Efficacy and Safety of Balcinrenone and Dapagliflozin Versus Dapagliflozin in Adults with Chronic Kidney Disease and Albuminuria: A Randomized, Double-Blind Study

The primary objective of this Phase IIb, multicentre, randomised, double-blind, dose-finding study is to evaluate whether **balcinrenone** in combination with **dapagliflozin** is superior to dapagliflozin alone in reducing **albuminuria** in patients with **chronic kidney disease**. This is clinically relevant as albuminuria is a key marker of kidney damage and its reduction is associated with improved renal outcomes and decreased progression of kidney disease.

The clinical trial involves a total of **215 participants** diagnosed with **Chronic Kidney Disease and Albuminuria**. 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 25 and less than 60 mL/min/1.73 m², and a urine albumin-to-creatinine ratio (UACR) greater than 100 mg/g to 5000 mg/g. Additionally, serum potassium levels must be between 3.5 mmol/L and 5.0 mmol/L. Participants are required to have been on stable treatment with RAAS inhibitors for at least four weeks prior to screening, although those unable to tolerate or not treated with RAAS inhibitors are also eligible. The trial includes a vulnerable population, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized, double-blind, controlled** study designed to evaluate the efficacy, safety, and tolerability of **balcinrenone** in combination with **dapagliflozin** compared to dapagliflozin alone in patients with **chronic kidney disease** and albuminuria. The trial is categorized as a Phase IIb study and is not considered low intervention. The primary objective is to determine whether the combination therapy is superior in reducing albuminuria. The trial is expected to commence recruitment on May 6, 2024, and conclude by July 8, 2025, with a total duration of approximately 12 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis of chronic kidney disease, and specific laboratory values. Following successful screening, participants will be randomized to receive either the combination therapy or dapagliflozin alone. The study involves regular follow-up visits to monitor safety, efficacy, and adherence to the treatment regimen. These visits will include assessments of urinary albumin-to-creatinine ratio (UACR) and other relevant clinical parameters. The primary endpoint is the relative change in UACR from baseline to Week 12.

The end-of-study visit will occur at the conclusion of the 12-week treatment period, where final assessments will be conducted to evaluate the overall impact of the treatment. Participant involvement is expected to last for the entire 12-week period unless conditions arise that necessitate early termination, such as adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Forxiga** 10 mg film-coated tablets, which contain the active substance **dapagliflozin**. This medication is provided in the form of film-coated tablets and is intended for **oral use**. The tablets are manufactured by AstraZeneca AB and are characterized by their synthetic small molecule composition. The clinical product differs from the commercial product only in colorant and engraving, with the clinical version being green, plain, and diamond-shaped. The maximum treatment period for this medication is 12 months. The dosage and frequency of administration are determined by the study protocol, and participant compliance is monitored throughout the trial.

Another treatment used in the study is a combination of **balcinrenone** and dapagliflozin, provided in the form of hard capsules. This investigational product is also manufactured by AstraZeneca AB and is intended for oral use. The combination of these active substances is designed to evaluate the efficacy, safety, and tolerability in patients with chronic kidney disease and albuminuria. The maximum treatment period for this combination is also 12 months. The dosing schedule and participant compliance are closely monitored as per the study protocol.

In addition to the experimental treatments, the study may include a comparator treatment, which is not specified in the provided data. The comparator could potentially be a placebo or another standard-of-care therapy, depending on the study design. The role of the comparator is to provide a baseline for evaluating the efficacy of the experimental treatments. The administration and monitoring of the comparator treatment follow the same rigorous standards as the experimental medications.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the relative change in **UACR** (Urinary Albumin-to-Creatinine Ratio) from baseline to Week 12. This endpoint is chosen to determine the effectiveness of the combination of balcinrenone and dapagliflozin compared to dapagliflozin alone in reducing albuminuria in patients with chronic kidney disease and albuminuria. The measurement of UACR will be conducted at baseline and at the 12-week mark to assess the change over the treatment period. The data collected will be analyzed to determine the relative change in UACR, providing insights into the efficacy of the treatment regimen. The trial is designed as a Phase IIb, multicenter, randomized, double-blind, dose-finding study, ensuring a robust evaluation of the treatment's efficacy.