A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension

Sponsor: Actelion

Sommario: 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.


TIPOLOGIA STUDIO

Interventistico

FASE

Fase 3


TRATTAMENTO

  • Selexipag
  • Placebo

OBIETTIVO PRIMARIO

  • Misura: Time to Disease Progression
  • Tempo: From randomization up to 7 days after study treatment discontinuation (up to 5 years)
  • Descrizione: 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.

OBIETTIVO SECONDARIO

  • Misura: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs
  • Tempo: Up to 5 years
  • Descrizione: 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.
  • Misura: Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment
  • Tempo: Up to 5 years
  • Descrizione: Percentage of participants with AEs leading to premature discontinuation of study treatment will be reported.
  • Misura: Change from Baseline in Systolic and Diastolic Arterial Blood Pressure
  • Tempo: Baseline up to end of treatment (EOT) (up to 8 years)
  • Descrizione: Change from baseline in systolic and diastolic arterial blood pressure to all assessed time points will be reported.
  • Misura: Change from Baseline in Pulse Rate
  • Tempo: Baseline up to EOT (up to 8 years)
  • Descrizione: Change from baseline in pulse rate to all assessed time points will be reported.
  • Misura: Change from Baseline in Body Weight
  • Tempo: Baseline up to EOT (up to 8 years)
  • Descrizione: Change from baseline in body weight to all assessed time points will be reported.
  • Misura: Change from Baseline in Height
  • Tempo: Baseline up to EOT (up to 8 years)
  • Descrizione: Change from baseline in height to all assessed time points will be reported.
  • Misura: Sexual Maturation (Tanner Stage) Change from Baseline to all Assessed Time Points
  • Tempo: Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8 years)
  • Descrizione: 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.
  • Misura: Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities
  • Tempo: Baseline up to EOT (up to 8 years)
  • Descrizione: Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.
  • Misura: Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities
  • Tempo: Baseline up to EOT (up to 8 years)
  • Descrizione: Percentage of participants with treatment-emergent marked laboratory (serum chemistry [including pregnancy testing and thyroid markers] and hematology) abnormalities will be reported.
  • Misura: Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone
  • Tempo: Baseline up to EOT (up to 8 years)
  • Descrizione: Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.
  • Misura: Time to First Clinical Event Committee (CEC)-confirmed Hospitalization or Death for PAH
  • Tempo: Until 7 days after study treatment discontinuation (Up to 8 years)
  • Descrizione: 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.
  • Misura: Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679
  • Tempo: Weeks 16, 24 and every 12 weeks thereafter (up to 8 years)
  • Descrizione: 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.
  • Misura: Change from Baseline at Week 24 in Log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
  • Tempo: Baseline up to Week 24
  • Descrizione: The change from baseline at week 24 in log2 NT-proBNP will be reported.

CRITERI DI ELIGIBILITA'

  • Criteri di inclusione e esclusione

    Inclusion Criteria: - Participants between greater than or equal to (>=) 2 and less than (<) 18 years of age weighing >=9 kilogram (kg) at randomization - Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's screening - PAH (World Health Organization [WHO] Group 1), including participants with Down syndrome, of the following etiologies: Idiopathic PAH (IPAH); Heritable PAH (HPAH); PAH associated with congenital heart disease (PAH-associated with congenital heart disease [aCHD]) (PAH with coincidental CHD [that is, a small atrial septal defect, ventricular septal defect, or patent ductus arteriosus that does not itself account for the development of elevated PVR] and if approved by the BCAC) and Post-operative PAH (persisting / recurring/ developing >=6 months after repair of CHD); Drug or toxin-induced; PAH associated with Human immunodeficiency virus (HIV) - WHO functional class (FC) II and III - Participants treated with at least 1 PAH-specific treatment, example, an Endothelin receptor antagonist (ERA) and/or a Phosphodiesterase type-5 (PDE-5) inhibitor/soluble guanylate cyclase stimulator, provided that the treatment dose(s) has been stable for at least 3 months prior to first dose of study intervention Exclusion Criteria: - PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis - PAH associated with Eisenmenger syndrome - Previous exposure to Uptravi (selexipag) - Known concomitant life-threatening disease with a life expectancy <12 months - Pregnant, planning to become pregnant, or lactating - Known allergies, hypersensitivity, or intolerance to selexipag or its excipients


SESSO

Tutti


ETA' MINIMA

Età Minima: 2 Years
Età Massima: 17 Years


LUOGO

Azienda Ospedaliera Policlinico S. Orsola-Malpighi
Bologna, 40138

ASST Grande Ospedale Metropolitano Niguarda
Milano, 20162

Universta Degli Studi Di Padova
Padova,

Ospedale Pediatrico Bambin Gesù
Roma, 00193

IRCCS Policlinico San Donato
S. Donato Milanese, 20097

AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
Torino, 10126