period from informed consent through to the 30-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 last dose of IMP. Eligible male subjects must agree 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-cell count <200/mm3 within 90 days of Baseline.
2. Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
3. Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
4. Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
5. Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
6. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec and female subjects with a QTcF >470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if 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 variceal hemorrhage, 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 the upper 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 requiring dialysis 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 prior to Baseline (use in vasoreactive testing is permitted).
13. Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for >6 months or within 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 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.
16. 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. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
17. Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
18. Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
19. Any reason that, in the opinion of the Investigator or Medical Monitor, 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ralinepag; Ralinepag once daily extended-release tablets (oral) 50, 250, and 400 mcg titrated to the highest tolerated dose.	Drug: Ralinepag; Active; Other Names: APD811
Placebo Comparator: Placebo; Matching placebo tablets (oral)	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	The study duration was event-based. This parameter was assessed from randomization until the conclusion of the study, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	Baseline to Week 28
Time to first all-cause nonelective hospitalization	All nonelective hopsitalizations during the study period were collected.	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.	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.	Baseline to Week 28
Safety and tolerability of ralinepag in subjects with PAH	Safety and tolerability were assessed by adverse events.	Baseline to Week 28

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2018
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: July 27, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prostacyclin; 6 Minute Walk Test; Connective Tissue Disease-Associated; 6 Minute Walk Distance; Pulmonary Vascular Resistance; Right Ventricular Function
• Additional Relevant MeSH Terms: Skin and Connective Tissue Diseases; Pulmonary Arterial Hypertension; Lung Diseases; Hypertension; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension; Connective Tissue Diseases; ralinepag
• Other Study ID Numbers: ROR-PH-301; APD811-301 (Other Identifier: Arena Pharmaceuticals)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No