Trial Outcomes & Findings for A Study to Evaluate the Effects of SAGE-718 in Participants With Parkinson's Disease Cognitive Impairment (NCT NCT05318937)

Last Updated: 2025-09-12

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

86 participants

Primary outcome timeframe

Baseline, Day 42

Results posted on

2025-09-12

Participant Flow

Participants were enrolled at 38 investigative sites in the United States from 06 June 2022 to 23 February 2024.

A total of 190 participants were screened, of which 86 participants were randomized to receive either SAGE-718 or placebo.

Participant milestones

Participant milestones
Measure	Placebo Participants received SAGE-718-matching placebo, oral capsules, once daily (QD), in the morning for 42 days.	SAGE-718 Participants received SAGE-718, 1.2 milligrams (mg), oral capsules, QD in the morning for 42 days.
Overall Study STARTED	43	43
Overall Study COMPLETED	42	39
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received SAGE-718-matching placebo, oral capsules, once daily (QD), in the morning for 42 days.	SAGE-718 Participants received SAGE-718, 1.2 milligrams (mg), oral capsules, QD in the morning for 42 days.
Overall Study Non-Compliance with Study Drug	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	2
Overall Study Protocol Violation	0	1

Baseline Characteristics

Number analyzed is the number of participants with data available for analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=43 Participants Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=43 Participants Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.	Total n=86 Participants Total of all reporting groups
Age, Continuous	68.5 years STANDARD_DEVIATION 4.76 • n=43 Participants	68.2 years STANDARD_DEVIATION 6.37 • n=43 Participants	68.3 years STANDARD_DEVIATION 5.59 • n=86 Participants
Sex: Female, Male Female	9 Participants n=43 Participants	14 Participants n=43 Participants	23 Participants n=86 Participants
Sex: Female, Male Male	34 Participants n=43 Participants	29 Participants n=43 Participants	63 Participants n=86 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=43 Participants	6 Participants n=43 Participants	17 Participants n=86 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=43 Participants	37 Participants n=43 Participants	69 Participants n=86 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=43 Participants	0 Participants n=43 Participants	0 Participants n=86 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=43 Participants	0 Participants n=43 Participants	1 Participants n=86 Participants
Race (NIH/OMB) Asian	0 Participants n=43 Participants	0 Participants n=43 Participants	0 Participants n=86 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=43 Participants	1 Participants n=43 Participants	1 Participants n=86 Participants
Race (NIH/OMB) Black or African American	1 Participants n=43 Participants	2 Participants n=43 Participants	3 Participants n=86 Participants
Race (NIH/OMB) White	41 Participants n=43 Participants	40 Participants n=43 Participants	81 Participants n=86 Participants
Race (NIH/OMB) More than one race	0 Participants n=43 Participants	0 Participants n=43 Participants	0 Participants n=86 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=43 Participants	0 Participants n=43 Participants	0 Participants n=86 Participants
Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score	40.5 score on a scale STANDARD_DEVIATION 13.27 • n=43 Participants • Number analyzed is the number of participants with data available for analysis.	39.7 score on a scale STANDARD_DEVIATION 13.06 • n=42 Participants • Number analyzed is the number of participants with data available for analysis.	40.1 score on a scale STANDARD_DEVIATION 13.10 • n=85 Participants • Number analyzed is the number of participants with data available for analysis.

PRIMARY outcome

Timeframe: Baseline, Day 42

Population: 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. Here, 'overall number of participants analyzed' signifies the number of participants with data available for analysis at specified timepoint.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=40 Participants Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.
Change From Baseline in the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding Test Score	2.0 score on a scale Standard Error 1.44	2.0 score on a scale Standard Error 1.48

SECONDARY outcome

Timeframe: Up to Day 70

Population: 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

Outcome measures
Measure	Placebo n=43 Participants Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=43 Participants Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	27 Participants	21 Participants

SECONDARY outcome

Timeframe: Up to Day 70

Population: 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

Outcome measures
Measure	Placebo n=43 Participants Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=43 Participants Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.
Number of Participants With at Least One TEAE by Severity Mild	15 Participants	14 Participants
Number of Participants With at Least One TEAE by Severity Moderate	10 Participants	5 Participants
Number of Participants With at Least One TEAE by Severity Severe	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Day 70

Population: 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

Outcome measures
Measure	Placebo n=43 Participants Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=43 Participants Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.
Number of Participants Who Withdrew From Study Due to TEAEs	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 4 other events

Deaths: 1 deaths

SAGE-718

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=43 participants at risk Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=43 participants at risk Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.
Musculoskeletal and connective tissue disorders Arthralgia	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.
Nervous system disorders Toxic encephalopathy	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	2.3% 1/43 • Up to Day 70 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) Breast cancer	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	2.3% 1/43 • Up to Day 70 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) Lung neoplasm malignant	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.
Cardiac disorders Acute myocardial infarction	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.
Infections and infestations Urosepsis	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.
Injury, poisoning and procedural complications Fall	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.

Other adverse events

Other adverse events
Measure	Placebo n=43 participants at risk Participants received SAGE-718-matching placebo, oral capsules, QD in the morning for 42 days.	SAGE-718 n=43 participants at risk Participants received SAGE-718, 1.2 mg, oral capsules, QD in the morning for 42 days.
Renal and urinary disorders Urinary tract infection	7.0% 3/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	7.0% 3/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.
Respiratory, thoracic and mediastinal disorders Cough	2.3% 1/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.	7.0% 3/43 • Up to Day 70 The safety set included all participants who were administered at least one dose of the IP.

Additional Information

Amy Bullock

Sage Therapeutics

Phone: 617-949-5151

Email: [email protected]

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