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

The primary objective of the study is to evaluate 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 slowing the progression of CKD can delay the onset of kidney failure and reduce the need for renal replacement therapies, improving patient outcomes and quality of life.

Secondary objectives include:

• Change in albuminuria between randomization and 24 weeks.
• Proportion of participants experiencing a 40% eGFR decline and those developing kidney failure at 108 weeks.
• Time to ≥40% eGFR decline from randomization or kidney failure.
• All-cause mortality at 108 weeks.
• Proportion of participants experiencing one or more cardiovascular events between randomization 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 randomization 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 **700 participants** diagnosed with **chronic kidney disease**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a known chronic kidney disease from any cause, with an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73m². All participants are currently receiving standard of care treatment as determined by their treating physician. The trial population was selected based on their eligibility for randomization in at least one recruiting domain-specific appendix, and both the participant and their treating physician must be willing and able to perform trial procedures. 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. They should be on a stable standard of care treatment for chronic kidney disease, including a sodium-glucose co-transporter-2 inhibitor (SGLT2i), unless there is a documented reason not to use it, for four weeks before screening. The treating physician must also believe that finerenone is clinically appropriate for the participant. The trial does not include a vulnerable population, and lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **finerenone** in reducing the rate of eGFR decline in patients with **chronic kidney disease** (CKD) compared to a placebo. This is a Phase III, randomized, double-blind, controlled trial. The trial will span approximately four years, with an estimated recruitment start date in September 2024 and an estimated end date in August 2028. Participants will be randomly assigned to receive either finerenone or a placebo, both administered as film-coated tablets orally. The maximum daily dose for finerenone is 20 mg, with a treatment period of up to 104 weeks.

The study will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. During the screening visit, eligibility criteria will be assessed, including age (≥18 years), known CKD with an eGFR ≥25 mL/min/1.73m², and current standard of care treatment. Participants must also have a urine albumin-creatinine ratio (uACR) >200 mg/g or urine protein-creatinine ratio (uPCR) >300 mg/g. Follow-up visits will occur at regular intervals to monitor the primary endpoint, which is the eGFR slope from randomization to week 108, and secondary endpoints such as changes in albuminuria, composite outcomes related to eGFR decline, and cardiovascular events.

The expected length of participant involvement is up to 108 weeks, with conditions for early termination including significant adverse events, withdrawal of consent, or non-compliance with trial procedures. The trial aims to provide comprehensive data on the safety and tolerability of finerenone, as well as its impact on quality of life, measured using the Quality of Life Impact Survey for Kidney Disease at six-month intervals. The trial's main objective is to identify investigational agents or combinations that effectively slow CKD progression, offering potential therapeutic benefits beyond standard care.

The clinical trial involves the administration of **Finerenone**, an investigational medication, in the form of a **film-coated tablet**. The product, identified by the sponsor product code BAY 94-8862, is manufactured by Bayer AG. Finerenone is a chemical substance administered orally. The trial includes two dosage regimens: a maximum daily dose of 20 mg and a maximum daily dose of 10 mg, with a total maximum dose of 20 mg over a treatment period of up to 104 weeks. The primary objective is to evaluate the efficacy of Finerenone in reducing the rate of eGFR decline in patients with chronic kidney disease (CKD) compared to placebo, while receiving standard-of-care therapy.

A **placebo** is also utilized in this study, serving as a comparator to the active treatment. The placebo is designed to mimic the appearance of the Finerenone film-coated tablet, ensuring blinding in the trial. The placebo does not contain any active pharmaceutical ingredients and is administered orally in the same manner as the active treatment. The use of a placebo allows for the assessment of the investigational drug's efficacy by providing a baseline for comparison.

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 **eGFR slope**, calculated using eGFR values from randomization to week 108, to evaluate the rate of decline in kidney function. Secondary endpoints include changes in albuminuria, measured by urine albumin-creatinine ratio (uACR) or urine protein-creatinine ratio (uPCR) between randomization and 24 weeks, and a composite outcome of the proportion of participants experiencing a 40% eGFR decline or developing kidney failure at 108 weeks. Additional secondary endpoints involve 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. The trial will also 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-monthly intervals, and a domain-specific secondary outcome of time to the composite of ≥57% eGFR decline or kidney failure.