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

Phase 2

Completed

Conditions: Huntington Disease

Interventions: Drug: SAGE-718
Drug: Placebo

Registration Number: NCT05358821

Lead Sponsor: Sage Therapeutics

Brief Summary: The primary purpose of this study is to assess the magnitude of the baseline difference between participants with early Huntington's Disease (HD) and healthy participants (HP) with respect to measures of cognitive performance.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 69

Inclusion Criteria

For all

Agree to refrain from drugs of abuse for the duration of the study and from alcohol during the 48 hours preceding each study visit.

Additional criteria for participants with HD only:
Be ambulatory, able to travel to the study center, and, judged by the investigator, is likely to be able to continue to travel to the study center to complete study visits for the duration of the study.
Have:
1. Genetically confirmed disease with cytosine, adenine, and guanine (CAG) expansion ≥36.
2. At screening, Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) >6 and <13, suggesting no more than a moderate level of functional impairment.
3. No features of juvenile HD.
CAG-Age-Product (CAP) score >70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49.
Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening, indicating the presence of cognitive impairment.

Additional criteria for HP only:

Score ≥26 on the MoCA at screening.
Have no known family history of HD; or, have known family history of HD but have genetic test results available that show a normal CAG repeat length for both Huntingtin (HTT) alleles (<36).

Exclusion Criteria

For All

Receive any prohibited medications within 30 days of Screening and during participation in the study
Have participated in a previous clinical study of SAGE-718, have previous exposure to gene therapy; or have participated in any HD investigational drug, biologic, or device trial within 180 days, or a non-HD drug, biologic, or device trial within 30 days or 5 half-lives (whichever is longer). (Note: participants with confirmation of enrolment in the placebo arm of these trials would not be excluded.)
Is known to be allergic to any of SAGE-718 excipients, including soy lecithin.

Additional criteria for participants with HD only:

Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit.
Receive any prohibited medications within 30 days of Screening and during participation in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAGE-718	SAGE-718	Participants with HD will receive SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days.
Placebo	Placebo	Participants with HD will receive SAGE-718-matching placebo, orally, once daily for up to 28 days.

Primary Outcome Measures

Name	Time	Method
Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline	Baseline	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	Up to Day 42	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.
Number of Participants With HD With Clinically Significant Change From Baseline in Vital Sign Measurements	Up to Day 42	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.
Number of Participants With HD With Clinically Significant Change From Baseline in Clinical Laboratory Assessments	Up to Day 42	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.