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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of Crenezumab (MABT5102A) in Patients with Mild to Moderate Alzheimer's Disease

    Summary
    EudraCT number
    2010-021926-37
    Trial protocol
    GB   DE   ES  
    Global end of trial date
    18 Feb 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    22 Apr 2016
    First version publication date
    07 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ABE4869g
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01343966
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Abby: ABE4869g, GN00761: ABE4869g
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline , F. Hoffmann-La Roche AG, 41 61 6878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline , F. Hoffmann-La Roche AG, 41 61 6878333, global.trial_information@roche.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
    18 Feb 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Feb 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Feb 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives for this trial were to evaluate the efficacy of crenezumab (MABT5102A) compared with placebo, when administered over 68 weeks to patients with mild to moderate Alzheimer's Disease (AD), in inhibiting disease progression using the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog [12-item]) and the Clinical Dementia Rating, Sum-of-Boxes (CDR-SOB); and to evaluate the safety and tolerability of MABT5102A compared with placebo when administered over 68 weeks to patients with mild to moderate AD.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    25 Apr 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    3 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    France: 26
    Country: Number of subjects enrolled
    Canada: 99
    Country: Number of subjects enrolled
    United Kingdom: 37
    Country: Number of subjects enrolled
    Germany: 31
    Country: Number of subjects enrolled
    United States: 232
    Worldwide total number of subjects
    444
    EEA total number of subjects
    113
    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)
    78
    From 65 to 84 years
    366
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Screening involved examination and determination of baseline clinical variables, including diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Subcutaneous injection crenezumab
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    crenezumab
    Investigational medicinal product code
    MABT5102A
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    300 mg crenezumab administered by subcutaneous injection every two weeks

    Arm title
    Subcutaneous injection placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo solution administered by subcutaneous injection every two weeks

    Arm title
    Intravenous infusion crenezumab
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Crenezumab
    Investigational medicinal product code
    MABT5102A
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    15 mg/kg crenezumab administered by intravenous infusion every 4 weeks

    Arm title
    Intravenous infusion placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Placebo administered by intravenous infusion every 4 weeks

    Arm title
    Intravenous infusion crenezumab (safety run-in)
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    crenezumab
    Investigational medicinal product code
    MABT5102A
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    15 mg/kg crenezumab administered by intravenous infusion every 4 weeks

    Number of subjects in period 1
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Intravenous infusion crenezumab (safety run-in)
    Started
    122
    62
    165
    82
    13
    Completed
    88
    45
    126
    62
    11
    Not completed
    34
    17
    39
    20
    2
         Adverse event, serious fatal
    -
    -
    1
    -
    -
         Physician decision
    1
    -
    2
    1
    -
         Consent withdrawn by subject
    -
    -
    -
    -
    1
         Adverse event, non-fatal
    2
    3
    5
    3
    -
         Other
    10
    1
    6
    6
    1
         Withdrawal by participant
    16
    11
    22
    7
    -
         Non-compliance with study drug
    -
    -
    1
    -
    -
         Lost to follow-up
    1
    1
    2
    2
    -
         Protocol deviation
    2
    1
    -
    1
    -
         Noncompliance
    2
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Subcutaneous injection crenezumab
    Reporting group description
    -

    Reporting group title
    Subcutaneous injection placebo
    Reporting group description
    -

    Reporting group title
    Intravenous infusion crenezumab
    Reporting group description
    -

    Reporting group title
    Intravenous infusion placebo
    Reporting group description
    -

    Reporting group title
    Intravenous infusion crenezumab (safety run-in)
    Reporting group description
    -

    Reporting group values
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Intravenous infusion crenezumab (safety run-in) Total
    Number of subjects
    122 62 165 82 13 444
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    71.2 ± 6.3 70.3 ± 7.2 70.9 ± 6.8 69.9 ± 7.2 71.5 ± 6.5 -
    Gender categorical
    Units: Subjects
        Female
    66 30 84 46 8 234
        Male
    56 32 81 36 5 210

    End points

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    End points reporting groups
    Reporting group title
    Subcutaneous injection crenezumab
    Reporting group description
    -

    Reporting group title
    Subcutaneous injection placebo
    Reporting group description
    -

    Reporting group title
    Intravenous infusion crenezumab
    Reporting group description
    -

    Reporting group title
    Intravenous infusion placebo
    Reporting group description
    -

    Reporting group title
    Intravenous infusion crenezumab (safety run-in)
    Reporting group description
    -

    Subject analysis set title
    Mild subgroup subcutaneous injection crenezumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Mild Alzheimer's Disease as defined by Mini-Mental State Examination score 20-26: subcutaneous injection crenezumab

    Subject analysis set title
    Mild subgroup subcutaneous injection Placebo
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Mild Alzheimer's Disease as defined by Mini-Mental State Examination 20-26: subcutaneous injection placebo

    Subject analysis set title
    Mild subgroup intravenous infusion crenezumab
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Mild Alzheimer's Disease as defined by Mini-Mental State Examination score 20-26: intravenous injection crenezumab

    Subject analysis set title
    Mild subgroup intravenous infusion placebo
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Mild Alzheimer's Disease as defined by Mini-Mental State Examination 20-26: intravenous injection placebo

    Primary: Change in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) Score

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    End point title
    Change in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) Score [1]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline to week 73
    Notes
    [1] - 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: This is a subgroup analysis.
    End point values
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Mild subgroup subcutaneous injection crenezumab Mild subgroup subcutaneous injection Placebo Mild subgroup intravenous infusion crenezumab Mild subgroup intravenous infusion placebo
    Number of subjects analysed
    88
    45
    122
    64
    62
    31
    93
    47
    Units: Score
        least squares mean (standard error)
    7.81 ± 0.81
    7.85 ± 1.13
    8.79 ± 0.79
    10.56 ± 1.09
    5.96 ± 0.97
    5.97 ± 1.36
    7.18 ± 0.85
    9.43 ± 1.2
    Statistical analysis title
    Mean difference in MITT1 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between intravenous infusion (IV) of placebo and crenezumab in Mild Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 20-26. MITT1: all mild IV cohort participants.
    Comparison groups
    Mild subgroup intravenous infusion crenezumab v Mild subgroup intravenous infusion placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.128
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    2.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.66
         upper limit
    5.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.47
    Statistical analysis title
    Mean difference in MITT2 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between subcutaneous injection (SC) of placebo and crenezumab in Mild Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 20-26. MITT2: all mild SC cohort participants.
    Comparison groups
    Mild subgroup subcutaneous injection crenezumab v Mild subgroup subcutaneous injection Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.995
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.33
         upper limit
    3.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.67
    Statistical analysis title
    Mean difference in MITT3 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between intravenous infusion (IV) of placebo and crenezumab in Mild-to-Moderate (M2M) Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 18-26. MITT3: all IV cohort participants.
    Comparison groups
    Intravenous infusion crenezumab v Intravenous infusion placebo
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.19
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    1.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.89
         upper limit
    4.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.35
    Statistical analysis title
    Mean difference in MITT4 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between subcutaneous injection (SC) of placebo and crenezumab in Mild-to-Moderate (M2M) Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 18-26. MITT1: all SC cohort participants.
    Comparison groups
    Subcutaneous injection crenezumab v Subcutaneous injection placebo
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.977
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.73
         upper limit
    2.81
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.4

    Primary: Change in Clinical Dementia Rating, Sum of Boxes (CDR-SOB) Score

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    End point title
    Change in Clinical Dementia Rating, Sum of Boxes (CDR-SOB) Score [2]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline to week 73
    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: This is a subgroup analysis.
    End point values
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Mild subgroup subcutaneous injection crenezumab Mild subgroup subcutaneous injection Placebo Mild subgroup intravenous infusion crenezumab Mild subgroup intravenous infusion placebo
    Number of subjects analysed
    88
    47
    126
    67
    62
    33
    96
    48
    Units: Score
        least squares mean (standard error)
    2.01 ± 0.26
    2.7 ± 0.36
    2.49 ± 0.25
    2.57 ± 0.35
    1.47 ± 0.31
    2.18 ± 0.43
    2.21 ± 0.28
    2.18 ± 0.4
    Statistical analysis title
    Mean difference in MITT1 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between intravenous infusion (IV) of placebo and crenezumab in Mild Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 20-26. MITT1: all mild IV cohort participants.
    Comparison groups
    Mild subgroup intravenous infusion placebo v Mild subgroup intravenous infusion crenezumab
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.964
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49
    Statistical analysis title
    Mean difference in MITT2 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between subcutaneous injection (SC) of placebo and crenezumab in Mild Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 20-26. MITT2: all mild SC cohort participants.
    Comparison groups
    Mild subgroup subcutaneous injection Placebo v Mild subgroup subcutaneous injection crenezumab
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.181
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.34
         upper limit
    1.75
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Statistical analysis title
    Mean difference in MITT3 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between intravenous infusion (IV) of placebo and crenezumab in Mild-to-Moderate (M2M) Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 18-26. MITT3: all IV cohort participants.
    Comparison groups
    Intravenous infusion crenezumab v Intravenous infusion placebo
    Number of subjects included in analysis
    193
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.853
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.77
         upper limit
    0.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.43
    Statistical analysis title
    Mean difference in MITT4 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between subcutaneous injection (SC) of placebo and crenezumab in Mild-to-Moderate (M2M) Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 18-26. MITT4: all mild SC cohort participants.
    Comparison groups
    Subcutaneous injection crenezumab v Subcutaneous injection placebo
    Number of subjects included in analysis
    135
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.128
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    0.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.2
         upper limit
    1.57
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45

    Secondary: Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Score

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    End point title
    Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Score [3]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to week 73
    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: This is a subgroup analysis.
    End point values
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Mild subgroup subcutaneous injection crenezumab Mild subgroup subcutaneous injection Placebo Mild subgroup intravenous infusion crenezumab Mild subgroup intravenous infusion placebo
    Number of subjects analysed
    88
    47
    125
    68
    63
    33
    95
    48
    Units: Score
        least squares mean (standard error)
    -7.02 ± 1.13
    -8.43 ± 1.54
    -9.55 ± 1.06
    -9.04 ± 1.44
    -5.04 ± 1.25
    -7.82 ± 1.73
    -8.14 ± 1.12
    -5.96 ± 1.57
    Statistical analysis title
    Mean difference in MITT1 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between intravenous infusion (IV) of placebo and crenezumab in Mild Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 20-26. MITT1: all mild IV cohort participants.
    Comparison groups
    Mild subgroup intravenous infusion crenezumab v Mild subgroup intravenous infusion placebo
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.26
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    2.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.64
         upper limit
    6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.93
    Statistical analysis title
    Mean difference in MITT2 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between subcutaneous injection (SC) of placebo and crenezumab in Mild Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 20-26. MITT1: all mild SC cohort participants.
    Comparison groups
    Mild subgroup subcutaneous injection Placebo v Mild subgroup subcutaneous injection crenezumab
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.196
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.02
         upper limit
    1.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.14
    Statistical analysis title
    Mean difference in MITT3 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between intravenous infusion (IV) of placebo and crenezumab in Mild-to-Moderate (M2M) Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 18-26. MITT3: all IV cohort participants.
    Comparison groups
    Intravenous infusion crenezumab v Intravenous infusion placebo
    Number of subjects included in analysis
    193
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.775
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    0.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.02
         upper limit
    4.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.79
    Statistical analysis title
    Mean difference in MITT4 population
    Statistical analysis description
    Least square means (standard error [SE]) for difference between subcutaneous injection (SC) of placebo and crenezumab in Mild-to-Moderate (M2M) Alzheimer's Disease (AD): Mini Mental State Examination (MMSE) 18-26. MITT4: all mild SC cohort participants.
    Comparison groups
    Subcutaneous injection crenezumab v Subcutaneous injection placebo
    Number of subjects included in analysis
    135
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.461
    Method
    MMRM
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.2
         upper limit
    2.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.91

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    84 weeks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Subcutaneous injection crenezumab
    Reporting group description
    -

    Reporting group title
    Subcutaneous injection placebo
    Reporting group description
    -

    Reporting group title
    Intravenous infusion crenezumab
    Reporting group description
    -

    Reporting group title
    Intravenous infusion placebo
    Reporting group description
    -

    Reporting group title
    Intravenous infusion crenezumab (safety run-in)
    Reporting group description
    -

    Serious adverse events
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Intravenous infusion crenezumab (safety run-in)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 122 (13.11%)
    6 / 62 (9.68%)
    32 / 165 (19.39%)
    11 / 82 (13.41%)
    1 / 13 (7.69%)
         number of deaths (all causes)
    2
    0
    1
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hip arthroplasty
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    2 / 165 (1.21%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    2 / 165 (1.21%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non−cardiac chest pain
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug interaction
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernia obstructive
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory paralysis
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 122 (0.82%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adjustment disorder
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Homicidal ideation
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 122 (0.82%)
    2 / 62 (3.23%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    2 / 165 (1.21%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    2 / 165 (1.21%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia alzheimer’s type
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    2 / 165 (1.21%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    2 / 165 (1.21%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral microhaemorrhage
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural hygroma
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spigelian hernia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    2 / 165 (1.21%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    4 / 165 (2.42%)
    2 / 82 (2.44%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    3 / 82 (3.66%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Subcutaneous injection crenezumab Subcutaneous injection placebo Intravenous infusion crenezumab Intravenous infusion placebo Intravenous infusion crenezumab (safety run-in)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    99 / 122 (81.15%)
    54 / 62 (87.10%)
    119 / 165 (72.12%)
    56 / 82 (68.29%)
    11 / 13 (84.62%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 122 (0.82%)
    4 / 62 (6.45%)
    1 / 165 (0.61%)
    2 / 82 (2.44%)
    0 / 13 (0.00%)
         occurrences all number
    1
    4
    1
    3
    0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 122 (0.82%)
    1 / 62 (1.61%)
    4 / 165 (2.42%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    4
    0
    1
    Vascular disorders
    Haematoma
         subjects affected / exposed
    2 / 122 (1.64%)
    4 / 62 (6.45%)
    3 / 165 (1.82%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    6
    3
    0
    2
    Hot flush
         subjects affected / exposed
    1 / 122 (0.82%)
    2 / 62 (3.23%)
    3 / 165 (1.82%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    3
    3
    0
    1
    Phlebitis
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    1 / 82 (1.22%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    2
    1
    Surgical and medical procedures
    Knee arthroplasty
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    4 / 122 (3.28%)
    7 / 62 (11.29%)
    2 / 165 (1.21%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences all number
    10
    36
    2
    1
    0
    Fatigue
         subjects affected / exposed
    10 / 122 (8.20%)
    5 / 62 (8.06%)
    9 / 165 (5.45%)
    4 / 82 (4.88%)
    0 / 13 (0.00%)
         occurrences all number
    13
    6
    11
    4
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 122 (1.64%)
    4 / 62 (6.45%)
    1 / 165 (0.61%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences all number
    2
    4
    1
    1
    0
    Influenza like illness
         subjects affected / exposed
    1 / 122 (0.82%)
    1 / 62 (1.61%)
    1 / 165 (0.61%)
    1 / 82 (1.22%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    1
    1
    1
    Oedema
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    0
    1
    Feeling cold
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 122 (8.20%)
    2 / 62 (3.23%)
    7 / 165 (4.24%)
    3 / 82 (3.66%)
    1 / 13 (7.69%)
         occurrences all number
    11
    3
    7
    3
    1
    Rhinorrhoea
         subjects affected / exposed
    3 / 122 (2.46%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    3 / 82 (3.66%)
    1 / 13 (7.69%)
         occurrences all number
    3
    1
    0
    3
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    10 / 122 (8.20%)
    3 / 62 (4.84%)
    11 / 165 (6.67%)
    2 / 82 (2.44%)
    0 / 13 (0.00%)
         occurrences all number
    11
    25
    11
    2
    0
    Anxiety
         subjects affected / exposed
    11 / 122 (9.02%)
    6 / 62 (9.68%)
    11 / 165 (6.67%)
    5 / 82 (6.10%)
    0 / 13 (0.00%)
         occurrences all number
    11
    6
    11
    7
    0
    Confusional state
         subjects affected / exposed
    8 / 122 (6.56%)
    3 / 62 (4.84%)
    8 / 165 (4.85%)
    3 / 82 (3.66%)
    0 / 13 (0.00%)
         occurrences all number
    9
    3
    9
    3
    0
    Depression
         subjects affected / exposed
    4 / 122 (3.28%)
    5 / 62 (8.06%)
    8 / 165 (4.85%)
    5 / 82 (6.10%)
    0 / 13 (0.00%)
         occurrences all number
    4
    5
    9
    5
    0
    Insomnia
         subjects affected / exposed
    0 / 122 (0.00%)
    4 / 62 (6.45%)
    8 / 165 (4.85%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences all number
    0
    4
    9
    1
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    5 / 122 (4.10%)
    1 / 62 (1.61%)
    6 / 165 (3.64%)
    7 / 82 (8.54%)
    0 / 13 (0.00%)
         occurrences all number
    5
    1
    6
    8
    0
    Weight increased
         subjects affected / exposed
    4 / 122 (3.28%)
    5 / 62 (8.06%)
    6 / 165 (3.64%)
    2 / 82 (2.44%)
    0 / 13 (0.00%)
         occurrences all number
    4
    6
    6
    2
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    18 / 122 (14.75%)
    4 / 62 (6.45%)
    13 / 165 (7.88%)
    5 / 82 (6.10%)
    1 / 13 (7.69%)
         occurrences all number
    30
    6
    18
    6
    1
    Contusion
         subjects affected / exposed
    11 / 122 (9.02%)
    2 / 62 (3.23%)
    10 / 165 (6.06%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    17
    2
    12
    0
    1
    Laceration
         subjects affected / exposed
    8 / 122 (6.56%)
    2 / 62 (3.23%)
    5 / 165 (3.03%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    12
    2
    5
    0
    0
    Muscle strain
         subjects affected / exposed
    7 / 122 (5.74%)
    0 / 62 (0.00%)
    4 / 165 (2.42%)
    0 / 82 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    8
    0
    4
    0
    0
    Excoriation
         subjects affected / exposed
    4 / 122 (3.28%)
    2 / 62 (3.23%)
    1 / 165 (0.61%)
    2 / 82 (2.44%)
    1 / 13 (7.69%)
         occurrences all number
    4
    2
    1
    2
    1
    Procedural pain
         subjects affected / exposed
    2 / 122 (1.64%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    2
    0
    1
    0
    2
    Bone contusion
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    0
    1
    Hand fracture
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    0
    1
    Corneal abrasion
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    0
    1
    Nervous system disorders
    Cerebral microhaemorrhage
         subjects affected / exposed
    15 / 122 (12.30%)
    10 / 62 (16.13%)
    12 / 165 (7.27%)
    9 / 82 (10.98%)
    0 / 13 (0.00%)
         occurrences all number
    21
    12
    13
    13
    0
    Headache
         subjects affected / exposed
    15 / 122 (12.30%)
    3 / 62 (4.84%)
    15 / 165 (9.09%)
    7 / 82 (8.54%)
    1 / 13 (7.69%)
         occurrences all number
    19
    5
    22
    7
    3
    Dizziness
         subjects affected / exposed
    12 / 122 (9.84%)
    6 / 62 (9.68%)
    10 / 165 (6.06%)
    5 / 82 (6.10%)
    1 / 13 (7.69%)
         occurrences all number
    16
    7
    12
    5
    1
    Hyperreflexia
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    4 / 165 (2.42%)
    1 / 82 (1.22%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    5
    1
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 122 (0.82%)
    3 / 62 (4.84%)
    3 / 165 (1.82%)
    2 / 82 (2.44%)
    1 / 13 (7.69%)
         occurrences all number
    2
    3
    3
    2
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    15 / 122 (12.30%)
    7 / 62 (11.29%)
    12 / 165 (7.27%)
    7 / 82 (8.54%)
    1 / 13 (7.69%)
         occurrences all number
    18
    11
    16
    10
    1
    Nausea
         subjects affected / exposed
    7 / 122 (5.74%)
    5 / 62 (8.06%)
    13 / 165 (7.88%)
    6 / 82 (7.32%)
    0 / 13 (0.00%)
         occurrences all number
    12
    5
    14
    7
    0
    Vomiting
         subjects affected / exposed
    6 / 122 (4.92%)
    3 / 62 (4.84%)
    10 / 165 (6.06%)
    5 / 82 (6.10%)
    0 / 13 (0.00%)
         occurrences all number
    6
    4
    12
    5
    0
    Dental caries
         subjects affected / exposed
    1 / 122 (0.82%)
    1 / 62 (1.61%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    0
    0
    1
    Gastritis
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    0
    1
    Mouth ulceration
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    1 / 82 (1.22%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    1
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    5 / 122 (4.10%)
    5 / 62 (8.06%)
    2 / 165 (1.21%)
    3 / 82 (3.66%)
    0 / 13 (0.00%)
         occurrences all number
    11
    8
    4
    7
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 62 (1.61%)
    2 / 165 (1.21%)
    2 / 82 (2.44%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    2
    2
    1
    Actinic keratosis
         subjects affected / exposed
    1 / 122 (0.82%)
    2 / 62 (3.23%)
    1 / 165 (0.61%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    2
    1
    0
    1
    Rash pruritic
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    3 / 165 (1.82%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    3
    0
    1
    Glycosuria
         subjects affected / exposed
    0 / 122 (0.00%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 122 (4.92%)
    7 / 62 (11.29%)
    9 / 165 (5.45%)
    5 / 82 (6.10%)
    0 / 13 (0.00%)
         occurrences all number
    7
    9
    11
    5
    0
    Arthralgia
         subjects affected / exposed
    9 / 122 (7.38%)
    5 / 62 (8.06%)
    10 / 165 (6.06%)
    2 / 82 (2.44%)
    0 / 13 (0.00%)
         occurrences all number
    9
    5
    10
    2
    0
    Pain in extremity
         subjects affected / exposed
    2 / 122 (1.64%)
    5 / 62 (8.06%)
    4 / 165 (2.42%)
    1 / 82 (1.22%)
    0 / 13 (0.00%)
         occurrences all number
    2
    7
    5
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    21 / 122 (17.21%)
    6 / 62 (9.68%)
    13 / 165 (7.88%)
    8 / 82 (9.76%)
    1 / 13 (7.69%)
         occurrences all number
    28
    6
    20
    16
    1
    Urinary tract infection
         subjects affected / exposed
    16 / 122 (13.11%)
    6 / 62 (9.68%)
    17 / 165 (10.30%)
    10 / 82 (12.20%)
    0 / 13 (0.00%)
         occurrences all number
    19
    8
    20
    11
    0
    Upper respiratory tract infection
         subjects affected / exposed
    16 / 122 (13.11%)
    10 / 62 (16.13%)
    7 / 165 (4.24%)
    4 / 82 (4.88%)
    1 / 13 (7.69%)
         occurrences all number
    18
    11
    9
    4
    1
    Bronchitis
         subjects affected / exposed
    3 / 122 (2.46%)
    2 / 62 (3.23%)
    5 / 165 (3.03%)
    1 / 82 (1.22%)
    1 / 13 (7.69%)
         occurrences all number
    4
    2
    6
    1
    1
    Pneumonia
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    3 / 165 (1.82%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    3
    0
    1
    Diverticulitis
         subjects affected / exposed
    1 / 122 (0.82%)
    0 / 62 (0.00%)
    0 / 165 (0.00%)
    0 / 82 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 122 (0.82%)
    1 / 62 (1.61%)
    1 / 165 (0.61%)
    4 / 82 (4.88%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    1
    4
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Jul 2011
    Increased flexibility in the timing of the first lumbar puncture for CSF sample collection. Change in fasting requirements for laboratory assessments.
    20 Aug 2012
    Eligibility criteria which would allow patients to roll over to an open-label extension study. A requirement for additional safety assessments 8- and 12-weeks after ET assessments was added for those patients who discontinue prematurely from the study. To allow nurse practitioners and equivalently qualified personnel (under applicable law) to review and sign-off on the MMSE and the C-SSRS before the patient is discharged. To allow collection of PK samples 60−90 minutes post infusion.
    04 Jan 2013
    For concomitant medications, intermittent use of benzodiazepines was changed to restrict use within 5 half-lives prior to neurocognitive assessment to ensure complete pharmacological washout.

    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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