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

• ClinicalTrials.gov Identifier: NCT05619692
• Recruitment Status: Active, not recruiting
• First Posted: November 17, 2022
• Last Update Posted: April 22, 2024
• Sponsor: Sage Therapeutics
• Information provided by (Responsible Party): Sage Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mild Cognitive Impairment; Mild Dementia; Alzheimer's Disease	Drug: SAGE-718; Drug: SAGE-718-matching Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease
• Actual Study Start Date: December 27, 2022
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: January 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAGE-718; Participants will receive 1.2mg of SAGE-718 orally once daily for the first 6 weeks Days 1 to 42 [±2 days], followed by 0.9 mg of SAGE-718 for the remainder of the Treatment period up to Day 84 Visit [±7 days].	Drug: SAGE-718; Softgel lipid capsules.
Placebo Comparator: Placebo; Participants will receive placebo-matching capsule once daily orally throughout the treatment period for up to Day 84.	Drug: SAGE-718-matching Placebo; Softgel lipid capsules.

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in the Wechsler Adult Intelligence Scale Fourth Edition-IV (WAIS-IV) Coding Test [ Time Frame: Baseline to Day 84 ]
   The WAIS-IV Coding Test is a valid and sensitive measure of cognitive dysfunction. Administration of the WAIS-IV Coding Test will use the traditional paper-and-pen format, in which the participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The score will be based on the total number of codes correctly completed over a 120-second time limit.

Secondary Outcome Measures :

1. Percentage of Participants With At least One or More Treatment-emergent Adverse Events (TEAEs) and by Severity [ Time Frame: From the inform consent signing up to end of the study (Up to approximately Day 119) ]
   An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.
2. Number of Participants Who Withdraw Due to Adverse Events (AEs) [ Time Frame: From the inform consent signing up to end of the study (Up to approximately Day 119) ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Sage Investigational Site

Gilbert, Arizona, United States, 85297

Sage Investigational Site

Phoenix, Arizona, United States, 85297

United States, California

Sage Investigational Site

Lafayette, California, United States, 94549

Sage Investigational Site

Long Beach, California, United States, 90808

Sage Investigational Site

Redlands, California, United States, 92374

Sage Investigational Site

San Diego, California, United States, 92123

Sage Investigational Site

Sherman Oaks, California, United States, 91403

United States, Colorado

Sage Investigational Site

Englewood, Colorado, United States, 80120

United States, Florida

Sage Investigational Site

Hollywood, Florida, United States, 33024

Sage Investigational Site

Jacksonville, Florida, United States, 32256

Sage Investigational Site

Miami, Florida, United States, 33155

Sage Investigational Site

Palm Beach Gardens, Florida, United States, 33410

Sage Investigational Site

Pensacola, Florida, United States, 32504

Sage Investigational Site

Tampa, Florida, United States, 33609

Sage Investigational Site

Winter Park, Florida, United States, 32789

United States, Georgia

Sage Investigational Site

Decatur, Georgia, United States, 30030

Sage Investigational Site

Savannah, Georgia, United States, 31404

United States, Idaho

Sage Investigational Site

Meridian, Idaho, United States, 83642

United States, Illinois

Sage Investigational Site

Chicago, Illinois, United States, 60640

United States, Massachusetts

Sage Investigational Site

Charlestown, Massachusetts, United States, 02129

Sage Investigational Site

Methuen, Massachusetts, United States, 01844

United States, Missouri

Sage Investigational Site

Chesterfield, Missouri, United States, 63005

United States, Nebraska

Sage Investigational Site

Papillion, Nebraska, United States, 68046

United States, New Jersey

Sage Investigational Site

Toms River, New Jersey, United States, 08755

United States, New Mexico

Sage Investigational Site

Albuquerque, New Mexico, United States, 87109

United States, New York

Sage Investigational Site

Brooklyn, New York, United States, 11229

Sage Investigational Site

Buffalo, New York, United States, 14203

Sage Investigational Site

Staten Island, New York, United States, 10312

United States, North Carolina

Sage Investigational Site

Raleigh, North Carolina, United States, 27607

United States, Pennsylvania

Sage Investigational Site

Abington, Pennsylvania, United States, 19001

United States, Tennessee

Sage Investigational Site

Memphis, Tennessee, United States, 38119

United States, Texas

Sage Investigational Site

Austin, Texas, United States, 78731

Sage Investigational Site

Dallas, Texas, United States, 75231

Sage Investigational Site

Houston, Texas, United States, 77030

United States, Virginia

Sage Investigational Site

Fairfax, Virginia, United States, 22031

Puerto Rico

Sage Investigational Site

Bayamon, Puerto Rico, 00961

Sponsors and Collaborators

Sage Therapeutics

More Information

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT05619692
• Other Study ID Numbers: 718-CNA-202
• First Posted: November 17, 2022
• Last Update Posted: April 22, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sage Therapeutics:

SAGE-718; Cognitive dysfunction; NMDA

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Cognitive Dysfunction; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders