A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension

Hypertension Clinical Trial

Official title:

A Phase 3 Open-label Extension (OLE) Study to Evaluate the Long-term Safety and Efficacy of Ralinepag in Subjects With World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03683186
• Other study ID #: ROR-PH-303
• Secondary ID: APD811-303
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: September 23, 2019
• Est. completion date: September 2024

Study information

• Verified date: May 2024
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study ROR-PH-303, ADVANCE EXTENSION, is an open-label extension (OLE) study for participants with WHO Group 1 PAH who have participated in another Phase 2 or Phase 3 study of ralinepag.

Description:

Study ROR-PH-303 is a multicenter, open-label extension (OLE) study for subjects with WHO Group 1 PAH who have participated in another Phase 2 or Phase 3 study of ralinepag and who qualify for entry based upon participation in the prior study. Subjects who discontinue participation in a prior study due to safety issues related to study medication or who fail to complete study procedures will not be eligible to enter Study ROR-PH-303. Subjects who meet all OLE entry criteria will be enrolled and will receive ralinepag in addition to their pre-existing PAH disease-specific background therapy.

For subjects who are enrolled from an ongoing double-blind Phase 2 or Phase 3 ralinepag study, a 16-week blinded Dose Titration Period will be completed following enrollment into the OLE. Subjects previously on ralinepag will continue on the same dose during the Dose Titration Period as received in the original study and will also initiate placebo treatment in the OLE.

Subjects who are enrolled from a non-blinded study or another OLE will not participate in the blinded Dose Titration Period in Study ROR-PH-303 but will be enrolled directly into the Treatment Period and continue on the dose of ralinepag received in the original study.

All subjects will receive ralinepag in the OLE study until premature discontinuation of ralinepag due to an AE/serious adverse event (SAE) or other reason, marketing approval of ralinepag is granted in the region in which the study is conducted, or the study is discontinued by the Sponsor.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1000
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

3. Completed the protocol-defined Study Drug Termination Visit or End of Study Visit procedures in the preceding ralinepag study.

4. Both male and female subjects agree to use a medically acceptable method of contraception throughout the entire study period from informed consent through 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 (i.e., actively attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 30 days after the last dose of ralinepag.

Exclusion Criteria:

1. Subjects who prematurely discontinued investigational medicinal product (IMP) due to a drug-related AE/SAE or tolerability issue in the preceding ralinepag study in which they were enrolled, or subjects who did not complete all protocol defined study procedures at a Study Drug Termination Visit or End of Study Visit in the preceding ralinepag study.

2. Subjects who withdrew consent during participation in another ralinepag study.

3. Female subjects who wish to become pregnant or who have a positive pregnancy test on Day 1 (OLE Entry Visit), or are lactating or breastfeeding.

4. Subjects who have undergone lung or heart/lung transplant or the initiation of long-term parenteral or inhaled therapy with a prostacyclin during the time since participation in their original ralinepag study.

5. Subjects who had an emergency unblinding procedure in a prior Phase 2 or 3 study.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ralinepag
Active

Locations

Country	Name	City	State
Argentina	Sanatorio de la Trinidad Mitre	Buenos Aires
Argentina	Cardiologia Palmero	Caba
Argentina	Fundacion Favaloro	Ciudad Autonoma Buenos Aires
Argentina	Fundacion Respirar	Ciudad Autonoma Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Hospital Italiano	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba S.A	Cordoba
Argentina	Hospital Italiano de Cordoba	Córdoba
Argentina	Instituto de Cardiologia de Corrientes	Corrientes
Argentina	Instituto de Investigaciones Clinicas	Mar Del Plata
Argentina	Sanatorio Parque S.A.	Rosario	Santa Fe
Argentina	Hospital PROVINCIAL "Dr. Jose Maria Cullen"	Santa Fe	Santa Fe De La Vera Cruz
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Perth	Western Australia
Australia	Macquarie University	Sydney	New South Wales
Australia	Nepean Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Ordensklinikum Linz GmbH - Elisabethinen, Fadingerstrasse 1	Linz
Austria	AKH Wien, Innere Med. II, Kardiologie, Währingergürtel 18-20	Wien
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Bruxelles
Belgium	UZ Leuven, UZ Leuven Campus Gasthuisberg, Herestraat 49	Leuven
Brazil	Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa	Belo Horizonte	MG
Brazil	UNESP-Faculdade de Medicina da Universidade Estadual Paulista Campus Botucatu	Botucatu	Sao Paulo
Brazil	HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás	Goiânia	Goias
Brazil	Hospital Sao Lucas da PUC-RS	Porto Alegre	R.S
Brazil	Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre	RS
Brazil	Hospital Sao Paulo	Sao Paulo	SP
Brazil	Instituto do Coracao	Sao Paulo	SP
Bulgaria	MHAT "Sveta Anna" Sofia AD	Sofia
Bulgaria	MHAT - "National Heart Hospital" EAD, 65, Konyovitza Str.	Sofia
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	LHSC - Victoria Hospital	London	Ontario
Canada	SMBD Jewish General Hospital d/b/a Jewish General Hospital	Montreal	Quebec
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Québec	Quebec
Canada	University Health Network-Toronto General Hospital	Toronto	Ontario
Chile	Instiuto Nacional del Torax	Providencia	Santiago De Chile
China	Beijing Shijitan Hospital, Capital Medical University	Beijing	Beijing
China	Fuwai Hospital, Chinese Academy of Medical Sciences	Beijing
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
Croatia	Clinical Hospital Dubrava Zagreb, Avenija G.Šuška 6	Zagreb
Croatia	University Clinic for Pulmonary Diseases, Jordanovac 104	Zagreb
Czechia	Vseobecna fakultni nemocnice v Praze, II. interni klinika kardiologie a angiologie VFN a 1. LF UK, U nemocnice 2	Praha 2
Denmark	Århus Universitetshospital	Århus
Denmark	Copenhagen University Hospital (Rigshospitalet)	Copenhagen
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	CHU de Brest - Hôpital de la Cavale Blanche	Brest cedex 2
France	CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel, Service de Pneumologie, 59 Boulevard Pinel	Bron cedex	Rhone
France	CHU de Grenoble - Hôpital Albert Michallon, Clinique de Cardiologie, Boulevrad de la Chantourne	Grenoble	Isere
France	Groupement Hospitalier Sud - Hôpital Bicêtre, Service de Pneumologie, 78 Avenue du General Leclerc	Le Kremlin-Bicêtre	Val De Marne
France	CHRU de Lille - Hopital Cardiologique	Lille Cedex
France	Hôpital Nord - CHU Marseille	Marseille
France	CHU de Rouen - Hôpital Charles Nicolle	Rouen cedex	Seine Maritime
France	CHU de Saint-Etienne - Hopital Nord, Service de Medecine vasculaire et therapeutique, 81 Avenue A. Raimond	Saint-Étienne	Loire
France	CHU de Strasbourg - Nouvel Hôpital Civil, Ctre de competence Hypertension Arterielle Pulmona, 1 place de l Hopital	Strasbourg	Bas Rhin
France	CHU Nancy - Hôpital de Brabois Adultes, Pneumologie- Oncologie Médicale, Rue du Morvan	Vandoeuvre les Nancy	Meurthe Et Moselle
Germany	Schwarzwald-Baar Klinikum	Donaueschingen
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitätsmedizin Greifswald	Greifswald	Mecklenburg-Vorpommern
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Thoraxklinik-Heidelberg Zentrum für Pulmonale Hypertonie	Heidelberg	Baden-Württemberg
Germany	Universitaetsklinikum des Saarlandes, Innere Medizin V, IMED, Kirrberger Strasse 100, Gebäude 41	Homburg	Saarland
Germany	Universitätsklinikum Leipzig, Medizinische Klinik II, Pneumologie	Leipzig	Sachsen
Germany	Universitaetsmedizin der Johannes-Gutenberg-Universitaet Mainz, Zentrum für Kardiologie I, Centrum für Thrombose und Hämostase (CTH), Langenbeckstrasse 1	Mainz	Rheinland Pfalz
Greece	University General Hospital of Alexandroupolis	Alexandroupolis
Greece	"Onasseio" Cardiosurgery Hospital, Hemodynamic Research and Interventional Cardiology Dept., 356, Syggrou Avenue	Athens
Greece	University General Hospital Attikon	Chaidari
Greece	AHEPA General Hospital of Thessaloniki, A' Cardiology Clinic, 1 St. Kyriakidi Street	Thessaloniki
Hungary	Gottsegen György Országos Kardiovaszkuláris Intézet	Budapest
Hungary	Pecsi Tudomanyegyetem, Szivgyogyaszati Klinika, Ifjusag u. 13.	Pecs
Israel	The Lady Davis Carmel Medical Center, 7 Michal st.	Haifa
Israel	Hadassah Ein Kerem Medical Center, Kiryat Hadassah	Jerusalem
Israel	Meir Medical Center, 59 Tshernichovski st.	Kfar- Sava
Israel	Rabin Medical Center-Beilinson Campus, Pulmonary Institute, 39 Jabotinsky St Ground floor	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center, 6 Weizmann St.	Tel Aviv
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia, S.C. di Cardiologia, Viale Luigi Pinto, 1	Foggia
Italy	IRCC Ospedale Policlinico San Martino	Genova
Italy	Centro Cardiologico Monzino, IRCCS U.O. Scompenso	Milan
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35	Milano
Italy	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza
Italy	Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT)	Palermo	PA
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza, Viale del Policlinico, 155	Roma
Korea, Republic of	Gachon University Hospital Gil Medical Center	Incheon	Namdong-gu
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu
Korea, Republic of	Seoul National University Hospital	Seoul	Jongno-gu
Mexico	CICUM San Miguel	Guadalajara	Jalisco
Mexico	Instituto Nacional de Cardiologia Dr Ignacio Chavez Rivera	Mexico	Distrito Federal
Mexico	Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran	Mexico	Distrito Federal
Mexico	Unidad de Investigacion Clinica en Medicina, S.C.	Monterrey	N.l.
Netherlands	VU Medisch Centrum, De Boelelaan 1117	Amsterdam
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Kardiologii z Oddzialem Intensywnego Nazdoru Kardiologicznego, M. Sklodowskiej 24a	Bialystok
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II, Oddzial Kliniczny Chorób Serca i Naczyn z Pododdzialem Intensywnego Nadzoru Kardiologicznego, Pradnicka 80	Krakow
Poland	NZOZ Europejskie Centrum Zdrowia, ul. Borowa 14/18	Otwock
Poland	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu, Oddzial Kardiologii - F, ul. Dluga 1/2	Poznan
Poland	Premium Clinic Wroclaw CM, Podwale 83/17	Wroclaw
Portugal	Hospital Garcia de Orta, E.P.E	Almada
Portugal	Centro Hospitalar e Universitário de Coimbra, E.P.E.	Coimbra
Portugal	Centro Hospitalar Universitário Lisboa Norte, E.P.E. Hospital Pulido Valente	Lisboa
Portugal	Centro Hospitalar de Santo António, E.P.E.	Porto
Romania	Institutul de Urgenta pentru Boli Cardiovasculare "Prof. Dr. C.C. Iliescu", Sos. Fundeni nr. 258	Bucharest
Romania	Institutul de Pneumoftiziologie "Marius Nasta", Sos. Viilor nr. 90, Sector 5	Bucuresti
Romania	Institutul Inimii "Niculae Stancioiu" Cluj-Napoca, Cardiologie, Str. Motilor nr. 19-21	Cluj-Napoca
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie "Dr. Victor Babes" Timisoara, Str. Gheorghe Adam nr. 13	Timisoara
Serbia	Clinical Center of Serbia, Koste Todorovica 8	Belgrade
Serbia	Clinical Center Zemun. Clinic for internal medicine, Department of Cardiology	Belgrade
Serbia	Institute for Pulmonary Diseases of Vojvodina, Put Dr Goldmana 4	Sremska Kamenica
Singapore	National Heart Centre	Singapore
Singapore	National University Hospital	Singapore
Spain	Hospital Clinic de Barcelona, C/ Villarroel, 170	Barcelona
Spain	Hospital Universitari Vall d'Hebron, Respiratory Dept., Passeig Vall d'Hebron,119-129, Neumologia	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Linköping Universitetssjukhuset	Linköping
Sweden	Norrlands Universitetssjukhus, Hjärtcentrum	Umeå
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Balcali, Çukurova Üniversitesi Kardiyoloji ABD	Adana	Saricam
Turkey	Gazi University Medical Faculty Hospital	Ankara
Turkey	Uludag Universitesi Tip Fakültesi, Gorukle Kampusu	Bursa
Turkey	Osmangazi Uni Medical Faculty	Eskisehir	Odumpazari
Turkey	Marmara Universitesi Istanbul Pendik Egitim ve Arastirma Hastanesi, Fevzi Cakmak Mahallesi Muhsin Yazicioglu Cad. No: 10	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi, Mithatpasa caddesi Inciralti Balcova	Izmir
Turkey	Mersin Üniversitesi Tip Fakültesi Ciftlikköy Kampüsü	Mersin	Yenisehir
Ukraine	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.	Dnipro
Ukraine	SI F.H.Yanovskyi National Institute of Phthisiology and Pulmonology of NAMSU, Clinical and Functional Dept, 10, Amosova St.	Kyiv
Ukraine	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.	Lviv
United Kingdom	Golden Jubilee National Hospital	Glasgow	West Dunbartonshire
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Brompton Hospital	London	Greater London
United Kingdom	Royal Free London NHS Foundation Trust, Pond Street	London	Greater London
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust, Sir William Leech Lung Research Centre, Freeman Hospital	Newcastle upon Tyne	Tyne & Wear
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Piedmont Healthcare Pulmonary and Critical Care Research	Austell	Georgia
United States	Ascension Texas Cardiovascular	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Vermont Lung Center	Burlington	Vermont
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati-Medical Science Building	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Ascension Alexian Brothers	Elk Grove Village	Illinois
United States	University of Florida	Gainesville	Florida
United States	Spectrum Health Medical Group	Grand Rapids	Michigan
United States	East Carolina University	Greenville	North Carolina
United States	Memorial Hermann Hospital	Houston	Texas
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	Community Heart and Vascular Hospital	Indianapolis	Indiana
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	St. Vincent Medical Group, Inc.	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	StatCare Pulmonary Consultants	Knoxville	Tennessee
United States	UCSD Health Sciences	La Jolla	California
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Keck Hospital of USC	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	Kentuckiana Pulmonary Research Center	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin
United States	Winthrop Hospital	Mineola	New York
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Weill-Cornell-New York Presbyterian Hospital	New York	New York
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	Nebraska Medical Center	Omaha	Nebraska
United States	University of California, Irvine	Orange	California
United States	Central Florida Pulmonary Group	Orlando	Florida
United States	Investigational Drug Services, AdventHealth Orlando (Drug Shipment Address)	Orlando	Florida
United States	Temple University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center-Norton Thoracic Institute	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Oregon Clinic-Pulmonary West	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Carilion Clinic Pulmonary and Sleep Medicine	Roanoke	Virginia
United States	University of Rochester	Rochester	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Chest Medicine Associates	South Portland	Maine
United States	Stanford University Medical Center	Stanford	California
United States	University of Arizona	Tucson	Arizona
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Croatia,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Serbia,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with treatment-emergent adverse events [Safety and Tolerability]	The safety and tolerability of ralinepag will be evaluated by the Number of subjects with treatment-emergent adverse events	Up to 6 years