Phase 3
Completed N=165
A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)
Source: ClinicalTrials.gov NCT02932410 ↗Enrolled (actual)
165
Serious AEs
30.2%
Results posted
Sep 2025
Primary outcomePrimary: Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Body Weight — 150.133; 153.892; 200.975; 208.067 nanograms per milliliter (ng/mL)
◆ Published Evidence
Not yet cited
0citations
Macitentan in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial.
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).
Linked Publications
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Macitentan in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Body Weight |
150.133; 153.892; 200.975; 208.067; 1165.000; 859.333 | — |
| PRIMARY Participants >=2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 Based on Age Group |
159.767; 184.792; 196.484; 1063.333; 957.211; 970.842 | — |
| PRIMARY Participants <2 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 4 |
101.822; 707.089 | — |
| PRIMARY Participants From China With >=12 to <18 Years of Age: Observed Steady-State Trough (Pre-dose) Plasma Concentration of Macitentan and Aprocitentan (Active Metabolite) at Week 12 |
201.61; 1313.75 | — |
| SECONDARY Time to the First Clinical Event Committee (CEC)-Confirmed Disease Progression Event |
— | — |
| SECONDARY Time to First CEC-confirmed Hospitalization for PAH |
— | — |
| SECONDARY Time to CEC-confirmed Death Due to PAH |
— | — |
| SECONDARY Time to Death (All Causes) |
— | — |
| SECONDARY Percentage of Participants With World Health Organization (WHO) Functional Class (FC) I or II Versus III or IV |
— | — |
| SECONDARY Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Weeks 12 and 24 |
— | — |
| SECONDARY Change From Baseline in Mean Daily Time Spent in Moderate to Vigorous Physical Activity as Measured by Accelerometry at Week 48 |
— | — |
| SECONDARY Change From Baseline in Body Surface Area (BSA) Normalized Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography at Week 24 |
— | — |
| SECONDARY Change From Baseline in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography at Week 24 |
— | — |
| SECONDARY Change From Baseline in Quality of Life Measured by Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales Short Form (SF-15) |
— | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
— | — |
| SECONDARY Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) |
— | — |
| SECONDARY Number of Participants With AEs Leading to Premature Discontinuation of Macitentan or Standard of Care (SoC) |
— | — |
| SECONDARY Number of Participants With AEs of Special Interest |
— | — |
| SECONDARY Number of Participants With Marked Laboratory Abnormalities |
— | — |
| SECONDARY Change From Baseline in Selected Laboratory Parameters |
— | — |
| SECONDARY Change From Baseline in Vital Signs (Blood Pressure, Heart Rate) |
— | — |
| SECONDARY Change From Baseline in Growth Variable |
— | — |
| SECONDARY Change From Baseline in Sexual Maturation Measured by Tanner Stage |
— | — |
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 ( = 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 ) 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
Data sourced from ClinicalTrials.gov (NCT02932410) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.