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

NCT05358821 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 718-CIH-202
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 14

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.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  Up to Day 42

• Number of Participants With HD With Clinically Significant Change From Baseline in Vital Sign Measurements

  Up to Day 42

• Number of Participants With HD With Clinically Significant Change From Baseline in Clinical Laboratory Assessments

  Up to Day 42

Study Arms (3)

SAGE-718

EXPERIMENTAL

Participants with HD will receive SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days.

Drug: SAGE-718

Placebo

PLACEBO COMPARATOR

Participants with HD will receive SAGE-718-matching placebo, orally, once daily for up to 28 days.

Drug: Placebo

Healthy Participants

NO INTERVENTION

HP enrolled in this study will not receive any investigational product (IP) (SAGE-718 or placebo).

Interventions

SAGE-718 DRUG

SAGE-718 oral softgel lipid capsules

SAGE-718

Placebo DRUG

SAGE-718-matching oral capsules

Placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (14)

Sage Investigational Site

Birmingham, Alabama, 35233, United States

Location

Sage Investigational Site

Los Alamitos, California, 90720, United States

Location

Sage Investigational Site

Englewood, Colorado, 80113, United States

Location

Sage Investigational Site

Washington D.C., District of Columbia, 20057, United States

Location

Sage Investigational Site

Boca Raton, Florida, 33431, United States

Location

Sage Investigational Site

Tampa, Florida, 33602, United States

Location

Sage Investigational Site

Chicago, Illinois, 60612, United States

Location

Sage Investigational Site

Baltimore, Maryland, 21218, United States

Location

Sage Investigational Site

New York, New York, 10027, United States

Location

Sage Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

Sage Investigational Site

Cincinnati, Ohio, 45221, United States

Location

Sage Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Sage Investigational Site

Houston, Texas, 77030, United States

Location

Sage Investigational Site

Montreal, H2X 3E4, Canada

Location

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Amy Bullock
• Organization: Sage Therapeutics

amy.bullock@sagerx.com

617-949-5151

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 3, 2022
• Study Start: May 26, 2022
• Primary Completion: February 29, 2024
• Study Completion: April 10, 2024
• Last Updated: September 15, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); CA (1)