A Study to Verify the Clinical Benefit of Aducanumab in P... | NCT05310071

ID	Type	Description	Link
2022-001671-14	EudraCT Number

Label	Type	Description	Intervention Names
Aducanumab	Experimental	Participants will receive aducanumab, up to 10 milligrams per kilogram (mg/kg), monthly (once every four weeks), administered as intravenous (IV) infusion.	Drug: Aducanumab
Placebo	Placebo Comparator	Participants will receive placebo, monthly (once every four weeks), administered as IV infusion.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Aducanumab	Drug	Administered as specified in the treatment arm.	Aducanumab

Measure	Description	Time Frame
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78	The Clinical Dementia Rate 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.	Baseline, Week 78

Measure	Description	Time Frame
Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Weeks 78 and 106	The iADRS composite captures a decline in both cognition and daily function. It is a simple linear combination of the Alzheimer's disease assessment scale, cognitive subscale (ADAS-Cog13), and the Alzheimer's disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). The ADAS-Cog13 scale ranges from 0 to 85 (higher scores indicate worse performance) and the ADCS-ADL-MCI scale ranges from 0 to 53 (higher scores indicate greater independent, healthy functioning). The total score for iADRS scale ranges from 0 to 138, where higher scores indicate better performance.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

The participant must have confirmed amyloid beta pathology by cerebrospinal fluid (CSF) or amyloid PET
Must have a history of subjective memory decline with gradual onset and slow progression over the 6 months before Screening, confirmed by study partner
The participant must have 1 informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the participant (at least 10 hours/week in person or by phone) as to be able to provide accurate information about the participant's cognitive and functional abilities over time
Must meet all of the following clinical criteria for MCI due to Alzheimer's disease or mild Alzheimer's disease according to National Institute on Aging and Alzheimer's Association (NIA-AA) criteria
1. Have an MMSE score between 22 and 30 inclusive
2. Have a CDR memory score >0.5
3. Have a Clinical Dementia Rating Scale Global Score (CDR-GS) of 0.5 or 1.0
4. Have a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score of 85 or lower indicative of objective cognitive impairment
Apart from a clinical diagnosis of early Alzheimer's disease, the participant must be in good health as determined by the Investigator based on medical history and screening assessments
Must consent to apolipoprotein E (ApoE) genotyping. (Note: Participants are not required to be ApoE ε4 carriers)

Key Exclusion Criteria:

Any uncontrolled medical or neurological/neurodegenerative condition (other than Alzheimer's disease) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment
Clinically significant and/or unstable psychiatric illness within 6 months prior to Screening
Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening
History of severe allergic or anaphylactic reactions or of hypersensitivity to any of the inactive ingredients in the drug product
Participation in any study with purported disease-modifying effect in Alzheimer's disease within 12 months prior to Screening unless documentation of receipt of placebo is available
Current use or previous use of medications with a purported disease-modifying effect in Alzheimer's disease, outside of investigational studies
Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participant at higher risk for AEs, or impair the participant's ability to perform cognitive testing or complete study procedures
Use of any investigational drug
Prior exposure to aducanumab either commercially or by participation in a previous study with aducanumab. (Participants are eligible if they did not receive active aducanumab.)
A negative PET scan result with any amyloid-targeting ligand within 12 months prior to Screening

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Gilbert Neurology Partners, PLLC		Gilbert	Arizona	85297	United States
Xenoscience Inc.

ID	Title	Description
FG000	Placebo	Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.
FG001	Aducanumab	Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 15, 2022	Feb 25, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

The Clinical Dementia Rate 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.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 78

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Units	Counts
Participants	OG0006 OG0018

Title

Denominators

Categories

Title	Measurements
	OG0000.67± 0.408 OG0011.56± 1.635

Secondary

Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Weeks 78 and 106

The iADRS composite captures a decline in both cognition and daily function. It is a simple linear combination of the Alzheimer's disease assessment scale, cognitive subscale (ADAS-Cog13), and the Alzheimer's disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). The ADAS-Cog13 scale ranges from 0 to 85 (higher scores indicate worse performance) and the ADCS-ADL-MCI scale ranges from 0 to 53 (higher scores indicate greater independent, healthy functioning). The total score for iADRS scale ranges from 0 to 138, where higher scores indicate better performance.

FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' 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.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 78 and 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

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 and 106

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 randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here 'overall number of participants analyzed' 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.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 78 and 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Secondary

Change From Baseline in Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog13) at Weeks 78 and 106

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.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 78 and 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Secondary

Change From Baseline in Mini-Mental State Examination (MMSE) Scale Score at Weeks 78 and 106

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.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 78 and 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Units

Secondary

Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Weeks 78 and 106

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).

Posted

Mean

Standard Deviation

score on a scale

Baseline, Weeks 78 and 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Secondary

Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Weeks 78 and 104

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 randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Due to the decision of early termination, only one participant had an amyloid scan at week 78 and data was reported below. In addition, the assessment planned for Week 104 was not performed due to early termination.

Posted

Mean

Standard Deviation

SUVR

Baseline, Weeks 78 and 104

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Units	Counts
Participants

Secondary

Change From Baseline in Tau PET Signal at Weeks 78 and 104

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 randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Due to decision of early termination, the Tau PET scan was not performed in any participant at scheduled visits of Weeks 78 and 104.

Posted

Baseline, Weeks 78 and 104

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Units	Counts
Participants

Secondary

Change From Baseline in CDR-SB Score at Week 106

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.

Posted

Baseline, Week 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.
OG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.

Units	Counts
Participants

Secondary

Change From Baseline in Global Statistical Test (GST) Composite Z-Score at Weeks 78 and 106

GST z-score is an average of z-scores of CDR-SB, ADASCog13 and ADCS-ADL-MCI. CDR-SB assesses 3 cognitive (memory,orientation, judgment/problem-solving)and 3 functional(community affairs,home/hobbies,personal care) domains. Sum of Boxes method combines scores across 6 domains, ranging from 0-18(higher scores=greater impairment). ADAS-Cog13 evaluates cognitive tasks like word recall, naming, orientation and memory, with scores from 0-85 (higher scores=worse performance). ADCS-ADL-MCI rates 17 tasks (e.g.,shopping, preparing meal) and 1 basic task(dressing) with scores from 0-53 (higher scores=greater independence/healthy functioning). z-score>0 indicates greater impairment/worse performance for CDR-SB and ADASCog13 scales and improved functioning for ADCS-ADL-MCI. For ADCS-ADL-MCI, z-score were reversed (new reversed value=original value-1) to make interpretation consistent. The GST z-score of 0 indicates population mean and score>0 indicate greater impairment/worse performance.

Posted

Mean

Standard Deviation

z-score

Baseline, Weeks 78 and 106

ID	Title	Description
OG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected343 at risk EG0010 affected681 at risk
Atrial flutter	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Bradycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0011 affected681 at risk
Cardiac arrest	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Coronary artery disease	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Myocardial infarction	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Tachycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Obstructive pancreatitis	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Asthenia	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Fatigue	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Gait disturbance	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Bronchitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Cellulitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Covid-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Erysipelas	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Sepsis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 affected343 at risk EG0011 affected681 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0003 affected343 at risk EG0017 affected681 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0012 affected681 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Poisoning	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Procedural pneumothorax	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Blood pressure increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Troponin increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0013 affected681 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Breast cancer stage i	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Pleural mesothelioma malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0012 affected681 at risk
Amyloid related imaging abnormality-oedema/effusion	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0017 affected681 at risk
Aphasia	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0011 affected681 at risk
Dizziness	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Embolic cerebral infarction	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Headache	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Lacunar stroke	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Neurological symptom	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Normal pressure hydrocephalus	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Seizure	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0013 affected681 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0012 affected681 at risk
Superficial siderosis of central nervous system	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0012 affected681 at risk
Syncope	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0016 affected681 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Tremor	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Completed suicide	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Suicide attempt	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Aortic aneurysm	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0012 affected681 at risk
Hypertensive emergency	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected343 at risk EG0010 affected681 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected343 at risk EG0011 affected681 at risk

ID	Title	Description
BG000	Placebo	Participants received placebo, Q4W, administered as an IV infusion.
BG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as an IV infusion.
BG002	Total	Total of all reporting groups

ID	Term
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo, Q4W, administered as IV infusion.	0	343	23	343	127	343
EG001	Aducanumab	Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.	3	681	59	681	359	681