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

Phase 2

Completed

Conditions: ST Elevation Myocardial Infarction

Interventions: Biological: MEDI6012
Other: Placebo

Registration Number: NCT03578809

Lead Sponsor: MedImmune LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 593

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort B: MEDI6012	MEDI6012	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.
Cohort A: Placebo	Placebo	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.
Cohort A: MEDI6012	MEDI6012	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.
Cohort B: Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Global Infarct Size	70 to 84 days post Day 1 dose	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.

Secondary Outcome Measures

Name	Time	Method
Left Ventricular Ejection Fraction (LVEF)	70 to 84 days post Day 1 dose	The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported.
Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)	70 to 84 days post Day 1 dose	The left ventricular mass by cine MRI is reported.
Left Ventricular End-diastolic and End-systolic Volume	70 to 84 days post Day 1 dose	Left ventricular end-diastolic and end-systolic volume is reported.
Left Ventricular End-diastolic and End-systolic Volume Index	70 to 84 days post Day 1 dose	Left ventricular end-diastolic and end-systolic volume index is reported.
Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B	Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose	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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	Day 1 through Day 195 post Day 1 dose	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.
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012	Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose	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.
Left Ventricular Mass by Late Gadolinium Enhancement (LGE)	70 to 84 days post Day 1 dose	The left ventricular mass by LGE is reported.
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass)	Pre- and post-dose on Days 1, 3, 17, and 31	Serum concentration of MEDI6012 is reported.