A study to find out whether the medicine macitentan works in children with pulmonary arterial hypertension (PAH)

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2016-001062-28-HU
• Date of registration: 15/12/2016
• Prospective Registration: Yes
• Primary sponsor: ACTELION Pharmaceuticals Ltd
• Public title: A study to find out whether the medicine macitentan works in children with pulmonary arterial hypertension (PAH)
• Scientific title: A multicenter, open-label, randomized, event-driven study to assess efficacy, safety and pharmacokinetics of macitentan versus standard of care in children with pulmonary arterial hypertension - TOMORROW: pediaTric use Of Macitentan tO delay disease pRogRessiOn in PAH Worldwide
• Date of first enrolment: 25/01/2017
• Target sample size: 300
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001062-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard of Care Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Bulgaria, Canada, China, France, Germany, Hungary, Israel, Korea, Republic of, Mexico, Philippines, Poland, Portugal, Russian Federation, South Africa, Spain, Thailand, Ukraine, United States, Vietnam

Contacts

• Name: Clinical trial disclosure desk
• Affiliation: Actelion Pharmaceuticals Ltd

• Name: Clinical trial disclosure desk
• Affiliation: Actelion Pharmaceuticals Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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.
2. Males or females between = 2 years and < 18 years of age.
3. Subjects with body weight = 10 kg at randomization.
4. PAH diagnosis, confirmed by historical RHC (mPAP = 25 mmHg, and PAWP = 15 mmHg, and PVRi > 3 WUxm2).
5. PAH belonging to the Nice 2013 Updated Classification Group 1 (including subjects with Down syndrome) and of following etiologies:
• iPAH
• hPAH
• PAH associated with CHD
• Drug or toxin induced PAH
• PAH associated with HIV
• PAH-aCTD
6. WHO FC I to III.
7. 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 EOS.
Are the trial subjects under 18? yes
Number of subjects for this age range: 300
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Subjects 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.
2. Subjects with PAH associated with Eisenmenger syndrome, or with moderate to large left-to-right shunts.
3. Subjects receiving a combination of > 2 PAH-specific treatments at randomization.
4. Treatment with i.v. or s.c. prostanoids within 4 weeks before randomization, unless given for vasoreactivity testing.
5. Hemoglobin or hematocrit <75% of the lower limit of normal range
6. Serum AST and/or ALT > 3 times the upper limit of normal range'
7. Pregnancy (including family planning) or breastfeeding.
8. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Pulmonary arterial hypertension
MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: macitentan
Product Code: ACT-064992
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: MACITENTAN
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Product Name: macitentan
Product Code: ACT-064992
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: MACITENTAN
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Product Name: macitentan
Product Code: ACT-064992
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: MACITENTAN
CAS Number: 441798-33-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the time to the first of the following CEC-confirmed disease progression events occurring between randomization and EOS:
• Death (all causes)
• Atrial septostomy or Potts’ anastomosis, or registration on lung transplant list
• Hospitalization due to worsening PAH
• Clinical worsening of PAH

Timepoint(s) of evaluation of this end point: Between randomization and End-of-Study (EOS)

Main Objective: The primary objective of the study is to evaluate macitentan in comparison to Standard of Care (SoC) with regard to delaying disease progression in children with PAH.

Secondary Objective: To assess safety and tolerability of macitentan in children with PAH.
To assess PK of macitentan in children with PAH.

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints are analyzed in the following hierarchical order:
• Time to first CEC-confirmed hospitalization for PAH occurring between randomization and EOS.
• Time to CEC-confirmed death due to PAH occurring between randomization and EOS.
• Time to death (all causes) occurring between randomization and Study Closure.

Timepoint(s) of evaluation of this end point: Between randomization and End-of-Study (EOS)

Secondary ID(s)

AC-055-312

Source(s) of Monetary Support

ACTELION Pharmaceuticals Ltd