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

Sage Therapeutics

Status and phase: Completed; Phase 2

Conditions: Alzheimer's Disease; Mild Dementia; Mild Cognitive Impairment

Treatments: Drug: SAGE-718; Drug: SAGE-718-matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05619692

718-CNA-202

Details and patient eligibility

About

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

Enrollment: 174 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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174 participants in 2 patient groups, including a placebo group

SAGE-718

Experimental group

Description:

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 \[±7 days\].

Treatment:

Drug: SAGE-718

Placebo

Placebo Comparator group

Description:

Participants will receive placebo-matching capsule once daily orally throughout the treatment period for up to Day 84.

Treatment:

Drug: SAGE-718-matching Placebo