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

NCT ID: NCT05619692

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-29
• Study Completion Date: 2024-07-09

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SAGE-718

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.

Group Type: EXPERIMENTAL

SAGE-718

Intervention Type: DRUG

Softgel lipid capsules.

Placebo

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

Group Type: PLACEBO_COMPARATOR

SAGE-718-matching Placebo

Intervention Type: DRUG

Softgel lipid capsules.

Interventions

SAGE-718

Softgel lipid capsules.

Intervention Type: DRUG

SAGE-718-matching Placebo

Softgel lipid capsules.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Meet the following criteria for mild cognitive impairment (MCI) or mild dementia due to Alzheimer's Disease (AD) at Screening:

1. A memory complaint reported by the participant or their study partner

2. A Clinical Dementia Rating (CDR) score of 0.5 to 1.0 (inclusive) with a memory box score ≥ 0.5

3. Essentially preserved activities of daily living, in the opinion of the investigator

4. 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

2. Have a score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) with years of education adjustment at Screening.

Exclusion Criteria

1. 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

2. 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

3. Have any medical or neurological condition (other than AD) that might be contributing to the participant's cognitive impairment or history of cognitive decline

4. Have a history, presence, and/or current evidence of

1. Brain surgery, deep brain stimulation, or any history of hospitalization due to a brain injury

2. Possible or probable cerebral amyloid angiopathy, according to the Boston Criteria

3. Treatment with an anti-amyloid therapy (including biologics) without subsequent MRI demonstrating the absence of amyloid-related imaging abnormalities

4. Seizures or epilepsy, with the exception of childhood febrile seizures

5. 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

6. Have any of the following medical conditions:

1. Any clinically significant finding on 12-lead electrocardiogram (ECG) during Screening in the opinion of the investigator

2. Any clinically significant supine vital signs (heart rate, systolic and diastolic blood pressure) during Screening (note: vital sign measurements may be repeated once)

7. 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

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

9. Is known to be allergic to any of SAGE-718 excipients, including soy lecithin

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Supernus Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sage Investigational Site

Gilbert, Arizona, United States

Sage Investigational Site

Phoenix, Arizona, United States

Sage Investigational Site

Lafayette, California, United States

Sage Investigational Site

Long Beach, California, United States

Sage Investigational Site

Redlands, California, United States

Sage Investigational Site

San Diego, California, United States

Sage Investigational Site

Sherman Oaks, California, United States

Sage Investigational Site

Englewood, Colorado, United States

Sage Investigational Site

Hollywood, Florida, United States

Sage Investigational Site

Jacksonville, Florida, United States

Sage Investigational Site

Miami, Florida, United States

Sage Investigational Site

Palm Beach Gardens, Florida, United States

Sage Investigational Site

Pensacola, Florida, United States

Sage Investigational Site

Tampa, Florida, United States

Sage Investigational Site

Winter Park, Florida, United States

Sage Investigational Site

Decatur, Georgia, United States

Sage Investigational Site

Savannah, Georgia, United States

Sage Investigational Site

Honolulu, Hawaii, United States

Sage Investigational Site

Meridian, Idaho, United States

Sage Investigational Site

Chicago, Illinois, United States

Sage Investigational Site

Charlestown, Massachusetts, United States

Sage Investigational Site

Methuen, Massachusetts, United States

Sage Investigational Site

Chesterfield, Missouri, United States

Sage Investigational Site

Papillion, Nebraska, United States

Sage Investigational Site

Toms River, New Jersey, United States

Sage Investigational Site

Albuquerque, New Mexico, United States

Sage Investigational Site

Brooklyn, New York, United States

Sage Investigational Site

Buffalo, New York, United States

Sage Investigational Site

Staten Island, New York, United States

Sage Investigational Site

Raleigh, North Carolina, United States

Sage Investigational Site

Abington, Pennsylvania, United States

Sage Investigational Site

Memphis, Tennessee, United States

Sage Investigational Site

Nashville, Tennessee, United States

Sage Investigational Site

Austin, Texas, United States

Sage Investigational Site

Dallas, Texas, United States

Sage Investigational Site

Houston, Texas, United States

Sage Investigational Site

Fairfax, Virginia, United States

Sage Investigational Site

Bayamón, , Puerto Rico

Sage Investigational Site

Rio Piedras, , Puerto Rico

Countries

United States; Puerto Rico

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

718-CNA-202

Identifier Type: -

Identifier Source: org_study_id