A Study of Acute Myocardial Infarction Using FDY-5301

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics (PK) of three dose levels of FDY-5301 compared to placebo in STEMI patients undergoing PCI.

Detailed Description
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The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called FDY-5301 as a possible treatment to reduce the size of the injury to the heart caused by the heart attack. An experimental drug is one that is being tested and is not approved by the United States Food and Drug Administration (FDA). A heart attack occurs when a heart (coronary) artery supplying blood to the heart muscle becomes blocked and the heart muscle is injured. You will be having a cardiac catheterization procedure to clear the blockage in your coronary artery that caused your heart attack. This procedure works well but may not completely prevent some injury to the heart muscle which occurs when the blood supply is initially restored to the heart. This is known as reperfusion injury. FDY-5301 is a single intravenous injection. About 80 subjects are expected to participate in this study at about 20 research sites in the United States and Europe. Each subject's participation is expected to last about 6 months after receiving the study drug. Subjects who meet all inclusion criteria will be randomly assigned to one of 4 study groups. Three groups will receive FDY-5301 (low, intermediate, or high dose) and 1 group will receive a placebo.The study drug (FDY-5301 or placebo) will be given through a vein (intravenously) during the catheterization procedure. This is a double-blind study so neither the patient nor study personnel will know whether the dose is active drug or placebo until the end of the study.

Official Title
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A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of Intravenous FDY-5301 in Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction, STEMI

Intervention / Treatment
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* Drug: FDY-5301
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 year old male subjects 18 to 80 year old female subjects who are not of child-bearing potential. Accepted for Primary PCI with diagnosis of first STEMI, based on clinical and ECG criteria (ST-elevation at the J-point in two contiguous leads with the cut-off points: ≥0.2 millivolt (mV) in men or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in other leads), within 12 hours of symptom onset. Written informed consent prior to study participation (either by the subject or a legally authorized representative of the subject) Exclusion Criteria: Previous myocardial infarction Left bundle branch block (LBBB) Previous coronary artery bypass graft surgery (CABG) Major hemodynamic instability or uncontrolled ventricular arrhythmias Known contraindication to CMR Patients with known thyroid disease Subjects with past or current renal impairment requiring dialysis Pregnant or females of child bearing potential Body weight > 120 kg or Body Mass Index (BMI) > 35 kg/m2 Use of investigational drugs or devices within 30 days prior to enrollment into the study. Life expectancy of less than 1 year due to non-cardiac pathology Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All subjects who fulfill all study eligibility criteria will be randomized to receive one of the 4 treatments.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDY-5301 Low Dose<br>Anticipated n=20 | Drug: FDY-5301<br>* FDY-5301 will be administered once, intravenously, by a healthcare professional. Dosage will be administered on a body weight basis, according to treatment assignment and using the subject's body weight determined on the dose administration day.<br>|
| Experimental: FDY-5301 Intermediate Dose<br>Anticipated n=20 | Drug: FDY-5301<br>* FDY-5301 will be administered once, intravenously, by a healthcare professional. Dosage will be administered on a body weight basis, according to treatment assignment and using the subject's body weight determined on the dose administration day.<br>|
| Experimental: FDY-5301 High Dose<br>Anticipated n=20 | Drug: FDY-5301<br>* FDY-5301 will be administered once, intravenously, by a healthcare professional. Dosage will be administered on a body weight basis, according to treatment assignment and using the subject's body weight determined on the dose administration day.<br>|
| Placebo Comparator: Placebo<br>Anticipated n=20 | Other: Placebo<br>* Placebo will be administered intravenously by a healthcare professional. Dosage will be administered on a body weight basis, according to treatment assignment and using the subject's body weight determined on the dose administration day.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arrhythmias of Interest, 48 Hours (Overall) | Number of patients experiencing clinically relevant arrhythmias during the first 48 hours post-treatment. | First 48 hours post-treatment | 
| Arrhythmias of Interest Incidence Rate, 48 Hours (Overall) | Incidence rate of clinically relevant arrhythmias during the first 48 hours post-treatment defined as the number of patients who experienced an arrhythmia divided by the total person-monitoring time within each treatment group | 48 hours post-treatment | 
| Arrhythmias of Interest, 14 Days (Overall) | Number of patients experiencing clinically relevant arrhythmias 48 hours to 14 days post-treatment. | 48 hours to 14 days Post Percutaneous Coronary Intervention (PCI) | 
| Arrhythmias of Interest Incidence Rate, 14 Days (Overall) | Incidence rate of clinically relevant arrhythmias 48 hours to 14 days post-treatment defined as the number of patients who experienced an arrhythmia divided by the total person-monitoring time within each treatment group | 48 hours to 14 days Post Percutaneous Coronary Intervention (PCI) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct Size Relative to Ventricular Volume, 72 Hours (Overall) | Infarct size relative to ventricular volume (INF/VV) at 72 hours post-treatment | 72 hours post-treatment | 
| Infarct Size Relative to Ventricular Volume, 3 Months (Overall) | Infarct size relative to ventricular volume (INF/VV) at 3 months post-treatment) | 3 months post-treatment | 
| Infarct Size Relative to Ventricular Volume, 72 Hours (Anterior Infarcts) | Infarct size relative to ventricular volume (INF/VV) at 72 hours post-treatment) | 72 hours post-treatment | 
| Infarct Size Relative to Ventricular Volume, 3 Months (Anterior Infarcts) | Infarct size relative to ventricular volume (INF/VV) at 3 months post-treatment) | 3 months post-treatment | 
| Left Ventricular End Systolic Volume Index, 72 Hours (Overall) | Left ventricular end systolic volume index (LVESVi) at 72 hours post-treatment | 72 hours post-treatment | 
| Left Ventricular End Systolic Volume Index, 3 Months (Overall) | Left ventricular end systolic volume index (LVESVi) at 3 Months post-treatment | 3 months post-treatment | 
| Left Ventricular End Systolic Volume Index, 72 Hours (Anterior Infarcts) | Left ventricular end systolic volume index (LVESVi) at 72 Hours post-treatment | 72 hours post-treatment | 
| Left Ventricular End Systolic Volume Index, 3 Months (Anterior Infarcts) | Left ventricular end systolic volume index (LVESVi) at 3 Months post-treatment | 3 months post-treatment | 
| Left Ventricular Ejection Fraction, 72 Hours (Overall) | Left ventricular ejection fraction at 72 hours post-treatment | 72 hours post-treatment | 
| Left Ventricular Ejection Fraction, 3 Months (Overall) | Left Ventricular Ejection Fraction at 3 Months (Overall) | 3 months post-treatment | 
| Left Ventricular Ejection Fraction, 72 Hours (Anterior Infarcts) | Left ventricular ejection fraction at 72 hours post-treatment | 72 hours post-treatment | 
| Left Ventricular Ejection Fraction, 3 Months (Anterior Infarcts) | Left Ventricular Ejection Fraction at 3 Months (Anterior Infarcts) | 3 months post-treatment | 
| Serum Troponin Concentrations, 48 Hours (Overall) | Area under the curve of serum troponins measured over 48 hours post-treatment | 48 hours post-treatment | 
| Serum Troponin Concentrations, 48 Hours (Anterior Infarcts) | Area under the curve of serum troponins measured over 48 hours post-treatment | 48 hours post-treatment | 
| ST-segment Resolution | Proportion of patients with ST-segment resolution at 4 hours post-dose | 4 hours post-dose |