Trial Outcomes & Findings for A Study to Evaluate the Effects of SAGE-718 in Participants With Mild Cognitive Impairment or Mild Dementia Due to Alzheimer's Disease (AD) (NCT NCT05619692)
NCT ID: NCT05619692
Last Updated: 2025-09-15
Results Overview
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.
COMPLETED
PHASE2
174 participants
Baseline, Day 84
2025-09-15
Participant Flow
Participants were enrolled at 40 investigative sites in the United States and Puerto Rico from 29 November 2022 to 09 July 2024.
174 participants were randomized to receive either SAGE-718 or placebo, of which 4 participants were not treated.
Participant milestones
| Measure |
Placebo
Participants received SAGE-718-matching placebo, orally, once daily (QD), throughout the treatment period up to Day 84.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
87
|
87
|
|
Overall Study
COMPLETED
|
79
|
77
|
|
Overall Study
NOT COMPLETED
|
8
|
10
|
Reasons for withdrawal
| Measure |
Placebo
Participants received SAGE-718-matching placebo, orally, once daily (QD), throughout the treatment period up to Day 84.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
2
|
|
Overall Study
Withdrawal by Participant
|
3
|
4
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Randomized but not treated
|
1
|
3
|
Baseline Characteristics
Number analyzed is the number of participants with data available for analysis.
Baseline characteristics by cohort
| Measure |
Placebo
n=86 Participants
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=84 Participants
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.
|
Total
n=170 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.5 years
STANDARD_DEVIATION 6.80 • n=86 Participants
|
69.6 years
STANDARD_DEVIATION 6.83 • n=84 Participants
|
69.6 years
STANDARD_DEVIATION 6.80 • n=170 Participants
|
|
Sex: Female, Male
Female
|
51 Participants
n=86 Participants
|
52 Participants
n=84 Participants
|
103 Participants
n=170 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=86 Participants
|
32 Participants
n=84 Participants
|
67 Participants
n=170 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=86 Participants
|
17 Participants
n=84 Participants
|
40 Participants
n=170 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
62 Participants
n=86 Participants
|
67 Participants
n=84 Participants
|
129 Participants
n=170 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=86 Participants
|
0 Participants
n=84 Participants
|
1 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · American Indian or Alaska Native
|
1 Participants
n=86 Participants
|
0 Participants
n=84 Participants
|
1 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · Asian
|
5 Participants
n=86 Participants
|
5 Participants
n=84 Participants
|
10 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · Native Hawaiian or Other Pacific Islander
|
2 Participants
n=86 Participants
|
0 Participants
n=84 Participants
|
2 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · Black or African American
|
14 Participants
n=86 Participants
|
6 Participants
n=84 Participants
|
20 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · White
|
62 Participants
n=86 Participants
|
71 Participants
n=84 Participants
|
133 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · More than one race
|
2 Participants
n=86 Participants
|
2 Participants
n=84 Participants
|
4 Participants
n=170 Participants
|
|
Race (NIH/OMB)
Race · Unknown or Not Reported
|
0 Participants
n=86 Participants
|
0 Participants
n=84 Participants
|
0 Participants
n=170 Participants
|
|
Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score
|
43.9 score on a scale
STANDARD_DEVIATION 14.44 • n=86 Participants • Number analyzed is the number of participants with data available for analysis.
|
46.5 score on a scale
STANDARD_DEVIATION 16.04 • n=83 Participants • Number analyzed is the number of participants with data available for analysis.
|
45.2 score on a scale
STANDARD_DEVIATION 15.26 • n=169 Participants • Number analyzed is the number of participants with data available for analysis.
|
PRIMARY outcome
Timeframe: Baseline, Day 84Population: FAS included all participants in the Safety Set (which included all participants who were administered at least one dose of the IP) who had baseline and at least 1 post-baseline efficacy evaluation. Overall number of participants analyzed indicates number of participants with data available for analysis at a specified timepoint.
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.
Outcome measures
| Measure |
Placebo
n=80 Participants
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=76 Participants
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.
|
|---|---|---|
|
Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score
|
3.8 score on a scale
Standard Error 0.77
|
5.3 score on a scale
Standard Error 0.79
|
SECONDARY outcome
Timeframe: Up to Day 112Population: The Safety Set included all participants who were administered at least one dose of the IP.
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.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=84 Participants
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.
|
|---|---|---|
|
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
|
50 Participants
|
42 Participants
|
SECONDARY outcome
Timeframe: Up to Day 112Population: The Safety Set included all participants who were administered at least one dose of the IP.
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.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=84 Participants
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.
|
|---|---|---|
|
Number of Participants With at Least One TEAE by Severity
Moderate
|
19 Participants
|
20 Participants
|
|
Number of Participants With at Least One TEAE by Severity
Severe
|
2 Participants
|
2 Participants
|
|
Number of Participants With at Least One TEAE by Severity
Mild
|
29 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: Up to Day 112Population: The Safety Set included all participants who were administered at least one dose of the IP.
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.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=84 Participants
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.
|
|---|---|---|
|
Number of Participants Who Withdrew From Study Due to TEAEs
|
2 Participants
|
2 Participants
|
Adverse Events
Placebo
SAGE-718
Serious adverse events
| Measure |
Placebo
n=86 participants at risk
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=84 participants at risk
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.
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer recurrent
|
1.2%
1/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
0.00%
0/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
1.2%
1/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
0.00%
0/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the tongue
|
1.2%
1/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
0.00%
0/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Injury, poisoning and procedural complications
Fall
|
1.2%
1/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
1.2%
1/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
0.00%
0/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Nervous system disorders
Carotid artery stenosis
|
0.00%
0/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Psychiatric disorders
Completed suicide
|
1.2%
1/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
0.00%
0/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
Other adverse events
| Measure |
Placebo
n=86 participants at risk
Participants received SAGE-718-matching placebo, orally, QD, throughout the treatment period up to Day 84.
|
SAGE-718
n=84 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Headache
|
10.5%
9/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
8.3%
7/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
5.8%
5/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
2.4%
2/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
|
Nervous system disorders
Dizziness
|
5.8%
5/86 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
1.2%
1/84 • Up to Day 112
The Safety Set included all participants who were administered at least one dose of the IP.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
- Publication restrictions are in place
Restriction type: OTHER