Clinical trial NCT04175600: A Study of Selexipag as Add-On Treatment to Standard of Care in Children With Pulmonary Arterial Hypertension
Official title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group Study With Open-Label Extension Period to Assess the Efficacy and Safety of Selexipag as Add-On Treatment to Standard of Care in Children Aged >=2 to <18 Years With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypertension, Pulmonary
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2019-11-25
Enrollment: 138
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to Disease Progression
timeFrame: From randomization up to 7 days after study treatment discontinuation (up to 5 years)
Secondary outcomes:
measure: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious AEs
timeFrame: Up to 5 years
measure: Percentage of Participants with AEs Leading to Premature Discontinuation of Study Treatment
timeFrame: Up to 5 years
measure: Change from Baseline in Systolic and Diastolic Arterial Blood Pressure
timeFrame: Baseline up to end of treatment (EOT) (up to 8 years)
measure: Change from Baseline in Pulse Rate
timeFrame: Baseline up to EOT (up to 8 years)
measure: Change from Baseline in Body Weight
timeFrame: Baseline up to EOT (up to 8 years)
measure: Change from Baseline in Height
timeFrame: Baseline up to EOT (up to 8 years)
measure: Sexual Maturation (Tanner Stage) Change from Baseline to all Assessed Time Points
timeFrame: Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8 years)
measure: Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities
timeFrame: Baseline up to EOT (up to 8 years)
measure: Percentage of Participants with Treatment-emergent Marked Laboratory Abnormalities
timeFrame: Baseline up to EOT (up to 8 years)
measure: Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone
timeFrame: Baseline up to EOT (up to 8 years)
measure: Time to First Clinical Event Committee (CEC)-confirmed Hospitalization or Death for PAH
timeFrame: Until 7 days after study treatment discontinuation (Up to 8 years)
measure: Trough Plasma Concentration at Steady-state (Ctrough,ss) of Selexipag and its Metabolite ACT-333679
timeFrame: Weeks 16, 24 and every 12 weeks thereafter (up to 8 years)
measure: Change from Baseline at Week 24 in Log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Congenital Heart Center of the University of Florida
state: Florida
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Detroit
country: United States
facility: Detroit Medical Center
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Childrens Hospital Of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Division of Pediatric Cardiology
state: Virginia
city: South Brisbane
country: Australia
facility: Queensland CHILDREN'S HOSPITAL
city: Minsk
country: Belarus
facility: State Institution Republican Scientific And Practical Center For Pediatric Surgery
city: Minsk
country: Belarus
facility: Health Institution 4Th City Children'S Clinical Hospital
city: Brussels
country: Belgium
facility: ULB Hôpital Erasme
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Blumenau
country: Brazil
facility: Complexo de Prevencao,Diagnostico,Terapia e Reabilitacao Respiratoria LTDA Hospital Dia do Pulmao
city: Brasilia
country: Brazil
facility: Fundacao Universitaria de Cardiologia - Instituto de Cardiologia e Transplantes do DF
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe
city: Fortaleza
country: Brazil
facility: Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Fundacao Universitaria de Cardiologia
city: Sao Paulo
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Sao Paulo
city: Sao Paulo
country: Brazil
facility: SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Beijing
country: China
facility: Beijing Anzhen Hospital
city: Guangzhou
country: China
facility: Guangzhou Women And Children's Medical Center
city: Qingdao
country: China
facility: Qingdao Women and Children's Hospital
city: Shanghai
country: China
facility: Shanghai Childrens Medical Center
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Shenyang
country: China
facility: The General Hospital of Northern Theater Command
city: Bogota
country: Colombia
facility: Clinica San Rafael
city: Bogota
country: Colombia
facility: Fundacion Neumologica Colombiana
city: Bogota
country: Colombia
facility: Fundacion Santa Fe de Bogota
city: Cali
country: Colombia
facility: Clínica Imbanaco S.A.S.
city: Piedecuesta
country: Colombia
facility: Fundacion Cardiovascular de Colombia
city: Soledad
country: Colombia
facility: Hospital Universidad del Norte
city: Helsinki
country: Finland
facility: New Children's Hospital of the Helsinki University Hospital (HUS)
city: Lille Cedex
country: France
facility: Hôpital Cardiologique - Chru Lille
city: Marseille Cedex 5
country: France
facility: Hopital de la Timone
city: Montpellier Cedex 5
country: France
facility: CHU Arnaud de Villeneuve
city: Paris
country: France
facility: Hôpital Necker - Enfants Malades
city: Pessac
country: France
facility: Hôpital Cardiologique Du Haut-Lévêque
city: Toulouse Cedex 9
country: France
facility: Chu Hopital Des Enfants
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg Zentrum
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: München
country: Germany
facility: Klinikum der Universitaet Muenchen
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliera Policlinico S. Orsola-Malpighi
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Padova
country: Italy
facility: Universta Degli Studi Di Padova
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambin Gesù
city: S. Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinics
city: Kuala Lumpur
country: Malaysia
facility: National Heart Institute
city: Guadalajara
country: Mexico
facility: CICUM San Miguel
city: Mexico
country: Mexico
facility: Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Poznan
country: Poland
facility: Szpital Kliniczny im Karola Jonschera
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu
city: Zabrze
country: Poland
facility: Slaskie Centrum Chorob Serca
city: Lisboa
country: Portugal
facility: Uls Sao Jose - Hosp. Santa Marta
city: Porto
country: Portugal
facility: Uls Sao Joao - Hosp. Sao Joao
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Kemerovo
country: Russian Federation
facility: Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
city: Moscow
country: Russian Federation
facility: Childrens City Clinical Hospital n.a. Bashlyaeva
city: Moscow
country: Russian Federation
facility: Veltischev Research and Clinical Institute for Pediatrics of the Pirogov RNRMU
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Cardiological Dispensary
city: Belgrade
country: Serbia
facility: Univerzitetska Dečja Klinika
city: A Coruña
country: Spain
facility: Hosp Univ A Coruna
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Esplugues de Llobregat
country: Spain
facility: Hosp. Sant Joan de Deu
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Gothenburg
country: Sweden
facility: Drottning Silvias barn- och ungdomssjukhus
city: Lund
country: Sweden
facility: Skanes universitetssjukhus
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois CHUV
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind hospital
city: Adana
country: Turkey
facility: Cukurova Balcali Hospital Application and Research Center
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Istanbul
country: Turkey
facility: CAPA Istanbul University Medical Faculty
city: Istanbul
country: Turkey
facility: Mehmet Akif Ersoy Training and Research Hospital
city: Izmir
country: Turkey
facility: Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital
city: Izmir
country: Turkey
facility: Izmir Tepecik Training and Research Hospital
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk clinical medical center of Mother and Child after prof. Rudnev
city: Dnipro
country: Ukraine
facility: MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
city: Kyiv
country: Ukraine
facility: Scientific Practical Medical Center for Pediatric Cardiology and Cardio Surgery of the MOH
city: Zaporizhzhya
country: Ukraine
facility: MI Zaporizhzhia Regional Clinical Childrens Hospital of Zaporizhzhia Regional Council
city: Hanoi
country: Vietnam
facility: Hanoi Medical University Hospital
city: Ho Chi Minh
country: Vietnam
facility: Tam Anh Hospital
city: Ho Chi Minh
country: Vietnam
facility: University Medical Center Ho Chi Minh city
city: Ho Chi Minh
country: Vietnam
facility: Children's Hospital 1
Study officials:
affiliation: Actelion
name: Actelion Clinical Trial
role: STUDY_DIRECTOR
References: