E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial Infarction |
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E.1.1.1 | Medical condition in easily understood language |
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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 | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 evaluate the safety, efficacy and pharmacokinetics (PK) of 3 dose levels of FDY-5301 compared to placebo in patients
presenting with an acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). |
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E.2.2 | Secondary objectives of the trial |
To examine the effect of FDY-5301 on heart function (assessed using cardiac MRI) and its effect on cardiac biomarkers (e.g. troponin I) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18-80 year old male subjects
2. 18 to 80 year old female subjects who are not of childbearing potential
3. Accepted for Primary PCI with diagnosis of first STEMI, based on clinical and ECG criteria (ST-elevation at the Jpoint 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
4. Assent/Informed consent to study participation |
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E.4 | Principal exclusion criteria |
1. Previous myocardial infarction
2. Left bundle branch block (LBBB)
3. Previous coronary artery bypass graft surgery (CABG)
4. Major hemodynamic instability or uncontrolled ventricular arrhythmias
5. Known contraindication to CMR (e.g. pacemaker)
6. Patients with known thyroid disease, or known allergy to iodide
7. Subjects with past or current renal impairment requiring dialysis
8. Body weight > 120 kg or Body Mass Index (BMI) > 35 kg/m2
9. Use of investigational drugs or devices within 30 days prior to enrollment into the study
10. Life expectancy of less than 1 year due to non-cardiac pathology
11. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome for this study will be the combined number and incidence rate of several arrhythmias of interest for 14 days post study drug. These arrhythmias include ventricular fibrillation, sustained and non-sustained ventricular tachycardia and high degree AV block. Continuous cardiac monitoring will occur for 14 days post PCI by means of wearable patch devices. |
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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) |
1. Infarct size parameters will be assessed by cardiac magnetic resonance (CMR) at 72 +/-24 hours post-study drug and 3 months post-study drug; the following will be compared between groups; infarct size as a proportion of ventricular volume (INF/VV), myocardial salvage index (MSI) and absolute myocardial infarction size (INF)
2. The proportion of patients with ST-segment resolution at 4 hours post-study drug
3. Serum levels of troponin calculated as AUC over 48 hours post treatment
4. Persistent arrhythmias at 30 days and 3 months
5. Measures of cardiac function by CMR including enddiastolic volume (EDV), end-systolic volume (ESV), fractional shortening (FS) and ejection fraction (EF) at discharge and 3 months
6. Biomarkers of cardiac injury, inflammation and remodeling out to 3 months of follow up
7. Cardiac related adverse events including the development of heart failure out to 3 months of follow up
8. Incidence of all cause and cardiac mortality out to 6 months of follow up |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 72 +/-24 hours post-study drug and 3 months post-study drug
3. 4 hours post study drug
3. 48 hours post treatment
4. at 30 days and 3 months
5. at discharge and 3 months
6. 3 months of follow up
7. to 3 months of follow up
8. to 6 months of follow up
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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 | Yes |
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 | No |
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 | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | No |
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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Last Visit of the Last Subject |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 25 |