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NCT05714085PHASE2, PHASE3Recruiting

Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)

Merck Sharp & Dohme LLC

Start Date

5/31/2023

Completion Date

4/15/2032

Summary

This study aims to compare the efficacy of vericiguat versus placebo on change in n-terminal pro-brain natriuretic peptide (NTproBNP) from baseline to Week 16 of the Base Period. The primary hypothesis is that vericiguat is superior to placebo in reducing NT-proBNP at Week 16 of the Base Period.

Detailed Description

As of Protocol Amendment 2, the separate open-label extension arm of study MK-1242-043 (NCT06428383) will be incorporated into the present MK-1242-036 study as an extension period. Participants from the Base Period will be provided the opportunity to participate in the optional open-label Extension Period if eligible. After all ongoing participants are transferred into the extension period of MK-1242-036, MK-1242-043 (NCT06428383) will be formally closed.

Eligibility Criteria

Age Range: No minimum to 17 years

Inclusion Criteria: * Has symptomatic chronic heart failure (HF) resulting from systemic left ventricular (LV) systolic dysfunction. * Has biventricular physiology with a morphologic systemic left ventricle. * Is currently receiving stable medical therapy for HF. * Has left ventricular ejection fraction (LVEF) \<45% assessed within 3 months before randomization. * Is of any sex/gender, from \>28 days to \<18 years of age inclusive. Must weigh ≥3 kg to participate. * Female is eligible to participate if not pregnant or breastfeeding, and at least one of the following: is not a participant of childbearing potential (POCBP); or is a POCBP who uses a highly effective contraceptive method; has a negative highly sensitive pregnancy test; abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention; and their medical history; their menstrual history, and recent sexual activity has been reviewed. * Extension Period: Was randomized, received at least 1 dose of study intervention (vericiguat or placebo), did not permanently discontinue study intervention, and completed the Week 52 visit and safety follow-up period of the Base Period Exclusion Criteria: * Is clinically unstable-with at least one of the following: has symptomatic hypotension or is hypotensive for age, recent use of intravenous (IV) inotrope and/or IV vasodilator, or recent IV diuretic. * Has a known allergy or sensitivity to vericiguat, any of its constituents, or any other soluble guanylate cyclase (sGC) stimulator. * Has a history of single ventricle heart disease or has a morphologic systemic right ventricle. * Has undergone heart transplantation, is awaiting heart transplantation United Network for Organ Sharing (UNOS) Class 1A or equivalent, is receiving continuous IV infusion of an inotrope, or has an implanted ventricular assist device. * Has sustained or symptomatic dysrhythmia uncontrolled with drug or device therapy. * Has had recent cardiovascular (CV) surgical procedure or percutaneous intervention to palliate or correct congenital CV malformations. * Has unoperated or residual hemodynamically significant congenital cardiac malformations. * Has hypertrophic or restrictive cardiomyopathy. * Has active myocarditis or has been recently diagnosed with presumed or definitive myocarditis. * Has acute coronary syndrome, undergone recent coronary intervention, or indication for coronary revascularization. * Has symptomatic carotid stenosis or other symptomatic cerebrovascular disease * Has severe pulmonary hypertension. * Requires continuous home oxygen for significant pulmonary disease and/or has known interstitial lung disease. * Has severe chronic kidney disease. * Has hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities or Child Pugh Class C. * Has a gastrointestinal or biliary disorder that could impair absorption, metabolism, or excretion of medications. * Has significant bone disease (other than osteopenia) that in the assessment of the investigator can alter bone formation * Has concurrent or anticipated concomitant use of phosphodiesterase type 5 inhibitors or an sGC stimulator. * Has received a COVID-19 vaccination within 1 week before randomization.

Interventions

DRUG

Vericiguat tablet

DRUG

Vericiguat suspension

DRUG

Placebo tablet

DRUG

Placebo suspension

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Conditions

Heart FailureLeft Ventricular Systolic Dysfunction

Locations

The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 0002)

Los Angeles, California 90095

United States

Lucile Packard Children's Hospital ( Site 0040)

Palo Alto, California 94304

United States

Loma Linda University Health System ( Site 0008)

San Bernardino, California 92408

United States

Children's Hospital Colorado ( Site 0012)

Aurora, Colorado 80045

United States

Children's National Medical Center ( Site 0020)

Washington D.C., District of Columbia 20010

United States

Johns Hopkins All Children's Hospital ( Site 0029)

St. Petersburg, Florida 33701

United States

Children's Healthcare of Atlanta - Arthur M. Blank Hospital ( Site 0001)

Atlanta, Georgia 30329

United States

Boston Children's Hospital ( Site 0035)

Boston, Massachusetts 02115

United States

C.S. Mott Children's Hospital ( Site 0033)

Ann Arbor, Michigan 48109

United States

Washington University-Pediatric Cardiology/ St. Louis Children's Hospital ( Site 0006)

St Louis, Missouri 63110

United States

Columbia University Medical Center-Pediatric Cardiology ( Site 0016)

New York, New York 10032

United States

The Children's Hospital at Montefiore ( Site 0030)

The Bronx, New York 10467

United States

Cincinnati Children's Hospital Medical Center ( Site 0034)

Cincinnati, Ohio 45229

United States

Cleveland Clinic-Cleveland Clinic Chidren's ( Site 0022)

Cleveland, Ohio 44195

United States

Children's Hospital of Philadelphia (CHOP) ( Site 0004)

Philadelphia, Pennsylvania 19104

United States

Children's Hospital of Pittsburgh ( Site 0010)

Pittsburgh, Pennsylvania 15224

United States

Le Bonheur Children's Hospital ( Site 0007)

Memphis, Tennessee 38103

United States

Children's Health-The Heart Center ( Site 0015)

Dallas, Texas 75235

United States

Texas Children's Hospital ( Site 0039)

Houston, Texas 77030

United States

Seattle Children's Hospital-Cardiology/Fetal Therapy ( Site 0019)

Seattle, Washington 98105

United States

Centre Hospitalier Régional de la Citadelle ( Site 0302)

Liège, Liege 4000

Belgium

UZ Gent ( Site 0301)

Ghent, Oost-Vlaanderen 9000

Belgium

UZ Leuven ( Site 0300)

Leuven, Vlaams-Brabant 3000

Belgium

Instituto Dante Pazzanese de Cardiology ( Site 0402)

São Paulo, São Paulo 04012-909

Brazil

Incor - Instituto do Coracao ( Site 0400)

São Paulo, 05403-900

Brazil

Stollery Children's Hospital ( Site 0501)

Edmonton, Alberta T6G 2B7

Canada

Centre intégré universitaire de santé et de services sociaux-Centre de recherche du CHUS ( Site 0502)

Sherbrooke, Quebec J1H 5H4

Canada

Clinica Somer ( Site 0607)

Rionegro, Antioquia 054040

Colombia

Ciensalud Ips S A S ( Site 0608)

Barranquilla, Atlántico 08001

Colombia

Fundación Cardioinfantil Instituto de Cardiología ( Site 0603)

Bogotá, Bogota D.C. 110131

Colombia

Fundación Valle del Lili ( Site 0604)

Cali, Valle del Cauca Department 760032

Colombia

Clínica Imbanaco S.A.S ( Site 0602)

Cali, Valle del Cauca Department 760042

Colombia

Klinički bolnički centar Zagreb ( Site 3700)

Zagreb, City of Zagreb 10000

Croatia

Rigshospitalet-BørneUngeAfdelingen ( Site 0800)

Copenhagen, Capital Region DK-2100

Denmark

Tampereen yliopistollinen sairaala-Pediatric Early Phase Trials Unit ( Site 0900)

Tampere, Pirkanmaa 33520

Finland

CHU Bordeaux Haut-Leveque ( Site 1000)

Pessac, Aquitaine 33600

France

Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes ( Site 1002)

Nantes, Loire-Atlantique 44093

France

CHU Lille - Institut Coeur Poumon ( Site 1005)

Lille, Nord 59037

France

Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1003)

Marseille, Provence-Alpes-Côte d'Azur Region 13005

France

Hôpital Universitaire Necker Enfants Malades ( Site 1001)

Paris, 75015

France

Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita ( Site 1004)

Paris, 75019

France

Universitaetsklinikum Freiburg ( Site 1102)

Freiburg im Breisgau, Baden-Wurttemberg 79106

Germany

Universitaetsklinikum Heidelberg ( Site 1100)

Heidelberg, Baden-Wurttemberg 69120

Germany

Kinderklinik des Uni-Klinikums Erlangen ( Site 1104)

Erlangen, Bavaria 91054

Germany

Medizinische Hochschule Hannover ( Site 1108)

Hanover, Lower Saxony 30625

Germany

Deutsches Herzzentrum Berlin ( Site 1101)

Berlin, 13353

Germany

Gottsegen György Országos Kardiovaszkuláris Intézet-Gyermeksziv Kozpont ( Site 1300)

Budapest, 1096

Hungary

Children's Health Ireland (CHI) at Crumlin ( Site 1400)

Dublin, D12 N512

Ireland

IRCCS Istituto Giannina Gaslini ( Site 1603)

Genoa, Liguria 16147

Italy

Ospedale dei Bambini "Vittore Buzzi" ( Site 1606)

Milan, Lombardy 20154

Italy

Ospedale Infantile Regina Margherita ( Site 1604)

Turin, Piedmont 10126

Italy

Ospedale Pediatrico Bambino Gesù IRCCS ( Site 1602)

Rome, Roma 00165

Italy

A.O.Universitaria Meyer ( Site 1600)

Florence, Tuscany 50139

Italy

Azienda Ospedale - Università Padova ( Site 1601)

Padova, Veneto 35128

Italy

Hospital Universiti Sains Malaysia ( Site 1703)

Kota Bharu, Kelantan 16150

Malaysia

University Malaya Medical Centre ( Site 1701)

Lembah Pantai, Kuala Lumpur 59100

Malaysia

Hospital Queen Elizabeth II ( Site 1706)

Kota Kinabalu, Sabah Kota Kinab

Malaysia

Hospital Tunku Azizah-Paediatric ( Site 1700)

Kuala Lumpur, 50300

Malaysia

Institut Jantung Negara ( Site 1705)

Kuala Lumpur, 50400

Malaysia

Morales Vargas Centro de Investigacion ( Site 1810)

León, Guanajuato 37000

Mexico

CINVEC Medica ( Site 1814)

Guadalajara, Jalisco 44690

Mexico

Instituto Nacional de Pediatria ( Site 1803)

Mexico City, Mexico City 04530

Mexico

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"-Pediatria ( Site 1816)

Monterrey, Nuevo León 66460

Mexico

INVECORDIS S.C. ( Site 1808)

Hacienda de Las Palmas, State of Mexico 52763

Mexico

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 1800)

Ciudad Madero, Tamaulipas 89440

Mexico

Centro de Atención e Investigación Clínica ( Site 1813)

Aguascalientes, 20129

Mexico

UROLAP ( Site 1812)

Colima, 28000

Mexico

Instituto Nacional de Cardiologia Ignacio Chavez ( Site 1804)

México, 14080

Mexico

Erasmus Medisch Centrum ( Site 1900)

Rotterdam, South Holland 3015 CN

Netherlands

University Medical Center Groningen ( Site 1901)

Groningen, 9713 GZ

Netherlands

Universitair Medisch Centrum Utrecht ( Site 1902)

Utrecht, 3584 CX

Netherlands

Auckland City Hospital ( Site 2000)

Auckland, 1023

New Zealand

Instituto Nacional Cardiovascular INCOR Carlos Peschiera Carrillo - EsSalud ( Site 2100)

Jesús María, Lima 15072

Peru

Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca ( Site 2302)

Gdansk, Pomeranian Voivodeship 80-952

Poland

Unidade Local de Saude Lisboa Ocidental - Hospital de Santa Cruz ( Site 2401)

Lisbon, Lisbon District 2790-134

Portugal

Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 2402)

Lisbon, 1649-035

Portugal

Unidade Local de Saúde de São João ( Site 2403)

Porto, 4200-319

Portugal

Childrens University Hospital ( Site 4200)

Belgrade, Beograd 11000

Serbia

Institut za zdravstvenu zastitu majke i deteta Srbije ( Site 4220)

Belgrade, Beograd 11000

Serbia

Institute for Child and Youth Helth Care of Vojvodina ( Site 4210)

Novi Sad, Vojvodina 21000

Serbia

National University Hospital-Paediatrics ( Site 2600)

Singapore, South West 119074

Singapore

KK Women's and Children's Hospital ( Site 2601)

Singapore, South West 229899

Singapore

TREAD Research ( Site 2700)

Cape Town, Western Cape 7500

South Africa

Children's Heart Disease Research Unit ( Site 2704)

Cape Town, Western Cape 7700

South Africa

Pusan National University Yangsan Hospital ( Site 2802)

Pusan, Kyongsangnam-do 50612

South Korea

Seoul National University Hospital ( Site 2803)

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System ( Site 2800)

Seoul, 03722

South Korea

Samsung Medical Center ( Site 2801)

Seoul, 06351

South Korea

Hospital Sant Joan de Déu-Pediatric cardiology ( Site 2902)

Esplugues de Llobregat, Barcelona 08950

Spain

Hospital Universitari Vall d'Hebron ( Site 2903)

Barcelona, Catalonia 08035

Spain

Hospital Materno-Infantil Teresa Herrera ( Site 2905)

A Coruña, La Coruna 15009

Spain

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 2904)

Madrid, Madrid, Comunidad de 28007

Spain

Hospital Universitario La Paz ( Site 2912)

Madrid, 28046

Spain

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2907)

Seville, 41013

Spain

Skånes Universitetssjukhus Lund ( Site 3000)

Lund, Skåne County 22185

Sweden

Astrid Lindgrens Barnsjukhus ( Site 3001)

Solna, Stockholm County 171 64

Sweden

Faculty of Medicine Siriraj Hospital ( Site 3200)

Bangkoknoi, Bangkok 10700

Thailand

Faculty of Medicine - Khon Kaen University ( Site 3202)

Muang, Changwat Khon Kaen 40002

Thailand

Maharaj Nakorn Chiang Mai Hospital-Department of Pediatrics ( Site 3201)

Chiang Mai, 50200

Thailand

Hacettepe Universite Hastaneleri ( Site 3304)

Ankara, 06230

Turkey (Türkiye)

Baskent Universitesi Ankara Hastanesi ( Site 3301)

Ankara, 06490

Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi. ( Site 3300)

Ankara, 06800

Turkey (Türkiye)

Dr. Siyami Ersek Göğüs Kalp Ve Damar Cerrahisi Eğitim Ve Araştırma Hastanesi ( Site 3302)

Istanbul, 34668

Turkey (Türkiye)

S.B.Ü. DR. BEHÇET UZ ÇOCUK HASTALIKLARI VE CERRAHİSİ EĞİTİM VE ARAŞTIRMA HASTANESİ ( Site 3303)

Izmir, 35210

Turkey (Türkiye)

Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 3401)

London, London, City of WC1N 3JH

United Kingdom

Freeman Hospital ( Site 3400)

Newcastle upon Tyne, NE7 7DN

United Kingdom