To describe the design of a Phase 2, randomized, double-blind, placebo-controlled study evaluating the effect of SAGE-718 on cognitive performance in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD).

Executive functioning and learning and memory deficits associated with AD occur early in the disease. There is an unmet need for effective treatments that address early cognitive impairment in patients with AD. SAGE-718, an investigational N-methyl-D-aspartate receptor positive allosteric modulator, is being evaluated for the treatment of cognitive impairment due to AD and other neurodegenerative disorders.

Approximately 150 patients will be enrolled across 40 US sites. Eligible patients aged 50-80 years meeting diagnostic criteria for MCI or mild dementia due to AD with a baseline Montreal Cognitive Assessment score of 15-25, a baseline Clinical Dementia Rating score of 0.5-1.0 (inclusive), and a memory box score ≥0.5 will be randomized to receive oral SAGE-718 or placebo for 3 months.

The study includes: a 3-week screening period, 1-week baseline period, 12-week treatment period, and a 4-week follow-up period. During the 12-week treatment period, patients will either receive SAGE-718 (initial dose for 6 weeks followed by a lower dose for the next 6 weeks) or matching placebo.

The primary endpoint is change from baseline to Day 84 in the Coding Test (total correct) from the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV). Secondary endpoints are safety and tolerability, including the number of study withdrawals due to treatment-emergent adverse events and study discontinuations. Other exploratory cognitive and functional endpoints will be evaluated.

Study initiation is planned for late 2022.