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

NCT05619692 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 718-CNA-202
• Study Type: interventional
• Target: 174
• Locations: 2 countries
• Sites: 39

Brief Summary

The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance in participants with Alzheimer's Disease.

Conditions

Mild Cognitive Impairment; Mild Dementia; Alzheimer's Disease

Keywords

SAGE-718; Cognitive dysfunction; N-methyl-D-aspartate (NMDA)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score

  The WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with real-world functional outcomes (e.g., the ability to accomplish everyday tasks) and recovery from functional disability, used to assess processing speed. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 120-second time limit. Higher scores indicate better processing speed. Positive change from baseline indicates better processing speed. Least Squares (LS) Means were calculated using a mixed-effects model for repeated measures (MMRM) approach.

  Baseline, Day 84

Secondary Outcomes (3)

• Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

  Up to Day 112

• Number of Participants With at Least One TEAE by Severity

  Up to Day 112

• Number of Participants Who Withdrew From Study Due to TEAEs

  Up to Day 112

Study Arms (2)

SAGE-718

EXPERIMENTAL

Participants will receive SAGE-718, 1.2 milligrams (mg), orally, once daily (QD) for the first 6 weeks (Days 1 to 42), followed by 0.9 mg of SAGE-718 for the remainder of the treatment period up to Day 84.

Drug: SAGE-718

Placebo

PLACEBO COMPARATOR

Participants will receive SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.

Drug: SAGE-718-matching Placebo

Interventions

SAGE-718 DRUG

Softgel lipid capsules.

SAGE-718

SAGE-718-matching Placebo DRUG

Softgel lipid capsules.

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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
• 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
• 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
• Have a positive pregnancy test, or be lactating, or intend to breastfeed during the study
• Is known to be allergic to any of SAGE-718 excipients, including soy lecithin

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (39)

Sage Investigational Site

Gilbert, Arizona, 85297, United States

Location

Sage Investigational Site

Phoenix, Arizona, 85297, United States

Location

Sage Investigational Site

Lafayette, California, 94549, United States

Location

Sage Investigational Site

Long Beach, California, 90808, United States

Location

Sage Investigational Site

Redlands, California, 92374, United States

Location

Sage Investigational Site

San Diego, California, 92123, United States

Location

Sage Investigational Site

Sherman Oaks, California, 91403, United States

Location

Sage Investigational Site

Englewood, Colorado, 80120, United States

Location

Sage Investigational Site

Hollywood, Florida, 33024, United States

Location

Sage Investigational Site

Jacksonville, Florida, 32256, United States

Location

Sage Investigational Site

Miami, Florida, 33155, United States

Location

Sage Investigational Site

Palm Beach Gardens, Florida, 33410, United States

Location

Sage Investigational Site

Pensacola, Florida, 32504, United States

Location

Sage Investigational Site

Tampa, Florida, 33609, United States

Location

Sage Investigational Site

Winter Park, Florida, 32789, United States

Location

Sage Investigational Site

Decatur, Georgia, 30030, United States

Location

Sage Investigational Site

Savannah, Georgia, 31404, United States

Location

Sage Investigational Site

Honolulu, Hawaii, 96817, United States

Location

Sage Investigational Site

Meridian, Idaho, 83642, United States

Location

Sage Investigational Site

Chicago, Illinois, 60640, United States

Location

Sage Investigational Site

Charlestown, Massachusetts, 02129, United States

Location

Sage Investigational Site

Methuen, Massachusetts, 01844, United States

Location

Sage Investigational Site

Chesterfield, Missouri, 63005, United States

Location

Sage Investigational Site

Papillion, Nebraska, 68046, United States

Location

Sage Investigational Site

Toms River, New Jersey, 08755, United States

Location

Sage Investigational Site

Albuquerque, New Mexico, 87109, United States

Location

Sage Investigational Site

Brooklyn, New York, 11229, United States

Location

Sage Investigational Site

Buffalo, New York, 14203, United States

Location

Sage Investigational Site

Staten Island, New York, 10312, United States

Location

Sage Investigational Site

Raleigh, North Carolina, 27607, United States

Location

Sage Investigational Site

Abington, Pennsylvania, 19001, United States

Location

Sage Investigational Site

Memphis, Tennessee, 38119, United States

Location

Sage Investigational Site

Nashville, Tennessee, 37212, United States

Location

Sage Investigational Site

Austin, Texas, 78731, United States

Location

Sage Investigational Site

Dallas, Texas, 75231, United States

Location

Sage Investigational Site

Houston, Texas, 77030, United States

Location

Sage Investigational Site

Fairfax, Virginia, 22031, United States

Location

Sage Investigational Site

Bayamón, 00961, Puerto Rico

Location

Sage Investigational Site

Rio Piedras, 00935, Puerto Rico

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Amy Bullock
• Organization: Sage Therapeutics

amy.bullock@sagerx.com

617-949-5151

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 17, 2022
• Study Start: November 29, 2022
• Primary Completion: June 5, 2024
• Study Completion: July 9, 2024
• Last Updated: September 15, 2025
• Results First Posted: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (37); PR (2)