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

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

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: SAGE-718; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada, H2X 3E4
    • Sage Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Sage Investigational Site
  • California
    • Los Alamitos, California, United States, 90720
      • Sage Investigational Site
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Sage Investigational Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20057
      • Sage Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Sage Investigational Site
    • Tampa, Florida, United States, 33602
      • Sage Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Sage Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Sage Investigational Site
  • New York
    • New York, New York, United States, 10027
      • Sage Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Sage Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Sage Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Sage Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For all

1. 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:

2. 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.

3. 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.
4. CAG-Age-Product (CAP) score >70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49.
5. 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:

1. Score ≥26 on the MoCA at screening.
2. 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

1. Receive any prohibited medications within 30 days of Screening and during participation in the study
2. 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.)
3. Is known to be allergic to any of SAGE-718 excipients, including soy lecithin.

Additional criteria for participants with HD only:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAGE-718; Participants with HD will receive SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days.	Drug: SAGE-718; SAGE-718 oral softgel lipid capsules
Placebo Comparator: Placebo; Participants with HD will receive SAGE-718-matching placebo, orally, once daily for up to 28 days.	Drug: Placebo; SAGE-718-matching oral capsules
No Intervention: Healthy Participants; HP enrolled in this study will not receive any investigational product (IP) (SAGE-718 or placebo).

What is the study measuring?

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	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).	Baseline

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cambridge Neuropsychological Test Automated Battery (CANTAB) Test at Baseline	The CANTAB evaluates cognitive function via following subtests: N-Back Test (optional); Multitasking Test (optional); Spatial Working Memory Task Test; Spatial Span Test (optional); Paired Associates Learning (optional) This outcome measure will compare the CANTAB test results between participants with HD vs HP at Baseline.	Baseline
Virtual Reality Functional Capacity Assessment Tool (VRFCAT) Score at Baseline	The VRFCAT is a tablet-based measure that assesses ability to perform instrumental activities of daily living serve as a measure of functional improvement. Participants complete a series of tasks corresponding to functional capacity for meal preparation, use of public transportation, shopping, and managing currency. The total completion time is recorded for these activities, which ranges from 0 - 60000 milliseconds. Lesser time required to complete activity indicates better function.	Baseline
Change From Baseline in the Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score	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 with an expected z-score distribution of approximately -3 to +3, with higher score indicating improvement. A positive HD-CAB composite at follow-up indicates improvement in cognitive function; a negative composite score indicates worsening in cognitive function; and a composite of "0" would reflect no change relative to baseline. This outcome measure will compare the HD-CAB composite change from baseline scores between participants with HD in SAGE-718 and placebo arms.	Baseline, Day 28
Change From Baseline in the Cambridge Neuropsychological Test Automated Battery (CANTAB) Test	The CANTAB evaluates cognitive function via following subtests: N-Back Test (optional); Multitasking Test (optional); Spatial Working Memory Task Test; Spatial Span Test (optional); Paired Associates Learning (optional)	Baseline, Day 28
Change From Baseline in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) score	The VRFCAT is a tablet-based measure that assesses ability to perform instrumental activities of daily living serve as a measure of functional improvement. Participants complete a series of tasks corresponding to functional capacity for meal preparation, use of public transportation, shopping, and managing currency. The total completion time is recorded for these activities, which ranges from 0 - 60000 milliseconds. Lesser time required to complete activity indicates better function.	Baseline, Day 28

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2022
• Primary Completion (Actual): February 29, 2024
• Study Completion (Actual): April 10, 2024

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Chorea; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Huntington Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 718-CIH-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No