Safety Evaluation of Long-term Finerenone with ACE Inhibitor or Angiotensin Receptor Blocker in Pediatric Chronic Kidney Disease with Proteinuria

The primary objective of this study is to demonstrate that **finerenone**, when administered in addition to an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB), is safe for long-term use in children and young adults aged 1 to 18 years with chronic kidney disease and proteinuria. This is clinically relevant as it addresses the safety profile of finerenone, a mineralocorticoid receptor antagonist, in a pediatric population, which is crucial for ensuring effective and safe management of chronic kidney disease in this age group.

Secondary objectives include assessing the long-term treatment effects of finerenone on proteinuria and kidney function when used alongside standard care. This evaluation is important for understanding the potential benefits of finerenone in improving renal outcomes and reducing proteinuria, which are key factors in the progression of chronic kidney disease.

The clinical trial involves a total of **40 participants** who are children diagnosed with **chronic kidney disease** (CKD) and proteinuria. The study population includes both male and female subjects, ranging in age from **1 to 18 years**. Participants were selected based on their prior involvement in the finerenone Phase 3 study FIONA, provided they were not permanently discontinued from treatment by the end of that study. All participants have CKD stages 1-3, with an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73m². They are required to be on stable doses of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 30 days prior to the trial. The trial includes children who can receive enteral feeding, with or without breastfeeding. The study population is considered vulnerable, given the age range and health condition of the participants.

The clinical trial is designed as an **open-label**, single-arm safety extension study to evaluate the long-term safety of **finerenone** in combination with an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) for the treatment of children and young adults aged 1 to 18 years with **chronic kidney disease** and **proteinuria**. The trial will span 18 months, with the primary objective to demonstrate the safety of finerenone when administered over an extended period. Participants eligible for this study must have previously participated in the Phase 3 FIONA study and not have been permanently discontinued from treatment at the end of that study. The trial will assess primary endpoints such as the number of participants with treatment-emergent adverse events (TEAEs), changes in serum potassium levels, and changes in systolic blood pressure from baseline to Day 540±7. Secondary endpoints include changes in urinary protein-to-creatinine ratio, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR) over the same period.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, prior study participation, and current treatment regimen. Participants must be on a stable dose of ACEI or ARB for at least 30 days prior to the screening visit. Follow-up visits will be scheduled throughout the trial to monitor safety and efficacy parameters, with the end-of-study visit marking the conclusion of the participant's involvement. The expected duration of participant involvement is approximately 18 months, aligning with the overall trial duration. Conditions that may lead to early termination from the study include significant adverse events or non-compliance with the study protocol. The study will utilize both film-coated tablets and granules for oral suspension of finerenone, with dosing adjusted based on age and body weight. The trial is not categorized as a low-intervention study and is classified as a Phase 5 trial, focusing on the long-term safety of the investigational product.

The clinical trial involves the administration of **finerenone**, a chemical compound, in various pharmaceutical forms. The first experimental medication is BAY 94-8862, presented as a **film-coated tablet**. This formulation is intended for **oral use** and is not a pediatric formulation. The maximum daily dose is 20 mg, with a total treatment period of up to 6 months. The administration frequency is determined by the study protocol, ensuring adherence to the maximum daily dosage. Participant compliance is monitored through regular assessments and documentation of dosing schedules.

The second experimental medication is BAY 948862, formulated as **granules for oral suspension**. This pediatric formulation is also administered orally, with a maximum daily dose of 20 mg over a 6-month period. The administration of this formulation involves the use of various dosing devices, including LDD-Liquid Dosing Devices (1 mL, 5 mL, and 10 mL), an Adapter Non-Luer, Henke-Ject® 50 mL Catheter Syringe, and SOL-M™ 100ml catheter tip syringe without needle. These devices are equipped with locking mechanisms to ensure accurate dosing and are CE marked for compliance with safety standards.

The third experimental medication is Finerenone, also in the form of a **film-coated tablet** for oral administration. This formulation is not specifically designed for pediatric use and has a maximum daily dose of 10 mg, with a treatment duration of up to 6 months. The dosing schedule is aligned with the study protocol to maintain participant safety and efficacy of the treatment. Compliance is monitored through systematic tracking of medication intake and participant adherence to the prescribed regimen.

In addition to the experimental medications, participants may receive standard-of-care therapy, including an ACEI or ARB, as part of the treatment regimen for chronic kidney disease and proteinuria. The combination of finerenone with these standard treatments aims to evaluate the long-term safety and efficacy of the experimental medication in the target population. The study protocol includes detailed instructions for the administration of both experimental and non-experimental treatments to ensure consistency and reliability of the trial outcomes.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the number of participants with treatment emergent adverse events (TEAEs), changes in serum potassium levels from baseline to Day 540±7, and changes in systolic blood pressure (SBP) from baseline to Day 540±7. Secondary endpoints focus on changes in urinary protein-to-creatinine ratio (UPCR) and urinary albumin-to-creatinine ratio (UACR) from baseline to Day 540±7, as well as changes in estimated glomerular filtration rate (eGFR) from baseline to Day 540±7.

The trial involves the administration of **finerenone** in addition to an ACEI or ARB, targeting children and young adults aged 1 to 18 years with chronic kidney disease and proteinuria. The efficacy parameters will be measured and collected at specified timepoints, with the primary focus on long-term safety and efficacy over an 18-month period. The trial is designed to ensure that the treatment regimen is safe and effective when administered over an extended duration, with careful monitoring of key biomarkers and clinical outcomes.