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

NCT ID: NCT02932410

Last Updated: 2025-10-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 165 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-24
• Study Completion Date: 2025-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Macitentan

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.

Group Type: EXPERIMENTAL

Macitentan

Intervention Type: DRUG

Dispersible tablet; Oral use

Standard-of-care

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.

Group Type: OTHER

Standard-of-care

Intervention Type: 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.

Interventions

Macitentan

Dispersible tablet; Oral use

Intervention Type: DRUG

Standard-of-care

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.

Intervention Type: OTHER

Other Intervention Names

ACT-064992

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Phoenix Childrens Hospital

Phoenix, Arizona, United States

UCLA Children's Heart Center

Los Angeles, California, United States

UCSF Medical Center

San Francisco, California, United States

Childrens Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

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

Riley Hospital For Children

Indianapolis, Indiana, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Detroit Medical Center

Detroit, Michigan, United States

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Children's Heart Center

Las Vegas, Nevada, United States

Columbia University Medical Center - PIN

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Primary Children's Medical Center

Salt Lake City, Utah, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Childrens Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Royal Children's Hospital Melbourne - PIN

Parkville, , Australia

Lady Cilento Children's Hospital

South Brisbane, , Australia

Children's Hospital at Westmead

Westmead, , Australia

Medizinische Universität Graz

Graz, , Austria

Landes Frauen Und Kinderklinik Linz

Linz, , Austria

Medizinische Universitat Wien

Linz, , Austria

Irmandade Da Santa Casa de Misericórdia de São Paulo

São Paulo, , Brazil

Sainte Justine Hospital

Montreal, , Canada

Stollery Children's Hospital

Toronto, , Canada

Beijing Anzhen Hospital of The Capital University of Medical Sciences

Beijing, , China

Qingdao Women and Children's Hospital

Qingdao, , China

Childrens Hospital of Shanghai

Shanghai, , China

Shanghai Children's Medical Center

Shanghai, , China

Fundacion Santa Fe de Bogota

Bogotá, , Colombia

Centro Medico Imbanaco de Cali SA

Cali, , Colombia

HUS Uusi lastensairaala

Helsinki, , Finland

Hôpital de la Timone Enfants

Marseille, , France

Groupe Hospitalier Necker Enfants Malades

Paris, , France

Hôpital Haut-Lévêque - Hôpital cardiologique

Pessac, , France

Hôpital Des Enfants

Toulouse, , France

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, , Hungary

Rambam Medical Center - PPDS

Haifa, , Israel

Schneider Children's Medical Center of Israel - PIN

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Institut Jantung Negara

Kuala Lumpur, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

CICUM San Miguel

Guadalajara, , Mexico

Instituto Nacional de Pediatría

Mexico City, , Mexico

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, , Mexico

Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas

México, , Mexico

Unidad de Investigación Clínica En Medicina SC

Monterrey, , Mexico

Makati Medical Center

Makati City, , Philippines

Philippine Heart Center

Quezon City, , Philippines

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

Poznan, , Poland

Instytut Pomnik - Centrum Zdrowia Dziecka

Warsaw, , Poland

Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo-Rozwojowy

Wroclaw, , Poland

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

Carnaxide, , Portugal

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, , Portugal

Hospital Santa Marta

Lisbon, , Portugal

Centro Hospitalar de Sao Joao EPE

Porto, , Portugal

Research Institute of Complex Cardiovascular Pathology

Kemerovo, , Russia

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

Moscow, , Russia

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

Moscow, , Russia

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

Novosibirsk, , Russia

Saint Petersburg State Pediatric Medical Academy

Saint Petersburg, , Russia

Clinical Hospital №1

Tyumen, , Russia

Bashkiria State Medical University

Ufa, , Russia

University of The Free State

Bloemfontein, , South Africa

Inkosi Albert Luthuli Central Hospital

Durban, , South Africa

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System - PPDS

Seoul, , South Korea

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

C.H. Regional Reina Sofia

Córdoba, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Maharaj Nakorn Chiang Mai Chiang Mai University

Chiang Mai, , Thailand

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

Dnipro, , Ukraine

Municipal Institution of Health Care Regional Children's Clinical Hospital

Kharkiv, , Ukraine

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

Kyiv, , Ukraine

Hanoi Heart Hospital

Hanoi, , Vietnam

Hanoi Medical University Hospital

Hanoi, , Vietnam

Children's Hospital 1

Ho Chi Minh City, , Vietnam

Tam Duc Hospital

Ho Chi Minh City, , Vietnam

Countries

Argentina; Bulgaria; United States; Australia; Austria; Brazil; Canada; China; Colombia; Finland; France; Hungary; Israel; Malaysia; Mexico; Philippines; Poland; Portugal; Russia; South Africa; South Korea; Spain; Thailand; Ukraine; Vietnam

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-055-312

Identifier Type: -

Identifier Source: org_study_id