A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)

NCT02932410 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AC-055-312
• Study Type: interventional
• Target: 165
• Locations: 22 countries
• Sites: 82

Brief Summary

This is a prospective, multicenter, open-label, randomized, controlled, parallel Phase 3 study with an open-label single-arm extension period to evaluate pharmacokinetics (PK), safety and efficacy of macitentan in children with pulmonary arterial hypertension (PAH).

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (4)

• Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Body Weight

  Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 based on body weight were reported. This outcome measure was planned to be analyzed for specified arms only.

  Pre-dose at Week 12

• Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Age Group

  Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 based on age group were reported. This outcome measure was planned to be analyzed for specified arms only.

  Pre-dose at Week 12

• Participants <2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 4

  Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 4 were reported. This outcome measure was planned to be analyzed for specified arms only.

  Pre-dose at Week 4

• Participants From China With >=12 to <18 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12

  Observed steady-state trough (pre-dose) plasma concentration of macitentan and aprocitentan (active metabolite) at Week 12 were reported.

  Pre-dose at Week 12

Secondary Outcomes (19)

• Time to the First Clinical Event Committee (CEC)-Confirmed Disease Progression Event

  Baseline (Day 1) up to end of core study period (EOCP; up to 7.08 years)

• Time to First CEC-confirmed Hospitalization for PAH

  Baseline (Day 1) up to EOCP (up to 7.08 years)

• Time to CEC-confirmed Death Due to PAH

  Baseline (Day 1) up to EOCP (up to 7.08 years)

• Time to Death (All Causes)

  Baseline (Day 1) up to 7.26 years

• Percentage of Participants With World Health Organization (WHO) Functional Class (FC) I or II Versus III or IV

  At Weeks 12 and 24

Study Arms (2)

Macitentan

EXPERIMENTAL

Macitentan is administered once daily via oral route. Children less than (\<) 2 years old (y.o.) will be assigned as a cohort to the macitentan group without randomization. The dose will be adjusted to the participant's age (for those \< 2 y.o.) or to the participant's body weight (for those greater than or equal to (\>=) 2 y.o.). single-arm extension period (SAEP) will start at end of core period (EOCP) visit and ends at end of study (EOS) visit.

Drug: Macitentan

Standard-of-care

OTHER

Standard-of-care as per site's clinical practice which may comprise treatment with pulmonary arterial hypertension (PAH) non-specific treatment and/or up to two PAH-specific medications excluding macitentan and intravenous/subcutaneous (IV/SC) prostanoids.

Other: Standard-of-care

Interventions

Macitentan DRUG

Dispersible tablet; Oral use

Also known as: ACT-064992

Macitentan

Standard-of-care OTHER

Standard-of-care as per site's clinical practice which may comprise treatment with PAH non-specific treatment and/or up to two PAH-specific medications excluding macitentan and IV/SC prostanoids.

Standard-of-care

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent by the parent(s) or legally designated representative and assent from developmentally capable children prior to initiation of any study-mandated procedure
• Males or females between greater than or equal to (\>=) 1 month and less than (\<) 18 years of age
• Participants with body weight \>= 3.5 kilograms (kg) at randomization
• Pulmonary arterial hypertension (PAH) diagnosis confirmed by historical RHC (mPAP greater than or equal to \[\>=\] 25 millimeters of mercury \[mmHg\], and Pulmonary artery wedge pressure \[PAWP\] less than or equal to \[\<=\] 15 mmHg, and Pulmonary vascular resistance index \[PVRi\] greater than \[\>\] 3 WU × m2), where in the absence of pulmonary vein obstruction and/or significant lung disease PAWP can be replaced by Left atrium pressure \[LAP\] or Left ventricular end diastolic pressure \[LVEDP\] (in absence of mitral stenosis) assessed by heart catheterization
• PAH belonging to the Nice 2013 Updated Classification Group 1 (including participants with Down Syndrome) and of following etiologies: idiopathic PAH; heritable PAH; PAH associated with congenital heart disease (CHD); Drug or toxin induced PAH; PAH associated with HIV; PAH associated with connective tissue diseases (PAH-aCTD); and World health organization (WHO) Functional class I to III
• Females of childbearing potential must have a negative pregnancy test at Screening and at Baseline, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) up to the end of study (EOS)

You may not qualify if:

• Participants with PAH due to portal hypertension, schistosomiasis, or with pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn
• Participants with PAH associated with Eisenmenger syndrome, or with moderate to large left-to-right shunts
• Participants receiving a combination of \> 2 PAH-specific treatments at randomization.
• Treatment with intravenous (IV) or subcutaneous (SC) prostanoids within 4 weeks before randomization, unless given for vasoreactivity testing
• Hemoglobin or hematocrit \<75 percent (%) of the lower limit of normal range
• Serum Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) greater than (\>) 3 times the upper limit of normal range
• Pregnancy (including family planning) or breastfeeding.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
• Severe hepatic impairment, for example Child-Pugh Class C
• Clinical signs of hypotension which in the investigator's judgment would preclude initiation of a PAH-specific therapy
• Severe renal insufficiency (estimated creatinine clearance \<30 mL/min or serum creatinine \>221 micro-moles per liter \[micro-mol/L\])
• Participants with known diagnosis of bronchopulmonary dysplasia

Sponsors & Collaborators

• Actelion: lead

Study Sites (85)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

UCLA Children's Heart Center

Los Angeles, California, 90095, United States

Location

UCSF Medical Center

San Francisco, California, 94143-2202, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Riley Hospital For Children

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Detroit Medical Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

Children's Heart Center

Las Vegas, Nevada, 89109, United States

Location

Columbia University Medical Center - PIN

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 19803, United States

Location

Childrens Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Children's Hospital Melbourne - PIN

Parkville, 3052, Australia

Location

Lady Cilento Children's Hospital

South Brisbane, 4101, Australia

Location

Children's Hospital at Westmead

Westmead, 2145, Australia

Location

Medizinische Universität Graz

Graz, 8036, Austria

Location

Landes Frauen Und Kinderklinik Linz

Linz, 4020, Austria

Location

Medizinische Universitat Wien

Linz, 4020, Austria

Location

Irmandade Da Santa Casa de Misericórdia de São Paulo

São Paulo, 01221-020, Brazil

Location

Sainte Justine Hospital

Montreal, H3T 1C5, Canada

Location

Beijing Anzhen Hospital of The Capital University of Medical Sciences

Beijing, 100029, China

Location

Qingdao Women and Children's Hospital

Qingdao, 26600, China

Location

Childrens Hospital of Shanghai

Shanghai, 200062, China

Location

Shanghai Children's Medical Center

Shanghai, 200127, China

Location

Fundacion Santa Fe de Bogota

Bogotá, 220246, Colombia

Location

Centro Medico Imbanaco de Cali SA

Cali, 760042, Colombia

Location

HUS Uusi lastensairaala

Helsinki, 00290, Finland

Location

Hôpital de la Timone Enfants

Marseille, 13385, France

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75743, France

Location

Hôpital Haut-Lévêque - Hôpital cardiologique

Pessac, 33604, France

Location

Hôpital Des Enfants

Toulouse, 31059, France

Location

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, 1096, Hungary

Location

Rambam Medical Center - PPDS

Haifa, 31096, Israel

Location

Schneider Children's Medical Center of Israel - PIN

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Institut Jantung Negara

Kuala Lumpur, 50400, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

CICUM San Miguel

Guadalajara, 44160, Mexico

Location

Instituto Nacional de Pediatría

Mexico City, 04530, Mexico

Location

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, 14080, Mexico

Location

Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas

México, 52763, Mexico

Location

Unidad de Investigación Clínica En Medicina SC

Monterrey, 64716, Mexico

Location

Makati Medical Center

Makati City, 1229, Philippines

Location

Philippine Heart Center

Quezon City, 0850, Philippines

Location

Szpital Kliniczny im. Karola Jonschera Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, 60-572, Poland

Location

Instytut Pomnik - Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo-Rozwojowy

Wroclaw, 51-124, Poland

Location

Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa Cruz

Carnaxide, 2790-134, Portugal

Location

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

Hospital Santa Marta

Lisbon, 1169-024, Portugal

Location

Centro Hospitalar de Sao Joao EPE

Porto, 4200-319, Portugal

Location

Research Institute of Complex Cardiovascular Pathology

Kemerovo, 650002, Russia

Location

GBUZ Children's Hospital named after Bashlyaeva Z.A. Moscow

Moscow, 125408, Russia

Location

Russian National Research Medical University n.a. N.I.Pirogov

Moscow, 125412, Russia

Location

Novosibirsk Research Institue of Blood Circulation Pathology n.a. E.N. Meshalkin

Novosibirsk, 630055, Russia

Location

Saint Petersburg State Pediatric Medical Academy

Saint Petersburg, 194100, Russia

Location

Clinical Hospital №1

Tyumen, 625023, Russia

Location

Bashkiria State Medical University

Ufa, 450000, Russia

Location

University of The Free State

Bloemfontein, 9300, South Africa

Location

Inkosi Albert Luthuli Central Hospital

Durban, 4001, South Africa

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System - PPDS

Seoul, 03722, South Korea

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 08035, Spain

Location

C.H. Regional Reina Sofia

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Maharaj Nakorn Chiang Mai Chiang Mai University

Chiang Mai, 50200, Thailand

Location

MI Dnipropetrovsk Specialized Clin. Med. Center of Mother and Child n.a. prof. M.F. Rudnev of DRC

Dnipro, 49000, Ukraine

Location

Municipal Institution of Health Care Regional Children's Clinical Hospital

Kharkiv, 61093, Ukraine

Location

MI Scientific Practical Medical Center for Children Cardiology and Cardiosurgery of MOH of Ukraine

Kyiv, 04050, Ukraine

Location

Hanoi Heart Hospital

Hanoi, 100000, Vietnam

Location

Hanoi Medical University Hospital

Hanoi, 100000, Vietnam

Location

Children's Hospital 1

Ho Chi Minh City, 700000, Vietnam

Location

Tam Duc Hospital

Ho Chi Minh City, 700000, Vietnam

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

macitentan; Standard of Care

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Executive Medical Director CP
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: October 13, 2016
• Study Start: October 24, 2017
• Primary Completion: August 28, 2024
• Study Completion: November 27, 2025
• Last Updated: March 13, 2026
• Results First Posted: September 12, 2025

Record last verified: 2026-03

Locations

HU (1); TH (1); BR (1); AU (3); CA (1); CO (2); CN (4); FR (4); ZA (2); KR (2); FI (1); ES (7); VN (4); PH (2); PT (4); US (20); UA (3); IL (3); PL (3); MY (2); ME (5); RU (7)