A Phase 2, Randomized, Placebo-Controlled Trial to Evaluate the Effects of SAGE-718 in Patients with Alzheimer’s Disease: Study Design (P8-6.010)
Bibliographic record
Abstract
Objective: 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). Background: 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. Design/Methods: 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. Results: Study initiation is planned for late 2022. Conclusions: This randomized, placebo-controlled study is intended to evaluate the effects of SAGE-718 on cognitive performance and assess safety and tolerability in patients with MCI or mild dementia due to AD. Results will further inform the emerging clinical profile of SAGE-718. Disclosure: Dr. Lago has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Lago has stock in Sage Therapeutics. Aaron Koenig has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Johannesen has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Johannesen has stock in Sage Therapeutics . Dr. Johannesen has received research support from National Institute of Health. Dr. Johannesen has received research support from Brain & Behavior Research Foundation . Dr. Johannesen has received research support from VA office of Rehabilitation Research & Development. Dr. Park has nothing to disclose. Sigui Li has received personal compensation for serving as an employee of SAGE Therapeutics. Ms. Freitag has nothing to disclose. Jeffrey Wald has received personal compensation for serving as an employee of Sage Therapeutics. Jeffrey Wald has received stock or an ownership interest from Sage Thereapeutics. Dr. Paumier has nothing to disclose. Michael Quirk has received personal compensation for serving as an employee of Sage Therapeutics. Michael Quirk has received stock or an ownership interest from Sage Therapeutics. Dr. Doherty has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Doherty has received stock or an ownership interest from Sage Therapeutics.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.012 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".