A Study to Evaluate the Effect of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease
Study Details
Study Description
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 and the effect of SAGE-718 on cognitive performance and functioning in participants with HD.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SAGE-718 Participants will receive SAGE-718 1.2 mg capsule orally once daily in the morning for up to 28 days |
Drug: SAGE-718
SAGE-718 capsules
|
| Placebo Comparator: Placebo Participants will receive placebo capsule orally once daily in the morning for up to 28 days |
Drug: Placebo
SAGE-718-matching oral capsules
|
Outcome Measures
Primary Outcome Measures
- Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score at Baseline [Baseline]
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; 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 a 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. The primary outcome measure will compare the HD-CAB composite scores between participants with HD vs HP at Baseline.
Secondary Outcome Measures
- Cambridge Neuropsychological Test Automated Battery (CANTAB) Test Score at Baseline [Baseline]
The CANTAB evaluates cognitive function via following subtests: N-Back Test, Multitasking Test, Spatial Working Memory Task Test, Spatial Span Test, Paired Associates Learning. This outcome measure will compare the CANTAB test scores between participants with HD vs HP at Baseline. The CANTAB composite score will be derived based on the individual subtests score, with a higher score indicating a better outcome.
- Virtual Reality Functional Capacity Assessment Tool (VRFCAT) Score at Baseline [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.
- Change From Baseline in the Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score [Baseline, Day 28]
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; 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 vs HP.
- Change From Baseline in the Cambridge Neuropsychological Test Automated Battery (CANTAB) Test [Baseline, Day 28]
The CANTAB evaluates cognitive function via following subtests: N-Back Test, Multitasking Test, Spatial Working Memory Task Test, Spatial Span Test, Paired Associates Learning. The CANTAB composite score will be derived based on the individual subtests score, with a higher score indicating a better outcome.
- Change From Baseline in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) score [Baseline, Day 28]
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.
- Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Form first dose of study drug up to Day 42]
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death, 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.
- Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements [Form first dose of study drug up to Day 42]
- Percentage of Participants With Clinically Significant Changes in Laboratory Assessments [Form first dose of study drug up to Day 42]
Eligibility Criteria
Criteria
Inclusion Criteria:
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
-
Have:
-
Genetically confirmed disease with cytosine, adenine, and guanine (CAG) expansion ≥36
-
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 [ie, Unified Huntington's Disease Rating Scale(UHDRS) Diagnostic Confidence Level (DCL) = 4 before age 25].
-
CAG-Age-Product (CAP) score >70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49.
-
Score <26 on the Montreal Cognitive Assessment (MoCA) at Screening, indicating the presence of cognitive impairment.
Exclusion Criteria:
For All
-
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.
-
Receive any prohibited medications within 30 days of Screening and during participation in the study
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.
-
Have participated in a previous clinical study of SAGE-718, have participated in a previous gene therapy study, or have participated in any other drug, biologic, or device trial within 90 days or 5 half-lives (whichever is longer), unless the participant was enrolled solely in the placebo arm of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sage Investigational Site | Long Beach | California | United States | 90806 |
Sponsors and Collaborators
- Sage Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 718-CIH-202