The purpose of this study is to evaluate whether the addition of selexipag to standard of care treatment delays disease progression in children with Pulmonary Arterial Hypertension (PAH) in comparison to placebo.
Pediatric PAH is a rare and progressive disorder associated with considerable morbidity and mortality. Given the significant medical need to develop treatments in children with PAH, further clinical studies in the pediatric population are therefore needed to provide more data for the management of PAH in children. Selexipag (JNJ-67896049) is an orally available, selective, and long-acting non-prostanoid agonist of the prostacyclin receptor approved and commercially available for the treatment of adult participants with PAH. Selexipag and its metabolite possess anti-fibrotic, anti-proliferative, and anti-thrombotic properties. Currently, no medicines targeting prostacyclin pathway are approved for pediatric use in PAH. An effective and orally available therapy acting on the prostacyclin receptor such as selexipag introduced at medically appropriate stage of PAH disease, and primarily in combination with current first-line oral PAH-specific medicines in participants in need of additional therapy because of insufficient disease control would represents a major advance to the therapeutic management of PAH pediatric participants. This study consists of a screening period of up to 6 weeks and a double-blind treatment period, including up-titration and maintenance periods, followed by a 3-year open-label extension period (OLEP) and a 30-day safety follow-up period that occurs after the last dose of study intervention (either double-blind or open-label). Safety, pharmacokinetic and efficacy assessments will be performed during the study. An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an ongoing basis, to review interim data, and to ensure the continuing safety of the participants enrolled in this study. The approximate duration of the study is 8 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
138
Time to Disease Progression
Time to disease progression is the time from randomization up to 7 days after study treatment discontinuation. Disease progression is defined as the first occurrence of either of the following components: Death (all causes), Atrial septostomy or Potts' anastomosis, or registration on lung transplant list, Hospitalization due to worsening pulmonary arterial hypertension (PAH), Clinical worsening of PAH.
Time frame: From randomization up to 7 days after study treatment discontinuation (up to 5 years)
Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs
An adverse event (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. TEAEs are AEs with onset during the intervention period or that are a consequence of a pre-existing condition that has worsened since baseline. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Up to 5 years
Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment
Percentage of participants with AEs leading to premature discontinuation of study treatment will be reported.
Time frame: Up to 5 years
Change from Baseline in Systolic and Diastolic Arterial Blood Pressure
Change from baseline in systolic and diastolic arterial blood pressure to all assessed time points will be reported.
Time frame: Baseline up to end of treatment (EOT) (up to 8 years)
Change from Baseline in Pulse Rate
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PDE-5 inhibitor will be administered as SOC therapy.
Soluble guanylate cyclase stimulator will be administered as SOC therapy.
Phoenix Children's Hospital
Phoenix, Arizona, United States
UCLA Medical Center
Los Angeles, California, United States
UCSF
San Francisco, California, United States
Childrens Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Congenital Heart Center of the University of Florida
Gainesville, Florida, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Detroit Medical Center
Detroit, Michigan, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Childrens Hospital Of Philadelphia
Philadelphia, Pennsylvania, United States
...and 106 more locations
Change from baseline in pulse rate to all assessed time points will be reported.
Time frame: Baseline up to EOT (up to 8 years)
Change from Baseline in Body Weight
Change from baseline in body weight to all assessed time points will be reported.
Time frame: Baseline up to EOT (up to 8 years)
Change from Baseline in Height
Change from baseline in height to all assessed time points will be reported.
Time frame: Baseline up to EOT (up to 8 years)
Sexual Maturation (Tanner Stage) Change from Baseline to all Assessed Time Points
The sexual maturation change as per Tanner stage will be assessed from baseline to all assessed time points. Tanner stage I is defined as no pubic hair at all (prepubertal Dominic state); stage II is defined as a small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females); stage III is defined as when the hair becomes more coarse and curly, and begins to extend laterally; stage IV is defined as adult-like hair quality, extending across pubis but sparing medial thighs; and stage V is defined as when the: hair extends to medial surface of the thighs.
Time frame: Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8 years)
Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities
Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.
Time frame: Baseline up to EOT (up to 8 years)
Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities
Percentage of participants with treatment-emergent marked laboratory (serum chemistry \[including pregnancy testing and thyroid markers\] and hematology) abnormalities will be reported.
Time frame: Baseline up to EOT (up to 8 years)
Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone
Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.
Time frame: Baseline up to EOT (up to 8 years)
Time to First Clinical Event Committee (CEC)-confirmed Hospitalization or Death for PAH
Time to first CEC-confirmed hospitalization or death for PAH is the time (days) from randomization to first occurrence of CEC-confirmed hospitalization for PAH or death due to PAH up to 7 days after study intervention discontinuation.
Time frame: Until 7 days after study treatment discontinuation (Up to 8 years)
Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679
Ctrough,ss is defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the pharmacokinetic sampling and will be reported for Selexipag and its metabolite ACT-333679.
Time frame: Weeks 16, 24 and every 12 weeks thereafter (up to 8 years)
Change from Baseline at Week 24 in Log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
The change from baseline at week 24 in log2 NT-proBNP will be reported.
Time frame: Baseline up to Week 24