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

Sponsor

Sage Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05619692

Collaborator

(none)

150

Enrollment

Locations

Arms

24.2

Anticipated Duration (Months)

37.5

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Dec 27, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Jan 1, 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.	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.

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.

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

Change from Baseline in the Wechsler Adult Intelligence Scale Fourth Edition-IV (WAIS-IV) Coding Test [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

Percentage of Participants With At least One or More Treatment-emergent Adverse Events (TEAEs) and by Severity [From the inform consent signing up to end of the study (Up to approximately Day 116)]
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.
Number of Participants Who Withdraw Due to Adverse Events (AEs) [From the inform consent signing up to end of the study (Up to approximately Day 116)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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) at Screening.

Exclusion Criteria:

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
Be at risk for suicidal ideation as per Columbia-Suicide Severity Rating Scale (C-SSRS) and/or 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
Supine vital signs outside of the following ranges during Screening (vital sign measurements may be repeated once if initial values exceed these ranges):

Heart rate <50 or >100 bpm ii. Systolic blood pressure <100 or >160 mmHg iii. Diastolic blood pressure <60 or >100 mmHg

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sage Investigational Site	Redlands	California	United States	92374
2	Sage Investigational Site	Sherman Oaks	California	United States	91403
3	Sage Investigational Site	Decatur	Georgia	United States	30030
4	Sage Investigational Site	Brooklyn	New York	United States	11229