A Study to Learn More About How Safe Finerenone is, When it is Taken for a Longer Time With Standard Treatment, in Children and Young Adults With Heart Failure and Left Ventricular Systolic Dysfunction

Official title

A Phase 3, Single-arm, Open-label Extension Study to Evaluate the Safety of Finerenone in Addition to Standard of Care, in Pediatric Heart Failure Patients, From Birth to 18 Years of Age, With Left Ventricular Systolic Dysfunction (LVSD)

Overview

Researchers are looking for a better way to treat children and young adults who have heart failure with left ventricular systolic dysfunction (LVSD). Heart failure with left ventricular systolic dysfunction (LVSD) is a condition where the left side of the heart is weak and struggles to pump blood effectively, leading to symptoms like shortness of breath, fatigue, and poor growth. The study treatment, finerenone (also called BAY94-8862), is under development to treat newborns, children, and young adults with heart failure and LVSD. It works by blocking a protein that contributes to inflammation, scarring, and thickening in the heart and blood vessels, which may help the heart pump more blood effectively. The main purpose of this study is to learn about how safe finerenone is and how well it works in the long-term treatment of heart failure and LVSD. To understand how safe the treatment is, the study team will gather information on the number of patients who experience medical problems after taking finerenone, also known as "treatment emergent adverse events" (TEAEs). Additionally, they will collect blood samples to measure levels of an electrolyte called potassium and monitor blood pressure. They will also assess kidneys function using the estimated glomerular filtration rate (eGFR). In this study, which is an extension of the earlier done FIORE study, finerenone will also be studied in newly enrolled newborns under 6 months with heart failure and LVSD and children and young adults from the FIORE study. The participants will be aged from newborns up to 18 years. All the participants will continue to receive their standard treatment as routine care for heart failure, along with finerenone during the study. The participants will be in the study for around 10 to 11 months, depending on whether they rolled-over from the FIORE study or are newly enrolled newborns and infants \<6 months of age. They will take study treatment for up to 9 months. During this period, at least 6 visits are planned for participants. During these visits, the study team will: * have their blood pressure, heart rate, temperature, respiratory rate, height and weight measured * have blood samples taken * have physical examinations * have their heart examined by an electrocardiogram and echocardiography * answer questions about their medication and whether they have any adverse events, or have their parents or guardians' answer * for newborns and infants, evaluate the acceptability of the study drug formulation through parents or guardians' feedback. 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. The doctors will check the participants' health a month after the participants take their last treatment.

Interventions

• Drug Finerenone (Kerendia, BAY94-8862)
  Finerenone in different doses, treatment duration will be 270±7 days.

Primary outcome measures

• Number of participants with treatment-emergent adverse events (TEAEs) [Time frame: From the start of study intervention to last study intervention (up to 277 days) + 3 days]
• Change in serum potassium levels [Time frame: From baseline to Day 270±7]
• Change in systolic blood pressure (SBP) [Time frame: From baseline to Day 270±7]
• Change in estimated glomerular filtration rate (eGFR) [Time frame: From baseline to Day 270±7]

Secondary outcome measures (5)

• Change in NT-proBNP levels [Time frame: From baseline to Day 270±7]
• Change in left ventricular systolic function [Time frame: From baseline to Day 270±7]
• 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 270±7]
• 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 270±7]
• Taste and Texture Questionnaire of the pediatric formulation [Time frame: On Day 30±3 and Day 270±7]

Eligibility criteria

Inclusion criteria

• For participants rolling over from randomized controlled trial (RCT): Prior participation in the finerenone Phase 3 study FIORE (21466) and not permanently discontinued from the study intervention prior to the end of treatment (EoT) visit in FIORE.
• For newly enrolled infants <6 months of age: Left ventricular systolic dysfunction (LVSD) with left ventricular ejection fraction (LVEF) ≤ 50% at screening assessed by echocardiography.
• For newly enrolled infants <6 months of age: Elevated NT-pro BNP levels (> 500 mg/L) at screening.
• For newly enrolled infants <6 months of age: Heart failure (HF) etiologies include 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 at least 3 months prior to treatment assignment); neuromuscular disorder; inborn error of metabolism; mitochondrial disorder; acquired (chemotherapy, iatrogenic, infection, rheumatic, or nutritional); ischemic (e.g., Kawasaki disease and postoperative HF); LV noncompaction.
• For newly enrolled infants <6 months of age: Receiving standard of care (SoC) treatment for heart failure according to local guidelines or investigator´s discretion (on a stable regimen for 30 days before baseline).
• Newly enrolled newborns and infants < 6 months of age must have a body weight of ≥3 kg at Visit 1.

Exclusion criteria

• For participants rolling over from randomized controlled trial (RCT): To roll-over to FIORELLO, all participants: Potassium (K+) >5.5 mmol/L. After unblinding:

• For participants who received finerenone in FIORE: K+ >5.5 mmol/ L
• For participants who received placebo in FIORE: K+ >5.0 mmol/L for children ≥2 years of age, and >5.3 mmol/L for children <2 years of age (if eGFR is <60 mL/min/1.73m² for participants <2 years of age, the serum potassium threshold of >5.0 mmol/L will be used for exclusion)
• For newly enrolled newborns and infants < 6 months of age: Potassium ≥ 5.3 mmol/l (if eGFR is <60 mL/min/1.73m², the serum potassium threshold of >5.0 mmol/L will be used for exclusion).
• For participants rolling over from RCT: Severe renal dysfunction with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m² at FIORE EoT or Visit 1.
• For newly enrolled infants < 6 months of age: Severe renal dysfunction with eGFR < 30 ml/min/1.73m2 at screening or Visit 1.
• Treatment with a mineralocorticoid receptor antagonist, other than the study intervention, (e.g., spironolactone, eplerenone) within 30 days of Visit 1.
• Requirement of any intravenous (IV) vasoactive agents; mechanical ventilation; mechanical circulatory support; sustained or symptomatic arrhythmias not controlled by drug or device therapy within 30 days prior to study treatment.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

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
• 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 — Buenos Aires
• Consultorios Médicos Dr. Doreski — Buenos Aires
• Hospital General de Ninos Ricardo Gutierrez | Cardiology Department — 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
• Azienda Ospedaliera Dei Colli_Monaldi - Malattie Rare e Genetiche Cardiovascolari — Naples
• … and 3 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 Antwerpen - Pediatric Cardiology — Edegem
• Cliniques Universitaires St-Luc (UCL) - Pediatric Cardiology — Brussels
• UZ Gent - Pediatric Cardiology — Ghent
• UZ Leuven - Pediatric Cardiology — Leuven
• 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

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

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

Finland · 1 center

• 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: NCT07192952 · 21467 · 2024-519830-22-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗