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    Clinical Trial Results:
    A Randomized, Placebo-controlled, Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (REAL-TIMI 63B)

    Summary
    EudraCT number
    		 2017-004521-32
    Trial protocol
    		 GB   ES   NL   CZ   SK   HU   PL  
    Global end of trial date
    18 Jan 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Jan 2022
    First version publication date
    29 Jan 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D5780C00007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03578809
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MedImmune LLC
    Sponsor organisation address
    OneMedImmune Way, Gaithersburg, United States, MD 20878
    Public contact
    Global Clinical Lead, MedImmune LLC, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, MedImmune LLC, +1 877-240-9479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Sep 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Jan 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the effect of MEDI6012 on reduction of infarct size compared with placebo.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 7
    Country: Number of subjects enrolled
    Czechia: 156
    Country: Number of subjects enrolled
    Hungary: 101
    Country: Number of subjects enrolled
    Israel: 53
    Country: Number of subjects enrolled
    Netherlands: 116
    Country: Number of subjects enrolled
    Poland: 11
    Country: Number of subjects enrolled
    Russian Federation: 26
    Country: Number of subjects enrolled
    Slovakia: 51
    Country: Number of subjects enrolled
    Spain: 49
    Country: Number of subjects enrolled
    United Kingdom: 23
    Worldwide total number of subjects
    593
    EEA total number of subjects
    484
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    370
    From 65 to 84 years
    223
    85 years and over
    0

    Subject disposition

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

    Pre-assignment
    Screening details
    		 In total, 593 participants were randomized into the study and 575 participants were treated with the study drug.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind [1]
    Roles blinded
    		 Subject, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A: Placebo
    Arm description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo matched to MEDI6012 was administered on Day 1 prior to pPCI followed by a second inpatient dose on Day 3 by IV push.

    Arm title
    		 Cohort A: MEDI6012
    Arm description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI6012
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Loading dose of MEDI6012 300 mg was administered on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push.

    Arm title
    		 Cohort B: Placebo
    Arm description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo matched to MEDI6012 was administered on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push.

    Arm title
    		 Cohort B: MEDI6012
    Arm description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI6012
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Loading dose of MEDI6012 300 mg was administered on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push.

    Notes
    [1] - The roles blinded appear to be inconsistent with a double blind trial.
    Justification: For this ‘Double blind’ study, number of roles blinded were greater than one (Subject, Monitor, Carer, Data analyst, Assessor) and the Investigators were unblinded.
    Number of subjects in period 1
    		Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Started
    94
    185
    112
    202
    Treated
    90
    179
    111
    195
    Completed
    88
    171
    108
    193
    Not completed
    6
    14
    4
    9
         Adverse event, serious fatal
    -
    2
    -
    1
         Consent withdrawn by subject
    3
    5
    2
    -
         Unspecified
    3
    6
    2
    8
         Lost to follow-up
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: Placebo
    Reporting group description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.

    Reporting group title
    Cohort A: MEDI6012
    Reporting group description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push.

    Reporting group title
    Cohort B: Placebo
    Reporting group description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push.

    Reporting group title
    Cohort B: MEDI6012
    Reporting group description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push.

    Reporting group values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012 Total
    Number of subjects
    		 94 185 112 202 593
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 62 122 58 128 370
        From 65-84 years
    		 32 63 54 74 223
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 59.7 ( 10.3 ) 59.9 ( 10.2 ) 62.6 ( 10.8 ) 59.9 ( 10.0 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 20 35 27 49 131
        Male
    		 74 150 85 153 462
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 1 1 3 5
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 0 1 2 3
        White
    		 94 182 110 194 580
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 2 0 3 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 8 2 10 22
        Not Hispanic or Latino
    		 92 177 110 192 571
        Unknown or Not Reported
    		 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Cohort A: Placebo
    Reporting group description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.

    Reporting group title
    Cohort A: MEDI6012
    Reporting group description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push.

    Reporting group title
    Cohort B: Placebo
    Reporting group description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push.

    Reporting group title
    Cohort B: MEDI6012
    Reporting group description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push.

    Primary: Global Infarct Size

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    End point title
    		 Global Infarct Size [1]
    End point description
    Global infarct size expressed as a percentage of left ventricle (LV) mass measured on delayed-enhanced cardiovascular magnetic resonance (CMR) imaging in 10-12 weeks post myocardial infarction (MI) is reported. Primary efficacy analysis population was analysed which included randomised participants with a Thrombolysis in Myocardial Infarction (TIMI) flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment.
    End point type
    Primary
    End point timeframe
    70 to 84 days post Day 1 dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since the inferential statistics was not performed for the reported groups.
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    43
    97
    61
    108
    Units: Percentage of global infarct size
        geometric mean (confidence interval 90%)
    5.453 (3.781 to 7.865)
    8.598 (7.228 to 10.229)
    9.004 (7.219 to 11.230)
    7.819 (6.658 to 9.183)
    No statistical analyses for this end point

    Secondary: Left Ventricular Ejection Fraction (LVEF)

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    End point title
    		 Left Ventricular Ejection Fraction (LVEF)
    End point description
    The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported. Primary efficacy analysis population was analysed which included randomised participants with a TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    70 to 84 days post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    43
    99
    61
    108
    Units: Percentage of LVEF
        geometric mean (confidence interval 90%)
    47.626 (44.344 to 51.152)
    47.083 (45.167 to 49.079)
    47.329 (45.158 to 49.604)
    49.722 (48.117 to 51.381)
    No statistical analyses for this end point

    Secondary: Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B

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    End point title
    		 Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B [2]
    End point description
    Change in NCPV in the coronary arteries from index computed tomography angiography (CTA) to 10-12 weeks post-MI is reported. The index CTA was preferably to be performed between 48 to 72 hours post Dose 1 (could be done up to 5 days post Dose 1) but no earlier than 40 hours post Dose 1. Participants with creatinine clearance >= 60 mL/min (Cockcroft Gault equation) within 6 hours underwent an index coronary CTA no earlier than 40 hours following the first dose. The CTA analysis population was analysed which included randomised participants in the 6-dose regimen who received a full treatment course of study drug, were eligible, and had coronary CTA.
    End point type
    Secondary
    End point timeframe
    Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    60
    121
    Units: mm^3
        geometric mean (confidence interval 90%)
    1.049 (0.915 to 1.203)
    0.998 (0.919 to 1.085)
    No statistical analyses for this end point

    Secondary: Left Ventricular Mass by Late Gadolinium Enhancement (LGE)

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    End point title
    		 Left Ventricular Mass by Late Gadolinium Enhancement (LGE)
    End point description
    The left ventricular mass by LGE is reported. Primary efficacy analysis population was analysed which included randomised participants with a TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    70 to 84 days post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    43
    97
    61
    108
    Units: grams
        arithmetic mean (standard deviation)
    119.740 ( 31.384 )
    119.581 ( 23.949 )
    115.221 ( 28.328 )
    117.920 ( 24.821 )
    No statistical analyses for this end point

    Secondary: Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)

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    End point title
    		 Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)
    End point description
    The left ventricular mass by cine MRI is reported. Primary efficacy analysis population was analysed which included randomised participants with a TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    70 to 84 days post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    43
    99
    61
    108
    Units: grams
        arithmetic mean (standard deviation)
    113.953 ( 31.261 )
    113.870 ( 23.885 )
    110.244 ( 28.009 )
    111.533 ( 23.329 )
    No statistical analyses for this end point

    Secondary: Left Ventricular End-diastolic and End-systolic Volume

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    End point title
    		 Left Ventricular End-diastolic and End-systolic Volume
    End point description
    Left ventricular end-diastolic and end-systolic volume is reported. Primary efficacy analysis population was analysed which included randomised participants with a TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    70 to 84 days post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    43
    99
    61
    108
    Units: mL
    geometric mean (confidence interval 90%)
        Left ventricular end-diastolic volume
    174.059 (161.956 to 187.066)
    176.523 (169.259 to 184.098)
    167.480 (157.010 to 178.649)
    172.733 (166.031 to 179.706)
        Left ventricular end-systolic volume
    87.038 (78.229 to 96.838)
    89.594 (83.818 to 95.768)
    84.977 (77.205 to 93.532)
    83.676 (78.606 to 89.073)
    No statistical analyses for this end point

    Secondary: Left Ventricular End-diastolic and End-systolic Volume Index

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    End point title
    		 Left Ventricular End-diastolic and End-systolic Volume Index
    End point description
    Left ventricular end-diastolic and end-systolic volume index is reported. Primary efficacy analysis population was analysed which included randomised participants with a TIMI flow Grade 0-1 on initial angiography who received at least 2 doses of study drug and grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    70 to 84 days post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    42
    99
    61
    108
    Units: mL/m^2
    geometric mean (confidence interval 90%)
        Left ventricular end-diastolic volume index
    89.158 (84.324 to 94.269)
    90.280 (86.818 to 93.880)
    86.118 (81.401 to 91.107)
    87.258 (84.211 to 90.416)
        Left ventricular end-systolic volume index
    44.491 (40.537 to 48.830)
    45.821 (42.970 to 48.863)
    43.695 (40.024 to 47.703)
    42.270 (39.845 to 44.842)
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed which included all treated participants, grouped according to actual treatment received.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 195 post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    90
    179
    111
    195
    Units: Participants
        Any TEAEs
    49
    114
    70
    136
        Any TESAEs
    11
    34
    24
    41
    No statistical analyses for this end point

    Secondary: Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass)

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    End point title
    		 Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) [3]
    End point description
    Serum concentration of MEDI6012 is reported. Pharmacokinetic population was analysed which included all participants in the As-treated population who had at least one detectable serum concentration measurement for LCAT mass or activity. Here, ‘n' denotes the number of participants who had adequate pharmacokinetic sample of MEDI6012 for the specified days, the arbitrary number '999999' denotes that no participants were evaluated for the specified time point, and the arbitrary numbers ‘99999’ and ‘99999.9’ denotes the data for mean and standard deviation (SD), respectively, which were not calculated because the concentration was below limit of quantification.
    End point type
    Secondary
    End point timeframe
    Pre- and post-dose on Days 1, 3, 17, and 31
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    		 Cohort A: MEDI6012 Cohort B: MEDI6012
    Number of subjects analysed
    179
    193
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 (pre-dose) (n = 3, 6)
    99999 ( 99999.9 )
    99999 ( 99999.9 )
        Day 1 (post-dose) (n = 172, 183)
    76795.9 ( 31136.7 )
    74661.2 ( 24561.6 )
        Day 3 (pre-dose) (n = 167, 180)
    28017.9 ( 11019.6 )
    27738.8 ( 12892.4 )
        Day 3 (post-dose) (n = 160, 176)
    94653.8 ( 115895.1 )
    87663.1 ( 93166.2 )
        Day 17 (pre-dose) (n = 0, 100)
    999999 ( 999999 )
    4509.9 ( 2372.6 )
        Day 17 (post-dose) (n = 0, 153)
    999999 ( 999999 )
    49111.0 ( 71552.1 )
        Day 31 (pre-dose) (n = 0, 80)
    999999 ( 999999 )
    4954.8 ( 4193.9 )
        Day 31 (post-dose) (n = 0, 147)
    999999 ( 999999 )
    67519.7 ( 224677.3 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012

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    End point title
    		 Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012
    End point description
    Number of participants with positive ADA titer to MEDI6012 are reported in 3 categories, ADA positive at any visit up to Day 70-84 follow-up visit, ADA positive with > 30% decrease in HDL-C from baseline (on the same date) at any visit up to D70-84 FU V, and ADA positive and > 30% decrease in HDL-C from baseline at Day 70-84 Follow-up Visit. Immunogenicity population was analysed which included all treated participants, grouped according to actual treatment received and had at least one serum sample for immunogenicity testing.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose
    End point values
    		 Cohort A: Placebo Cohort A: MEDI6012 Cohort B: Placebo Cohort B: MEDI6012
    Number of subjects analysed
    90
    179
    111
    194
    Units: Participants
        At any visit up to Day 70-84
    1
    13
    1
    93
        with >30% decrease HDL-C, up to Day 70-84
    1
    3
    0
    1
        With >30% decrease HDL-C, at Day 70-84
    1
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through Day 195 post Day 1 dose
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    MEDI6012 Cohort A
    Reporting group description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push.

    Reporting group title
    Placebo Cohort B
    Reporting group description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push.

    Reporting group title
    Placebo Cohort A
    Reporting group description
    		 Participants received placebo matched to MEDI6012 on Day 1 prior to primary percutaneous coronary intervention (pPCI) followed by a second inpatient dose on Day 3 by intravenous (IV) push.

    Reporting group title
    MEDI6012 Cohort B
    Reporting group description
    		 Participants received loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push.

    Serious adverse events
    		 MEDI6012 Cohort A Placebo Cohort B Placebo Cohort A MEDI6012 Cohort B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    34 / 179 (18.99%)
    24 / 111 (21.62%)
    11 / 90 (12.22%)
    41 / 195 (21.03%)
         number of deaths (all causes)
    2
    0
    0
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 179 (0.56%)
    2 / 111 (1.80%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post thrombotic syndrome
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular stent thrombosis
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatic haemorrhage
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental disorder
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Troponin increased
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periprocedural myocardial infarction
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postpericardiotomy syndrome
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    3 / 179 (1.68%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    3 / 195 (1.54%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    3 / 179 (1.68%)
    0 / 111 (0.00%)
    2 / 90 (2.22%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 179 (1.12%)
    2 / 111 (1.80%)
    1 / 90 (1.11%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 179 (0.00%)
    2 / 111 (1.80%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    5 / 179 (2.79%)
    2 / 111 (1.80%)
    1 / 90 (1.11%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 179 (0.00%)
    2 / 111 (1.80%)
    0 / 90 (0.00%)
    3 / 195 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery dissection
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dressler's syndrome
         subjects affected / exposed
    1 / 179 (0.56%)
    2 / 111 (1.80%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Palpitations
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial haemorrhage
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prinzmetal angina
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 179 (0.00%)
    2 / 111 (1.80%)
    1 / 90 (1.11%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 179 (1.12%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis erosive
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis haemorrhagic
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic skin eruption
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 179 (1.68%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    0 / 195 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 MEDI6012 Cohort A Placebo Cohort B Placebo Cohort A MEDI6012 Cohort B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    74 / 179 (41.34%)
    47 / 111 (42.34%)
    28 / 90 (31.11%)
    89 / 195 (45.64%)
    Vascular disorders
    Brachiocephalic arteriosclerosis
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 111 (0.90%)
    1 / 90 (1.11%)
    4 / 195 (2.05%)
         occurrences all number
    2
    1
    1
    4
    Haematoma
         subjects affected / exposed
    4 / 179 (2.23%)
    2 / 111 (1.80%)
    0 / 90 (0.00%)
    3 / 195 (1.54%)
         occurrences all number
    4
    2
    0
    3
    Hypertension
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    6 / 195 (3.08%)
         occurrences all number
    4
    1
    0
    6
    Hypotension
         subjects affected / exposed
    3 / 179 (1.68%)
    7 / 111 (6.31%)
    0 / 90 (0.00%)
    11 / 195 (5.64%)
         occurrences all number
    3
    7
    0
    12
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 179 (2.23%)
    4 / 111 (3.60%)
    3 / 90 (3.33%)
    2 / 195 (1.03%)
         occurrences all number
    4
    4
    3
    2
    Pyrexia
         subjects affected / exposed
    4 / 179 (2.23%)
    4 / 111 (3.60%)
    1 / 90 (1.11%)
    3 / 195 (1.54%)
         occurrences all number
    4
    4
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 179 (1.12%)
    0 / 111 (0.00%)
    2 / 90 (2.22%)
    0 / 195 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Cough
         subjects affected / exposed
    8 / 179 (4.47%)
    3 / 111 (2.70%)
    2 / 90 (2.22%)
    9 / 195 (4.62%)
         occurrences all number
    8
    3
    2
    9
    Dyspnoea
         subjects affected / exposed
    4 / 179 (2.23%)
    3 / 111 (2.70%)
    2 / 90 (2.22%)
    6 / 195 (3.08%)
         occurrences all number
    4
    3
    2
    6
    Epistaxis
         subjects affected / exposed
    2 / 179 (1.12%)
    2 / 111 (1.80%)
    2 / 90 (2.22%)
    2 / 195 (1.03%)
         occurrences all number
    2
    2
    2
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    6 / 195 (3.08%)
         occurrences all number
    4
    1
    0
    6
    Insomnia
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    5 / 195 (2.56%)
         occurrences all number
    2
    1
    0
    5
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    4 / 179 (2.23%)
    4 / 111 (3.60%)
    2 / 90 (2.22%)
    6 / 195 (3.08%)
         occurrences all number
    5
    4
    2
    6
    Atrial fibrillation
         subjects affected / exposed
    6 / 179 (3.35%)
    5 / 111 (4.50%)
    2 / 90 (2.22%)
    7 / 195 (3.59%)
         occurrences all number
    6
    5
    2
    7
    Bradycardia
         subjects affected / exposed
    0 / 179 (0.00%)
    3 / 111 (2.70%)
    1 / 90 (1.11%)
    5 / 195 (2.56%)
         occurrences all number
    0
    3
    1
    5
    Cardiac failure
         subjects affected / exposed
    4 / 179 (2.23%)
    3 / 111 (2.70%)
    1 / 90 (1.11%)
    9 / 195 (4.62%)
         occurrences all number
    4
    4
    1
    9
    Cardiac ventricular thrombosis
         subjects affected / exposed
    5 / 179 (2.79%)
    0 / 111 (0.00%)
    1 / 90 (1.11%)
    0 / 195 (0.00%)
         occurrences all number
    5
    0
    1
    0
    Palpitations
         subjects affected / exposed
    5 / 179 (2.79%)
    1 / 111 (0.90%)
    1 / 90 (1.11%)
    2 / 195 (1.03%)
         occurrences all number
    6
    1
    1
    2
    Supraventricular extrasystoles
         subjects affected / exposed
    3 / 179 (1.68%)
    1 / 111 (0.90%)
    2 / 90 (2.22%)
    3 / 195 (1.54%)
         occurrences all number
    3
    1
    2
    3
    Ventricular extrasystoles
         subjects affected / exposed
    5 / 179 (2.79%)
    2 / 111 (1.80%)
    0 / 90 (0.00%)
    5 / 195 (2.56%)
         occurrences all number
    5
    2
    0
    5
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    13 / 179 (7.26%)
    5 / 111 (4.50%)
    1 / 90 (1.11%)
    4 / 195 (2.05%)
         occurrences all number
    13
    5
    1
    4
    Headache
         subjects affected / exposed
    7 / 179 (3.91%)
    5 / 111 (4.50%)
    4 / 90 (4.44%)
    12 / 195 (6.15%)
         occurrences all number
    7
    5
    4
    13
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 179 (1.68%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    6 / 195 (3.08%)
         occurrences all number
    3
    1
    0
    6
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    3 / 90 (3.33%)
    2 / 195 (1.03%)
         occurrences all number
    0
    0
    3
    2
    Constipation
         subjects affected / exposed
    1 / 179 (0.56%)
    2 / 111 (1.80%)
    1 / 90 (1.11%)
    5 / 195 (2.56%)
         occurrences all number
    1
    2
    1
    5
    Diarrhoea
         subjects affected / exposed
    4 / 179 (2.23%)
    2 / 111 (1.80%)
    1 / 90 (1.11%)
    8 / 195 (4.10%)
         occurrences all number
    4
    2
    1
    9
    Nausea
         subjects affected / exposed
    2 / 179 (1.12%)
    3 / 111 (2.70%)
    1 / 90 (1.11%)
    11 / 195 (5.64%)
         occurrences all number
    2
    3
    1
    14
    Toothache
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 111 (0.00%)
    2 / 90 (2.22%)
    0 / 195 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Vomiting
         subjects affected / exposed
    2 / 179 (1.12%)
    2 / 111 (1.80%)
    3 / 90 (3.33%)
    3 / 195 (1.54%)
         occurrences all number
    2
    2
    3
    4
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    5 / 179 (2.79%)
    1 / 111 (0.90%)
    1 / 90 (1.11%)
    1 / 195 (0.51%)
         occurrences all number
    5
    1
    1
    1
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    3 / 179 (1.68%)
    1 / 111 (0.90%)
    2 / 90 (2.22%)
    0 / 195 (0.00%)
         occurrences all number
    3
    1
    2
    0
    Renal impairment
         subjects affected / exposed
    1 / 179 (0.56%)
    2 / 111 (1.80%)
    2 / 90 (2.22%)
    2 / 195 (1.03%)
         occurrences all number
    1
    2
    2
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 179 (2.23%)
    0 / 111 (0.00%)
    0 / 90 (0.00%)
    1 / 195 (0.51%)
         occurrences all number
    4
    0
    0
    1
    Back pain
         subjects affected / exposed
    2 / 179 (1.12%)
    3 / 111 (2.70%)
    2 / 90 (2.22%)
    3 / 195 (1.54%)
         occurrences all number
    2
    3
    2
    3
    Pain in extremity
         subjects affected / exposed
    1 / 179 (0.56%)
    4 / 111 (3.60%)
    0 / 90 (0.00%)
    2 / 195 (1.03%)
         occurrences all number
    1
    4
    0
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    5 / 195 (2.56%)
         occurrences all number
    2
    1
    0
    5
    Respiratory tract infection viral
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 111 (0.90%)
    0 / 90 (0.00%)
    4 / 195 (2.05%)
         occurrences all number
    2
    1
    0
    4
    Urinary tract infection
         subjects affected / exposed
    3 / 179 (1.68%)
    2 / 111 (1.80%)
    2 / 90 (2.22%)
    3 / 195 (1.54%)
         occurrences all number
    3
    2
    2
    3
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    5 / 179 (2.79%)
    2 / 111 (1.80%)
    2 / 90 (2.22%)
    6 / 195 (3.08%)
         occurrences all number
    5
    2
    2
    6
    Hypokalaemia
         subjects affected / exposed
    5 / 179 (2.79%)
    2 / 111 (1.80%)
    5 / 90 (5.56%)
    1 / 195 (0.51%)
         occurrences all number
    5
    2
    7
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    3 / 179 (1.68%)
    3 / 111 (2.70%)
    1 / 90 (1.11%)
    3 / 195 (1.54%)
         occurrences all number
    3
    3
    1
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Jan 2018
    Updated Table 'Treatment Period and Follow up Procedures: Cohort A (2 Dose Regimen)' to correct previous omissions and errors.
    28 Mar 2018
    The word ‘prevent’ was replaced with ‘reduce’ in the third secondary hypothesis. The use of estimated glomerular filtration rate (eGFR) criteria was removed and changed to creatinine clearance (CrCl) criteria throughout. Updated exclusion criteria. Subsection ‘Cardiovascular MRI’ was revised to remove ‘no known history of contrast-induced nephropathy’ and instead to give conditions for receiving contrast. Clarified that randomization will be stratified by infarct location. Updated Table ‘Treatment Period and Follow-up Procedures’ for Cohort A and Cohort B. The text that radiation dose would be calculated using a K factor of 0.014. Text was added to specify that the sponsor and principal investigator were to monitor the statistical assumptions in a blinded fashion and decide the exact time for interim analyses.
    14 Jun 2018
    For Inpatient Phase, Cohorts A and B, text was added that following Doses 1 and 2 for Cohort A, or Doses 1-3 for Cohort B, participants would 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 participants who did not undergo index CTA for any reason would not undergo the CTA at the end of the study. The title of the Cardiovascular MRI subsection was revised to read ‘Administration of gadolinium Contrast for Cardiovascular MRI’. Under Coronary CTA, a sixth requirement was added that for follow up CTA, participants would need to have undergone an index CTA. The table footnote of Tables 9 and 10 were updated. Text was revised to read, “For CMR, participants will be required to meet Additional Study Requirements listed in the clinical study protocol Section 4.1.4, including no contraindication to MR imaging (eg, metallic implant, claustrophobia, implantable cardioverter-defibrillator, pacemaker) and, for the administration of gadolinium-based contrast, confirmation of CrCl ≥ 30 mL/min (Cockcroft Gault equation) is required’. The text was revised to say that due to the acute nature of the study, members of the research team, and possibly the investigator, may be unblinded.
    18 Apr 2019
    Provided clarification for the exploratory safety objective and endpoints related to major cardiovascular events. Index CTA window altered from ‘no earlier than 48 hours’ to ‘no earlier than 40 hours’ post Dose 1. CMR window for repeat scans increased from 1 week to 4 weeks following the end-of-study visit (up to 112 days post Dose 1). The table footnote of Tables 9 and 10 were updated. The time frame of Day 70 to 84 was added to text in the extended follow up section. Text related to pharmacokinetics and ADA samples was revised. Text added to increase the window for repeat CMR scans from 1 week to 4 weeks following the end-of-study visit (up to 112 days post Dose 1) and removed tagged MRI and T1 mapping procedures. Text added regarding CTA in participants who had planned or underwent coronary artery bypass graft surgery.
    26 Jul 2019
    Sample size 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. The alpha threshold was amended to be a 1-sided alpha of 0.05. Number of study sites updated from 40 to 43. 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). 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 participant from coronary CTA”. Descriptions of analysis populations updated.
    04 May 2020
    The guidance was added to the protocol in response to the coronavirus disease (COVID-19) pandemic to enable safety monitoring of participants through an extended blood sampling window, updated the footnotes of Table 9 and Table 10 accordingly. It was added that during the Extended Follow-up period, if the ADA test result became negative or the HDL-C was no longer > 30% decreased compared with baseline, the participant did not need to return for additional Extended Follow-up visit(s) and would be considered as having completed the Extended Follow-up period. It was clarified that 2 independent database locks may be conducted and details of these database locks were given. The end of the study (study completion) was defined as the date of the last protocol specified visit/assessment, which could 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 participant in the study, whichever occurred last. Throughout the protocol where ‘> 30% decrease in HDL-C’ was cited, it was clarified that this refers to ‘> 30% decrease from baseline in HDL-C’.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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