A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction

Study Overview
=================
Brief Summary
-----------------
This is a Phase 2b randomized, blinded, placebo controlled study to evaluate the efficacy, safety, PK/pharmacodynamic, and immunogenicity of repeat doses of MEDI6012 in adult participants presenting with acute STEMI (ST segment elevation myocardial infarction). The study will enrol participants presenting with acute STEMI who are planned for primary percutaneous coronary intervention (pPCI). For all participants, an end of study CMR will be performed at 10-12 weeks (70-84 days following Dose 1). A subset of participants will also undergo an index and an end of study CTA.

Official Title
-----------------
A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction

Conditions
-----------------
ST Elevation Myocardial Infarction

Intervention / Treatment
-----------------
* Biological: MEDI6012
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute STEMI (ST segment elevation myocardial infarction) diagnosed by ST elevation Planned for primary PCI (percutaneous coronary intervention) Men and women without child-bearing potential aged 30-80 years of age Capable and willing to provide informed consent. Capable of completing study visits Exclusion Criteria: Fibrinolytic administration for index event Known prior MI or prior coronary artery bypass graft (CABG) surgery Known pre-existing cardiomyopathy History of anaphylaxis Suspected non-thrombotic etiology (ie, vasospasm, dissection, Takotsubo cardiomyopathy)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort A: Placebo<br>Participants will receive placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3 by IV push. | Other: Placebo<br>* Placebo<br>* Other names: Placebo matched to MEDI6012 will be administered on Day 1 and Day 3 by IV push in Cohorts A and B, and on Days 10, 17, 24, and 31 by IV push in Cohort B.;|
| Experimental: Cohort A: MEDI6012<br>Participants will receive loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push. | Biological: MEDI6012<br>* MEDI6012<br>* Other names: MEDI6012 300 mg will be administered on Day 1 and MEDI6012 150 mg on Day 3 by IV push in Cohorts A and B. In Cohort B, MEDI6012 100 mg will be administered on Days 10, 17, 24, and 31 by IV push.;|
| Placebo Comparator: Cohort B: Placebo<br>Participants will receive placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push. | Other: Placebo<br>* Placebo<br>* Other names: Placebo matched to MEDI6012 will be administered on Day 1 and Day 3 by IV push in Cohorts A and B, and on Days 10, 17, 24, and 31 by IV push in Cohort B.;|
| Experimental: Cohort B: MEDI6012<br>Participants will receive loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push. | Biological: MEDI6012<br>* MEDI6012<br>* Other names: MEDI6012 300 mg will be administered on Day 1 and MEDI6012 150 mg on Day 3 by IV push in Cohorts A and B. In Cohort B, MEDI6012 100 mg will be administered on Days 10, 17, 24, and 31 by IV push.;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Infarct Size | Global infarct size expressed as a percentage of left ventricle (LV) mass measured on delayed-enhanced cardiovascular magnetic resonance (CMR) imaging in 10-12 weeks post myocardial infarction (MI) is reported. | 70 to 84 days post Day 1 dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction (LVEF) | The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported. | 70 to 84 days post Day 1 dose | 
| Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B | Change in NCPV in the coronary arteries from index computed tomography angiography (CTA) to 10-12 weeks post-MI is reported. The index CTA was preferably to be performed between 48 to 72 hours post Dose 1 (could be done up to 5 days post Dose 1) but no earlier than 40 hours post Dose 1. Participants with creatinine clearance >= 60 mL/min (Cockcroft Gault equation) within 6 hours underwent an index coronary CTA no earlier than 40 hours following the first dose. | Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose | 
| Left Ventricular Mass by Late Gadolinium Enhancement (LGE) | The left ventricular mass by LGE is reported. | 70 to 84 days post Day 1 dose | 
| Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI) | The left ventricular mass by cine MRI is reported. | 70 to 84 days post Day 1 dose | 
| Left Ventricular End-diastolic and End-systolic Volume | Left ventricular end-diastolic and end-systolic volume is reported. | 70 to 84 days post Day 1 dose | 
| Left Ventricular End-diastolic and End-systolic Volume Index | Left ventricular end-diastolic and end-systolic volume index is reported. | 70 to 84 days post Day 1 dose | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | Day 1 through Day 195 post Day 1 dose | 
| Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) | Serum concentration of MEDI6012 is reported. | Pre- and post-dose on Days 1, 3, 17, and 31 | 
| Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012 | Number of participants with positive ADA titer to MEDI6012 are reported in 3 categories, ADA positive at any visit up to Day 70-84 follow-up visit, ADA positive with > 30% decrease in HDL-C from baseline (on the same date) at any visit up to D70-84 FU V, and ADA positive and > 30% decrease in HDL-C from baseline at Day 70-84 Follow-up Visit. | Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose |