A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants with Huntington’s Disease

Inclusion Criteria: 1. Meet all the following criteria for HD at Screening (Days -28 to -2): 1. Genetically confirmed disease with huntingtin gene CAG expansion ≥36. 2. At screening, UHDRS-Total Functional Capacity (TFC) score \>6 and \<13 suggesting no more than a moderate level of functional impairment. 3. No features of juvenile HD. 2. Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening indicating the presence of cognitive impairment. 3. Be willing to invite a study partner, if available, who is reliable, competent, and at least 18 years of age to participate in the study. 4. Be ambulatory (use of assistance devices such as a walker or cane is acceptable, as is occasional use of wheelchair, as judged by the investigator. Individuals requiring a wheelchair on a regular basis are excluded), able to travel to the study center, and, as judged by the investigator, is likely to be able to continue to travel to the study center to complete study visits for the duration of the study. 5. Completion of Huntington's Disease Cognitive Assessment Battery (HD-CAB) Trail Making-B Test in less than 240 seconds at Screening (Days -28 to -2).

Exclusion Criteria: 1. Have participated in a previous clinical study of SAGE-718, have previous exposure to gene therapy, have participated in any HD investigational drug, biologic, or device trial within 180 days, or a non-HD drug, biologic, or device trial within 30- days or 5-half-lives (whichever is longer). (Note: Participants with confirmation of enrollment in the placebo arm of these trials would not be excluded.) 2. Have a diagnosis of an ongoing neurodegenerative condition other than HD, including but not limited to Alzheimer's Disease, vascular dementia, dementia with Lewy bodies, or Parkinson's Disease.