Evaluation of Dapagliflozin Propanediol, Finerenone, and Semaglutide in Biomarker-Targeted Therapy for Chronic Kidney Disease Patients

The primary objective of this clinical trial is to evaluate the effect of a **biomarker**-targeted treatment approach compared to the standard of care on the chronic estimated glomerular filtration rate (eGFR) slope in patients with chronic kidney disease. This is clinically relevant as the eGFR slope is a critical indicator of kidney function decline, and optimizing treatment strategies could potentially slow disease progression.

Secondary objectives include:

• Comparing the effect of the biomarker-targeted treatment versus standard care on the change in eGFR from baseline to the end of the study.
• Assessing the change in eGFR from baseline to the end of treatment.
• Evaluating the impact on albuminuria, a marker of kidney damage.
• Analyzing changes in the KidneyIntelX score, a validated and guideline-endorsed kidney risk score.

The clinical trial involves a total of **10 participants** diagnosed with **chronic kidney disease**. The study population includes both male and female subjects, aged between 18 and 75 years. Participants were selected based on specific criteria, including a **urinary albumin-to-creatinine ratio (UACR)** of 100-5000 mg/g in two consecutive first-morning void urine samples, or 80-100 mg/g if historical measurements are above 100 mg/g and cannot be explained by any new treatment. All participants are required to have been on a stable treatment with the maximum tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least four weeks prior to randomization, unless contraindicated or not tolerated. The trial does not include a vulnerable population, and participants must be able to communicate effectively with the study staff and provide informed consent. Lifestyle factors such as diet and physical activity were not specified in the trial data provided.

The clinical trial is designed to evaluate the efficacy of a **biomarker-targeted treatment** approach compared to the standard of care in patients with **chronic kidney disease**. This study is a randomized, open-label, controlled trial with a focus on optimizing treatment based on specific biomarkers. The trial will span a total duration of 104 weeks, with an estimated recruitment start date in March 2025 and an anticipated end date in December 2028. Participants will be randomly assigned to receive either the biomarker-guided treatment or the standard care regimen. The primary endpoint is the chronic eGFR slope, defined as the mean annual rate of change in eGFR from week 26 to week 104. Secondary endpoints include changes in eGFR and albuminuria from baseline to week 104, as well as changes in the KidneyIntelX score.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will assess eligibility based on criteria such as age (18-75 years), UACR levels, and stable treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Following randomization, participants will undergo regular follow-up visits to monitor treatment effects and safety. The end-of-study visit will occur at week 112, where final assessments will be conducted to evaluate the long-term impact of the treatment. Participant involvement is expected to last approximately 112 weeks, including the follow-up period. Conditions that may lead to early termination from the study include adverse reactions to the treatment, non-compliance with study protocols, or withdrawal of consent by the participant.

The clinical trial involves the administration of three experimental medications, each with distinct active substances and administration routes. **Dapagliflozin propanediol** is administered in an oral pharmaceutical form, with a maximum daily dose of 10 mg. The treatment period for this medication is up to 104 weeks. The administration route is oral, and the medication is not formulated for pediatric use. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

**Finerenone** is also administered orally, with a maximum daily dose of 10 mg. Similar to dapagliflozin propanediol, the treatment period extends up to 104 weeks. The pharmaceutical form is consistent with the oral administration route, and the formulation is not intended for pediatric patients. Participant compliance is closely monitored to maintain the integrity of the dosing schedule.

**Semaglutide** is administered via subcutaneous injection, with a maximum daily dose of 0.14 mg. The treatment duration for semaglutide is also up to 104 weeks. This medication is delivered in a different pharmaceutical form suitable for subcutaneous administration. As with the other medications, semaglutide is not formulated for pediatric use, and participant adherence to the dosing schedule is rigorously monitored.

In addition to the experimental medications, the trial may include standard-of-care therapy as a comparator treatment. The trial's objective is to evaluate the effect of a biomarker-targeted treatment approach on the chronic eGFR slope in patients with chronic kidney disease. The study design ensures that all participants receive appropriate monitoring and support to adhere to the treatment protocols.

Efficacy in this clinical trial will be assessed primarily through the evaluation of the **chronic eGFR slope**, which is defined as the mean annual rate of change in estimated glomerular filtration rate (eGFR) from week 26 to week 104. This primary endpoint will provide insight into the long-term impact of the biomarker-targeted treatment approach compared to the standard of care on kidney function in patients with chronic kidney disease.

Secondary endpoints will include several additional measures of kidney function and health. These are the change in eGFR from baseline to week 112 (end of study) and from baseline to week 104 (end of treatment), the change in albuminuria from baseline to week 104, and the change in KidneyIntelX score from baseline to week 104. These parameters will be measured at specified timepoints to capture both short-term and long-term effects of the treatment.

The collection and analysis of these efficacy parameters will be conducted using validated laboratory tests and patient-reported outcomes, ensuring the reliability and accuracy of the data. The trial is designed to follow participants closely, with all assessments conducted by qualified medical staff to ensure the integrity of the efficacy evaluations.