(22419) A randomized, double-blind, placebo-controlled, parallel group Phase 2a study with an extension phase to evaluate the efficacy and safety of BAY 3401016 in participants aged 18 to 45 with Alport syndrome

The primary objective of this study is to assess the effect of BAY 3401016 on albuminuria in participants with Alport syndrome. Albuminuria represents a critical marker of renal function decline in this hereditary chronic kidney disease, and its reduction may indicate therapeutic benefit in slowing disease progression.

The secondary objective is to investigate the safety and tolerability of BAY 3401016 in participants with Alport syndrome.

The clinical trial enrolled a total of **29 participants** diagnosed with **Alport syndrome**, a form of **chronic kidney disease**. The study population consisted of both **male** and **female** participants aged **18 to 45 years**. Participants were selected based on specific clinical characteristics, including a diagnosis of either **X-linked Alport syndrome** (male participants) or **autosomal recessive Alport syndrome** (male or female participants). Eligible participants were required to have an **estimated glomerular filtration rate** of at least 45 mL/min/1.73m² and a **urine albumin-to-creatinine ratio** of at least 500 mg/g. All participants were receiving treatment with **angiotensin-converting enzyme inhibitors** and/or **angiotensin receptor blockers** at the time of enrollment. The trial population was classified as a vulnerable population.

This is a randomized, double-blind, placebo-controlled, parallel group Phase 2a study with an extension phase designed to evaluate the efficacy and safety of BAY 3401016 in participants aged 18 to 45 years with Alport syndrome. The study will also assess participants with chronic kidney disease. The trial employs a methodology where participants will be randomly assigned to receive either the active investigational medicinal product BAY 3401016, administered as a solution for injection, or a matching placebo. The investigational product contains BAY 3401016 as the active substance, which is classified as a protein of other origin, and is manufactured by Bayer AG.

The primary objective of this trial is to assess the effect of BAY 3401016 on albuminuria in participants with Alport syndrome. The primary endpoint is defined as the mean urine albumin-to-creatinine ratio (UACR) ratio to baseline averaged over 16, 20, and 24 weeks of treatment. Secondary endpoints include the number of participants experiencing treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs).

Eligible participants must meet the following principal inclusion criteria: age between 18 and 45 years inclusive, diagnosis of Alport syndrome (either X-linked Alport syndrome in males or autosomal recessive Alport syndrome in males or females), estimated glomerular filtration rate (eGFR) of at least 45 mL/min/1.73m², UACR of at least 500 mg/g, and ongoing treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB).

The overall trial duration is estimated to extend from the recruitment start date in February 2026 to the estimated end date in July 2028. Participant involvement will include a screening visit to determine eligibility based on the inclusion criteria, followed by treatment visits at specified intervals including assessments at 16, 20, and 24 weeks during the initial treatment phase. An extension phase is incorporated into the study design to evaluate longer-term outcomes. The end-of-study visit will be conducted upon completion of the extension phase or upon early termination. Early termination from the study may occur under specific conditions including withdrawal of consent, development of safety concerns, protocol violations, or at the discretion of the investigator based on the participant's best interest.

The experimental medication **BAY 3401016** is administered as a **solution for injection**. The active substance is BAY 3401016, which is classified as a protein-based therapeutic agent. The product is manufactured by BAYER AG. The specific dosage, frequency of administration, and route of administration details are to be determined according to the study protocol. The maximum daily dose is specified as 99999 mg, and the maximum total dose is 99999 mg, with a maximum treatment period of 99999 days. BAY 3401016 serves as the test product in this randomized, double-blind, placebo-controlled trial designed to evaluate its efficacy and safety in participants aged 18 to 45 years with **Alport syndrome**.

A **placebo** matching BAY 3401016 is utilized as the comparator treatment in this study. The placebo is designed to be indistinguishable from the active treatment to maintain blinding throughout the trial. Participants in the control group will receive the placebo according to the same administration schedule as those receiving the experimental medication. The use of placebo allows for the assessment of the true therapeutic effect of BAY 3401016 by providing a baseline comparison for efficacy and safety outcomes.

The trial follows a parallel group design with an extension phase, allowing for the evaluation of both short-term and longer-term effects of the investigational product. Participant compliance monitoring and adherence to the dosing schedule will be implemented throughout the study duration to ensure the integrity of the efficacy and safety data collected.

Efficacy will be assessed using the primary endpoint of mean urinary albumin-to-creatinine ratio (UACR) change from baseline, averaged over measurements taken at 16, 20, and 24 weeks of treatment. This parameter evaluates the effect of BAY 3401016 on albuminuria in participants with Alport syndrome. The UACR measurements will be collected at the specified timepoints during the treatment period to determine the impact of the investigational product compared to placebo on urinary protein excretion, which serves as a key indicator of kidney function in this patient population.