A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

NCT04271475 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: CR10874267896062CTP30012019-004131-24
• Study Type: interventional
• Target: 127
• Locations: 32 countries
• Sites: 165

Brief Summary

The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28

  Change from baseline in 6MWD as measured by 6-minute walk test (6MWT) at Week 28 was reported. The purpose of the 6MWT was to quantify exercise tolerance and capacity. This standardized test measured the distance an individual was able to walk over a total of six minutes on a hard, flat surface with no obstacles. The goal was for the individual to walk as far as possible in 6 minutes.

  Baseline (Day 1), Week 28

Secondary Outcomes (6)

• Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period

  From Baseline (Day 1) up to EODBT: median 24.5 weeks (min 3.9 weeks; max 160.4 weeks) for macitentan, median 44 weeks (min 4 weeks; max 147.9 weeks) for placebo

• Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28

  From Baseline (Day 1) up to Week 28

• Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score

  From Baseline (Day 1) up to Week 28

• Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score

  From Baseline (Day 1) up to Week 28

• Change From Baseline to Week 28 in Euro Quality of Life-5-Dimension-5-Level (EQ-5D-5L) Utility Score and Visual Analog Scale (VAS) Score

  From Baseline (Day 1) up to Week 28

Study Arms (2)

Macitentan

EXPERIMENTAL

Participant will receive macitentan at a dose of 10 milligram (mg) once daily (OD) for 4 weeks, followed by a dose of macitentan 37.5 mg for another 4 weeks and continue with the target dose of macitentan 75 mg. Participants who have reached the target dose of 75 mg, completed the Double-blind (DB) period up to Week 28 (either on treatment or in Post-treatment observation period \[PTOP\]) at minimum, may be eligible for transitioning into the Open label (OL) extension period once all participants have completed the DB part of the study, or earlier if they experienced a Clinical event committee (CEC) confirmed clinical worsening event.

Drug: Macitentan

Placebo

EXPERIMENTAL

Participants will receive placebo tablets matching the macitentan 10 mg, macitentan 37.5mg and macitentan 75 mg tablets, respectively. Participants who completed the DB period as per protocol either on treatment or in PTOP are eligible for transitioning to the OL extension period and will receive macitentan 75 mg after an 8-week double-dummy uptitration (macitentan 10 mg for 4 weeks, followed by 37.5 mg for another 4 weeks).

Drug: Macitentan; Drug: Placebo

Interventions

Macitentan DRUG

Participants will receive Macitentan film-coated tablets orally od.

Also known as: ACT-064992,, Opsumit

Macitentan; Placebo

Placebo DRUG

Participant will receive matching placebo tablets orally od.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization \[WHO\] Group 4) fulfilling one of the following criteria: a) inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA), and deemed inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue pulmonary endarterectomy (PEA)
• minute walk distance (6MWD) greater than or equal to (\>=) 100 meter (m) and less than or equal to (\<=) 450 meters (m), documented by an eligibility and a baseline 6-minute walk test (6MWT). The baseline 6MWD must not differ by more than 15 percent (%) from the eligibility test
• World Health Organization functional class (WHO FC) \>= II
• Participants are to receive riociguat as per local standard of care, unless it is contraindicated or unavailable

You may not qualify if:

• Acute pulmonary embolism within 3 months prior to or during Screening
• Planned balloon pulmonary angioplasty (BPA) during the fixed duration part of the double-blind period
• Significant obstructive and restrictive lung disease
• Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (for example, intermittent claudication).
• Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the fixed duration part of the study
• Decompensated cardiac failure if not under close supervision
• Known and documented life-threatening cardiac arrhythmias
• Acute myocardial infarction within 6 months prior to, or during Screening
• Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening
• Known or suspicion of pulmonary veno-occlusive disease (PVOD)
• Administration of ERAs, intravenous prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization
• Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral, inhaled or subcutaneous (SC) prostacyclins / prostacyclin analogues, prostacyclin receptor agonists or riociguat, a) within 90 days prior to Randomization, or b) anticipated during the fixed duration part of the double-blind \[DB\] period
• Hypotension, that is, systolic blood pressure (SBP) less than (\<) 90 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) \<50 mmHg at Screening.
• Severe renal dysfunction with an estimated Glomerular Filtration Rate \<30 milliliters per minute per 1.73 meter square (mL/min/1.73 m\^2) using the Chronic Kidney Disease Epidemiology Collaboration formula at Screening
• Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history

Sponsors & Collaborators

• Actelion: lead

Study Sites (168)

University of California San Diego Medical Center

La Jolla, California, 92037, United States

Location

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

Location

UC Davis Medical Center

Sacramento, California, 95817-2201, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06519, United States

Location

University of Florida Health Jacksonville

Gainesville, Florida, 32608, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Tufts Medical Center

Boston, Massachusetts, 21118, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-2265, United States

Location

VA Sierra Nevada Health Care System

Reno, Nevada, 89509, United States

Location

University of New Mexico School of Medicine

Albuquerque, New Mexico, 87131, United States

Location

Syracuse VA Medical Center

Syracuse, New York, 13210, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Legacy Hospital

Portland, Oregon, 97210, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor Scott White - Plano

Plano, Texas, 75093, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Utah Cardiovascular Center

Salt Lake City, Utah, 84132, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792-2442, United States

Location

Nexo Salud Investigacion Clinica

Buenos Aires, C1006ACC, Argentina

Location

Sanatorio de la Trinidad Mitre

Buenos Aires, C1039AAO, Argentina

Location

Sanatorio Guemes

C.a.b.a., C1180AAX, Argentina

Location

Queensland Lung Transplant Service

Chermside, 4032, Australia

Location

St Vincent's hospital

Darlinghurst, 2010, Australia

Location

LKH-Univ. Klinikum Graz

Graz, 8036, Austria

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

Location

Medizinische Universitaet Wien

Vienna, 1090, Austria

Location

Military Medical Academy

Sofia, 1606, 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

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Beijing Chaoyang Hospital

Beijing, 100020, China

Location

Beijing Anzhen Hospital

Beijing, 100029, China

Location

China Japan Friendship Hospital

Beijing, 100029, China

Location

Beijing Shijitan Hospital

Beijing, 100038, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, 400016, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510140, China

Location

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, 310016, China

Location

Zhongda Hospital Southeast University

Nanjing, 210009, China

Location

The Affiliated Hospital of Medical College Qingdao University

Qingdao, 266003, China

Location

Huashan Hospital of Fudan University

Shanghai, 200040, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Zhongshan Hospital Fudan University

Shanghai, China

Location

The General Hospital of Northern Theater Command

Shenyang, 110000, China

Location

Tianjin Medical University General Hospital

Tianjin, 300052, China

Location

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, 710061, China

Location

Fundacion Neumologica Colombiana

Bogotá, 1101131, Colombia

Location

Fundación Abood Shaio

Bogotá, 85369, Colombia

Location

Clínica Imbanaco S.A.S.

Cali, 760042, Colombia

Location

Centro Cardiovascular Colombiano Clínica Santa María

Medellín, 681004, Colombia

Location

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

Prague, 128 08, Czechia

Location

Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B

Aarhus N, 8200, Denmark

Location

CHU de Brest - Hopital de la Cavale Blanche

Brest, 29200, France

Location

CHU de Grenoble Hopital Albert Michallon

Grenoble, 38043, France

Location

Hopital Bicetre Aphp Hopitaux Universitaires Paris Sud

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Cardiologique - Chru Lille

Lille, 59037, France

Location

CHU de Montpellier - Arnaud de Villeneuve

Montpellier, 34295, France

Location

CHU Saint Etienne Hopital Nord

Saint-Priest-en-Jarez, 42277, France

Location

Hopital Larrey CHU de Toulouse

Toulouse, France

Location

CHU de Nancy - Hopital de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Universitatsklinikum Bonn

Bonn, 53127, Germany

Location

Medizinische Fakultaet Carl Gustav Carus Technische Universitaet Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Giessen

Giessen, 35392, Germany

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie

Hanover, 30625, Germany

Location

Thoraxklinik Heidelberg

Heidelberg, 69126, Germany

Location

Universitaetsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Universitatsklinikum Jena

Jena, 07747, Germany

Location

Krankenhaus Neuwittelsbach

München, 80639, Germany

Location

Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet Felnott kardiologiai osztaly

Budapest, 1096, Hungary

Location

Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő

Szeged, 6720, Hungary

Location

Tel Aviv Medical Center

Tel Aviv, 6423906, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 5265601, Israel

Location

Ospedale SS. Annunziata

Chieti, 66100, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Fondazione Toscana Gabriele Monasterio CNR

Pisa, 56124, Italy

Location

Policlinico Gemelli Universita Cattolica

Roma, 00168, Italy

Location

A.O.U. Città della Salute e della Scienza

Torino, 10126, Italy

Location

The University of Tokyo Hospital

Bunkyō City, 113-8655, Japan

Location

Kyushu University Hospital

Fukuoka, 812 8582, Japan

Location

Kure Kyosai Hospital

Hiroshima, 737-8505, Japan

Location

St Marianna University Hospital

Kanagawa, 216 8511, Japan

Location

Kobe University Hospital

Kobe, 650 0017, Japan

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Kyoto University Hospital

Kyoto, 606 8507, Japan

Location

Shinshu University Hospital

Matsumoto, 390 8621, Japan

Location

Toho University Medical Center, Ohashi Hospital

Meguro-ku, 153-8515, Japan

Location

Kyorin University Hospital

Mitaka, 181-8611, Japan

Location

Nagoya University Hospital

Nagoya, 466 8560, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, 701-1192, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

National Cerebral and Cardiovascular Center

Suita-Shi, 564-8565, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

University of Tsukuba Hospital

Tsukuba, 305 8576, Japan

Location

Lietuvos sveikatos mokslų universiteto ligoninė Kauno klinik

Kaunas, 50161, Lithuania

Location

Vilnius University Hospital Santariskiu Klinikos

Vilnius, LT-08661, Lithuania

Location

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, 14080, Mexico

Location

Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas

México, 52787, Mexico

Location

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

Monterrey, 64718, Mexico

Location

Centro de Investigacion Clinica Chapultepec

Morelia, 58260, Mexico

Location

CRI Centro Regiomontano de Investigacion SC

Nuevo León, 64060, Mexico

Location

Krakowski Szpital Specjalistyczny im Jana Pawla II

Krakow, 31 202, Poland

Location

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego PZOZ

Lublin, 20 708, Poland

Location

Europejskie Centrum Zdrowia Otwock Sp z o o

Otwock, 05 400, Poland

Location

Uls Almada Seixal - Hosp. Garcia de Orta

Almada, 2805 267, Portugal

Location

Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu

Bucharest, 022328, Romania

Location

Spitalul Clinic Judetean de Urgenta

Tg. Mures, 540136, Romania

Location

State Autonomous HealthCare Institution 'Interregional Clinical Diagnostic Center'

Kazan', 420101, 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

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

Saint Petersburg, 197341, Russia

Location

Volgograd Regional Clinical Cardiology Center

Volgograd, 400008, Russia

Location

King Faisal Specialist Hospital & Research Center

Riyadh, 12713, Saudi Arabia

Location

King Fahad Medical City

Riyadh, 59046, Saudi Arabia

Location

University Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Institute for Pulmonary Disease of Vojvodina

Kamenitz, 21204, Serbia

Location

National University Heart Centre, Singapore

Singapore, 119228, Singapore

Location

National Heart Centre (NHC) Singapore

Singapore, 169609, Singapore

Location

Narodny ustav srdcovych a cievnych chorob

Bratislava, 833 48, Slovakia

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

Hosp. Costa Del Sol

Málaga, 29603, Spain

Location

Hosp. Gral. Univ. de Toledo

Toledo, 45007, Spain

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 813, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang-Gung Memorial Hospital, LinKou Branch

Taoyuan District, 333, Taiwan

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Thammasat Hospital

Pathum Thani, 12120, Thailand

Location

Adana City Hospital

Adana, 01170, Turkey (Türkiye)

Location

Cukurova University Medical Faculty

Adana, 01250, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06230, Turkey (Türkiye)

Location

Ankara Bilkent Sehir Hastanesi

Ankara, 06800, Turkey (Türkiye)

Location

Pamukkale University Medical Faculty

Denizli, 20070, Turkey (Türkiye)

Location

Eskisehir Osmangazi University Medical Faculty Hospital

Eskişehir, 26040, Turkey (Türkiye)

Location

Istanbul University - Cerrahpasa Cardiology Institution

Istanbul, 34096, Turkey (Türkiye)

Location

Siyami Ersek Training and Research Hospital

Istanbul, 34668, Turkey (Türkiye)

Location

Marmara University Medical Faculty

Istanbul, 34899, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Dokuz Eylul University Medical Faculty

Izmir, 35340, Turkey (Türkiye)

Location

Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi

Kartal Istanbul, 34865, Turkey (Türkiye)

Location

Mersin University Medical Faculty

Mersin, 33110, Turkey (Türkiye)

Location

CNE 'Cherkasy Regional Cardiological Center of Cherkasy Regional Council'

Cherkasy, 18009, Ukraine

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

State Institute Of Phthisiology And Pulmonology N.A. F.G. Yanovskiy Of Ams Ukraine

Kyiv, 03680, Ukraine

Location

Communal Noncommercial Enterprise of Lviv Regional Council 'Lviv Regional Clinical Hospital'

Lviv, 79010, Ukraine

Location

Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council

Ternopil, 46002, 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

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Sheffield, S10 2RX, United Kingdom

Location

MeSH Terms

Interventions

macitentan

Limitations and Caveats

Limitations of the trial such as small numbers of participants analysed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Clinical Science Director CP
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Actelion Clinical Trial

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: July 7, 2020
• Primary Completion: December 21, 2023
• Study Completion: December 21, 2023
• Last Updated: June 27, 2025
• Results First Posted: April 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

RU (5); DE (9); PT (1); SE (2); FR (8); AU (2); US (24); CN (15); TU (13); BU (2); KR (5); UA (6); HU (2); CZ (1); TW (4); GB (6); AR (3); CA (3); PL (3); JP (16); RO (2); DK (1); ME (5); SA (2); ES (6); SL (1); CO (4); TH (3); SG (2); IT (5); IL (2); LI (2)