Phase 3 N=7 Treatment

A Study of Macitentan in Japanese Pediatric Participants With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension

Bottom Line

View on ClinicalTrials.gov: NCT05167825 ↗

Enrolled (actual)

Serious AEs

28.6%

Results posted

Oct 2025

Primary outcome: Primary: Fold Change From Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI) — 59.43 Fold change (percentage)

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Macitentan (Drug)
Age: Pediatric · 0+ yrs
Sex: All
Sponsor: Janssen Pharmaceutical K.K.
Primary completion: Aug 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Fold Change From Baseline at Week 24 in Pulmonary Vascular Resistance Index (PVRI)	59.43	—
PRIMARY Change From Baseline in Hematology Parameter: Neutrophils Band Form (NBF)	0.120; 0.480; 0.055; -0.050; -0.030	—
SECONDARY Change From Baseline to Week 24 in Hemodynamic Variable: Pulmonary Vascular Resistance (PVR)	-3.734	—
SECONDARY Change From Baseline to Week 24 in Hemodynamic Variable: Mean Right Atrial Pressure (mRAP)	-2.9	—
SECONDARY Change From Baseline to Week 24 in Hemodynamic Variable: Mean Pulmonary Arterial Pressure (mPAP)	-8.0	—
SECONDARY Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Index (CI)	-0.03	—
SECONDARY Change From Baseline to Week 24 in Hemodynamic Variable: Cardiac Output (CO)	0.07	—
SECONDARY Change From Baseline to Week 24 in Hemodynamic Variable: Total Pulmonary Resistance (TPR)	-243.0	—
SECONDARY Percent Change From Baseline to Week 24 in Hemodynamic Variable: Mixed Venous Oxygen Saturation (SvO[2])	-2.9	—
SECONDARY Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in World Health Organization (WHO) Functional Class (FC)	0; 0; 0; 0; 0; 0	—
SECONDARY Number of Participants With Change From Baseline at Weeks 4, 8, 12, 16, 20, 24, 28, 40, and 52 in Panama Functional Class (FC)	0; 0; 0; 0; 0; 0	—
SECONDARY Change From Baseline to Weeks 24 and 52 in 6-minute Walk Distance (6MWD) as Measured by the 6-minute Walk Test (6MWT)	4.897; 24.710	—
SECONDARY Change From Baseline to Weeks 12, 24, 28, 40, and 52 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)	6.5911; -3.7423; -3.1663; -5.7146; -0.2360	—
SECONDARY Change From Baseline to Weeks 12, 24, and 52 in Tricuspid Annular Plane Systolic Excursion (TAPSE)	2.766; 1.873; 2.412	—
SECONDARY Change From Baseline to Week 12, 24, and 52 in Left Ventricular Eccentricity Index (LVEI)	0.116; 0.125; 0.128; 0.237; 0.229; 0.237	—
SECONDARY Change From Baseline to Week 12, 24, and 52 in Quality of Life (QoL) as Assessed by Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales Short Form (SF-15)	8.905; 8.190; 15.810; 8.889; -2.222; 16.667	—
SECONDARY Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Number of Hours of Daytime Activity	-0.929; -0.280; 0.144	—
SECONDARY Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Count Per Minute of Daily Activity	73.946; 112.733; 125.427	—
SECONDARY Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Light Physical Activity	1.600; 35.159; 38.852	—
SECONDARY Change From Baseline to Weeks 12, 24, and 52 in Physical Activity as Measured by Accelerometry: Mean Daily Time Spent in Moderate to Vigorous Physical Activity	0.032; 0.169; 0.493	—
SECONDARY Change From Baseline to Week 24 and Week 52 in Borg Dyspnea Index (BDI)	0.00; -1.17	—
SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs)	7	—
SECONDARY Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)	2	—
SECONDARY Number of Participants With AEs Leading to Premature Discontinuation of Study Drug	—	—
SECONDARY Number of Participants With TEAEs of Special Interest	1	—
SECONDARY Number of Participants With Postbaseline Markedly Abnormal Hematology Laboratory Values	1; 1; 1; 1	—
SECONDARY Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Potassium and Calcium	1; 1	—
SECONDARY Number of Participants With Postbaseline Markedly Abnormal Clinical Chemistry Laboratory Values: Alkaline Phosphatase (ALP)	1	—
SECONDARY Change From Baseline in Hematology Parameters: Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, and Basophils	-20.4; -47.9; -23.3; -41.3; -42.4; -42.6	—
SECONDARY Change From Baseline in Hematology Parameter: Hematocrit	0.009; 0.016; 0.004; -0.006; -0.004; 0.006	—
SECONDARY Change From Baseline in Hematology Parameters: Hemoglobin	1.9; 2.3; -0.1; -3.0; -4.1; -0.3	—
SECONDARY Change From Baseline in Hematology Parameter: Erythrocytes	0.03; 0.13; 0.04; -0.07; -0.06; 0.04	—
SECONDARY Change From Baseline in Chemistry Parameters: Sodium, Potassium, Urea Nitrogen, Glucose, and Calcium	-0.1; 0.1; 0.2; -0.7; -0.1; 0.3	—
SECONDARY Change From Baseline in Chemistry Parameters: Creatinine (Jaffe Reaction), Bilirubin, and Direct Bilirubin	-0.2947; -4.0411; -1.9153; -2.5257; -2.5257; 0.1263	—
SECONDARY Change From Baseline in Chemistry Parameter: Creatinine Clearance	0.08337; 0.19291; 0.13057; 0.16670; 0.23817; 0.07384	—
SECONDARY Change From Baseline in Chemistry Parameters: Glomerular Filtration Rate (GFR) From Cystatin C Adjusted for Body Surface Area (BSA)	0.05670; 0.11014; 0.12838; 0.05853; 0.07144; 0.04350	—
SECONDARY Change From Baseline in Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP)	4.2; 4.5; -0.8; -2.0; 0.1; 0.8	—
SECONDARY Change From Baseline in Vital Signs: Blood Pressure	-5.3; -5.3; 0.4; -1.7; -1.1; -5.3	—
SECONDARY Change From Baseline in Vital Signs: Pulse Rate	-4.4; -1.7; -12.1; -13.4; -7.4; -2.4	—
SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameter: Heart Rate	-4.0; -3.6; -12.0	—
SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameter: PR, QRS, QT, Corrected QT Interval-Bazett's Formula (QTcB), and Corrected QT Interval-Fridericia's Formula (QTcF)	3.4; 14.6; 4.0; -0.3; 0.3; 0.3	—
SECONDARY Plasma Concentration of Macitentan: Participants >=2 Years Old	94.4; 93.4; 121; 227; 192; 166	—
SECONDARY Plasma Concentration of Aprocitentan (Active Metabolite): Participants >=2 Years Old	993; 789; 763; 944; 773; 789	—
SECONDARY Plasma Concentration of Macitentan: Participants <2 Years Old	33.6; 120; 24.2; 55.1; 59.4; 81.4	—
SECONDARY Plasma Concentration of Aprocitentan (Active Metabolite): Participants <2 Years Old	7.98; 65.9; 162; 864; 982; 7.62	—

Summary

The purpose of this study is to evaluate the effect of macitentan on hemodynamic measures at Week 24 in pediatric populations.

Eligibility Criteria

Inclusion Criteria

Pulmonary arterial hypertension (PAH) belonging to the nice 2013 updated classification group 1
PAH diagnosis confirmed by historical right heart catheterization where in the absence of pulmonary vein obstruction and/or significant lung disease pulmonary artery wedge pressure (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
World Health Organization (WHO) functional class (FC) I to IV
PAH-specific treatment-naïve participants or participants on PAH-specific treatment
A female of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) test at screening and a negative urine pregnancy test at the first administration of study intervention
A female participant must not get pregnant and must agree not to donate eggs during the study and for a period of up to 4 weeks following the end of study

Exclusion Criteria

Participants with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension of the newborn
Participants with the following diseases: pulmonary vein stenosis; bronchopulmonary dysplasia
Severe hepatic impairment, example, Child-Pugh Class C, at screening
Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 weeks after the last dose of study intervention
Known allergies, hypersensitivity, or intolerance to macitentan or its excipients
Participant with PAH associated with open shunts, with congenital cardiac abnormalities such as univentricular heart, with pulmonary hypertension due to lung disease, and renal dysfunction

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05167825). 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.