FINE-START; A parallel-group, randomized, prospective, interventional, double-blind, multicenter global Phase 3 study to investigate the efficacy and safety of finerenone versus placebo, in participants with chronic kidney disease not using renin-angiotensin-system inhibitors

The primary objective of this study is to demonstrate the superiority of finerenone compared to placebo in reducing urinary albumin-to-creatinine ratio (UACR) over 6 months in participants with chronic kidney disease not using renin-angiotensin-system inhibitors. This objective addresses a clinically significant gap in the management of patients with chronic kidney disease who are not receiving standard renin-angiotensin-system inhibitor therapy, potentially offering an alternative therapeutic approach to reduce albuminuria, a key marker of kidney damage progression.

The secondary objective is to assess the safety of finerenone compared to placebo.

This clinical trial enrolled a total of **125 participants** diagnosed with **chronic kidney disease**. The study population included both **male and female** adults aged **18 years and older**. Participants were required to have a clinical diagnosis of chronic kidney disease with specific renal function parameters, including an **estimated glomerular filtration rate (eGFR)** between 25 and 120 mL/min/1.73 m² and **urine albumin-to-creatinine ratio (UACR)** ranging from 100 mg/g to less than 5000 mg/g at screening. A key selection criterion was the absence of current or recent treatment with **renin-angiotensin system (RAS) inhibitors**, including **angiotensin-converting enzyme inhibitors (ACEi)**, **angiotensin receptor blockers (ARB)**, or **renin inhibitors** within 8 weeks prior to screening. Participants were also required to have **potassium levels** at or below 5.0 mmol/L at the time of screening. Documentation of elevated **albuminuria** or **proteinuria** in medical records at least 3 months prior to screening was necessary for inclusion. All participants were capable of providing informed consent and complying with trial requirements.

This is a parallel-group, randomized, prospective, interventional, double-blind, multicenter global Phase 3 clinical trial designed to investigate the efficacy and safety of **finerenone** versus **placebo** in participants with **chronic kidney disease** not using renin-angiotensin-system inhibitors. The primary objective is to demonstrate that finerenone is superior to placebo in reducing **urinary albumin-to-creatinine ratio** (UACR) over 6 months when compared to placebo in participants with chronic kidney disease not using RAS inhibitors.

The trial will enroll participants who are at least 18 years of age or the legal age of consent according to local legislation at the time of signing the informed consent. Eligible participants must have a clinical diagnosis of chronic kidney disease with an **estimated glomerular filtration rate** (eGFR) of at least 25 and less than 120 mL/min/1.73 m² using the CKD-EPI 2009 formula at the screening visit. Additionally, participants must have a UACR of at least 100 mg/g (11.3 mg/mmol) to less than 5000 mg/g (565 mg/mmol) at the screening visit, based on the geometric mean of three measurements, and documentation of elevated **albuminuria** or **proteinuria** in the participant's medical records at least 3 months prior to screening. Participants must not have current or previous treatment with RAS inhibition, including ACE inhibitors, ARBs, or renin inhibitors, within 8 weeks prior to the screening visit. Potassium levels must be 5.0 mmol/L or less at screening based on local assessment.

The investigational medicinal products include finerenone administered as **film-coated tablets** via the **oral** route and a matching placebo. The maximum daily dose of finerenone is 20 mg, with a maximum total dose of 3500 mg over a maximum treatment period of 175 days. The active substance in the test product is finerenone, which is of chemical origin.

The primary endpoint is the change in UACR from baseline, expressed as a ratio to baseline, over 6 months. Secondary endpoints include the number of participants with **treatment-emergent adverse events** (TEAEs), **treatment-emergent serious adverse events** (TESAEs), and the number of participants with **hyperkalemia** as an adverse event of special interest.

The estimated recruitment start date for the trial is January 1, 2026, with an estimated end date of December 31, 2027. Participants will undergo a screening visit to assess eligibility criteria, followed by randomization and treatment initiation. The study involves follow-up visits at specified intervals to monitor efficacy and safety parameters, including laboratory assessments and adverse event monitoring. The expected length of participant involvement includes the treatment period of up to 175 days and subsequent follow-up visits. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, non-compliance with the protocol, withdrawal of consent, or investigator decision based on safety concerns.

The experimental medication investigated in this clinical trial is **finerenone**, administered as **film-coated tablets** for **oral** use. Finerenone is supplied under the sponsor product code BAY 94-8862 by BAYER AG. The active substance is finerenone, which is of chemical origin. The maximum daily dose is **20 mg**, with a maximum total dose of **3500 mg** over a treatment period of up to **175 days**. The dosing regimen and administration schedule are designed to evaluate the efficacy and safety of finerenone in participants with **chronic kidney disease** not using **renin-angiotensin-system inhibitors**.

The comparator treatment used in this study is a **placebo** matching BAY 94-8862. The placebo is formulated to be indistinguishable from the active treatment to maintain the double-blind nature of the trial. The placebo is administered according to the same schedule and route as the experimental medication to ensure consistency in treatment administration across study arms. The pharmaceutical form, route of administration, and frequency of the placebo correspond to those of the finerenone formulation.

The study employs a parallel-group, randomized, double-blind design to compare finerenone with placebo. Participants are assigned to receive either the experimental medication or placebo for the duration of the treatment period. The primary objective is to demonstrate the superiority of finerenone over placebo in reducing **urine albumin-to-creatinine ratio** over 6 months. Compliance monitoring and adherence to the prescribed dosing schedule are integral components of the trial to ensure the validity and reliability of the efficacy and safety assessments.

Efficacy will be assessed using the change in **urinary albumin-to-creatinine ratio** (UACR) from baseline (ratio to baseline) over 6 months as the primary endpoint. At the Screening visit, UACR will be measured as the geometric mean of 3 measurements, with participants required to have a UACR of ≥100 mg/g (11.3 mg/mmol) to <5000 mg/g (565 mg/mmol) at baseline. The estimated glomerular filtration rate (eGFR) will be assessed at Screening using the CKD-EPI 2009 formula, with participants required to have an eGFR ≥25 and <120 mL/min/1.73 m² for inclusion. Local laboratory assessments will be utilized for these measurements. Secondary endpoints include the number of participants with treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and the number of participants with **hyperkalemia** as an adverse event of special interest (AESI). Potassium levels will be monitored, with participants required to have serum potassium ≤5.0 mmol/L at Screening. The treatment period will extend for up to 175 days, with efficacy and safety assessments conducted throughout this period to evaluate the superiority of **finerenone** compared to placebo in participants with **chronic kidney disease** not using renin-angiotensin-system inhibitors.