A Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD)

Prior treatment

• Have participated in a previous clinical study of SAGE-718, have participated in a previous gene therapy study, or have received study treatment in any other drug, biologic, or device trial within 30 days or 5 half-lives (whichever is longer), unless the participant participated solely in the placebo arm of the study. Additionally, participants who have received treatment with antisense oligonucleotides (ASO) will be excluded
• Have a history, presence, and/or current evidence of
  • Brain surgery, deep brain stimulation, or any history of hospitalization due to a brain injury
  • Possible or probable cerebral amyloid angiopathy, according to the Boston Criteria
  • Treatment with an anti-amyloid therapy (including biologics) without subsequent MRI demonstrating the absence of amyloid-related imaging abnormalities
  • Seizures or epilepsy, with the exception of childhood febrile seizures

Other illness

• Have a condition that precludes undergoing an MRI, in accordance with standard operating procedures at the imaging facility (eg, ferromagnetic metal in the body, claustrophobia), in a participant requiring MRI during Screening
• Have any medical or neurological condition (other than AD) that might be contributing to the participant's cognitive impairment or history of cognitive decline
• Participants has a history of suicidal behavior within 2 years or answers "YES" to Questions 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or at Day 1 or is currently at risk of suicide in the opinion of the investigator
• Have any of the following medical conditions:
  • Any clinically significant finding on 12-lead electrocardiogram (ECG) during Screening in the opinion of the investigator
  • Any clinically significant supine vital signs (heart rate, systolic and diastolic blood pressure) during Screening (note: vital sign measurements may be repeated once)
• Have a history, presence, and/or current evidence of serologic positive results for human immunodeficiency virus (HIV)-1 or HIV-2, or hepatitis B or C
• Is known to be allergic to any of SAGE-718 excipients, including soy lecithin

Other

• Have a positive pregnancy test, or be lactating, or intend to breastfeed during the study

• Meet the following criteria for mild cognitive impairment (MCI) or mild dementia due to Alzheimer's Disease (AD) at Screening:
  • A memory complaint reported by the participant or their study partner
  • A Clinical Dementia Rating (CDR) score of 0.5 to 1.0 (inclusive) with a memory box score ≥ 0.5
  • Essentially preserved activities of daily living, in the opinion of the investigator
  • Brain Magnetic Resonance Imaging (MRI) report, obtained within the 2 years preceding the Baseline Period, that is consistent with the diagnosis of AD with no clinically significant findings of non-AD pathology that could account for the observed cognitive impairment
• Have a score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) with years of education adjustment at Screening.