A Study to Assess if BIIB080 Can Change Clinical Dementia Rating-Sum of Boxes Scores, and BIIB080 Safety and Tolerability When Injected Into the Cerebrospinal Fluid of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age

About the study

In this study, researchers will learn more about a study drug called BIIB080. The study will focus on participants with mild cognitive impairment or mild dementia due to AD. The main question researchers are trying to answer is if BIIB080 can slow the worsening of AD more than placebo. It will focus on what dose of BIIB080 slows worsening of AD the most. To help answer this question, researchers will use the Clinical Dementia Rating-Sum of Boxes, also known as the CDR-SB. Clinicians use the CDR-SB to measure several categories of dementia symptoms. The results for each category are added together for a total score. Lower scores are better. Researchers will also learn more about the safety of BIIB080. A description of how the study will be done is given below. Participants will receive either a low dose or high dose of BIIB080 or a placebo as an injection into the fluid around the spinal cord. A placebo looks like the study drug but contains no real medicine. The fluid around the spinal cord is called the cerebrospinal fluid. Participants will be in the study for 105 weeks, or a little over 2 years. This includes the screening and follow-up periods. Participants will be given BIIB080 or placebo once every 12 weeks for a total of 72 weeks. Participants can continue to take certain medications for AD. Participants must be on the same dose of medication for at least 8 weeks before the screening period. After the screening period, most participants will visit the clinic every 6 weeks.

Who can take part

You may be eligible to participate in the study if you meet the following criteria:

INCLUSION CRITERIA

Key Inclusion Criteria:

Must meet all the clinical staging criteria for MCI due to AD (Stage 3) or mild AD dementia (Stage 4) according to the National Institute on Aging at National Institutes of Health and the Alzheimer's Association (NIA-AA) and must have the following at Screening Visit 1:

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index score of ≤85, indicative of objective evidence of memory impairment
CDR global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD dementia
MMSE score of 22 to 30 (inclusive)
CDR Memory Box score of ≥0.5
Evidence of amyloid pathology as measured by positive emission tomography (PET) or cerebrospinal fluid (CSF) sampling

EXCLUSION CRITERIA

Key Exclusion Criteria:

Known allergy to BIIB080 or a history of hypersensitivity to any of the inactive ingredients in the drug product
Previous participation in this study or previous studies with BIIB080
Use of non-disease-modifying AD medications (including but not limited to donepezil, rivastigmine, galantamine, tacrine, and memantine) 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
Prior participation in any active or passive immunotherapy study targeting Aβ, unless documentation of receipt of placebo is available
Prior participation in any passive immunotherapy study targeting tau, unless the last administration occurred 6 months or 5 half-lives, whichever is sooner, prior to Screening or documentation of receipt of placebo is available
Participation in any study involving an investigational treatment targeting tau that is not an immunotherapy, unless documentation of receipt of placebo is available

Participation in a study of any other agent(s) [including gene therapy] not included in exclusion criteria 4, 5, and 6 with a purported disease-modifying effect in AD, unless documentation of receipt of placebo is available

Current use or previous use of medications with a purported disease-modifying effect in AD, outside of investigational studies
Any vaccination given within 10 days prior to Day -1. Coronavirus disease 2019 (COVID-19) vaccinations using RNA or deoxyribonucleic acid (DNA) technology are allowed during the study, as well as other types of immunization/vaccination/booster, except during the 10 days before and after clinic visits
Contraindications to having a brain magnetic resonance imaging (MRI) [e.g., MRI-incompatible pacemaker; MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed]. If the MRI compatibility of implanted devices is unknown, the participant must be excluded from the study
Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 52 weeks prior to the Baseline Visit

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply