22 July 2022 - - The first patient in Germany-based clinical-stage biotech company Cardior Pharmaceuticals' multicenter Phase 2 trial assessing efficacy and safety of CDR132L in 280 patients with reduced left ventricular ejection fraction after myocardial infarction (HF-REVERT), the company said.

CDR132L is an oligonucleotide-based ncRNA inhibitor that targets microRNA-132, a central regulator of pathological cardiac remodeling processes.

Cardiac remodeling is a debilitating and often life-threatening consequence of myocardial infarction that contributes to the development of heart failure.

Myocardial infarction, commonly known as a heart attack, is an extremely severe condition caused by a blockage in the coronary arteries limiting the blood supply to the heart.

Even if resolved, MI can lead to permanent damage of the heart cells initiating pathological cardiac remodeling resulting in the development of heart failure.

Heart failure remains one of the leading causes of death globally with only limited intervention options.

Cardior's lead candidate is designed to address the root cause of the pathological remodeling of the heart following MI to halt and reverse the detrimental signaling cascade and restore normal function of the heart.

CDR132L is the first-ever ncRNA-based therapy to enter Phase 2 studies in heart disease.

CDR132L's target is the well-established microRNA, miR-132, which plays a key role in pathological cardiac remodeling processes.

Levels of miR-132 are elevated in the cardiac tissue of heart failure patients, triggering well-defined molecular pathways.

Inhibition of miR-132 by CDR132L normalizes those pathways leading to a transformational change at the tissue level aiming to restore normal cardiac muscle function.

HF-REVERT (NCT05350969) is a multicenter, randomized, parallel, three-arm, placebo-controlled clinical proof-of-concept study designed to evaluate the safety and efficacy of CDR132L in 280 patients with heart failure and reduced left ventricular ejection fraction after MI.

The study consists of a 6-month double-blind period, and a 6-month extension period.

Patients enrolled in the Phase 2 study will be randomized to receive three intravenous CDR132L infusions at either 5 mg/kg, 10 mg/kg or placebo, administered 28 days apart as an add-on to Standard of Care treatment.

The primary endpoint of the study is defined as percentage change from baseline in the left ventricular end-systolic volume assessed by echocardiography. The left ventricular end-systolic volume index is used as a clinical assessment of the systolic function of the heart.

Additional outcome measures include changes in biomarkers such as NT-proBNP, as well as safety assessments including frequency of adverse events and quality of life questionnaires. The study will be conducted at locations across Europe involving approximately 60 clinical study centers.

The Phase 2 HF-REVERT trial has been designed in collaboration with Cardior's Scientific advisory board including renowned cardiology experts Prof. Johann Bauersachs, who is also the trial's primary investigator, and Prof. Scott Solomon, Co-chair of the trial. Cardior will initiate subsequent clinical trials for CDR132L in the US following discussions with the US Food and Drug Administration.