Evaluation of BAY 3283142 Efficacy and Safety in Reducing Albuminuria in Chronic Kidney Disease Patients: A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to estimate and assess a **dose-response relationship** in the primary endpoint of mean change in urine albumin-creatinine ratio (UACR) from baseline after 16 weeks of treatment with BAY3283142 compared with placebo, in addition to standard of care (SoC) in patients with **chronic kidney disease** (CKD). This objective is clinically relevant as it aims to support the dose selection for Phase 3, which is crucial for optimizing therapeutic efficacy and safety in CKD management.

Secondary objectives include:

• Investigating the course of estimated glomerular filtration rate (**eGFR**) over time, which is important for understanding the impact of the treatment on kidney function.
• Investigating the mean change from baseline in UACR over time, providing insights into the long-term effects of the treatment on albuminuria.
• Investigating the overall safety and tolerability of treatment with BAY3283142 compared with placebo in addition to SoC, ensuring that the treatment is safe and well-tolerated by patients.

The clinical trial involves a total of **843 participants** diagnosed with **chronic kidney disease**. The study population includes both male and female subjects, aged 18 years and older. Participants were selected based on specific health criteria, including an estimated glomerular filtration rate (eGFR) between 20 and 75 mL/min/1.73 m² and a urine albumin-creatinine ratio (UACR) between 200 mg/g and 3500 mg/g. All participants are required to be on a stable dose of either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) unless contraindicated, and any additional treatments such as sodium-glucose co-transporter-2 (SGLT2) inhibitors or diuretics must also be stable for at least four weeks prior to screening. The trial does not include a vulnerable population, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of BAY 3283142 in patients with **chronic kidney disease**. The primary objective is to assess the dose-response relationship in the mean change of urine albumin-creatinine ratio (UACR) from baseline after 16 weeks of treatment with BAY 3283142 compared to placebo, in addition to standard care. The trial is expected to commence recruitment on August 30, 2024, and conclude by June 17, 2026.

Participants will be involved in the study for a total duration of 16 weeks. The study will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits at specified intervals, and a final end-of-study visit. The inclusion criteria require participants to be at least 18 years old, with an estimated glomerular filtration rate (eGFR) between 20 and 75 mL/min/1.73 m², and a UACR between 200 mg/g and 3500 mg/g. Participants must be on a stable dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, unless contraindicated, and any additional treatments should be stable for at least four weeks prior to screening.

The primary endpoint is the change from baseline to Week 16 in the logarithm of UACR. Secondary endpoints include changes in eGFR and UACR over time, as well as the incidence of treatment-emergent adverse events. Participants may be withdrawn from the study if they experience serious adverse events or if they do not adhere to the study protocol. The investigational product, BAY 3283142, is administered orally in the form of a coated tablet, with a placebo group included for comparison. The study aims to support dose selection for a subsequent Phase 3 trial.

The clinical trial involves the administration of **BAY 3283142**, an experimental medication developed by Bayer AG. This medication is presented in the form of a **coated tablet** and is intended for **oral** administration. The active substance, also named BAY 3283142, is of chemical origin. The trial does not specify a maximum daily or total dose amount, indicating that dosing will be determined based on the study protocol. The treatment period for BAY 3283142 is set for a maximum of 16 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental medication, a **placebo** is used as a comparator in this study. The placebo is referred to as BAY 3283142 PLACEBO. The pharmaceutical form and route of administration for the placebo are not specified in the trial data. The placebo serves as a control to evaluate the efficacy and safety of BAY 3283142 in reducing albuminuria in patients with chronic kidney disease. The study is designed as a randomized, placebo-controlled, double-blind trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias.

The efficacy of BAY 3283142 in patients with chronic kidney disease will be assessed through a randomized, placebo-controlled, double-blind clinical trial. The primary endpoint for evaluating efficacy is the change from baseline to Week 16 in the logarithm of the urine albumin-creatinine ratio (**UACR**). This measurement will help determine the dose-response relationship and support dose selection for a subsequent Phase 3 trial.

Secondary endpoints include changes from baseline over time in estimated glomerular filtration rate (**eGFR**) and the logarithm of UACR at specific visits (Visits 5, 6, and 7). Additionally, the number of subjects experiencing treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to permanent discontinuation of the study intervention will be recorded. These parameters will be measured and analyzed to provide a comprehensive assessment of the drug's efficacy and safety profile.