Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled study to assess efficacy and safety of CDR132L in patients with reduced Left Ventricular Ejection Fraction (LVEF) (≤ 45%) after myocardial infarction (MI). This study consists of a screening period (to occur at least 3 days after MI diagnosis), a 6-month double-blind period, and a 6-month extension period with the End of Study (EOS) Visit at Day 360/Month 12. Two dosages of CDR132L will be tested against placebo on their effects on patients, who just had a heart attack in addition to standard care. The aim of the study is to show that CDR132L is safe and effective to improve heart failure in such patients.

Official Title
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Phase 2, Multicenter, Randomized, Parallel, 3-arm, Placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction (≤ 45%) After Myocardial Infarction

Conditions
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Myocardial Infarction, Acute, Heart Failure, Left Sided

Intervention / Treatment
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* Drug: CDR132L
* Drug: Placebo to CDR132L


Participation Criteria
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Eligibility Criteria
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Main 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. 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 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDR132L 5 mg<br>CDR132L 5 mg/kg body weight intravenous in single dose on Day 1, Day 29 and Day 57 | Drug: CDR132L<br>* CDR132L is a synthetic antisense oligonucleotide (ASO) and a selective inhibitor of microRNA-132-3p (miR-132). miR-132 in cardiomyocytes is a central switch affecting the expression of genes that are crucially involved in maladaptive cardiac remodeling, transformation, and pathological cardiac growth (hypertrophy), contributing to adverse cardiac remodeling and heart failure (HF).1-5 Aberrant expression of miR-132 in cardiac cells is causally associated with cardiac remodeling and HF progression.<br>|
| Experimental: CDR132L 10 mg<br>CDR132L 10 mg/kg body weight intravenous in single dose on Day 1, Day 29 and Day 57 | Drug: CDR132L<br>* CDR132L is a synthetic antisense oligonucleotide (ASO) and a selective inhibitor of microRNA-132-3p (miR-132). miR-132 in cardiomyocytes is a central switch affecting the expression of genes that are crucially involved in maladaptive cardiac remodeling, transformation, and pathological cardiac growth (hypertrophy), contributing to adverse cardiac remodeling and heart failure (HF).1-5 Aberrant expression of miR-132 in cardiac cells is causally associated with cardiac remodeling and HF progression.<br>|
| Placebo Comparator: Placebo<br>Placebo intravenous in single dose on Day 1, Day 29 and Day 57 | Drug: Placebo to CDR132L<br>* Placebo to CDR132L<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiography (ECHO) | Percent change from baseline (screening to occur at least 3 days after MI diagnosis as measured by ECHO [central laboratory]) in Left Ventricular End-Systolic Volume (LVESVI) at Month 6. | 6 months |