Trial Outcomes & Findings for 28-Day Study of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease (NCT NCT05358821)

Last Updated: 2025-09-15

Results Overview

HD-CAB assesses cognitive function using 6 subtests:Symbol Digit Modalities Test-correctly coded items(0-110); One Touch Stockings of Cambridge(OTS)-mean time to reach correct response(range not defined); Trail Making Test Trail B (TMT-B)-time to complete task(0-240 sec); Hopkins Verbal Learning Test Revised-total correct recall trials(0-48); Paced Tapping Test-reciprocal of standard deviation(SD) of intertap intervals (range not defined); Emotion Recognition Test-negative emotions correctly identified(0-24). Values of OTS \& TMT B are multiplied by -1 to represent higher is better direction as other tests. Each of 6 subtests scores was transformed to z-score(range not defined;low negative value represents cognitive impairment), which is calculated by subtracting mean and dividing by SD of HP at baseline. HD-CAB composite=average of 6 z-scores. Negative HD-CAB of HD participants=decline in cognitive function relative to HP. Assessment is relative to reference group(healthy population).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

69 participants

Primary outcome timeframe

Baseline

Results posted on

2025-09-15

Participant Flow

Participants were enrolled at 14 investigative sites in the United States and Canada from 26 May 2022 to 10 April 2024.

A total of 69 adult participants, comprising 29 healthy participants (HP) and 40 participants with Huntington's disease (HD) were enrolled in the study. Participants with HD received either SAGE-718 or placebo. As pre-specified in the protocol, HP enrolled in the study followed the same assessment schedule as participants with HD, but did not receive any investigational product (IP) (SAGE-718 or placebo).

Participant milestones

Participant milestones
Measure	Placebo Participants with HD received SAGE-718-matching placebo, orally, once daily for up to 28 days.	SAGE-718 Participants with HD received SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days.	Healthy Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Overall Study STARTED	19	21	29
Overall Study COMPLETED	19	20	28
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants with HD received SAGE-718-matching placebo, orally, once daily for up to 28 days.	SAGE-718 Participants with HD received SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days.	Healthy Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Overall Study Withdrawal by Subject	0	1	0
Overall Study Withdrawal of Consent	0	0	1

Baseline Characteristics

28-Day Study of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=19 Participants Participants with HD received SAGE-718-matching placebo, orally, once daily for up to 28 days.	SAGE-718 n=21 Participants Participants with HD received SAGE-718 1.2 mg, orally, once daily for up to 28 days.	Healthy Participants n=29 Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).	Total n=69 Participants Total of all reporting groups
Age, Continuous	49.5 years STANDARD_DEVIATION 8.45 • n=5 Participants	49.5 years STANDARD_DEVIATION 7.44 • n=7 Participants	43.5 years STANDARD_DEVIATION 11.15 • n=5 Participants	47.0 years STANDARD_DEVIATION 9.76 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants	36 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	20 Participants n=7 Participants	25 Participants n=5 Participants	60 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	58 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline

Population: FAS included all randomized participants with HD \& all HP who met eligibility criteria \& had at least 1 baseline assessment of HD-CAB (participants with HD \& HP). As primary analysis was to estimate baseline differences between participants with HD \& HP in HD-CAB composite score, data from SAGE-718 \& placebo arms were combined for analysis. Baseline for HD participants=last non-missing measurement prior to first dose of IP. Baseline for HP=last non-missing measurement on or prior to Day 1.

Outcome measures

Outcome measures
Measure	Participants With HD n=40 Participants All participants with HD who were enrolled and randomized into the study to receive either Sage-718 or placebo.	Healthy Participants n=29 Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline	-3.3657 Z score Standard Deviation 1.4613	0.0000 Z score Standard Deviation 0.5673

SECONDARY outcome

Timeframe: Up to Day 42

Population: Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and was used to describe the safety data.

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent adverse events are defined as any adverse events with onset on or after the first dose of IP. A serious TEAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death (a life-threatening event), requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.

Outcome measures

Outcome measures
Measure	Participants With HD n=19 Participants All participants with HD who were enrolled and randomized into the study to receive either Sage-718 or placebo.	Healthy Participants n=21 Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs TEAEs	6 Participants	11 Participants
Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Serious TEAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 42

Population: Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and was used to describe the safety data.

Vital signs including oral temperature, respiratory rate, heart rate (supine and standing), and blood pressures (supine and standing). Number of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Participants With HD n=19 Participants All participants with HD who were enrolled and randomized into the study to receive either Sage-718 or placebo.	Healthy Participants n=21 Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Number of Participants With HD With Clinically Significant Change From Baseline in Vital Sign Measurements	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 42

Population: Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and was used to describe the safety data.

Clinical laboratory assessments including hematology, serum chemistry, coagulation, and urinalysis were performed. Number of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Participants With HD n=19 Participants All participants with HD who were enrolled and randomized into the study to receive either Sage-718 or placebo.	Healthy Participants n=21 Participants HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Number of Participants With HD With Clinically Significant Change From Baseline in Clinical Laboratory Assessments	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

SAGE-718

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Healthy Participants

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=19 participants at risk Participants with HD received SAGE-718-matching placebo, orally, once daily for up to 28 days.	SAGE-718 n=21 participants at risk Participants with HD received SAGE-718 1.2 mg, orally, once daily for up to 28 days.	Healthy Participants n=29 participants at risk HP enrolled in this study did not receive any IP (SAGE-718 or placebo).
Gastrointestinal disorders Nausea	0.00% 0/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	14.3% 3/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	3.4% 1/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Gastrointestinal disorders Dyspepsia	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
General disorders Fatigue	0.00% 0/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	9.5% 2/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Infections and infestations Nasopharyngitis	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	9.5% 2/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	6.9% 2/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Nervous system disorders Somnolence	0.00% 0/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	9.5% 2/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	6.9% 2/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Psychiatric disorders Depression	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Renal and urinary disorders Micturition urgency	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Nervous system disorders Migraine	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Nervous system disorders Reflexes abnormal	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.
Infections and infestations Sinusitis	5.3% 1/19 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/21 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.	0.00% 0/29 • Up to Day 42 Safety Set included all participants with HD who were administered IP or HP who met eligibility criteria and will be used to describe the safety data.

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