Evaluation of Finerenone and Drug Combination in Reducing Cardiovascular Disease Risk in Type 1 Diabetes Patients at High Cardiovascular Risk

The primary objective of the study is to evaluate the efficacy and safety of a **multifactorial intervention** (MFI) in individuals with **type 1 diabetes** (T1D) who are at high risk of cardiovascular disease (CVD). The study aims to compare the outcomes of intensified care based on MFI with ambitious treatment targets against standard care. Additionally, the study investigates the safety and efficacy of 40 mg **finerenone** in reducing the risk of cardiovascular death and hospitalization for heart failure (HHF) in this population. This is clinically relevant as it addresses the significant cardiovascular risks associated with T1D, potentially improving patient outcomes through targeted interventions.

Secondary objectives include:

• Determining whether MFI is superior to standard care concerning a composite endpoint of renal function, including end-stage kidney disease (ESKD), sustained eGFR <15 ml/min/1.73 m², or >50% sustained decline in eGFR.
• Evaluating the effect of MFI on the individual components of the composite endpoints.
• Assessing whether MFI is superior to standard care in reducing all-cause mortality.
• Investigating the effect of MFI on the development and progression of painful and painless diabetic peripheral neuropathy.
• Determining the effect of MFI on the composite endpoint of cardiovascular death and HHF.

The clinical trial involves a total of **50 participants** diagnosed with **Type 1 diabetes**. The study population includes both male and female subjects aged 40 years and older. Participants were selected based on specific health criteria, including a diagnosis of Type 1 diabetes before the age of 30 with insulin treatment from onset, or if diagnosed after 30, insulin from onset with diabetic ketoacidosis or positive autoantibodies. The trial targets individuals with additional health conditions such as chronic kidney disease, a history of ischemic heart disease, heart failure, or obesity (BMI >35 kg/m²), or those with a 10-year cardiovascular disease risk greater than 10% according to the Steno Type 1 Risk Engine. Participants are required to have the ability to communicate effectively with the investigator and comprehend informed consent. Fertile females must adhere to stringent contraceptive measures throughout the study duration and for a specified period afterward. The trial does not include a vulnerable population, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of a multifactorial intervention strategy in individuals with **type 1 diabetes** at high risk of cardiovascular disease. This is a randomized, double-blind, controlled trial with an estimated duration extending until June 2029. The trial will involve the administration of **finerenone** and other investigational products, such as **sotagliflozin** and **semaglutide**, in various formulations, including film-coated tablets and solutions for injection. The primary objective is to assess whether the intervention strategy is superior to standard care in reducing the time to first major adverse cardiovascular events and hospitalization for heart failure.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, duration of diabetes, and presence of chronic kidney disease or cardiovascular history. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the intervention, and any adverse events. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the outcomes of the intervention.

The expected length of participant involvement is approximately five years, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will also explore secondary endpoints, such as renal function and all-cause mortality, to provide a comprehensive evaluation of the intervention's impact. Participants will be required to adhere to the study protocol, including the use of contraceptives for fertile females, and will be monitored for compliance throughout the trial duration.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. The primary experimental medication is **Finerenone**, marketed under the product name BAY 94-8862, which is provided in the form of a **film-coated tablet**. This medication is administered orally with varying dosages: 10 mg, 20 mg, and 40 mg per day, depending on the specific treatment group. The maximum treatment period for Finerenone is 60 days. The active substance, Finerenone, is of chemical origin and is produced by Bayer AG. Participant compliance with the dosing schedule is monitored throughout the trial.

Another experimental medication used in the trial is **Sotagliflozin**, which is also administered orally in the form of a film-coated tablet. The maximum daily dose for Sotagliflozin is 200 mg, with a total treatment period of 60 days. The active substance, Sotagliflozin, is chemically derived, and its administration is closely monitored to ensure adherence to the prescribed dosing regimen.

The trial also includes the use of **Semaglutide**, marketed as Ozempic, which is provided as a solution for injection in a pre-filled pen. Semaglutide is administered subcutaneously with dosages of 0.25 mg, 0.5 mg, and 1 mg, depending on the treatment group. The maximum treatment period for Semaglutide is 60 days. The active substance, Semaglutide, is a protein of other origin, produced by Novo Nordisk A/S. The administration of Semaglutide is monitored to ensure participant compliance with the dosing schedule.

In addition to the experimental medications, the trial may involve the use of standard-of-care therapies as comparator treatments. These treatments are administered according to established medical guidelines and are used to evaluate the efficacy and safety of the experimental medications in comparison to existing therapeutic options. Participant adherence to all treatment protocols is systematically monitored to ensure the integrity of the trial data.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the time to first major adverse cardiovascular events (MACE) and first hospitalization for heart failure (HHF). This will involve analyzing whether a multifactorial intervention strategy is superior to standard care in terms of the time to the first event of a composite endpoint, which includes first non-fatal myocardial infarction, first non-fatal stroke, cardiovascular death, or first hospitalization for heart failure, evaluated five years after the inclusion of the first patient.

Secondary endpoints will assess the superiority of the multifactorial intervention over standard care concerning renal function and all-cause mortality. Specifically, the trial will evaluate the time to a composite endpoint of renal function, including end-stage kidney disease (ESKD), sustained eGFR <15 ml/min/1.73 m², or a >50% sustained decline in eGFR from baseline. Additionally, the trial will determine the effect of the intervention on the individual components of the composite endpoints and overall mortality rates.

The trial will involve the administration of **finerenone** at a dose of 40 mg to individuals with type 1 diabetes at risk of cardiovascular death and hospitalization for heart failure. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial duration, which is estimated to conclude by June 2029. The trial aims to provide comprehensive data on the efficacy of the intervention strategy in reducing cardiovascular disease in type 1 diabetes patients.