A Study to Find Out if Selexipag is Effective and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension When the Disease is Inoperable or Persistent/Recurrent After Surgery and/or Interventional Treatment

Chronic Thromboembolic Pulmonary Hypertension Clinical Trial

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Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Group-sequential, Adaptive, Phase 3 Study With Open-label Extension Period to Assess the Efficacy and Safety of Selexipag as an add-on to Standard of Care Therapy in Subjects With Inoperable or Persistent/Recurrent After Surgical and/or Interventional Treatment Chronic Thromboembolic Pulmonary Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03689244
• Other study ID #: AC-065B302
• Secondary ID: 2018-002823-41
• Status: Terminated
• Phase: Phase 3
• Start date: January 23, 2019
• Est. completion date: June 7, 2022

Study information

• Verified date: July 2023
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Selexipag is available in many countries for the treatment of pulmonary arterial hypertension (PAH). Due to the similarities between PAH and chronic thromboembolic pulmonary hypertension (CTEPH) and the observed efficacy of other PAH medicines in CTEPH, it is believed that selexipag could benefit to patients with CTEPH. This study aims to assess the efficacy and safety of selexipag in participants with inoperable or persistent/recurrent CTEPH.

Description:

Participants will be recruited in two sequential cohorts: approximately the first 90 randomized participants will undergo a right heart catheterization (RHC) (and left heart catheterization LHC, if needed) with measurement of pulmonary vascular resistance (PVR) at Week 20 and will constitute the hemodynamic cohort; the remaining participants will constitute the non-hemodynamic cohort; who do not require a post-baseline hemodynamic assessment. They will undergo the same overall study assessments as the hemodynamic cohort excepted for RHC at Week 20.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 128
• Est. completion date: June 7, 2022
• Est. primary completion date: June 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Main Inclusion Criteria:

• Signed and dated informed consent form
• Male and female participants from greater than or equal to (>) 18 (or the legal age of consent in the jurisdiction in which the study is taking place) and less then or equal to (<=85) years old at Screening (Visit 1)
• With established diagnosis of inoperable CTEPH (i.e., technically non-operable) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA), as confirmed by the corresponding adjudication committee
• With pulmonary hypertension (PH) in WHO FC I-IV.
• Participant able to perform the 6-minute walk test (6MWT) with a minimum distance of 100 m and a maximum distance of 450 m at screening visit.
• Women of childbearing potential must have a negative pregnancy test at screening and randomization and must agree to undertake monthly urine pregnancy tests, and to use a reliable method of birth control from screening visit up to at least 30 days after study treatment discontinuation. If a hormonal contraceptive is chosen it must be taken for at least 1 month prior to randomization.

Main Exclusion Criteria:

• Planned or current treatment with another investigational treatment up to 3 months prior to randomization.
• Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
• Known concomitant life-threatening disease with a life expectancy < 12 months.
• Planned balloon pulmonary angioplasty within 26 weeks after randomization.
• Change in dose or initiation of new PH-specific therapy within 90 days prior to the baseline RHC (and LHC, if needed) qualifying for enrollment for the hemodynamic cohort and within 90 days prior to randomization (Visit 2) for the non-hemodynamic cohort
• Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e., selexipag) within 90 days prior to randomization (visit 2) except those given at vasodilator testing during RHC
• Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC (and LHC, if needed)
• Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc).
• Any other criteria as per selexipag Summary of Product Characteristics (SmPC).
• Exclusion criteria related to comorbidities: severe coronary heart disease or unstable angina as assessed by the investigator; mocardial infarction within the last 6 months prior to or during Screening; decompensated cardiac failure if not under close supervision; severe arrhythmias as assessed by the investigator; cerebrovascular events (example transient ischemic attack, stroke) within the last 3 months prior to or during screening; congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension. (PH); known or suspicion of pulmonary veno-occlusive disease

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• Selexipag
oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration
• Placebo
Oral tablets without active compound

Locations

Country	Name	City	State
Argentina	Sanatorio de la Trinidad Mitre	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Caba
Argentina	Hospital General de Agudos Dr Cosme Argerich	Caba
Argentina	Hospital Italiano de Buenos Aires	Caba
Argentina	Instituto de Cardiología y Cirugía Cardiovascular - Fundación Favaloro	Caba
Argentina	Sanatorio Ramon Cereijo	Caba
Argentina	Centro Médico Dra. De Salvo	Ciudad Autónoma de Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide
Australia	Queensland Lung Transplant Service	Chermside
Australia	St Vincent's hospital	Darlinghurst
Australia	Pulmonary Arterial Hypertension Clinic	Hobart
Australia	The Alfred Hospital	Melbourne
Australia	Westmead Hospital	Westmead
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz
Austria	Medical University Vienna	Vienna
Belgium	ULB Hôpital Erasme	Brussels
Belgium	UZ Leuven	Leuven
Brazil	Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa	Belo Horizonte
Brazil	Universidade Federal De Minas Gerais - Hospital das Clínicas	Belo Horizonte
Brazil	Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)	Botucatu
Brazil	Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes	Fortaleza
Brazil	Universidade Federal de Goias - Hospital das Clinicas da UFG	Goiânia
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	União Brasileira de Educação e Assistência-Hospital São Lucas da PUCRS	Porto Alegre
Brazil	Fundacao do ABC - Centro Universitario FMABC	Santo Andre
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da USP	Sao Paulo
Brazil	SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo	Sao Paulo
Bulgaria	UMHAT 'Heart and Brain Center for Excellence'	Pleven
Bulgaria	National Cardiology Hospital	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD	Sofia
Canada	University Of Calgary - Peter Lougheed Centre	Calgary	Alberta
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Institut Universitaire De Cardiologie Et De Pneumologie De Québec	Quebec
Canada	Vancouver General Hospital	Vancouver	British Columbia
China	Chinese Academy of Medical Sciences(CAMS) & Peking Union Medical College(PUMC)	Beijing
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Shengjing Hospital of China Medical University	Shenyang
China	The General Hospital of Northern Theater Command	Shenyang
China	Shanxi Cardiovascular Hospital	Taiyuan
China	Tianjin Medical University General Hospital	Tian Jin
Czechia	General University Hospital II.department of Internal Medicine-cardiology and angiology	Praha 2
Denmark	Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B	Arhus
Denmark	Rigshospitalet Kardiologisk Klinisk	Copenhagen
Germany	Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie	Dresden
Germany	Universitätsklinikum Giessen Medizinische Klinik Und Poliklinik Ii, Pneumologie	Giessen
Germany	Universität Greifswald - Klinik Für Innere Medizin Bereich Pneumologie/Infektiologie	Greifswald
Germany	Universitätsklinikum Hamburg-Eppendorf - Pneumologie	Hamburg
Germany	Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie	Hannover
Germany	Thoraxklinik am Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V	Homburg/Saar
Germany	Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Abteilung für Pneumologie	Leipzig
Germany	Klinikum Würzburg Mitte gGmbH Standort Missioklinik	Würzburg
Hungary	Gottsegen György Országos Kardiológiai Intézet, Felnott kardiológiai osztály	Budapest
Hungary	Semmelweis Egyetem,Pulmonológiai Klinika	Budapest
Hungary	Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum	Debrecen
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs
Hungary	Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelo	Szeged
Israel	Rabin Medical Center, Beilinson Campus	Petah Tikva
Israel	The Chaim Sheba Medical Center	Tel-Hashomer
Italy	Azienda Ospedaliera Policlinico S. Orsola-Malpighi	Bologna
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Policlinico Umberto I	Roma
Italy	Ospedale di Cattinara - Struttura complessa di Pneumologia	Trieste
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Malaysia	Hospital Pulau Pinang	George Town
Malaysia	Hospital Serdang	Kajang
Malaysia	Institut Jantung Negara (National Heart Institute)	Kuala Lumpur
Mexico	Instituto Nacional de Cardiologia Dr. Ignacio Chavez	Ciudad de Mexico
Mexico	CICUM San Miguel	Guadalajara
Mexico	Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)	Monterrey
Netherlands	VUMC Amsterdam	Amsterdam
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Krakowski Szpital Specjalistyczny im Jana Pawla II	Krakow
Poland	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ	Lublin
Poland	NZOZ Europejskie Centrum Zdrowia Otwock	Otwock
Poland	Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu	Poznan
Poland	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM	Szczecin
Poland	Warszawski Uniwersytet Medyczny, Szpital Kliniczny Dzieciatka Jezus	Warszawa
Poland	Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy	Wroclaw
Portugal	Hospital Garcia de Orta	Almada
Portugal	Hospitais da universidade de Coimbra	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte	Lisbon
Portugal	Hospital Geral de Santo Antonio	Porto
Russian Federation	Irkutsk Regional Clinical Hospital	Irkutsk
Russian Federation	Cardiovascular Pathology Research Institute of Siberian Branch of RAMS	Kemerovo
Russian Federation	Moscow City Clinical Hospital #1 n.a. N.I.Pirogov	Moscow
Russian Federation	Moscow City Clinical Hospital No.51	Moscow
Russian Federation	National Medical Research Center of Cardiology of MoH of Russian Federation	Moscow
Russian Federation	E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation	Novosibirsk
Russian Federation	National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation	Saint-Petersburg
Slovakia	Narodny ustav srdcovych a cievnych chorob	Bratislava
Spain	Hosp. Clinic I Provincial de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Sweden	Norrlands Universitetssjukhus	Umea
Sweden	Uppsala Akademiska Sjukhuset, Kardiologkliniken	Uppsala
Switzerland	Universitatsspital Zurich	Zürich
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	Srinagarind Hospital, Khon Kaen University	Khon Kaen
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty	Istanbul
Turkey	Marmara University Medical Faculty	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi	Kartal-Istanbul
Ukraine	CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'	Dnipro
Ukraine	SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'	Kyiv
Ukraine	SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine	Kyiv
Ukraine	Lviv Regional Clinical Hospital	Lviv
United Kingdom	Papworth Hospital NHS Trust	Cambridge
United Kingdom	National Waiting Times Centre Board Golden Jubilee National Hospital	Glasgow
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital	Sheffield
United States	University of New Mexico Clinical & Translational Science Center	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Piedmont Healthcare	Atlanta	Georgia
United States	University of Colorado - Anschutz Medical Campus	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of Chicago Hospitals - Chicago	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Colorado Springs Pulmonary Consultants	Colorado Springs	Colorado
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Houston Methodist Hospital	Houston	Texas
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of California San Diego Medical Center	La Jolla	California
United States	Sparrow Clinical Research Institute	Lansing	Michigan
United States	South Denver Cardiology Associates PC	Littleton	Colorado
United States	University of Southern California, Keck School of Medicine	Los Angeles	California
United States	Aurora Saint Lukes Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin-Froedtert Hospital	Milwaukee	Wisconsin
United States	Intermountain Medical Center	Murray	Utah
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Allegheny	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Baylor Scott & White Research Institute at The Heart Hospital Baylor Plano	Plano	Texas
United States	St. Mary's Cardiology	Reno	Nevada
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah Cardiovascular Center	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 20	Change from baseline in PVR at Week 20 was reported. PVR was measured by accessing the vessel either from right heart catheterization or left heart catheterization, if required. Change from baseline in PVR was measured as percent ratio of post treatment value (Week 20) to pre-treatment value (baseline).	Baseline (Day 1, pre-dose), within 2 to 5 hours post-dose on Week 20