A Study to Learn More About How Well Finerenone Works, How Safe it is, and How it Moves Into, Through, and Out of the Body Compared to Placebo When Taken With Standard Treatment in Children With Heart Failure and Left Ventricular Systolic Dysfunction

Official title

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Investigate the Efficacy, Safety, and PK/ PD of Finerenone, in Addition to Standard-of-care, in Pediatric Patients, 6 Months to < 18 Years of Age With Heart Failure (HF) and Left Ventricular Systolic Dysfunction (LVSD)

Overview

Researchers are looking for a better way to treat children who have heart failure with left ventricular systolic dysfunction (LVSD). Heart failure is a serious condition where the heart is unable to pump enough blood to meet the body's needs. This can lead to symptoms like shortness of breath, fatigue, and poor growth in children. The study treatment, finerenone (also called BAY94-8862), works by blocking a protein involved in inflammation, scarring, and thickening of the heart and blood vessels. This may help the heart to pump blood more effectively. This is the first study to explore its use specifically for children with heart failure and LVSD. The main purpose of this study is to learn if finerenone works to help the heart compared to placebo in children with heart failure and LVSD. For this, the researchers will collect and analyze data on the levels of a protein called NT-proBNP in the blood, which indicates heart stress, and monitor the safety of the treatment. The study will include children with heart failure and LVSD aged from 6 months to less than 18 years. The study participants will be randomly assigned to one of two treatment groups. Based on their group, they will receive either finerenone or a placebo for a duration of 3 months. A placebo looks like a treatment but does not have any medicine in it. Throughout the study, all participants will continue to receive their standard heart failure treatments. At the start of this study, the doctors will check each participant's medical history and current medications. If participants qualify for the treatment phase, they will undergo treatment for about 90 days. During this time, they will visit the study site at least 3 times. During these visits, the participants will: * have their blood pressure, heart rate, temperature, respiratory rate, height and weight measured * have their heart examined by electrocardiogram (ECG) and echocardiogram * have blood samples taken * have physical examinations * answer questions about their medication and whether they have any adverse events, or have their parents or guardians' answers An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. After the initial three-month study, eligible participants will have the option to join a nine-month open-label extension study where all will receive finerenone. Participants who choose not to enroll in the extension will have a follow-up visit 30 days after their last treatment.

Interventions

• Drug Finerenone (Kerendia, BAY94-8862)
  Finerenone in different doses, treatment duration will be 90±3 days
• Drug Placebo
  Placebo to finerenone, treatment duration will be 90±3 days

Primary outcome measures

• Change in NT-proBNP levels [Time frame: From baseline to Day 90±3]

Secondary outcome measures (8)

• Number of participants with treatment-emergent adverse events (TEAEs) [Time frame: From the start of study intervention to last study intervention (up to 93 days) + 3 days]
• Change in serum potassium levels [Time frame: From baseline to Day 90±3]
• Change in estimated glomerular filtration rate (eGFR) [Time frame: From baseline to Day 90±3]
• Change in systolic blood pressure (SBP) [Time frame: From baseline to Day 90±3]
• Change in left ventricular systolic function [Time frame: From baseline to Day 90±3]
• Total number of cardiovascular outcome events, including cardiovascular death, heart transplantation, and clinical worsening of heart failure [Time frame: From baseline to Day 90±3]
• Maximum observed finerenone concentration in plasma after multiple doses (Cmax, md) [Time frame: Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 90±3]
• Area under the curve for finerenone concentration in plasma after multiple doses (AUCτ,md) [Time frame: Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 90±3]

Eligibility criteria

Inclusion criteria

• Participants must be 6 months to <18 years old at the time when the informed consent/assent is signed.
• Left ventricular systolic dysfunction (LVSD) with left ventricular ejection fraction (LVEF) ≤ 50% at screening assessed by echocardiography.
• Elevated NT-pro BNP levels

• >500 ng/l for children ≥ 6 months to < 2 years of age
• >300 ng/l, for children ≥ 2 years to <18 years
• Heart failure etiologies including congenital heart defects (CHD) with biventricular physiology and systemic LV; idiopathic cardiomyopathy (CM); familial/inherited and/or genetic CM; history of myocarditis (diagnosis of an acute episode was at least 3 months prior to randomization); neuromuscular disorder (eg, duchenne muscular dystrophy); inborn error of metabolism; mitochondrial disorder; acquired (chemotherapy, iatrogenic, infection, rheumatic, or nutritional); ischemic (eg, Kawasaki disease and postoperative heart failure \[HF\]); LV noncompaction.
• Receiving standard of care (SoC) treatment for heart failure according to local guidelines or investigator´s discretion and being on a stable regimen for 30 days prior to randomization.
• Study participants must have a body weight ≥ 4.0 kg at Visit 1.

Exclusion criteria

• Serum potassium:

• > 5.0 mmol/L for children ≥ 2 years of age at either screening or randomization visit
• > 5.3 mmol/L for children ≥ 6 months to < 2 years of age at either screening or randomization visit (if estimated glomerular filtration rate \[eGFR\] < 60 mL/min/1.73m², threshold of > 5.0 mmol/L will be used)
• Severe renal dysfunction with eGFR < 30 ml/min/1.73m² at screening or randomization visit.
• Systolic blood pressure (SBP) < 5th percentile for age, sex and height at screening or randomization.
• Sustained or symptomatic arrhythmias not controlled by drug or device therapy within 30 days prior to randomization.
• Treatment with a mineralocorticoid receptor antagonist (e.g., spironolactone, eplerenone) within 30 days of randomization.
• Requirement of any intravenous (IV) vasoactive agents, mechanical ventilation, mechanical circulatory support within 30 days prior to randomization.
• Recent surgical procedure or other intervention to correct or palliate CHD within 3 months prior to randomization or anticipated to undergo cardiac surgery during the 3 months after randomization.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 22 centers

• Children's Hospital Colorado - Anschutz Medical Campus - Cardiology — Aurora
• Nemours Children's Hospital - Delaware - Cardiology — Wilmington
• UF Health Shands Hospital - Pediatric Cardiology — Gainesville
• Joe Dimaggio Children's Hospital - Cardiology — Hollywood
• Emory University Hospital - Children's Healthcare of Atlanta Cardiology - Atlanta — Atlanta
• Riley Hospital For Children - Cardiology — Indianapolis
• Boston Children's Hospital - Main Campus - Cardiology — Boston
• C.S. Mott Children's Hospital - Cardiology — Ann Arbor
• … and 14 more centers

Argentina · 10 centers

• Hospital de Niños Sor María Ludovica — La Plata
• Instituto De Investigaciones Clinicas Zarate | Zarate, Argentina — Zárate
• Hospital General de Ninos Ricardo Gutierrez | Cardiology Department — Buenos Aires
• Consultorios Integrados Rosario | Instituto Medico de la Fundacion de Estudios Clinicos — Rosario
• Hospital Italiano de Buenos Aires — Buenos Aires
• Hospital de Pediatría Juan P. Garrahan — Buenos Aires
• Hospital General de Ninos Pedro de Elizalde | Nephrology Department — Ciudad Autonoma de Buenos Aire
• Consultorios Médicos Dr. Doreski — Ciudad Autónoma de Buenos Aire
• … and 2 more centers

Brazil · 10 centers

• Hospital de Clínicas da Universidade Federal de Uberlândia Empresa Brasileira de Serviços — Uberlândia
• Hospital Pequeno Principe — Curitiba
• Centro de Pesquisa Clinica e Populacional Hospitalize — Porto Alegre
• Fundação Universidade de Caxias do Sul — Marília
• Liga Alvaro Bahia Contra a Mortalidade Infantil - Hospital Martagão Gesteira — Salvador
• Hospital Infantil Sabará - Instituto PENSI - Pesquisa e Ensino em Saúde Infantil — São Paulo
• Instituto Dante Pazzanese de Cardiologia | Divisao de Pesquisa — São Paulo
• Campinas Clinical Research Institute (IPECC) | Campinas, Brazil — São Paulo
• … and 2 more centers

Italy · 8 centers

• Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - Cardiologia 2 - Cardiopatie Con — Bergamo
• Azienda Ospedaliero-Universitaria di Bologna IRCCS Policlinico Sant'Orsola-Cardiologia ped — Bologna
• IRCCS Istituto Giannina Gaslini - Cardiologia — Genova
• ASST Grande Ospedale Metropolitano Niguarda - Struttura semplice dipartimentale cardiologi — Milan
• … and 4 more centers

Mexico · 8 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 7 centers

Center list to be confirmed — check the primary protocol.

Canada · 6 centers

• Stollery Children's Hospital | Cardiology — Edmonton
• BC Children's Hospital | Children's Heart Centre — Vancouver
• Children's Hospital | Cardiology — London
• The Hospital for Sick Children (SickKids) — Toronto
• Centre hospitalier universitaire Sainte-Justine | Cardiology — Montreal
• Royal University Hospital | Cardiology — Saskatoon

Taiwan · 6 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 6 centers

Center list to be confirmed — check the primary protocol.

Belgium · 5 centers

• UZ Leuven - Pediatric Cardiology — Leuven
• Cliniques Universitaires St-Luc (UCL) - Pediatric Cardiology — Brussels
• UZ Antwerpen - Pediatric Cardiology — Edegem
• UZ Gent - Pediatric Cardiology — Ghent
• CHC MontLegia - Pediatric Cardiology — Liège

Israel · 5 centers

• Rambam Health Corporation — Haifa
• Edith Wolfson Medical Center (EWMC) — Holon
• Shaare Zedek Medical Center — Jerusalem
• Dana-Dwek Children's Hospital — Tel Aviv
• Chaim Sheba Medical Center — Tel Litwinsky

Portugal · 5 centers

Center list to be confirmed — check the primary protocol.

Bulgaria · 4 centers

• University Multiprofile Hospital for Active Treatment 'Sveti Georgi' EAD, Plovdiv Pediatri — Plovdiv
• National Heart Hospital (NHH) - Dept. Pediatric Cardiology — Sofia
• Medical Center Nora- Heart ?OOD Child Cardiology — Sofia
• University Multiprofile Hospital for Active Treatment 'Sveta Ekaterina' EAD, Sofia — Sofia

Greece · 4 centers

• Onassis Cardiac Surgery Center, Department of Pediatric Cardiology and Adult Congenital He — Kallithea
• Athens General Children's Hospital Panagioti And Aglaia Kyriakou -2nd University Departmen — Athens
• Athens General Children's Hospital Panagioti And Aglaia Kyriakou, Cardiology Department — Athens
• Nosokomeio Paidon I Agia Sofia, Cardiology Department — Athens

Poland · 4 centers

Center list to be confirmed — check the primary protocol.

South Korea · 4 centers

Center list to be confirmed — check the primary protocol.

Germany · 3 centers

• Universitaetsklinikum Giessen und Marburg GmbH - Kinderherzzentrum und Zentrum für angebor — Giessen
• Universitätsklinikum Köln - Kinderkardiologie — Cologne
• Universitätsklinikum Tübingen, Kinderheilkunde II - Kinderkardiologie, Pulmologie, Intensi — Tübingen

Austria · 2 centers

• Medizinische Universität Wien - Klinik für Kinder- und Jugendheilkunde, Abteilung für Pädi — Vienna
• Kepler Universitätsklinikum GmbH - Klinik für Kinderkardiologie — Innsbruck

Czechia · 2 centers

• Fakultní nemocnice Brno, Detská nemocnice - Pediatrická klinika — Brno
• Fakultní nemocnice Motol a Homolka, Pracovište MOTOL - Detské kardiocentrum 2. LF UK a FN — Prague

Finland · 2 centers

• Oulu University Hospital, Oulun yliopistollinen sairaala (OYS) - Lasten ja nuorten palvelu — Oulu
• HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Uusi lastensairaala, kardiologia — Helsinki

Hungary · 1 center

• Gottsegen Gyorgy Orszagos Kardiovaszkularis Intezet - Gyermeksziv Kozpont — Budapest

Sweden · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07188805 · 21466 · 2024-519829-38-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗