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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT02932410
• Date of registration: 12/10/2016
• Prospective Registration: Yes
• Primary sponsor: Actelion
• Public title: A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH) TOMORROW
• Scientific 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
• Date of first enrolment: October 24, 2017
• Target sample size: 300
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02932410
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Brazil, Bulgaria, Canada, China, Colombia, Finland, France, Hungary, Israel, Korea, Republic of, Malaysia, Mexico, Philippines, Poland, Portugal, Russian Federation, South Africa, Spain, Thailand, Ukraine, United States, Vietnam

Contacts

• Name: Study Contact

Key inclusion & 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



Age minimum: 1 Month
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Macitentan

Other: Standard-of-care

Primary Outcome(s)

Participants Less than (<) 2 Years: Observed Steady-state Trough Plasma Concentration of Macitentan and its Active Metabolite ACT-132577 at Week 4 [Time Frame: Week 4]

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 [Time Frame: Week 12]

Secondary Outcome(s)

The Percentage of Participants with World Health Organization (WHO) Functional Class (FC) I or II versus III or IV [Time Frame: Week 24]

Time to CEC-confirmed death due to PAH [Time Frame: Between randomization/visit 2 and EOCP; up to 7 years]

Change from Baseline to Week 24 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) [Time Frame: Baseline to Week 24]

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) [Time Frame: Baseline to Week 24]

Change from Baseline to Week 24 in Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography [Time Frame: Baseline to Week 24]

Change from Baseline to Week 48 in Moderate to Vigorous Physical Activity as Measured by Accelerometry [Time Frame: Baseline to Week 48]

Time to the first CEC-confirmed Disease Progression Event [Time Frame: Between randomization/visit 2 and end of core study period (EOCP); up to 7 years]

Time to First CEC-confirmed Hospitalization for PAH [Time Frame: Between randomization/visit 2 and EOCP/; up to 7 years]

Change from Baseline to Week 24 in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography [Time Frame: Baseline to Week 24]

Time to death (all causes) [Time Frame: Between randomization/visit 2 and EOCP; up to 7 years]

Secondary ID(s)

AC-055-312

Source(s) of Monetary Support

Please refer to primary and secondary sponsors