We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH) (TOMORROW)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02932410
Recruitment Status : Recruiting
First Posted : October 13, 2016
Last Update Posted : September 14, 2022
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE October 12, 2016
First Posted Date  ICMJE October 13, 2016
Last Update Posted Date September 14, 2022
Actual Study Start Date  ICMJE October 24, 2017
Estimated Primary Completion Date February 29, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2021)
  • 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 [ Time Frame: Week 12 ]
    Observed steady-state trough plasma concentration of macitentan and its active metabolite ACT-132577 will be reported.
  • Participants Less than (<) 2 Years: Observed Steady-state Trough Plasma Concentration of Macitentan and its Active Metabolite ACT-132577 at Week 4 [ Time Frame: Week 4 ]
    Observed steady-state trough plasma concentration of macitentan and its active metabolite ACT-132577 will be reported.
Original Primary Outcome Measures  ICMJE
 (submitted: October 12, 2016)
Time to the first CEC-confirmed disease progression event [ Time Frame: Between randomization and EOS/study closure; up to 6 years ]
Time to the first of the following CEC-confirmed disease progression events: • Death (all causes) • Atrial septostomy or Potts' anastomosis, or registration on lung transplant list • Hospitalization due to worsening PAH • Clinical worsening of PAH
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2021)
  • Time to the first CEC-confirmed Disease Progression Event [ Time Frame: Between randomization/visit 2 and end of core study period (EOCP); up to 7 years ]
    Time to the first of the following CEC-confirmed disease progression events: • Death (all causes) • Atrial septostomy or Potts' anastomosis, or registration on lung transplant list • Hospitalization due to worsening PAH • Clinical worsening of PAH.
  • Time to First CEC-confirmed Hospitalization for PAH [ Time Frame: Between randomization/visit 2 and EOCP/; up to 7 years ]
    Time to first CEC-confirmed hospitalization for PAH occurring between randomization/visit 2 and EOCP.
  • Time to CEC-confirmed death due to PAH [ Time Frame: Between randomization/visit 2 and EOCP; up to 7 years ]
    Time to CEC-confirmed death due to PAH occurring between randomization/visit 2 and EOCP.
  • Time to death (all causes) [ Time Frame: Between randomization/visit 2 and EOCP; up to 7 years ]
    Time to death (all causes) occurring between randomization/visit 2 and EOCP.
  • The Percentage of Participants with World Health Organization (WHO) Functional Class (FC) I or II versus III or IV [ Time Frame: Week 24 ]
    Percentage of participants with WHO FC I or II versus III or IV will be reported.
  • Change from Baseline to Week 24 in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline to Week 24 ]
    The quantitation of NT-proBNP plasma levels will be performed and reported.
  • Change from Baseline to Week 48 in Moderate to Vigorous Physical Activity as Measured by Accelerometry [ Time Frame: Baseline to Week 48 ]
    Change from baseline to Week 48 in moderate to vigorous physical activity as measured by accelerometry will be reported.
  • Change from Baseline to Week 24 in Tricuspid Annular Plane Systolic Excursion (TAPSE) Measured by Echocardiography [ Time Frame: Baseline to Week 24 ]
    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.
  • Change from Baseline to Week 24 in Left Ventricular Eccentricity Index (LVEI) Measured by Echocardiography [ Time Frame: Baseline to Week 24 ]
    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.
  • 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) [ Time Frame: Baseline to Week 24 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2016)
  • Time to first CEC-confirmed hospitalization for PAH occurring between randomization and EOS [ Time Frame: Between randomization and EOS/study closure; up to 6 years ]
  • Time to CEC-confirmed death due to PAH occurring between randomization and EOS [ Time Frame: Between randomization and EOS/study closure; up to 6 years ]
  • Time to death (all causes) occurring between randomization and Study Closure [ Time Frame: Between randomization and EOS/study closure; up to 6 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH)
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE
  • Drug: Macitentan
    Dispersible tablet; Oral use
    Other Name: ACT-064992
  • Other: 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Macitentan
  • 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.
    Intervention: Other: Standard-of-care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 12, 2016)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 29, 2024
Estimated Primary Completion Date February 29, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   Canada,   China,   Colombia,   Finland,   France,   Hungary,   Israel,   Korea, Republic of,   Malaysia,   Mexico,   Philippines,   Poland,   Portugal,   Russian Federation,   South Africa,   Spain,   Thailand,   Ukraine,   United States,   Vietnam
Removed Location Countries Argentina,   Bulgaria
 
Administrative Information
NCT Number  ICMJE NCT02932410
Other Study ID Numbers  ICMJE AC-055-312
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Actelion
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Actelion
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Actelion
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP