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

NCT04175600 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 4 other identifiers: CR108716AC-065A3102019-002817-212022-501012-34-00
• Study Type: interventional
• Target: 138
• Locations: 30 countries
• Sites: 111

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.

Conditions

Hypertension, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Double-blind Period: Time to Disease Progression

  Time to disease progression: time from randomization to first Clinical Event Committee (CEC)-confirmed disease progression event occurring between date of randomization until double-blind end date (DBED) + 7 days. Disease progression event as adjudicated by CEC, defined as any of the following: 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. Clinical worsening of PAH was defined as initiation of new PAH-specific therapy or intravenous diuretics or continuous oxygen use and at least 1 of the following: worsening in World Health Organization (WHO) functional class (FC); new occurrence or worsening: of syncope, of at least 2 PAH symptoms (shortness of breath/dyspnea, chest pain, cyanosis, dizziness/near syncope, or fatigue), of signs of right heart failure not responding to oral diuretics. Kaplan-Meier method was used for estimation.

  Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)

Secondary Outcomes (19)

• Double-blind Period: Change in log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 24

  Baseline (Day 1), Week 24

• Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious AEs (TESAEs)

  Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)

• Double-blind Period: Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment

  Placebo arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 198 weeks); Selexipag arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 212 weeks)

• Double-blind Period: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Day 1), Weeks 24, 48, 72, and 96

• Double-blind Period: Change From Baseline in Vital Signs: Pulse Rate

  Baseline (Day 1), Weeks 24, 48, 72, and 96

Study Arms (3)

Selexipag

EXPERIMENTAL

Participants will receive selexipag based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Selexipag will be uptitrated during the first 12 weeks until the participants reaches the individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline body-weight category is achieved. Uptitration is followed by a maintenance period after Week 12 until end of treatment (EOT), at the maximum tolerated dose. Participants will continue to receive pulmonary arterial hypertension (PAH)-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care.

Drug: Selexipag; Drug: Standard of Care (SOC): Endothelin receptor antagonist; Drug: SOC: Phosphodiesterase type 5 (PDE-5) inhibitor; Drug: SOC: Soluble guanylate cyclase stimulator

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care.

Drug: Placebo; Drug: Standard of Care (SOC): Endothelin receptor antagonist; Drug: SOC: Phosphodiesterase type 5 (PDE-5) inhibitor; Drug: SOC: Soluble guanylate cyclase stimulator

Open-Label Extension Period: Selexipag

EXPERIMENTAL

Participants with a positive benefit/risk ratio of selexipag for PAH will be offered selexipag in the open label extension period. Participants on selexipag during the double-blind treatment period will continue treatment at their iMTD during the OLEP, for those previously on placebo, the iMTD will uptitrate selexipag during first 12 weeks until participant reaches iMTD. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care.

Drug: Selexipag; Drug: Standard of Care (SOC): Endothelin receptor antagonist; Drug: SOC: Phosphodiesterase type 5 (PDE-5) inhibitor; Drug: SOC: Soluble guanylate cyclase stimulator

Interventions

SOC: Phosphodiesterase type 5 (PDE-5) inhibitor DRUG

PDE-5 inhibitor will be administered as SOC therapy.

Open-Label Extension Period: Selexipag; Placebo; Selexipag

Selexipag DRUG

Selexipag tablet will be administered orally.

Also known as: JNJ-67896049

Open-Label Extension Period: Selexipag; Selexipag

Placebo DRUG

Matching placebo tablets will be administered orally.

Placebo

SOC: Soluble guanylate cyclase stimulator DRUG

Soluble guanylate cyclase stimulator will be administered as SOC therapy.

Open-Label Extension Period: Selexipag; Placebo; Selexipag

Standard of Care (SOC): Endothelin receptor antagonist DRUG

ERAs will be administered as SOC therapy.

Open-Label Extension Period: Selexipag; Placebo; Selexipag

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead

Study Sites (116)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCSF

San Francisco, California, 94158, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Congenital Heart Center of the University of Florida

Gainesville, Florida, 32610, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Detroit Medical Center

Detroit, Michigan, 48201, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

University of Virginia Division of Pediatric Cardiology

Charlottesville, Virginia, 22908, United States

Location

Queensland CHILDREN'S HOSPITAL

South Brisbane, 4101, Australia

Location

State Institution Republican Scientific And Practical Center For Pediatric Surgery

Minsk, 220013, Belarus

Location

Health Institution 4Th City Children'S Clinical Hospital

Minsk, 220118, Belarus

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, 3000, Belgium

Location

Complexo de Prevencao,Diagnostico,Terapia e Reabilitacao Respiratoria LTDA Hospital Dia do Pulmao

Blumenau, 89030-101, Brazil

Location

Fundacao Universitaria de Cardiologia - Instituto de Cardiologia e Transplantes do DF

Brasília, 70310-500, Brazil

Location

Hospital Pequeno Principe

Curitiba, 80250-060, Brazil

Location

Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes

Fortaleza, 60840-285, Brazil

Location

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90020-090, Brazil

Location

Fundacao Universitaria de Cardiologia

Porto Alegre, 90620-001, Brazil

Location

Irmandade Santa Casa de Misericordia de Sao Paulo

São Paulo, 01221-020, Brazil

Location

SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo

São Paulo, 04024 002, Brazil

Location

Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead

Sofia, 1309, Bulgaria

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Beijing Anzhen Hospital

Beijing, 100029, China

Location

Guangzhou Women And Children's Medical Center

Guangzhou, 510623, China

Location

Qingdao Women and Children's Hospital 1

Qingdao, 266000, China

Location

Qingdao Women and Children's Hospital

Qingdao, 266000, China

Location

Shanghai Childrens Medical Center

Shanghai, 200127, China

Location

Children's Hospital of Fudan University

Shanghai, 201102, China

Location

The General Hospital of Northern Theater Command

Shenyang, 110000, China

Location

Clinica San Rafael

Bogotá, 0000000, Colombia

Location

Fundacion Neumologica Colombiana

Bogotá, 0000000, Colombia

Location

Fundacion Santa Fe de Bogota

Bogotá, Colombia

Location

Clínica Imbanaco S.A.S.

Cali, 760042, Colombia

Location

Fundacion Cardiovascular de Colombia

Piedecuesta, 681017, Colombia

Location

Hospital Universidad del Norte

Soledad, 0000000, Colombia

Location

New Children's Hospital of the Helsinki University Hospital (HUS)

Helsinki, 29, Finland

Location

Hôpital Cardiologique - Chru Lille

Lille, 59037, France

Location

Hopital de la Timone

Marseille, 13385, France

Location

CHU Arnaud de Villeneuve

Montpellier, 34295, France

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Hôpital Cardiologique Du Haut-Lévêque

Pessac, 33604, France

Location

Chu Hopital Des Enfants

Toulouse, 31059, France

Location

Universitätsklinikum Freiburg Zentrum

Freiburg im Breisgau, 70106, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, D-69120, Germany

Location

Herzzentrum Leipzig GmbH

Leipzig, 04289, Germany

Location

Klinikum der Universitaet Muenchen

München, 81377, Germany

Location

Gottsegen György Országos Kardiológiai Intézet

Budapest, 1096, Hungary

Location

Our Lady's Children's Hospital

Dublin, Ireland

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Azienda Ospedaliera Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Universta Degli Studi Di Padova

Padova, Italy

Location

Ospedale Pediatrico Bambin Gesù

Roma, 00193, Italy

Location

IRCCS Policlinico San Donato

S. Donato Milanese, 20097, Italy

Location

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

Torino, 10126, Italy

Location

Vilnius University Hospital Santariskiu Clinics

Vilnius, LT08661, Lithuania

Location

National Heart Institute

Kuala Lumpur, 50400, Malaysia

Location

CICUM San Miguel

Guadalajara, 44160, Mexico

Location

Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas

México, 52787, Mexico

Location

Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)

Monterrey, 64718, Mexico

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 952, Poland

Location

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, 30-663, Poland

Location

Szpital Kliniczny im Karola Jonschera

Poznan, 60 572, Poland

Location

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu

Wroclaw, 51 124, Poland

Location

Slaskie Centrum Chorob Serca

Zabrze, 41-800, Poland

Location

Uls Sao Jose - Hosp. Santa Marta

Lisbon, 1169-024, Portugal

Location

Uls Sao Joao - Hosp. Sao Joao

Porto, 4200 319, Portugal

Location

Kazan State Medical University

Kazan', 420012, Russia

Location

Kazan State Medical University 1

Kazan', 420059, Russia

Location

Scientific and Research Institution of Cardiovascular Diseases Complex Problems

Kemerovo, 650002, Russia

Location

Childrens City Clinical Hospital n.a. Bashlyaeva

Moscow, 125373, Russia

Location

Veltischev Research and Clinical Institute for Pediatrics of the Pirogov RNRMU

Moscow, 125412, Russia

Location

Samara Regional Clinical Cardiological Dispensary

Samara, 443070, Russia

Location

Univerzitetska Dečja Klinika

Belgrade, 11000, Serbia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 120-752, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

Hosp Univ A Coruna

A Coruña, 15006, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp. Sant Joan de Deu

Esplugues de Llobregat, 08950, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28009, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Drottning Silvias barn- och ungdomssjukhus

Gothenburg, 416 50, Sweden

Location

Skanes universitetssjukhus

Lund, 222 42, Sweden

Location

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, 1011, Switzerland

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 813414, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Chiang Mai University Hospital

Chiang Mai, 50200, Thailand

Location

Songklanagarind hospital

Songkhla, 90110, Thailand

Location

Cukurova Balcali Hospital Application and Research Center

Adana, 01790, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06230, Turkey (Türkiye)

Location

CAPA Istanbul University Medical Faculty

Istanbul, 34093, Turkey (Türkiye)

Location

Mehmet Akif Ersoy Training and Research Hospital

Istanbul, 34303, Turkey (Türkiye)

Location

Izmir Tepecik Training and Research Hospital

Izmir, 35020, Turkey (Türkiye)

Location

Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital

Izmir, 35210, Turkey (Türkiye)

Location

Dnipropetrovsk clinical medical center of Mother and Child after prof. Rudnev

Dnipro, 49006, Ukraine

Location

MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'

Dnipro, 49070, Ukraine

Location

Scientific Practical Medical Center for Pediatric Cardiology and Cardio Surgery of the MOH

Kyiv, 04050, Ukraine

Location

MI Zaporizhzhia Regional Clinical Childrens Hospital of Zaporizhzhia Regional Council

Zaporizhzhya, 69063, Ukraine

Location

Hanoi Medical University Hospital

Hanoi, Vietnam

Location

Tam Anh Hospital

Ho Chi Minh City, 700000, Vietnam

Location

University Medical Center Ho Chi Minh city

Ho Chi Minh City, 700000, Vietnam

Location

Children's Hospital 1

Ho Chi Minh City, Vietnam

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

selexipag; Standard of Care; PDE5A protein, human

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Executive Medical Director CP
• Organization: Actelion Pharmaceuticals Ltd.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Actelion Clinical Trial

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 25, 2019
• Study Start: January 16, 2020
• Primary Completion: October 11, 2024
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 31, 2026
• Results First Posted: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

IE (1); ES (6); LI (1); PT (2); RU (6); IL (2); KR (4); ME (3); CN (7); US (13); PL (6); IT (6); SE (1); CA (2); TU (6); HU (1); FI (1); UA (4); FR (6); TW (3); MY (1); DE (4); BE (2); AU (1); CO (6); CH (1); TH (2); BR (8); BU (1); VN (4)