A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH) (TOMORROW)
Pulmonary Arterial Hypertension
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
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
Sites / Locations
- Phoenix Childrens Hospital
- UCLA Children's Heart CenterRecruiting
- UCSF Medical Center
- Childrens Hospital ColoradoRecruiting
- Children's National Medical CenterRecruiting
- Riley Hospital For ChildrenRecruiting
- Boston Children's HospitalRecruiting
- Detroit Medical Center
- Mayo Clinic - PPDS
- Children's Heart CenterRecruiting
- Montefiore Medical CenterRecruiting
- Columbia University Medical Center - PINRecruiting
- Duke University Medical CenterRecruiting
- East Carolina University
- Cincinnati Children's Hospital Medical CenterRecruiting
- University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital
- Nationwide Children's Hospital
- Texas Children's Hospital
- Primary Children's Medical Center
- University of Virginia Health SystemRecruiting
- Childrens Hospital of Wisconsin
- Royal Children's Hospital Melbourne - PINRecruiting
- Lady Cilento Children's HospitalRecruiting
- Children's Hospital at Westmead
- Medizinische Universität GrazRecruiting
- Landes Frauen Und Kinderklinik Linz
- Medizinische Universitat WienRecruiting
- Irmandade Da Santa Casa de Misericórdia de São PauloRecruiting
- Sainte Justine HospitalRecruiting
- Stollery Children's HospitalRecruiting
- Beijing Anzhen Hospital of The Capital University of Medical SciencesRecruiting
- Beijing Children's Hospital,Capital Medical University
- Fuwai Hospital
- The Children's Hospital, Zhejiang University school of Medicine
- Qingdao Women and Children's HospitalRecruiting
- Childrens Hospital of ShanghaiRecruiting
- Shanghai Children's Medical CenterRecruiting
- General Hospital of Shenyang Military Region
- Wuhan Asia Heart Hospital
- Fundacion Santa Fe de BogotaRecruiting
- Centro Medico Imbanaco de Cali SARecruiting
- HUS Uusi lastensairaala
- Hôpital de la Timone EnfantsRecruiting
- Groupe Hospitalier Necker Enfants MaladesRecruiting
- Hôpital Haut-Lévêque - Hôpital cardiologiqueRecruiting
- Hôpital Des EnfantsRecruiting
- Gottsegen Gyorgy Orszagos Kardiologiai IntezetRecruiting
- Rambam Medical Center - PPDSRecruiting
- Schneider Children's Medical Center of Israel - PINRecruiting
- Chaim Sheba Medical Center
- Seoul National University HospitalRecruiting
- Severance Hospital Yonsei University Health System - PPDSRecruiting
- Institut Jantung NegaraRecruiting
- University Malaya Medical CentreRecruiting
- Instituto Nacional de PediatríaRecruiting
- Instituto Nacional de Cardiologia Dr. Ignacio ChavezRecruiting
- CICUM San MiguelRecruiting
- Operadora de Hospitales Angeles SA de CV Hospital Angeles LomasRecruiting
- Unidad de Investigación Clínica En Medicina SCRecruiting
- Makati Medical Center
- Philippine Heart CenterRecruiting
- Szpital Kliniczny im. Karola Jonschera Uniwersytetu Medycznego im. Karola Marcinkowskiego w PoznaniuRecruiting
- Instytut Pomnik - Centrum Zdrowia DzieckaRecruiting
- Wojewodzki Szpital Specjalistyczny we Wroclawiu Osrodek Badawczo-RozwojowyRecruiting
- Centro Hospitalar de Lisboa Ocidental, EPE - Hospital de Santa CruzRecruiting
- Centro Hospitalar E Universitário de Coimbra EPERecruiting
- Hospital Santa MartaRecruiting
- Centro Hospitalar de Sao Joao EPERecruiting
- Research Institute of Complex Cardiovascular PathologyRecruiting
- GBUZ Children's Hospital named after Bashlyaeva Z.A. MoscowRecruiting
- Russian National Research Medical University n.a. N.I.PirogovRecruiting
- Novosibirsk Research Institue of Blood Circulation Pathology n.a. E.N. MeshalkinRecruiting
- Saint Petersburg State Pediatric Medical AcademyRecruiting
- Clinical Hospital №1Recruiting
- Bashkiria State Medical University
- University of The Free State
- Inkosi Albert Luthuli Central Hospital
- Hospital Universitario Vall d'Hebron - PPDS
- C.H. Regional Reina Sofia
- Hospital General Universitario Gregorio MarañonRecruiting
- Hospital Universitario Ramon y CajalRecruiting
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
- Hospital Universitari i Politecnic La Fe de ValenciaRecruiting
- Ramathibodi Hospital Mahidol University
- Siriraj Hospital Mahidol University
- Maharaj Nakorn Chiang Mai Chiang Mai UniversityRecruiting
- MI Dnipropetrovsk Specialized Clin. Med. Center of Mother and Child n.a. prof. M.F. Rudnev of DRCRecruiting
- Municipal Institution of Health Care Regional Children's Clinical HospitalRecruiting
- MI Scientific Practical Medical Center for Children Cardiology and Cardiosurgery of MOH of UkraineRecruiting
- Hanoi Heart HospitalRecruiting
- Hanoi Medical University HospitalRecruiting
- Children's Hospital 1Recruiting
- Tam Duc HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Other
Macitentan
Standard-of-care
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.
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.