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    Clinical Trial Results:
    A Phase 3b/4 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants With Alzheimer's Disease

    Summary
    EudraCT number
    		 2022-001671-14
    Trial protocol
    		 DE   ES   FI   PT   BE   IT   PL  
    Global end of trial date
    12 Aug 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Mar 2025
    First version publication date
    16 Mar 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    221AD305
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05310071
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Biogen
    Sponsor organisation address
    225 Binney Street, Cambridge, Massachusetts, United States, 02142
    Public contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Scientific contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.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
    12 Aug 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Aug 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to verify the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score as compared with placebo in participants with early Alzheimer’s disease.
    Protection of trial subjects
    Written informed consent was obtained from each subject’s legally authorized representative or (e.g., legal guardian), as applicable prior to evaluations being performed for eligibility. Subjects or the subject’s legally authorized representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered questions concerning all portions of the conduct of the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Jun 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 21
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Brazil: 2
    Country: Number of subjects enrolled
    Canada: 53
    Country: Number of subjects enrolled
    Finland: 17
    Country: Number of subjects enrolled
    France: 74
    Country: Number of subjects enrolled
    Germany: 59
    Country: Number of subjects enrolled
    Italy: 65
    Country: Number of subjects enrolled
    Japan: 86
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Mexico: 5
    Country: Number of subjects enrolled
    Poland: 110
    Country: Number of subjects enrolled
    Spain: 133
    Country: Number of subjects enrolled
    Sweden: 8
    Country: Number of subjects enrolled
    United Kingdom: 40
    Country: Number of subjects enrolled
    United States: 327
    Worldwide total number of subjects
    1024
    EEA total number of subjects
    471
    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)
    124
    From 65 to 84 years
    894
    85 years and over
    6

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in the study at the investigative sites in Australia, Belgium, Brazil, Canada, Finland, France, Germany, Italy, Japan, Mexico, Poland, South Korea, Spain, Sweden, United Kingdom, and United States from 02 Jun 2022 to 12 Aug 2024.

    Pre-assignment
    Screening details
    		 A total of 1027 participants with Alzheimer's Disease (AD) were enrolled and randomised in this study. Of these, 1024 participants were dosed to receive placebo or aducanumab. None of the participants completed the study due to early termination of the study. [Change in Treatment (CIT)].

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as specified in the treatment arm.

    Arm title
    		 Aducanumab
    Arm description
    		 Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aducanumab
    Investigational medicinal product code
    BIIB037
    Other name
    ADUHELM
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as specified in the treatment arm.

    Number of subjects in period 1
    		Placebo Aducanumab
    Started
    344
    680
    Completed
    0
    0
    Not completed
    344
    680
         Adverse event, serious fatal
    -
    3
         Reason Not Specified
    1
    3
         Withdrawal by Participant - Relocation
    1
    3
         Site Terminated by Sponsor
    -
    2
         Study Terminated by Sponsor
    282
    559
         Failure to Meet Continuation Criteria
    2
    -
         Adverse event, non-fatal
    4
    31
         Failure to Meet Randomization Criteria
    1
    2
         Lack of Efficacy - Based on Participant Perception
    -
    2
         Withdrawal by Participant - Other
    25
    30
         Randomised by Mistake
    -
    1
         Withdrawal by Participant - Concern About Study
    2
    6
         Lost to follow-up
    2
    4
         Withdrawal by Participant - Scheduling Conflicts
    14
    17
         Withdrawal by Participant - Desire for CIT
    8
    17
         Protocol deviation
    2
    -

    Baseline characteristics

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    Subject analysis sets

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.

    Subject analysis set title
    Aducanumab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.

    Subject analysis sets values
    		 Placebo Aducanumab
    Number of subjects
    344
    680
    Age Categorical
    Units: Subjects
    Age continuous
    Full Analysis Set (FAS) included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo).
    Units: years
        arithmetic mean (standard deviation)
    72.4 ( 6.18 )
    72.2 ( 5.81 )
    Gender categorical
    Units: Subjects
        Male
    157
    327
        Female
    187
    353
    Race
    Units: Subjects
        American Indian or Alaska Native
    1
    0
        Asian
    39
    73
        Black or African American
    3
    9
        Native Hawaiian or Other Pacific Islander
    1
    0
        White
    273
    533
        Not Reported Due to Confidentiality Regulations
    26
    57
        Other
    0
    3
        American Indian or Alaska Native and White
    0
    1
        Unknown
    1
    4
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    27
    51
        Not Hispanic or Latino
    293
    585
        Not Reported Due to Confidentiality Regulations
    24
    43
        Unknown
    0
    1

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.

    Reporting group title
    Aducanumab
    Reporting group description
    		 Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.

    Subject analysis set title
    Aducanumab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.

    Primary: Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78

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    End point title
    		 Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78 [1]
    End point description
    The Clinical Dementia Rating Scale integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following the caregiver interview and systematic participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18. Higher scores indicate greater impairment. A positive change from baseline indicates greater impairment. FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analysed' signifies the number of participants available for outcome measure analysis.
    End point type
    Primary
    End point timeframe
    Baseline, Week 78
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistical data were planned for this endpoint.
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    6
    8
    Units: score on a scale
        arithmetic mean (standard deviation)
    0.67 ( 0.408 )
    1.56 ( 1.635 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Week 78

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    End point title
    		 Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Week 78
    End point description
    The iADRS composite captures a decline in both cognition and daily function. It is a simple linear combination of Alzheimer’s disease assessment scale, cognitive subscale (ADAS-Cog13), and Alzheimer’s disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). ADAS-Cog13 scale ranges from 0 to 85 (higher scores indicate worse performance) and ADCS-ADL-MCI scale ranges from 0 to 53 (higher scores indicate greater independent, healthy functioning). Total score for iADRS scale ranges from 0 to 138, where higher scores indicate better performance. A negative change from baseline indicates worse performance. FAS. Here, ‘overall number of participants analysed’ signifies number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    3
    5
    Units: score on a scale
        arithmetic mean (standard deviation)
    -14.667 ( 4.4869 )
    -7.796 ( 6.7805 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Alzheimer’s Disease Cooperative Study for Activities of Daily Living in Mild Cognitive Impairment (ADCS-ADL-MCI) Scale Score at Weeks 78

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    End point title
    		 Change From Baseline in Alzheimer’s Disease Cooperative Study for Activities of Daily Living in Mild Cognitive Impairment (ADCS-ADL-MCI) Scale Score at Weeks 78
    End point description
    The ADCS-ADL-MCI scale consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances.etc.) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the participant’s actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53. Higher scores indicate greater independent, healthy functioning. A positive change from baseline indicates healthy functioning while a negative change from baseline indicates a decline in independent functioning. FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here ‘overall number of participants analysed’ signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    3
    5
    Units: score on a scale
        arithmetic mean (standard deviation)
    -5.0 ( 3.61 )
    -0.4 ( 7.60 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Alzheimer’s Disease Assessment Scale, Cognitive Subscale (ADAS-Cog13) at Week 78

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    End point title
    		 Change From Baseline in Alzheimer’s Disease Assessment Scale, Cognitive Subscale (ADAS-Cog13) at Week 78
    End point description
    ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The cognitive subscale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. Higher scores indicate worse performance. A positive change from baseline indicates decline in cognitive performance. FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, ‘overall number of participants analysed’ signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    3
    5
    Units: score on a scale
        arithmetic mean (standard deviation)
    9.667 ( 0.8844 )
    7.396 ( 2.3262 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Mini-Mental State Examination (MMSE) Scale Score at Week 78

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    End point title
    		 Change From Baseline in Mini-Mental State Examination (MMSE) Scale Score at Week 78
    End point description
    The MMSE scale is a performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30. Higher scores indicate better performance. A negative change from baseline indicates decline in cognitive performance. FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analysed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    3
    5
    Units: score on a scale
        arithmetic mean (standard deviation)
    -6.0 ( 1.00 )
    -1.2 ( 1.48 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Tau PET Signal at Weeks 38

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    End point title
    		 Change From Baseline in Tau PET Signal at Weeks 38
    End point description
    The cerebral tau level was measured by tau PET imaging. Tau PET imaging was conducted using radiotracer. SUVR is a ratio of PET uptake measured in brain region of interest and a disease-free reference region. A higher SUVR is an indication of increased PET radiotracer uptake and worsening disease. FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). 9999 indicates that standard deviation was not estimable as there was only 1 participant analysed. Here, ‘overall number of participants analysed’ signifies the number of participants available for outcome measure analysis. Assessment was planned for Weeks 78 and 104 for this outcome measure but was not performed due to early termination (ET). The analysis was performed at week 38, hence data for week 38 is reported here.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 38
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    1
    0 [2]
    Units: SUVR
    arithmetic mean (standard deviation)
        Total Anterior Cingulate Cortex:Early Termination
    1.130 ( 9999 )
    ( )
        Total Braak 1 and 2: Early Termination
    1.320 ( 9999 )
    ( )
        Total Braak 3 and 4: Early Termination
    1.270 ( 9999 )
    ( )
        Total Braak 5 and 6: Early Termination
    1.150 ( 9999 )
    ( )
        Total Frontal Cortex: Early Termination
    1.190 ( 9999 )
    ( )
        Total Inferior Temporal Cortex:Early Termination
    1.420 ( 9999 )
    ( )
        Total Lateral Temporal Cortex: Early Termination
    1.320 ( 9999 )
    ( )
        Total Medial Temporal Lobe Gray Matter: ET
    1.480 ( 9999 )
    ( )
        Total Occipital Cortex: Early Termination
    1.220 ( 9999 )
    ( )
        Total Parietal Cortex: Early Termination
    1.110 ( 9999 )
    ( )
        Total Post Cingulate Cortex: Early Termination
    1.100 ( 9999 )
    ( )
        Total Temporal Cortex: Early Termination
    1.360 ( 9999 )
    ( )
    Notes
    [2] - ‘Overall number of participants analysed’ = number of participants available for analysis.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Week 78

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    End point title
    		 Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Week 78
    End point description
    The NPI-10 is a questionnaire administered to the informant, designed to obtain information on the presence of neuropsychiatric symptoms and behaviors in a participant with Alzheimer's disease. Ten areas are assessed: delusions, hallucinations, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability and aberrant motor behavior. The NPI total score ranges from 0 to 120. Higher scores indicate greater impairment. A negative change from baseline indicates improvement (symptom reduction). FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analysed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    3
    5
    Units: score on a scale
        arithmetic mean (standard deviation)
    -8.3 ( 16.20 )
    -1.8 ( 6.94 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Week 78

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    End point title
    		 Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Week 78
    End point description
    Amyloid PET scan assesses cerebral amyloid load using radiotracers which is standardized into centiloids. Centiloid values on centiloid scale is based on mean composite standardized uptake value ratio (SUVR). FAS included all randomised participants who had received at least 1 dose of study treatment (aducanumab or placebo). 9999 indicates that standard deviation was not estimable as there was only 1 participant analysed. Here, 'overall number of participants analysed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 104 for this outcome measure, but no assessments were conducted at Week 104 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    0 [3]
    1
    Units: SUVR
        arithmetic mean (standard deviation)
    ( )
    -2.360 ( 9999 )
    Notes
    [3] - ‘Overall number of participants analysed’ = number of participants available for analysis.
    No statistical analyses for this end point

    Secondary: Change From Baseline in CDR-SB Score at Week 106

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    End point title
    		 Change From Baseline in CDR-SB Score at Week 106
    End point description
    The CDR integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic participant examination, the rater assigns a score describing the participant’s current performance level in each of these domains of life functioning. The CDR-SB sums the score for each of the 6 domains and provides a value ranging from 0 to 18. Higher scores indicate greater impairment. Positive change from baseline indicates greater impairment. Assessment was planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 106
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    0 [4]
    0 [5]
    Units: score on a scale
        arithmetic mean (standard deviation)
    ( )
    ( )
    Notes
    [4] - Data is not reported for week 106 as no assessments were conducted due to the ET of the study.
    [5] - Data is not reported for week 106 as no assessments were conducted due to the ET of the study.
    No statistical analyses for this end point

    Secondary: Change From Baseline in Global Statistical Test (GST) Composite Z-Score at Week 78

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    End point title
    		 Change From Baseline in Global Statistical Test (GST) Composite Z-Score at Week 78
    End point description
    GST is composite z-score defined as average of standardized z-scores of CDR-SB,ADASCog13,and ADCS-ADL-MCI.CDR-SB assess 3 cognitive (memory,orientation,judgment/problem-solving)and 3 functional(community affairs,home/hobbies,personal care)domains,with scores based on caregiver interviews and participant exams.“SB”method combines scores across 6 domains,ranging from 0-18(Higher score=greater impairment).ADAS-Cog13 evaluates cognitive tasks like word recall,naming,orientation,and memory,with a total score from 0-85(Higher score=worse performance).ADCS-ADL-MCI rates 17 instrumental tasks(e.g,shopping,preparing meal)and 1 basic task(dressing),with scores from 0-53(Higher score=greater independent,healthy functioning).A positive change from baseline indicates improvement.FAS.Overall number of participants analysed=number of participants available for outcome measure analysis.Assessment was also planned for Week 106, but no assessments were conducted due to early termination.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Aducanumab
    Number of subjects analysed
    3
    4
    Units: z-score
        arithmetic mean (standard deviation)
    0.88 ( 0.116 )
    0.48 ( 0.515 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months)
    Adverse event reporting additional description
    Safety analysis set included all randomised participants who had received at least 1  dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Aducanumab
    Reporting group description
    		 Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo, Q4W, administered as IV infusion.

    Serious adverse events
    		 Aducanumab Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    59 / 681 (8.66%)
    23 / 343 (6.71%)
         number of deaths (all causes)
    3
    0
         number of deaths resulting from adverse events
    3
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer stage i
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural mesothelioma malignant
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive emergency
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 681 (0.29%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (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
    Asthenia
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Investigations
    Blood pressure increased
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Procedural pneumothorax
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    7 / 681 (1.03%)
    3 / 343 (0.87%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    2 / 681 (0.29%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Poisoning
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 681 (0.15%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 681 (0.00%)
    2 / 343 (0.58%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
         subjects affected / exposed
    2 / 681 (0.29%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    3 / 681 (0.44%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological symptom
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic cerebral infarction
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 681 (0.15%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amyloid related imaging abnormality-oedema/effusion
         subjects affected / exposed
    7 / 681 (1.03%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    7 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    2 / 681 (0.29%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    6 / 681 (0.88%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superficial siderosis of central nervous system
         subjects affected / exposed
    2 / 681 (0.29%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 681 (0.44%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 681 (0.15%)
    2 / 343 (0.58%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 681 (0.15%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 681 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Aducanumab Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    359 / 681 (52.72%)
    127 / 343 (37.03%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    55 / 681 (8.08%)
    32 / 343 (9.33%)
         occurrences all number
    66
    36
    Nervous system disorders
    Superficial siderosis of central nervous system
         subjects affected / exposed
    69 / 681 (10.13%)
    5 / 343 (1.46%)
         occurrences all number
    87
    5
    Amyloid related imaging abnormality-oedema/effusion
         subjects affected / exposed
    159 / 681 (23.35%)
    8 / 343 (2.33%)
         occurrences all number
    228
    8
    Dizziness
         subjects affected / exposed
    42 / 681 (6.17%)
    17 / 343 (4.96%)
         occurrences all number
    59
    19
    Headache
         subjects affected / exposed
    81 / 681 (11.89%)
    33 / 343 (9.62%)
         occurrences all number
    123
    48
    Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
         subjects affected / exposed
    167 / 681 (24.52%)
    34 / 343 (9.91%)
         occurrences all number
    238
    40
    Infections and infestations
    Covid-19
         subjects affected / exposed
    49 / 681 (7.20%)
    19 / 343 (5.54%)
         occurrences all number
    50
    21
    Nasopharyngitis
         subjects affected / exposed
    42 / 681 (6.17%)
    26 / 343 (7.58%)
         occurrences all number
    45
    27

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Apr 2022
    Typographical errors were corrected in the Schedule of Assessment.

    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.
    The study was terminated prematurely based on the sponsor's decision.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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