Evaluation of Camostat Mesilate on Renal Function and Blood Pressure in Patients with Chronic Kidney Disease and Proteinuria

The primary objective of this study is to evaluate the effect of **Camostat mesilate** on salt and water excretion, including total body water content and blood pressure, in patients with **chronic kidney disease** with proteinuria compared to healthy controls. This is clinically relevant as it may provide insights into the potential of Camostat mesilate to manage fluid balance and blood pressure in this patient population, which are critical factors in the progression of chronic kidney disease.

Secondary objectives include:

• Evaluating the effect of Camostat mesilate on tubular serine protease activity and complement activation in patients with chronic kidney disease and proteinuria compared to healthy controls.
• Assessing whether proteolytic activation of ENaC plays a role in normal physiological regulation.

The clinical trial involves participants diagnosed with **Chronic Kidney Disease** (CKD) with proteinuria. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants are required to have a clinical diagnosis of CKD with an estimated glomerular filtration rate (eGFR) greater than 30 ml/min/1.73m² and a urine albumin-to-creatinine ratio (U-ACR) exceeding 300 mg/g. They must be on stable antihypertensive treatment for at least two weeks prior to the commencement of the investigational medical product and maintain this regimen throughout the study. The office blood pressure at screening should be between 120/70 mmHg and 150/90 mmHg. Women of childbearing potential are required to have a negative pregnancy test and use contraception during the study and for one week after completing the study treatment. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the effect of **Camostat mesilate** on salt and water excretion, total body water content, and blood pressure in patients with **chronic kidney disease** (CKD) compared to healthy controls. This is a Phase 4, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on August 1, 2024, and conclude by December 31, 2025. Participants will be involved in the study for a maximum treatment period of 5 days, with a daily dose of 600 mg of Camostat mesilate administered orally. The primary endpoints include urine sodium excretion, water excretion, body composition monitoring, and home blood pressure measurements. Secondary endpoints involve urine protease activity, tubular complement activation, urine microvesicles, 24-hour urine albumin excretion, and plasma concentrations of renin, NT-proBNP, angiotensin II, and aldosterone.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is assessed based on criteria such as age over 18 years, a clinical diagnosis of CKD with an estimated glomerular filtration rate (eGFR) greater than 30 ml/min/1.73m², and a urine albumin-to-creatinine ratio (U-ACR) greater than 300 mg/g. Participants must have stable antihypertensive treatment for at least two weeks prior to the start of the investigational medicinal product (IMP) and maintain this treatment throughout the study. Office blood pressure at screening should be between 120/70 mmHg and 150/90 mmHg. Women of childbearing potential must have a negative pregnancy test and use contraception during the study and for one week after completion of the study treatment. Follow-up visits will be scheduled to monitor the primary and secondary endpoints, ensuring adherence to the study protocol. The end-of-study visit will conclude the participant's involvement, with a comprehensive assessment of all study parameters.

Participants may be subject to early termination from the study if they fail to comply with the study requirements, experience adverse effects that necessitate discontinuation, or withdraw consent. The trial aims to provide valuable insights into the potential benefits of Camostat mesilate for kidney protection in patients with chronic kidney disease, contributing to the understanding of its therapeutic role in this population.

The clinical trial involves the administration of **Camostat Mesilate**, an experimental medication, to evaluate its effects on kidney protection in patients with chronic kidney disease. **Camostat Mesilate** is a serine protease inhibitor provided in the form of a tablet. The active substance, **Camostat Mesilate**, is administered orally. The dosage regimen for this trial specifies a maximum daily dose of 600 mg, with a total maximum dose of 3 grams over the course of the treatment period. The treatment duration is limited to a maximum of 5 days. The trial does not involve a pediatric formulation, and the medication is not classified as an orphan drug.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, although specific details of these are not provided in the available data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The primary objective of the trial is to assess the impact of **Camostat Mesilate** on salt and water excretion, total body water content, and blood pressure in patients with chronic kidney disease compared to healthy controls.

Efficacy in the clinical trial titled "Effect of Camostat for Kidney Protection in Chronic Kidney Disease (CamKid)" will be assessed using both primary and secondary endpoints. The primary endpoints include measurements of urine sodium excretion, water excretion, body composition monitor/weight, and home blood pressure. These parameters will provide insights into the effect of **Camostat mesilate** on salt and water excretion, total body water content, and blood pressure in patients with chronic kidney disease compared to healthy controls.

Secondary endpoints will further evaluate efficacy through the assessment of urine protease activity using zymography and protease activity assays, tubular complement activation markers such as urine C3a, MAC-sC5b-9, C3dg, and MBL, and urine microvesicles including gammaENaC cleavage and complement deposition (sC5b-9). Additionally, 24-hour urine albumin excretion and plasma concentrations of renin, NT-proBNP, angiotensin II, and aldosterone will be measured. These endpoints will be collected and analyzed to provide a comprehensive evaluation of the drug's impact on kidney function and related physiological processes.