A Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants With Huntington's Disease (HD)

NCT05107128 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 718-CIH-2012021-005577-16
• Study Type: interventional
• Target: 189
• Locations: 4 countries
• Sites: 49

Brief Summary

The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance and functioning in participants with HD.

Conditions

Huntington's Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the SDMT

  The SDMT evaluates the tracking of cognitive function over time and for the early detection of cognitive impairment. The test assesses sustained attention, processing speed, visual scanning, and psychomotor speed, with the total score reflecting the number of correct pairings (out of 110 possible) completed within 90 seconds. Scores range from 0 to 110, with higher scores indicating better cognitive performance.

  Baseline, Day 84

Secondary Outcomes (7)

• Change From Baseline in the Unified Huntington's Disease Rating Scale (UHDRS) - Independence Scale

  Baseline, Day 84

• Change From Baseline in the Trail Making Test Part B

  Baseline, Day 84

• Change From Baseline in the One Touch Stockings of Cambridge (OTS-Mean Latency Until Correct Response)

  Baseline, Day 84

• Change From Baseline in the Paced Tapping Test (PTAP)

  Baseline, Day 84

• Change From Baseline in the Huntington's Disease Everyday Functioning (Hi-DEF) Home Subdomain Score

  Baseline, Day 84

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will receive SAGE-718-matching placebo, orally, once daily (QD) for up to Day 84.

Drug: Placebo

SAGE-718

EXPERIMENTAL

Participants will receive SAGE-718, 1.2 milligrams (mg), capsules, orally, QD for Days 1 to 27, followed by 0.9 mg for the remainder of the treatment period up to Day 84.

Drug: SAGE-718

Interventions

SAGE-718 DRUG

Oral capsules.

SAGE-718

Placebo DRUG

SAGE-718-matching oral capsules.

Placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet all the following criteria for HD at Screening (Days -28 to -2):
• Genetically confirmed disease with huntingtin gene CAG expansion greater than or equal to (≥) 36.
• At screening, Unified Huntington's Disease Rating Scale (UHDRS)-Total Functional Capacity (TFC) score greater than (\>) 6 and less than (\<)13, suggesting no more than a moderate level of functional impairment.
• No features of juvenile HD.
• Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening indicating the presence of cognitive impairment.
• Be willing to invite a study partner, if available, who is reliable, competent, and at least 18 years of age to participate in the study.
• Be ambulatory (use of assistance devices such as a walker or cane is acceptable, as is occasional use of wheelchair, as judged by the investigator. Individuals requiring a wheelchair on a regular basis are excluded), able to travel to the study center, and, as 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.
• Completion of Huntington's Disease Cognitive Assessment Battery (HD-CAB) Trail Making-B Test in less than 240 seconds at Screening (Days -28 to -2).

You may not qualify if:

• Have participated in a previous clinical study of SAGE-718, have previous exposure to gene therapy, 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 enrollment in the placebo arm of these trials would not be excluded.)
• Have a diagnosis of an ongoing neurodegenerative condition other than HD, including but not limited to Alzheimer's Disease, vascular dementia, dementia with Lewy bodies, or Parkinson's Disease.

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (49)

Sage Investigational Site

Little Rock, Arkansas, 72205, United States

Location

Sage Investigational Site

La Jolla, California, 92037, United States

Location

Sage Investigational Site

Los Angeles, California, 90095, United States

Location

Sage Investigational Site

Sacramento, California, 95817, United States

Location

Sage Investigational Site

Englewood, Colorado, 80113, United States

Location

Sage Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

Sage Investigational Site

Boca Raton, Florida, 33431, United States

Location

Sage Investigational Site

Boca Raton, Florida, 33486, United States

Location

Sage Investigational Site

Tampa, Florida, 33612, United States

Location

Sage Investigational Site

Honolulu, Hawaii, 96817, United States

Location

Sage Investigational Site

Chicago, Illinois, 60611, United States

Location

Sage Investigational Site

Chicago, Illinois, 60612, United States

Location

Sage Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Sage Investigational Site

Iowa City, Iowa, 52242, United States

Location

Sage Investigational Site

Kansas City, Kansas, 66160, United States

Location

Sage Investigational Site

Baltimore, Maryland, 21287, United States

Location

Sage Investigational Site

Boston, Massachusetts, 02129, United States

Location

Sage Investigational Site

Boston, Massachusetts, 02215, United States

Location

Sage Investigational Site

Farmington Hills, Michigan, 48334, United States

Location

Sage Investigational Site

Buffalo, New York, 14221, United States

Location

Sage Investigational Site

New York, New York, 10032, United States

Location

Sage Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

Sage Investigational Site

Durham, North Carolina, 27705, United States

Location

Sage Investigational Site

Cincinnati, Ohio, 45219, United States

Location

Sage Investigational Site

Toledo, Ohio, 43614, United States

Location

Sage Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

Sage Investigational Site

Charleston, South Carolina, 29425, United States

Location

Sage Investigational Site

Memphis, Tennessee, 38157, United States

Location

Sage Investigational Site

Nashville, Tennessee, 37212, United States

Location

Sage Investigational Site

Houston, Texas, 77030, United States

Location

Sage Investigational Site

Richmond, Virginia, 23298, United States

Location

Sage Investigational Site

Kirkland, Washington, 98034, United States

Location

Sage Investigational Site

Spokane, Washington, 99202, United States

Location

Sage Investigational Site

Madison, Wisconsin, 53792, United States

Location

Sage Investigational Site

Westmead, New South Wales, 2145, Australia

Location

Sage Investigational Site

Herston, Queensland, 4029, Australia

Location

Sage Investigational Site

Bethlehem, Victoria, 3162, Australia

Location

Sage Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

Sage Investigational Site

Halifax, Nova Scotia, B3S 1N2, Canada

Location

Sage Investigational Site

North York, Ontario, M2K 1E1, Canada

Location

Sage Investigational Site

Montreal, Quebec, H2X 0A9, Canada

Location

Sage Investigational Site

Tooting, London, SW17 0QT, United Kingdom

Location

Sage Investigational Site

Aberdeen, AB25 2ZA, United Kingdom

Location

Sage Investigational Site

Birmingham, B15 2FG, United Kingdom

Location

Sage Investigational Site

Cardiff, CF10 3AX, United Kingdom

Location

Sage Investigational Site

Leeds, LS7 4SA, United Kingdom

Location

Sage Investigational Site

Newcastle upon Tyne, NE6 4QD, United Kingdom

Location

Sage Investigational Site

Plymouth, PL6 8BT, United Kingdom

Location

Sage Investigational Site

Southampton, SO16 6YD, United Kingdom

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, PhD
• 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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2021
• First Posted: November 4, 2021
• Study Start: January 26, 2022
• Primary Completion: September 4, 2024
• Study Completion: October 3, 2024
• Last Updated: September 15, 2025
• Results First Posted: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (8); US (34); AU (4); CA (3)