Huntington DiseasePhase 2NCT05358821
28-Day Study of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease
A Phase 2 study testing SAGE-718 in people with Huntington Disease, run by Supernus Pharmaceuticals, Inc. at 14 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Huntington Disease
- What is being tested?
- SAGE-718
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 26 May 2022to 10 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- Have:
- Genetically confirmed disease with cytosine, adenine, and guanine (CAG) expansion ≥36.
Show all 13Show fewer
- 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.
- No features of juvenile HD.
- CAG-Age-Product (CAP) score >70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49.
- 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:
- Score ≥26 on the MoCA at screening.
- 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).
Who cannot join
- For All
- 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 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.)
- Is known to be allergic to any of SAGE-718 excipients, including soy lecithin.
- 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.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States13 sites
Sage Investigational Site
Baltimore, Maryland, 21218
Sage Investigational Site
Birmingham, Alabama, 35233
Sage Investigational Site
Boca Raton, Florida, 33431
Sage Investigational Site
Chapel Hill, North Carolina, 27599
Sage Investigational Site
Chicago, Illinois, 60612
Sage Investigational Site
Cincinnati, Ohio, 45221
Sage Investigational Site
Englewood, Colorado, 80113
Sage Investigational Site
Houston, Texas, 77030
Sage Investigational Site
Los Alamitos, California, 90720
Sage Investigational Site
New York, New York, 10027
Sage Investigational Site
Philadelphia, Pennsylvania, 19104
Sage Investigational Site
Tampa, Florida, 33602
Sage Investigational Site
Washington D.C., District of Columbia, 20057
About this study
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
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.
- Conditions
- Huntington Disease
- Being tested
- SAGE-718, Placebo
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAGE-718Drug
SAGE-718 oral softgel lipid capsules
PlaceboDrug
SAGE-718-matching oral capsules
| Study group | Role | What they receive |
|---|---|---|
| SAGE-718 | Experimental | Participants with HD will receive SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days. Receives: Drug: SAGE-718 |
| Placebo | Placebo comparator | Participants with HD will receive SAGE-718-matching placebo, orally, once daily for up to 28 days. Receives: Drug: Placebo |
| Healthy Participants | No intervention | HP enrolled in this study will not receive any investigational product (IP) (SAGE-718 or placebo). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline
HD-CAB assesses cognitive function using 6 subtests:Symbol Digit Modalities Test-correctly coded items(0-110); One Touch Stockings of Cambridge(OTS)-mean time to reach correct response(range not defined); Trail Making Test Trail B (TMT-B)-time to complete task(0-240 sec); Hopkins Verbal Learning Test Revised-total correct recall trials(0-48); Paced Tapping Test-reciprocal of standard deviation(SD) of intertap intervals (range not defined); Emotion Recognition Test-negative emotions correctly identified(0-24). Values of OTS \& TMT B are multiplied by -1 to represent higher is better direction as other tests. Each of 6 subtests scores was transformed to z-score(range not defined;low negative value represents cognitive impairment), which is calculated by subtracting mean and dividing by SD of HP at baseline. HD-CAB composite=average of 6 z-scores. Negative HD-CAB of HD participants=decline in cognitive function relative to HP. Assessment is relative to reference group(healthy population).
Measured: Baseline
Secondary outcomes (3)
Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent adverse events are defined as any adverse events with onset on or after the first dose of IP. A serious TEAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death (a life-threatening event), 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.
Measured: Up to Day 42
Number of Participants With HD With Clinically Significant Change From Baseline in Vital Sign Measurements
Vital signs including oral temperature, respiratory rate, heart rate (supine and standing), and blood pressures (supine and standing). Number of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.
Measured: Up to Day 42
Number of Participants With HD With Clinically Significant Change From Baseline in Clinical Laboratory Assessments
Clinical laboratory assessments including hematology, serum chemistry, coagulation, and urinalysis were performed. Number of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.
Measured: Up to Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start26 May 2022
- Primary completion29 Feb 2024
- Study completion10 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Supernus Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05358821
- Sponsor's protocol ID
- 718-CIH-202
- Status last verified
- Apr 2025
- First submitted
- 27 Apr 2022
- Last updated
- 15 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05358821
- Acronym / sponsor ID
- 718-CIH-202
- Conditions
- Huntington Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Supernus Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 May 2022 (actual)
- Primary completion
- 29 Feb 2024 (actual)
- Study completion
- 10 Apr 2024 (actual)
- First posted
- 3 May 2022 (actual)
- Results
- Posted 6 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SAGE-718 | Experimental | Drug: SAGE-718Participants with HD will receive SAGE-718 1.2 milligrams (mg), orally, once daily for up to 28 days. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants with HD will receive SAGE-718-matching placebo, orally, once daily for up to 28 days. |
| Healthy Participants | No intervention | –HP enrolled in this study will not receive any investigational product (IP) (SAGE-718 or placebo). |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 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.
- Have:
- CAG-Age-Product (CAP) score >70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49.
Key exclusion criteria (7 listed)
- For All
- 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 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.)
- Is known to be allergic to any of SAGE-718 excipients, including soy lecithin.
- Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAGE-718SAGE-718 oral softgel lipid capsules | Drug | SAGE-718 |
| PlaceboSAGE-718-matching oral capsules | Drug | Placebo |
Primary outcome
Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline
Time frame: Baseline
HD-CAB assesses cognitive function using 6 subtests:Symbol Digit Modalities Test-correctly coded items(0-110); One Touch Stockings of Cambridge(OTS)-mean time to reach correct response(range not defined); Trail Making Test Trail B (TMT-B)-time to complete task(0-240 sec); Hopkins Verbal Learning Test Revised-total correct recall trials(0-48); Paced Tapping Test-reciprocal of standard deviation(SD) of intertap intervals (range not defined); Emotion Recognition Test-negative emotions correctly identified(0-24). Values of OTS \& TMT B are multiplied by -1 to represent higher is better direction as other tests. Each of 6 subtests scores was transformed to z-score(range not defined;low negative value represents cognitive impairment), which is calculated by subtracting mean and dividing by SD of HP at baseline. HD-CAB composite=average of 6 z-scores. Negative HD-CAB of HD participants=decline in cognitive function relative to HP. Assessment is relative to reference group(healthy population).
3 secondary outcomes
Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Up to Day 42
Number of Participants With HD With Clinically Significant Change From Baseline in Vital Sign Measurements
Time frame: Up to Day 42
Number of Participants With HD With Clinically Significant Change From Baseline in Clinical Laboratory Assessments
Time frame: Up to Day 42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SAGE-718 in people with Huntington Disease, run by Supernus Pharmaceuticals, Inc. at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.