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

Actelion Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Macitentan; Other: Standard-of-care

Study type: Interventional

Funder types: Industry

Identifiers

NCT02932410

AC-055-312

Details and patient eligibility

About

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).

Enrollment: 300 estimated patients

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

Macitentan

Experimental group

Description:

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.

Treatment:

Drug: Macitentan

Standard-of-care

Other group

Description:

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.

Treatment:

Other: Standard-of-care