A Study to Evaluate the Effects of SAGE-718 in Participan... | NCT05619692

Status Module

Label	Type	Description	Intervention Names
SAGE-718	Experimental	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.	Drug: SAGE-718
Placebo	Placebo Comparator	Participants will receive SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.	Drug: SAGE-718-matching Placebo

Name	Type	Description	Arm Group Labels	Other Names
SAGE-718	Drug	Softgel lipid capsules.	SAGE-718
SAGE-718-matching Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score	The WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with real-world functional outcomes (e.g., the ability to accomplish everyday tasks) and recovery from functional disability, used to assess processing speed. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 120-second time limit. Higher scores indicate better processing speed. Positive change from baseline indicates better processing speed. Least Squares (LS) Means were calculated using a mixed-effects model for repeated measures (MMRM) approach.	Baseline, Day 84

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Facility	Status	City	State	ZIP	Country	Contacts
Sage Investigational Site		Gilbert	Arizona	85297	United States
Sage Investigational Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received SAGE-718-matching placebo, orally, once daily (QD), throughout the treatment period up to Day 84.
FG001	SAGE-718	Participants received SAGE-718, 1.2 milligrams (mg), orally, 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 22, 2023	Jun 3, 2025

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0003.8± 0.77 OG0015.3± 0.79

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MRMM		0.1642	The p-value was obtained using MMRM model which included treatment, visit, treatment-by-visit interaction as categorical covariates, and WAIS-IV at baseline as continuous covariates.	Difference in LS Means	1.5	Standard Error of the Mean	1.11	2-Sided	95	-0.64	3.73			Difference was calculated as SAGE-718 - placebo.		Superiority

Secondary

Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

The Safety Set included all participants who were administered at least one dose of the IP.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Placebo	Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
OG001	SAGE-718	Participants received SAGE-718, 1.2 mg, orally, 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.

Secondary

Number of Participants With at Least One TEAE by Severity

A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Severity was assessed as:

Mild: symptoms barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptoms
Moderate: symptoms of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptoms may be needed
Severe: symptoms cause severe discomfort; symptoms cause incapacitation or significant impact on participant's daily life; severity may cause cessation of treatment with IP; treatment for symptoms may be given and/or participant hospitalized.

Participant with multiple instances of events is counted only once using maximum intensity.

The Safety Set included all participants who were administered at least one dose of the IP.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Placebo	Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
OG001	SAGE-718	Participants received SAGE-718, 1.2 mg, orally, 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.

Secondary

Number of Participants Who Withdrew From Study Due to TEAEs

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE on or after the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

The Safety Set included all participants who were administered at least one dose of the IP.

Posted

Count of Participants

Participants

Up to Day 112

ID	Title	Description
OG000	Placebo	Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
OG001	SAGE-718	Participants received SAGE-718, 1.2 mg, orally, 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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Prostate cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 affected86 at risk EG0010 affected84 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 affected86 at risk EG0010 affected84 at risk
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 affected86 at risk EG0010 affected84 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 affected86 at risk EG0011 affected84 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 affected86 at risk EG0010 affected84 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 affected86 at risk EG0011 affected84 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 affected86 at risk EG0011 affected84 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected86 at risk EG0011 affected84 at risk
Cellulitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected86 at risk EG0011 affected84 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected86 at risk EG0011 affected84 at risk
Completed suicide	Psychiatric disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected86 at risk EG0010 affected84 at risk

ID	Term
D060825	Cognitive Dysfunction
D000544	Alzheimer Disease

ID	Term
D003072	Cognition Disorders
D019965	Neurocognitive Disorders
D001523	Mental Disorders
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases

ID	Title	Description
BG000	Placebo	Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
BG001	SAGE-718	Participants received SAGE-718, 1.2 mg, orally, 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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.	1	86	5	86	17	86
EG001	SAGE-718	Participants received SAGE-718, 1.2 mg, orally, 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.	0	84	4	84	10	84

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0009 affected86 at risk EG0017 affected84 at risk
Upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0005 affected86 at risk EG0012 affected84 at risk
Dizziness	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0005 affected86 at risk EG0011 affected84 at risk