Efficacy and Safety Evaluation of CDR132L in Patients with Post-Myocardial Infarction Reduced Left Ventricular Ejection Fraction: A Phase 2 Randomized Controlled Trial

Trial ID: 2023-507569-24-00
Protocol: CDR132L-P2-01
Sponsor: Cardior Pharmaceuticals GmbH

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Diseases & Conditions

Cardiac failure Cardiac failure chronic Cardiac failure acute Left ventricular failure

Objectives

The primary objective of this study is to evaluate the **efficacy** of two dose levels (5 and 10 mg/kg) of CDR132L compared with placebo. This is administered in three single intravenous doses given 28 days apart in patients with reduced left ventricular ejection fraction (LVEF ≤ 45%) following myocardial infarction (MI), either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), as an add-on therapy to standard of care (SoC) treatment. The clinical relevance of this objective lies in its potential to improve cardiac function and outcomes in patients with compromised heart function post-MI.

Secondary objectives include: - Assessing the **safety** of the two dose levels of CDR132L compared with placebo. - Evaluating the effects of CDR132L on cardiac function, efficacy-related biomarkers, and patient well-being. - Determining the effects of CDR132L on heart failure (HF) episodes, cardiac parameters, and exploratory biomarkers and immunogenicity compared with placebo.

Participants

The clinical trial involves a total of **50 participants** who are both male and female, aged between **30 to 80 years**. The study population consists of individuals who have experienced a **myocardial infarction** and have a left ventricular ejection fraction (LVEF) of 45% or less. Participants were selected based on specific criteria, including a history of spontaneous acute myocardial infarction (type I) and a body weight of 120 kg or less. The trial includes patients who have undergone percutaneous coronary intervention for their myocardial infarction event. The participants are required to have an N-terminal pro B-type natriuretic peptide level between 125 pg/ml and 8000 pg/ml at screening. The trial population is characterized by a vulnerable group, as it includes individuals with significant cardiac conditions. Lifestyle factors such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is a **Phase 2**, multicenter, randomized, parallel, 3-arm, placebo-controlled study designed to assess the efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction (LVEF ≤ 45%) following a **myocardial infarction**. The trial involves administering two dose levels of CDR132L (5 mg/kg and 10 mg/kg) compared to a placebo, with each treatment given as a single intravenous infusion every 28 days over a period of three months. The study is expected to conclude by April 2025, with recruitment having commenced in June 2022.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, history of myocardial infarction, and specific biomarker levels. Randomization will occur no later than 14 days post-diagnosis of the index myocardial infarction event. Following the initial treatment, participants will attend follow-up visits at months 3, 6, and 12 to monitor changes in LVEF and other cardiac parameters, as well as to assess the frequency of adverse events and abnormalities in clinical laboratory assessments. The primary endpoint is the percent change from baseline in left ventricular end-systolic volume index (LVESVI) at month 6, with secondary endpoints including changes in LVEF, troponin T levels, and other efficacy-related biomarkers.

The expected duration of participant involvement is approximately 12 months, with conditions for early termination including significant adverse events or withdrawal of consent. The study aims to provide valuable insights into the therapeutic potential of CDR132L as an add-on therapy to standard care in patients with heart failure following myocardial infarction.

Treatment

The clinical trial involves the administration of **CDR132L**, an experimental medication developed by Cardior Pharmaceuticals GmbH. **CDR132L** is formulated as a **powder for concentrate for solution for infusion**. The active substances in this formulation are **CDR132L** and **CDR132L sodium**, both of which are derived from nucleic acids. The medication is administered via **intravenous infusion**. Participants receive two dose levels, 5 mg/kg and 10 mg/kg, administered in three single doses, each given 28 days apart. The maximum daily dose is 10 mg/kg, with a total maximum dose of 30 mg/kg over the treatment period. The treatment period spans a maximum of three months. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** group, which receives a **solvent and diluting agent** classified under the ATC code V07AB. This placebo is also administered as an **intravenous infusion**. The pharmaceutical form of the placebo is denoted as PHF00017MIG. The maximum daily dose for the placebo is 24 ml, with a total maximum dose of 72 ml over the treatment period, which is consistent with the experimental treatment duration of three months. The placebo serves as a comparator to evaluate the efficacy and safety of **CDR132L** in patients with reduced left ventricular ejection fraction (≤ 45%) following myocardial infarction. The trial is designed to assess the efficacy of **CDR132L** as an add-on therapy to standard-of-care treatment.

Efficacy

The efficacy of the investigational product CDR132L in patients with reduced left ventricular ejection fraction (LVEF ≤ 45%) following myocardial infarction will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percent change from baseline in left ventricular end-systolic volume index (LVESVI) at Month 6, as measured by echocardiography (ECHO) conducted by a central laboratory. Secondary endpoints include changes from baseline in LVEF and LVESVI at Months 3, 6, and 12, as well as changes in troponin T levels and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels over the same time periods.

Additional secondary endpoints involve assessments of patient well-being using the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, heart failure events such as cardiovascular mortality and hospitalizations, and changes in New York Heart Association (NYHA) class. ECHO will also be used to evaluate parameters such as left ventricular end-diastolic volume, diastolic flow velocities, and strain analysis. Electrocardiograms (ECGs) will be analyzed for QRS complex and other interpretations. Exploratory biomarkers, including MicroRNA-132 (miR-132) and cardiac fibrosis markers, will be monitored for target engagement and immunogenic responses, such as anti-drug antibodies, over time.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female patients, aged ≥ 30 to ≤ 80 years at the date of signing informed consent which is defined as the beginning of the Screening Period.
Spontaneous acute mycardial infarction (AMI) (type I) based on the universal MI definition with randomization to occur no later than 14 days after index event diagnosis.
Patient with a LVEF ≤ 45% as measured by ECHO after MI diagnosis (STEMI or NSTEMI).
Patient with previous MI events in history can be included.
Patient with body weight of ≤ 120 kg.
N-terminal pro B-type natriuretic peptide level ≥ 125 pg/ml and < 8000 pg/ml at screening.
Patient with STEMI/NSTEMI who underwent percutaneous coronary intervention for this event.

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Exclusion Criteria

A woman of childbearing potential (WOCBP).
Patient with HF of non-ischemic origin; e.g., myocarditis, alcoholic cardiomyopathy.
Patient with New York Heart Association (NYHA) class IV at screening or randomization.
Patient has any planned cardiac intervention (angiogram without angioplasty is acceptable) or any other planned surgery after the Screening Period.
Patient has severe valvular heart disease.
Patient has systolic BP < 90 mmHg or > 180 mmHg, diastolic BP < 50 mmHg or > 110 mmHg, and/or heart rate < 50 or > 100 beats/minute at screening or randomization.
Patient with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on dialysis.
Patient with hepatic insufficiency classified as Child-Pugh B or C.
Patient has medical history of disease(s) affecting the blood-brain-barrier, e.g., stroke within 6 months or multiple sclerosis.
Patient has medical history of bleeding disorders or has thrombocytopenia (platelets < 100,000/μL).
Patient has poorly controlled diabetes as determined by the Investigator.
Patient has a history or presence of any of the following cardiac conditions: known structural cardiac abnormalities beyond HF, family history of long QT syndrome, cardiac syncope, or recurrent, idiopathic syncope.
Any clinically significant abnormalities, at the discretion of the Investigator, in rhythm, conduction, or morphology of resting ECG that pose an additional safety risk to patients.
Patient with active and clinical relevant "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" infection confirmed as per the local testing guidelines at screening.
Patient is not to be enrolled into the study if they received any prohibited therapy within 3 months of screening.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Czechia	Not Recruiting	27 Jun 2022	28
Germany	Not Recruiting	27 Jun 2022	20
Greece	Not Recruiting	27 Jun 2022	50
Hungary	Not Recruiting	27 Jun 2022	20
The Netherlands	Not Recruiting	27 Jun 2022	—
Poland	Not Recruiting	27 Jun 2022	72
Spain	Not Recruiting	27 Jun 2022	20
Netherlands	—	—	20