Efficacy and Safety of Finerenone in Non-Diabetic Chronic Kidney Disease: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

The primary objective of this study is to demonstrate that **finerenone**, in addition to Standard of Care (SoC), is superior to placebo in delaying the progression of kidney disease in patients with non-diabetic chronic kidney disease. This is clinically relevant as it addresses the need for effective treatments to slow disease progression in this patient population, potentially improving long-term renal outcomes and reducing the burden of kidney disease.

Secondary objectives include:

• To demonstrate the beneficial effect of finerenone in addition to SoC as compared to placebo.
• To assess the safety of finerenone in addition to SoC as compared to placebo.

The clinical trial involves a total of **1193 participants** diagnosed with **non-diabetic chronic kidney disease**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific health criteria, including a clinical diagnosis of chronic kidney disease with a urine albumin/creatinine ratio between 200 and 3500 mg/g, and an estimated glomerular filtration rate between 25 and 90 mL/min/1.73m² at screening. Additionally, participants were required to have stable and maximum tolerated doses of an Angiotensin converting enzyme inhibitor or Angiotensin receptor blocker for at least four weeks prior to screening, and a potassium level of 4.8 mmol/L or less at screening. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being throughout the study. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 study**. The primary objective is to evaluate the efficacy and safety of **Finerenone**, in addition to standard of care, in delaying the progression of kidney disease in patients with **non-diabetic chronic kidney disease**. The trial is expected to span from November 2021 to February 2026, with the primary endpoint being the mean rate of change in the total slope of estimated glomerular filtration rate (eGFR) from baseline to Month 32. Secondary endpoints include time to composite outcomes such as kidney failure, sustained eGFR decline, heart failure hospitalization, or cardiovascular death, as well as the incidence of treatment-emergent adverse events.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a clinical diagnosis of chronic kidney disease, specific urine albumin/creatinine ratio, and stable use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Follow-up visits will be conducted to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will conclude the trial for each participant, assessing the final outcomes and any long-term effects of the treatment.

The expected length of participant involvement is approximately 32 months, with conditions for early termination including significant adverse events or non-compliance with the study protocol. Participants will be randomly assigned to receive either Finerenone or a placebo, both administered as film-coated tablets for oral use. The maximum daily dose of Finerenone is 20 mg, with a treatment period not exceeding 49 days. The trial aims to provide robust data on the potential benefits of Finerenone in managing non-diabetic chronic kidney disease, contributing to the understanding of its role in standard care practices.

The clinical trial involves the administration of **Finerenone**, a small molecule investigational drug, in the form of a film-coated tablet. The active substance, finerenone, is chemically derived and is provided by Bayer AG. The pharmaceutical form is a film-coated tablet, and the drug is administered orally. The maximum daily dose is 20 mg, with a total maximum dose of 20 mg over a treatment period of up to 49 days. The trial aims to evaluate the efficacy and safety of finerenone in delaying the progression of kidney disease in patients with non-diabetic chronic kidney disease, in addition to standard-of-care therapy.

In this study, a **placebo** is used as a comparator treatment. The placebo is designed to match the experimental medication in appearance and administration route but does not contain the active substance. The placebo is administered orally in a similar manner to the experimental drug, ensuring blinding in the study. The use of a placebo allows for the assessment of the true efficacy of finerenone by providing a control group for comparison.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. This is crucial for maintaining the integrity of the study results and for accurately assessing the efficacy and safety of the investigational drug. The trial is conducted in a double-blind manner, meaning neither the participants nor the investigators know which treatment the participants are receiving, to prevent bias in the results.

The efficacy of the clinical trial will be assessed by evaluating the impact of **Finerenone** on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease. The primary endpoint for efficacy assessment is the mean rate of change in the estimated glomerular filtration rate (eGFR) as measured by the total slope from baseline to Month 32. Secondary endpoints include the time to the composite of kidney failure, sustained eGFR decline of ≥57%, heart failure hospitalization, or cardiovascular death. Additional secondary endpoints involve the time to the composite of kidney failure or sustained eGFR decline of ≥57%, and the time to the composite of heart failure hospitalization or cardiovascular death. The number of participants experiencing treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and adverse events of special interest (AESIs) will also be recorded as part of the efficacy assessment.