Evaluation of Finerenone in Combination with ACEI or ARB for Proteinuria and Chronic Kidney Disease in Pediatric Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to demonstrate that **finerenone**, in addition to an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), is superior to placebo in reducing urine protein excretion in pediatric patients with chronic kidney disease (CKD) and proteinuria. This is clinically relevant as reducing proteinuria is a key therapeutic target in managing CKD, potentially slowing disease progression and improving renal outcomes.

Secondary objectives include:

• Assessing the safety profile of finerenone in addition to standard of care (SoC) in pediatric CKD patients compared to placebo.
• Further supporting the efficacy of finerenone in addition to SoC compared to placebo.
• Confirming the dose and systemic exposure of finerenone in CKD patients.
• Assessing the acceptability and palatability of the age-appropriate pediatric formulation.

The clinical trial involves a total of **235 participants** diagnosed with **chronic kidney disease** and **proteinuria**. The study population includes both male and female subjects, ranging in age from 6 months to less than 18 years. Participants were selected based on specific criteria, including a clinical diagnosis of chronic kidney disease at screening, with stages 1-3 for children aged 1 year to less than 18 years, and a serum creatinine level of ≤ 0.40 mg/dL for infants aged 6 months to less than 1 year. Additionally, participants must exhibit severely increased proteinuria, defined by a urinary protein-to-creatinine ratio (UPCR) of ≥ 0.50 g/g for those aged 2 years and older with CKD stage 2 and 3, or UPCR ≥ 1.0 g/g for patients under 2 years of age or those aged 2 years and older with CKD stage 1. The trial population is required to have stable kidney function between screening and Day 0 and must be treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at optimized doses. The study also considers vulnerable populations, ensuring that participants meet potassium level criteria appropriate for their age group. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and pharmacokinetics/pharmacodynamics of an age- and body weight-adjusted oral **finerenone** regimen. The trial targets children aged 6 months to less than 18 years with **chronic kidney disease** and **proteinuria**, who are already receiving an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). The primary objective is to demonstrate that finerenone, in addition to an ACEI or ARB, is superior to placebo in reducing urine protein excretion. The trial is expected to last for approximately six months, with an estimated end date in March 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, clinical diagnosis, and stable kidney function. Following the screening, participants will be randomized to receive either finerenone or placebo. The study includes regular follow-up visits to monitor safety, efficacy, and any adverse events. These visits will assess changes in serum potassium levels, serum creatinine, estimated glomerular filtration rate (eGFR), and systolic blood pressure. The end-of-study visit will occur at the conclusion of the six-month treatment period, where final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately six months, aligning with the trial's treatment duration. Conditions that may lead to early termination from the study include significant adverse events, such as severe treatment-emergent adverse events (TEAEs) or serious TEAEs leading to discontinuation of treatment, as well as hospitalization due to hyperkalemia or worsening renal function. The trial will ensure that all participants are treated with optimized doses of ACEI or ARB, unchanged for at least 30 days prior to screening, to maintain consistent baseline conditions throughout the study.

The clinical trial involves the administration of **BAY 94-8862**, a film-coated tablet containing the active substance **finerenone**. This medication is a small molecule developed by Bayer AG, intended for oral use. The maximum daily dose is 20 mg, with a total treatment period of up to 6 months. Participants will receive the medication once daily. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

Another formulation of **finerenone** used in the trial is marketed under the name **Finerenone**. This product is also a film-coated tablet, with a maximum daily dose of 10 mg, administered orally. The treatment duration is similarly set for a maximum of 6 months. Participant adherence to the dosing regimen will be closely monitored to maintain the integrity of the study results.

The trial also includes **BAY 948862**, a pediatric formulation of **finerenone** in the form of granules for oral suspension. This formulation is designed for oral use and is accompanied by various dosing devices, such as liquid dosing devices and syringes, to facilitate accurate administration. The maximum daily dose is 20 mg, with a treatment period of up to 6 months. The use of these devices ensures precise dosing and enhances compliance monitoring.

Placebo treatments are utilized in the study to serve as controls. These include the **Placebo to BAY 948862**, **Placebo to Finerenone 10 film-coated tablets**, and **Placebo to Finerenone 20 film-coated tablets**. These placebos are designed to match the appearance and administration route of their respective active treatments, ensuring blinding in the study. The placebo treatments are administered with the same frequency and duration as the active treatments to maintain consistency across the study arms.

The efficacy of the clinical trial will be assessed primarily through the evaluation of the mean reduction in the **Urinary Protein-to-Creatinine Ratio (UPCR)** from baseline to Month 6. This primary endpoint will measure the percent change in UPCR from baseline to day 180±7. Secondary endpoints will include the number of participants experiencing adverse events (AEs), serious treatment-emergent adverse events (TEAEs), and TEAEs leading to discontinuation of treatment. Additionally, changes in serum potassium levels, serum creatinine, estimated glomerular filtration rate (eGFR), and systolic blood pressure from baseline to day 180±7 will be monitored. The proportion of responders, defined as participants achieving at least a 30% reduction in UPCR from baseline to day 180±7, will also be evaluated. Further assessments will include changes in the Urinary Albumin-to-Creatinine Ratio (UACR) and pharmacokinetic parameters such as finerenone Cmax,md and AUCτ,md based on total concentrations in plasma. The taste and texture of the pediatric formulation will be assessed as well.