(21466) 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)

The primary objective is to evaluate the effect of finerenone in addition to standard of care on reducing NT-proBNP levels compared to placebo in pediatric patients with left ventricular systolic dysfunction. NT-proBNP is an established biomarker of cardiac stress and myocardial dysfunction, making its reduction clinically relevant as an indicator of improved cardiac function and potentially reduced disease progression in this population.

The secondary objectives include:

• To assess the safety profile of finerenone in addition to standard of care in pediatric left ventricular systolic dysfunction patients as compared to placebo

• To demonstrate the beneficial effect of finerenone in addition to standard of care as compared to placebo

• To confirm the dose and systemic exposure of finerenone in pediatric left ventricular systolic dysfunction patients

This clinical trial enrolled a total of **51 participants** ranging from **6 months to less than 18 years of age**. Both **male and female** subjects were included in the study population. All participants presented with **heart failure** due to systemic **left ventricular systolic dysfunction**, characterized by a **left ventricular ejection fraction** of 50% or less as assessed by echocardiography at screening. The study population comprised pediatric patients with elevated **NT-proBNP levels**, with specific thresholds defined by age: greater than 500 ng/L for children aged 6 months to less than 2 years, and greater than 300 ng/L for children aged 2 years to less than 18 years. Participants exhibited various etiologies of heart failure, including **congenital heart defects** with biventricular physiology and systemic left ventricle, **idiopathic cardiomyopathy**, familial or inherited and genetic cardiomyopathy, history of **myocarditis**, **neuromuscular disorders** such as Duchenne muscular dystrophy, inborn errors of metabolism, mitochondrial disorders, acquired causes including chemotherapy-related or iatrogenic origins, ischemic causes such as Kawasaki disease, and left ventricular noncompaction. All participants were receiving standard of care treatment for heart failure according to local guidelines or investigator discretion and maintained a stable treatment regimen for at least 30 days prior to randomization. A minimum body weight of 4.0 kg at the initial visit was required for study inclusion.

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 clinical trial evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of finerenone when added to standard-of-care treatment in pediatric patients aged 6 months to less than 18 years with heart failure and left ventricular systolic dysfunction. The study investigates heart failure due to systemic left ventricular systolic dysfunction in children with various underlying etiologies including congenital heart defects with biventricular physiology and systemic left ventricle, idiopathic cardiomyopathy, familial or inherited and genetic cardiomyopathy, history of myocarditis, neuromuscular disorders, inborn errors of metabolism, mitochondrial disorders, acquired causes, ischemic causes, and left ventricular noncompaction.

The primary objective is to evaluate the effect of finerenone in addition to standard of care on reducing NT-proBNP levels compared to placebo. The primary endpoint is the change in NT-proBNP from baseline to 3 months in participants receiving active study intervention compared to placebo. Secondary endpoints include the number of participants with treatment-emergent adverse events, change in serum potassium levels from baseline to end of treatment, change in systolic blood pressure from baseline to end of treatment, change in renal function from baseline to end of treatment, change in echocardiographic parameters of left ventricular systolic function and size from baseline to end of treatment, total number of cardiovascular outcome events including cardiovascular death, heart transplantation, and clinical worsening of heart failure from baseline to end of treatment, maximum observed finerenone concentration in plasma after multiple doses, and area under the curve for finerenone concentration in plasma after multiple doses.

Eligible participants must be 6 months to less than 18 years old at the time of informed consent or assent, have left ventricular systolic dysfunction with left ventricular ejection fraction equal to or less than 50% at screening assessed by echocardiography, and elevated NT-proBNP levels greater than 500 ng/L for children aged 6 months to less than 2 years or greater than 300 ng/L for children aged 2 years to less than 18 years. Participants must be receiving standard of care treatment for heart failure according to local guidelines or investigator's discretion and be on a stable regimen for 30 days prior to randomization. Study participants must have a body weight equal to or greater than 4.0 kg at the screening visit.

The investigational medicinal products include finerenone administered as film-coated tablets in doses of 10 mg, 20 mg, and 40 mg, finerenone administered as granules for oral suspension with a maximum daily dose of 40 mg, and matching placebo formulations. All active formulations are administered via the oral route. The maximum treatment period for the active intervention is 3 months. Dosing devices for the oral suspension formulation include various syringes and adapters with locking mechanisms for oral administration of liquids.

The estimated recruitment start date is November 2025, with an estimated study end date in December 2029. The overall trial duration encompasses the recruitment period, treatment phase, and follow-up assessments. Participant involvement includes a screening visit to assess eligibility criteria, randomization to either finerenone or placebo in addition to standard of care, regular study visits during the 3-month treatment period for safety and efficacy assessments, and an end-of-study visit. Conditions that may lead to early termination from the study are not specified in the available data.

The experimental medication finerenone (also designated as BAY 94-8862) is administered as the active investigational product in this clinical trial. Finerenone is provided in multiple pharmaceutical formulations to accommodate different dosing requirements and patient populations. The medication is available as film-coated tablets in three different strengths, with maximum daily doses of 10 mg, 20 mg, and 40 mg. All tablet formulations are administered via the oral route. The maximum treatment period for the tablet formulations is 3 years. The active substance in all formulations is finerenone, which is of chemical origin.

An additional formulation of finerenone is provided as granules for oral suspension under the product name Finerenone Bayer (sponsor product code BAY 948862). This formulation has a maximum daily dose of 40 mg and a maximum total dose of 40 mg, administered orally over a maximum treatment period of 3 years. This oral suspension formulation is supplied with multiple dosing devices to ensure accurate administration. The dosing devices include liquid dosing devices with locking mechanisms in volumes of 1 mL, 5 mL, and 10 mL for oral administration of liquids, an irrigation syringe with a capacity of 50 mL, a medical catheter syringe with a capacity of 100 mL without needle, and an adapter with locking mechanism for oral administration of liquids. All dosing devices are certified with CE marks.

Placebo is utilized as the comparator treatment in this double-blind, placebo-controlled study. Two placebo formulations are designated in the trial: Placebo BAY 948862 and Placebo BAY 948862 tablets. These placebo products are designed to match the active finerenone formulations to maintain blinding throughout the study. The placebo formulations contain no active pharmaceutical ingredient and serve as the control arm against which the efficacy and safety of finerenone in addition to standard-of-care therapy will be evaluated.

The primary efficacy endpoint is the change in NT-proBNP levels from baseline to 3 months in participants receiving finerenone compared to placebo. Secondary efficacy endpoints include changes in echocardiographic parameters of left ventricular systolic function and size from baseline to end of treatment. Additional secondary endpoints assess the change in serum potassium levels, systolic blood pressure, and renal function from baseline to end of treatment. The total number of cardiovascular outcome events, including cardiovascular death, heart transplantation, and clinical worsening of heart failure from baseline to end of treatment, will also be evaluated. Echocardiography will be utilized to measure left ventricular ejection fraction and other cardiac parameters. Laboratory tests will be performed to assess NT-proBNP levels, serum potassium, and renal function throughout the study. The treatment period is planned for 3 months with assessments conducted at baseline, at 3 months, and at end of treatment.