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Huntington's DiseasePhase 3NCT05655520

A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease

A Phase 3 study testing SAGE-718 in people with Huntington's Disease, run by Supernus Pharmaceuticals, Inc. at 43 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The primary purpose of the study is to evaluate the safety and tolerability of SAGE-718 softgel lipid capsule in participants with Huntington's Disease (HD) Read more about this study

Who is it for?
Ages 25 to 65 years
Conditions the study is for
Huntington's Disease
What is being tested?
SAGE-718
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
43 sitesin 4 countries
Study dates
14 Dec 2022to 20 Jan 2025
Phase
Phase 3
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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For all participants:
  • Completed 718-CIH-201 (NCT05107128) or 718-CIH-202 (NCT05358821) studies or meet eligibility criteria for the de novo cohort.
  • 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 willing to invite a study partner, if available, who is reliable, competent, and at least 18 years of age to participate in the study.
  • Be 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.
  • Additional inclusion criteria for the de novo cohort (Cohort 3):
Show all 11Show fewer
  • Be at least 25 years old, but not older than 65 years of age at Screening.
  • Genetically confirmed disease with cytosine-adenine-guanine (CAG) expansion ≥40
  • No features of juvenile HD
  • CAG-Age-Product (CAP) score ≥90, as calculated using the CAP formula: AGE × (CAG - 30) / 6.49.
  • At screening, scores of either: a) Unified Huntington's Disease Rating Scale (UHDRS) -Total Functional Capacity (TFC)=13 and Montreal Cognitive Assessment (MoCA) ≤25 score, or b) UHDRS-TFC ≤12 and MoCA >25

Who cannot join

  • For all participants
  • 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.
  • Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit.
  • Is known to be allergic to any of SAGE-718 excipients, including soy lecithin.
  • Receive any prohibited medications within 30 days of screening and during participation in the study.
  • Additional exclusion criteria for the de novo cohort (Cohort 3):
Show all 11Show fewer
  • Have previous exposure to gene therapy, or have participated in any other 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). Additionally, participants who have received treatment with antisense oligonucleotides or a messenger ribonucleic acid (mRNA) splicing modifier will be excluded.
  • Note: Participants with confirmation of enrolment in the placebo arm of these investigational trials would not be excluded.
  • Additional exclusion criteria for 718-CIH-201/202 completers (Cohorts 1 and 2):
  • Have one or more ongoing serious adverse events (SAEs) from the parent study.
  • Have ongoing, unresolved AE(s), which in the opinion of the investigator or sponsor, is likely to interfere with study conduct or compliance.

Trial locations and contacts

43 sites in 4 countries.

43 sites in 4 countries

United States29 sites
  • Sage Investigational Site

    Baltimore, Maryland, 21287

  • Sage Investigational Site

    Birmingham, Alabama, 35233

  • Sage Investigational Site

    Boca Raton, Florida, 33431

  • Sage Investigational Site

    Boston, Massachusetts, 02215

  • Sage Investigational Site

    Chapel Hill, North Carolina, 27599

  • Sage Investigational Site

    Charleston, South Carolina, 29425

  • Sage Investigational Site

    Chicago, Illinois, 60611

  • Sage Investigational Site

    Chicago, Illinois, 60612

  • Sage Investigational Site

    Cincinnati, Ohio, 45219

  • Sage Investigational Site

    Durham, North Carolina, 27705

  • Sage Investigational Site

    Englewood, Colorado, 80113

  • Sage Investigational Site

    Houston, Texas, 77030

  • Sage Investigational Site

    Indianapolis, Indiana, 46202

  • Sage Investigational Site

    Iowa City, Iowa, 52242

  • Sage Investigational Site

    Kansas City, Kansas, 66103

  • Sage Investigational Site

    La Jolla, California, 92037

  • Sage Investigational Site

    Little Rock, Arkansas, 72205

  • Sage Investigational Site

    Los Alamitos, California, 90720

  • Sage Investigational Site

    Los Angeles, California, 90095

  • Sage Investigational Site

    Memphis, Tennessee, 38157

  • Sage Investigational Site

    New York, New York, 10032

  • Sage Investigational Site

    Philadelphia, Pennsylvania, 19107

  • Sage Investigational Site

    Richmond, Virginia, 23298

  • Sage Investigational Site

    Sacramento, California, 95817

  • Sage Investigational Site

    Spokane, Washington, 99202

  • Sage Investigational Site

    Tampa, Florida, 33612

  • Sage Investigational Site

    Toledo, Ohio, 43614

  • Sage Investigational Site

    Washington D.C., District of Columbia, 20007

  • Sage Investigational Site

    Williamsville, New York, 14221

Other trials in United States

United Kingdom8 sites
  • Sage Investigational Site

    Aberdeen, Scotland, AB25 2ZA

  • Sage Investigational Site

    Birmingham, West Midlands, B15 2FG

  • Sage Investigational Site

    Cardiff, Wales, CF144XW

  • Sage Investigational Site

    Leeds, West Yorkshire, LS7 4SA

  • Sage Investigational Site

    Newcastle, Upon Tyne, NE6 4QD

  • Sage Investigational Site

    Plymouth, Derriford, PL6 8BT

  • Sage Investigational Site

    Southampton, England, SO16 6YD

  • Sage Investigational Site

    Tooting, London, SW17 0QT

Other trials in United Kingdom

Australia3 sites
  • Sage Investigational Site

    Caulfield South, Victoria, 3162

  • Sage Investigational Site

    Nedlands, Western Australia, 6009

  • Sage Investigational Site

    Westmead, New South Wales, 2145

Other trials in Australia

Canada3 sites
  • Sage Investigational Site

    Halifax, Nova Scotia, B3S1N2

  • Sage Investigational Site

    Montreal, Quebec, H2X1R9

  • Sage Investigational Site

    Toronto, Ontario, M2K 1E1

Other trials in Canada

About this study

Official title: A Phase 3, Multicenter, Open-label Safety Study to Evaluate the Long-term Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease

The primary purpose of the study is to evaluate the safety and tolerability of SAGE-718 softgel lipid capsule in participants with Huntington's Disease (HD)

Being tested
SAGE-718
Keywords
Huntington's Disease, SAGE-718
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

    Oral softgel lipid capsules

Study groups in NCT05655520
Study groupRoleWhat they receive
Cohort 1 (Direct Rollover)ExperimentalParticipants from the studies 718-CIH-201 (NCT05107128) and 718-CIH-202 (NCT05358821) who will sign the informed consent for study 718-CIH-301 ≤7 days after the last day of the corresponding parent study will be enrolled in this cohort. Participants will receive Sage-718, 0.9 milligrams (mg), orally once daily from Day 1 onwards.
Receives: Drug: SAGE-718
Cohort 2 (Gap Rollover)ExperimentalParticipants from the studies 718-CIH-201 (NCT05107128) and 718-CIH-202 (NCT05358821) who will sign the informed consent for study 718-CIH-301 after a gap of >7 days after the last day of the corresponding parent study will be enrolled in this cohort. Participants will receive Sage-718 0.9 mg, orally once daily from Day 1 onwards.
Receives: Drug: SAGE-718
Cohort 3 (De Novo)ExperimentalParticipants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 onwards.
Receives: Drug: SAGE-718

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)

    An Adverse Event (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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

    Measured: Up to 24 months

  2. Number of Participants With at Least One TEAE by Severity

    A TEAE is defined as an AE with onset after the start of IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Severity was assessed as:

    Mild: symptoms barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptoms.

    Moderate: symptoms of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptoms may be needed.

    Severe: symptoms cause severe discomfort; symptoms cause incapacitation or significant impact on participant's daily life; severity may cause cessation of treatment with IP; treatment for symptoms may be given and/or participant hospitalized.

    Participant with multiple instances of events is counted only once using maximum intensity.

    Measured: Up to 24 months

  3. Number of Participants Who Withdrew From Study Due to TEAEs

    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as any AE with onset or after the start of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.

    Measured: Up to 24 months

  4. Change From Baseline in Vital Signs: Blood Pressure

    Vital signs parameter for blood pressure included systolic blood pressure (supine), systolic blood pressure (standing 1 minute), systolic blood pressure (standing 3 minutes), diastolic blood pressure (supine), diastolic blood pressure (standing 1 minute), and diastolic blood pressure (standing 3 minutes).

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last Value on Study (up to 24 months)

  5. Change From Baseline in Vital Signs: Heart Rate

    Vital signs for heart rate included heart rate (supine), heart rate (standing 1 minute), and heart rate (standing 3 minute).

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  6. Change From Baseline in Vital Signs: Respiratory Rate

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  7. Change From Baseline in Vital Signs: Temperature

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  8. Change From Baseline in Clinical Laboratory Parameters: Hematology - Basophils, Eosinophils, Erythrocytes, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  9. Change From Baseline in Clinical Laboratory Parameters: Hematology- Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  10. Change From Baseline in Clinical Laboratory Parameters: Hematology- Erythrocytes (Ery.) Mean Corpuscular Hemoglobin (HGB) Concentration, Hemoglobin

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  11. Change From Baseline in Clinical Laboratory Parameters: Hematology - Erythrocytes Mean Corpuscular Hemoglobin

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  12. Change From Baseline in Clinical Laboratory Parameters: Hematology - Erythrocytes Mean Corpuscular Volume

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  13. Change From Baseline in Clinical Laboratory Parameters: Hematology - Hematocrit

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  14. Change From Baseline in Clinical Laboratory Parameters: Biochemistry- Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline, Last value on study (up to 24 months)

  15. Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Bicarbonate, Calcium, Chloride, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen

    HDL= high-density lipoprotein LDL= low-density lipoprotein

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  16. Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Albumin and Protein

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  17. Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Bilirubin, Creatinine, Direct Bilirubin, Indirect Bilirubin

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  18. Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Thyrotropin

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  19. Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Thyroxine Free, Triiodothyronine Free

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  20. Change From Baseline in Clinical Laboratory Parameters: Urinalysis- Erythrocytes in Urine, Leukocytes in Urine, Renal Epithelial Casts, Squamous Epithelial Cells, Transitional Epithelial Cells

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  21. Change From Baseline in Clinical Laboratory Parameters: Urinalysis- Hyaline Casts

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  22. Change From Baseline in Clinical Laboratory Parameters: Urinalysis- pH

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  23. Change From Baseline in Clinical Laboratory Parameters: Coagulation- Activated Partial Thromboplastin Time, Prothrombin Time

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  24. Change From Baseline in Clinical Laboratory Parameters: Coagulation- Prothrombin International (Intl) Normalized Ratio

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  25. Change From Baseline in Electrocardiograms (ECGs) Parameters: Mean Heart Rate

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  26. Change From Baseline in ECG Parameters - PR Interval Aggregate, QRS Duration Aggregate, QT Interval Aggregate and QTcF Interval Aggregate

    Last value on study is defined as the last post-baseline value on or after the first dose of IP and on or before the last date of the study.

    Measured: Baseline; Last value on study (up to 24 months)

  27. Number of Participants With Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Responses

    Columbia Suicide Severity Rating Scale evaluates and assesses the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and post-baseline evaluation that focuses on suicidality since last study visit. C-SSRS includes "yes" or "no"' responses for assessment of SI and SB as well as numeric ratings for severity of ideation. If present [from 1 (minor physical damage) to 5 (death), with 5 being most severe]. If any of the available assessments in suicidal behavior is Yes, the category is considered as 'Suicidal behavior'. If any of these available assessments in suicidal ideation is Yes but all available assessments in suicidal behavior is NO, the category is considered as 'Suicidal Ideation'. Data is reported for only those timepoints where there was a change in assessment (response) from Baseline. Baseline is the worst of assessments done in any question in SI/SB prior to first dose of IP, excluding lifetime assessment.

    Measured: Day 30, Day 60, Day 90, Day 365, Day 395, Safety Follow-up (up to 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2022
  2. Study start14 Dec 2022
  3. Primary completion20 Jan 2025
  4. Study completion20 Jan 2025

Why it stopped: Internal company decision

Resources

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 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05655520
Sponsor's protocol ID
718-CIH-301
Status last verified
Aug 2025
First submitted
9 Dec 2022
Last updated
17 Dec 2025
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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SAGE-718 in people with Huntington's Disease, run by Supernus Pharmaceuticals, Inc. at 43 sites in 4 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 11 inclusion and 11 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: stopped early, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States, United Kingdom, Australia, 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 17 Dec 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?

Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs) (time frame: Up to 24 months). The study lists 27 primary outcomes in all. 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 17 Dec 2025.

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