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

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).

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.