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 (ENVISION)

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.

Aducanumab is a human monoclonal antibody that is directed against the amyloid-β protein. Aducanumab was approved by the US FDA as a treatment for Alzheimer’s disease under the accelerated approval pathway based on aducanumab’s reduction in brain amyloid coupled with evidence that reduction in brain amyloid is reasonably likely to predict clinical benefit in Alzheimer’s disease. This is a Phase 3b/4, 2-year, placebo-controlled study designed to verify the clinical benefit of aducanumab compared to placebo in participants aged 60 to 85 with early Alzheimer’s disease.

Participants will be randomly assigned in a 2:1 ratio to receive up to 10 mg/kg of aducanumab or placebo administered intravenously every 4 weeks for up to 24 months (67% chance of receiving active study drug). All participants will undergo either a 18F-Florbetapir PET scan or a lumbar puncture to confirm the presence of cerebral Aβ accumulation, as well as 6 MRI scans. Participants will have the option of participating in amyloid (18F-Florbetapir) and/or tau (18F-MK6240) PET substudies, as well as a cerebrospinal fluid (CSF) lumbar puncture substudy. Permits concurrent treatment with cholinesterase inhibitors and memantine.

For more information please go to the Alzheimer's Disease Research Unit (ADRU) website for each of our studies: https://medicine.yale.edu/psychiatry/alzheimers/

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