A Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants With Huntington's Disease (HD)
- Registration Number
- NCT05107128
- Lead Sponsor
- Sage Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 189
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Meet all the following criteria for HD at Screening (Days -28 to -2):
- Genetically confirmed disease with huntingtin gene CAG expansion ≥36.
- At screening, UHDRS-Total Functional Capacity (TFC) score >6 and <13 suggesting no more than a moderate level of functional impairment.
- No features of juvenile HD.
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Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening indicating the presence of cognitive impairment.
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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.
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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.
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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.)
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAGE-718 SAGE-718 Participants will receive SAGE-718, once daily for 84 days. Placebo Placebo Participants will receive placebo, once daily for 84 days.
- Primary Outcome Measures
Name Time Method Change From Baseline in the Symbol Digit Modalities Test (SDMT) Baseline and Day 84 SDMT test measures the number of items correctly paired out of a maximum of 110 pairs in 90 seconds. Scores may range from 0 to 110, with higher scores indicating better cognitive functioning.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the Unified Huntington's Disease Rating Scale (UHDRS) - Independence Scale Baseline and Day 84 The UHDRS independence scale is a single item of independence rated from 10 to 100, with higher scores indicating better functioning than lower scores.
Change From Baseline in the Trial Making Test Part B Baseline and Day 84 The Trail Making test is a speeded graphomotor test of visual attention and task switching. Part B includes a set-switching component that requires participants to connect a series of alternating numbers and letters in order from lowest to highest (i.e., 1-A-2-B-3-C) in the shortest time possible. The time limit to complete the task is 240 seconds at which point the test is stopped and scored using the maximum allowable time if not yet completed. The number of errors is recorded as well. Greater time indicates greater impairment.
Change From Baseline in the One Touch Stockings of Cambridge (OTS-Mean Latency until Correct response) Baseline and Day 84 The OTS is a computerized test of executive function that measures time to correct response. Greater time indicates greater impairment.
Change From Baseline in the Paced Tapping Test (PTAP) Baseline and Day 84 The PTAP uses auditory pacing tones with participants instructed to synchronize their fingertaps to the rhythm of these tones. This is followed by a self-paced phase, where the auditory pacing cue is removed. The paced tapping consistency is calculated as 1/standard deviation (SD) of the intertap interval (1/msec). Higher scores indicate increased accuracy.
Change From Baseline in the Huntington's Disease Everyday Functioning (Hi-DEF) Home Subdomain Score Baseline and Day 84 The Hi-DEF scale is a self-reported questionnaire to capture difficulties experienced in daily life due to HD across four different areas of functioning including at home, at work, driving, and relationships. It is used to rate the functioning difficulty using a 5-point Likert scale from 1 (No Difficulty) to 5 (Cannot do this anymore) and the total score for the home subdomain will be obtained by summing the individual item scores. Lower scores indicate better daily functioning.
Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Cognitive Status Subdomain Score Baseline and Day 84 CGI-S is a scale that rates the severity of the participant's condition over the past 7 days. For this trial, CGI-S has been segmented into 4 subdomains: motor signs, motor complications, cognitive status, and disability. The responses are scored on a scale ranging from 0 (normal - no symptoms present) to 6 (severely disabled; helpless; complete assistance needed). Higher scores indicate greater disease symptom severity.
Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) Up to approximately 112 days 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.
Trial Locations
- Locations (1)
Sage Investigational Site
🇬🇧Southampton, United Kingdom