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

NCT03689244 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: AC-065B3022018-002823-41
• Study Type: interventional
• Target: 128
• Locations: 30 countries
• Sites: 160

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.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Keywords

CTEPH; selexipag

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Selexipag DB

EXPERIMENTAL

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

Placebo DB

PLACEBO COMPARATOR

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

Selexipag OL

EXPERIMENTAL

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

Interventions

Selexipag DRUG

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

Also known as: ACT-293987, JNJ-67896049

Selexipag DB; Selexipag OL

Placebo DRUG

Oral tablets without active compound

Placebo DB

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Actelion: lead

Study Sites (162)

University of California San Diego Medical Center

La Jolla, California, 92037, United States

Location

University of Southern California, Keck School of Medicine

Los Angeles, California, 90033, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Colorado Springs Pulmonary Consultants

Colorado Springs, Colorado, 80907, United States

Location

South Denver Cardiology Associates PC

Littleton, Colorado, 80120, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32259, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago Hospitals - Chicago

Chicago, Illinois, 60637, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Sparrow Clinical Research Institute

Lansing, Michigan, 48912, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

St. Mary's Cardiology

Reno, Nevada, 89503, United States

Location

University of New Mexico Clinical & Translational Science Center

Albuquerque, New Mexico, 87131, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140-5103, United States

Location

Allegheny

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

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

Plano, Texas, 75093, United States

Location

Intermountain Medical Center

Murray, Utah, 84175, United States

Location

University of Utah Cardiovascular Center

Salt Lake City, Utah, 84132, United States

Location

Medical College of Wisconsin Froedtert Hospital

Milwaukee, Wisconsin, 53211, United States

Location

Aurora Saint Lukes Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Sanatorio de la Trinidad Mitre

Buenos Aires, C1039AAO, Argentina

Location

Centro Médico Dra. De Salvo

Buenos Aires, C1426ABP, Argentina

Location

Hospital Italiano de Buenos Aires

Caba, 1199ABB, Argentina

Location

Sanatorio Ramon Cereijo

Caba, C1048AAN, Argentina

Location

Instituto de Cardiología y Cirugía Cardiovascular - Fundación Favaloro

Caba, C1093AAS, Argentina

Location

Hospital General de Agudos Dr Cosme Argerich

CABA, C1155AHD, Argentina

Location

Hospital Britanico de Buenos Aires

CABA, C1280AEB, Argentina

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Queensland Lung Transplant Service

Chermside, 4032, Australia

Location

St Vincent's hospital

Darlinghurst, 2010, Australia

Location

Pulmonary Arterial Hypertension Clinic

Hobart, 7000, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

Location

Medical University Vienna

Vienna, 1090, Austria

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Universidade Federal De Minas Gerais - Hospital das Clínicas

Belo Horizonte, 30130-100, Brazil

Location

Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa

Belo Horizonte, 30441-070, Brazil

Location

Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)

Botucatu, 18618-686, Brazil

Location

Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes

Fortaleza, 60840-285, Brazil

Location

Universidade Federal de Goias - Hospital das Clinicas da UFG

Goiânia, 74605-020, Brazil

Location

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90020-090, Brazil

Location

Hospital das Clinicas de Porto Alegre

Porto Alegre, 90035-003, Brazil

Location

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS

Porto Alegre, 90610-000, Brazil

Location

Fundacao do ABC - Centro Universitario FMABC

Santo André, 09060-870, Brazil

Location

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

São Paulo, 04037-003, Brazil

Location

Hospital Das Clinicas Da Faculdade De Medicina Da USP

São Paulo, 05403-000, Brazil

Location

UMHAT 'Heart and Brain Center for Excellence'

Pleven, 5800, Bulgaria

Location

National Cardiology Hospital

Sofia, 1392, Bulgaria

Location

University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD

Sofia, 1750, Bulgaria

Location

University Of Calgary - Peter Lougheed Centre

Calgary, Alberta, T1Y 6J4, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

London Health Sciences Centre - Victoria Hospital

London, Ontario, N6A 5W9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Institut Universitaire De Cardiologie Et De Pneumologie De Québec

Québec, Quebec, G1V 4G5, Canada

Location

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

Beijing, 100730, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120, China

Location

The General Hospital of Northern Theater Command

Shenyang, 110000, China

Location

Shengjing Hospital Of China Medical University

Shenyang, 110022, China

Location

Shanxi Cardiovascular Hospital

Taiyuan, 030001, China

Location

Tianjin Medical University General Hospital

Tianjin, 300052, China

Location

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

Prague, 128 08, Czechia

Location

Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B

Aarhus, 8200, Denmark

Location

Rigshospitalet Kardiologisk Klinisk

Copenhagen, 2100, Denmark

Location

Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie

Dresden, 01307, Germany

Location

Universitätsklinikum Giessen Medizinische Klinik Und Poliklinik Ii, Pneumologie

Giessen, 35392, Germany

Location

Universität Greifswald - Klinik Für Innere Medizin Bereich Pneumologie/Infektiologie

Greifswald, 17475, Germany

Location

Universitätsklinikum Hamburg-Eppendorf - Pneumologie

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie

Hanover, 30625, Germany

Location

Thoraxklinik am Universitatsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V

Homburg/Saar, 66421, Germany

Location

Universitätsklinikum Leipzig Medizinischen Klinik und Poliklinik I, Abteilung für Pneumologie

Leipzig, 04103, Germany

Location

Klinikum Würzburg Mitte gGmbH Standort Missioklinik

Würzburg, 97074, Germany

Location

Semmelweis Egyetem,Pulmonológiai Klinika

Budapest, 1083, Hungary

Location

Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály

Budapest, 1096, Hungary

Location

Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum

Debrecen, 4032, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7624, Hungary

Location

Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő

Szeged, 6720, Hungary

Location

Rabin Medical Center Beilinson Campus

Petah Tikva, 4941492, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 5265601, Israel

Location

Azienda Ospedaliera Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Ospedale di Cattinara - Struttura complessa di Pneumologia

Trieste, 34149, Italy

Location

Hospital Pulau Pinang

George Town, 10990, Malaysia

Location

Hospital Serdang

Kajang, 43000, Malaysia

Location

Institut Jantung Negara (National Heart Institute)

Kuala Lumpur, 50400, Malaysia

Location

CICUM San Miguel

Guadalajara, 44160, Mexico

Location

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, 14000, Mexico

Location

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

Monterrey, 64718, Mexico

Location

VUMC Amsterdam

Amsterdam, 1081 HV, Netherlands

Location

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, 3435 CM, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Krakowski Szpital Specjalistyczny im Jana Pawla II

Krakow, 31-202, Poland

Location

Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ

Lublin, 20-718, Poland

Location

NZOZ Europejskie Centrum Zdrowia Otwock

Otwock, 05-400, Poland

Location

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, 61-848, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 2 PUM

Szczecin, 70-111, Poland

Location

Warszawski Uniwersytet Medyczny, Szpital Kliniczny Dzieciątka Jezus

Warsaw, 02-005, Poland

Location

Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy

Wroclaw, 51-124, Poland

Location

Hospital Garcia de Orta

Almada, 2801-951, Portugal

Location

Hospitais da universidade de Coimbra

Coimbra, 3000-075, Portugal

Location

Centro Hospitalar de Lisboa Norte

Lisbon, 1649-028, Portugal

Location

Hospital Geral de Santo Antonio

Porto, 4099-001, Portugal

Location

Irkutsk Regional Clinical Hospital

Irkutsk, 664049, Russia

Location

Cardiovascular Pathology Research Institute of Siberian Branch of RAMS

Kemerovo, 650002, Russia

Location

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

Moscow, 119049, Russia

Location

Moscow City Clinical Hospital No.51

Moscow, 121309, Russia

Location

National Medical Research Center of Cardiology of MoH of Russian Federation

Moscow, 121552, Russia

Location

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

Novosibirsk, 630055, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

Narodny ustav srdcovych a cievnych chorob

Bratislava, 833 48, Slovakia

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. Univ. Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39011, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

Norrlands Universitetssjukhus

Umeå, 901 85, Sweden

Location

Uppsala Akademiska Sjukhuset, Kardiologkliniken

Uppsala, 751 85, Sweden

Location

Universitatsspital Zurich

Zurich, 8091, Switzerland

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 813, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Ramathibodi Hospital Mahidol University

Bangkok, 10400, Thailand

Location

Srinagarind Hospital, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Hacettepe University Medical Faculty

Ankara, 6100, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, 6500, Turkey (Türkiye)

Location

Istanbul University Istanbul Medical Faculty

Istanbul, 34093, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34096, Turkey (Türkiye)

Location

Marmara University Medical Faculty

Istanbul, 34899, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi

Kartal Istanbul, 34865, Turkey (Türkiye)

Location

CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'

Dnipro, 49059, Ukraine

Location

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

Kyiv, 02000, Ukraine

Location

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

Kyiv, 03038, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, 79000, Ukraine

Location

Papworth Hospital NHS Trust

Cambridge, CB2 0AY, United Kingdom

Location

National Waiting Times Centre Board Golden Jubilee National Hospital

Glasgow, G81 4DY, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Sheffield, S10 2RX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39326918 DERIVED

MeSH Terms

Interventions

selexipag

Limitations and Caveats

Failure to meet success on the primary outcome measure led to termination of the study for futility and thus the pre-planned testing hierarchy was no longer applicable, and all efficacy analyses other than the primary endpoint (PVR) were exploratory.

Results Point of Contact

• Title: Senior Clinical Leader
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Julian Borissoff, MD, PhD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: September 28, 2018
• Study Start: January 23, 2019
• Primary Completion: June 7, 2022
• Study Completion: June 7, 2022
• Last Updated: June 21, 2024
• Results First Posted: August 9, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); KR (5); US (32); PT (4); TW (4); SE (2); SL (1); CH (1); CA (5); BR (11); AR (7); MY (3); PL (8); CZ (1); NL (2); ME (3); UA (4); ES (6); GB (6); IT (4); RU (7); IL (2); DE (9); TH (2); CN (6); HU (5); BU (3); DK (2); TU (7); AU (6)