A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction
Phase: PHASE2
Conditions: ST Elevation Myocardial Infarction
Sponsor: MedImmune LLC

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A Randomized, Placebo-controlled Phase 2b Study to Evaluate the 
Safety and Efficacy of MEDI6012 in Acute ST Elevation 
Myocardial Infarction 
Sponsor Protocol Number: D5780C00007
Application Number:
EudraCT number 2017-004521-32
Investigational Product:
MEDI6012 
 
Sponsor:
MedImmune, LLC, a wholly owned subsidiary of AstraZeneca 
PLC, One MedImmune Way, Gaithersburg, Maryland, 20878, 
USA
Medical Monitor:
 MBBS, MRCP, PhD  
, Clinical Development, MedImmune
Study Chair:
 MD, MPH
Chairman, 
 MD, 
 
Brigham and Women’s Hospital
Professor of Medicine, Harvard Medical School
Principal/Coordinating 
Investigator:
 MD, MPH
Investigator, 
Associate Physician, Brigham and Women’s Hospital
Assistant Professor, Harvard Medical School
Contract Research
Organization:
Protocol History, Date:
Original Protocol, 03Jan2018
Protocol Amendment 1, 09Jan2018
Protocol Amendment 2, 28Mar2018
Protocol Amendment 3, 14Jun2018
Protocol Amendment 4, 18Apr2019

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Protocol Amendment 5, 26Jul2019
Protocol Amendment 6, 04May2020
This document contains trade secrets and commercial information that is privileged or 
confidential and may not be disclosed without prior authorization from MedImmune.

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STATISTICAL METHODS
Sample size:
 
 
 
 
 
 
 
 
 
 
 
Statistical analyses:
Intention-to-Treat Population: all subjects who are randomized, analyzed according to randomized treatment 
assignment. 
As-treated Population: all randomized subjects who receive any investigational product. Subjects who receive 
any dose of MEDI6012 will be assigned to the MEDI6012 group. Subjects who receive only placebo doses 
will be analyzed with the placebo group; conversely, subjects who receive any dose of MEDI6012 will be 
analyzed with the MEDI6012 group. Safety analyses will be performed on the As-treated Population.
Primary Efficacy Analysis Population: all randomized subjects with 
 
of investigational product. Subjects who receive only placebo doses will be analyzed 
with the placebo group; conversely, subjects who receive 
 doses of MEDI6012 will be analyzed with 
the MEDI6012 group.
Efficacy Analysis Population 
 all randomized subjects with 
 
 investigational product. Subjects who receive only placebo doses will be analyzed 
with the placebo group; conversely, subjects who receive 
 of MEDI6012 will be analyzed with 
the MEDI6012 group.
Efficacy Analysis Population -
 all randomized subjects with 
 
investigational product. Subjects who receive only placebo doses will be analyzed 
with the placebo group; conversely, subjects who receive 
 of MEDI6012 will be analyzed with 
the MEDI6012 group.
The CTA Analysis Population: randomized subjects in the 
 regimen who receive a full treatment course 
of investigational product and are eligible for 
 performed. The 
subjects who receive 
 doses will be analyzed with the placebo group; conversely, subjects who 
receive  doses of MEDI6012 will be analyzed with the MEDI6012 group.
Immunogenicity Population: includes all subjects in the As-treated Population who have at least one serum 
sample for immunogenicity testing.
PK Population: includes all subjects in the As-treated Population who have at least one detectable serum 
concentration measurement for LCAT mass.  
The primary efficacy endpoint of infarct size will be analyzed using t-test with log-transformation of the data 
based on the primary efficacy analysis population. The primary endpoint of infarct size will also be analyzed 
based on the Efficacy Analysis Population - TIMI 2-3, the Efficacy Analysis Population - TIMI 0-3, and the 
Intent-To-Treat population. 
Secondary efficacy endpoints include EF measured by cine MRI at 10-12 weeks post-MI, change in NCPV in 
the coronary arteries from index CTA to 10-12 weeks post-MI, and myocardial mass and left ventricular 

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volumes at end-systole and end-diastole. EF, myocardial mass, and left ventricular volumes will be analyzed 
similarly to infarct size without the log-transformation of the data. Change from index CTA in NCPV will be 
analyzed using t-test based on CTA analysis population.
Safety analysis will be based on the As-treated Population. Adverse event (AE) collection will begin after the 
subject signs the informed consent document and lasts until the end of the study. Adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA) by system organ class (SOC) and preferred 
term (PT). Specific AEs will be counted once for each subject for calculating rates, but will be presented in 
total in subject listings. In addition, if the same AE occurs multiple times within a particular subject, the 
highest severity and level of causality will be reported. All TEAEs will be summarized overall and by 
MedDRA SOC and PT, by severity and relationship to investigational product. In addition, summaries of 
deaths, SAEs, and treatment discontinuations due to AEs will be provided.
Clinical laboratory safety tests including serum chemistry and hematology parameters will be summarized 
using descriptive statistics at each time point by treatment group with placebo group combined when 
appropriate. Change from baseline to each post baseline time point in these data will also be summarized, 
where appropriate. A shift table will be provided for these clinical laboratory parameters as well where 
possible.
Vital sign results will be summarized using descriptive statistics at each time point by treatment group.
ADA incidence rate and titer will be tabulated for each treatment group. 
 
Serum MEDI6012 mass concentration time profiles will be summarized for MEDI6012 treated subjects by 
dose cohort.
The following PD markers will be collected: 
 
. The PD markers measured at each time point and change 
from baseline each post baseline time point will be summarized using descriptive statistics by treatment group 
with placebo group combined when appropriate.
Interim analysis:
 interim analyses are planned. The objective of the 
 interim analysis will be for 
 It will be conducted after 30% of the initially planned 
Primary Efficacy Analysis Population (N = 74) is enrolled and will require that > 50% of subjects (N > 37) 
 and 
. The
 interim analysis will be 
conducted through the Data Monitoring Committee with details in the DMC charter. The 
interim 
analysis is planned to accelerate decision on future development options for MEDI6012 and will be performed 
once 60% of the revised Primary Efficacy Analysis Population (N = 162) is enrolled and will require that > 
50% of subjects (N > 81) have 
 and 
. Details of the 
 interim analyses will be specified in the interim analysis plan. The sponsor and Principal Investigator 
will monitor the statistical assumptions in a blinded fashion and decide the exact time for interim analyses. 

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TABLE OF CONTENTS
PROTOCOL SYNOPSIS...................................................................................................... 3
LIST OF ABBREVIATIONS ............................................................................................. 12
1
INTRODUCTION............................................................................................ 14
1.1
Disease Background ......................................................................................... 14
1.2
MEDI6012 Background.................................................................................... 14
1.3
Summary of Nonclinical Experience................................................................. 15
1.4
Summary of Clinical Experience....................................................................... 15
1.4.1
Efficacy ............................................................................................................ 15
1.4.2
Safety ............................................................................................................... 16
1.4.3
Pharmacokinetics.............................................................................................. 16
1.5
Rationale for Conducting the Study .................................................................. 16
1.6
Benefit-Risk and Ethical Assessment................................................................ 28
1.7
Research Hypotheses ........................................................................................ 29
1.7.1
Primary Hypothesis .......................................................................................... 29
1.7.2
Secondary Hypotheses...................................................................................... 29
2
OBJECTIVES AND ENDPOINTS................................................................... 29
2.1
Objectives......................................................................................................... 29
2.1.1
Primary Objective............................................................................................. 29
2.1.2
Secondary Objectives........................................................................................ 30
2.1.3
Exploratory Objectives ..................................................................................... 31
3
STUDY DESIGN ............................................................................................. 32
3.1
Description of the Study ................................................................................... 32
3.1.1
Overview.......................................................................................................... 32
3.1.2
Treatment Regimen........................................................................................... 35
3.2
Rationale for Dose, Population, and Endpoints ................................................. 36
3.2.1
Dose Rationale.................................................................................................. 36
3.2.2
Rationale for Study Population ......................................................................... 37
3.2.3
Rationale for Endpoint(s).................................................................................. 37
3.2.3.1
Rationale for Primary Endpoints....................................................................... 37
3.2.3.2
Rationale for Secondary Endpoints ................................................................... 37
3.2.3.3
Rationale for PK Endpoints............................................................................... 38
3.2.3.4
Rationale for Exploratory Endpoints................................................................. 38
4
MATERIALS AND METHODS ...................................................................... 39
4.1
Subjects ............................................................................................................ 39
4.1.1
Number of Subjects .......................................................................................... 39
4.1.2
Inclusion Criteria .............................................................................................. 39
4.1.3
Exclusion Criteria ............................................................................................. 39
4.1.4
Additional Study Procedure Requirements........................................................ 40
4.1.5
Subject Enrollment and Randomization ............................................................ 41
4.1.6
Withdrawal from the Study............................................................................... 42

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4.1.7
Discontinuation of Investigational Product........................................................ 42
4.1.8
Lost to Follow-up Subjects ............................................................................... 44
4.1.9
Replacement of Subjects................................................................................... 44
4.1.10
Withdrawal of Informed Consent for Data and Biological Samples................... 44
4.2
Schedule of Study Procedures........................................................................... 45
4.2.1
Enrollment, Treatment, and Follow-up Periods ................................................. 45
4.2.1.1
Study Procedure Modifications in Response to the COVID-19 Pandemic ......... 45
4.2.2
Extended Follow-up Period for Subjects Testing Positive for Anti-Drug 
Antibodies Plus > 30% Decrease from Baseline in HDL-C at Day 70 to 84 or 
Presence of a Neutralizing Antibody on Day 70 to 84 ....................................... 55
4.3
Description of Study Procedures....................................................................... 55
4.3.1
Medical History and Physical Examination, Weight, and Vital Signs................ 56
4.3.2
ECG ................................................................................................................. 56
4.3.3
Systemic/Local Tolerability.............................................................................. 57
4.3.4
Clinical Laboratory Tests.................................................................................. 57
4.3.5
Pharmacokinetic Evaluation and Methods......................................................... 58
4.3.6
Pharmacodynamic Evaluation and Methods...................................................... 58
4.3.7
Immunogenicity Evaluation and Methods ......................................................... 58
4.3.8
Imaging Biomarker Evaluation and Methods .................................................... 59
4.3.9
Estimate of Volume of Blood to be Collected ................................................... 62
4.4
Study Suspension or Termination...................................................................... 62
4.5
Investigational Products.................................................................................... 63
4.5.1
Identity of Investigational Product(s) ................................................................ 63
4.5.1.1
Investigational Product Handling ...................................................................... 63
4.5.1.2
Investigational Product Inspection .................................................................... 64
4.5.1.3
Dose Preparation Steps ..................................................................................... 64
4.5.1.4
Treatment Administration................................................................................. 65
4.5.1.5
Monitoring of Dose Administration .................................................................. 66
4.5.1.6
Reporting Product Complaints .......................................................................... 66
4.5.2
Additional Study Medications........................................................................... 66
4.5.3
Labeling ........................................................................................................... 66
4.5.4
Storage ............................................................................................................. 66
4.5.5
Treatment Compliance...................................................................................... 67
4.5.6
Accountability .................................................................................................. 67
4.6
Treatment Assignment and Blinding ................................................................. 67
4.6.1
Methods for Assigning Treatment Groups......................................................... 67
4.6.2
Methods to Ensure Blinding.............................................................................. 68
4.6.3
Methods for Unblinding.................................................................................... 68
4.6.3.1
Unblinding in the Event of a Medical Emergency ............................................. 68
4.6.3.2
Unblinding for Interim Analysis Purposes......................................................... 68
4.7
Restrictions During the Study and Concomitant Treatment(s) ........................... 68
4.7.1
Permitted Concomitant Medications ................................................................. 69
4.7.2
Prohibited Concomitant Medications ................................................................ 69
4.8
Statistical Evaluation ........................................................................................ 69
4.8.1
General Considerations..................................................................................... 69

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4.8.1.1
Analysis Populations......................................................................................... 70
4.8.2
Sample Size...................................................................................................... 70
4.8.3
Efficacy ............................................................................................................ 71
4.8.3.1
Primary Efficacy Analysis ................................................................................ 71
4.8.3.2
Additional Analyses of the Primary Endpoint ................................................... 71
4.8.3.3
Secondary Efficacy Analyses............................................................................ 71
4.8.3.4
Exploratory Analyses........................................................................................ 71
4.8.4
Safety ............................................................................................................... 72
4.8.4.1
Analysis of Adverse Events .............................................................................. 72
4.8.4.2
Analysis of Clinical Laboratory Parameters ...................................................... 72
4.8.4.3
Other Safety Analyses....................................................................................... 72
4.8.5
Analysis of Immunogenicity/Pharmacokinetics................................................. 72
4.8.6
Analysis of Pharmacodynamic Parameters........................................................ 73
4.8.7
Data Monitoring Committee ............................................................................. 73
4.8.8
Interim Analysis ............................................................................................... 73
5
ASSESSMENT OF SAFETY ........................................................................... 74
5.1
Safety Monitoring............................................................................................. 74
5.2
Definition of Adverse Events............................................................................ 75
5.3
Definition of Serious Adverse Events ............................................................... 75
5.4
Recording of Adverse Events............................................................................ 76
5.4.1
Time Period for Collection of Adverse Events .................................................. 76
5.4.2
Follow-up of Unresolved Adverse Events......................................................... 77
5.5
Reporting of Serious Adverse Events................................................................ 77
5.6
Other Events Requiring Immediate Reporting................................................... 77
5.6.1
Overdose .......................................................................................................... 77
5.6.2
Hepatic Function Abnormality.......................................................................... 78
5.6.3
Pregnancy......................................................................................................... 78
5.6.3.1
Maternal Exposure............................................................................................ 78
5.6.3.2
Paternal Exposure............................................................................................. 78
6
STUDY AND DATA MANAGEMENT........................................................... 79
6.1
Training of Study Site Personnel....................................................................... 79
6.2
Monitoring of the Study.................................................................................... 79
6.2.1
Source Data ...................................................................................................... 79
6.2.2
Study Agreements............................................................................................. 80
6.2.3
Archiving of Study Documents......................................................................... 80
6.3
Study Timetable and End of Study.................................................................... 80
6.4
Data Management............................................................................................. 80
6.5
Medical Monitor Coverage ............................................................................... 81
7
ETHICAL AND REGULATORY REQUIREMENTS...................................... 81
7.1
Subject Data Protection..................................................................................... 81
7.2
Ethics and Regulatory Review .......................................................................... 81
7.3
Informed Consent ............................................................................................. 82

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7.4
Changes to the Protocol and Informed Consent Form........................................ 82
7.5
Audits and Inspections...................................................................................... 83
8
REFERENCES................................................................................................. 84
9
CHANGES TO THE PROTOCOL ................................................................... 88
9.1
Protocol Amendment 6, 04May2020................................................................. 88
9.2
Protocol Amendment 5, 26Jul2019 ................................................................... 89
9.3
Protocol Amendment 4, 18Apr2019.................................................................. 90
9.4
Protocol Amendment 3, 14Jun2018 .................................................................. 92
9.5
Protocol Amendment 2, 28Mar2018 ................................................................. 94
9.6
Protocol Amendment 1, 09Jan2018................................................................... 95
10
APPENDICES.................................................................................................. 97
10.1
Appendix 1 - Signatures.................................................................................... 97
10.2
Appendix 2 – Contraception Guidance.............................................................. 99
10.3
Appendix 3 - Additional Safety Guidance....................................................... 100
10.4
Appendix 4 - National Institute of Allergy and Infectious Disease and Food 
Allergy and Anaphylaxis Network Guidance for Anaphylaxis Diagnosis ........ 103
10.5
Appendix 5 - Actions Required in Cases of Increases in Liver Biochemistry 
and Evaluation of potential serious liver injury corresponding to Hy’s Law .... 104
10.5.1
Introduction .................................................................................................... 104
10.5.2
Definitions...................................................................................................... 104
10.5.2.1
Potential serious liver injury corresponding to Hy’s Law ................................ 104
10.5.2.2
Serious liver injury corresponding to Hy’s Law .............................................. 104
10.5.3
Identification of cases of (potential) serious liver injury corresponding to Hy’s 
law.................................................................................................................. 105
10.5.4
Follow-up ....................................................................................................... 106
10.5.4.1
Criteria for (potential) serious liver injury corresponding to Hy’s law Not Met106
10.5.4.2
Criteria for (potential) serious liver injury corresponding to Hy’s law Met...... 106
10.5.5
Review and Assessment of cases of (potential) serious liver injury 
corresponding to Hy’s law .............................................................................. 107
10.6
Appendix 6 - Management of Liver Toxicity .................................................. 108
10.6.1
References ...................................................................................................... 110

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LIST OF TABLES
Table 1
Baseline Adjusted AUC0-96h for Key PD Parameters After Ascending 
Weekly Doses of MEDI6012 – As-treated Population.............................. 19
Table 2
Baseline Adjusted AUC0-96h for Key PD Parameters 
 
 
As-treated Population..................................... 23
Table 3
Primary Objective and Associated Endpoint ............................................ 30
Table 4
Secondary Objectives and Associated Endpoints...................................... 30
Table 5
Exploratory Objectives and Associated Endpoints ................................... 31
Table 6
Dosing for Cohort A
 Regimen .................................................... 36
Table 7
Dosing for Cohort B: 
 Regimen .................................................... 36
Table 8
Treatment Period and Follow-up Procedures: Cohort A 
 
Regimen)................................................................................................. 47
Table 9
Treatment Period and Follow-up Procedures: Cohort B 
 
Regimen)................................................................................................. 51
Table 10
Extended Follow-up Procedures for Subjects Testing Positive for Anti-
Drug Antibodies Plus > 30% Decrease from Baseline in HDL-C at Day 
70 to 84 or Presence of a Neutralizing Antibody on Day 70 to 84 ............ 55
Table 11
Identification of Investigational Products................................................. 63
Table 12
MEDI6012 and Placebo Product Delivery Volume and Vial Usage.......... 65
Table 13
Highly Effective Methods of Contraception............................................. 99
Table 14
Actions to be Taken According to ALT, Glutamate Dehydrogenase, 
Total Bilirubin ....................................................................................... 108
LIST OF FIGURES
Figure 1
Mean Change from Baseline in Serum HDL-C After Ascending Weekly 
IV Doses of MEDI6012........................................................................... 17
Figure 2
Mean Change from Baseline in Serum HDL-C After 
 
MEDI6012............................................................................................... 18
Figure 3
Overall Study Schema ............................................................................. 32
Figure 4
Study Flow Diagram for Cohort A: 
 Regimen............................... 34
Figure 5
Study Flow Diagram for Cohort B -
 Regimen.............................. 35

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LIST OF ABBREVIATIONS
Abbreviation or 
Specialized Term
Definition
ACS
acute coronary syndrome
ADA
anti-drug antibody
AE
adverse event
ALT
alanine transaminase
AST
aspartate transaminase
AUC
area under the concentration-time curve
AUC0-∞
area under the concentration-time curve from 0 to infinity 
AUC0-72h
area under the concentration-time curve from 0 to 72 hours 
BP
blood pressure
CE
cholesteryl ester
CETP
cholesteryl ester transfer protein
Cmax
maximum plasma concentration
 
COVID-19
coronavirus disease
CrCl
creatinine clearance
eCRF
electronic case report form
EDC
electronic data capture
EF
ejection fraction
eGFR
estimated glomerular filtration rate
FAAN
Food and Allergy Anaphylaxis Network
FC
free cholesterol
HDL
high-density lipoprotein
HDL-C
high-density lipoprotein-cholesterol
HDL-CE
High-density lipoprotein-cholesterol ester
ICD
implantable cardioverter-defibrillator
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IRB
Institutional Review Board

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Abbreviation or 
Specialized Term
Definition
IV 
intravenous(ly)
IXRS
Interactive response system
LDL
low-density lipoprotein
LDL-C
low-density lipoprotein-cholesterol
LV
left ventricle
MACE
major adverse cardiac events
MedDRA
Medical Dictionary for Regulatory Activities
MR
magnetic resonance
MRI
magnetic resonance imaging
nAb
neutralizing antibody
NCPV
non-calcified plaque volume
NO
nitric oxide
NOAEL
no-observed-adverse-effect-level  
pPCI
primary percutaneous coronary intervention
PD
pharmacodynamics
PK
pharmacokinetics
PT
preferred term
RCT
reverse cholesterol transport
rhLCAT
recombinant human lecithin-cholesterol acyltransferase
SAE
serious adverse event
SID
subject identification
SOC
system organ class
STEMI
ST segment elevation myocardial infarction
sWFI
sterile water for injection
TEAE
treatment-emergent adverse event
TESAE
Treatment-emergent serious adverse event
ULN
upper limit of normal
USA
United States of America

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1
INTRODUCTION
1.1
Disease Background
Acute coronary syndrome (ACS) comprises a spectrum of life-threatening clinical conditions 
that include unstable angina and non-ST-segment elevation myocardial infarction 
(non-STEMI) and ST-segment elevation myocardial infarction (STEMI). STEMI patients 
generally have larger infarcts and are at higher risk for subsequent heart failure and death 
(Stone et al, 2016). Efforts to limit infarct size have focused on reducing door-to-balloon time 
and maintaining culprit artery patency after primary percutaneous coronary intervention 
(pPCI). Therapies that decrease infarct size or increase left ventricular ejection fraction (EF) 
are associated with reductions in cardiovascular (CV) death and heart failure (Breathett et al,
2016; Kramer et al, 2010). However, no acute drug therapies have demonstrated 
cardioprotection in humans.  
Infusion of high-density lipoprotein (HDL) or apolipoprotein A1 (apoA1) has demonstrated 
reductions in infarct size and improve hemodynamics in preclinical models of acute STEMI 
(Gomaraschi et al, 2016). Cross-sectional epidemiology studies (Framingham Study) 
demonstrated post-infarct EF is lower in patients with low HDL cholesterol, even after 
excluding baseline coronary heart disease (CHD) (Kempen et al, 1987; Wang et al, 1998). 
However, HDL and apoA1 infusions have not been tested for the purpose of cardioprotection 
in humans.
In addition to cardioprotection, acute STEMI patients could benefit from a therapy that rapidly 
removes plaque cholesterol, stabilizes vulnerable plaque, and thereby reduces the likelihood of 
subsequent ischemic events (Chen et al, 2010; Krause and Remaley, 2013; Libby and Aikawa, 
2003; Shah, 2007). Therapies that increase HDL-cholesterol (HDL-C) or apoA1 have the 
potential to regress atheroma.  
1.2
MEDI6012 Background
MEDI6012 is briefly described below. Refer to the current Investigator’s Brochure (IB) for 
details. 
MEDI6012 (formerly ACP501) 
 
. Lecithin-cholesterol acyltransferase (LCAT) is the rate-limiting enzyme in lipid 
metabolism that esterifies free cholesterol (FC) to cholesteryl ester (CE) and facilitates the 
maturation of HDL particles. 
 
EDI6012 relative to ACP501. In clinical studies (further described below), single 
and multiple doses of MEDI6012 increased HDL-C, HDL-C ester (HDL-CE), CE, and apoA1.  
In addition, in clinical and clinical ex vivo studies, MEDI6012 improves HDL function.

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1.3
Summary of Nonclinical Experience
Nonclinical pharmacology, pharmacokinetic (PK), pharmacodynamic (PD), and toxicology 
studies were conducted as part of the nonclinical program for MEDI6012. The nonclinical 
pharmacology data, summarized in the IB, show that MEDI6012
 
 In the 6-week repeat-dose toxicity study of MEDI6012 in 
 
This corresponded to mean maximum plasma 
concentration (Cmax) and area under the concentration-time curve from 0 to 72 hours 
(AUC0-72h) values of 904 μg/mL and 14200 μg·hr/mL, respectively, following Day 43 of 
dosing. 
1.4
Summary of Clinical Experience
Two completed studies with ACP501 are summarized in the IB (ACP501-01 and 13-H-0060). 
Study D5780C00002, was a Phase 2a study to evaluate the safety, PK, and PD of single doses 
of MEDI6012 in subjects with stable coronary artery disease (CAD). Forty-eight subjects 
were administered a single dose of MEDI6012 of 24, 80, 240, or 800 mg by 1-hour infusion or 
by SC injection at doses of 80 or 600 mg, or placebo (6:2 ratio). 
Study D5780C00005 was a Phase 2a study to evaluate the safety, PK, and PD of multiple 
doses of MEDI6012 in subjects with stable atherosclerotic cardiovascular disease. In this 
study, 32 subjects were administered multiple doses of MEDI6012 or placebo (6:2 ratio). 
MEDI6012 or placebo was administered three times weekly at 3 dose levels (1-hour IV 
infusion of 40, 120, or 300 mg on Days 1, 8, and 15) and a 4th cohort tested an IV push dosing 
regimen that included a loading dose of 300 mg followed by 150 mg second dose at 48 hours 
followed by a 100 mg maintenance dose 7 days later. 
1.4.1
Efficacy
Dose-dependent increases in HDL-C that were statistically significant at the 80, 240, and 
800 mg IV and the 600 mg SC dose levels were observed after 
 doses in 
Study D5780C00002. In addition, the study demonstrated: 1) dose dependent, statistically
significant increases in 
 at all IV dose levels and at the 600 mg SC dose; 2) statistically 
significant increase in
 only at the highest IV dose level (800 mg); and 3) a statistically 
significant decrease in 
 across all IV dose levels indicating a decrease in the number of 
 particles. 
After multiple doses of MEDI6012 in Study D5780C00005, the primary PD endpoints of 
sustainable and reversible dose-dependent response for HDL-C, HDL-CE and CE were met. 
In addition, the study demonstrated dose dependent, statistically significant increases in 

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and statistically significant increase in LDL-C at the 
 dose levels with 
no increase in 
.
1.4.2
Safety
In Study D5780C00002, single doses of MEDI6012 were generally well tolerated. There were 
no treatment-emergent serious adverse events (TESAEs), deaths, or life-threatening 
treatment-emergent adverse events (TEAEs), or TEAEs leading to withdrawal from the study. 
Non-serious TEAEs were reported by 55.6% 
 of all MEDI6012-treated subjects and 
41.7% 
) placebo-treated subjects. The majority of TEAEs were of mild or moderate 
severity. At the preferred term (PT) level, the most frequent TEAEs in all MEDI6012 subjects 
were headache (
), injection site reaction 
), and injection site erythema, 
medical device site irritation, and constipation 
). There were no clinically 
relevant changes in vital signs, electrocardiogram (ECG), or standard safety laboratory 
parameters. Of the 
subjects treated with MEDI6012, subjects (14%) tested positive for 
treatment-emergent anti-drug antibodies (ADAs) at 1 or more timepoints. None of these 
ADAs were neutralizing. 
In study D5780C00005, multiple doses of MEDI6012 were generally well tolerated. There 
was 
TESAE of atrial fibrillation felt due to external factors unrelated to Investigational 
Product or study procedures. There were no deaths, or life-threatening TEAEs or TEAEs 
leading to withdrawal from the study. Non-serious TEAEs were reported by 52% (
 
all MEDI6012-treated subjects and 43% 
) of all placebo-treated subjects. All TEAEs 
were of mild or moderate intensity. At the PT level, the most frequent TEAEs in all 
MEDI6012 subjects were dyspnea 
), injection site reaction (
), non-cardiac 
chest pain (
) and diarrhea (
). There were no clinically relevant changes in 
vital signs, ECG, or standard safety laboratory parameters. No subject treated with MEDI6012 
tested positive for treatment-emergent ADA. 
1.4.3
Pharmacokinetics
After 
 doses, exposure to MEDI6012 increased with the increase in IV dose level from 
 and exhibited linear PK with peak exposure (Cmax) generally increasing 
proportionally with increasing dose and systemic plasma area under the concentration-time 
curve from 0 to infinity (AUC0-∞) increasing proportionally between 
and 
 IV doses. 
The bioavailability derived based on mean dose-normalized AUC0-∞ between 
 SC and 
 IV dose was 49.8%. The PK profile of MEDI6012 supported 
 IV dosing. 
No multiple dose pharmacokinetic data are available at the time of writing.
1.5
Rationale for Conducting the Study
MEDI6012 increases HDL-C, HDL-CE, and CE consistent with its mechanism of action 
(Table 1 and Table 2). In addition, MEDI6012 increases apoA1 after both single and multiple 

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Figure 2
Mean Change from Baseline in Serum HDL-C After an IV Push 
Regimen of (Day 1 –
, Day 3 –
, and Day 10 –
) 
MEDI6012 
apoA1 = apolipoprotein A1; apoB = apolipoprotein B; HDL-C = high-density lipoprotein-cholesterol; 
IV = intravenous; LDL-C = low-density lipoprotein-C; SEM = standard error of the means. 

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Table 1
Baseline Adjusted AUC0-96h for Key PD Parameters After Ascending 
 Doses of MEDI6012 –
As-treated Population 
Placebo
N = 
MEDI6012
40 mg
N = 
MEDI6012
120 mg
N = 
MEDI6012
300 mg
N = 
MEDI6012
Total
N = 
      LS Mean
-135.76
1130.14
3054.01
5760.60
3315.29
      95% CI of LS Mean
(-1107.39, 835.87)
(153.33, 2106.95)
(2049.91, 4058.11)
(4787.11, 6734.08)
(2303.30, 4327.28)
      P-value
0.069
<0.001
<0.001
0.002
   Post 
      n
      Mean
373.04
2267.37
4047.38
9004.31
4877.06
      SD
1060.76
1126.43
1314.67
2086.47
3187.51
      Median
350.00
1930.24
3937.06
9011.63
4022.03
      (Min, Max)
(-871.3, 2011.5)
(1055.0, 4022.0)
(2836.0, 5450.1)
(6987.1, 12261.2)
(1055.0, 12261.2)
      LS Mean
389.20
2296.77
3989.87
9018.65
4873.95
      95% CI of LS Mean
(-855.77, 1634.17)
(1044.31, 3549.23)
(2707.55, 5272.18)
(7656.07, 10381.23)
(3405.99, 6341.90)
      P-value
0.035
<0.001
<0.001
0.004
Apolipoprotein A1 (mg.h/dL)
   Post 
      n
      Mean
309.57
1453.24
1856.43
2704.57
2004.75
      SD
347.45
354.56
972.15
1086.94
974.88
      Median
378.52
1333.08
1965.04
2755.66
1792.63
      (Min, Max)
(-229.6, 795.7)
(1214.6, 2146.1)
(424.2, 2864.7)
(1102.8, 4386.3)
(424.2, 4386.3)
      LS Mean
309.82
1454.45
1855.46
2704.09
2004.57
      95% CI of LS Mean
(-365.32, 984.95)
(778.65, 2130.26)
(1179.91, 2531.01)
(2028.87, 3379.31)
(1566.93, 2442.21)
      P-value
0.021
0.003
<0.001
<0.001

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Table 1
Baseline Adjusted AUC0-96h for Key PD Parameters After Ascending 
 Doses of MEDI6012 –
As-treated Population 
Placebo
N =
MEDI6012
40 mg
N = 
MEDI6012
120 mg
N = 
MEDI6012
300 mg
N = 
MEDI6012
Total
N = 
   Post 
      n
      Mean
821.33
2440.48
3740.59
5302.87
3741.22
      SD
1465.70
1021.34
1508.93
1739.86
1786.30
      Median
922.45
2276.28
3409.54
5672.88
3254.78
      (Min, Max)
(-1221.0, 2371.7)
(1258.4, 4005.6)
(2288.8, 5590.6)
(3254.8, 7331.4)
(1258.4, 7331.4)
      LS Meana
823.07
2444.76
3739.15
5297.36
3738.99
      95% CI of LS Mean
(-446.63, 2092.77)
(1173.03, 3716.50)
(2469.58, 5008.72)
(3903.24, 6691.48)
(2852.35, 4625.62)
      P-value
0.074
0.003
<0.001
0.002
Apolipoprotein B (mg.h/dL)
   Post 
      n
      Mean
-273.27
-205.08
-229.88
-817.97
-417.64
      SD
279.82
176.37
279.63
734.34
525.08
      Median
-269.46
-176.92
-300.37
-592.84
-296.84
      (Min, Max)
(-609.6, 60.2)
(-526.5, 4.9)
(-485.5, 263.8)
(-2144.1, -139.5)
(-2144.1, 263.8)
      LS Mean
-272.38
-173.50
-277.40
-802.92
-417.97
      95% CI of LS Mean
(-630.45, 85.69)
(-535.15, 188.15)
(-643.52, 88.73)
(-1161.81, -444.03)
(-649.86, -186.07)
      P-value
0.689
0.984
0.041
0.521
   Post 
      n
      Mean
-82.95
-40.06
145.42
-374.38
-72.93
      SD
667.65
477.21
283.62
588.54
479.14

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Table 1
Baseline Adjusted AUC0-96h for Key PD Parameters After Ascending 
 Doses of MEDI6012 –
As-treated Population 
Placebo
N = 6
MEDI6012
40 mg
N = 6
MEDI6012
120 mg
N = 6
MEDI6012
300 mg
N = 6
MEDI6012
Total
N = 18
      Median
-213.81
-121.10
36.39
-388.77
-91.85
      (Min, Max)
(-1047.1, 744.8)
(-577.2, 629.5)
(-99.3, 558.3)
(-1107.2, 458.6)
(-1107.2, 629.5)
      LS Mean
-76.29
16.97
72.64
-363.46
-75.41
      95% CI of LS Mean
(-498.68, 346.09)
(-410.52, 444.46)
(-358.08, 503.35)
(-826.25, 99.33)
(-327.34, 176.51)
      P-value
0.748
0.611
0.348
0.998
CI = confidence interval; HDL-C = high-density lipoprotein-cholesterol; LDL-C = low-density lipoprotein-cholesterol; LS = least squares; Max = maximum; 
Min = minimum; N = number of total subjects; n = number of subjects for assessment; PD = pharmacodynamic; SD = standard deviation.
Table 2
Baseline Adjusted AUC0-96h for Key PD Parameters After IV push dosing regimen (
 mg loading dose 
followed by 
 mg at 48 hours and 
mg 7 days later) - As-treated Population
Placebo IV PUSH
N = 
a
MEDI6012 IV PUSH
N = 
HDL Cholesterol (mg.h/dL)
   Post 
      n
      Mean
-675.69
4125.69
      SD
NA
552.08
      Median
-675.69
4402.63
      (Min, Max)
(-675.7, -675.7)
(3184.1, 4585.9)
   Post 
      n
      Mean
266.68
1803.12
      SD
NA
1684.32

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Table 2
Baseline Adjusted AUC0-96h for Key PD Parameters After IV push dosing regimen (
mg loading dose 
followed by 
mg at 48 hours and 
mg 7 days later) - As-treated Population
Placebo IV PUSH
N = 
a
MEDI6012 IV PUSH
N = 
      Median
266.68
658.73
      (Min, Max)
(266.7, 266.7)
(353.1, 4308.4)
LDL-C (Direct) (mg h/dL)
   Post 
      n
      Mean
-616.78
890.25
      SD
NA
840.94
      Median
-616.78
871.57
      (Min, Max)
(-616.8, -616.8)
(-192.5, 2334.8)
   Post 
      n
      Mean
-78.79
1364.12
      SD
NA
2375.93
      Median
-78.79
302.30
      (Min, Max)
(-78.8, -78.8)
(-152.0, 6542.5)
Cholesteryl Ester (mg.h/dL)
   Post 
      n
      Mean
-1316.90
4574.76
      SD
NA
708.37
      Median
-1316.90
4633.84
      (Min, Max)
(-1316.9, -1316.9)
(3546.7, 5418.1)

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Table 2
Baseline Adjusted AUC0-96h for Key PD Parameters After IV push dosing regimen 
 mg loading dose 
followed by 
mg at 48 hours and 
mg 7 days later) - As-treated Population
Placebo IV PUSH
N = 
a
MEDI6012 IV PUSH
N = 
   Post 
      n
      Mean
371.75
2649.56
      SD
NA
3039.83
      Median
371.75
761.94
      (Min, Max)
(371.8, 371.8)
(303.0, 8374.1)
Apolipoprotein A1 (mg.h/dL)
   Post 
      n
      Mean
-1208.16
1669.34
      SD
NA
691.14
      Median
-1208.16
2007.14
      (Min, Max)
(-1208.2, -1208.2)
(603.0, 2334.6)
   Post 
      n
      Mean
-20.42
2399.42
      SD
NA
2611.21
      Median
-20.42
744.70
      (Min, Max)
(-20.4, -20.4)
(401.0, 6694.4)
Apolipoprotein B (mg.h/dL)
   Post 

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Table 2
Baseline Adjusted AUC0-96h for Key PD Parameters After IV push dosing regimen (
 mg loading dose 
followed by 
mg at 48 hours and 
mg 7 days later) - As-treated Population
Placebo IV PUSH
N = 
a
MEDI6012 IV PUSH
N = 
      n
      Mean
-651.36
-681.99
      SD
NA
543.82
      Median
-651.36
-779.18
      (Min, Max)
(-651.4, -651.4)
(-1279.0, 381.1)
   Post 
      n
      Mean
-239.17
73.01
      SD
NA
864.30
      Median
-239.17
-209.54
      (Min, Max)
(-239.2, -239.2)
(-403.4, 2017.4)
CI = confidence interval; HDL-C = high-density lipoprotein-cholesterol; LDL-C = low-density lipoprotein-cholesterol; LS = least squares; Max = maximum; 
Min = minimum; N = number of total subjects; n = number of subjects for assessment; PD = pharmacodynamic; SD = standard deviation.
a
Analysis of LCAT levels in the placebo subject reveal that on day 10, the subject received MEDI6012 and not placebo

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In a separate study in acute STEMI patients, endogenous LCAT mass and activity levels were 
evaluated acutely, 48, and 72 hours after myocardial infarction (MI). Compared with baseline, 
LCAT mass and activity levels were significantly decreased at 48 and 72 hours post-MI and 
plasma from those patients demonstrated impaired HDL-induced nitric oxide (NO) 
production. NO production remained impaired for 30 days post-MI. Incubation of the plasma 
samples with MEDI6012 restored HDL function as measured by HDL-induced NO 
production. Together, this study provides supportive evidence that HDL function is impaired 
in acute STEMI patients and MEDI6012 can restore this function (Ossoli A).
Epidemiologic and pre-clinical studies have established that higher levels of HDL-C are 
cardioprotective in patients post-MI and infusions of HDL or apoA1 mimetics reduce 
myocardial infarct size and improve left ventricular systolic function in animal models of 
acute MI. Specifically, 1) post-infarct EF is lower in patients with low HDL-C, even after 
excluding baseline CHD (Kempen et al, 1987; Wang et al, 1998); infusion of the apoA1 
mimetic CSL-111 in two different mouse models of acute MI demonstrated an increase in 
viable myocardium of 54% - 61%, a reduction in infarct size by 21% - 26%, and 
a reduction in the recruitment of leukocytes and neutrophils in the area of infarction 
(Heywood et al, 2017); 2) infusion of the apoA1 mimetic ETC-216 in a rabbit model of 
ischemia-reperfusion resulted in a marked reduction in infarct size (Marchesi et al, 2004); 3) 
adenoviral transfer of apoA1 2 weeks prior to MI in a mouse model achieved apoA1 levels 
1.5× controls and showed increased survival (~ 2×), attenuated infarct expansion, inhibition of 
left ventricle (LV) dilation, and improved hemodynamics (Gordts et al, 2013); 4) infusion of 
HDL vs HDL and its constituent sphingosine-1-phosphate in a mouse model of ischemia-
reperfusion showed a 20% reduction in infarct size with HDL alone and a 40% reduction in 
infarct size when HDL and S1P (Theilmeier et al, 2006); and 5) apoA1 infusions reduced 
infarct size in Wistar rats via the RISK/SAFE pro-survival kinase pathways (Akt, ERK1/2, 
STAT-3) (Kalakech et al, 2014). The increases in apoA1 seen with the study by Gordts and 
Marchesi et al are similar to those increases seen with MEDI6012. Based on these data, this 
study will determine if acute treatment with MEDI6012 can reduce myocardial infarct size by 
increasing levels of HDL-C and apoA1. 
In addition to myocardial protection following acute MI, MEDI6012 also has the potential to 
regress coronary atherosclerosis and exhibit vasculo-protective properties. In rabbits that 
express endogenous CETP, transgenic overexpression of LCAT has been shown to protect 
against diet-induced atherosclerosis (Hoeg et al, 1996). Similarly, IV administration of 
rhLCAT to wild-type rabbits has also been shown to protect against atherosclerosis (Zhou M, 
2009). Clinical data have further suggested that low levels of LCAT may be associated with 
an increased incidence and/or severity of CAD (Asztalos et al, 2000; Lamon-Fava et al, 2008; 
Miida et al, 1996; Sethi et al, 2010; Solajic-Bozicevic et al, 1994; Tashiro et al, 2009). In the 
single ascending dose study (D5780C00002) in of patients with stable CHD on statin therapy, 
MEDI6012 decreased small atherogenic LDL particles by 41%, 88%, and 79% at 80, 240, and 

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800 mg respectively, supporting the potential that MEDI6012 may be beneficial in 
atherosclerosis. 
1.6
Benefit-Risk and Ethical Assessment
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with International Council for Harmonisation 
(ICH)/Good Clinical Practice, and applicable regulatory requirements.
This study will test MEDI6012 in acute STEMI patients. Patients with acute STEMI are at 
risk of future major adverse CV events, including death, MI, stroke, and heart failure. 
MEDI6012’s mechanism of action gives it the
 
 with a favourable benefit-risk 
ratio.
Nonclinical studies have established that therapies that increase HDL-C and/or apoA1 have 
the potential to protect the heart from ischemia/reperfusion injury that occurs during an acute 
STEMI. Reductions in ischemia reperfusion injury decrease infarct size and improved heart 
function. Nonclinical studies of MEDI6012 demonstrate that MEDI6012
 
In addition, nonclinical 
studies have established that MEDI6012 
 
. These nonclinical studies have supported clinical studies in patients with 
atherosclerotic CV disease.
Acute STEMI patients have decreases in LCAT mass and activity and HDL from acute 
STEMI patients is impaired in its ability to induce nitric oxide production. Treatment of 
plasma from acute STEMI patients with MEDI6012 
 
. Clinical studies of MEDI6012 have demonstrated that IV 
infusions of MEDI6012 result 
 and MEDI6012 can 
improve the function 
. MEDI6012 is being
developed so it can be administered rapidly as an IV push, 
 
in the acute STEMI setting.  
Clinical studies have demonstrated that single and multiple doses of MEDI6012 are generally 
well tolerated. Two identified risks with MEDI6012 are injection site reactions, which were 
observed at low frequencies when administered by IV, and ADAs. ADAs were observed in 
the MEDI6012 SAD study in 
 (14%) subjects. No ADAs were observed in the 
MEDI6012 MAD study when MEDI6012 was given IV, only, and in lower doses. A 
theoretical risk of MEDI6012 is 
 
has been detected in clinical studies of MEDI6012. In addition, 
the transient rise 
 with MEDI6012 is accompanied 
 

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, and is expected consistent with LCAT’s 
mechanism of action. Subjects enrolled in this study will undergo therapies which include 
LDL-C lowering with statins.
Acute STEMI is a major contributor to the development of heart failure (HF) and death in 
patients with CHD. The risk of HF and death is related to the size of the MI and the impact it 
has on heart function. Furthermore, the extent of coronary plaque burden is directly related to 
the risk of death and MI. The only therapy shown to reduce infarct size in humans with acute 
STEMI is pPCI. In addition, statins and proprotein convertase subtilisin kexin 9 inhibitors 
have demonstrated a reduction in the progression of coronary atheroma and reductions in 
major adverse CV events. MEDI6012, with its ability to 
 
, has the potential to be the first therapeutic that 
 
 
 Taken together, 
 
a favourable benefit-risk 
ratio.
1.7
Research Hypotheses
1.7.1
Primary Hypothesis
MEDI6012 will reduce MI size compared to placebo.
1.7.2
Secondary Hypotheses
Compared with placebo,
1
MEDI6012 will improve left ventricular ejection fraction (EF)
2
MEDI6012 will induce regression/reduce progression of non-calcified coronary plaque 
3
MEDI6012 will reduce adverse remodeling of the LV
4
MEDI6012 will exhibit an acceptable safety and immunogenicity profile in subjects with 
acute STEMI
2
OBJECTIVES AND ENDPOINTS
2.1
Objectives
2.1.1
Primary Objective
The primary objective and associated endpoint is presented in Table 3.

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Table 3
Primary Objective and Associated Endpoint
Type
Objective
Endpoint
Efficacy
To evaluate the effect of MEDI6012 on 
reduction of infarct size compared with 
placebo.
Infarct size as a percentage of LV mass 
measured on delayed-enhanced CMR 
imaging 10-12 weeks post-MI compared to 
placebo.
CMR = cardiovascular magnetic resonance; LV = left ventricle; MI = myocardial infarction. 
2.1.2
Secondary Objectives
Secondary objectives and associated endpoints are presented in Table 4.
Table 4
Secondary Objectives and Associated Endpoints
Type
Objective
Endpoint(s)
Efficacy
To evaluate the effect of MEDI6012 on 
systolic function of the LV compared to 
placebo.
EF measured by cine MRI at 10-12 weeks 
post-MI compared to placebo.
Efficacy
To evaluate the effect of MEDI6012 on 
non-calcified coronary plaque 
regression/progression from baseline to 
10-12 weeks compared with placebo.
Change in NCPV in the coronary arteries 
from index CTA to 10-12 weeks post-MI 
compared with placebo. 
Efficacy
To evaluate the effect of MEDI6012 on 
remodeling of the left ventricle measured by 
myocardial mass and volumes.
Myocardial mass and LV volumes at 
end-systole and end-diastole.
Safety 
To evaluate the safety and tolerability of 
MEDI6012.
Incidence of treatment-emergent adverse 
events (TEAEs) and 
treatment-emergent serious adverse 
events (TESAEs).
PK, and 
Immunogenicity 
To describe the PK and immunogenicity of 
MEDI6012.
LCAT mass and presence of ADAs.
ADAs = anti-drug antibodies; CTA = computed tomography; EF = ejection fraction; LCAT = lecithin-cholesterol 
acyltransferase; LV = left ventricular; MI = myocardial infarction; MRI = magnetic resonance imaging; 
NCPV = non-calcified plaque volume; PK = pharmacokinetic(s); TEAE = treatment-emergent adverse event; 
TESAE = treatment-emergent serious adverse event. 

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2.1.3
Exploratory Objectives
Exploratory objectives and associated endpoints are presented in Table 5.
Table 5
Exploratory Objectives and Associated Endpoints
Type
Objective
Endpoint(s)
 
 
 
 
.
 
 
 
 
 
 
 
 
 
 
.
 
 
 
 
.
 
 
 
.
 
 

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CMR = cardiovascular magnetic resonance (imaging); CTA = computed tomography angiography; D = study 
day; N = number of subjects; pPCI = primary percutaneous coronary intervention; STEMI = ST elevation 
myocardial infarction.
Inpatient Phase – Cohorts A and B
Both Cohorts A and B will receive their 
 doses in the inpatient setting.  
Following verbal or written informed consent (per local regulations) and prior to dosing, an 
assessment will be made of vital signs, and blood samples will be collected for clinical 
laboratory assessment, PK, PD, and immunogenicity. The
 of investigational product 
should be administered via IV infusion over 1-2 minutes prior to pPCI on Day 1 as soon as 
possible prior to the first pPCI procedure, defined as the time that the first angioplasty wire 
crosses the culprit lesion. Following dosing and pPCI, study procedures will be conducted in 
accordance with the Schedule of Study Procedures. On Day 3 (48±8 hours post
 
subjects will receive a 
dose of investigational product and additional study procedures 
will be conducted according to the Schedule of Study Procedures. 
For Cohort B only, those subjects with creatinine clearance (CrCl) > 60 mL/min (Cockcroft 
Gault equation) within 6 hours will undergo an index coronary computerized tomography 
angiography (CTA) no earlier than 40 hours following the 
 dose. It is preferred that the 
index CTA occur 48-72 hours post Dose , but it may be done up to 5 days post Dose . 
Subjects may be discharged following Day 3 assessments, if considered acceptable by the 
clinical team and investigator. 
Following Doses  and  (Cohort A) or Doses  through  (Cohort B), subjects will be 
monitored for 2 hours in a location with personnel trained in Adult Advanced Life Support 
with proper resuscitation equipment available.
Outpatient Phase – Cohort A
Subjects randomized to Cohort A 
 regimen) will undergo standard of care treatment 
post pPCI (Figure 4) and will follow-up according to the Schedule of Assessments. An end of 
study cardiovascular magnetic resonance (CMR) will be performed at 10-12 weeks 
(70-84 days post Dose 1).

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sub-acute phases of MI. For the 
 regimen, dosing will be complete. For the 
 
, subjects will receive 4 additional weekly 
 doses as an outpatient. A 
maintenance dose of 
 was selected to 
 at a level conferring benefit in 
epidemiology studies and at a level, predicted by PD/PK modeling from study D5780C00002 
and D5780C00005, not to result in an appreciable accumulation of 
. 
Increases in
 
3.2.2
Rationale for Study Population
The current study is intended to examine the cardioprotective and atherosclerotic effects of 
MEDI6012 in subjects with acute STEMI. In comparison to acute non-STEMI, patients with 
acute STEMI, particularly acute anterior STEMI, experience larger myocardial infarcts that 
result in greater reductions in EF. Since it is likely that subjects with larger infarcts will be 
more likely to benefit from MEDI6012, the study population is planned to have > 50% of 
subjects with acute anterior STEMI and > 60% with pre-PCI Thrombolysis in Myocardial 
Infarction (TIMI) flow grade (TFG) 0-1. However, this study will evaluate the effect of 
MEDI6012 in non-anterior STEMI and those with pre-PCI TFG 2-3 to fully characterize the 
potential efficacy of MEDI6012.
3.2.3
Rationale for Endpoint(s)
3.2.3.1
Rationale for Primary Endpoints
The primary endpoint is assessment of infarct size as a percentage of LV mass measured on 
delayed-enhanced CMR imaging at 10-12 weeks post MI. 
Infarct size measured at 10-12 weeks reflects final infarct size after remodeling of the LV and 
will reflect both the early and late effects of treatment with MEDI6012 (Mather et al, 2011). 
Infarct size is an independent predictor of secondary major adverse CV events, including 
mortality and hospitalization for heart failure (Stone et al, 2016; Wu et al, 2008). For every 
5% increase in infarct size, there is a 19% increase risk of all-cause mortality, 20% increase 
risk of heart failure hospitalization, and a 20% increase in the combined endpoint of death and 
heart failure hospitalization (Stone et al, 2016). CMR is considered the gold standard for the 
evaluation of infarct size and is considered the most relevant endpoint in cardioprotection 
trials (Hausenloy et al, 2013).
3.2.3.2
Rationale for Secondary Endpoints
Safety and tolerability of MEDI6012 as measured by the incidence of TEAEs, and TESAEs, 
and immunogenicity measured by ADAs, and nAbs over time to last study visit (Days 70-84), 
will support further drug development.
EF measured by cine magnetic resonance (MR) imaging at 10-12 weeks post-MI compared to 
placebo was selected since EF is a well-established measurement of the systolic function of 

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the LV. Additionally, pharmacologic improvements in EF have been linked to decreases in 
mortality and heart failure hospitalizations (Breathett et al, 2016; Kramer et al, 2010). EF will 
be calculated as the ratio of stroke volume divided by end-diastolic volume.
Change in non-calcified plaque volume (NCPV) in the coronary arteries from index computed 
tomography angiography (CTA) to 10-12 weeks post-MI compared with placebo was selected 
as a secondary endpoint over calcified and total plaque volume. When studied in ACS, 
specifically non-STEMI ACS, NCPV is a better predictor of major adverse cardiac events 
when compared to Agatston calcium score and total plaque volume (Kristensen et al, 2011). 
NCPV will be measured in all vessels ≥ 2 mm in diameter and expressed in mm3. Coronary 
segments with stents or otherwise deemed uninterpretable will be excluded from analysis.
Myocardial mass and LV volumes at end-systole and end-diastole are included since they are 
well-established predictors of clinical outcomes and will be measured by CMR. Ventricular 
volumes and myocardial mass will be measured in mL and g, respectively, and indexed to 
body surface area. 
3.2.3.3
Rationale for PK Endpoints
Serum concentration of MEDI6012 (mass) will be used to characterize MEDI6012 exposure. 
The PK may also be used to develop dose-exposure-PD response relationships to help inform 
dose selection for future clinical studies. 
3.2.3.4
Rationale for Exploratory Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4
MATERIALS AND METHODS
4.1
Subjects
4.1.1
Number of Subjects
Approximately 540 subjects are planned as described in Section 3.1.2.
4.1.2
Inclusion Criteria
Subjects must meet all of the following criteria:
1
Men and women without child-bearing potential (for definitions see Section 10.2) 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
4.1.3
Exclusion Criteria
Any of the following would exclude the subject from participation in the study:
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 
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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 < 30 mL/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
4.1.4
Additional Study Procedure Requirements
After randomization and prior to study-related imaging procedures, subjects will be required 
to meet the following criteria for CMR and CTA imaging.  
Administration of Gadolinium Contrast for Cardiovascular MRI
MRI is allowed if there is no contraindication to MR imaging (eg, metallic implant, 
claustrophobia, ICD, pacemaker), but in order for subjects to receive gadolinium contrast, the 
following requirements must also be met: 
1
CrCl ≥ 30 mL/min (Cockcroft Gault equation) within 7 days prior to the procedure
2
No known allergy to gadolinium contrast agents
Coronary CTA
1
CrCl ≥ 60 mL/min (Cockcroft Gault equation) within no more than 6 hours prior to index 
CTA and no more than 7 days prior to follow up CTA
2
Women must be 40 years of age or older
3
No known allergy to iodinated contrast
4
No known history of contrast induced nephropathy 
5
No contraindication to heart rate lowering using betablockers to allow for high quality, 
low-radiation dose CTA (per-protocol). Please note, if heart rate is well-controlled 
allowing for a high quality, low radiation CTA without betablocker, then a 
contraindication to betablocker does not exclude the subject from coronary CTA.  
6
For follow-up CTA at the end of the study, subjects would need to have undergone index 
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4.1.5
Subject Enrollment and Randomization
Subjects will be enrolled while they are having an acute STEMI. The time for consent, 
screening, randomization, and administration of the first dose of investigational product in this 
setting will require an efficient process that accomplishes this in a timely fashion. Typically, 
the standard of care in acute STEMI is to have a door-to-balloon time of 90 minutes or less 
from when a patient enters a healthcare facility (door time) to when they have pPCI (balloon 
time). Therefore, acute STEMI trials often use a short form consent (or verbal assent, 
depending on local regulations) to consent patients for the first dose of investigational 
product. This study will allow informed consent/verbal processes that include: 1) one-stage 
informed consent where full informed consent is obtained prior to required study procedures, 
2) two stage informed consent where the first stage, obtained prior to study procedures, uses a 
short-form consent that covers day 1 dosing and study procedures and a second stage 
informed consent, obtained prior to all subsequent procedures, that covers the remaining doses 
and study procedures, and 3) two stage informed consent where the first stage uses verbal 
consent, obtained prior to study procedures, that covers day 1 dosing and study procedures 
and a second stage informed consent, obtained prior to all subsequent procedures, that covers 
the remaining doses and study procedures. Verbal and short-form consent will only be applied 
when applicable to local regulations and standards. A one- or two-stage informed consent, that 
may or may not include a verbal option (depending on local regulations), will be undertaken 
for this study, depending on local standards and preferences. In addition, next of kin or an 
impartial physician may be included in the consenting process according to local regulations 
and standards. A subject may consent for study procedures that occur on Day 1 and decline 
subsequent consent of further study procedures.
Study participation begins on study Day 1 (ie, a subject is “enrolled”) once the first consent, 
whether written or verbal is obtained. Following first consent, evaluations to assess study 
eligibility (inclusion/exclusion criteria) will be performed. A SID (subject identification) 
number will be used to identify the subject. Dose 1, as assigned following randomization by a 
central system (eg, an interaction response system [IXRS], which includes interactive voice 
response system and interactive web response system) may be given once the pre-screening 
procedures have been completed.
A master log of all consented subjects will be maintained at the site and will document all 
screening failures (ie, subjects who are consented but do not meet study eligibility criteria 
and/or are not randomized), including the reason(s) for screening failure.
Subjects who fail to meet the inclusion/exclusion criteria (ie, screening failures) should not be 
randomized (if applicable) or receive investigational product.
Randomization will be stratified by infarct location, ensuring balanced randomization to 
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addition, the distribution of subjects with anterior vs non-anterior MIs will be monitored over 
the course of the study. The goal is that >50% of the final randomized population will be 
anterior MI. Therefore, the number with non-anterior MI will be monitored via the IXRS and 
capped by the study team.
4.1.6
Withdrawal from the Study
Subjects are free to withdraw consent from the study (which means permanent discontinuation 
of investigational product and all follow-up assessments) at any time without prejudice to 
further treatment. Discontinuation of investigational product in and of itself is not considered 
withdrawal of consent.
Withdrawal of consent should only occur if the subject refuses any further assessments or 
contact whatsoever. Subjects who do not want regular in-person follow-up after cessation of 
investigational product should be offered alternative methods of follow-up including periodic 
telephone follow-up, contact at study closure, or assessment of health status via treating 
physicians or medical records. Such subjects would then not be viewed as withdrawal of 
consent.
The investigator must explain to the subject all options for continued participation, and 
document which options were refused by the subject and the reason for refusal. Withdrawal of 
consent to all follow-up must be ascertained and documented in writing by the investigator 
who must inform the TIMI Hotline and document the withdrawal of consent in the eCRF and 
medical records.
Subjects who withdraw consent to all follow-up will be asked about the reason(s), and will be 
assessed for the presence of any adverse events. For confirmed withdrawal of consent 
subjects, direct ascertainment of health status at the end of the study or vital status via public 
records will be performed in compliance with local privacy laws/practices.
4.1.7
Discontinuation of Investigational Product
Subjects are free to discontinue investigational product at any time, without prejudice to 
further treatment. Subjects who choose to discontinue investigational product are expected to 
continue in the study according to the schedule of study procedures for the remainder of the 
study.
The investigator and/or medical monitor may determine that an individual subject will not 
receive any further investigational product if any of the following occur in that subject:
1
Safety reasons as judged by the investigator and/or sponsor where continued treatment 
may put patient at undue risk, eg, 

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(a) Severe adverse immune reaction (e.g., anaphylactic-type reactions, immune complex 
disease) deemed related to investigational product.
(b) Infusion site reaction assessed as intolerable and related to investigational product.
2
Incorrectly randomized patient in whom inclusion/exclusion criteria violation would put 
the patient at undue risk.
3
Before or after initial dosing, it is discovered that the subject has no coronary artery 
disease (obstructive or non-obstructive) on invasive angiography.
4
Subject noncompliance that, in the opinion of the investigator or Sponsor, warrants 
treatment discontinuation for safety reasons (e.g., refusal or inability to adhere to 
scheduled visits).
5
Pregnancy in any female subject.
Cases where subjects are incorrectly randomized (ie the subject does not meet the required 
inclusion/exclusion criteria for the study) should be discussed with the TIMI Hotline prior to 
any actions being taken with discontinuation of investigational product or follow up. Upon 
review by the TIMI Hotline or medical monitor, subjects found after randomization to have 
met an exclusion that is unrelated to safety may continue study treatment. For patients 
randomized but subsequently determined to not have a qualifying STEMI and who are 
therefore not planned to receive continued study treatment, follow up may be restricted to 
safety only at the discretion of the Sponsor. For subjects who never receive investigational 
product, follow up will consist of a minimum of a single phone call at the end of the study; 
however, visits are allowed at the discretion of the subject and investigator.  
Discontinuation of investigational product does not mean discontinuation of follow-up. 
Subjects who are permanently discontinued from receiving investigational product will be 
followed for protocol-specified assessments, including follow-up of any AEs, unless consent 
is withdrawn specifically from further study participation (Section 4.1.6), the subject is lost to 
follow-up (Section 4.1.8), or the subject is enrolled in another clinical study.
A subject who decides, and/or is recommended by treating physician or the investigator to 
permanently discontinue investigational product, will always be asked about the reason(s) for 
discontinuation and about the presence of any AEs. All efforts must be taken to ensure that the 
subject will be seen and assessed by an investigator and, as scheduled for other subjects, all 
end-of-treatment visit assessments should be completed at the time of discontinuation of 
investigational product.
Following discontinuation of investigational product, regularly scheduled study visits and 
follow-up procedures are expected to continue as planned. The follow-up visits should 
preferably be in-person and should include all procedures and assessments listed in the 
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follow-up visit option, a modified follow-up through regular telephone contacts or a contact at 
study closure should be arranged. Regardless of whether a subject comes to the site for an in-
person follow-up visit or is contacted by telephone, once a possible event that may require 
adjudication is noted, medical records must be obtained and submitted to the CEC for 
adjudication of the event.
In the setting of acute MI, transaminases used to monitor for liver toxicity (alanine 
transaminase [ALT] and aspartate transaminase [AST]) can be elevated and of cardiac origin. 
Section 10.6 describes actions to be taken. 
4.1.8
Lost to Follow-up Subjects
To prevent subjects being lost to follow-up, their contact details, including next of kin 
contacts should be collected by the site staff or representative. The investigator should educate 
the subject on the importance of contact with the investigator throughout the study. Repeated 
attempts will be made to locate and obtain pertinent medical information for subjects who are 
potentially lost to follow-up. A subject will be classified as confirmed lost to follow-up only if 
he/she has failed to return for the required study visits and his/her vital status remains 
unknown despite multiple attempts to contact him/her via telephone, fax, email, certified 
letter, or through subject locator agencies (if allowed by national regulation). Where 
permissible by local law, the informed consent forms will include language to grant the option 
to employ outside companies to assist in obtaining updated contact information or 
ascertainment of vital status of lost subjects using publicly available sources.
4.1.9
Replacement of Subjects
Subjects who are discontinued from further dosing or follow-up procedures from the study, or 
who withdraw their informed consent to all follow-up, prior to the end-of-study visit may be 
replaced, if deemed necessary, by the medical monitor to ensure that safety, PK, PD, and 
imaging data are collected from a sufficient number of subjects. The medical monitor should 
be notified within 48 hours if a subject is discontinued from the study or withdraws consent to 
all follow-up. A determination whether to replace the subject will be made jointly between the 
principal investigator and medical monitor.
4.1.10
Withdrawal of Informed Consent for Data and Biological Samples
Biological Samples Obtained for the Main Study
Study data are protected by the use of an SID number, which is a number specific to the 
subject. The investigator is in control of the information that is needed to connect a study 
sample to a subject. A subject’s consent to the use of data does not have a specific expiration 
date, but the subject may withdraw consent at any time by notifying the investigator. If 
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by the Sponsor but no new data or samples will be collected unless specifically required to 
monitor safety of the subject.
Samples Obtained for Future Research
Samples obtained for future research will be labeled with a sample identification number 
linked to the SID number, but will not be labeled with personal identifiers such as the 
subject’s name. If the subject withdraws consent for participating in the future research, the 
sponsor will locate the subject’s sample and destroy it. The coding of samples and results is to 
ensure that these research results are kept confidential by keeping the subject’s identity and 
these results separate.
If the subject consents to have his/her samples used for future research, this additional 
research may not start immediately and may start at any time during the storage period. The 
subject’s sample(s) will be stored by the sponsor with similar samples from other subjects at a 
secure central laboratory. The subject’s samples will not be kept for more than 25 years after 
the end of the study in which they were collected. If the subject chooses not to allow his/her 
study samples to be used for future research, the samples will be destroyed by the sponsor 
once they are no longer required for the main study.
If consent is withdrawn after a sample has been taken but before the subject’s sample is sent to 
the sponsor for future research, the investigator will arrange to have it destroyed. If consent is 
withdrawn after the subject’s sample(s) have been sent to the sponsor for future research, the 
sponsor and the investigator will ensure that these sample(s) are destroyed unless the sample 
identification number has been removed and the subject can no longer be linked to any 
sample(s). However, if the subject’s samples have already been used for research, the sponsor 
is not required to destroy results of this research. In this case only the remaining sample(s) 
will be destroyed.
4.2
Schedule of Study Procedures
4.2.1
Enrollment, Treatment, and Follow-up Periods
Due to the acute nature of the first treatment in this study, the screening period takes place on 
study Day 1, immediately prior to receiving investigational product. All procedures to be 
conducted during the screening, treatment, and follow-up periods are presented in the 
Schedule of Study Procedures (Table 8 and Table 9). 
4.2.1.1
Study Procedure Modifications in Response to the COVID-19 Pandemic 
The modifications listed below are designed to enable safety monitoring of subjects enrolled 
in the trial through an extended blood sampling window as well as to maintain trial integrity 
for the primary and secondary endpoints by enrolling all remaining patients in Cohort B (to 
obtain both the CMR and CTA as well as extended dosing data), which has had a greater
dropout rate further impacted by COVID-19.

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1
If the Visit 6 (Day 70-84) follow-up visit cannot be conducted in person due to the 
coronavirus disease (COVID-19) pandemic, the following study procedure modifications 
are permissible:
(a) Where possible, a subject should return to the clinic as soon as possible after the 
planned Visit 6 (Day 70-84) visit but no more than 150 days post dose 1 for blood 
sample collection (except for future use samples), including immunogenicity, PK, 
and PD, as listed in the Schedule of Study Procedures (Table 8 and Table 9) for Day 
70-84.
(b) However, assessment of AEs/SAEs and concomitant medications should be done via 
telephone contact within the originally specified window for Visit 6 (ie, Day 70-84).
(c) If a subject returns to the clinic for blood sample collection within the extended 
window, any AEs/SAEs that occur between the telephone contact and the date of this 
visit should also be recorded.
The modifications in study procedures listed above (1a-c) are only permitted due to 
COVID-19-related constraints impacting the subject, site, or health system;
otherwise, the study procedures should be conducted within the timeframes originally 
specified in the Schedule of Study Procedures (Table 8 and Table 9).
2
All subjects will be randomized into Cohort B 
Regimen). Subjects will be 
randomized in a 1:1 ratio to receive MEDI6012 or placebo. This modification will remain 
in place until the end of the study.

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Table 8
Treatment Period and Follow-up Procedures: Cohort A 
 Regimen)
Study Period
Treatment Period
Follow-
up
Visit Number
V1 (Inpatient)
V2
V3
V4
V5
V6
Procedure / 
Study Day
Day 1
Anytime 
between 
Days 1-
3
Day 3 
(48 ± 
8 
hours)
Day 
10 (±1 
day)
Phone
Day 
17 
(± 1 
day)
Day 
24 
(± 1 
day)
Phone
Day 31 
(± 1 
day)
Days 
70-84 a
Screening
Pre-PCI 
and 
Dose 1
Immediately 
Post-Dose/PCI 
1-1.5 hr Post-
Dose
12-18 hr 
Post-
Dose
g
Should be prior to PCI, preferably >10 minutes prior
h
Visits or missed doses that will potentially fall outside of the window specified in this table must be discussed with the TIMI Hotline as early as possible 
in order to adjust visit/dosing schedule.
i
AE collection begins after randomization and lasts until the end of the study. SAE collection begins after the subject signs the informed consent 
document and lasts until the end of the study.
j
For 
 observation, subjects will be monitored for 2 hours in a location with personnel trained in Adult Advanced Life Support with proper 
resuscitation equipment available.
k
Local values for creatinine can be used for imaging eligibility (in addition to collecting central samples). Creatinine values must be measured and 
reviewed prior to CMR and CTA within the timeframe specified in Section 4.1.4.
l
Within 20 minutes 
 
m
Fasting for 1-1.5 hours at the 1-1.5 hour timepoint, fasting for ≥6 hours on Days 3-70
n
Future use samples will only be obtained if the subject gives consent. Aliquots of future use samples will be stored at the core laboratory and the TIMI 
biobank.
o
In the case of a clinical indication for an intracardiac device (ie, pacemaker, implantable cardioverter-defibrillator), the CMR can be scheduled at an 
earlier time point, but not prior to 30 days 
. In addition, if the end of study CMR is determined to be of inadequate image quality by the CMR 
core laboratory, the subject may return for a repeat CMR within 4 weeks of the end of study window (up to 112 days post Dose 1).

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4.2.2
Extended Follow-up Period for Subjects Testing Positive for Anti-Drug 
Antibodies Plus > 30% Decrease from Baseline in HDL-C at Day 70 to 
84 or Presence of a Neutralizing Antibody on Day 70 to 84
Table 10 shows all procedures to be conducted during the Extended Follow-up period for 
subjects testing positive for ADAs plus > 30% decrease from baseline in HDL-C at Day 70 to 
84) or presence of nAb on Day 70 to 84). Assessments should be performed in the order 
shown in the table. During the Extended Follow-up period, if either the ADA test result 
becomes negative or the HDL-C is no longer > 30% decreased compared with baseline, the 
subject does not need to return for any additional Extended Follow-up visit(s) and will be 
considered as having completed the Extended Follow-up period.  
Table 10
Extended Follow-up Procedures for Subjects Testing Positive for 
Anti-Drug Antibodies Plus > 30% Decrease from Baseline in HDL-C 
at Day 70 to 84 or Presence of a Neutralizing Antibody on Day 70
to 84
Study Period
Extended Follow-up Period
Visit Number
Visit 7
Visit 8
Visit 9
Procedure / Study Day or Week
Week 25 
±2 Week
Week 39 
±2 Week
Week 52 
±2 Week
Targeted Physical examination 
X
X
X
Vital signs
X
X
X
PK blood sample
X
X
X
Immunogenicity blood sample
X
X
X
PD blood sample
X
X
X
Assessment of AEs/SAEs
X
X
X
Concomitant medications
X
X
X
AE = adverse event; PD = pharmacodynamics; PK = pharmacokinetics; SAE = serious adverse event. 
4.3
Description of Study Procedures
There are times where the protocol requires more than one procedure to be completed at the 
same time point. Whenever vital signs, 12-lead ECGs, and blood draws are scheduled for the 
same nominal time, the assessments should occur in the following order: 12-lead ECG, vital 
signs, and then blood draws (with the exception of Visit 1 [Day 1], where the order of vital 
signs and then blood draws may not be possible due to the acute nature of this visit and as the 
subject may have invasive blood pressure measurements). The timing of the first 
two assessments should be such that it allows the blood draw (eg, PK blood sample) to occur 
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4.3.1
Medical History and Physical Examination, Weight, and Vital Signs
A brief and targeted medical history screening will be performed focusing on 
inclusion/exclusion criteria.  
A full physical examination will be conducted anytime between Day 1 and 3 prior to 
administration of 
 and at the final study visit (Day 70-84). 
Physical examinations will be performed by a physician or a qualified designee with 
examination of the following body systems: respiratory; CV; gastrointestinal; 
musculoskeletal; focused neurologic (to the extent of determining whether or not the subject is 
willing and able to cooperate with the required study procedures in the investigator’s 
judgment); dermatologic; hematologic/lymphatic. When a targeted physical exam is required, 
evaluation of selective body systems will be at the judgement of the physician or qualified 
designee based on subject presentation.
Any focal deficit identified at baseline should be documented in the electronic case report 
form (eCRF). Clinically significant abnormal findings will be recorded at baseline and 
follow-up.
Weight will be measured immediately following PCI once feasible with regards to equipment 
availability and appropriateness for the patient’s clinical status. Height can be measured 
anytime between Days 1 and 3 and weight repeated on the days specified in the Schedules of 
Procedures.
Vital sign measurements (blood pressure [BP], respiratory rate, heart rate, and body 
temperature) will be measured at the time points specified in the Schedules of Procedures. 
Invasive blood pressure measurements may be recorded when intra-arterial monitoring is 
available. When non-invasive blood pressures are taken, the subject should be supine and the
subject’s arm must be at the same height (at the level of their heart) during each BP 
measurement. 
Subjects should refrain from smoking or drinking caffeinated beverages within 4 hours prior 
to vital signs measurements. 
4.3.2
ECG
ECGs will be conducted at the time points presented in the Schedules of Procedures.
The investigator may add extra 12-lead ECG safety assessments if there are any abnormal 
findings or if the investigator considers it is required for any other safety reason.  Scheduled 
ECGs and any ECGs done for safety purposes should be scanned for digital storage.  

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4.3.3
Systemic/Local Tolerability
Site staff will check the injection site(s) for local reactions and assess for systemic reactions at 
the times specified in the Schedules of Procedures. Local and systemic reactions will be 
recorded as AEs according to the criteria described in Section 5.4.
4.3.4
Clinical Laboratory Tests
A Laboratory Manual will be provided to the sites that specifies the procedures for collection, 
processing, storage, and shipment of samples, as well as laboratory contact information, 
specific to this clinical research study. 
Clinical laboratory safety will be performed in a central clinical laboratory, unless specified as 
“local labs” in the schedule of procedures. Abnormal laboratory results should be followed up 
at the principal investigator’s discretion. 
The following clinical laboratory tests will be performed: 
Serum Chemistry
•
Calcium
•
Alkaline phosphatase (ALP)
•
Chloride
•
Total bilirubin
•
Potassium
•
Gamma glutamyl transferase
•
Sodium
•
Creatinine
•
Bicarbonate
•
Glucose
•
AST
•
Albumin
•
ALT
•
Blood urea nitrogen
Note for serum chemistries: Tests for AST, ALT, ALP, and total bilirubin must be conducted concurrently and 
assessed concurrently.
Hematology
•
White blood cell count with automated 
differential (by central laboratory)
•
Platelet count
•
Red blood cell count
•
Mean corpuscular volume
•
Hematocrit
•
Mean corpuscular hemoglobin concentration
•
Hemoglobin
Other Laboratory Tests
•
Cystatin C
•
Glutamate Dehydrogenase
•
Creatine Kinase (CK)
•
Troponin
•
NT-proBNP
•
Luteinizing Hormone a

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•
Follicle Stimulating Hormone a
a
Female subjects only.
4.3.5
Pharmacokinetic Evaluation and Methods
Blood will be collected to evaluate PK of MEDI6012 in serum. Sampling within the specified 
time window around the specified time will not be considered a protocol deviation but the 
exact time of sampling must be recorded. The blood samples for PK taken at Visit 3 (Day 17), 
Visit 5 (Day 31) and Visit 6 (Day 70-84) from Cohort A, and Visit 6 (Day 70-84) from
Cohort B will be collected and will only be measured for MEDI6012 PK if the resulting 
analyses are deemed to be useful to further evaluation of MEDI6012 based on emerging study 
data (ie, assessment of immunogenicity). PK of MEDI6012 in serum will be measured by 
immunoassay. 
4.3.6
Pharmacodynamic Evaluation and Methods
Blood samples for key 
 will be 
collected at time points as presented in the Schedules of Procedures. The PD markers of 
primary interest are 
; however, additional lipids and lipoproteins 
will also be collected and analyzed to fully describe the effect of MEDI6012 on the 
cholesterol pathway including but not limited to other measures in the lipid profile. Sampling 
within the specified time window around the specified time will not be considered a protocol 
deviation but the exact time of sampling must be recorded.
PD blood sample for key 
 
 
 
 
 
4.3.7
Immunogenicity Evaluation and Methods
As with any 
, administration of MEDI6012 may 
. 
Because MEDI6012 is the 
 
 
Blood samples for ADA will be collected at time points specified in the Schedules of 
Procedures. A screening assay will be used to determine ADA-positive samples. This will be 
in the form of a traditional ligand-binding “bridging” assay using electrochemiluminescence. 

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Any positive samples will be tested in a confirmatory assay whereby the specificity of the 
ADA response will be confirmed as either positive or negative with respect to MEDI6012 
investigational product. Titer evaluation will be performed on samples that are confirmed 
positive for ADA, and these samples will be further characterized as either a neutralizing or a 
non-nAb response using an enzymatic assay that determines the ability of LCAT to esterify a 
fluorescent analogue of cholesterol. 
In addition, subjects whose follow up (Day 70-84) immunogenicity sample is confirmed as 
ADA positive plus > 30% decrease from baseline in HDL-C or presence of a nAb will return 
to the study site on Weeks 25, 39, and 52 for additional assessments (Table 10). However, 
during the Extended Follow-up period if the ADA test result becomes negative or the HDL-C 
is no longer > 30% decreased compared with baseline, the subject does not need to return for 
additional Extended Follow-up visit(s) and will be considered as having completed the 
Extended Follow-up period. These additional visits and assessments will be reported as an 
addendum to the clinical study report.
Serum samples collected for ADA should be stored for 2 years after marketing approval and 
may be utilized for further characterization of the antibody response. 
4.3.8
Imaging Biomarker Evaluation and Methods
Research CMR and coronary CTA imaging will be used for the primary endpoint and select 
secondary endpoints. CMR and coronary CTA imaging will be analyzed in separate, blinded, 
and independent core laboratories. Imaging personnel and equipment will undergo 
certification by the core laboratories.  Clinical invasive angiograms will be evaluated locally 
by the principal investigator and de-identified images will be transferred to a central 
repository for future analysis, if necessary.
CMR
Subjects randomized to the 
 regimens will undergo CMR imaging at Visit 6 
(Day 70-84). If the end of study CMR is determined to be of inadequate image quality by the 
CMR core laboratory, the subject may return for a repeat CMR within 4 weeks of the end of 
study window (up to 112 days post Dose 1). If CMR and CTA are scheduled on the same day, 
CMR should always be performed before coronary CTA and before the administration of 
betablockers for coronary CTA. For CMR, subjects will be required to meet the Additional 
Study Requirements listed in Section 4.1.4 including no contraindication to MR imaging (eg, 
metallic implant, claustrophobia, ICD, pacemaker) and, for the administration of 
gadolinium-based contrast, confirmation of CrCl ≥ 30 mL/min (Cockcroft Gault equation) is 
required. Prior to the scan, subjects will have a peripheral IV line placed for the administration 
of gadolinium-based contrast. Late Gadolinium-enhanced images will be obtained 15 minutes 
after an IV bolus injection of ionic, non-linear gadolinium contrast agent to identify regional 
fibrosis. Scan duration is estimated to be approximately 1 hour. The details of the imaging 

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protocol will be outlined in the CMR imaging manual. The imaging protocol will be refined to 
accommodate differences in imaging platforms at sites. The following imaging methods and 
evaluations will be performed:
Cine MRI for Quantification of LV Function and Volumes

Left Ventricular Ejection Fraction


Left Ventricular End Diastolic Volume

Left Ventricular End Systolic Volume





Late-gadolinium Enhancement MRI for Myocardial Scar Quantification



Scar Burden Expressed as a percentage of LV Mass 



Coronary CTA
Coronary CTA will be performed in subjects randomized to the 
 regimen only during 
the inpatient hospitalization. The index CTA will preferably be performed between 
48-72 hours post Dose 1 (may be done up to 5 days post Dose 1) but no earlier than 40 hours 
post Dose 1. The follow-up CTA will be performed 70-84 days following randomization. If 
CTA and CMR are done on the same day, CTA should always be performed after CMR.
Follow-up coronary CTA imaging will be done only for subjects with index CTA and can 
occur on a separate visit from CMR imaging, if needed for scheduling purposes. In subjects 
who have CABG surgery planned, index and follow-up CTA should not be performed. If a
subject completes
of investigational product and is scheduled for CABG surgery, 
follow-up CTA can be performed earlier to ensure that CTA occurs prior to the CABG
surgery, upon approval from the TIMI Hotline or Sponsor. For subjects who have received
fewer than 
 of investigational product or if CABG surgery has already been performed
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4.3.9
Estimate of Volume of Blood to be Collected
The maximum volume of blood to be collected from each subject from Day 1 to the end of the 
study (Day 70-84) is estimated to be 225 mL. Subjects who consent to collection of future use 
samples will have an additional 60 mL of blood drawn throughout the study for a total blood 
volume estimation of 285 mL. Additional blood may be collected at the discretion of the 
investigator in the event of abnormal laboratory findings or an AE. Furthermore, subjects with 
positive ADA test results plus > 30% decrease from baseline in HDL-C on Day 70 to 84 or 
presence of nAb on Day 70 to 84 will return on Weeks 25, 39, and 52 as applicable
(depending on ADA and HDL-C results at these visits; Section 4.2.2) and have blood drawn 
for a volume estimated to be 25 mL per visit.
4.4
Study Suspension or Termination
The sponsor reserves the right to temporarily suspend or permanently terminate this study at 
any time. The reasons for temporarily suspending or permanently terminating the study may 
include but are not limited to the following: 
1
The study may be terminated if, in the judgement of the sponsor, trial patients are placed 
at undue risk. The judgement may be based on recommendations from the Data 
Monitoring Committee (DMC)
2
Subject enrollment is unsatisfactory
3
Non-compliance that might significantly jeopardize the validity or integrity of the study 
4
Sponsor decision to terminate development of the investigational product for this 
indication
5
Sponsor decision to terminate the study based on a planned futility analysis
If MedImmune determines that temporary suspension or permanent termination of the study is 
required, MedImmune will discuss the reasons for taking such action with all participating 
investigators (or head of the medical institution, where applicable). When feasible, 
MedImmune will provide advance notice to all participating investigators (or head of the 
medical institution, where applicable) of the impending action.
If the study is suspended or terminated for safety reasons, MedImmune will promptly inform 
all investigators, heads of the medical institutions (where applicable), and/or institutions 
conducting the study. MedImmune will also promptly inform the relevant regulatory 
authorities of the suspension/termination along with the reasons for such action. Where 
required by applicable regulations, the investigator or head of the medical institution must 
inform the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) promptly 
and provide the reason(s) for the suspension/termination. If the study is suspended for safety 
reasons and it is deemed appropriate by the sponsor to resume the study, approval from the 

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relevant regulatory authorities (and IRBs/IECs when applicable) will be obtained prior to 
resuming the study.
4.5
Investigational Products
4.5.1
Identity of Investigational Product(s)
MedImmune will provide the investigator(s) with investigational product using designated 
distribution centers (Table 11). 
Table 11
Identification of Investigational Products
Investigational Product
Manufacturer
Concentration and Formulation as 
Supplied
MEDI6012  
MedImmune
 
 
Placebo
MedImmune
 
 
sWFI = sterile water for injection; w/v = weight by volume.
The MEDI6012 drug product 
 
 
Placebo is provided as a sterile colorless to slightly yellow solution. 
Investigational product will be supplied to the site in cartons containing a single vial of either 
MEDI6012 drug product or placebo 
Every investigational product vial assigned by the IXRS is to be used for dose preparation. 
Each kit has a unique number that is printed on all labels within the kit (ie, the outer carton 
label and the vial within the carton).
4.5.1.1
Investigational Product Handling
Dedicated study staff preparing MEDI6012 and placebo should do so in an area that is out of 
sight of other study and clinical staff, wherever possible. Although this is a single-blind study, 
caution should be taken to not reveal any information regarding the randomized treatment 
administered to other catheterization laboratory staff or to the subject at all times. Once 
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MEDI6012 and placebo does not contain preservatives and any unused portion must be 
discarded. 
 
Total in-use storage time from 
of investigational product 
or needle puncture of the investigational product vial to start of IV push administration should 
not exceed 4 hours at room temperature or 24 hours at 2°C to 8°C (36°F to 46°F). If in-use 
storage time before dose administration exceeds these limits, a new dose must be prepared 
from new vial(s). 
For each MEDI6012 or placebo dose level delivered, Table 12 describes the delivery volume 
(mL), the required number of vials, and the number of syringes required for each dose.
Table 12
MEDI6012 and Placebo Product Delivery Volume and Vial Usage
Dose (mg)
Total Delivery Volume 
(mL)
Number of Vials 
Required
Syringes Required for 
Administration
MEDI6012
Placebo
MEDI6012
Placebo
MEDI6012
Placebo
MEDI6012 or placebo is pooled in the appropriate syringe and dose prepared based on 
delivery volume. The IV push will be administered over 1-2 minutes and followed by a 10 mL 
normal saline flush.
4.5.1.4
Treatment Administration
The first day of dosing is considered Day 1. On Day 1, investigational product will be 
administered following verbal or written informed consent and should be prior to pPCI (as 
soon as possible prior to pPCI, defined as the time that the first angioplasty wire crosses the 
culprit lesion). In rare cases when investigational product is not administered prior to PCI in a 
subject who has already been randomized, then the first dose will be administered as soon as 
possible post-PCI. Subsequent doses will be administered following an overnight fast for a 
minimum of 6 hours, as soon as is practicable after rising. Subjects should be instructed on 
whether their regular medications can be taken while fasting.
Investigational product will be administered by IV push over approximately 1-2 minutes, 
inclusive of flush.

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4.5.1.5
Monitoring of Dose Administration
Vital signs and ECG assessments will be performed according to the Schedules of Study 
Procedures.
As with any biologic product, allergic reactions to dose administration are possible. Therefore, 
following Doses 
 (Cohort A) or Doses 
 (Cohort B), subjects will be 
monitored for 2 hours in a location with personnel trained in Adult Advanced Life Support 
with proper resuscitation equipment available. Appropriate drugs and medical equipment to 
treat acute anaphylactic reactions must be immediately available, and study personnel must be 
trained to recognize and treat anaphylaxis.
4.5.1.6
Reporting Product Complaints
Any defects with the investigational product must be reported immediately to the MedImmune 
Product Complaint Department by the site with further notification to the site monitor. All 
defects will be communicated to MedImmune and investigated further with the Product 
Complaint Department. During the investigation of the product complaint, all investigational 
product must be stored at labeled conditions unless otherwise instructed.
MedImmune contact information for reporting product complaints:
Email:
productcomplaints@medimmune.com
Phone: +1-301-398-2105
Mail: MedImmune
Attn: Product Complaint Department
One MedImmune Way,
Gaithersburg, MD USA 20878
4.5.2
Additional Study Medications
Subjects should undergo standard of care treatment and follow-up per local standards 
including high intensity statin therapy. 
4.5.3
Labeling
Labels for the investigational product will be prepared in accordance with Good 
Manufacturing Practice and local regulatory guidelines. Label text will be translated into local 
languages, as required.
4.5.4
Storage
Store investigational product at 2°C to 8°C (36°F to 46°F).

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4.5.5
Treatment Compliance
Investigational product is administered IV by study site personnel, who will monitor 
compliance.  
4.5.6
Accountability
The investigator’s or site’s designated investigational product manager is required to maintain 
accurate investigational product accountability records. Upon completion of the study, copies 
of investigational product accountability records will be returned to MedImmune. All unused 
investigational product will be returned to a MedImmune-authorized depot or disposed of 
upon authorization by MedImmune.
4.6
Treatment Assignment and Blinding
4.6.1
Methods for Assigning Treatment Groups
An IXRS will be used for randomization to a treatment regimen. A subject is considered 
randomized into the study when the investigator notifies the IXRS that the subject meets 
eligibility criteria. Subjects will be randomized in a 1:1 ratio to one of 2 cohorts, Cohort A 
(
) and Cohort B (
). Within each dose regimen, subjects will 
be randomized in a 2:1 ratio to receive MEDI6012 or placebo:
Cohort A

MEDI6012, 
 (n ~ 180)

Placebo, 
 (n ~ 90)
Cohort B

MEDI6012, 
 (n ~ 180)

Placebo, 
 (n ~ 90)
In the event that a dose regimen is dropped at the interim analysis, subjects will be 
randomized in a 1:1 ratio to receive MEDI6012 or placebo for the remaining dose regimen.
Infarct location will be controlled during the randomization process, ensuring a similar 
distribution of anterior vs. non-anterior infarcts between the active and placebo groups. In 
addition, the distribution of subjects with anterior versus non-anterior MIs will be monitored 
over the course of the study. The goal is that > 50% of the final randomized population will be 
anterior MI. Therefore, the number with non-anterior MI will be monitored via the IXRS and 
capped by the study team.
Investigational product (MEDI6012 or placebo) must be administered as soon as possible 
before pPCI (preferably > 10 minutes prior) and no later than 4 hours from the time 
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investigational product such that it will not be administered within the specified timeframe, 
the study monitor must be notified immediately.
4.6.2
Methods to Ensure Blinding
This is a blinded study in which MEDI6012 and placebo are nearly identical in appearance. 
The subject/legal representative and the Sponsor will not be aware of the treatment received 
(ICH E9) (see Section 4.6.3.2 for unblinding related to interim and planned analysis). The 
unblinded individual preparing the first dose of investigational product for administration in 
the catheterization laboratory will be aware of the treatment received. The unblinded 
administrator will be trained to not reveal treatment assignment to the investigator or other 
clinical and study staff. The site will be asked to take reasonable steps to maintain the blind. 
However, due to the acute nature of the study, members of the research team, and possibly the 
investigator, may be unblinded. Subsequent doses after Dose 1 will be prepared by an 
unblinded pharmacist. Sites are encouraged to take all reasonable steps to keep site staff 
involved in follow up assessments after Day1 blinded to randomization group.
4.6.3
Methods for Unblinding
4.6.3.1
Unblinding in the Event of a Medical Emergency 
In the event of a medical emergency, the investigator may unblind an individual subject’s 
investigational product allocation. Instructions for unblinding an individual subject’s 
investigational product allocation are contained in the IXRS manual. In general, unblinding 
should only occur if management of the medical emergency would be different based on the 
subject having received investigational product. In the majority of cases, the management of a 
medical emergency would be the same whether or not investigational product was received by 
the subject. If this was the case, the investigational product allocation should not be unblinded. 
4.6.3.2
Unblinding for Interim Analysis Purposes 
The objective of the 
 interim analysis will be for futility and potentially dropping a dose 
regimen. It will be conducted through the Data Monitoring Committee with details in the 
DMC charter. The 
 interim analysis is planned to accelerate decision on future 
development options for MEDI6012 and will be performed by a limited number of sponsor 
personnel who are not involved in the conduct of the study. An Unblinded Review Committee 
(URC) will be formed to review the second interim analysis according to standard operating 
procedure. Details of the second interim analyses will be specified in the interim analysis plan 
prior to unblinding.
4.7
Restrictions During the Study and Concomitant Treatment(s)
The investigator must be informed as soon as possible about any medication taken from the 
time of screening until the end of the clinical phase of the study (final study visit). Any 

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concomitant medication(s), including herbal preparations, taken during the study will be 
recorded in the eCRF.
4.7.1
Permitted Concomitant Medications
Investigators may prescribe concomitant medications or treatments deemed necessary to 
provide adequate supportive care. Specifically, subjects should receive full supportive care 
during the study in accordance with their institutional guidelines.
4.7.2
Prohibited Concomitant Medications
There are no prohibited concomitant medications.  
4.8
Statistical Evaluation
4.8.1
General Considerations
An initial database lock for the purpose of clinical study analysis and reporting will be 
performed when the last randomized subject completes the Day 70 to 84 visit or is
discontinued prior to that visit; if no subjects are ongoing in the Extended Follow-up period,
then this database lock will be considered the final database lock for the study.
If subjects are ongoing in the Extended Follow-up period, a second database lock will occur 
after all subjects who entered the Extended Follow-up period have completed their Week 25, 
39, or 52 visits as needed (see Section 4.2.2) or are discontinued prior to these visits, and this 
will be considered the final database lock. If the last Extended Follow-up visit occurs before 
the last Day 70 to 84 visit on the study, the second database lock will not be needed.
The study will be unblinded to the sponsor at the time of initial database lock. The site, 
subjects, and local CRO personnel will remain blinded to treatment assignment until the final 
database lock is declared. 
Safety data will be generated for the Extended Follow-up period and summarized as an 
addendum to the clinical study report.
Data will be provided in listings sorted by treatment group, and subject number. Tabular 
summaries will be presented by treatment group with placebo group combined when 
appropriate. Categorical data will be summarized by the number and percentage of subjects in 
each category. Continuous variables will be summarized by descriptive statistics. Baseline 
values will be defined as the last valid assessment prior to the first administration of 
investigational product on Day 1. Confidence intervals will be one-sided and nominal p-values 
will be reported when appropriate. Additional details of statistical analyses will be described 
in the statistical analysis plan.

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4.8.1.1
Analysis Populations
Intent-to-Treat (ITT) Population: all subjects that are randomized, analyzed according to 
randomized treatment assignment. 
As-treated Population: all randomized subjects who receive any investigational product. 
Subjects who receive any dose of MEDI6012 will be assigned to MEDI6012 group. Subjects 
who receive only placebo doses will be analyzed with the placebo group; conversely, subjects 
who receive any dose of MEDI6012 will be analyzed with the MEDI6012 group. Safety 
analyses will be performed on the As-treated Population.
Primary Efficacy Analysis Population: all randomized subjects who receive at 
 doses 
of investigational product with 
. Subjects who receive only
placebo doses will be analyzed with the placebo group; conversely, subjects who receive 2 or 
more doses of MEDI6012 will be analyzed with the MEDI6012 group.
Efficacy Analysis Population 
: all randomized subjects who receive at least 
two doses of investigational product with 
. Subjects who 
receive only placebo doses will be analyzed with the placebo group; conversely, subjects who 
receive 2 or more doses of MEDI6012 will be analyzed with the MEDI6012 group.
Efficacy Analysis Population 
: all randomized subjects who receive at least two 
doses of investigational product with 
. Subjects who receive 
only placebo doses will be analyzed with the placebo group; conversely, subjects who receive 
2 or more doses of MEDI6012 will be analyzed with the MEDI6012 group.
CTA Analysis Population: randomized subjects in
 who receive a full 
treatment course of investigational product and are eligible for coronary CTA and have 1 or 
more CTA performed. The subjects who receive  placebo doses will be analyzed with the 
placebo group; conversely, subjects who receive  doses of MEDI6012 will be analyzed with 
the MEDI6012 group.
Immunogenicity Population: all subjects in the As-treated Population who have at least 
one serum sample for immunogenicity testing.
PK Population: all subjects in the As-treated Population who have at least one detectable 
serum concentration measurement for LCAT mass or activity.
4.8.2
Sample Size
A total of 90 subjects per arm will provide 80% power to detect a 
 reduction in infarct 
size between MEDI6012 
 group and combined placebo group (
 placebo 
groups), and between MEDI6012 
 group and combined placebo group with one-sided 
alpha 0.05 assuming a coefficient of variation of 
. A total of 180 subjects per arm is 

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Incidence of CV death or heart failure and incidence of CV death, MI, unstable angina or 
urgent coronary revascularization from randomization to final study visit (10-12 weeks 
post-randomization) will be calculated. Time to first major adverse CV event will be analyzed 
using log-rank test.
The proportion of TFG at baseline (on initial angiography, pre-PCI) and the proportion of 
subjects with decline in renal functions at 48 hours will be compared between MEDI6012 and 
placebo using chi-square test.
4.8.4
Safety
4.8.4.1
Analysis of Adverse Events
Safety analysis will be based on the As-treated Population. AE collection begins after 
randomization and lasts until the end of the study. SAE collection begins after the subject 
signs the informed consent document and lasts until the end of the study. Adverse events will 
be coded using the Medical Dictionary for Regulatory Activities (MedDRA) by SOC and PT. 
Specific AEs will be counted once for each subject for calculating rates, but will be presented 
in total in subject listings. In addition, if the same AE occurs multiple times within a particular 
subject, the highest severity and level of causality will be reported. All TEAEs will be 
summarized overall and by MedDRA SOC and PT, by severity and relationship to 
investigational product. In addition, summaries of deaths, SAEs and treatment 
discontinuations due to AEs will be provided.
4.8.4.2
Analysis of Clinical Laboratory Parameters
Clinical laboratory safety tests including serum chemistry and hematology parameters will be 
summarized using descriptive statistics at each time point by treatment group with placebo 
group combined when appropriate. Change from baseline to each post baseline time point in 
these data will also be summarized, where appropriate. A shift table will be provided for these 
clinical laboratory parameters as well where possible.
4.8.4.3
Other Safety Analyses
Vital sign results will be summarized using descriptive statistics at each time point by 
treatment group.
4.8.5
Analysis of Immunogenicity/Pharmacokinetics 
ADA incidence rate and titer will be tabulated for each treatment group. Samples confirmed 
positive for ADA will be tested and analyzed for nAb and summarized similarly.

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Serum MEDI6012 mass concentration-time profiles will be summarized for MEDI6012 
treated subjects by dose cohort by visit. 
Additional PK analyses may be conducted as appropriate. Data obtained in this study may be 
pooled with other MEDI6012 studies to perform population PK analysis and/or PK/PD 
analysis.
4.8.6
Analysis of Pharmacodynamic Parameters
The following PD markers will be collected:
 
 
. 
The PD markers measured at each time point and change from baseline each post baseline 
time point will be summarized using descriptive statistics by treatment group with placebo 
group combined when appropriate. 
4.8.7
Data Monitoring Committee 
An independent DMC will be appointed. The DMC will be responsible for safeguarding the 
interests of the patients, by assessing the safety of the intervention during the study and for 
reviewing the overall conduct of the study. The DMC will have access to the individual 
treatment codes and will be able to merge these with the collected study data while the study 
is ongoing. DMC will review prespecified data periodically to ensure subject safety and make 
recommendations to the sponsor regarding further conduct of the study. This recommendation 
will be relayed to the MedImmune safety review committee and appropriate action will be 
taken. The DMC will have scheduled meetings at study initiation and at the following 
enrollment milestones – 15%, 30%, and 60% enrollment achieved. In addition, the DMC 
chairman will receive data once every two months and may schedule ad hoc meetings at 
his/her discretion. A separate charter will establish the rules, meeting frequency and scope of 
responsibilities of the DMC.  
4.8.8
Interim Analysis
 interim analyses are planned. The objective of the 
 interim analysis will be for futility 
and potentially dropping a dose regimen. It will be conducted after 30% of the initially 
planned Primary Efficacy Analysis Population (N = 74) is enrolled and will require that 
> 50% of subjects (N > 37) have acute anterior STEMI and have completed their final study 
visit. The 
 interim analysis will be conducted through Data Monitoring Committee with 
details in the DMC charter. The 
interim analysis is planned to accelerate decision on 
future development options for MEDI6012 and will be performed once 60% of the revised
Primary Efficacy Analysis Population (N = 162) is enrolled and will require that > 50% of 
subjects (N > 81) have acute anterior STEMI and have completed their final study visit. 
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sponsor and Principal Investigator will monitor the statistical assumptions in a blinded fashion 
and decide the exact time for interim analyses. 
5
ASSESSMENT OF SAFETY
5.1
Safety Monitoring
The details of safety monitoring will be detailed in the safety monitoring plan. Safety 
monitoring will be performed by the principal investigator, sponsor medical monitor in 
consultation with the global safety physician, TIMI safety desk and the DMC. 
The principal investigator is responsible for monitoring enrolled subjects for safety findings, 
including the recording in the eCRF (RAVE) of AEs, SAEs, and appropriate reporting, 
communication, and follow-up of laboratory abnormalities. The TIMI hotline is staffed by 
TIMI study physicians and will be available 24 hours per day, 7 days per week for protocol 
and safety related questions and concerns. When an SAE is entered into the eCRF, the TIMI 
safety desk, medical monitor, and global safety physician will be notified. The TIMI hotline 
and TIMI safety desk will be responsible for documenting protocol and safety related issue 
communications with PIs and communicating significant findings to Medimmune and the 
sponsor medical monitor. When an SAE is documented in the clinical database (RAVE), the 
TIMI safety desk will submit queries within 24 hours confirming seriousness, causality, and 
further details regarding the SAE to facilitate whether further information is needed. These 
assessments will be made urgently in order to comply with the timeframes for reporting to 
regulatory authorities. The investigator is required to respond to these queries within 24 hours.  
SAEs will be reviewed by the sponsor medical monitor, in consultation and with the global 
safety physician, and further queries issued, if necessary. If there is no evidence for the 
designation of an event as serious (in line with the appropriate protocol definition) or there is 
no apparent evidence for the positive investigator causality assessment, TIMI and the sponsor 
medical monitor may query or discuss with the investigator. However, if agreement is not 
reached, the investigator assessment will be respected and not changed by TIMI or 
Medimmune. The same is true if there is evidence to suggest a positive causality assessment 
for an SAE that has been assessed as unrelated by the investigator.  
SAE reconciliation between the safety database (Sapphire) and the clinical study database will 
be performed on a monthly basis by TIMI and reviewed by the global study physician and 
medical monitor via monthly meetings.
The details of safety monitoring will be detailed in the Safety Monitoring Plan.

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5.2
Definition of Adverse Events
The ICH Guideline for Good Clinical Practice E6(R1) defines an AE as: Any untoward 
medical occurrence in a patient or clinical investigation subject administered a pharmaceutical 
product and which does not necessarily have a causal relationship with this treatment. An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product.
An AE includes but is not limited to any clinically significant worsening of a subject’s 
pre-existing condition. An abnormal laboratory finding (including ECG finding) that requires 
medical intervention by the investigator, or a finding judged by the investigator as medically 
significant should be reported as an AE. If clinical sequelae are associated with a laboratory 
abnormality, the diagnosis or medical condition should be reported (eg, renal failure, 
hematuria) not the laboratory abnormality (eg, elevated creatinine, urine red blood cell 
increased). Abnormal laboratory values that are not, in the investigator's opinion, medically 
significant and do not require intervention should not be reported as AEs.
AEs may be treatment emergent (ie, occurring after initial receipt of investigational product) 
or nontreatment emergent. A non-TEAE is any new sign or symptom, disease, or other 
untoward medical event that begins after written informed consent has been obtained but 
before the subject has received investigational product. 
Elective treatment or surgery or preplanned treatment or surgery (that was scheduled prior to 
the subject being enrolled into the study) for a documented pre-existing condition that did not 
worsen from baseline is not considered an AE (serious or nonserious). An untoward medical 
event occurring during the prescheduled elective procedure or routinely scheduled treatment 
should be recorded as an AE or SAE.
5.3
Definition of Serious Adverse Events
An SAE is any AE that:

Results in death

Is immediately life-threatening

Requires inpatient hospitalization or prolongation of existing hospitalization 

Results in persistent or significant disability/incapacity 

Is a congenital anomaly/birth defect in offspring of the subject

Is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above

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Medical or scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in this situation. Examples of medically important events are intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions 
that do not result in hospitalizations; or development of drug dependency or drug abuse.
5.4
Recording of Adverse Events
AEs will be recorded on the eCRF using a recognized medical term or diagnosis that 
accurately reflects the event. AEs will be assessed by the investigator for severity, relationship 
to the investigational product, possible etiologies, and whether the event meets criteria of an 
SAE and therefore requires immediate notification to the sponsor (see Section 5.5). See 
Section 5.3 for the definition of SAEs and Section 10.2 for guidelines for assessment of 
severity and relationship. 
If an AE evolves into a condition that meets the regulatory definition of “serious,” it will be 
reported on the SAE Report Form.
Infusion of biological products is commonly associated with infusion related reactions. 
Anaphylaxis and infusion related reactions have some common manifestations and may be 
difficult to distinguish from each other. Infusion related reactions are commonly observed 
during or shortly after the first time of exposure to therapeutic monoclonal antibodies 
delivered through IV infusion. These reactions are less common following subsequent 
exposures. Unlike infusion related reactions, anaphylaxis is a rare event, usually occurring 
after subsequent exposure to an antigen, and it is most commonly accompanied by severe 
systemic, skin and/or mucosal reactions. The investigator is advised to carefully examine 
symptoms of adverse reactions observed during or shortly after exposure to MEDI6012, and 
consider the above mentioned facts prior to making a final diagnosis. Reactions occurring at 
the time of or shortly after subsequent infusions of investigational product are to be judged by 
the investigator at his/her own discretion. For the investigator’s convenience and in order to 
facilitate consistency in judgments a copy of the National Institute of Allergy and Infectious 
Disease and Food and Allergy Anaphylaxis Network (FAAN) guidance for anaphylaxis 
diagnosis is provided in Section 10.4.
5.4.1
Time Period for Collection of Adverse Events
AEs will be collected from time of randomization throughout the treatment period until the 
end of the follow-up period(s). 
All SAEs will be recorded from the time of informed consent.
Non-TEAEs (ie, AEs that occur during the period from the time informed consent is signed 
but prior to the subject receiving investigational product) should not be reported. However, 

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nontreatment SAEs associated with protocol related procedures should be reported. After the 
start of treatment, all TEAEs (Section 5.1) should be reported.
5.4.2
Follow-up of Unresolved Adverse Events
Any AEs that are unresolved at the subject’s last visit in the study are followed up by the 
investigator for as long as medically indicated, but without further recording in the eCRF. 
MedImmune retains the right to request additional information for any subject with ongoing 
AE(s)/SAE(s) at the end of the study, if judged necessary.
5.5
Reporting of Serious Adverse Events
All SAEs have to be reported, whether or not considered causally related to the investigational 
product, or to the study procedure(s). All SAEs will be recorded in the eCRF.
If any SAE occurs in the course of the study, then investigators or other site personnel must 
inform the appropriate sponsor representative(s) within 1 day, ie, immediately but no later 
than 24 hours after becoming aware of the event.
The designated sponsor representative works with the investigator to ensure that all the 
necessary information is provided to the sponsor’s patient safety data entry site within 
1 calendar day of initial receipt for fatal and life-threatening events and within 5 calendar days 
of initial receipt for all other SAEs.
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up is undertaken immediately. Investigators or other site personnel inform sponsor 
representatives of any follow-up information on a previously reported SAE within 1 calendar 
day, ie, immediately but no later than 24 hours after becoming aware of the event.
Once the investigators or other site personnel indicate an AE is serious in the electronic data 
capture (EDC) system, an automated email alert is sent to inform the designated sponsor 
representative(s).
If the EDC system is not available, then the investigator or other study site personnel reports 
an SAE to the appropriate sponsor representative by telephone. The sponsor representative 
will advise the investigator/study site personnel how to proceed. The AE/SAE should be 
reported in the EDC as soon as it becomes available.
5.6
Other Events Requiring Immediate Reporting
5.6.1
Overdose
An overdose is defined as a subject receiving a dose of investigational product in excess of 
that specified in this protocol.

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
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.

An overdose without associated symptoms is only reported on the Overdose eCRF 
module.
If an overdose on a MedImmune investigational product occurs during the course of the study, 
then the investigator or other site personnel inform appropriate sponsor representatives 
immediately, or no later than 24 hours after becoming aware of the event.
The designated sponsor representative works with the investigator to ensure that all relevant 
information is provided to the sponsor’s Patient Safety data entry site.
For overdoses associated with an SAE, the standard reporting timelines apply; see Section 5.5. 
For other overdoses, reporting must occur within 30 days.
5.6.2
Hepatic Function Abnormality
Patients with acute STEMI are very likely to show aminotransferase elevations at inclusion, 
either originating from cardiomyocytes, or, if released from hepatocytes, related to hepatic 
ischemia or congestion. Definition of potential signals for Drug-Induced Liver Injury and 
requirements for expedited reporting need to be adapted accordingly. Please refer to 
Section 10.5 for details.
5.6.3
Pregnancy
All pregnancies and outcomes of pregnancy should be reported to the Sponsor.
5.6.3.1
Maternal Exposure
Women of childbearing potential are not allowed to be included in this study. 
5.6.3.2
Paternal Exposure
Nonsterilized male study subjects who are sexually active with a female partner of 
childbearing potential must use condom and spermicide from Day 1 through the end of the 
study follow-up period. 
Male subjects should refrain from fathering a child or donating sperm during the study and for 
12 weeks following the last dose. 
Pregnancy of the subject’s partner is not considered to be an AE. However, the outcome of all 
pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, 
or congenital abnormality) should if possible be followed up and documented. 
The outcome of any conception occurring from the date of the first investigational product 
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followed up and documented. Information on the pregnancy of a subject’s partner must be 
obtained directly from the subject’s partner. Therefore, prior to obtaining information about 
the pregnancy, the Investigator must obtain the consent of the subject’s partner. 
6
STUDY AND DATA MANAGEMENT
6.1
Training of Study Site Personnel
Before the first subject is entered into the study, a MedImmune representative will review and 
discuss the requirements of the protocol and related documents with the investigational staff 
and also train them in any study-specific procedures and system(s) utilized.
The Principal Investigator will ensure that appropriate training relevant to the study is given to 
all of these staff, and that any new information relevant to the performance of this study is 
forwarded to the staff involved.
The Principal Investigator will maintain a record of all individuals involved in the study 
(medical, nursing, and other staff).
6.2
Monitoring of the Study
During the study, a MedImmune representative will have regular contacts with the study site, 
including visits to:

Provide information and support to the investigator(s)

Confirm that facilities remain acceptable

Confirm that the investigational team is adhering to the protocol, that data are being 
accurately and timely recorded in the eCRFs, that biological samples are handled in 
accordance with the Laboratory Manual and that study drug accountability checks are 
being performed

Perform source data verification (a comparison of the data in the eCRFs with the subject’s 
medical records at the hospital or practice, and other records relevant to the study) 
including verification of informed consent of participating subjects. This will require 
direct access to all original records for each subject (eg, clinic charts)

Ensure withdrawal of informed consent to the use of the subject’s biological samples is 
reported and biological samples are identified and disposed of/destroyed accordingly, and 
the action is documented, and reported to the subject.
The MedImmune representative will be available between visits if the investigator(s) or other 
staff at the center needs information and advice about the study conduct.
6.2.1
Source Data
Refer to the Clinical Study Agreement for location of source data.

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6.2.2
Study Agreements
The Principal Investigator at each/the center should comply with all the terms, conditions, and 
obligations of the Clinical Study Agreement, or equivalent, for this study. In the event of any 
inconsistency between this protocol and the Clinical Study Agreement, the terms of protocol 
shall prevail with respect to the conduct of the study and the treatment of subjects and in all 
other respects, not relating to study conduct or treatment of subjects, the terms of the Clinical 
Study Agreement shall prevail.
Agreements between MedImmune and the Principal Investigator must be in place before any 
study-related procedures can take place, or subjects are enrolled.
6.2.3
Archiving of Study Documents
The investigator follows the principles outlined in the Clinical Study Agreement.
6.3
Study Timetable and End of Study
An individual subject will be considered to have completed the study if the subject was 
followed through their last protocol-specified visit/assessment (including telephone contact), 
or death regardless of the number of doses of investigational product that was received. 
Subjects will be considered not to have completed the study if consent was withdrawn or the 
subject was lost to follow-up (see Sections 4.1.6 and 4.1.7).
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 to 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.
6.4
Data Management 
Data management will be performed by MedImmune Data Management staff or other party
according to the Data Management Plan.
An EDC system will be used for data collection and query handling. The investigator will 
ensure that data are recorded in the eCRFs as specified in the study protocol and in accordance 
with the eCRF instructions provided.
The investigator ensures the accuracy, completeness, and timeliness of the data recorded and 
of the provision of answers to data queries according to the Clinical Study Agreement. The 
investigator will sign the completed eCRFs. A copy of the completed eCRFs will be archived 
at the study site.

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6.5
Medical Monitor Coverage
Each subject will be provided with contact information for the principal investigator. In 
addition, each subject will receive a number intended to provide the subject’s physician access 
to a medical monitor 24 hours a day, 7 days a week in the event of an emergent situation 
where the subject’s health is deemed to be at risk using the TIMI Hotline number 
(+1-617-278-0900). In this situation, when a subject presents to a medical facility where the 
treating physician or health care provider requires access to a physician who has knowledge of 
the investigational product and the clinical study protocol and the principal investigator is not 
available, the treating physician or health care provider can contact a medical monitor through 
this system, which is managed by a third party vendor.
7
ETHICAL AND REGULATORY REQUIREMENTS
7.1
Subject Data Protection
Each subject will be assigned a SID to ensure that personally identifiable information is kept 
separate from the study data. Subject data that are relevant to the trial, eg, demographic 
information, physical or mental health condition, diagnosis, comorbidities, laboratory test 
results, etc. will only be collected with the subject’s informed consent. The Informed Consent 
Form (ICF) will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that describes how subject data will be collected, used, and distributed 
in compliance with relevant data protection and privacy legislation.
7.2
Ethics and Regulatory Review
The IRB/IEC responsible for each site must review and approve the final study protocol, 
including the final version of the ICF and any other written information and/or materials to be 
provided to the subjects. The IRB/IEC must also approve all advertising used to recruit 
subjects for the study. The investigator is responsible for submitting these documents to the 
applicable IRB/IEC, and distributing them to the study site staff.
The opinion of the IRB/IEC must be given in writing. The investigator must provide a copy of 
the written approval to MedImmune before enrollment of any subject into the study. 
MedImmune should approve any substantive modifications to the ICF that are needed to meet 
local requirements.
If required by local regulations, the protocol must be re-approved by the IRB/IEC annually.
Before the study is initiated, MedImmune will ensure that the national regulatory authority in 
each country has been notified and their approval has been obtained, as required. MedImmune 
will provide safety updates/reports according to local requirements, including suspected 

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unexpected serious adverse reactions where relevant, to regulatory authorities, IRB/IEC, and 
principal investigators.
7.3
Informed Consent
Informed consent of each subject will be obtained through a written and verbal explanation 
process that addresses all elements required by ICH/GCP. MedImmune will develop a core 
ICF as well as alternate short-form consent for use by all investigators in the clinical study 
(according to local regulations). MedImmune must approve any modifications to the ICF that 
are needed to meet local requirements.
The Principal Investigator(s) at each center will:

Ensure each subject is given full and adequate oral and written information about the 
nature, purpose, possible risk and benefit of the study

Ensure each subject is notified that they are free to discontinue from the study at any time

Ensure that each subject is given the opportunity to ask questions and allowed time to 
consider the information provided

Ensure each subject provides written or verbal informed consent before conducting any 
procedure specifically for the study

Ensure the original, signed ICF(s) is/are stored in the Investigator’s Study File

Ensure a copy of the signed ICF is given to the subject

Ensure that any incentives for subjects who participate in the study as well as any 
provisions for subjects harmed as a consequence of study participation are described in 
the ICF that is approved by an IRB/IEC
7.4
Changes to the Protocol and Informed Consent Form
Study procedures will not be changed without the mutual agreement of the Principal 
Investigator and MedImmune.
Substantial changes must be documented in a study protocol amendment. MedImmune will 
distribute amended versions of the protocol to the principle investigator(s). Before 
implementation, amended protocols must be approved by relevant IRB/IEC (see Section 7.2) 
and according to local requirements, the national regulatory authority approval. The IRB/IEC 
must also approve revisions to the ICF, advertising, and any other written information and/or 
materials resulting from the change to the protocol.
If local regulations require, any unsubstantial changes will be communicated to or approved 
by each IRB/IEC.

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7.5
Audits and Inspections
Authorized representatives of MedImmune, a regulatory authority, or an IRB/IEC may 
perform audits or inspections at the center, including source data verification. The purpose of 
an audit or inspection is to systematically and independently examine all study-related 
activities and documents, to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, Good Clinical Practice 
(GCP), guidelines of the ICH, and any applicable regulatory requirements. The investigator 
will contact MedImmune immediately if contacted by a regulatory agency about an inspection 
at the site.

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8
REFERENCES
Asztalos BF, Roheim PS, Milani RL, Lefevre M, McNamara JR, Horvath KV et al. 
Distribution of ApoA-I-containing HDL subpopulations in patients with coronary heart 
disease. Arterioscler Thromb Vasc Biol. 2000;20(12):2670-6.
Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ et al. Remote 
ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect 
on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 
2010;375(9716):727-34.
Breathett K, Allen LA, Udelson J, Davis G, Bristow M. Changes in Left Ventricular Ejection 
Fraction Predict Survival and Hospitalization in Heart Failure With Reduced Ejection 
Fraction. Circ Heart Fail. 2016;9(10).
Chen Z, Ichetovkin M, Kurtz M, Zycband E, Kawka D, Woods J et al. Cholesterol in human 
atherosclerotic plaque is a marker for underlying disease state and plaque vulnerability. Lipids 
Health Dis. 2010;961.
Gomaraschi M, Calabresi L, Franceschini G. Protective Effects of HDL Against 
Ischemia/Reperfusion Injury. Front Pharmacol. 2016;72.
Gordts SC, Muthuramu I, Nefyodova E, Jacobs F, Van Craeyveld E, De Geest B. Beneficial 
effects of selective HDL-raising gene transfer on survival, cardiac remodelling and cardiac 
function after myocardial infarction in mice. Gene Ther. 2013;20(11):1053-61.
Hausenloy DJ, Erik Botker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G et al. 
Translating cardioprotection for patient benefit: position paper from the Working Group of 
Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 
2013;98(1):7-27.
Heywood SE, Richart AL, Henstridge DC, Alt K, Kiriazis H, Zammit C et al. High-density 
lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function 
in mice. Sci Transl Med. 2017;9(411).
Hoeg JM, Santamarina-Fojo S, Berard AM, Cornhill JF, Herderick EE, Feldman SH et al. 
Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents 
diet-induced atherosclerosis. Proc Natl Acad Sci U S A. 1996;93(21):11448-53.

MedImmune
Protocol Amendment 6 D5780C00007
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85 of 110
Template 17.0
Kalakech H, Hibert P, Prunier-Mirebeau D, Tamareille S, Letournel F, Macchi L et al. RISK 
and SAFE signaling pathway involvement in apolipoprotein A-I-induced cardioprotection. 
PLoS One. 2014;9(9):e107950.
http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf
Kempen HJ, van Gent CM, Buytenhek R, Buis B. Association of cholesterol concentrations in 
low-density lipoprotein, high-density lipoprotein, and high-density lipoprotein subfractions, 
and of apolipoproteins AI and AII, with coronary stenosis and left ventricular function. J Lab 
Clin Med. 1987;109(1):19-26.
Kramer DG, Trikalinos TA, Kent DM, Antonopoulos GV, Konstam MA, Udelson JE. 
Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of 
therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: a 
meta-analytic approach. J Am Coll Cardiol. 2010;56(5):392-406.
Krause BR, Remaley AT. Reconstituted HDL for the acute treatment of acute coronary 
syndrome. Curr Opin Lipidol. 2013;24(6):480-6.
Kristensen TS, Kofoed KF, Kuhl JT, Nielsen WB, Nielsen MB, Kelbaek H. Prognostic 
implications of nonobstructive coronary plaques in patients with non-ST-segment elevation 
myocardial infarction: a multidetector computed tomography study. J Am Coll Cardiol. 
2011;58(5):502-9.
Lamon-Fava S, Herrington DM, Reboussin DM, Sherman M, Horvath KV, Cupples LA et al. 
Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of 
angiographically-defined coronary artery disease in postmenopausal women. Arterioscler 
Thromb Vasc Biol. 2008;28(3):575-9.
Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am J Cardiol. 
2003;91(4A):4B-8B.
Marchesi M, Booth EA, Davis T, Bisgaier CL, Lucchesi BR. Apolipoprotein A-IMilano and 
1-palmitoyl-2-oleoyl phosphatidylcholine complex (ETC-216) protects the in vivo rabbit heart 
from regional ischemia-reperfusion injury. J Pharmacol Exp Ther. 2004;311(3):1023-31.
Mather AN, Fairbairn TA, Artis NJ, Greenwood JP, Plein S. Timing of cardiovascular MR 
imaging after acute myocardial infarction: effect on estimates of infarct characteristics and 
prediction of late ventricular remodeling. Radiology. 2011;261(1):116-26.

MedImmune
Protocol Amendment 6 D5780C00007
04May2020; Final
86 of 110
Template 17.0
Miida T, Nakamura Y, Inano K, Matsuto T, Yamaguchi T, Tsuda T et al. Pre beta 
1-high-density lipoprotein increases in coronary artery disease. Clin Chem. 
1996;42(12):1992-5.
Ossoli A SS, Varrenti M, Morici N, Oliva F, Stucchi M et al. Recombinant LCAT rescues 
defective HDL mediated endothelial protection in acute coronary syndrome.  
ATVB/2017/310249, submitted.
Sethi AA, Sampson M, Warnick R, Muniz N, Vaisman B, Nordestgaard BG et al. High 
pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are 
strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol. 
Clin Chem. 2010;56(7):1128-37.
Shah PK. High-density lipoprotein mimetics: focus on synthetic high-density lipoprotein. Am 
J Cardiol. 2007;100(11 A):S62-7.
Solajic-Bozicevic N, Stavljenic-Rukavina A, Sesto M. Lecithin-cholesterol acryltransferase 
activity in patients with coronary artery disease examined by coronary angiography. Clin 
Investig. 1994;72(12):951-6.
Stone GW, Selker HP, Thiele H, Patel MR, Udelson JE, Ohman EM et al. Relationship 
Between Infarct Size and Outcomes Following Primary PCI: Patient-Level Analysis From 
10 Randomized Trials. J Am Coll Cardiol. 2016;67(14):1674-83.
Tashiro J, Miyazaki O, Nakamura Y, Miyazaki A, Fukamachi I, Bujo H et al. Plasma pre 
beta1-HDL level is elevated in unstable angina pectoris. Atherosclerosis. 
2009;204(2):595-600.
Theilmeier G, Schmidt C, Herrmann J, Keul P, Schafers M, Herrgott I et al. High-density 
lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against 
ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation. 
2006;114(13):1403-9.
Wang TD, Wu CC, Chen WJ, Lee CM, Chen MF, Liau CS et al. Dyslipidemias have a 
detrimental effect on left ventricular systolic function in patients with a first acute myocardial 
infarction. Am J Cardiol. 1998;81(5):531-7.
Wu E, Ortiz JT, Tejedor P, Lee DC, Bucciarelli-Ducci C, Kansal P et al. Infarct size by 
contrast enhanced cardiac magnetic resonance is a stronger predictor of outcomes than left 

MedImmune
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ventricular ejection fraction or end-systolic volume index: prospective cohort study. Heart. 
2008;94(6):730-6.
Zhou M SJ, Kelley K, Fordstrom P, Chan J, Tonn G et al. Abstract 5920: Lecithin cholesterol 
acyltransferase promotes reverse cholesterol transport and attenuates atherosclerosis 
progression in New Zealand white rabbits. Circulation. 2009;120S1175.

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to return for additional Extended Follow-up visit(s) and will be considered as having 
completed the Extended Follow-up period.

Section 4.5.1.6 (Reporting Product Complaints): Deleted an obsolete phone number and 
fax number.

Section 4.8.1 (General Considerations): It was clarified that 2 independent database locks 
may be conducted. The initial database lock for the purpose of clinical study analysis and 
reporting will occur after all randomized subjects in the study either complete the Day 70 
to 84 visit or are discontinued prior to the visit. If no subjects are ongoing in the Extended 
Follow-up period, then this database lock will be considered the final database lock for 
the study. If subjects are ongoing in the Extended Follow-up period, a second database 
lock will occur after all subjects who entered the Extended Follow-up period have 
completed their Week 25, 39, or 52 visits (as described in Section 4.2.2) or are 
discontinued prior to these visits and this will be considered the final database lock. If the 
last Extended Follow-up visit occurs before the last Day 70 to 84 visit on the study, the 
second database lock will not be needed. The site, subjects, and local CRO personnel will 
remain blinded to treatment assignment until the final database lock is declared. Safety 
data will be generated for the Extended Follow-up period and summarized as an 
addendum to the clinical study report.

Section 6.3 (Study Timetable and End of Study): It was clarified that 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 to 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.

Appendix 10.1 (Appendix 1 – Signatures): The sponsor signature page in Appendix 10.1
was deleted in lieu of an attached electronic signature page.

Throughout the protocol where “> 30% decrease in HDL-C” is cited, it has been clarified 
that this refers to “> 30% decrease from baseline in HDL-C”.
9.2
Protocol Amendment 5, 26Jul2019
Text revisions resulting from this amendment are incorporated into the body of Protocol 
Amendment 5. All changes made to the body of the protocol have been reflected in the 
Protocol Synopsis and minor copyediting issues were addressed.
Changes to the protocol considered substantial are summarized below: 
1
Section 3.1.1 (Overview), Figure 3 (Overall Study Schema), 3.1.2 (Treatment Regimen), 
4.1.1 (Number of Subjects), 4.6.1 (Methods for Assigning Treatment Groups), 4.8.1 
(General Considerations), 4.8.2 (Sample Size), and 4.8.8 (Interim Analysis): the 
approximate number of subjects was changed from at least 414 to approximately 540;
total numbers per cohort, sample size calculation and second interim analysis were 
updated to reflect this. Sample size change was implemented to reflect the observed 
coefficient of variation of blinded data relative to the expected in the statistical 
assumption. The alpha threshold was amended to be a one-sided alpha of 0.05 to reflect 

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the one-sided hypothesis testing (superiority of MEDI6012) for this Phase 2b program
designed to inform future drug development.
Changes to the protocol considered non-substantial are summarized below: 
2
Title Page: medical monitor changed to 
 
3
Section 3.1.1 (Overview) and 4.8.2 (Sample Size): number of study sites updated from 
40 to 43. 
4
Table 5 (Exploratory Objectives and Associated Endpoints), and Section 3.2.3.4 
(Rationale for Exploratory Endpoints): 
 
5
Section 4.1.4 (Additional Study Procedure Requirements): under Coronary CTA, the fifth 
requirement was revised to read, “No contraindication to heart rate lowering using 
betablockers to allow for high quality, low-radiation dose CTA (per-protocol). Please 
note, if heart rate is well-controlled allowing for a high quality, low radiation CTA 
without betablocker, then a contraindication to betablocker does not exclude the subject 
from coronary CTA”. The text was revised to clarify that if betablockers are 
contraindicated, subject could still undergo CTA if their heart rate is low enough to assure 
a low radiation dose can be achieved. Nitroglycerin contraindication was removed from 
the list of requirements since subjects could undergo CTA without nitroglycerin 
administration. 
6
Section 4.8.1.1 (Analysis Populations): descriptions of analysis populations updated to 
reflect the statistical analysis plan.
9.3
Protocol Amendment 4, 18Apr2019
Text revisions resulting from this amendment are incorporated into the body of Protocol 
Amendment 4. Minor copyediting was addressed; “coronary vessel volume” was corrected to 
“lumen volume” and “myocardial area at risk” was changed to “resting perfusion deficit”.
1
Protocol Synopsis: Update made to the exploratory objectives (bullet point 3) and 
endpoints (third bullet) for 
 in line with the updates to Table 5 in 
the main body of the protocol.
2
Table 5 (Exploratory Objectives and Associated Endpoints): Clarification to wording of 
the safety objective and endpoints related 
.
3
Section 3.1.1 (Overview): Index CTA window altered from “no earlier than 48 hours” to 
“no earlier than 40 hours” post Dose 1 as previous language was inconsistent within the 
protocol between the time periods stated in the heading of Table 9, and the time periods 
stated in footnote o of Table 9 and the overview section. CMR window for repeat scans
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Dose 1) to accommodate scheduling of a repeat scan if needed due to inadequate image 
quality.
4
Section 3.2.3.4 (Rationale for Exploratory Endpoints) and Section 4.8.3.4 (Exploratory 
Analyses): 
 included in this study in line with the updates to 
the exploratory objectives and endpoints in Table 5.
5
Table 8 (Treatment Period and Follow-up Procedures: Cohort A [
]) and 
Table 9 (Treatment Period and Follow-up Procedures: Cohort B 
]):
Footnote c was added in Tables 8 and 9, to clarify that screening vital signs taken as part 
of standard of care can be used as long as they are taken within 30 minutes pre-dose (must
be repeated if more than 30 minutes pre-dose), to avoid unnecessary repeating of vital 
signs assessments in the acute setting of this study where there is a very short screening 
period, and to clarify that screening vitals and pre-dose vitals do not need to be duplicated 
if one set has been taken within 30 minutes pre-dose, to reduce patient burden and avoid 
interfering with standard of care procedures. Footnote j updated in both tables to clarify 
the timeframe for creatinine measurement and review prior to MRI and CTA. Footnote n
updated in both tables to reflect change in MRI window for repeat scans from 1 week to 
4 weeks following the end of study visit (up to 112 days post Dose 1) as MRI results are 
still clinically relevant in this time period. Footnote g in both tables adjusted to state that 
missed doses or visits outside the specified window may be adjusted with approval from 
TIMI Hotline to clarify when the sites should contact TIMI Hotline in this instance.
Footnote o in Table 9 updated to correct discrepancy with table contents stating that index 
CTA may be performed no earlier than 40 hours post Dose 1. Footnotes o and p in 
Table 9 adjusted to specify CTA procedure in cases of CABG surgery as the comparison 
of pre- and post-CABG surgery CTAs would be difficult. All footnote labels in Tables 8 
and 9 readjusted to accommodate additional footnotes.
6
Section 4.2.2 (Extended Follow-up Period for Subjects with Anti-Drug Antibodies Plus 
> 30% Decrease in HDL-C and/or Presence of a Neutralizing Antibody on Day 70 to 84) 
and Table 10 (Extended Follow-up Period for Subjects with Anti-Drug Antibodies Plus 
> 30% Decrease in HDL-C and/or Presence of a Neutralizing Antibody on Day 70 to 84): 
The time frame of Day 70 to 84 was added in line with protocol main text to clarify that 
this extended follow-up period would apply only for subjects with ADA in addition to
> 30% decrease in HDL-C and/or presence of nAb on Day 70 to 84.
7
Section 4.3 (Description of Study Procedures): Added exception to order of vital signs
and blood draw to be exclusive of Visit 1 (Day 1) as due to compressed timeframes at this 
point in clinical procedures, it is not always possible to take vital signs and blood draws in 
this same order.
8
Section 4.3.5 (Pharmacokinetic Evaluation and Methods): Added text to clarify that PK 
samples taken from subjects on Visits 3, 5, and 6 (Days 17, 31, and 70-84, respectively) 
from Cohort A, and Visit 6 (Day 70-84) from Cohort B will be collected but not measured 
unless deemed useful by the study team based on emerging data (ie, assessment of 

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immunogenicity) as the results from these time points may not be required for all subjects
since the level of investigational product will be below the limit of quantification for 
MEDI6012. The samples are still useful as they can be used to determine if ADAs have 
an impact on LCAT levels to assess immunogenicity.
9
Section 4.3.8 (Imaging Biomarker Evaluation and Methods):
 
 
 
 
9.4
Protocol Amendment 3, 14Jun2018
Text revisions resulting from this amendment are incorporated into the body of Protocol 
Amendment 3. Text under the heading “Additional Study Procedure Requirements” and 
“Coronary CTA” was revised to clarify the requirement as “no” contraindications to 
betablockers and nitroglycerin. Text was also revised to add clarification to the length of time 
subjects will be under medical supervision following administration of investigational 
product. Minor copyediting was also addressed, in particular, “baseline” CTA was changed to 
“index” CTA. Major changes to the protocol are summarized below.
1
Section 3.1.1 (Overview), Cohorts A and B: For Inpatient Phase – Cohorts A and B, text 
was added that following Doses 
 for Cohort A, or 
 Cohort B, subjects 
will be monitored for 2 hours in a location with personnel trained in Adult Advanced Life 
Support with resuscitation equipment available. For Outpatient Phase – Cohort B, text 
was added that “subjects who did not undergo index CTA for any reason will not undergo 
the CTA at the end of the study.”
2
Section 4.1.4 (Additional Study Procedure Requirements): The title of the Cardiovascular 
MRI subsection was revised to read, “Administration of Gadolinium Contrast for 
Cardiovascular MRI.” Additionally, the word “gadolinium” was added to clarify the 
contrast agent. Under Coronary CTA, the fifth requirement was revised to read, “No” 
contraindications to betablockers and nitroglycerin. The text was revised to clarify that 
betablockers and nitroglycerin are to be used. Betablockers enable a lower radiation dose 
and lack of betablocker use can result in some study sites exceeding the radiation dose 
limitation; also, betablockers and nitroglycerin improve the quality of the images. A sixth 
requirement was added that for follow-up CTA, subjects would need to have undergone 
an index CTA.
3
Section 4.1.7 (Discontinuation of Investigational Product): Text was added to clarify that 
in cases where a subject is incorrectly randomized, upon review by the TIMI Hotline or 

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medical monitor, subjects found after randomization to have met an exclusion criterion 
that is unrelated to safety may continue treatment. Additional text was added that for 
subjects who never receive investigational product, follow up will consist of a minimum 
of a single phone call at the end of the study; however, visits are allowed at the discretion 
of the subject and investigator.
4
Table 8 (Treatment Period and Follow-up Procedures: Cohort A [
]) and 
Table 9 (Treatment Period and Follow-Up Procedures: Cohort B [
]): 
Procedure and footnotes were added to both tables for post-dose subject observation and 
monitoring to clarify the period of time that subjects will be monitored following 
administration of investigational product. Footnote “m” was added to Table 8 for 
Investigational product administration under Day 3 (48 ± 8 hours) and footnote “o” was 
added under Days 3-31 to Table 9 to clarify and instruct that “Planned dosing times that 
will potentially fall outside of the window specified in this table must be discussed with 
the TIMI Hotline and sponsor,” and “visit intervals will need to be adjusted accordingly.” 
Footnote “n” in Table 9 was revised for clarification that follow-up CTA will be done 
only for subjects with an index CTA.
5
Section 4.3.1 (Medical History and Physical Examination, Weight, and Vital Signs): The 
word “oral” was removed from body temperature measurements to clarify that other 
methods for taking body temperature will be permitted. 
6
Section 4.3.4 (Clinical Laboratory Tests): The word “automated” was added to white 
blood cell count and “by central laboratory” to clarify that blood smears should not be 
done. A footnote added to “Other Laboratory Tests” to indicate that luteinizing hormone 
and follicle stimulating hormone will be conducted only for female subjects. 
7
Section 4.3.8 (Imaging Biomarker Evaluation and Methods): 
 
 
 
 
 
 
8
Section 4.5.1.5 (Monitoring of Dose Administration): Text added to clarify that subjects
will be monitored for 2 hours following Doses 
 for Cohorts A or Doses 
 for 
Cohort B.
9
Section 4.6.2 (Methods to Ensure Blinding): Text was added for further clarification that 
due to the acute nature of the study, members of the research team, and possibly the 
investigator, may be unblinded.

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9.5
Protocol Amendment 2, 28Mar2018
Text revisions resulting from this amendment are incorporated into the body of Protocol 
Amendment 2. Estimated GFR criteria were removed and changed to CrCl throughout. 
Copyediting and formatting errors were corrected throughout; notably, the term “glutamine” 
dehydrogenase was corrected to “glutamate” dehydrogenase throughout the document. 
Breastfeeding exclusion criterion was added. Additionally, table numbering was changed to 
sequential numbering to align with new in-house authoring style. Major changes to the 
protocol are summarized below.
1
Section 1.7.2 (Secondary Hypotheses): The word “prevent” was replaced with “reduce” to 
align with the Protocol Synopsis.
2
Section 3.1.1 (Overview – Inpatient Phase – Cohorts A and B): Text was revised for 
Cohort B to remove eGFR ≥60 and replace with subjects with CrCl ≥ 60 mL/min 
(Cockcroft Gault equation) within 6 hours will undergo an index coronary CTA no earlier 
than 48 hours following the first dose. Changes were made to eGFR to correctly change 
to CrCl throughout as the Cockcroft Gault equation applies to CrCl. 
3
Section 4.1.3 (Exclusion Criteria): Criterion 8 was revised to remove known eGFR 
< 30 mL/min/1.7.3 m2 and replace with known CrCl < 30 mL/min (Cockcroft Gault 
equation) as a contraindication to MR imaging. Criterion 9 was revised to exclude women 
who are breastfeeding. Criterion 10 was added to exclude subjects who are currently or 
had previously participated in a study using an investigational therapy or devices within 
the last 30 days. 
4
Section 4.1.4 (Additional Study Procedure Requirements – Cardiovascular MRI and 
Coronary CTA): Text in Cardiovascular MRI subsection was revised to remove eGFR 
≥30 mL/min/1.73 m2 and replace with CrCl to read that MRI would be allowed if there 
were no contraindications to MR imagining (eg, metallic implant, claustrophobia, ICD, 
pacemaker), but for subjects to receive contrast they must meet the requirements of CrCl 
≥30 mL/min (Cockcroft Gault equation) within 7 days prior to the procedure, and no 
known allergy to gadolinium contrast agents. This was revised for clarification and to 
provide a breakdown of MRI criteria to allow MRI (without using contrast) in subjects 
with no MRI contraindications who cannot receive contrast. The Coronary CTA 
subsection was revised to remove eGFR ≥60 mL/min/1.73 m2 and replace with CrCl 
≥60 mL/min (Cockcroft Gault equation) within no more than 6 hours prior to index CTA 
and no more than 7 days prior to follow up.
5
Section 4.1.5 (Subject Enrollment and Randomization): Text was revised to clarify that 
randomization will be stratified by infarct location, ensuring balanced randomization to 
active treatment vs placebo within the anterior and the non-interior MI groups.
6
Table 8 (Treatment Period and Follow-up Period Procedures: Cohort A [
 
]) and Table 9 (Treatment Period and Follow-up Period Procedures: Cohort B 

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[
 A PK blood sample was added to Table 8 (Cohort A) for Day 31 to 
align with Cohort B. Record vital signs at Screening was added to Table 9 (Cohort B) to 
align with Cohort A. 
7
Section 4.3.1 (Medical History and Physical Examination, Weight, and Vital Signs): Text 
was revised to correct that full physical examination will be conducted anytime between 
Day 1 and 3 prior to administration of Dose . Additionally, “on all days” was deleted 
from text for measurement of vital signs to align with Schedule of Study Procedures. 
8
Section 4.3.8 (Imaging Biomarker Evaluation and Methods –
 
 
 
 
 
9
Section 4.5.1.4 (Treatment Administration): Text was revised to add that subjects should 
be instructed on whether their regular medication can be taken while fasting. This was 
added for clarification and as a reminder to the investigator to review specific 
concomitant medication instructions with subjects.
10 Section 4.5.1.5 (Monitoring of Dose Administration): Text was revised to remove “before 
and after dose administration” to align with Schedule of Study Procedures. 
11 Section 4.8.8 (Interim Analysis) and Synopsis: Text was added to clarify that the sponsor 
and Principal Investigator will monitor the statistical assumptions in a blinded fashion and 
decide the exact time for interim analyses.
9.6
Protocol Amendment 1, 09Jan2018
Text revisions resulting from this amendment are incorporated in the body of Protocol 
Amendment 1. Copyediting and formatting errors were corrected throughout. Major changes 
to the protocol are summarized below.
1
Section 4.2.1 (Enrollment and Treatment Period), Table 8 (Treatment Period and Follow-
up Procedures: Cohort A 
]): Footnotes a and b were added due to 
previous omission; footnote h was replaced by footnote g for PK blood sample on Day 1 
due to previous error; footnote i was replaced by footnote h for PD blood sample on Day 
1, 1-1.5 hour post-dose due to previous error. 
2
Section 4.5.1.1 (Investigational Product Handling):
 
3
Section 4.3.8 (Imaging Biomarker Evaluation and Methods), 
 
 
 

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10
APPENDICES
10.1
Appendix 1 - Signatures

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Signature of Principal Investigator
A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of 
MEDI6012 in Acute ST Elevation Myocardial Infarction
I, the undersigned, have reviewed this protocol and all amendments, and I agree to conduct 
this protocol in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and are consistent with the International Conference on Harmonisation (ICH) 
guidelines on Good Clinical Practice (GCP), any applicable laws and requirements, and any 
conditions required by a regulatory authority and/or Institutional Review Board/Independent 
Ethics Committee (IRB/IEC). 
I understand that the protocol may not be modified without written approval of the sponsor. 
All changes to the protocol must be submitted to the applicable regulatory authority and 
IRB/IEC, and must be approved by the IRB/IEC prior to implementation except when 
necessary to eliminate immediate hazards to the subjects or when the change(s), as deemed by 
the sponsor, involves only logistical or administrative changes. Documentation of IRB/IEC 
approval must be sent to the sponsor immediately upon receipt.
Signature and date: 
Name and title:  
Address including postal code: 
Telephone number: 
Site/Center Number (if available)
This document contains confidential information, which should not be copied, referred to, 
released, or published without written approval from MedImmune or AstraZeneca. 
Investigators are cautioned that the information in this protocol may be subject to change and 
revision.

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10.2
Appendix 2 – Contraception Guidance
For females:
Females without childbearing potential will be included in this study. Females without 
childbearing potential are defined as those who are surgically sterile (ie, surgical sterilization 
includes bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or those who are 
postmenopausal (defined as 12 months with no menses without an alternative medical cause). 
For males:
Nonsterilized males who are sexually active with a female partner of childbearing potential 
must use condom and spermicide from Day 1 through the end of their participation in the 
study. Because male condom and spermicide is not a highly effective contraception method it 
is strongly recommended that female partners of a male study subjects also use a highly 
effective method of contraception throughout this period. A highly effective method of 
contraception is defined as one that results in a low failure rate (ie, less than 1% per year) 
when used consistently and correctly. The acceptable methods of contraception are described 
in Table 13.
Table 13
Highly Effective Methods of Contraception
Barrier Methods
Hormonal Methods
•
Intrauterine device
•
Intrauterine hormone-releasing system (UIS) a
•
Bilateral tubal occlusion
•
Vasectomized partner b
•
Sexual abstinence c
Combined (estrogen and progestogen containing 
hormonal contraception)

Oral (combined pill)

Injectable

Transdermal (patch)
Progestogen-only hormonal contraception associated 
with inhibition of ovulation d

Injectable

Implantable

Intravaginal
a
This is also considered a hormonal method.
b
With appropriate post-vasectomy documentation of surgical success (absence of sperm in ejaculate).
c
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the subject.
d
Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of 
action (eg, minipill), is not accepted as a highly effective method).

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10.3
Appendix 3 - Additional Safety Guidance
Further Guidance on the Definition of a Serious Adverse Event (SAE)
Life threatening
‘Life-threatening’ means that the subject was at immediate risk of death from AE as it 
occurred or it is suspected that use or continued use of the product would result in the 
subject’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (eg, hepatitis that resolved without hepatic failure).
Hospitalization
Outpatient treatment in an emergency room is not in itself a serious AE, although the reasons 
for it may be (eg, bronchospasm, laryngeal edema). Hospital admissions and/or surgical 
operations planned before or during a study are not considered AEs if the illness or disease 
existed before the subject was enrolled in the study, provided that it did not deteriorate in an 
unexpected way during the study.
Important Medical Event or Medical Intervention
Medical and scientific judgment should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life threatening or result in 
death, hospitalization, disability or incapacity but may jeopardize the subject or may require 
medical intervention to prevent one or more outcomes listed in the definition of serious. These 
should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgment must be used.
Examples of such events are:

Angioedema not severe enough to require intubation but requiring intravenous 
hydrocortisone treatment

Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment with 
N-acetylcysteine

Intensive treatment in an emergency room or at home for allergic bronchospasm

Blood dyscrasias (eg, neutropenia or anemia requiring blood transfusion) or convulsions 
that do not result in hospitalization

Development of drug dependency or drug abuse
Assessment of Severity
Assessment of severity is one of the responsibilities of the investigator in the evaluation of 
AEs and SAEs. The determination of severity should be made by the investigator based upon 
medical judgment and the severity categories of Grade 1 to 5 as defined below.

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Grade 1
An event of mild intensity that is usually transient and may 
require only minimal treatment or therapeutic intervention. The 
event does not generally interfere with usual activities of daily 
living.
Grade 2
An event of moderate intensity that is usually alleviated with 
additional specific therapeutic intervention. The event interferes 
with usual activities of daily living, causing discomfort but 
poses no significant or permanent risk of harm to the subject.
Grade 3
A severe event that requires intensive therapeutic intervention. 
The event interrupts usual activities of daily living, or 
significantly affects the clinical status of the subject.
Grade 4
An event, and/or its immediate sequelae, that is associated with 
an imminent risk of death 
Grade 5
Death as a result of an event.
It is important to distinguish between serious criteria and severity of an AE. Severity is a 
measure of intensity whereas seriousness is defined by the criteria in Section 5.3. A Grade 3 
AE need not necessarily be considered an SAE. For example, a Grade 3 headache that persists 
for several hours may not meet the regulatory definition of an SAE and would be considered a 
nonserious event, whereas a Grade 2 seizure resulting in a hospital admission would be 
considered an SAE.
Assessment of Relationship
Relationship to Investigational Product
The investigator is required to provide an assessment of relationship of AEs and SAEs to the 
investigational product. The following factors should be considered when deciding if there is a 
“reasonable possibility” that an AE may have been caused by the investigational product.

Time Course. Exposure to suspect investigational product. Has the subject actually 
received the suspect investigational product? Did the AE occur in a reasonable temporal 
relationship to the administration of the suspect investigational product?

Consistency with known investigational product profile. Was the AE consistent with the 
previous knowledge of the suspect investigational product (pharmacology and toxicology) 
or products of the same pharmacological class? OR could the AE be anticipated from its 
pharmacological properties? 

De-challenge experience. Did the AE resolve or improve on stopping or reducing the dose 
of the suspect investigational product?

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
No alternative cause. The AE cannot be reasonably explained by another etiology such as 
the underlying disease, other drugs, or other host or environmental factors.

Re-challenge experience. Did the AE reoccur if the suspected investigational product was 
reintroduced after having been stopped? MedImmune would not normally recommend or 
support a re-challenge.

Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship?
In difficult cases, other factors could be considered such as:

Is this a recognized feature of overdose of the investigational product?

Is there a known mechanism?
Causality of ‘related’ is made if following a review of the relevant data, there is evidence for a 
‘reasonable possibility’ of a causal relationship for the individual case.  The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship.
The causality assessment is performed based on the available data including enough 
information to make an informed judgment.  With limited or insufficient information in the 
case, it is likely that the event(s) will be assessed as ‘not related’.
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as no reasonable possibility.
Relationship to Protocol Procedures
The investigator is also required to provide an assessment of relationship of SAEs to protocol 
procedures on the SAE Report Form. This includes nontreatment-emergent SAEs (ie, SAEs 
that occur prior to the administration of investigational product) as well as treatment-emergent 
SAEs. A protocol-related SAE may occur as a result of a procedure or intervention required 
during the study (eg, blood collection, washout of an existing medication). The following 
guidelines should be used by investigators to assess the relationship of SAEs to the protocol:
Protocol related:
The event occurred due to a procedure/intervention that was described 
in the protocol for which there is no alternative etiology present in the 
subject’s medical record.
Not protocol related: The event is related to an etiology other than the procedure/ 
intervention that was described in the protocol (the alternative etiology 
must be documented in the study subject’s medical record).

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10.4
Appendix 4 - National Institute of Allergy and Infectious Disease 
and Food Allergy and Anaphylaxis Network Guidance for 
Anaphylaxis Diagnosis
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson FN Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: Summary report --
Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol. 2006;117:391-7.
National Institute of Allergy and Infectious Disease (NAID) and Food Allergy and 
Anaphylaxis Network (FAAN) define anaphylaxis as a serious allergic reaction that is rapid in 
onset and may cause death. They recognize 3 categories of anaphylaxis, with criteria 
designated to capture from 80% of cases (category 1) to > 95% of all cases of anaphylaxis (for 
all 3 categories). 
1
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal 
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING:
(a) Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow (PEF), hypoxemia)
(b) Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (eg, 
hypotonia [collapse], syncope, incontinence)
2
Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):
(a) Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips-tongue-uvula)
(b) Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
(c) Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence)
(d) Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)
3
Reduced BP after exposure to known allergen for that patient (minutes to several hours):
(a) Infants and children: low systolic BP (age specific) or greater than 30% decrease in 
systolic BP
(b) Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
person’s baseline

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10.5
Appendix 5 - Actions Required in Cases of Increases in Liver 
Biochemistry and Evaluation of potential serious liver injury 
corresponding to Hy’s Law
10.5.1
Introduction
This appendix describes the process to be followed to identify and appropriately report cases 
of potential serious liver injury corresponding to Hy’s Law. It is not intended to be a 
comprehensive guide to the management of elevated liver biochemistries.
During the course of the study, the investigator will remain vigilant for increases in liver 
biochemistry. The investigator is responsible for determining whether a subject meets criteria 
for potential serious liver injury corresponding to Hy’s Law at any point during the study.
The investigator participates, together with MedImmune clinical project representatives, in 
review and assessment of cases meeting criteria for potential serious liver injury 
corresponding to Hy’s Law to agree whether these criteria are met. This is the case if there is 
no alternative explanation for the elevations in liver biochemistry other than drug-induced 
liver injury (DILI) caused by the investigational product. 
The investigator is responsible for recording data pertaining to cases of potential serious liver 
injury corresponding to Hy’s Law, and for reporting AEs and SAEs according to the outcome 
of the review and assessment in line with standard safety reporting processes.
10.5.2
Definitions
10.5.2.1
Potential serious liver injury corresponding to Hy’s Law

ALT and total bilirubin (TBL) normal at baseline:
ALT > 3 x upper limit of normal (ULN), with associated elevation in glutamate 
dehydrogenase (GLDH), without corresponding CK and/or troponin elevation, together 
with TBL ≥ 2 × ULN, at any point during the study following the start of study 
medication, irrespective of an increase in alkaline phosphatase (ALP). 

ALT or TBIL abnormal at baseline:
ALT > 3 x baseline or > 300 U/L (whichever occurs ﬁrst), with associated elevation 
in GLDH, without corresponding CK and/or troponin elevation, together with TBL ≥2 × 
ULN, or, if abnormal at baseline, > 2 x bsl, at any point during the study following the
start of study medication, irrespective of an increase in alkaline phosphatase (ALP). 
If ALT is decreasing from baseline, nadir will be new baseline
10.5.2.2
Serious liver injury corresponding to Hy’s Law

ALT and TBIL normal at baseline:

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ALT > 3 x ULN, with associated elevation in GLDH, without corresponding CK and/or 
troponin elevation, together with TBL ≥ 2 × ULN, where no other reason, other than the 
investigational product, can be found to explain the combination of increases; eg, elevated 
ALP indicating cholestasis, viral hepatitis, or another drug.

ALT or TBIL abnormal at baseline: 
ALT > 3 x baseline or > 300 U/L (whichever occurs ﬁrst), with associated elevation in 
GLDH, without corresponding CK and/or troponin elevation, together with TBL ≥ 2 × 
ULN, or, if abnormal at baseline, > 2 x bsl, where no other reason, other than the 
investigational product, can be found to explain the combination of increases; eg, elevated 
ALP indicating cholestasis, viral hepatitis, or another drug.
If ALT is decreasing from baseline, nadir will be new baseline
For (potential) serious liver injury corresponding to Hy’s law, the elevation in ALT must 
precede or be coincident with (ie, on the same day) the elevation in TBL, but there is no 
specified timeframe within which the elevations in ALT and TBL must occur.
10.5.3
Identification of cases of (potential) serious liver injury 
corresponding to Hy’s law
In order to identify cases of (potential) serious liver injury corresponding to Hy’s law, it is 
important to perform a comprehensive review of laboratory data for any subject who meets 
any of the following identification criteria in isolation or in combination:
ALT and TBIL normal at baseline: 

ALT > 3 x ULN, with associated elevation in GLDH

TBL ≥ 2 × ULN 
ALT or TBIL abnormal at baseline: 

ALT > 3 x ULN, with associated elevation in GLDH, or, if abnormal at baseline, ALT > 3 
x baseline or > 300 U/L (whichever occurs ﬁrst), with associated elevation in GLDH, 

TBL ≥ 2 × ULN, or, if abnormal at baseline, > 2 x bsl
If ALT is decreasing from baseline, nadir will be new baseline
When a subject meets any of the identification criteria, in isolation or in combination, the 
central laboratory will immediately send an alert to the investigator (also sent to sponsor study 
representative). 

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The investigator will also remain vigilant for any local laboratory reports where the 
identification criteria are met, where this is the case the investigator will:

Notify the sponsor study representative

Request a repeat of the test (new blood draw) by the central laboratory

Complete the appropriate unscheduled laboratory case report form (CRF) module(s) with 
the original local laboratory test result
When the identification criteria are met from central or local laboratory results the investigator 
will without delay:

Determine whether the subject meets criteria for (potential) serious liver injury 
corresponding to Hy’s law (see Section 10.5.4.2) by reviewing laboratory reports from all 
previous visits (including both central and local laboratory results)
10.5.4
Follow-up             
10.5.4.1
Criteria for (potential) serious liver injury corresponding to Hy’s law Not 
Met
If the subject does not meet criteria for (potential) serious liver injury corresponding to Hy’s 
law, the investigator will:

Inform the study representative that the subject has not met criteria for (potential) serious 
liver injury corresponding to Hy’s law.

Perform follow-up on subsequent laboratory results according to the guidance provided in 
the study protocol.
10.5.4.2
Criteria for (potential) serious liver injury corresponding to Hy’s law Met
If the subject does meet criteria for (potential) serious liver injury corresponding to Hy’s law, 
the investigator will:

Determine whether criteria for (potential) serious liver injury corresponding to Hy’s law 
were met at any study visit prior to starting study treatment 

Notify the sponsor study representative who will then inform the study team
The medical monitor contacts the investigator, to provide guidance, discuss and agree an 
approach for the study subjects’ follow-up and the continuous review of data. Subsequent to 
this contact the investigator will:

Monitor the subject until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically indicated

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
Investigate the etiology of the event and perform diagnostic investigations as discussed 
with the medical monitor. This includes deciding which the tests available in the Hy’s 
Law lab kit should be used.

Complete the Liver CRF Modules as information becomes available

If at any time (in consultation with the medical monitor) the criteria for potential serious 
liver injury corresponding to Hy’s law are met, report it as an SAE using standard 
reporting procedures
10.5.5
Review and Assessment of cases of (potential) serious liver injury 
corresponding to Hy’s law
The instructions in this section should be followed for all cases where criteria for (potential) 
serious liver injury corresponding to Hy’s law are met.
No later than 12 days after the biochemistry abnormality was initially detected, the medical 
monitor will contact the investigator in order to review available data and agree on whether 
there is an alternative explanation for meeting criteria for (potential) serious liver injury 
corresponding to Hy’s law other than DILI caused by the investigational product. The medical 
monitor and Global Safety Physician will also be involved in this review together with other 
subject matter experts as appropriate. It is recommended to also consult with the hepatic SKG 
for review of these cases.
According to the outcome of the review and assessment, the investigator will follow the 
instructions below.
If there is an agreed alternative explanation for the ALT and TBL elevations, a determination 
of whether the alternative explanation is an AE will be made and subsequently whether the 
AE meets the criteria for a SAE:

If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate CRF

If the alternative explanation is an AE/SAE, record the AE /SAE in the CRF accordingly 
and follow the sponsor’s standard processes
If it is agreed that there is no explanation that would explain the ALT and TBL elevations 
other than the investigational product:

Report an SAE (report term ‘Drug-induced liver injury’) according to the sponsor’s 
standard processes.

The ‘Medically Important’ serious criterion should be used if no other serious criteria 
apply

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As there is no alternative explanation for the case of (potential) serious liver injury 
corresponding to Hy’s law, a causality assessment of ‘related’ should be assigned
If, there is an unavoidable delay of over 12 days in obtaining the information necessary to 
assess whether or not the case meets the criteria for (potential) serious liver injury 
corresponding to Hy’s law, then it is assumed that there is no alternative explanation until 
such time as an informed decision can be made:

Report an SAE (report term ‘Drug-induced liver injury’) applying serious criteria and 
causality assessment as per above

Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether criteria for (potential) serious liver injury corresponding to Hy’s law are met. 
Update the SAE report according to the outcome of the review
10.6
Appendix 6 - Management of Liver Toxicity
In the setting of acute MI, transaminases used to monitor for liver toxicity (ALT and AST) can 
be elevated and of cardiac origin. Table 14 describes actions to be taken according to ALT; 
GLDH; total bilirubin; and subject symptoms.
Table 14
Actions to be Taken According to ALT, Glutamate Dehydrogenase, 
Total Bilirubin
Treatment-emergent ALT
Treatment-emergent 
TBL
Liver 
Symptoms
Action
1
If normal at baseline:
ALT > 3 x ULN, with 
associated elevation in GLDH, 
without corresponding CK and 
troponin elevation
Normal
None
Repeat ALT, AST, ALP, 
TBL, in 24-48 hours
Follow-up for 
symptoms.
If abnormal at baseline: 
ALT > 2 x baseline or > 200 
U/L (whichever occurs ﬁrst), 
with associated elevation in 
GLDH, without corresponding 
CK and troponin elevation
If ALT is decreasing from 
baseline, nadir will be new 
baseline.
For patients with 
abnormal bsl, 
No change in baseline 
TBL

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Table 14
Actions to be Taken According to ALT, Glutamate Dehydrogenase, 
Total Bilirubin
Treatment-emergent ALT
Treatment-emergent 
TBL
Liver 
Symptoms
Action
2
If normal at baseline:
ALT > 5 x ULN, with 
associated elevation in GLDH, 
without corresponding CK and 
troponin elevation
Normal
None
Interrupt study drug.
Initiate close monitoring 
and workup for 
competing etiologies. 
Study drug can be 
restarted only if another 
etiology is identiﬁed and 
liver enzymes return to 
baseline.
If abnormal at baseline: 
ALT > 3 x baseline or > 300 
U/L (whichever occurs ﬁrst), 
with associated elevation in 
GLDH, without corresponding 
CK and troponin elevation
If ALT is decreasing from 
baseline, nadir will be new 
baseline
For patients with 
abnormal bsl, 
No change in baseline 
TBL
3
If normal at baseline:
ALT > 3 x ULN, with 
associated elevation in GLDH, 
without corresponding CK and 
troponin elevation
TBL > 2 x ULN
None
Interrupt study drug.
Initiate close monitoring 
and workup for 
competing etiologies. 
Study drug can be 
restarted only if another 
etiology is identiﬁed and 
liver enzymes return to 
baseline.
If abnormal at baseline: 
ALT > 2 x baseline or > 200 
U/L (whichever occurs ﬁrst), 
with associated elevation in 
GLDH, without corresponding 
CK and troponin elevation
If ALT is decreasing from 
baseline, nadir will be new 
baseline.
For patients with 
abnormal bsl,
> 2 x bsl
4
If normal at baseline:
ALT > 3 x ULN, with 
associated elevation in GLDH, 
without corresponding CK and 
troponin elevation
Normal or elevated
Severe 
fatigue, 
nausea, 
vomiting, 
right upper 
quadrant pain
Interrupt study drug.
Initiate close monitoring 
and workup for 
competing etiologies. 
Study drug can be 
restarted only if another 
etiology is identiﬁed and 
If abnormal at baseline: 

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Table 14
Actions to be Taken According to ALT, Glutamate Dehydrogenase, 
Total Bilirubin
Treatment-emergent ALT
Treatment-emergent 
TBL
Liver 
Symptoms
Action
ALT > 2 x baseline or > 200 
U/L (whichever occurs ﬁrst), 
with associated elevation in 
GLDH, without corresponding 
CK and troponin elevation
If ALT is decreasing from 
baseline, nadir will be new 
baseline
liver enzymes return to 
baseline.
ALT = alanine transaminase; AST = aspartate transaminase; bsl = baseline; CK = creatine kinase; GLDH = 
glutamate dehydrogenase; TBL = total bilirubin; ULN = upper limit of normal. 
10.6.1
References
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: Premarketing 
clinical evaluation’: 
http://www fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf

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D5780C00007 Clinical Study Protocol Amendment 6
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