E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ST-elevation 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 | LLT |
E.1.2 | Classification code | 10064345 |
E.1.2 | Term | ST segment elevation myocardial infarction |
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 evaluate the effect of MEDI6012 on infarct size compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of MEDI6012 on LV systolic function compared to placebo.
2. To evaluate the effect of MEDI6012 on non-calcified coronary plaque regression/progression from baseline to 10-12 weeks compared with placebo.
3. To evaluate the effect of MEDI6012 on remodeling of the LV measured by myocardial mass and volumes.
4. To evaluate the safety and tolerability of MEDI6012.
5. To describe the pharmacokinetics (PK) and immunogenicity of MEDI6012. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women without child-bearing potential aged 30-80 years of age who are capable and willing to provide informed consent.
2. Acute STEMI diagnosed by ST elevation (≥ 0.1 mV) in 2 contiguous leads
3. Planned for pPCI
4. Ischemic symptoms for ≤ 6 hours
5. Capable of completing study visits |
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E.4 | Principal exclusion criteria |
1. Pre-randomization cardiogenic shock or cardiopulmonary resuscitation
2. Fibrinolytic administration for index event
3. Known prior MI or prior coronary artery bypass graft (CABG) surgery
4. Known pre-existing cardiomyopathy
5. History of anaphylaxis
6. Suspected non-thrombotic etiology (ie, vasospasm, dissection, Takotsubo cardiomyopathy)
7. Other condition or severe illness that the investigator feels would limit the prognosis of the patient (eg, malignancy with life-expectancy < 3 months) or would make the patient otherwise unsuitable for enrollment (eg, pose a hazard or undue burden to the patient [known chronic renal or hepatic impairment, recent (< 30 days), cerebrovascular accident or transient ischemic attack] unable to complete study visits)
8. Known contraindication to MR imaging (eg, metallic implant, claustrophobia, implantable cardioverter-defibrillator[ICD], pacemaker), known CrCl<30mL/min (Cockcroft Gault equation)
9. Pregnant women and/or breastfeeding women
10. Current or previous participation within the last 30 days in a study using an investigational therapy or device. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Infarct size as a percentage of LV mass measured on delayed-enhanced (CV magnetic resonance [CMR]) imaging 10-12 weeks post-MI compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
10-12 weeks post myocardial infarction |
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E.5.2 | Secondary end point(s) |
• EF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI compared to placebo.
• Change in NCPV in the coronary arteries from index computed tomography angiography (CTA) to 10-12 weeks post-MI compared with placebo.
• Myocardial mass and LV volumes at end-systole and end-diastole.
• Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs).
• Lecithin-cholesterol acyltransferase (LCAT) mass and anti-drug antibodies (ADAs). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
10-12 weeks post myocardial infarction |
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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 | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
subject/MedImmune blinded, investigator unblinded |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Czech Republic |
Hungary |
Israel |
Netherlands |
Poland |
Russian Federation |
Slovakia |
Spain |
United Kingdom |
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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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The end of the study (“study completion”) is defined as the date of the last protocol -specified visit/assessment, which may be the date of the last Day 70 84 visit (including telephone contact), or the Extended Follow-up if required at Week 25, 39, or 52, or death for the last subject in the study, whichever occurs last.
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |