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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02932410




Registration number
NCT02932410
Ethics application status
Date submitted
12/10/2016
Date registered
13/10/2016
Date last updated
22/05/2024

Titles & IDs
Public title
A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)
Scientific title
A Multicenter, Open-label, Randomized, Study With Single-arm Extension Period to Assess the Pharmacokinetics, Safety and Efficacy of Macitentan Versus Standard of Care in Children With Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
AC-055-312
Universal Trial Number (UTN)
Trial acronym
TOMORROW
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Macitentan
Other interventions - Standard-of-care

Experimental: Macitentan - Macitentan is administered once daily via oral route. Children less than (<) 2 years old (y.o.) will be assigned as a cohort to the macitentan group without randomization. The dose will be adjusted to the participant's age (for those < 2 y.o.) or to the participant's body weight (for those greater than or equal to (>=) 2 y.o.). single-arm extension period (SAEP) will start at end of core period (EOCP) visit and ends at end of study (EOS) visit.

Other: Standard-of-care - Standard-of-care as per site's clinical practice which may comprise treatment with pulmonary arterial hypertension (PAH) non-specific treatment and/or up to two PAH-specific medications excluding macitentan and intravenous/subcutaneous (IV/SC) prostanoids.


Treatment: Drugs: Macitentan
Dispersible tablet; Oral use

Other interventions: Standard-of-care
Standard-of-care as per site's clinical practice which may comprise treatment with PAH non-specific treatment and/or up to two PAH-specific medications excluding macitentan and IV/SC prostanoids.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants Greater than or Equal to (>=) 2 Years: Observed Steady-state Trough Plasma Concentration of Macitentan and its Active Metabolite ACT-132577 at Week 12
Timepoint [1] 0 0
Week 12
Primary outcome [2] 0 0
Participants Less than (<) 2 Years: Observed Steady-state Trough Plasma Concentration of Macitentan and its Active Metabolite ACT-132577 at Week 4
Timepoint [2] 0 0
Week 4
Secondary outcome [1] 0 0
Time to the first CEC-confirmed Disease Progression Event
Timepoint [1] 0 0
Between randomization/visit 2 and end of core study period (EOCP); up to 7 years
Secondary outcome [2] 0 0
Time to First CEC-confirmed Hospitalization for PAH
Timepoint [2] 0 0
Between randomization/visit 2 and EOCP/; up to 7 years
Secondary outcome [3] 0 0
Time to CEC-confirmed death due to PAH
Timepoint [3] 0 0
Between randomization/visit 2 and EOCP; up to 7 years
Secondary outcome [4] 0 0
Time to death (all causes)
Timepoint [4] 0 0
Between randomization/visit 2 and EOCP; up to 7 years
Secondary outcome [5] 0 0
The Percentage of Participants with World Health Organization (WHO) Functional Class (FC) I or II versus III or IV
Timepoint [5] 0 0
Week 24
Secondary outcome [6] 0 0
Change from Baseline to Week 24 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Timepoint [6] 0 0
Baseline to Week 24
Secondary outcome [7] 0 0
Change from Baseline to Week 48 in Moderate to Vigorous Physical Activity as Measured by Accelerometry
Timepoint [7] 0 0
Baseline to Week 48
Secondary outcome [8] 0 0
Change from Baseline to Week 24 in Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography
Timepoint [8] 0 0
Baseline to Week 24
Secondary outcome [9] 0 0
Change from Baseline to Week 24 in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
Change from Baseline to Week 24 in Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) Generic Core Scales Short Form (SF-15)
Timepoint [10] 0 0
Baseline to Week 24

Eligibility
Key inclusion criteria
Key

- 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

- Males or females between greater than or equal to (>=) 1 month and less than (<) 18
years of age

- Participants with body weight >= 3.5 kilograms (kg) at randomization

- Pulmonary arterial hypertension (PAH) diagnosis confirmed by historical RHC (mPAP
greater than or equal to [>=] 25 millimeters of mercury [mmHg], and Pulmonary artery
wedge pressure [PAWP] less than or equal to [<=] 15 mmHg, and Pulmonary vascular
resistance index [PVRi] greater than [>] 3 WU × m2), where in the absence of pulmonary
vein obstruction and/or significant lung disease 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

- PAH belonging to the Nice 2013 Updated Classification Group 1 (including participants
with Down Syndrome) and of following etiologies: idiopathic PAH; heritable PAH; PAH
associated with congenital heart disease (CHD); Drug or toxin induced PAH; PAH
associated with HIV; PAH associated with connective tissue diseases (PAH-aCTD); and
World health organization (WHO) Functional class I to III

- 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 the end of study (EOS)

Key
Minimum age
1 Month
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants 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

- Participants with PAH associated with Eisenmenger syndrome, or with moderate to large
left-to-right shunts

- Participants receiving a combination of > 2 PAH-specific treatments at randomization.

- Treatment with intravenous (IV) or subcutaneous (SC) prostanoids within 4 weeks before
randomization, unless given for vasoreactivity testing

- Hemoglobin or hematocrit <75 percent (%) of the lower limit of normal range

- Serum Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) greater
than (>) 3 times the upper limit of normal range

- Pregnancy (including family planning) or breastfeeding.

- Any circumstances or conditions, which, in the opinion of the investigator, may affect
full participation in the study or compliance with the protocol

- Severe hepatic impairment, for example Child-Pugh Class C

- Clinical signs of hypotension which in the investigator's judgment would preclude
initiation of a PAH-specific therapy

- Severe renal insufficiency (estimated creatinine clearance <30 mL/min or serum
creatinine >221 micro-moles per liter [micro-mol/L])

- Participants with known diagnosis of bronchopulmonary dysplasia

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Children's Hospital Melbourne - PIN - Parkville
Recruitment hospital [2] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
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United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
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Indiana
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Nevada
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New York
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North Carolina
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United States of America
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Ohio
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Texas
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United States of America
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Utah
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United States of America
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Virginia
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United States of America
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Wisconsin
Country [17] 0 0
Austria
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Graz
Country [18] 0 0
Austria
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Linz
Country [19] 0 0
Brazil
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São Paulo
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Canada
State/province [20] 0 0
Montreal
Country [21] 0 0
Canada
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Toronto
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China
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Beijing
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China
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Hangzhou
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China
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Qingdao
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China
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Shanghai
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China
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Shenyang
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China
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Wuhan
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Colombia
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Bogota
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Colombia
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Cali
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Finland
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Helsinki
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France
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Paris cedex 15
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Pessac
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France
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Toulouse Cedex 9
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Hungary
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Budapest
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Israel
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Haifa
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Israel
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Petah-Tikva
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Israel
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Ramat Gan
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Korea, Republic of
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Seoul
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Malaysia
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Kuala Lumpur
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Mexico
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Ciudad De México
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Mexico
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Guadalajara
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Mexico
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Makati City
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Quezon City
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Poznan
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Warszawa
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Wroclaw
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Portugal
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Carnaxide
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Russian Federation
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Kemerovo
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Moscow
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Novosibirsk
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St. Petersburg
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Russian Federation
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Tyumen
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Russian Federation
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Ufa
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South Africa
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Bloemfontein
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South Africa
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Durban
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Spain
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Barcelona
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Cordoba
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Madrid
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Spain
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Valencia
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Ukraine
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Dnipro
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Vietnam
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Hanoi
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Vietnam
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Ho Chi Minh City
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Vietnam
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Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a prospective, multicenter, open-label, randomized, controlled, parallel Phase 3
study with an open-label single-arm extension period to evaluate pharmacokinetics (PK),
safety and efficacy of macitentan in children with pulmonary arterial hypertension (PAH).
Trial website
https://clinicaltrials.gov/ct2/show/NCT02932410
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02932410