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 (SELECT)

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Drug: Selexipag; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1039AAO
    • Sanatorio de la Trinidad Mitre
  • Caba, Argentina, C1280AEB
    • Hospital Britanico de Buenos Aires
  • Caba, Argentina, 1199ABB
    • Hospital Italiano de Buenos Aires
  • Caba, Argentina, C1048AAN
    • Sanatorio Ramon Cereijo
  • Caba, Argentina, C1093AAS
    • Instituto de Cardiología y Cirugía Cardiovascular - Fundación Favaloro
  • Caba, Argentina, C1155AHD
    • Hospital General de Agudos Dr Cosme Argerich
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
    • Centro Médico Dra. De Salvo
• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Chermside, Australia, 4032
    • Queensland Lung Transplant Service
  • Darlinghurst, Australia, 2010
    • St Vincent's Hospital
  • Hobart, Australia, 7000
    • Pulmonary Arterial Hypertension Clinic
  • Melbourne, Australia, 3004
    • The Alfred Hospital
  • Westmead, Australia, 2145
    • Westmead Hospital
• Austria
  • Linz, Austria, 4020
    • Ordensklinikum Linz Gmbh Elisabethinen
  • Vienna, Austria, 1090
    • Medical University Vienna
• Belgium
  • Brussels, Belgium, 1070
    • ULB Hôpital Erasme
  • Leuven, Belgium, 3000
    • UZ Leuven
• Brazil
  • Belo Horizonte, Brazil, 30441-070
    • Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
  • Belo Horizonte, Brazil, 30130-100
    • Universidade Federal De Minas Gerais - Hospital das Clínicas
  • Botucatu, Brazil, 18618-686
    • Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)
  • Fortaleza, Brazil, 60840-285
    • Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
  • Goiânia, Brazil, 74605-020
    • Universidade Federal de Goias - Hospital das Clinicas da UFG
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS
  • Porto Alegre, Brazil, 90020-090
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90035-003
    • Hospital das Clinicas de Porto Alegre
  • Santo Andre, Brazil, 09060-870
    • Fundacao do ABC - Centro Universitario FMABC
  • Sao Paulo, Brazil, 05403-000
    • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • Sao Paulo, Brazil, 04037-003
    • SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT 'Heart and Brain Center for Excellence'
  • Sofia, Bulgaria, 1750
    • University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
  • Sofia, Bulgaria, 1392
    • National Cardiology Hospital
• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire De Cardiologie Et De Pneumologie De Québec
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • University Of Calgary - Peter Lougheed Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre - Victoria Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• China
  • Beijing, China, 100730
    • Chinese Academy of Medical Sciences(CAMS) & Peking Union Medical College(PUMC)
  • Guangzhou, China, 510120
    • The First Affiliated Hospital of Guangzhou Medical University
  • Shenyang, China, 110000
    • The General Hospital of Northern Theater Command
  • Shenyang, China, 110022
    • Shengjing Hospital of China Medical University
  • Taiyuan, China, 030001
    • Shanxi Cardiovascular Hospital
  • Tian Jin, China, 300052
    • Tianjin Medical University General Hospital
• Czechia
  • Praha 2, Czechia, 128 08
    • General University Hospital II.department of Internal Medicine-cardiology and angiology
• Denmark
  • Arhus, Denmark, 8200
    • Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
  • Copenhagen, Denmark, 2100
    • Rigshospitalet Kardiologisk Klinisk
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
  • Giessen, Germany, 35392
    • Universitätsklinikum Giessen Medizinische Klinik Und Poliklinik Ii, Pneumologie
  • Greifswald, Germany, 17475
    • Universität Greifswald - Klinik Für Innere Medizin Bereich Pneumologie/Infektiologie
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf - Pneumologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitatsklinikum Heidelberg
  • Homburg/Saar, Germany, 66421
    • Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Abteilung für Pneumologie
  • Würzburg, Germany, 97074
    • Klinikum Würzburg Mitte gGmbH Standort Missioklinik
• Hungary
  • Budapest, Hungary, 1096
    • Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem,Pulmonológiai Klinika
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Orvos és Egeszsegtudomanyi Centrum
  • Pecs, Hungary, 7624
    • Pécsi Tudományegyetem Klinikai Központ
  • Szeged, Hungary, 6720
    • Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
• Israel
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center, Beilinson Campus
  • Tel-Hashomer, Israel, 5265601
    • The Chaim Sheba Medical Center
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliera Policlinico S. Orsola-Malpighi
  • Pavia, Italy, 27100
    • Fondazione Irccs Policlinico San Matteo
  • Roma, Italy, 00161
    • Policlinico Umberto I
  • Trieste, Italy, 34149
    • Ospedale di Cattinara - Struttura complessa di Pneumologia
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Malaysia
  • George Town, Malaysia, 10990
    • Hospital Pulau Pinang
  • Kajang, Malaysia, 43000
    • Hospital Serdang
  • Kuala Lumpur, Malaysia, 50400
    • Institut Jantung Negara (National Heart Institute)
• Mexico
  • Ciudad de Mexico, Mexico, 14000
    • Instituto Nacional de Cardiologia Dr. Ignacio Chavez
  • Guadalajara, Mexico, 44160
    • CICUM San Miguel
  • Monterrey, Mexico, 64718
    • Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VUMC Amsterdam
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis Nieuwegein
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im Jana Pawla II
  • Lublin, Poland, 20-718
    • Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ
  • Otwock, Poland, 05-400
    • NZOZ Europejskie Centrum Zdrowia Otwock
  • Poznań, Poland, 61-848
    • Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
  • Szczecin, Poland, 70-111
    • Samodzielny Publiczny Szpital Kliniczny nr 2 PUM
  • Warszawa, Poland, 02-005
    • Warszawski Uniwersytet Medyczny, Szpital Kliniczny Dzieciątka Jezus
  • Wroclaw, Poland, 51-124
    • Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy
• Portugal
  • Almada, Portugal, 2801-951
    • Hospital Garcia de Orta
  • Coimbra, Portugal, 3000-075
    • Hospitais da universidade de Coimbra
  • Lisbon, Portugal, 1649-028
    • Centro Hospitalar de Lisboa Norte
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio
• Russian Federation
  • Irkutsk, Russian Federation, 664049
    • Irkutsk Regional Clinical Hospital
  • Kemerovo, Russian Federation, 650002
    • Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
  • Moscow, Russian Federation, 121552
    • National Medical Research Center of Cardiology of MoH of Russian Federation
  • Moscow, Russian Federation, 121309
    • Moscow City Clinical Hospital No.51
  • Moscow, Russian Federation, 119049
    • Moscow City Clinical Hospital #1 n.a. N.I.Pirogov
  • Novosibirsk, Russian Federation, 630055
    • E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation
  • Saint-Petersburg, Russian Federation, 197341
    • National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
• Slovakia
  • Bratislava, Slovakia, 833 48
    • Narodny ustav srdcovych a cievnych chorob
• Spain
  • Barcelona, Spain, 8035
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 08036
    • Hosp. Clinic I Provincial de Barcelona
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Santander, Spain, 39011
    • Hosp. Univ. Marques de Valdecilla
  • Sevilla, Spain, 41013
    • Hosp. Virgen Del Rocio
  • Valencia, Spain, 46026
    • Hosp. Univ. I Politecni La Fe
• Sweden
  • Umea, Sweden, 901 85
    • Norrlands Universitetssjukhus
  • Uppsala, Sweden, 751 85
    • Uppsala Akademiska Sjukhuset, Kardiologkliniken
• Switzerland
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich
• Taiwan
  • Kaohsiung, Taiwan, 813
    • Kaohsiung Veterans General Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital, Mahidol University
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Khon Kaen University
• Turkey
  • Ankara, Turkey, 6100
    • Hacettepe University Medical Faculty
  • Ankara, Turkey, 6500
    • Ankara University Medical Faculty
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul Medical Faculty
  • Istanbul, Turkey, 34096
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey, 34899
    • Marmara University Medical Faculty
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
  • Kartal-Istanbul, Turkey, 34865
    • Kartal Koşuyolu Yüksek İhtisas Eğitim ve Araştirma Hastanesi
• Ukraine
  • Dnipro, Ukraine, 49059
    • CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
  • Kyiv, Ukraine, 02000
    • SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
  • Kyiv, Ukraine, 03038
    • SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'
  • Lviv, Ukraine, 79000
    • Lviv Regional Clinical Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0AY
    • Papworth Hospital NHS Trust
  • Glasgow, United Kingdom, G81 4DY
    • National Waiting Times Centre Board Golden Jubilee National Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Sheffield, United Kingdom, S10 2RX
    • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California, Keck School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Anschutz Medical Campus
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Pulmonary Consultants
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates PC
  • Florida
    • Jacksonville, Florida, United States, 32259
      • Mayo Clinic in Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospitals - Chicago
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Clinical Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Reno, Nevada, United States, 89503
      • St. Mary's Cardiology
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Clinical & Translational Science Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140-5103
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Plano, Texas, United States, 75093
      • Baylor Scott & White Research Institute at The Heart Hospital Baylor Plano
  • Utah
    • Murray, Utah, United States, 84175
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Cardiovascular Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Lukes Medical Center
    • Milwaukee, Wisconsin, United States, 53211
      • Medical College of Wisconsin-Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.).	Drug: Selexipag; oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration; Other Names: ACT-293987, JNJ-67896049
Placebo Comparator: 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.	Drug: Placebo; Oral tablets without active compound
Experimental: 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.	Drug: Selexipag; oral tablets containing 200 µg of selexipag. Depending on the iMTD, participants will receive 1 to 8 tablets at each administration; Other Names: ACT-293987, JNJ-67896049

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 26 in 6-minute walk distance (6MWD)	The 6MWD test is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. The distance walked in 6 minutes is measured in meters at baseline (before double-blind study treatment initiation) and Week 26 (within 2-5 hours post-dose). Absolute change from baseline to Week 26 in 6MWD is expressed in meters.	Week 26
Time to clinical worsening	Time to clinical worsening is defined as at least one of the following components confirmed by the clinical event committee (CEC): all-cause death, non-planned PH-related hospitalization, PH-related deterioration identified by increase from baseline in World Health Organization Functional Class (WHO FC) or deterioration from baseline in exercise capacity by at least 15 % or new or worsening signs/symptoms of right heart failure. Time from randomization to the first clinical worsening event up to end of DB treatment visit will be analyzed with the Kaplan-Meier survival estimates for each treatment arm.	From baseline up to end of double-blind (DB) treatment visit (maximum 59 months)
All-Cause Death or Hospitalizations Related to PH Worsening	All-cause death or hospitalizations related to PH worsening will be assessed.	Up to end of DB treatment visit (maximum 59 months)
World Health Organization Functional Class (WHO FC) improvement at Week 26	The following WHO FC classes are defined: Class I: no limitation of usual physical activity (PA); Class II: mild limitation of PA; Class III: marked limitation of PA; Class IV: unable to perform any PA without symptoms, Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA. Changes to a lower WHO FC class (for instance from Class III to Class II) corresponds to a WHO FC improvement.	Week 26
Change from baseline to Week 26 in Pulmonary arterial hypertension-symptoms and impact questionnaire (PAH-SYMPACT) Cardiopulmonary and Cardiovascular Symptom Domains	The PAH-SYMPACT questionnaire (including cardiopulmonary and cardiovascular symptoms domains). Absolute changes in symptom scores from baseline to week 26 will be calculated for each treatment arm.	Week 26
Change from Baseline to Week 26 in Borg Dyspnea index or Borg CR10 Scale	Absolute changes in BDI/ borg category-ratio 10 (Borg CR10) scores from baseline to Week 26 will be calculated for each treatment arm. The Borg dyspnea index (BDI) or Borg CR10 scale rates the severity of dyspnea ((shortness of breath) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the BDI/Borg CR10 scores indicates an improvement. For each participant, BDI/Borg CR10 will be evaluated immediately after the exercise test (6MWD test).	Week 26
Change from baseline to Week 26 in N-terminal pro b-type natriuretic peptide (NT pro-BNP)	Absolute changes in NT-pro BNP concentrations (pg/mL) from baseline to Week 26 will be calculated for each treatment arm.	Week 26

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Julian Borissoff, MD, PhD, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2019
• Primary Completion (Actual): June 7, 2022
• Study Completion (Actual): June 7, 2022

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: selexipag; CTEPH
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Selexipag
• Other Study ID Numbers: AC-065B302; 2018-002823-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Actelion is a Janssen pharmaceutical company of Johnson & Johnson. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No