Clinical trial NCT02932410: A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)
Official title: A Multicenter, Open-label, Randomized, Study With Single-arm Extension Period to Assess the Pharmacokinetics, Safety and Efficacy of Macitentan Versus Standard of Care in Children With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2016-10-13
Enrollment: 165
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Key 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)

Key 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

Primary outcomes:
measure: Participants Greater than or Equal to (>=) 2 Years: Observed Steady-state Trough Plasma Concentration of Macitentan and its Active Metabolite ACT-132577 at Week 12
timeFrame: Week 12
measure: Participants Less than (<) 2 Years: Observed Steady-state Trough Plasma Concentration of Macitentan and its Active Metabolite ACT-132577 at Week 4
timeFrame: Week 4
Secondary outcomes:
measure: Time to the first CEC-confirmed Disease Progression Event
timeFrame: Between randomization/visit 2 and end of core study period (EOCP); up to 7 years
measure: Time to First CEC-confirmed Hospitalization for PAH
timeFrame: Between randomization/visit 2 and EOCP/; up to 7 years
measure: Time to CEC-confirmed death due to PAH
timeFrame: Between randomization/visit 2 and EOCP; up to 7 years
measure: Time to death (all causes)
timeFrame: Between randomization/visit 2 and EOCP; up to 7 years
measure: The Percentage of Participants with World Health Organization (WHO) Functional Class (FC) I or II versus III or IV
timeFrame: Week 24
measure: Change from Baseline to Week 24 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline to Week 24
measure: Change from Baseline to Week 48 in Moderate to Vigorous Physical Activity as Measured by Accelerometry
timeFrame: Baseline to Week 48
measure: Change from Baseline to Week 24 in Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography
timeFrame: Baseline to Week 24
measure: Change from Baseline to Week 24 in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography
timeFrame: Baseline to Week 24
measure: Change from Baseline to Week 24 in Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) Generic Core Scales Short Form (SF-15)
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Children's Heart Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Detroit Medical Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - PPDS
state: Minnesota
city: Las Vegas
country: United States
facility: Children's Heart Center
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - PIN
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Milwaukee
country: United States
facility: Childrens Hospital of Wisconsin
state: Wisconsin
city: Parkville
country: Australia
facility: Royal Children's Hospital Melbourne - PIN
city: South Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Linz
country: Austria
facility: Landes Frauen Und Kinderklinik Linz
city: Linz
country: Austria
facility: Medizinische Universitat Wien
city: São Paulo
country: Brazil
facility: Irmandade Da Santa Casa de Misericórdia de São Paulo
city: Montreal
country: Canada
facility: Sainte Justine Hospital
city: Toronto
country: Canada
facility: Stollery Children's Hospital
city: Beijing
country: China
facility: Beijing Anzhen Hospital of The Capital University of Medical Sciences
city: Qingdao
country: China
facility: Qingdao Women and Children's Hospital
city: Shanghai
country: China
facility: Childrens Hospital of Shanghai
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
city: Bogota
country: Colombia
facility: Fundacion Santa Fe de Bogota
city: Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali SA
city: Helsinki
country: Finland
facility: HUS Uusi lastensairaala
city: Marseille
country: France
facility: Hôpital de la Timone Enfants
city: Paris cedex 15
country: France
facility: Groupe Hospitalier Necker Enfants Malades
city: Pessac
country: France
facility: Hôpital Haut-Lévêque - Hôpital cardiologique
city: Toulouse Cedex 9
country: France
facility: Hôpital Des Enfants
city: Budapest
country: Hungary
facility: Gottsegen Gyorgy Orszagos Kardiologiai Intezet
city: Haifa
country: Israel
facility: Rambam Medical Center - PPDS
city: Petah-Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel - PIN
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS
city: Kuala Lumpur
country: Malaysia
facility: Institut Jantung Negara
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Ciudad De México
country: Mexico
facility: Instituto Nacional de Pediatría
city: Ciudad De México
country: Mexico
facility: Instituto Nacional de Cardiologia Dr. Ignacio Chavez
city: Guadalajara
country: Mexico
facility: CICUM San Miguel
city: Mexico
country: Mexico
facility: Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
city: Monterrey
country: Mexico
facility: Unidad de Investigación Clínica En Medicina SC
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Quezon City
country: Philippines
facility: Philippine Heart Center
city: Poznań
country: Poland
facility: Szpital Kliniczny im. Karola Jonschera Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
city: Warszawa
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo-Rozwojowy
city: Carnaxide
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa Cruz
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitário de Coimbra EPE
city: Lisboa
country: Portugal
facility: Hospital Santa Marta
city: Porto
country: Portugal
facility: Centro Hospitalar de Sao Joao EPE
city: Kemerovo
country: Russian Federation
facility: Research Institute of Complex Cardiovascular Pathology
city: Moscow
country: Russian Federation
facility: GBUZ Children's Hospital named after Bashlyaeva Z.A. Moscow
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University n.a. N.I.Pirogov
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk Research Institue of Blood Circulation Pathology n.a. E.N. Meshalkin
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical Academy
city: Tyumen
country: Russian Federation
facility: Clinical Hospital №1
city: Ufa
country: Russian Federation
facility: Bashkiria State Medical University
city: Bloemfontein
country: South Africa
facility: University of The Free State
city: Durban
country: South Africa
facility: Inkosi Albert Luthuli Central Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Cordoba
country: Spain
facility: C.H. Regional Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Chiang Mai University
city: Dnipro
country: Ukraine
facility: MI Dnipropetrovsk Specialized Clin. Med. Center of Mother and Child n.a. prof. M.F. Rudnev of DRC
city: Kharkiv
country: Ukraine
facility: Municipal Institution of Health Care Regional Children's Clinical Hospital
city: Kyiv
country: Ukraine
facility: MI Scientific Practical Medical Center for Children Cardiology and Cardiosurgery of MOH of Ukraine
city: Hanoi
country: Vietnam
facility: Hanoi Heart Hospital
city: Hanoi
country: Vietnam
facility: Hanoi Medical University Hospital
city: Ho Chi Minh City
country: Vietnam
facility: Children's Hospital 1
city: Ho Chi Minh
country: Vietnam
facility: Tam Duc Hospital
Study officials:
References: