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

Study Overview
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Brief Summary
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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.

Official Title
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A 28-Day Randomized, Placebo-Controlled, Double-Blind, Parallel Groups and Normative Comparison Study to Evaluate the Effect of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease

Conditions
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Huntington Disease

Intervention / Treatment
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* Drug: SAGE-718
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Genetically confirmed disease with cytosine, adenine, and guanine (CAG) expansion ≥36 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. 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAGE-718<br>Participants will receive SAGE-718 1.2 mg softgel lipid capsule orally once daily in the morning for up to 28 days. | Drug: SAGE-718<br>* SAGE-718 oral softgel lipid capsules<br>|
| Placebo Comparator: Placebo<br>Participants will receive SAGE-718-matching placebo capsule orally once daily in the morning for up to 28 days. | Drug: Placebo<br>* SAGE-718-matching oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline | The HD-CAB evaluates cognitive function via the following subtests: Symbol Digit Modalities Test; One Touch Stockings of Cambridge; Trail Making; Hopkins Verbal Learning Test Revised; Paced Tapping Test; and the Emotion Recognition Test. The HD-CAB composite is derived by transforming individual participants' scores on each of the 6 subtests to z-scores, and averaging z-scores to represent global performance relative to the reference sample (HP). A negative HD-CAB composite score of participants with HD will indicate a decline in cognitive function relative to HP. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death, 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. | Form first dose of study drug up to Day 42 | 
| Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements |  | Form first dose of study drug up to Day 42 | 
| Percentage of Participants With Clinically Significant Changes in Laboratory Assessments |  | Form first dose of study drug up to Day 42 |