Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (NCT NCT03578809)

Last Updated: 2022-02-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

593 participants

Primary outcome timeframe

70 to 84 days post Day 1 dose

Results posted on

2022-02-09

Participant Flow

This study was conducted in 10 countries (Brazil, Czech Republic, Hungary, Israel, Netherlands, Poland, Russian Federation, Slovakia, Spain, and the United Kingdom).

In total, 593 participants were randomized into the study and 575 participants were treated with the study drug.

Participant milestones

Participant milestones
Measure	Cohort A: Placebo Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.	Cohort A: MEDI6012 Participants received 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 Participants received 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.	Cohort B: MEDI6012 Participants received 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.
Overall Study STARTED	94	185	112	202
Overall Study Treated	90	179	111	195
Overall Study COMPLETED	88	171	108	193
Overall Study NOT COMPLETED	6	14	4	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Placebo Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.	Cohort A: MEDI6012 Participants received 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 Participants received 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.	Cohort B: MEDI6012 Participants received 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.
Overall Study Death	0	2	0	1
Overall Study Lost to Follow-up	0	1	0	0
Overall Study Withdrawal by Subject	3	5	2	0
Overall Study Other	3	6	2	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Placebo n=94 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.	Cohort A: MEDI6012 n=185 Participants Participants received 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 n=112 Participants Participants received 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.	Cohort B: MEDI6012 n=202 Participants Participants received 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.	Total n=593 Participants Total of all reporting groups
Age, Continuous	59.7 Years STANDARD_DEVIATION 10.3 • n=5 Participants	59.9 Years STANDARD_DEVIATION 10.2 • n=7 Participants	62.6 Years STANDARD_DEVIATION 10.8 • n=5 Participants	59.9 Years STANDARD_DEVIATION 10.0 • n=4 Participants	60.4 Years STANDARD_DEVIATION 10.3 • n=21 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	35 Participants n=7 Participants	27 Participants n=5 Participants	49 Participants n=4 Participants	131 Participants n=21 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	150 Participants n=7 Participants	85 Participants n=5 Participants	153 Participants n=4 Participants	462 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants	22 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	92 Participants n=5 Participants	177 Participants n=7 Participants	110 Participants n=5 Participants	192 Participants n=4 Participants	571 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants	182 Participants n=7 Participants	110 Participants n=5 Participants	194 Participants n=4 Participants	580 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants

PRIMARY outcome

Timeframe: 70 to 84 days post Day 1 dose

Population: Primary efficacy analysis population included randomized participants with a Thrombolysis in Myocardial Infarction (TIMI) flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=97 Participants Participants received 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 n=61 Participants Participants received 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.	Cohort B: MEDI6012 n=108 Participants Participants received 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 n=43 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Global Infarct Size	8.598 Percentage of global infarct size Interval 7.228 to 10.229	9.004 Percentage of global infarct size Interval 7.219 to 11.23	7.819 Percentage of global infarct size Interval 6.658 to 9.183	5.453 Percentage of global infarct size Interval 3.781 to 7.865

SECONDARY outcome

Timeframe: 70 to 84 days post Day 1 dose

Population: Primary efficacy analysis population included randomized participants with a TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure.

The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=99 Participants Participants received 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 n=61 Participants Participants received 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.	Cohort B: MEDI6012 n=108 Participants Participants received 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 n=43 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Left Ventricular Ejection Fraction (LVEF)	47.083 Percentage of LVEF Interval 45.167 to 49.079	47.329 Percentage of LVEF Interval 45.158 to 49.604	49.722 Percentage of LVEF Interval 48.117 to 51.381	47.626 Percentage of LVEF Interval 44.344 to 51.152

SECONDARY outcome

Timeframe: Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose

Population: The CTA analysis population included randomized participants in the 6-dose regimen who received a full treatment course of study drug, were eligible, and had coronary CTA. 'Number of participants analyzed' denotes the number of participants evaluated for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=121 Participants Participants received 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 Participants received 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.	Cohort B: MEDI6012 Participants received 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 n=60 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B	0.998 mm^3 Interval 0.919 to 1.085	—	—	1.049 mm^3 Interval 0.915 to 1.203

SECONDARY outcome

Timeframe: 70 to 84 days post Day 1 dose

The left ventricular mass by LGE is reported.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=97 Participants Participants received 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 n=61 Participants Participants received 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.	Cohort B: MEDI6012 n=108 Participants Participants received 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 n=43 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Left Ventricular Mass by Late Gadolinium Enhancement (LGE)	119.581 g Standard Deviation 23.949	115.221 g Standard Deviation 28.328	117.920 g Standard Deviation 24.821	119.740 g Standard Deviation 31.384

SECONDARY outcome

Timeframe: 70 to 84 days post Day 1 dose

The left ventricular mass by cine MRI is reported.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=99 Participants Participants received 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 n=61 Participants Participants received 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.	Cohort B: MEDI6012 n=108 Participants Participants received 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 n=43 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)	113.870 g Standard Deviation 23.885	110.244 g Standard Deviation 28.009	111.533 g Standard Deviation 23.329	113.953 g Standard Deviation 31.261

SECONDARY outcome

Timeframe: 70 to 84 days post Day 1 dose

Left ventricular end-diastolic and end-systolic volume is reported.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=99 Participants Participants received 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 n=61 Participants Participants received 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.	Cohort B: MEDI6012 n=108 Participants Participants received 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 n=43 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Left Ventricular End-diastolic and End-systolic Volume Left ventricular end-diastolic volume	176.523 mL Interval 169.259 to 184.098	167.480 mL Interval 157.01 to 178.649	172.733 mL Interval 166.031 to 179.706	174.059 mL Interval 161.956 to 187.066
Left Ventricular End-diastolic and End-systolic Volume Left ventricular end-systolic volume	89.594 mL Interval 83.818 to 95.768	84.977 mL Interval 77.205 to 93.532	83.676 mL Interval 78.606 to 89.073	87.038 mL Interval 78.229 to 96.838

SECONDARY outcome

Timeframe: 70 to 84 days post Day 1 dose

Left ventricular end-diastolic and end-systolic volume index is reported.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=99 Participants Participants received 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 n=61 Participants Participants received 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.	Cohort B: MEDI6012 n=108 Participants Participants received 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 n=42 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Left Ventricular End-diastolic and End-systolic Volume Index Left ventricular end-diastolic volume index	90.280 mL/m^2 Interval 86.818 to 93.88	86.118 mL/m^2 Interval 81.401 to 91.107	87.258 mL/m^2 Interval 84.211 to 90.416	89.158 mL/m^2 Interval 84.324 to 94.269
Left Ventricular End-diastolic and End-systolic Volume Index Left ventricular end-systolic volume index	45.821 mL/m^2 Interval 42.97 to 48.863	43.695 mL/m^2 Interval 40.024 to 47.703	42.270 mL/m^2 Interval 39.845 to 44.842	44.491 mL/m^2 Interval 40.537 to 48.83

SECONDARY outcome

Timeframe: Day 1 through Day 195 post Day 1 dose

Population: As-treated population included all treated participants, grouped according to actual treatment received.

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.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=179 Participants Participants received 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 n=111 Participants Participants received 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.	Cohort B: MEDI6012 n=195 Participants Participants received 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 n=90 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TEAEs	114 Participants	70 Participants	136 Participants	49 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TESAEs	34 Participants	24 Participants	41 Participants	11 Participants

SECONDARY outcome

Timeframe: Pre- and post-dose on Days 1, 3, 17, and 31

Population: Pharmacokinetic population included all participants in the As-treated population who had at least one detectable serum concentration measurement for LCAT mass or activity. 'Number analyzed' denotes participants who had adequate pharmacokinetic sample of MEDI6012 for the specified time point.

Serum concentration of MEDI6012 is reported.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=193 Participants Participants received 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 Participants received 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.	Cohort B: MEDI6012 Participants received 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 n=179 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 1 (pre-dose)	NA ng/mL Standard Deviation NA Data were not calculated because the concentration was below limit of quantification.	—	—	NA ng/mL Standard Deviation NA Data were not calculated because the concentration was below limit of quantification.
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 1 (post-dose)	74661.2 ng/mL Standard Deviation 24561.6	—	—	76795.9 ng/mL Standard Deviation 31136.7
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 3 (pre-dose)	27738.8 ng/mL Standard Deviation 12892.4	—	—	28017.9 ng/mL Standard Deviation 11019.6
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 3 (post-dose)	87663.1 ng/mL Standard Deviation 93166.2	—	—	94653.8 ng/mL Standard Deviation 115895.1
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 17 (pre-dose)	4509.9 ng/mL Standard Deviation 2372.6	—	—	—
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 17 (post-dose)	49111.0 ng/mL Standard Deviation 71552.1	—	—	—
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 31 (pre-dose)	4954.8 ng/mL Standard Deviation 4193.9	—	—	—
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) Day 31 (post-dose)	67519.7 ng/mL Standard Deviation 224677.3	—	—	—

SECONDARY outcome

Timeframe: Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose

Population: Immunogenicity population included all treated participants, grouped according to actual treatment received and had at least one serum sample for immunogenicity testing.

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.

Outcome measures

Outcome measures
Measure	Cohort A: MEDI6012 n=179 Participants Participants received 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 n=111 Participants Participants received 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.	Cohort B: MEDI6012 n=194 Participants Participants received 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 n=90 Participants Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012 ADA positive and > 30% decrease in HDL-C from baseline at any visit up to Day 70-84 Follow-up Visit	3 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012 ADA positive at any visit up to Day 70-84 Follow-up Visit	13 Participants	1 Participants	93 Participants	1 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012 ADA positive and > 30% decrease in HDL-C from baseline at Day 70-84 Follow-up Visit	0 Participants	0 Participants	1 Participants	1 Participants

Adverse Events

Placebo Cohort A

Serious events: 11 serious events

Other events: 28 other events

Deaths: 0 deaths

MEDI6012 Cohort A

Serious events: 34 serious events

Other events: 74 other events

Deaths: 2 deaths

Placebo Cohort B

Serious events: 24 serious events

Other events: 47 other events

Deaths: 0 deaths

MEDI6012 Cohort B

Serious events: 41 serious events

Other events: 89 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Cohort A n=90 participants at risk Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.	MEDI6012 Cohort A n=179 participants at risk Participants received 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.	Placebo Cohort B n=111 participants at risk Participants received 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.	MEDI6012 Cohort B n=195 participants at risk Participants received 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	1.7% 3/179 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	3.1% 6/195 • Number of events 6 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Angina pectoris	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	3.6% 4/111 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	3.1% 6/195 • Number of events 6 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Atrial fibrillation	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	3.4% 6/179 • Number of events 6 • Day 1 through Day 195 post Day 1 dose	4.5% 5/111 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	3.6% 7/195 • Number of events 7 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Bradycardia	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	0.00% 0/179 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	2.6% 5/195 • Number of events 5 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Cardiac failure	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	4.6% 9/195 • Number of events 9 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Cardiac ventricular thrombosis	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.8% 5/179 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	0.00% 0/111 • Day 1 through Day 195 post Day 1 dose	0.00% 0/195 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Palpitations	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.8% 5/179 • Number of events 6 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.0% 2/195 • Number of events 2 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Supraventricular extrasystoles	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.7% 3/179 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 3 • Day 1 through Day 195 post Day 1 dose
Cardiac disorders Ventricular extrasystoles	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	2.8% 5/179 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.6% 5/195 • Number of events 5 • Day 1 through Day 195 post Day 1 dose
Gastrointestinal disorders Abdominal pain upper	3.3% 3/90 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	0.00% 0/179 • Day 1 through Day 195 post Day 1 dose	0.00% 0/111 • Day 1 through Day 195 post Day 1 dose	1.0% 2/195 • Number of events 2 • Day 1 through Day 195 post Day 1 dose
Gastrointestinal disorders Constipation	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	0.56% 1/179 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.6% 5/195 • Number of events 5 • Day 1 through Day 195 post Day 1 dose
Gastrointestinal disorders Diarrhoea	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	4.1% 8/195 • Number of events 9 • Day 1 through Day 195 post Day 1 dose
Gastrointestinal disorders Nausea	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	5.6% 11/195 • Number of events 14 • Day 1 through Day 195 post Day 1 dose
Gastrointestinal disorders Toothache	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.00% 0/179 • Day 1 through Day 195 post Day 1 dose	0.00% 0/111 • Day 1 through Day 195 post Day 1 dose	0.00% 0/195 • Day 1 through Day 195 post Day 1 dose
Gastrointestinal disorders Vomiting	3.3% 3/90 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 4 • Day 1 through Day 195 post Day 1 dose
General disorders Fatigue	3.3% 3/90 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	3.6% 4/111 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	1.0% 2/195 • Number of events 2 • Day 1 through Day 195 post Day 1 dose
General disorders Pyrexia	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	3.6% 4/111 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 3 • Day 1 through Day 195 post Day 1 dose
Hepatobiliary disorders Hepatic steatosis	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.8% 5/179 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	0.51% 1/195 • Number of events 1 • Day 1 through Day 195 post Day 1 dose
Infections and infestations Nasopharyngitis	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.6% 5/195 • Number of events 5 • Day 1 through Day 195 post Day 1 dose
Infections and infestations Respiratory tract infection viral	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.1% 4/195 • Number of events 4 • Day 1 through Day 195 post Day 1 dose
Infections and infestations Urinary tract infection	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.7% 3/179 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 3 • Day 1 through Day 195 post Day 1 dose
Metabolism and nutrition disorders Dyslipidaemia	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.8% 5/179 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	3.1% 6/195 • Number of events 6 • Day 1 through Day 195 post Day 1 dose
Metabolism and nutrition disorders Hypokalaemia	5.6% 5/90 • Number of events 7 • Day 1 through Day 195 post Day 1 dose	2.8% 5/179 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.51% 1/195 • Number of events 1 • Day 1 through Day 195 post Day 1 dose
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.7% 3/179 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 3 • Day 1 through Day 195 post Day 1 dose
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	0.00% 0/111 • Day 1 through Day 195 post Day 1 dose	0.51% 1/195 • Number of events 1 • Day 1 through Day 195 post Day 1 dose
Musculoskeletal and connective tissue disorders Back pain	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 3 • Day 1 through Day 195 post Day 1 dose
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	0.56% 1/179 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	3.6% 4/111 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	1.0% 2/195 • Number of events 2 • Day 1 through Day 195 post Day 1 dose
Nervous system disorders Dizziness	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	7.3% 13/179 • Number of events 13 • Day 1 through Day 195 post Day 1 dose	4.5% 5/111 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	2.1% 4/195 • Number of events 4 • Day 1 through Day 195 post Day 1 dose
Nervous system disorders Headache	4.4% 4/90 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	3.9% 7/179 • Number of events 7 • Day 1 through Day 195 post Day 1 dose	4.5% 5/111 • Number of events 5 • Day 1 through Day 195 post Day 1 dose	6.2% 12/195 • Number of events 13 • Day 1 through Day 195 post Day 1 dose
Psychiatric disorders Anxiety	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	3.1% 6/195 • Number of events 6 • Day 1 through Day 195 post Day 1 dose
Psychiatric disorders Insomnia	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.6% 5/195 • Number of events 5 • Day 1 through Day 195 post Day 1 dose
Renal and urinary disorders Renal failure	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.7% 3/179 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	0.00% 0/195 • Day 1 through Day 195 post Day 1 dose
Renal and urinary disorders Renal impairment	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.56% 1/179 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.0% 2/195 • Number of events 2 • Day 1 through Day 195 post Day 1 dose
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.00% 0/111 • Day 1 through Day 195 post Day 1 dose	0.00% 0/195 • Day 1 through Day 195 post Day 1 dose
Respiratory, thoracic and mediastinal disorders Cough	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	4.5% 8/179 • Number of events 8 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	4.6% 9/195 • Number of events 9 • Day 1 through Day 195 post Day 1 dose
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	2.7% 3/111 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	3.1% 6/195 • Number of events 6 • Day 1 through Day 195 post Day 1 dose
Respiratory, thoracic and mediastinal disorders Epistaxis	2.2% 2/90 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.0% 2/195 • Number of events 2 • Day 1 through Day 195 post Day 1 dose
Vascular disorders Brachiocephalic arteriosclerosis	1.1% 1/90 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	1.1% 2/179 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	2.1% 4/195 • Number of events 4 • Day 1 through Day 195 post Day 1 dose
Vascular disorders Haematoma	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	1.8% 2/111 • Number of events 2 • Day 1 through Day 195 post Day 1 dose	1.5% 3/195 • Number of events 3 • Day 1 through Day 195 post Day 1 dose
Vascular disorders Hypertension	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	2.2% 4/179 • Number of events 4 • Day 1 through Day 195 post Day 1 dose	0.90% 1/111 • Number of events 1 • Day 1 through Day 195 post Day 1 dose	3.1% 6/195 • Number of events 6 • Day 1 through Day 195 post Day 1 dose
Vascular disorders Hypotension	0.00% 0/90 • Day 1 through Day 195 post Day 1 dose	1.7% 3/179 • Number of events 3 • Day 1 through Day 195 post Day 1 dose	6.3% 7/111 • Number of events 7 • Day 1 through Day 195 post Day 1 dose	5.6% 11/195 • Number of events 12 • Day 1 through Day 195 post Day 1 dose