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

Huntington's Disease Clinical Trial

Official title:

A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants With Huntington's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05107128
• Other study ID #: 718-CIH-201
• Secondary ID: 2021-005577-16
• Status: Recruiting
• Phase: Phase 2
• Start date: February 10, 2022
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Sage Therapeutics
• Contact: Grant Rutledge, PhD
• Phone: 339-368-8432
• Email: grant.rutledge[@]sagerx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 178
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Meet all the following criteria for HD at Screening (Days -28 to -2):

1. Genetically confirmed disease with huntingtin gene CAG expansion =36.

2. At screening, UHDRS-Total Functional Capacity (TFC) score >6 and <13 suggesting no more than a moderate level of functional impairment.

3. No features of juvenile HD.

2. Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening indicating the presence of cognitive impairment.

3. 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.

4. 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.

Exclusion Criteria:

1. 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.)

2. 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.

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• SAGE-718
Oral capsules.
• Placebo
SAGE-718-matching oral capsules.

Locations

Country	Name	City	State
Australia	Sage Investigational Site	Herston	Queensland
Australia	Sage Investigational Site	Nedlands	Western Australia
Australia	Sage Investigational Site	Parkdale	Victoria
Australia	Sage Investigational Site	Westmead	New South Wales
Canada	Sage Investigational Site	Halifax	Nova Scotia
Canada	Sage Investigational Site	Montréal	Quebec
Canada	Sage Investigational Site	North York	Ontario
United Kingdom	Sage Investigational Site	Aberdeen
United Kingdom	Sage Investigational Site	Birmingham
United Kingdom	Sage Investigational Site	Cardiff
United Kingdom	Sage Investigational Site	Leeds
United Kingdom	Sage Investigational Site	Leeds
United Kingdom	Sage Investigational Site	Newcastle Upon Tyne
United Kingdom	Sage Investigational Site	Plymouth
United Kingdom	Sage Investigational Site	Southampton
United Kingdom	Sage Investigational Site	Tooting	London
United States	Sage Investigational Site	Baltimore	Maryland
United States	Sage Investigational Site	Boca Raton	Florida
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Chapel Hill	North Carolina
United States	Sage Investigational Site	Charleston	South Carolina
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Cincinnati	Ohio
United States	Sage Investigational Site	Durham	North Carolina
United States	Sage Investigational Site	Englewood	Colorado
United States	Sage Investigational Site	Honolulu	Hawaii
United States	Sage Investigational Site	Houston	Texas
United States	Sage Investigational Site	Indianapolis	Indiana
United States	Sage Investigational Site	Iowa City	Iowa
United States	Sage Investigational Site	Kansas City	Kansas
United States	Sage Investigational Site	Kirkland	Washington
United States	Sage Investigational Site	La Jolla	California
United States	Sage Investigational Site	Little Rock	Arkansas
United States	Sage Investigational Site	Los Angeles	California
United States	Sage Investigational Site	Memphis	Tennessee
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Richmond	Virginia
United States	Sage Investigational Site	Sacramento	California
United States	Sage Investigational Site	Spokane	Washington
United States	Sage Investigational Site	Tampa	Florida
United States	Sage Investigational Site	Toledo	Ohio
United States	Sage Investigational Site	Washington	District of Columbia
United States	Sage Investigational Site	Williamsville	New York

Sponsors (1)

Lead Sponsor	Collaborator
Sage Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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. Change from baseline will be computed using baseline mean and standard deviation, with an expected z-score distribution of approximately -3 to +3. 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.	Baseline and Day 84
Secondary	Change From Baseline in the Unified Huntington's Disease Rating Scale (UHDRS) - Independence Scale	The UHDRS independence scale is a single item of independence rated from 10 to 100, with higher scores on the function scales indicating better functioning than lower scores.	Baseline and Day 84
Secondary	Change From Baseline in the UHDRS - Total Motor Score (TMS)	The motor section of the UHDRS assesses motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. Each item is scored on a scale of 0-4, where 0 is "normal," and 4 is the "highest motor dysfunction." The total motor impairment score is the sum of all the individual motor ratings. The total score range is 0-24, with higher scores indicating more severe motor impairment than lower scores.	Baseline and Day 84
Secondary	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE with onset after the start of the investigational product, or any worsening of a pre-existing medical condition/AE with onset after the start of the investigational product and throughout the study.	Up to approximately 112 days