Evaluation of Finerenone and Semaglutide for Albuminuria Reduction in Patients with Chronic Kidney Disease

The primary objective of this study is to demonstrate that a **30% reduction in albuminuria** can be achieved in a substantial proportion of patients with **Chronic Kidney Disease** (CKD) using a single drug, either **mineralocorticoid receptor antagonist (MRA) finerenone** or **glucagon-like peptide-1 receptor agonist (GLP1-RA) semaglutide**, when the optimal drug for each patient is selected. This is clinically relevant as reducing albuminuria is associated with slowing the progression of CKD and reducing the risk of cardiovascular events.

Secondary objectives include: - Evaluating whether combination treatment with finerenone and semaglutide further lowers albuminuria at a population level, although it may only marginally improve the proportion of patients achieving a 30% reduction when the best drug for each patient is selected. - Assessing the feasibility of remotely monitoring an individual's drug response and selecting the appropriate drug for each patient, potentially allowing for at-home management.

The clinical trial focuses on individuals diagnosed with **Chronic Kidney Disease**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a urinary albumin to creatinine ratio between 100 mg/g and 3500 mg/g, an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min/1.73m², and HbA1c levels ranging from 5.7% to less than 11%. All participants must be on a stable dose of an ACE inhibitor or ARB, as well as a stable dose of an SGLT2 inhibitor for at least four weeks, provided these medications are tolerated. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their willingness to sign informed consent and meet the specified inclusion criteria. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **finerenone** and **semaglutide** in reducing albuminuria in patients with **Chronic Kidney Disease**. This is a phase IV, randomized, double-blind, controlled trial. The trial aims to demonstrate that a significant reduction in albuminuria can be achieved with a single drug when the optimal medication is selected for each patient. The trial is expected to commence recruitment on June 30, 2024, and conclude by December 31, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥18 years), urinary albumin to creatinine ratio, eGFR, HbA1c levels, and stable doses of ACEi/ARB and SGLT2 inhibitors. Following successful screening, participants will be randomized to receive either **Rybelsus** (3 mg, 7 mg, or 14 mg tablets) or **Kerendia** (20 mg film-coated tablets), both administered orally. The maximum treatment period for **Rybelsus** is 4 to 6 weeks, while **Kerendia** is up to 12 weeks.

Study visits will include baseline assessments, periodic follow-up visits to monitor safety and efficacy, and an end-of-study visit to evaluate the primary endpoint, which is the percentage change from baseline in urinary albumin to creatinine ratio (UACR). Secondary endpoints include the number of missed urine collections in a remote setting. The expected duration of participant involvement is up to 12 weeks, depending on the assigned treatment. Conditions that may lead to early termination from the study include adverse events, non-compliance with study procedures, or withdrawal of consent.

The clinical trial involves the administration of **Rybelsus 7 mg tablets**, which contain the active substance **semaglutide**. This medication is provided in tablet form and is administered orally. The maximum daily dose is 7 mg, with a total treatment period of up to 4 weeks. The tablets are manufactured by Novo Nordisk A/S and have undergone repackaging and relabelling for the trial. Participant compliance with the dosing schedule will be monitored throughout the study.

Another treatment used in the trial is **Kerendia 20 mg film-coated tablets**, containing the active substance **finerenone**. These tablets are also administered orally, with a maximum daily dose of 20 mg and a total treatment period of up to 12 weeks. The manufacturer, Bayer AG, has repackaged and relabelled the tablets for the purposes of the trial. Compliance with the dosing regimen will be closely monitored to ensure adherence.

Additionally, the trial includes the use of **Rybelsus 3 mg tablets**, which also contain **semaglutide** as the active ingredient. These tablets are administered orally, with a maximum daily dose of 3 mg and a treatment period of up to 4 weeks. The tablets are produced by Novo Nordisk A/S and have been repackaged and relabelled for the study. Participant adherence to the dosing schedule will be tracked throughout the trial.

Lastly, the trial involves the administration of **Rybelsus 14 mg tablets**, containing **semaglutide**. These tablets are administered orally, with a maximum daily dose of 14 mg and a treatment period of up to 6 weeks. Manufactured by Novo Nordisk A/S, the tablets have been repackaged and relabelled for the trial. Monitoring of participant compliance with the dosing schedule will be conducted to ensure proper adherence.

Efficacy in the clinical trial titled "FINESSE; Optimization of albuminuria lowering therapies to individual patients with CKD using FINErenone and SEmaglutide (FINESSE-CKD)" will be assessed primarily through the percentage change from baseline in the **Urinary Albumin to Creatinine Ratio (UACR)**. This parameter serves as the primary endpoint, with the objective of demonstrating that at least a 30% reduction in albuminuria can be achieved in a substantial proportion of patients when the optimal drug, either the mineralocorticoid receptor antagonist (MRA) finerenone or the glucagon-like peptide-1 receptor agonist (GLP1-RA) semaglutide, is selected for each patient.

Secondary endpoints include the percentage change from baseline in UACR and the number of missed urine collections in a remote, at-home setting. These efficacy parameters will be measured and collected at specified timepoints throughout the trial. The trial is designed to optimize existing therapies for chronic kidney disease (CKD) and is categorized as a phase 4 trial. The study aims to provide insights into the individualization of treatment regimens to achieve significant reductions in albuminuria, thereby potentially improving patient outcomes in CKD management.