Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability, and Efficacy of BIIB092 in Subjects With Mild Cognitive Impairment Due to Alzheimer’s Disease or With Mild Alzheimer’s Disease

– Must have a gradual and progressive change in memory function over more than 6 months.

– Must meet all of the clinical criteria for mild cognitive impairment (MCI) due to
Alzheimer’s disease (AD) or mild AD and must have

– Objective evidence of cognitive impairment at Screening

– Clinical Dementia Rating Scale (CDR) global score of 0.5 for MCI due to AD or 0.5 or 1
for mild AD

– Mini-Mental State Examination (MMSE) score of 22 to 30 (inclusive)

– CDR Memory Box score of ≥0.5

– Must consent to apolipoprotein E (ApoE) genotyping

– Must have 1 informant/study partner

– Must have amyloid beta positivity confirmed at Screening

Key Exclusion Criteria:

– Any medical or neurological/neurodegenerative condition (other than AD) that, in the
opinion of the Investigator, might be a contributing cause to the participant’s
cognitive impairment or could lead to discontinuation, lack of compliance,
interference with study assessments, or safety concerns

– Clinically significant, unstable psychiatric illness

– Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of
consciousness in the past 1 year

– Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities

– History of unstable angina, myocardial infarction, chronic heart failure or clinically
significant conduction abnormalities within 1 year prior to Screening Visit 1

– Indication of impaired renal or liver function

– Alcohol or substance abuse in past 1 year

– Clinically significant systemic illness or serious infection within 30 days prior to
or during the screening period

– Use of allowed medications for chronic conditions at doses that have not been stable
for at least 4 weeks prior to Screening Visit 1 and during the screening period up to
Study Day 1, or use of AD medications at doses that have not been stable for at least
8 weeks prior to Screening Visit 1 and during the screening period up to Study Day 1.

– Use of any medications that, in the opinion of the Investigator, may contribute to
cognitive impairment, put the participants at higher risk for adverse events (AEs), or
impair the participant’s ability to perform cognitive testing or complete study
procedures.

– Contraindications to study procedures

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply