Evaluation of Finerenone and Drug Combinations in Slowing eGFR Decline in Patients with Chronic Kidney Disease: A Randomized, Placebo-Controlled Trial

The primary objective of the study is to determine the efficacy of investigational agents or combinations of agents in reducing the rate of estimated **glomerular filtration rate** (eGFR) decline, thereby slowing the progression of **Chronic Kidney Disease** (CKD), compared to placebo in patients receiving standard care. This is clinically relevant as it aims to identify potential treatments that can effectively manage CKD progression, which is a significant concern in patient care.

Secondary objectives include:

• Change in albuminuria between randomisation and 24 weeks.
• Change in eGFR from randomisation to the end of washout.
• Proportion of participants experiencing a ≥40% eGFR decline, and proportion developing kidney failure at 108 weeks.
• Time to ≥40% eGFR decline from randomisation or kidney failure.
• All-cause mortality at 108 weeks.
• Proportion of participants experiencing one or more cardiovascular events between randomisation and 108 weeks.
• Time to first occurrence of a cardiovascular event.
• Safety and tolerability of the intervention.
• Change in quality of life measured using the Quality of Life Impact Survey for Kidney Disease (QDIS-CKD) at 6-monthly intervals from randomisation to week 108.
• Effect of the interventions on the time to the composite of ≥57% eGFR decline or kidney failure.

The clinical trial involves a total of **850 participants** diagnosed with **Chronic Kidney Disease**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on specific criteria, including a known diagnosis of chronic kidney disease from any cause, with an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73m². Additionally, participants must have a urine albumin-creatinine ratio (uACR) greater than 200 mg/g or a urine protein-creatinine ratio (uPCR) greater than 300 mg/g from the most recent result in the previous three months. All participants are required to be on a stable standard of care treatment for chronic kidney disease, including an SGLT2 inhibitor unless contraindicated, for at least four weeks prior to screening. The trial does not include a vulnerable population, and participants are expected to adhere to trial procedures as agreed upon with their treating physician. The study does not specify any particular lifestyle considerations such as diet or physical activity. The selection process ensures that participants and their treating physicians are willing and able to perform the trial's core procedures, with informed consent obtained prior to participation.

The clinical trial is designed to evaluate the efficacy of investigational agents in reducing the rate of estimated glomerular filtration rate (eGFR) decline in patients with **chronic kidney disease** (CKD). This is a Phase III, randomized, double-blind, controlled trial involving the administration of **finerenone** in the form of film-coated tablets, with a placebo group for comparison. The trial is set to commence recruitment in July 2025 and is expected to conclude by March 2029, with a total duration of approximately 108 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, CKD status, and current treatment regimen. Following randomization, participants will attend regular follow-up visits to monitor eGFR and other health parameters. The primary endpoint is the chronic eGFR slope estimated from all available eGFR values from week 4 to week 104. Secondary endpoints include changes in albuminuria, composite outcomes related to eGFR decline and kidney failure, cardiovascular events, and quality of life assessments.

The expected length of participant involvement is approximately 108 weeks, with visits scheduled at intervals to ensure comprehensive data collection. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide valuable insights into the potential benefits of finerenone in slowing CKD progression, thereby informing future therapeutic strategies.

The clinical trial involves the administration of **Kerendia** in two different dosages as the experimental treatment. **Kerendia** is available in the form of film-coated tablets and is manufactured by Bayer AG. The active substance in Kerendia is **finerenone**, a chemical compound with the synonym BAY 94-8862. The trial includes two dosage forms of Kerendia: 20 mg and 10 mg film-coated tablets. Both dosages are administered orally. The maximum daily dose for the 20 mg tablet is 20 mg, and for the 10 mg tablet, it is 10 mg. The maximum treatment period for both dosages is 24 weeks. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

The trial also includes a **placebo** as a non-experimental treatment. The placebo is a coated tablet designed to match the appearance of the Kerendia tablets, ensuring blinding in the study. The placebo is administered orally, with a maximum daily dose of 20 mg, and the treatment period is also set at 24 weeks. The use of a placebo allows for the comparison of the investigational agent's efficacy in reducing the rate of eGFR decline in patients with chronic kidney disease. Participant compliance with the placebo regimen is similarly monitored to maintain the integrity of the trial results.

Efficacy in the clinical trial titled "The Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect (CAPTIVATE)" will be assessed using both primary and secondary endpoints. The primary endpoint is the chronic **eGFR** slope, which will be estimated from all available eGFR values from week 4 to week 104. This measurement will help determine the rate of decline in kidney function over the course of the trial.

Secondary endpoints include several parameters: the change in albuminuria, measured by urine albumin-creatinine ratio (uACR) or urine protein-creatinine ratio (uPCR) between randomization and 24 weeks; a composite outcome of the proportion of participants experiencing a ≥40% eGFR decline between randomization and 108 weeks, and the proportion developing kidney failure at 108 weeks; time to a composite outcome of ≥40% eGFR decline or kidney failure; all-cause mortality at 108 weeks; and the proportion of participants experiencing cardiovascular events between randomization and 108 weeks. Additionally, the trial will assess the safety and tolerability of the treatment, changes in quality of life using the Quality of Life Impact Survey for Kidney Disease (QDIS-CKD) at 6-month intervals, and a domain-specific secondary outcome of time to the composite of ≥57% eGFR decline or kidney failure. The change in eGFR from randomization to the end of washout will also be evaluated.