A Study of Macitentan in Children Below 2 Years of Age

Phase 1

Withdrawn

• Conditions: Arterial Hypertension, Pulmonary
• Interventions: Drug: Macitentan

• Registration Number: NCT05731492
• Lead Sponsor: Actelion

Brief Summary

The purpose of this study is to learn what happens to macitentan and its active metabolite (aprocitentan) in the body of children aged between 1 month and 2 years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-09
• Study First Submitted QC: 2023-02-09
• Study First Posted: 2023-02-16
• Study Start: 2024-03-14
• Primary Completion: 2024-04-01
• Study Completion: 2024-04-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Pulmonary arterial hypertension (PAH): 1) including participants with Down syndrome. Diagnosis must have been confirmed by (historical, any time before screening) right heart catheterization mean pulmonary arterial pressure (mPAP) greater than or equal to (>=) 25 millimeter of mercury (mmHg), pulmonary arterial wedge pressure (PAWP) less than or equal to (=<)15 mmHg, pulmonary vascular resistance index greater than (>) 3 Wood units * meter square (m^2) where in the absence of pulmonary vein obstruction and/or significant lung disease PAWP can be replaced left atrium pressure or left ventricular end diastolic pressure (in the absence of mitral stenosis) assessed by heart catheterization. a) Idiopathic PAH, or b) Heritable PAH, or c) PAH associated with congenital heart disease: i) Eisenmenger syndrome (Qp/Qs less than (<) 1.5 and saturation of peripheral oxygen ≤ 90 percent (%) measured by pulse oximetry at room air), or ii) Inoperable open left-to-right shunts (with a Pulmonary vascular resistance [PVR] > 8 WU and Qp/Qs <2), or iii) Co-incidental shunt (that is, not explaining hemodynamically the presence of PAH), or iv) Post-operative PAH (persisting/recurring/developing ≥ 6 months after repair of shunt), or d) Drug or toxin induced PAH, or e) PAH associated with Human immunodeficiency viruses (HIV)
• World Health Organization Functional Class (WHO FC) I, II, or III
• PAH-specific treatment-naive participants or participants on PAH specific monotherapy or combination of 2 therapies. Use of macitentan before or during screening is allowed
• Body weight of greater than or equal to (>=) 3.5 kilogram (kg)
• Parent(s) (preferably both if available or as per local requirements) or participant's legally designated representative must sign an informed consent form (ICF) indicating that they understand the purpose of, and procedures required for, the study and is/are willing to allow the child to participate in the study

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Exclusion Criteria

• PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
• Persistent pulmonary hypertension of the newborn
• The following congenital cardiac abnormalities: a) Cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, pulmonary atresia with ventricular septal defect, unless operatively repaired and with no residual shunt. b) Univentricular heart and/or participants with Fontan-palliation
• Pulmonary hypertension due to lung disease
• Known diagnosis of bronchopulmonary dysplasia

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-label Core Treatment Period: Macitentan	Macitentan	Participants will receive macitentan as a monotherapy or add-on to an existing therapy daily for 24 weeks during core treatment period. Optional treatment extension period of up to 1 year for those participants who completed the core treatment period.

Primary Outcome Measures

Name	Time	Method
Trough Concentration of Macitentan and its Active Metabolite Aprocitentan at Week 4 in Steady-State	Predose (at Week 4)	Trough concentration of macitentan and its active metabolite aprocitentan at week 4 in steady-state will be reported.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Serious Adverse Events (SAEs)	Up to 1.5 years	A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Number of Participants with Clinical Laboratory Abnormalities	Up to 1.5 years	Number of participants with clinical laboratory abnormalities (serum, chemistry and hematology) will be reported.
Number of Participants with Change from Baseline in Clinical laboratory Values.	Up to 1.5 years	Number of participants with change from baseline in clinical laboratory values will be reported.
Change From Baseline in Heart Rate	Up to 1.5 years	Change from baseline in heart rate will be reported.
Number of Participants with Adverse Events (AEs)	Up to 1.5 years	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
Change from Baseline in Blood Pressure	Up to 1.5 years	Change from baseline in blood pressure will be reported.
Change from Baseline in Height	Up to 1.5 years	Change from baseline in height will be reported.
Trough Concentrations of Macitentan and its Active Metabolite Aprocitentan at Week 8 in Steady-State Conditions	Predose (at Week 8)	Trough concentrations of macitentan and its active metabolite aprocitentan at week 8 in steady-state conditions will be reported.
Number of Participants with AEs Leading to Premature Discontinuation of Macitentan	Up to 1.5 years	Number of participants with AEs Leading to premature discontinuation of macitentan will be reported.
Change From Baseline in Body Weight	Up to 1.5 years	Change from baseline in body weight will be reported.
Number of Participants with Adverse Event of Special Interests (AESIs)	Up to 1.5 years	Number of participants with AESI will be reported. AEs considered to be of special interest are as hypotension, edema/fluid retention, hemoglobin decrease/anemia, liver events.
Change From Baseline in Length	Up to 1.5 years	Change from baseline in length will be reported.
Plasma Concentration of Macitentan and its Active Metabolite (Aprocitentan) for Macitentan Naive Participants	At 2, 5, and 24 hours after the first dose of macitentan on Day 1	Plasma concentrations of macitentan and its active metabolite (aprocitentan) after the first dose of macitentan for macitentan naive participants will be reported.

Trial Locations

Locations (4)

Universitatsmedizin Gottingen; 🇩🇪 Goettingen, Germany

Universitatsklinikum Freiburg; 🇩🇪 Freiburg im Breisgau, Germany

Instytut Pomnik Centrum Zdrowia Dziecka; 🇵🇱 Warszawa, Poland

Wojewodzki Szpital Specjalistyczny We Wroclawiu; 🇵🇱 Wroclaw, Poland