E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Reduced Left Ventricular Ejection Fraction After Myocardial Infarction |
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E.1.1.1 | Medical condition in easily understood language |
Heart Failure after Myocardial Infarction |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036233 |
E.1.2 | Term | Post myocardial infarction syndrome |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of 2 dose levels (5 and 10 mg/kg) of CDR132L compared with placebo administered in 3 single IV doses given 28 days apart in patients with reduced LVEF ≤ 45% after MI (STEMI or NSTEMI) as add-on therapy to SoC treatment |
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E.2.2 | Secondary objectives of the trial |
•To assess the safety of 2 dose levels (5 and 10 mg/kg) of CDR132L compared with placebo •To assess the effects of CDR132L compared with placebo on cardiac function •To assess the effects of CDR132L compared with placebo on efficacy related biomarkers •To assess the effects of CDR132L compared with placebo on patient well being |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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. 2. Spontaneous AMI (type I) based on the universal MI definition with randomization to occur no later than 14 days after index event diagnosis. 3. Patient with a LVEF ≤ 45% as measured by ECHO after MI diagnosis (STEMI or NSTEMI). 4. Patient with NSTEMI with evidence of significant myocardial necrosis, evidenced through a troponin T or troponin I increase to at least 5 times the upper limit of normal (ULN) at MI index event diagnosis. 5. Patient with previous MI events in history can be included. 6. A male patient must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 30 days after the last dose of study treatment and refrain from donating sperm during this period. 7. Patient with body weight of ≤ 120 kg. 8. N-terminal pro B-type natriuretic peptide level ≥ 125 pg/ml and < 8000 pg/ml at screening. Note: NT-proBNP values required for eligibility confirmation may be collected at any time post MI either through medical history (e.g., site has collected it as SoC once the patient came to the hospital), through a local laboratory assessment, or by sending a sample to the central laboratory (if sites use the SoC sample or the local laboratory sample for eligibility confirmation, no additional sample for central laboratory assessment is needed). 9. Patient with STEMI/NSTEMI who underwent percutaneous coronary intervention for this event. 10. Capable of giving signed informed consent as described in Appendix 2 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. |
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E.4 | Principal exclusion criteria |
1.A woman of childbearing potential (WOCBP) as defined in Appendix 5. 2.Patient with HF of non-ischemic origin; e.g., myocarditis, alcoholic cardiomyopathy. 3.Patient with history of decompensated HF or a history of LVEF < 30% within 6 months prior to the Screening Period. 4.Patient with NYHA class IV at screening or randomization. 5.Patient has any planned cardiac intervention (angiogram without angioplasty is acceptable) or any other planned surgery after the Screening Period. 6.Patient has severe valvular heart disease. 7.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. 8.Patient with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on dialysis. 9.Patient with hepatic insufficiency classified as Child Pugh B or C. 10.Patient with known active human immunodeficiency virus, Hepatitis B, or Hepatitis C infection at screening. 11.Impaired hepatic function defined by a total bilirubin level of ≥ 2 × the ULN and ALT levels of ≥ 3 × ULN. 12.Patient has medical history of disease(s) affecting the blood-brain-barrier, e.g., stroke within 6 months or multiple sclerosis. 13.Patient has medical history of bleeding disorders or has thrombocytopenia (platelets < 100,000/µL). 14.Patient has poorly controlled diabetes as determined by the Investigator. 15.Patient is currently on treatment for epilepsy. 16.Patient has a current or relevant history of physical or psychiatric illness that is/are not stable or may require a change in treatment, use of prohibited therapies during the study, or cause the patient to be unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the study drug or study procedures. 17.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. 18.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. This will include patients with any of the following (at Screening Visit or Day -1): a)Clinically significant PR (PQ) interval prolongation. b)Intermittent second- or third degree atrioventricular block. c)Sustained cardiac arrhythmia including (but not limited to) supraventricular tachycardia, any symptomatic arrhythmia with the exception of isolated extra systoles. 19.Patient with active “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” infection confirmed as per the local testing guidelines at screening. 20.Patient has other significant disease or disorder which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence the result of the study or the patient's ability to participate in the study. 21.Patient has received an investigational product or treated with an investigational device within 90 days prior to first study drug administration. 22.Patient has known or suspected intolerance or hypersensitivity to the study drug, any closely related compound, or any of the stated ingredients. 23.Patient is not to be enrolled into the study if they received any prohibited therapy within 3 months of screening. a)Treatment with anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy, or gene therapy) at any time during the study. b)Administration of any other investigational agent within 3 months before the first administration of study drug or at any time before the patient’s completion of the study. 24.Patient is involved in the planning and/or conduct of the study (applies to Sponsor staff, staff at the study site, and third-party vendors). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in LVESVI (screening to occur at least 3 days after MI diagnosis as measured by ECHO [central laboratory]) at Month 6 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Endpoint 1: Frequency of adverse events and abnormalities in clinical laboratory assessments, vital signs, physical examination, ECGs, and urinalysis Secondary Endpoint 2: Change from baseline LVEF (absolute/relative) at Months 3, 6, and 12. Change from baseline LVESVI at Month 3 (absolute/relative), Month 6 (absolute), and Month 12 (absolute/relative) Secondary Endpoint 3: Change from baseline in absolute/relative troponin T (ng/L) at Months 3, 6, and 12. Change from baseline in absolute/relative values over time for the following efficacy related biomarkers: oN-terminal pro B-type natriuretic peptide (NT-proBNP) Secondary Endpoint 4: oWell-being as evaluated by change from baseline at Months 6 and 12 in the following parameters: oMean KCCQ score and mean scores of subdomains (symptom burden, physical limitation, and quality of life) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Endpoint 1: Through out the study Secondary Endpoint 2: 3,6 and 12 months Secondary Endpoint 3: 3,6 and 12 months Secondary Endpoint 4: 6 and 12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
Last Subject Last Visit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |