Efficacy and Safety of Anakinra in Inflammatory Dilated Cardiomyopathy: A Phase IIa Randomized, Double-Blind, Monocentric Clinical Trial

The primary objective of this clinical trial is to evaluate the **efficacy** of IL-1 therapeutic blockade with **Anakinra** in improving Left Ventricular Ejection Fraction (LVEF) in patients with inflammatory dilated cardiomyopathy. This will be assessed using Trans Thoracic Echocardiography (TTE) at 4 weeks. The improvement in LVEF is clinically significant as it may indicate enhanced cardiac function and potential benefits in the management of dilated cardiomyopathy, a condition characterized by impaired heart muscle function leading to heart failure. No secondary objectives are specified for this study.

The clinical trial focuses on participants diagnosed with **inflammatory dilated cardiomyopathy**. The study population includes both male and female subjects, aged between 18 and 75 years, who are not part of a vulnerable population. Participants were selected based on specific criteria, including a diagnosis of dilated cardiomyopathy according to current guidelines, symptoms of heart failure that have not improved or have worsened despite at least three months of optimal therapy, and a left ventricular ejection fraction of less than 50% as assessed by echocardiography. Additionally, participants must have increased high-sensitive troponin T levels or findings suggestive of myocardial inflammation on cardiac MRI within the past six months, and no significant coronary artery disease. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The ability to provide informed consent is required for participation. The trial does not include a vulnerable population, ensuring a focus on individuals who meet the outlined health criteria.

The clinical trial is designed to evaluate the efficacy and safety of **anakinra** in the treatment of **inflammatory dilated cardiomyopathy**. This is a Phase IIa, randomized, double-blind, monocentric trial comparing the effects of anakinra plus standard of care versus standard of care alone. The primary objective is to assess the improvement in left ventricular ejection fraction (LVEF) using transthoracic echocardiography at four weeks. The trial is expected to run from May 25, 2023, to December 31, 2025, with a maximum treatment period of 12 weeks for each participant.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age (18 to 75 years), diagnosis of dilated cardiomyopathy, and absence of coronary artery disease. The inclusion visit will involve baseline assessments, including echocardiography and cardiac MRI, to establish initial LVEF and myocardial inflammation status. Subsequent follow-up visits will occur at regular intervals to monitor safety, adherence, and efficacy outcomes, with the primary endpoint being the improvement in LVEF at four weeks. The end-of-study visit will include a final assessment of cardiac function and overall health status.

Participant involvement is expected to last up to 12 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study procedures. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the findings, contributing valuable insights into the therapeutic potential of anakinra for this patient population.

The clinical trial involves the administration of **Anakinra**, a biological medicinal product, as the experimental treatment. Anakinra is a protein-based therapeutic agent classified under the ATC code L04AC03. It is formulated for **subcutaneous use** and is provided in a pharmaceutical form identified as PHF00231MIG. The maximum daily dose of Anakinra is 100 mg, with a total maximum dose also set at 100 mg. The treatment period is limited to a maximum of 12 weeks. The administration of Anakinra is intended to evaluate its efficacy in improving Left Ventricular Ejection Fraction (LVEF) in patients with dilated cardiomyopathy, as assessed by Trans Thoracic Echocardiography (TTE) at 4 weeks.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of Anakinra as the investigational product. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to decipher IL-1 mediated inflammation and its impact on cardiac function, specifically targeting the improvement of LVEF in the study population.

The clinical trial aims to assess the efficacy of **Anakinra** in the treatment of dilated cardiomyopathy by evaluating the improvement in left ventricular function. The primary endpoint for efficacy assessment is the increase in Left Ventricular Ejection Fraction (LVEF), which will be measured using transthoracic echocardiography (TTE) at the 4-week mark. This method provides a non-invasive means to evaluate cardiac function and is a standard tool in cardiology for assessing ejection fraction.