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    Clinical Trial Results:
    A phase IIa, placebo-controlled, double blind, randomised multicentre pilot study to investigate the efficacy, safety and tolerability of the monoclonal antibody ATH3G10 in patients with ST-elevation myocardial infarction

    Summary
    EudraCT number
    		 2018-003676-12
    Trial protocol
    		 SE   DK   NL  
    Global end of trial date
    12 Mar 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Nov 2021
    First version publication date
    03 Nov 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ATH3G10-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03991143
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Athera Biotechnologies AB
    Sponsor organisation address
    Olof Palmes gata 29, Stockholm, Sweden, 11122
    Public contact
    James Hall, CEO, Athera Biotechnologies AB, +46 8501 37000, j.hall@athera.se
    Scientific contact
    James Hall, CEO, Athera Biotechnologies AB, +46 8501 37000, j.hall@athera.se
    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
    21 Apr 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Mar 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main goal of this study was to evaluate the efficacy of a single administration of ATH3G10 in patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI).
    Protection of trial subjects
    The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements. Informed consent was obtained from all subjects prior to initiation of the study. To avoid antibody aggregates in the solution, the investigational medicinal product (IMP) was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an adverse event assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes. Patients previously exposed to ATH3G10 were excluded. Any apparent side effect experienced by a patient was assessed from the time of the IMP dose and throughout the the study (until the 12-month follow-up visit, Visit 5) and were reported as adverse events (AEs).
    Background therapy
    		 No background therapy was used in this study.
    Evidence for comparator
    		 No comparator was used in this study.
    Actual start date of recruitment
    01 Feb 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 16
    Country: Number of subjects enrolled
    Sweden: 60
    Country: Number of subjects enrolled
    Denmark: 6
    Worldwide total number of subjects
    82
    EEA total number of subjects
    82
    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)
    38
    From 65 to 84 years
    44
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The first patient’s first visit in the study (first patient screened) was on 2019-04-25 and the last patient’s last visit was on 2021-03-12.

    Pre-assignment
    Screening details
    		 A total of 82 patients were screened. All 82 patients (43 patients in the ATH3G10 group and 39 patients in the placebo group) were randomised and treated, as planned.

    Period 1
    Period 1 title
    Visit 1- prior to treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Carer, Assessor, Subject
    Blinding implementation details
    This was a double-blinded study, the treatment was blinded to the patient, the Investigators and the personnel administrating the IMP. The Investigator could only break the treatment code if the appropriate future management of the patient necessitated knowledge of current treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ATH3G10
    Arm description
    		 Patients were allocated to the ATH3G10 group.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ATH3G10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The test product, ATH3G10, was a clear to slightly opalescent, colourless to faintly yellowish concentrated solution in 10 mL clear type 1 glass vials filled with 5 mL. The vials were sealed with bromobutyl rubber stoppers, covered with aluminium caps and stored at 2-8 °C. Each patient received a single intravenous dose of the IMP within 120 minutes of the PCI procedure start, defined as the time when the guide wire was passed through the stenosis. To avoid antibody aggregates in the solution, the IMP was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to the placebo group.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The placebo was a sterile sodium chloride 0.9% solution for infusion in 10 mL clear type 1 glass vials filled with 5 mL. The reference product was stored at 2-8 °C. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Number of subjects in period 1
    		ATH3G10 Placebo
    Started
    43
    39
    Completed
    43
    39
    Period 2
    Period 2 title
    Visit 1- treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This was a double-blinded study, the treatment was blinded to the patient, the Investigators and the personnel administrating the IMP. The Investigator could only break the treatment code if the appropriate future management of the patient necessitated knowledge of current treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ATH3G10
    Arm description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ATH3G10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The test product, ATH3G10, was a clear to slightly opalescent, colourless to faintly yellowish concentrated solution in 10 mL clear type 1 glass vials filled with 5 mL. The vials were sealed with bromobutyl rubber stoppers, covered with aluminium caps and stored at 2-8 °C. Each patient received a single intravenous dose of the IMP within 120 minutes of the PCI procedure start, defined as the time when the guide wire was passed through the stenosis. To avoid antibody aggregates in the solution, the IMP was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The placebo was a sterile sodium chloride 0.9% solution for infusion in 10 mL clear type 1 glass vials filled with 5 mL. The reference product was stored at 2-8 °C. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Number of subjects in period 2
    		ATH3G10 Placebo
    Started
    43
    39
    Completed
    41
    37
    Not completed
    2
    2
         Consent withdrawn by subject
    2
    2
    Period 3
    Period 3 title
    Visit 2- MRI examination
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This was a double-blinded study, the treatment was blinded to the patient, the Investigators and the personnel administrating the IMP. The Investigator could only break the treatment code if the appropriate future management of the patient necessitated knowledge of current treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ATH3G10
    Arm description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ATH3G10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The test product, ATH3G10, was a clear to slightly opalescent, colourless to faintly yellowish concentrated solution in 10 mL clear type 1 glass vials filled with 5 mL. The vials were sealed with bromobutyl rubber stoppers, covered with aluminium caps and stored at 2-8 °C. Each patient received a single intravenous dose of the IMP within 120 minutes of the PCI procedure start, defined as the time when the guide wire was passed through the stenosis. To avoid antibody aggregates in the solution, the IMP was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The placebo was a sterile sodium chloride 0.9% solution for infusion in 10 mL clear type 1 glass vials filled with 5 mL. The reference product was stored at 2-8 °C. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Number of subjects in period 3
    		ATH3G10 Placebo
    Started
    41
    37
    Completed
    41
    37
    Period 4
    Period 4 title
    Visit 3- 3-month follow-up and 2nd MRI
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This was a double-blinded study, the treatment was blinded to the patient, the Investigators and the personnel administrating the IMP. The Investigator could only break the treatment code if the appropriate future management of the patient necessitated knowledge of current treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ATH3G10
    Arm description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ATH3G10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The test product, ATH3G10, was a clear to slightly opalescent, colourless to faintly yellowish concentrated solution in 10 mL clear type 1 glass vials filled with 5 mL. The vials were sealed with bromobutyl rubber stoppers, covered with aluminium caps and stored at 2-8 °C. Each patient received a single intravenous dose of the IMP within 120 minutes of the PCI procedure start, defined as the time when the guide wire was passed through the stenosis. To avoid antibody aggregates in the solution, the IMP was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The placebo was a sterile sodium chloride 0.9% solution for infusion in 10 mL clear type 1 glass vials filled with 5 mL. The reference product was stored at 2-8 °C. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Number of subjects in period 4
    		ATH3G10 Placebo
    Started
    41
    37
    Completed
    41
    37
    Period 5
    Period 5 title
    Visit 4- 6-month follow-up
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This was a double-blinded study, the treatment was blinded to the patient, the Investigators and the personnel administrating the IMP. The Investigator could only break the treatment code if the appropriate future management of the patient necessitated knowledge of current treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ATH3G10
    Arm description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ATH3G10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The test product, ATH3G10, was a clear to slightly opalescent, colourless to faintly yellowish concentrated solution in 10 mL clear type 1 glass vials filled with 5 mL. The vials were sealed with bromobutyl rubber stoppers, covered with aluminium caps and stored at 2-8 °C. Each patient received a single intravenous dose of the IMP within 120 minutes of the PCI procedure start, defined as the time when the guide wire was passed through the stenosis. To avoid antibody aggregates in the solution, the IMP was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The placebo was a sterile sodium chloride 0.9% solution for infusion in 10 mL clear type 1 glass vials filled with 5 mL. The reference product was stored at 2-8 °C. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Number of subjects in period 5
    		ATH3G10 Placebo
    Started
    41
    37
    Completed
    41
    36
    Not completed
    0
    1
         not willing to continue the study
    -
    1
    Period 6
    Period 6 title
    Visit 5- 12-month follow-up
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This was a double-blinded study, the treatment was blinded to the patient, the Investigators and the personnel administrating the IMP. The Investigator could only break the treatment code if the appropriate future management of the patient necessitated knowledge of current treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ATH3G10
    Arm description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ATH3G10
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The test product, ATH3G10, was a clear to slightly opalescent, colourless to faintly yellowish concentrated solution in 10 mL clear type 1 glass vials filled with 5 mL. The vials were sealed with bromobutyl rubber stoppers, covered with aluminium caps and stored at 2-8 °C. Each patient received a single intravenous dose of the IMP within 120 minutes of the PCI procedure start, defined as the time when the guide wire was passed through the stenosis. To avoid antibody aggregates in the solution, the IMP was passed through a 0.2 μm filter just before the connection to the intravenous catheter. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The placebo was a sterile sodium chloride 0.9% solution for infusion in 10 mL clear type 1 glass vials filled with 5 mL. The reference product was stored at 2-8 °C. If a patient experienced an AE assessed as related to the IMP during the slow injection, the dosing was to be immediately stopped. If the dosing was stopped due to technical reason (e.g. change of needle), a re-start of dosing was allowed within 30 minutes.

    Number of subjects in period 6
    		ATH3G10 Placebo
    Started
    41
    36
    Completed
    41
    36

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to the ATH3G10 group.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to the placebo group.

    Reporting group values
    		 ATH3G10 Placebo Total
    Number of subjects
    		 43 39 82
    Age categorical
    Units: Subjects
        Adults 40-85 years old
    		 43 39 82
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.6 ± 10.4 64.8 ± 8.7 -
    Gender categorical
    Units: Subjects
        Female
    		 6 9 15
        Male
    		 37 30 67
    Body weight
    Units: kg
        arithmetic mean (standard deviation)
    		 84.36 ± 12.23 84.34 ± 11.72 -
    Body mass index (BMI)
    Units: kg/x2
        arithmetic mean (standard deviation)
    		 27.34 ± 3.45 27.19 ± 3.22 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to the ATH3G10 group.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to the placebo group.
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.

    Reporting group title
    Placebo
    Reporting group description
    		 -
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to receive a single dose of 250 mg of ATH3G10 at Visit 1.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive a single dose of placebo at Visit 1.

    Subject analysis set title
    ATH3G10- FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) was defined as all randomised patients who received 1 dose of IMP and for whom at least 1 post-baseline efficacy assessment was made. The FAS included 78 patients (41 patients in the ATH3G10 group and 37 patients in the placebo group). There were 4 patients (2 in the ATH3G10 group and 2 in the placebo group) that were excluded from the FAS because they had no post-baseline efficacy data, due to early withdrawal.

    Subject analysis set title
    Placebo- FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) was defined as all randomised patients who received 1 dose of IMP and for whom at least 1 post-baseline efficacy assessment was made. The FAS included 78 patients (41 patients in the ATH3G10 group and 37 patients in the placebo group). There were 4 patients (2 in the ATH3G10 group and 2 in the placebo group) that were excluded from the FAS because they had no post-baseline efficacy data, due to early withdrawal.

    Primary: Left ventricular end-diastolic volume index (LV EDVi) Least squares (LS) mean

    		 Close Top of page
    End point title
    		 Left ventricular end-diastolic volume index (LV EDVi) Least squares (LS) mean
    End point description
    The primary objective was to investigate effects on left ventricular remodelling as change in end diastolic volume measured by MRI. The primary endpoint, change in LV EDVi from Visit 2 to Visit 3, was analysed using an analysis of covariance (ANCOVA) model to test for the difference between treatment with ATH3G10 and placebo. The model included the treatment group as fixed effect and LV EDVi at Visit 2 as covariate. The model included the change from Visit 2 to Visit 3 as dependent variable. The active treatment group was tested against the placebo group and the null hypothesis that the mean difference in change in LV EDVi is equal to zero was tested against the two-sided alternative hypothesis that the difference is not equal to zero.
    End point type
    Primary
    End point timeframe
    The primary endpoint was the comparison of the change in LV EDVi between Visit 2 (Day 2 to 4 after IMP administration) and Visit 3 (Day 60 to 180 after IMP administration).
    End point values
    		 ATH3G10- FAS Placebo- FAS
    Number of subjects analysed
    41
    37
    Units: mL/m2
    least squares mean (confidence interval 95%)
        Change in LV EDVi from Visit 2 to Visit 3
    3.69 (-0.61 to 7.99)
    7.17 (2.81 to 11.53)
    Statistical analysis title
    		 Difference in LV EDVi change from V2 to V3
    Statistical analysis description
    The primary endpoint was the comparison of the change in left ventricular end-diastolic volume index (LV EDVi) between Visit 2 (V2, i.e., Day 2 to 4 after IMP administration) and Visit 3 (V3, i.e., Day 60 to 180 after IMP administration).
    Comparison groups
    ATH3G10- FAS v Placebo- FAS
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [1]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.63
         upper limit
    		 2.67
    Variability estimate
    Standard deviation
    Notes
    [1] - Difference in LS Means (95% CI): -3.48 (-9.63, 2.67) p-value = 0.263

    Primary: LV EDVi arithmetic mean

    		 Close Top of page
    End point title
    		 LV EDVi arithmetic mean [2]
    End point description
    The primary objective was to investigate effects on left ventricular remodelling as change in end diastolic volume measured by MRI. The primary endpoint, change in LV EDVi from Visit 2 to Visit 3, was analysed using an analysis of covariance (ANCOVA) model to test for the difference between treatment with ATH3G10 and placebo. The model included the treatment group as fixed effect and LV EDVi at Visit 2 as covariate. The model included the change from Visit 2 to Visit 3 as dependent variable. The active treatment group was tested against the placebo group and the null hypothesis that the mean difference in change in LV EDVi is equal to zero was tested against the two-sided alternative hypothesis that the difference is not equal to zero.
    End point type
    Primary
    End point timeframe
    The primary endpoint was the comparison of the change in left ventricular end-diastolic volume index (LV EDVi) between Visit 2 (Day 2 to 4 after IMP administration) and Visit 3 (Day 60 to 180 after IMP administration).
    Notes
    [2] - 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: The statistical analysis "Difference in LV EDVi change from V2 to V3" applies also to this primary endpoint.
    End point values
    		 ATH3G10- FAS Placebo- FAS
    Number of subjects analysed
    41
    37
    Units: mL/m2
    arithmetic mean (standard deviation)
        LV EDVi at Visit 2
    85.89 ± 14.37
    89.28 ± 11.85
        LV EDVi at Visit 3
    89.60 ± 17.95
    96.27 ± 18.67
        Change in LV EDVi from Visit 2 to Visit 3
    3.71 ± 10.97
    7.15 ± 14.43
    No statistical analyses for this end point

    Secondary: Myocardial Salvage index (MSi) at Visit 2- LS mean

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    End point title
    		 Myocardial Salvage index (MSi) at Visit 2- LS mean
    End point description
    The secondary objective was to investigate effects on MSi measured by MRI. The secondary efficacy variable, MSi at Visit 2, was analysed using an analysis of variance (ANOVA) model to test for the difference between treatment with ATH3G10 and placebo. The model included the treatment group as fixed effect. The active treatment group was tested against the placebo group and the null hypothesis that the mean difference in MSi is equal to zero was tested against the two-sided alternative hypothesis that the difference is not equal to zero.
    End point type
    Secondary
    End point timeframe
    The secondary endpoint was the comparison of MSi at Visit 2 (Day 2 to 4 after IMP administration).
    End point values
    		 ATH3G10- FAS Placebo- FAS
    Number of subjects analysed
    41
    37
    Units: percentage
    least squares mean (confidence interval 95%)
        MSi LS mean at Visit 2 (%)
    39.77 (32.24 to 47.29)
    39.90 (32.81 to 46.99)
    Statistical analysis title
    		 Difference in MSi at Visit 2
    Statistical analysis description
    The secondary endpoint was the comparison of MSi at Visit 2 (Day 2 to 4 after IMP administration).
    Comparison groups
    ATH3G10- FAS v Placebo- FAS
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.47
         upper limit
    		 10.21
    Variability estimate
    Standard deviation
    Notes
    [3] - Difference in LS Means (95% CI) at Visit 2: -0.13 (-10.47, 10.21) p-value = 0.980

    Secondary: MSi at Visit 2- arithmetic mean

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    End point title
    		 MSi at Visit 2- arithmetic mean
    End point description
    The secondary objective was to investigate effects on MSi measured by MRI. The secondary efficacy variable, MSi at Visit 2, was analysed using an analysis of variance (ANOVA) model to test for the difference between treatment with ATH3G10 and placebo. The model included the treatment group as fixed effect.
    End point type
    Secondary
    End point timeframe
    The secondary endpoint was the comparison of MSi at Visit 2 (Day 2 to 4 after IMP administration).
    End point values
    		 ATH3G10- FAS Placebo- FAS
    Number of subjects analysed
    41
    37
    Units: percentage
    arithmetic mean (standard deviation)
        MSi at Visit 2
    39.77 ± 19.40
    39.90 ± 22.87
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were reproted from the time of IMP administration and until the end of the study (i.e., Visit 1-treatment to Visit 5- 12 month follow-up).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    ATH3G10
    Reporting group description
    		 Patients were allocated to the ATH3G10 group.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to the placebo group.

    Serious adverse events
    		 ATH3G10 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 43 (16.28%)
    10 / 39 (25.64%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon adenoma
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Colectomy
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 39 (5.13%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Melaena
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Jaundice
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 39 (2.56%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 39 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 ATH3G10 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 43 (62.79%)
    22 / 39 (56.41%)
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 39 (5.13%)
         occurrences all number
    1
    2
    Vascular disorders
    Hypotension
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 39 (5.13%)
         occurrences all number
    2
    2
    Hypertension
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 39 (5.13%)
         occurrences all number
    1
    2
    Thrombosis
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    6 / 43 (13.95%)
    3 / 39 (7.69%)
         occurrences all number
    6
    3
    Atrial fibrillation
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 39 (7.69%)
         occurrences all number
    2
    3
    Ventricular tachycardia
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 39 (7.69%)
         occurrences all number
    1
    3
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 39 (5.13%)
         occurrences all number
    1
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 43 (9.30%)
    3 / 39 (7.69%)
         occurrences all number
    4
    3
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    4 / 43 (9.30%)
    5 / 39 (12.82%)
         occurrences all number
    4
    5
    Pyrexia
         subjects affected / exposed
    4 / 43 (9.30%)
    2 / 39 (5.13%)
         occurrences all number
    5
    2
    Fatigue
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 39 (2.56%)
         occurrences all number
    3
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 43 (9.30%)
    4 / 39 (10.26%)
         occurrences all number
    4
    4
    Diarrhoea
         subjects affected / exposed
    3 / 43 (6.98%)
    3 / 39 (7.69%)
         occurrences all number
    3
    3
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    4 / 43 (9.30%)
    6 / 39 (15.38%)
         occurrences all number
    4
    6
    Cough
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 39 (5.13%)
         occurrences all number
    1
    2
    Epistaxis
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2
    Pain in extremity
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 39 (5.13%)
         occurrences all number
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Apr 2019
    The first clinical study protocol (CSP) version used for patient enrolment in Sweden was CSP Version 2.0, dated 2019-01-07. Substantial amendment 2.0 led to CSP Version 3.0, dated 2019-04-04. The CSP version used for patient enrolment in Denmark was CSP Version 4.0, while CSP Version 3.0 was used in The Netherlands. Substantial amendment 2.0 included: 1) clarification of the defiinition of the percutaneous coronary intervention (PCI) start. “PCI less than 4 hours after symptom onset” was replaced by “Start of PCI, defined as when the guide wire is passed through the stenosis, less than 4 hours after symptom onset” 2) clarification of the allowed time window of the IMP administration. “IMP will be administered as soon as possible after randomization and within 120 minutes of performed PCI procedure.” was replaced by “IMP will be administered as soon as possible after randomization and within 120 minutes of start of the PCI procedure, defined as when the guide wire is passed through the stenosis.” 3) Addition/update of assesements. “12-lead ECG” was replaced by “ECG monitoring at visit 1 and 2” and “Blood sampling for other biomarkers related to cardiovascular disease” was added for visit 1 (baseline sample).”
    23 Oct 2019
    Substantial amendment 3.0 led to CSP Version 4.0, dated 2019-10-23 (first CSP verison used for enrollment in Denmark) and included: 1) The use of Gadolinium-based contrast agents has been associated with severe reactions (Nephrogenic Systemic Fibrosis, NSF) in patients with severely reduced renal function. Clinical use is therefore contraindicated below an eGFR of 30 mL/min/1.73 m2 for all Gadolinium based contrast agents. Since no direct clinical benefit is gained by the study patients from the examination a conservative limit for the use of contrast agents, eGFR 50 mLl/min/1.73 m2, was initially selected. An increasing amount of clinical evidence suggests that the above mentioned risk for NSF is very low, if at all present for macrocyclic chelate complex contrast agents. (Young et al., Eur Radiol. 2019). As a consequence, the lower eGFR limit was changed from 50 to 30 mL/min/1.73 m2. As a further safety precaution in the eGFR interval 30 to 50mL/min/1.73m2 half the dose of contrast (macrocyclic chelate complex agents) was employed. 2) There is no literature available showing the time course of very early changes in cardiac dimensions following a ST elevation infarction, but it is likely that the mechanisms driving these changes are in place early after reperfusion. Therefore, it was desirable that the initial measurement of cardiac dimensions was carried out as soon as it was clinically and logistically acceptable for the patients to undergo an MRI investigation, as the result wouls be used as the baseline dimensions. For patients admitted shortly before weekends it was not be possible to perform MRI within 72 hours, but 96 hours were possible. The visit window for MRI baseline examination was therefore changed to within 96 hours. 3) Requirement that physical examination, blood pressure and ECG assessments must be performed “before the MRI examination” was removed to facilitate MRI booking. 4) Additional sites were added to increase recruitment.

    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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