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

NCT ID: NCT03689244

Last Updated: 2024-06-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-23
• Study Completion Date: 2022-06-07

Brief 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.

Detailed 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.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Selexipag DB

During the double blind treatment period, participants in this group will receive selexipag. Each participant will start with one oral tablet of selexipag 200 µg in the evening of Day 1 and will continue with 200 µg twice daily (b.i.d.) on Day 2. If this dose is well-tolerated, selexipag is up-titrated with weekly increments of 200 µg until reaching the individual maximal tolerated dose (iMTD) in the range of 200 to 1600 µg b.i.d. The up-titration period up to Week 12 is followed by a stable maintenance treatment period from Week 12 to Week 26, at the iMTD. After Week 26, further up-titration can be allowed (but not above 1600 µg b.i.d.).

Group Type: EXPERIMENTAL

Selexipag

Intervention Type: DRUG

oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration

Placebo DB

During the double-blind treatment period, participants in this group will receive the oral matching placebo, twice daily. A (mock) up-titration scheme will be followed.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablets without active compound

Selexipag OL

All participants who completed the double-blind treatment period, whether they received placebo or selexipag during the double-blind period, will receive selexipag during the open-label extension period, using the same up-titration schedule as in the double-blind period.

Group Type: EXPERIMENTAL

Selexipag

Intervention Type: DRUG

oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration

Interventions

Selexipag

oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration

Intervention Type: DRUG

Placebo

Oral tablets without active compound

Intervention Type: DRUG

Other Intervention Names

ACT-293987, JNJ-67896049

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julian Borissoff, MD, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

University of California San Diego Medical Center

La Jolla, California, United States

University of Southern California, Keck School of Medicine

Los Angeles, California, United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Colorado Springs Pulmonary Consultants

Colorado Springs, Colorado, United States

South Denver Cardiology Associates PC

Littleton, Colorado, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Piedmont Healthcare

Atlanta, Georgia, United States

Emory University

Atlanta, Georgia, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

University of Chicago Hospitals - Chicago

Chicago, Illinois, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

University of Maryland

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Sparrow Clinical Research Institute

Lansing, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

St. Mary's Cardiology

Reno, Nevada, United States

University of New Mexico Clinical & Translational Science Center

Albuquerque, New Mexico, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Allegheny

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Baylor Scott & White Research Institute at The Heart Hospital Baylor Plano

Plano, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

University of Utah Cardiovascular Center

Salt Lake City, Utah, United States

Medical College of Wisconsin Froedtert Hospital

Milwaukee, Wisconsin, United States

Aurora Saint Lukes Medical Center

Milwaukee, Wisconsin, United States

Sanatorio de la Trinidad Mitre

Buenos Aires, , Argentina

Centro Médico Dra. De Salvo

Buenos Aires, , Argentina

Hospital Italiano de Buenos Aires

Caba, , Argentina

Sanatorio Ramon Cereijo

Caba, , Argentina

Instituto de Cardiología y Cirugía Cardiovascular - Fundación Favaloro

Caba, , Argentina

Hospital General de Agudos Dr Cosme Argerich

CABA, , Argentina

Hospital Britanico de Buenos Aires

CABA, , Argentina

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, , Australia

Ordensklinikum Linz GmbH Elisabethinen

Linz, , Austria

Medical University Vienna

Vienna, , Austria

ULB Hôpital Erasme

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

Universidade Federal De Minas Gerais - Hospital das Clínicas

Belo Horizonte, , Brazil

Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa

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

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Hospital das Clinicas de Porto Alegre

Porto Alegre, , Brazil

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS

Porto Alegre, , Brazil

Fundacao do ABC - Centro Universitario FMABC

Santo André, , Brazil

SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo

São Paulo, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, , Brazil

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, , Bulgaria

University Of Calgary - Peter Lougheed Centre

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, 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

Québec, Quebec, Canada

Chinese Academy of Medical Sciences(CAMS) & Peking Union Medical College(PUMC)

Beijing, , China

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, , China

The General Hospital of Northern Theater Command

Shenyang, , China

Shengjing Hospital Of China Medical University

Shenyang, , China

Shanxi Cardiovascular Hospital

Taiyuan, , China

Tianjin Medical University General Hospital

Tianjin, , China

General University Hospital II.department of Internal Medicine-cardiology and angiology

Prague, , Czechia

Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B

Aarhus, , Denmark

Rigshospitalet Kardiologisk Klinisk

Copenhagen, , Denmark

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

Hanover, , Germany

Thoraxklinik am Universitatsklinikum 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, , Germany

Semmelweis Egyetem,Pulmonológiai Klinika

Budapest, , Hungary

Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály

Budapest, , Hungary

Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum

Debrecen, , Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, , Hungary

Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő

Szeged, , Hungary

Rabin Medical Center Beilinson Campus

Petah Tikva, , Israel

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

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, , Italy

Hospital Pulau Pinang

George Town, , Malaysia

Hospital Serdang

Kajang, , Malaysia

Institut Jantung Negara (National Heart Institute)

Kuala Lumpur, , Malaysia

CICUM San Miguel

Guadalajara, , Mexico

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, , Mexico

Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)

Monterrey, , Mexico

VUMC Amsterdam

Amsterdam, , Netherlands

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, , Netherlands

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 Dzieciątka Jezus

Warsaw, , Poland

Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy

Wroclaw, , Poland

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, , Portugal

Irkutsk Regional Clinical Hospital

Irkutsk, , Russia

Cardiovascular Pathology Research Institute of Siberian Branch of RAMS

Kemerovo, , Russia

Moscow City Clinical Hospital #1 n.a. N.I.Pirogov

Moscow, , Russia

Moscow City Clinical Hospital No.51

Moscow, , Russia

National Medical Research Center of Cardiology of MoH of Russian Federation

Moscow, , Russia

E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation

Novosibirsk, , Russia

National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation

Saint Petersburg, , Russia

Narodny ustav srdcovych a cievnych chorob

Bratislava, , Slovakia

Pusan National University Hospital

Busan, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Hosp Clinic 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

Seville, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Norrlands Universitetssjukhus

Umeå, , Sweden

Uppsala Akademiska Sjukhuset, Kardiologkliniken

Uppsala, , Sweden

Universitatsspital Zurich

Zurich, , Switzerland

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Ramathibodi Hospital Mahidol University

Bangkok, , Thailand

Srinagarind Hospital, Khon Kaen University

Khon Kaen, , Thailand

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Marmara University Medical Faculty

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi

Kartal Istanbul, , Turkey (Türkiye)

CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'

Dnipro, , Ukraine

SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine

Kyiv, , Ukraine

SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'

Kyiv, , Ukraine

Lviv Regional Clinical Hospital

Lviv, , Ukraine

Papworth Hospital NHS Trust

Cambridge, , United Kingdom

National Waiting Times Centre Board Golden Jubilee National Hospital

Glasgow, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Royal Brompton Hospital

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Bulgaria; Canada; China; Czechia; Denmark; Germany; Hungary; Israel; Italy; Malaysia; Mexico; Netherlands; Poland; Portugal; Russia; Slovakia; South Korea; Spain; Sweden; Switzerland; Taiwan; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

Kim NH, Channick R, Delcroix M, Madani M, Pepke-Zaba J, Borissoff JI, Easton V, Gesang S, Richard D, Ghofrani HA. Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial). Eur Respir J. 2024 Oct 3;64(4):2400193. doi: 10.1183/13993003.00193-2024. Print 2024 Oct.

Reference Type: DERIVED

PMID: 39326918 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002823-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-065B302

Identifier Type: -

Identifier Source: org_study_id