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

Hypertension, Pulmonary Clinical Trial

— SALTO  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04175600
• Other study ID #: CR108716
• Secondary ID: 2019-002817-21AC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 16, 2020
• Est. completion date: January 10, 2028

Study information

• Verified date: April 2024
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 138
• Est. completion date: January 10, 2028
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Selexipag
Selexipag tablet will be administered orally.
• Placebo
Matching placebo tablets will be administered orally.

Locations

Country	Name	City	State
Australia	Queensland CHILDREN'S HOSPITAL	South Brisbane
Belarus	Health Institution 4Th City Children'S Clinical Hospital	Minsk
Belarus	State Institution Republican Scientific And Practical Center For Pediatric Surgery	Minsk
Belgium	ULB Hôpital Erasme	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Brazil	Complexo de Prevencao,Diagnostico,Terapia e Reabilitacao Respiratoria LTDA Hospital Dia do Pulmao	Blumenau
Brazil	Fundacao Universitaria de Cardiologia - Instituto de Cardiologia e Transplantes do DF	Brasilia
Brazil	Hospital Pequeno Principe	Curitiba
Brazil	Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes	Fortaleza
Brazil	Fundacao Universitaria de Cardiologia	Porto Alegre
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Irmandade Santa Casa de Misericordia de Sao Paulo	Sao Paulo
Brazil	SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo	São Paulo
Bulgaria	Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead	Sofia
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	Hospital For Sick Children	Toronto	Ontario
China	Beijing Anzhen Hospital	Beijing
China	Guangzhou Women And Children's Medical Center	Guangzhou
China	Qingdao Women and Children's Hospital	Qingdao
China	Children's Hospital of Fudan University	Shanghai
China	Shanghai Childrens Medical Center	Shanghai
China	The General Hospital of Northern Theater Command	Shenyang
Colombia	Clinica San Rafael	Bogota
Colombia	Fundacion Neumologica Colombiana	Bogota
Colombia	Fundacion Santa Fe de Bogota	Bogota
Colombia	Clínica Imbanaco S.A.S.	Cali
Colombia	Fundacion Cardiovascular de Colombia	Piedecuesta
Colombia	Hospital Universidad del Norte	Soledad
Finland	New Children's Hospital of the Helsinki University Hospital (HUS)	Helsinki
France	Hôpital Cardiologique - Chru Lille	Lille Cedex
France	Hopital de la Timone	Marseille Cedex 5
France	CHU Arnaud de Villeneuve	Montpellier Cedex 5
France	Hôpital Necker - Enfants Malades	Paris
France	Hôpital Cardiologique Du Haut-Lévêque	Pessac
France	Chu Hopital Des Enfants	Toulouse Cedex 9
Germany	Universitätsklinikum Freiburg Zentrum	Freiburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Herzzentrum Leipzig GmbH	Leipzig
Germany	Klinikum der Universitaet Muenchen	München
Hungary	Gottsegen György Országos Kardiológiai Intézet	Budapest
Ireland	Our Lady's Children's Hospital	Dublin
Israel	Rambam Medical Center	Haifa
Israel	Sheba Medical Center	Ramat Gan
Italy	Azienda Ospedaliera Policlinico S. Orsola-Malpighi	Bologna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Universta Degli Studi Di Padova	Padova
Italy	Ospedale Pediatrico Bambin Gesù	Roma
Italy	IRCCS Policlinico San Donato	S. Donato Milanese
Italy	AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita	Torino
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan-si
Lithuania	Vilnius University Hospital Santariskiu Clinics	Vilnius
Malaysia	National Heart Institute	Kuala Lumpur
Mexico	CICUM San Miguel	Guadalajara
Mexico	Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas	Mexico
Mexico	Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)	Monterrey
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie	Kraków
Poland	Szpital Kliniczny im. Karola Jonschera	Poznan
Poland	Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa
Poland	Wojewodzki Szpital Specjalistyczny we Wroclawiu	Wroclaw
Poland	Slaskie Centrum Chorob Serca	Zabrze
Portugal	Hospital De Santa Marta	Lisboa
Portugal	Centro Hospitalar de Sao Joao EPE	Porto
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	Cardiovascular Pathology Research Institute of Siberian Branch of RAMS	Kemerovo
Russian Federation	Childrens City Clinical Hospital n.a. Bashlyaeva	Moscow
Russian Federation	Veltischev Research and Clinical Institute for Pediatrics of the Pirogov RNRMU	Moscow
Russian Federation	Samara Regional Clinical Cardiological Dispensary	Samara
Serbia	Univerzitetska Decja Klinika	Belgrade
Spain	Hosp. Univ. A Coruna	A Coruña
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Sant Joan de Deu	Esplugues de Llobregat
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Virgen Del Rocio	Sevilla
Sweden	Drottning Silvias barn- och ungdomssjukhus	Gothenburg
Sweden	Skanes universitetssjukhus	Lund
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Chiang Mai University Hospital	Chiang Mai
Thailand	Songklanagarind hospital	Songkhla
Turkey	Cukurova Balcali Hospital Application and Research Center	Adana
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	CAPA Istanbul University Medical Faculty	Istanbul
Turkey	Mehmet Akif Ersoy Training and Research Hospital	Istanbul
Turkey	Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital	Izmir
Turkey	Izmir Tepecik Training and Research Hospital	Izmir
Ukraine	Dnipropetrovsk clinical medical center of Mother and Child after prof. Rudnev	Dnipro
Ukraine	MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'	Dnipro
Ukraine	Scientific Practical Medical Center for Pediatric Cardiology and Cardio Surgery of the MOH	Kyiv
Ukraine	MI Zaporizhzhia Regional Clinical Childrens Hospital of Zaporizhzhia Regional Council	Zaporizhzhya
United States	Childrens Hospital Colorado	Aurora	Colorado
United States	University of Virginia Division of Pediatric Cardiology	Charlottesville	Virginia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Detroit Medical Center	Detroit	Michigan
United States	Congenital Heart Center of the University of Florida	Gainesville	Florida
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	UCLA Medical Center	Los Angeles	California
United States	Childrens Hospital Of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	UCSF	San Francisco	California
United States	Children's National Medical Center	Washington	District of Columbia
Vietnam	Hanoi Medical University Hospital	Hanoi
Vietnam	Children's Hospital 1	Ho Chi Minh
Vietnam	Tam Anh Hospital	Ho Chi Minh
Vietnam	University Medical Center Ho Chi Minh city	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Belarus,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Colombia,  Finland,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  Poland,  Portugal,  Russian Federation,  Serbia,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From randomization up to 7 days after study treatment discontinuation (up to 5 years)
Secondary	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.	Up to 5 years
Secondary	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.	Up to 5 years
Secondary	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.	Baseline up to end of treatment (EOT) (up to 8 years)
Secondary	Change from Baseline in Pulse Rate	Change from baseline in pulse rate to all assessed time points will be reported.	Baseline up to EOT (up to 8 years)
Secondary	Change from Baseline in Body Weight	Change from baseline in body weight to all assessed time points will be reported.	Baseline up to EOT (up to 8 years)
Secondary	Change from Baseline in Height	Change from baseline in height to all assessed time points will be reported.	Baseline up to EOT (up to 8 years)
Secondary	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.	Up to 3 days after study treatment discontinuation (up to EOT) (multiple timepoints up to 8 years)
Secondary	Percentage of Participants with Treatment-emergent Electrocardiogram Abnormalities	Percentage of participants with treatment-emergent electrocardiogram abnormalities will be reported.	Baseline up to EOT (up to 8 years)
Secondary	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.	Baseline up to EOT (up to 8 years)
Secondary	Treatment-emergent Change from Baseline in Thyroid Stimulating Hormone	Treatment-emergent change from baseline in thyroid stimulating hormone over time will be reported.	Baseline up to EOT (up to 8 years)
Secondary	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.	Until 7 days after study treatment discontinuation (Up to 8 years)
Secondary	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.	Weeks 16, 24 and every 12 weeks thereafter (up to 8 years)
Secondary	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.	Baseline up to Week 24