Clinical trial NCT05619692: A Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Mild Dementia
Alzheimer's Disease
Keywords: SAGE-718
Cognitive dysfunction
N-methyl-D-aspartate (NMDA)
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-11-17
Enrollment: 174
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score
timeFrame: Baseline, Day 84
Secondary outcomes:
measure: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to Day 112
measure: Number of Participants With at Least One TEAE by Severity
timeFrame: Up to Day 112
measure: Number of Participants Who Withdrew From Study Due to TEAEs
timeFrame: Up to Day 112
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Sage Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Sage Investigational Site
state: Arizona
city: Lafayette
country: United States
facility: Sage Investigational Site
state: California
city: Long Beach
country: United States
facility: Sage Investigational Site
state: California
city: Redlands
country: United States
facility: Sage Investigational Site
state: California
city: San Diego
country: United States
facility: Sage Investigational Site
state: California
city: Sherman Oaks
country: United States
facility: Sage Investigational Site
state: California
city: Englewood
country: United States
facility: Sage Investigational Site
state: Colorado
city: Hollywood
country: United States
facility: Sage Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Palm Beach Gardens
country: United States
facility: Sage Investigational Site
state: Florida
city: Pensacola
country: United States
facility: Sage Investigational Site
state: Florida
city: Tampa
country: United States
facility: Sage Investigational Site
state: Florida
city: Winter Park
country: United States
facility: Sage Investigational Site
state: Florida
city: Decatur
country: United States
facility: Sage Investigational Site
state: Georgia
city: Savannah
country: United States
facility: Sage Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Sage Investigational Site
state: Hawaii
city: Meridian
country: United States
facility: Sage Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Sage Investigational Site
state: Illinois
city: Charlestown
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Methuen
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Chesterfield
country: United States
facility: Sage Investigational Site
state: Missouri
city: Papillion
country: United States
facility: Sage Investigational Site
state: Nebraska
city: Toms River
country: United States
facility: Sage Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: Sage Investigational Site
state: New Mexico
city: Brooklyn
country: United States
facility: Sage Investigational Site
state: New York
city: Buffalo
country: United States
facility: Sage Investigational Site
state: New York
city: Staten Island
country: United States
facility: Sage Investigational Site
state: New York
city: Raleigh
country: United States
facility: Sage Investigational Site
state: North Carolina
city: Abington
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Memphis
country: United States
facility: Sage Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Sage Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Sage Investigational Site
state: Texas
city: Dallas
country: United States
facility: Sage Investigational Site
state: Texas
city: Houston
country: United States
facility: Sage Investigational Site
state: Texas
city: Fairfax
country: United States
facility: Sage Investigational Site
state: Virginia
city: Bayamon
country: Puerto Rico
facility: Sage Investigational Site
city: Rio Piedras
country: Puerto Rico
facility: Sage Investigational Site
Study officials:
References: