(21467) 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)

The primary objective is to demonstrate that finerenone in addition to standard of care is safe when administered long-term in pediatric patients with left ventricular systolic dysfunction (LVSD). This objective addresses the critical need to establish the long-term safety profile of finerenone in the pediatric heart failure population, ranging from birth to 18 years of age, where data on mineralocorticoid receptor antagonist therapy remains limited.

The secondary objectives include:

• To assess the long-term treatment effect of finerenone in addition to standard of care in pediatric LVSD patients, evaluating the sustained therapeutic benefit beyond initial treatment periods.

• To further confirm the systemic exposure of finerenone in pediatric LVSD patients, providing pharmacokinetic data essential for dose optimization in this age-diverse population.

• To assess the acceptability and palatability of the age-appropriate pediatric formulation in newborns less than 6 months of age, addressing practical considerations for medication administration in the youngest patient subgroup.

This clinical trial enrolled a total of **56 participants** comprising **pediatric patients** with **left ventricular systolic dysfunction** (LVSD) secondary to **heart failure**. The study population included both **male** and **female** subjects categorized as **newborns** and **infants** under 6 months of age, representing a vulnerable population. Participants were selected through two pathways: individuals rolling over from a prior randomized controlled trial (FIORE, study 21466) who had not permanently discontinued treatment, and newly enrolled infants under 6 months of age meeting specific clinical criteria. Newly enrolled participants were required to demonstrate LVSD with a **left ventricular ejection fraction** (LVEF) of 50% or less as assessed by **echocardiography**, elevated **NT-pro BNP levels** exceeding 500 mg/L at screening, and a minimum body weight of 3 kg or greater at enrollment. The etiologies of heart failure in this population encompassed a broad spectrum including **congenital heart defects** with biventricular physiology and systemic left ventricle, **idiopathic cardiomyopathy**, familial or genetic cardiomyopathy, history of **myocarditis**, **neuromuscular disorders**, **inborn errors of metabolism**, **mitochondrial disorders**, acquired causes such as chemotherapy-induced or infectious etiologies, **ischemic** causes including **Kawasaki disease**, and left ventricular noncompaction. All newly enrolled participants were maintained on stable standard of care treatment for heart failure according to local guidelines or investigator discretion for at least 30 days prior to baseline assessment.

This is a Phase 3, single-arm, open-label extension study designed to evaluate the long-term safety of **finerenone** administered in addition to **standard of care** in pediatric patients with **heart failure** and **left ventricular systolic dysfunction**. The study will enroll participants from birth to 18 years of age who either completed a previous randomized controlled trial or are newly enrolled infants younger than 6 months of age. The trial design does not include randomization or blinding, as all participants will receive active treatment with finerenone. The estimated study duration spans from February 2026 to December 2030, with an anticipated recruitment period beginning in early 2026.

The investigational medicinal product finerenone will be administered orally in various pharmaceutical formulations, including **film-coated tablets** and **granules for oral suspension**, to accommodate different age groups and body weights. Maximum daily doses range from 10 mg to 40 mg depending on the formulation used, with treatment administered daily over a period of 3 months. The oral suspension formulation is accompanied by several dosing devices to ensure accurate administration, including liquid dosing devices of various volumes, irrigation syringes, and adapters with locking mechanisms for oral administration. All participants must be receiving standard of care treatment for heart failure according to local guidelines or investigator discretion on a stable regimen for at least 30 days prior to baseline. Newly enrolled infants must have a body weight of at least 3 kg at the initial visit.

Eligible participants rolling over from the previous randomized controlled trial must have completed the study without permanent discontinuation of the study intervention prior to the end of treatment visit. Newly enrolled infants younger than 6 months must present with **left ventricular ejection fraction** of 50% or less at screening as assessed by **echocardiography**, along with elevated **NT-proBNP** levels exceeding 500 mg/L. Acceptable heart failure etiologies for newly enrolled participants include **congenital heart defects** with biventricular physiology and systemic left ventricle, **idiopathic cardiomyopathy**, familial or inherited and genetic cardiomyopathy, history of **myocarditis** diagnosed at least 3 months prior to treatment assignment, **neuromuscular disorders**, inborn errors of metabolism, mitochondrial disorders, acquired causes such as chemotherapy-induced or iatrogenic heart failure, ischemic causes including **Kawasaki disease**, and left ventricular noncompaction.

The primary endpoints of the study focus on safety assessment and include the number of participants experiencing **treatment-emergent adverse events**, changes in **serum potassium** levels from baseline to Day 270, changes in **systolic blood pressure** from baseline to Day 270, and changes in **estimated glomerular filtration rate** from baseline to Day 270. Secondary endpoints encompass changes in NT-proBNP levels, key echocardiographic parameters of left ventricular systolic function, pharmacokinetic parameters including maximum observed finerenone concentration in plasma after multiple doses and area under the curve for finerenone concentration, and evaluation of taste and texture of the pediatric formulation through a questionnaire.

The study visit schedule includes a screening visit for assessment of eligibility criteria, followed by a baseline visit where treatment initiation occurs. Subsequent follow-up visits are scheduled at regular intervals throughout the treatment period to monitor safety parameters, laboratory values, and efficacy measures. The end of treatment visit occurs at Day 270, with a visit window of ±7 days, designated as Visit 6. At this visit, comprehensive assessments including physical examination, laboratory tests, echocardiography, and adverse event documentation are performed. Participant involvement in the study is expected to last approximately 9 months from baseline to the end of treatment visit. Early termination from the study may occur due to withdrawal of consent, investigator decision based on safety concerns, protocol violations, loss to follow-up, or other circumstances that preclude continued participation as determined by the investigator or sponsor.

The experimental medication utilized in this clinical trial is finerenone, a chemically synthesized active substance identified by the sponsor product code BAY 94-8862. Finerenone is administered as an adjunct to standard of care therapy in pediatric patients with left ventricular systolic dysfunction. The investigational medicinal product is available in multiple pharmaceutical formulations to accommodate different patient needs and age groups. The maximum treatment period for all formulations is 3 years.

Finerenone is provided as film-coated tablets for oral use in varying dosage strengths. One formulation delivers a maximum daily dose of 10 mg, with a maximum total dose of 10 mg per administration. Another film-coated tablet formulation provides a maximum daily dose of 20 mg, with a maximum total dose of 20 mg per administration. A third film-coated tablet formulation allows for a maximum daily dose of 40 mg, with a maximum total dose of 40 mg per administration. These tablet formulations are designed for patients capable of swallowing solid oral dosage forms.

For patients requiring alternative dosing options, finerenone is also available as granules for oral suspension under the trade name Finerenone Bayer, with sponsor product code BAY 948862. This formulation is administered via oral use and provides a maximum daily dose of 40 mg, with a maximum total dose of 40 mg per administration. The granules for oral suspension formulation is supplied with multiple dosing devices to ensure accurate dose measurement and administration. These devices include liquid dosing devices with locking mechanisms for oral administration in volumes of 1 mL, 5 mL, and 10 mL, an Omnifix 50 mL Type Irrigation Syringe, a SOL-MTM 100 mL Catheter Tip Syringe without Needle, and an Adapter Non-Luer with locking mechanism for oral liquid administration. All dosing devices are CE-marked medical devices certified by notified bodies TÜV SÜD Product Service GmbH or BSI NL 2797.

This is a single-arm, open-label extension study design, and all participants receive finerenone in addition to their existing standard of care regimen. No placebo or active comparator treatment arm is included in this trial. The study evaluates the long-term safety of finerenone when administered to pediatric patients with heart failure and left ventricular systolic dysfunction, ranging from birth to 18 years of age. Participant compliance monitoring and adherence to the prescribed dosing schedules are integral components of the study protocol to ensure accurate safety assessments throughout the treatment period.

Efficacy will be assessed through secondary endpoints in this clinical trial. The change in NT-proBNP levels from baseline to Day 270± 7 (Visit 6, end-of-treatment) will be measured as a biomarker of heart failure status. Key echocardiographic parameters of left ventricular systolic function will be evaluated, with changes from baseline to Day 270± 7 (Visit 6, end-of-treatment) documented to assess cardiac function improvement. Additionally, pharmacokinetic parameters will be analyzed, including maximum observed finerenone concentration in plasma after multiple doses (Cmax, md) and area under the curve for finerenone concentration in plasma after multiple doses (AUCτ,md). A taste and texture questionnaire of the pediatric formulation will also be administered to evaluate patient acceptability of the investigational product.