a study to assess whether macitentan delays disease progression in children with pulmonary arterial hypertension (pah)

Conditions: Pulmonary Arterial Hypertension

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 \[\ \] 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 \ 221 micro-moles per liter \[micro-mol/l\]) * participants with known diagnosis of bronchopulmonary dysplasia