Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
- Conditions
- Left Ventricular Systolic DysfunctionHeart Failure
- Interventions
- Registration Number
- NCT05714085
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 342
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Base Period: Vericiguat Vericiguat tablet Participants in the Base Period receive 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form for 52 weeks; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form for 52 weeks. Base Period: Vericiguat Vericiguat suspension Participants in the Base Period receive 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form for 52 weeks; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form for 52 weeks. Base Period: Placebo Placebo tablet Participants in the Base Period receive placebo for vericiguat administered orally once daily in tablet form for 52 weeks, or administered orally once daily in suspension form for 52 weeks. Base Period: Placebo Placebo suspension Participants in the Base Period receive placebo for vericiguat administered orally once daily in tablet form for 52 weeks, or administered orally once daily in suspension form for 52 weeks. Extension Period: Vericiguat Vericiguat tablet Participants in the Extension Period receive either 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form; following completion of the Base Period. Extension Period: Vericiguat Vericiguat suspension Participants in the Extension Period receive either 2.5 mg or 5 mg or 10 mg vericiguat administered orally once daily in tablet form; or 0.2 mg/mL or 1 mg/mL vericiguat administered orally once daily in suspension form; following completion of the Base Period.
- Primary Outcome Measures
Name Time Method Base Period: Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) Baseline and Week 16 of Base Period The change from baseline to Week 16 of the Base Period in log-transformed NT-proBNP will be reported.
Extension Period: Percentage of participants with one or more adverse events (AEs) Includes data collected up to a maximum of approximately 8 years An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with one or more AEs in the Extension Period will be reported.
Extension Period: Percentage of participants who discontinued study drug due to an AE Includes data collected up to a maximum of approximately 8 years An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug in the Extension Period due to an AE will be reported.
- Secondary Outcome Measures
Name Time Method Base Period: Change from baseline to Week 52 in log-transformed NT-proBNP Baseline and Week 52 of Base Period The change from baseline to Week 52 of the Base Period in log-transformed NT-proBNP will be reported.
Base Period: First event of cardiovascular (CV) death, heart failure hospitalization (HFH), or worsening of heart failure (HF) without hospitalization Up to Week 54 of Base Period The time from randomization to the first event of CV death, HFH, or worsening of HF without hospitalization will be reported for the Base Period.
Base Period: Percentage of participants with one or more adverse events (AEs) Up to Week 54 of Base Period An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with one or more AEs in the Base Period will be reported.
Base Period: Percentage of participants who discontinued study drug due to an AE Up to Week 52 of Base Period An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug in the Base Period due to an AE will be reported.
Base Period: Area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period) Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat.
Base Period: Half-life (t1/2) of vericiguat in plasma Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period) Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the t1/2 of vericiguat in plasma.
Base Period: Oral clearance (CL/F) of plasma vericiguat Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose (Base Period) Blood samples were collected at pre-specified time points pre- and post-dose and used to estimate the CL/F of vericiguat in plasma.
Extension Period: Change from extension period baseline to extension period Week 16 in NT-proBNP Extension Period Baseline (Study Week 54) and Extension Period Week 16 (Study Week 70) The change from the Extension Period baseline to Week 16 of the Extension Period in log-transformed NT-proBNP will be reported.
Trial Locations
- Locations (91)
Loma Linda University Health System ( Site 0008)
🇺🇸Loma Linda, California, United States
The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 0002)
🇺🇸Los Angeles, California, United States
Children's Hospital Colorado ( Site 0012)
🇺🇸Aurora, Colorado, United States
Children's National Medical Center ( Site 0020)
🇺🇸Washington, District of Columbia, United States
Johns Hopkins All Children's Hospital ( Site 0029)
🇺🇸Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta - Arthur M. Blank Hospital ( Site 0001)
🇺🇸Atlanta, Georgia, United States
C.S. Mott Children's Hospital ( Site 0033)
🇺🇸Ann Arbor, Michigan, United States
Washington University-Pediatric Cardiology/ St. Louis Children's Hospital ( Site 0006)
🇺🇸Saint Louis, Missouri, United States
The Children's Hospital at Montefiore ( Site 0030)
🇺🇸Bronx, New York, United States
Columbia University Medical Center-Pediatric Cardiology ( Site 0016)
🇺🇸New York, New York, United States
Cincinnati Children's Hospital Medical Center ( Site 0034)
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic-Cleveland Clinic Chidren's ( Site 0022)
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia (CHOP) ( Site 0004)
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh ( Site 0010)
🇺🇸Pittsburgh, Pennsylvania, United States
Le Bonheur Children's Hospital ( Site 0007)
🇺🇸Memphis, Tennessee, United States
Children's Health-The Heart Center ( Site 0015)
🇺🇸Dallas, Texas, United States
Seattle Children's Hospital-Cardiology/Fetal Therapy ( Site 0019)
🇺🇸Seattle, Washington, United States
Centre Hospitalier Régional de la Citadelle ( Site 0302)
🇧🇪Liège, Liege, Belgium
UZ Gent ( Site 0301)
🇧🇪Gent, Oost-Vlaanderen, Belgium
UZ Leuven ( Site 0300)
🇧🇪Leuven, Vlaams-Brabant, Belgium
Instituto Dante Pazzanese de Cardiology ( Site 0402)
🇧🇷São Paulo, Sao Paulo, Brazil
Incor - Instituto do Coracao ( Site 0400)
🇧🇷Sao Paulo, Brazil
Stollery Children's Hospital ( Site 0501)
🇨🇦Edmonton, Alberta, Canada
Centre intégré universitaire de santé et de services sociaux-Centre de recherche du CHUS ( Site 0502)
🇨🇦Sherbrooke, Quebec, Canada
Clinica Somer ( Site 0607)
🇨🇴Rionegro., Antioquia, Colombia
Ciensalud Ips S A S ( Site 0608)
🇨🇴Barranquilla, Atlantico, Colombia
Fundación Cardioinfantil Instituto de Cardiología ( Site 0603)
🇨🇴Bogotá, Distrito Capital De Bogota, Colombia
Fundación Valle del Lili ( Site 0604)
🇨🇴Cali, Valle Del Cauca, Colombia
Clínica Imbanaco S.A.S ( Site 0602)
🇨🇴Cali, Valle Del Cauca, Colombia
Rigshospitalet-BørneUngeAfdelingen ( Site 0800)
🇩🇰Copenhagen, Hovedstaden, Denmark
Tampereen yliopistollinen sairaala-Pediatric Early Phase Trials Unit ( Site 0900)
🇫🇮Tampere, Pirkanmaa, Finland
CHU Bordeaux Haut-Leveque ( Site 1000)
🇫🇷Pessac, Aquitaine, France
CHU Lille - Institut Coeur Poumon ( Site 1005)
🇫🇷Lille Cedex, Nord, France
Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes ( Site 1002)
🇫🇷Nantes, Pays-de-la-Loire, France
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1003)
🇫🇷Marseille, Provence-Alpes-Cote-d Azur, France
Hôpital Universitaire Necker Enfants Malades ( Site 1001)
🇫🇷Paris, France
Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita ( Site 1004)
🇫🇷Paris, France
Universitaetsklinikum Freiburg ( Site 1102)
🇩🇪Freiburg, Baden-Wurttemberg, Germany
Universitaetsklinikum Heidelberg ( Site 1100)
🇩🇪Heidelberg, Baden-Wurttemberg, Germany
Kinderklinik des Uni-Klinikums Erlangen ( Site 1104)
🇩🇪Erlangen, Bayern, Germany
Medizinische Hochschule Hannover ( Site 1108)
🇩🇪Hannover, Niedersachsen, Germany
Deutsches Herzzentrum Berlin ( Site 1101)
🇩🇪Berlin, Germany
Gottsegen György Országos Kardiovaszkuláris Intézet-Gyermeksziv Kozpont ( Site 1300)
🇭🇺Budapest, Hungary
Children's Health Ireland (CHI) at Crumlin ( Site 1400)
🇮🇪Dublin, Ireland
IRCCS Istituto Giannina Gaslini ( Site 1603)
🇮🇹Genova, Liguria, Italy
A.O.Universitaria Meyer ( Site 1600)
🇮🇹Firenze, Toscana, Italy
Pusan National University Yangsan Hospital ( Site 2802)
🇰🇷Pusan, Kyongsangnam-do, Korea, Republic of
Seoul National University Hospital ( Site 2803)
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System ( Site 2800)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 2801)
🇰🇷Seoul, Korea, Republic of
University Malaya Medical Centre ( Site 1701)
🇲🇾Lembah Pantai, Kuala Lumpur, Malaysia
Hospital Tunku Azizah-Paediatric ( Site 1700)
🇲🇾Kuala Lumpur, Malaysia
Institut Jantung Negara ( Site 1705)
🇲🇾Kuala Lumpur, Malaysia
Instituto Nacional de Pediatria ( Site 1803)
🇲🇽Mexico City, Distrito Federal, Mexico
Morales Vargas Centro de Investigacion ( Site 1810)
🇲🇽León, Guanajuato, Mexico
Hospital Universiti Sains Malaysia ( Site 1703)
🇲🇾Kota Bharu, Kelantan, Malaysia
CINVEC Medica ( Site 1814)
🇲🇽Guadalajara, Jalisco, Mexico
Centro de Atención e Investigación Clínica ( Site 1813)
🇲🇽Aguascalientes, Mexico
INVECORDIS S.C. ( Site 1808)
🇲🇽Hacienda De Las Palmas, Mexico
Instituto Nacional de Cardiologia Ignacio Chavez ( Site 1804)
🇲🇽Mexico, Mexico
Erasmus Medisch Centrum ( Site 1900)
🇳🇱Rotterdam, Zuid-Holland, Netherlands
University Medical Center Groningen ( Site 1901)
🇳🇱Groningen, Netherlands
Universitair Medisch Centrum Utrecht ( Site 1902)
🇳🇱Utrecht, Netherlands
Auckland City Hospital ( Site 2000)
🇳🇿Auckland, New Zealand
Instituto Nacional Cardiovascular INCOR Carlos Peschiera Carrillo - EsSalud ( Site 2100)
🇵🇪Jesús María, Lima, Peru
Uniwersyteckie Centrum Kliniczne-Klinika Kardiologii Dziecięcej i Wad Wrodzonych Serca ( Site 2302)
🇵🇱Gdańsk, Pomorskie, Poland
Unidade Local de Saude Lisboa Ocidental - Hospital de Santa Cruz ( Site 2401)
🇵🇹Lisbon, Lisboa, Portugal
Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 2402)
🇵🇹Lisboa, Portugal
Unidade Local de Saúde de São João ( Site 2403)
🇵🇹Porto, Portugal
National University Hospital-Paediatrics ( Site 2600)
🇸🇬Singapore, South West, Singapore
KK Women's and Children's Hospital ( Site 2601)
🇸🇬Singapore, South West, Singapore
TREAD Research ( Site 2700)
🇿🇦Cape Town, Western Cape, South Africa
Children's Heart Disease Research Unit ( Site 2704)
🇿🇦Cape Town, Western Cape, South Africa
Hospital Sant Joan de Déu-Pediatric cardiology ( Site 2902)
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Hospital Universitari Vall d'Hebron ( Site 2903)
🇪🇸Barcelona, Cataluna, Spain
Hospital Materno-Infantil Teresa Herrera ( Site 2905)
🇪🇸A Coruna, La Coruna, Spain
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 2904)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario La Paz ( Site 2912)
🇪🇸Madrid, Madrid, Comunidad De, Spain
HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2907)
🇪🇸Sevilla, Spain
Skånes Universitetssjukhus Lund ( Site 3000)
🇸🇪Lund, Skane Lan, Sweden
Astrid Lindgrens Barnsjukhus ( Site 3001)
🇸🇪Stockholm, Stockholms Lan, Sweden
Faculty of Medicine - Khon Kaen University ( Site 3202)
🇹🇭Muang, Khon Kaen, Thailand
Faculty of Medicine Siriraj Hospital ( Site 3200)
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Maharaj Nakorn Chiang Mai Hospital-Department of Pediatrics ( Site 3201)
🇹🇭Chiang Mai, Thailand
Hacettepe Universite Hastaneleri ( Site 3304)
🇹🇷Ankara, Turkey
Baskent Universitesi Ankara Hastanesi ( Site 3301)
🇹🇷Ankara, Turkey
Ankara Bilkent Şehir Hastanesi. ( Site 3300)
🇹🇷Ankara, Turkey
Dr. Siyami Ersek Göğüs Kalp Ve Damar Cerrahisi Eğitim Ve Araştırma Hastanesi ( Site 3302)
🇹🇷Istanbul, Turkey
S.B.Ü. DR. BEHÇET UZ ÇOCUK HASTALIKLARI VE CERRAHİSİ EĞİTİM VE ARAŞTIRMA HASTANESİ ( Site 3303)
🇹🇷Izmir, Turkey
Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 3401)
🇬🇧London, London, City Of, United Kingdom
Freeman Hospital ( Site 3400)
🇬🇧Newcastle upon Tyne, United Kingdom