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

Huntington Disease Clinical Trial

Official title:

A 28-Day Randomized, Placebo-Controlled, Double-Blind, Parallel Groups and Normative Comparison Study to Evaluate the Effect of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05358821
• Other study ID #: 718-CIH-202
• Status: Completed
• Phase: Phase 2
• Start date: June 22, 2022
• Est. completion date: April 10, 2024

Study information

• Verified date: May 2024
• Source: Sage Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: April 10, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

For all

1. 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:

2. 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.

3. Have:

1. Genetically confirmed disease with cytosine, adenine, and guanine (CAG) expansion =36

2. 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.

3. No features of juvenile HD

4. CAG-Age-Product (CAP) score >70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49.

5. 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:

1. Score =26 on the MoCA at Screening.

2. 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).

Exclusion Criteria:

For All

1. Receive any prohibited medications within 30 days of Screening and during participation in the study

2. 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.)

3. Is known to be allergic to any of SAGE-718 excipients, including soy lecithin.

Additional criteria for participants with HD only

1. Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit.

2. Receive any prohibited medications within 30 days of Screening and during participation in the Study.

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• SAGE-718
SAGE-718 oral softgel lipid capsules
• Placebo
SAGE-718-matching oral capsules

Locations

Country	Name	City	State
United States	Sage Investigational Site	Baltimore	Maryland
United States	Sage Investigational Site	Birmingham	Alabama
United States	Sage Investigational Site	Boca Raton	Florida
United States	Sage Investigational Site	Chapel Hill	North Carolina
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Cincinnati	Ohio
United States	Sage Investigational Site	Houston	Texas
United States	Sage Investigational Site	Los Alamitos	California
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Tampa	Florida
United States	Sage Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sage Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cambridge Neuropsychological Test Automated Battery (CANTAB) Test at Baseline	The CANTAB evaluates cognitive function via following subtests: N-Back Test (optional); Multitasking Test (optional); Spatial Working Memory Task Test; Spatial Span Test (optional); Paired Associates Learning (optional) This outcome measure will compare the CANTAB test results between participants with HD vs HP at Baseline.	Baseline
Other	Virtual Reality Functional Capacity Assessment Tool (VRFCAT) Score at 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.	Baseline
Other	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 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 in SAGE-718 and placebo arms.	Baseline, Day 28
Other	Change From Baseline in the Cambridge Neuropsychological Test Automated Battery (CANTAB) Test	The CANTAB evaluates cognitive function via following subtests: N-Back Test (optional); Multitasking Test (optional); Spatial Working Memory Task Test; Spatial Span Test (optional); Paired Associates Learning (optional)	Baseline, Day 28
Other	Change From Baseline in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) score	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.	Baseline, Day 28
Primary	Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at 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 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 (HP). A negative HD-CAB composite score of participants with HD will indicate a decline in cognitive function relative to HP.	Baseline
Secondary	Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	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.	Form first dose of study drug up to Day 42
Secondary	Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements		Form first dose of study drug up to Day 42
Secondary	Percentage of Participants With Clinically Significant Changes in Laboratory Assessments		Form first dose of study drug up to Day 42