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

Pulmonary Arterial Hypertension Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05167825
• Other study ID #: CR109128
• Secondary ID: 67896062PAH3001
• Status: Recruiting
• Phase: Phase 3
• Start date: November 14, 2022
• Est. completion date: March 17, 2025

Study information

• Verified date: June 2024
• Source: Janssen Pharmaceutical K.K.
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: March 17, 2025
• Est. primary completion date: August 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Macitentan
Macitentan will be administered orally as a tablet.

Locations

Country	Name	City	State
Japan	Nagano Children's Hospital	Azumino-shi, Nagano
Japan	Tokyo Medical and Dental University Hospital	Bunkyo Ku
Japan	Fukuoka Children's Hospital	Fukuoka
Japan	Okayama University Hospital	Okayama
Japan	Toho University Medical Center Omori Hospital	Ota
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	National Center for Child Health and Development	Setagaya Ku
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku
Japan	National Cerebral and Cardiovascular Center	Suita-Shi
Japan	Osaka University Hospital	Suita-shi
Japan	The University of Tokyo Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fold Change in Pulmonary Vascular Resistance Index (PVRI)	PVRI fold change at Week 24 is calculated as 100*(PVRI at Week 24 divided by PVRI at baseline).	Week 24
Secondary	Change from Baseline at Week 24 in Pulmonary Vascular Resistance (PVR)	Change from baseline at Week 24 in PVR as a part of pulmonary hemodynamic parameter will be reported.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Mean Right Atrial Pressure (mRAP)	Change from baseline at Week 24 in mRAP as a part of pulmonary hemodynamic parameter will be reported.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Mean Pulmonary Arterial Pressure (mPAP)	Change from baseline at Week 24 in mPAP as a part of pulmonary hemodynamic parameter will be reported. mPAP is calculated as (2*diastolic pulmonary arterial pressure plus systolic pulmonary arterial pressure) divided by 3.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Cardiac Index (CI)	Change from baseline at Week 24 in CI will be reported. CI is calculated as cardiac output divided by body surface area.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Cardiac Output (CO)	The CO was a measured cardiopulmonary hemodynamic parameter. It is the volume of blood expelled by the ventricles of the heart with each beat. It was calculated as the product of stroke volume (output of either ventricle per heartbeat) and the number of beats per minute.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Total Pulmonary Resistance (TPR)	TPR is a measured hydrodynamic parameter. Change from baseline at Week 24 in TPR will be reported.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Mixed Venous Oxygen Saturation (SvO2) at Rest	SvO2 is a measured hydrodynamic parameter. Change from baseline at Week 24 in Svo2 at rest will be reported.	Baseline and Week 24
Secondary	Improvement in World Health Organization (WHO) Functional Class (FC) from Baseline at Week 24	Improvement in WHO FC from baseline at Week 24 will be assessed as per the low (I, II), intermediate (III), and high-risk category (IV).	Baseline and Week 24
Secondary	Improvement in Panama FC from Baseline at Week 24	Improvement in Panama FC from baseline at Week 24 will be assessed as per the low (I, II), intermediate (III), and high-risk category (IV).	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Exercise Capacity (6-Minute Walk Distance [6MWD] as Measured by the 6-Minute walk Test [6MWT]).	The 6MWT is a non-encouraged test that measures the distance covered by the participant during a 6-minute walk in developmentally capable children equal or above 6 years of age.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in N-terminal pro-brain natriuretic peptide (NT-proBNP)	The quantitation of NT-proBNP plasma levels will be performed and reported.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography	TAPSE is a dimension used to evaluate right ventricle (RV) longitudinal systolic function; it measures the extent of systolic motion of the lateral portion of the tricuspid ring towards the apex.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography	For LVEI, left ventricle (LV) internal diameters will be measured and recorded in millimeter (mm) with up to 1 decimal place, using the parasternal short axis view at the level of the papillary muscles.	Baseline and Week 24
Secondary	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)	The PedsQL 4.0 SF-15 is a questionnaire for quality of life assessment which will assess the general physical, emotional, social and school functioning (15 questions). The questionnaires are adapted for different age groups: toddlers (2-4 years of age), young children (5-7 years of age), children (8-12 years of age), and adolescents (13-14 years of age). It is rated on the scale of 0 to 4 where 0=never, 1=almost never, 2=sometimes, 3=often, and 4=almost always.	Baseline and Week 24
Secondary	Change from Baseline at Week 24 in Physical Activity as Measured by Accelerometry	The physical activity (counts/minute) of the participant is assessed via accelerometer. It is used as a tool to assess functional capacity, disease severity, and prognosis.	Baseline and Week 24
Secondary	Plasma Concentration of Macitentan and Aprocitentan	Plasma concentration of macitentan and active metabolite (aprocitentan) at all assessed timepoints will be reported.	Day 1 and Week 12
Secondary	Change from Baseline to all Assessed Timepoints in Exercise Capacity (6MWD, as Measured by the 6MWT)	Change from baseline to all assessed timepoints in exercise capacity (6MWD, as measured by the 6MWT) will be reported.	Baseline up to Week 52
Secondary	Change from Baseline to all Assessed Timepoints in Dyspnea on Exertion Assessed by the Borg CR10 Scale	Dyspnea on exertion will be assessed by the Borg CR10 scale. The scale is used to assess how strong participant's perception of dyspnea and level of exertion is. It ranges from "Very weak", that is 1, to "Extremely strong", that is 10. If perception or feeling is stronger than 10, "Maximal" - it can vary beyond 10, example, 12 or still higher (that's why "Absolute maximum" is marked with a dot "•").	Baseline up to Week 52
Secondary	Change from Baseline to all Assessed Timepoints in Physical Activity as Measured by Accelerometry	Change from baseline to all assessed timepoints in physical activity as measured by accelerometry will be reported. The physical activity (counts/minute) of the participant is assessed via accelerometer. It is used as a tool to assess functional capacity, disease severity, and prognosis.	Baseline up to Week 52
Secondary	Improvement in WHO FC from Baseline to all Assessed Timepoints	Improvement in WHO FC from baseline to all assessed timepoints will be reported.	Baseline up to Week 52
Secondary	Improvement in Panama FC from Baseline to all Assessed Timepoints	Improvement in Panama FC from baseline to all assessed timepoints will be reported.	Baseline up to Week 52
Secondary	Percent Change from Baseline in Plasma NT-proBNP at Each Timepoint of Assessment	Percent change from baseline in plasma NT-proBNP at each timepoint of assessment will be reported.	Baseline up to Week 52
Secondary	Percent Change from Baseline in TAPSE Measured by Echocardiography to all Assessed Timepoints	Percent change from baseline in TAPSE measured by echocardiography to all assessed timepoints will be reported.	Baseline up to Week 52
Secondary	Percent Change from Baseline in LVEI Measured by Echocardiography to all Assessed Timepoints	Percent change from baseline in LVEI measured by echocardiography to all assessed timepoints will be reported.	Baseline up to Week 52
Secondary	Change from Baseline to all Assessed Timepoints in PedsQL 4.0 Generic Core Scales Short Form (SF-15)	Change from baseline to all assessed timepoints in PedsQL 4.0 Generic Core Scales Short Form (SF-15) will be reported.	Baseline up to Week 52
Secondary	Number of Participants with Adverse Events (AEs)	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 3 years
Secondary	Number of Participants with Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event.	Up to 3 years
Secondary	Number of Participants with AEs Leading to Premature Discontinuation of Macitentan	Number of participants with AEs leading to premature discontinuation of macitentan will be reported.	Up to 3 years
Secondary	Number of Participants with AEs of Special Interests (AESIs)	Number of participants with AESIs will be reported. AESI in this study are: anemia/decreased hemoglobin level, edema/fluid retention, hepatic impairment/ alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) increase, and hypotension.	Up to 3 years
Secondary	Number of Participants with Clinical Safety Laboratory Abnormalities	Number of participants with clinical safety laboratory abnormalities (including serum chemistry, hematology, and urinalysis) will be reported.	Up to 3 years
Secondary	Number of Participants with Change from Baseline in Laboratory Parameters to all Timepoints of Assessments	Number of participants with change from baseline in laboratory parameters (including serum chemistry, hematology, and urinalysis) to all timepoints of assessments will be reported.	Baseline up to 3 years
Secondary	Number of Participants with Change from Baseline in Vital Signs to all Timepoints of Assessments	Number of participants with change from baseline in vital signs (including diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR], height, and body weight) to all timepoints of assessments will be reported.	Baseline up to 3 years
Secondary	Number of Participants with Change from Baseline in Electrocardiogram (ECG) Parameters	Number of participants with change from baseline in ECG parameters will be reported.	Baseline up to 3 years