Clinical trial NCT05167825: A Study of Macitentan in Japanese Pediatric Participants With Pulmonary Arterial Hypertension
Official title: A Multicenter, Open-label, Phase III Study to Assess the Efficacy, Safety, and Pharmacokinetics of Macitentan in Japanese Pediatric Patients (>=3 Months to <15 Years) With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2021-12-22
Enrollment: 7
Sex: ALL
Minimum age (years): 3
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Fold Change in Pulmonary Vascular Resistance Index (PVRI)
timeFrame: Week 24
Secondary outcomes:
measure: Change from Baseline at Week 24 in Pulmonary Vascular Resistance (PVR)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Mean Right Atrial Pressure (mRAP)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Mean Pulmonary Arterial Pressure (mPAP)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Cardiac Index (CI)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Cardiac Output (CO)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Total Pulmonary Resistance (TPR)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Mixed Venous Oxygen Saturation (SvO2) at Rest
timeFrame: Baseline and Week 24
measure: Improvement in World Health Organization (WHO) Functional Class (FC) from Baseline at Week 24
timeFrame: Baseline and Week 24
measure: Improvement in Panama FC from Baseline at Week 24
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Exercise Capacity (6-Minute Walk Distance [6MWD] as Measured by the 6-Minute walk Test [6MWT]).
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) Generic Core Scales Short Form (SF-15)
timeFrame: Baseline and Week 24
measure: Change from Baseline at Week 24 in Physical Activity as Measured by Accelerometry
timeFrame: Baseline and Week 24
measure: Plasma Concentration of Macitentan and Aprocitentan
timeFrame: Day 1 and Week 12
measure: Change from Baseline to all Assessed Timepoints in Exercise Capacity (6MWD, as Measured by the 6MWT)
timeFrame: Baseline up to Week 52
measure: Change from Baseline to all Assessed Timepoints in Dyspnea on Exertion Assessed by the Borg CR10 Scale
timeFrame: Baseline up to Week 52
measure: Change from Baseline to all Assessed Timepoints in Physical Activity as Measured by Accelerometry
timeFrame: Baseline up to Week 52
measure: Improvement in WHO FC from Baseline to all Assessed Timepoints
timeFrame: Baseline up to Week 52
measure: Improvement in Panama FC from Baseline to all Assessed Timepoints
timeFrame: Baseline up to Week 52
measure: Percent Change from Baseline in Plasma NT-proBNP at Each Timepoint of Assessment
timeFrame: Baseline up to Week 52
measure: Percent Change from Baseline in TAPSE Measured by Echocardiography to all Assessed Timepoints
timeFrame: Baseline up to Week 52
measure: Percent Change from Baseline in LVEI Measured by Echocardiography to all Assessed Timepoints
timeFrame: Baseline up to Week 52
measure: Change from Baseline to all Assessed Timepoints in PedsQL 4.0 Generic Core Scales Short Form (SF-15)
timeFrame: Baseline up to Week 52
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 3 years
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to 3 years
measure: Number of Participants with AEs Leading to Premature Discontinuation of Macitentan
timeFrame: Up to 3 years
measure: Number of Participants with AEs of Special Interests (AESIs)
timeFrame: Up to 3 years
measure: Number of Participants with Clinical Safety Laboratory Abnormalities
timeFrame: Up to 3 years
measure: Number of Participants with Change from Baseline in Laboratory Parameters to all Timepoints of Assessments
timeFrame: Baseline up to 3 years
measure: Number of Participants with Change from Baseline in Vital Signs to all Timepoints of Assessments
timeFrame: Baseline up to 3 years
measure: Number of Participants with Change from Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to 3 years
Other outcomes:
Locations:
city: Azumino-shi
country: Japan
facility: Nagano Children's Hospital
city: Bunkyo ku
country: Japan
facility: Institute of Science Tokyo Hospital
city: Fukuoka
country: Japan
facility: Fukuoka Children's Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Ota
country: Japan
facility: Toho University Medical Center Omori Hospital
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Setagaya Ku
country: Japan
facility: National Center for Child Health and Development
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Suita-Shi
country: Japan
facility: National Cerebral and Cardiovascular Center
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K. Clinical Trial
role: STUDY_DIRECTOR
References: