Evaluation of Safety and Tolerability of MZE829 in Adults with Proteinuric APOL1-Associated Chronic Kidney Disease: A Phase 2 Open-Label Study

The primary objective of this study is to evaluate the **safety** and **tolerability** of MZE829 in adults with proteinuric **APOL1 Kidney Disease (AKD)**. This is clinically relevant as it aims to determine the potential adverse effects and the degree to which patients can tolerate the investigational drug, which is crucial for assessing its viability as a treatment option for this specific patient population. The study does not list any secondary objectives.

The clinical trial involves a total of **54 participants** diagnosed with **APOL1 Kidney Disease (AKD)**. The study population includes both male and female adults aged between **18 to 65 years**, with a body mass index (BMI) ranging from 18 to 45 kg/m² and a total body weight of at least 40 kg. Participants were selected based on the presence of a confirmed APOL1 high-risk genotype (G1/G1, G2/G2, or G1/G2) and a diagnosis of chronic kidney disease characterized by persistent high urine albuminuria. The estimated glomerular filtration rate (eGFR) of participants ranges from 25 to less than 90 mL/min/1.73 m², as determined by the Chronic Kidney Disease Epidemiology Collaboration (2021 CKD-EPI Creatinine-Cystatin C) equation. The trial includes a vulnerable population, and lifestyle factors such as diet and physical activity were not specified in the provided data.

The clinical trial is designed to evaluate the **safety** and tolerability of MZE829 in adults with proteinuric **APOL1 kidney disease**. This is an open-label, Phase 2 study, which will involve participants aged 18 to 65 years who have a confirmed APOL1 high-risk genotype and a diagnosis of chronic kidney disease with persistent high urine albuminuria. The trial will assess the primary endpoint of safety and tolerability based on the incidence of adverse events, changes in vital signs, clinical laboratory assessments, and 12-lead electrocardiograms. The study will be conducted over an estimated duration from May 2025 to September 2026.

Participants will be administered MZE829 in the form of a hard capsule, taken orally. The maximum treatment period is set at 84 days. The trial will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and a final end-of-study visit to assess overall outcomes. The expected length of participant involvement is approximately 12 weeks, contingent upon adherence to the study protocol. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or non-compliance with study procedures.

The clinical trial involves the administration of the experimental medication **MZE829**, which is a chemical compound developed by Maze Therapeutics, Inc. The pharmaceutical form of **MZE829** is a hard capsule, designed for oral use. The active substance in the medication is also referred to as **MZE829**. The trial does not involve a pediatric formulation, and the medication is not classified as an orphan drug. The maximum treatment period for **MZE829** is 84 days. The dosage is expressed in milligrams, with a maximum daily dose and total dose amount set at 999,999 mg, although specific dosing schedules are not detailed in the provided data.

In this study, **MZE829** is the sole experimental treatment being evaluated for its safety, tolerability, and effect on albuminuria in adults with proteinuric chronic kidney disease and the APOL1 high-risk genotype. There is no mention of any non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, being used in conjunction with **MZE829**. The trial is open-label, meaning that both the researchers and participants are aware of the treatment being administered. Participant compliance with the dosing regimen will be monitored throughout the study, although specific methods for compliance monitoring are not detailed in the available information.

The efficacy of MZE829 in the clinical trial will be assessed primarily through the evaluation of safety and tolerability. The primary endpoints include the incidence of adverse events (AEs) and changes in vital signs, clinical laboratory assessments, and 12-lead electrocardiograms (ECGs). These parameters will be systematically measured and collected throughout the study to ensure comprehensive monitoring of the participants' health status. The trial is designed to evaluate the effects of MZE829 in adults with proteinuric chronic kidney disease and the **APOL1** high-risk genotype. The study will follow a structured schedule for data collection, although specific timepoints for these assessments are not detailed in the provided information. The analysis of these endpoints will be conducted using standard clinical trial methodologies to determine the safety profile of MZE829.