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

NCT05655520 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: 718-CIH-301
• Study Type: interventional
• Target: 153
• Locations: 4 countries
• Sites: 43

Brief 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)

Conditions

Huntington's Disease

Keywords

Huntington's Disease; SAGE-718

Outcome Measures

Primary Outcomes (27)

• 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.

  Up to 24 months

• 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.

  Up to 24 months

• 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.

  Up to 24 months

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

Study Arms (3)

Cohort 1 (Direct Rollover)

EXPERIMENTAL

Participants 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.

Drug: SAGE-718

Cohort 2 (Gap Rollover)

EXPERIMENTAL

Participants 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.

Drug: SAGE-718

Cohort 3 (De Novo)

EXPERIMENTAL

Participants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 onwards.

Drug: SAGE-718

Interventions

SAGE-718 DRUG

Oral softgel lipid capsules

Cohort 1 (Direct Rollover); Cohort 2 (Gap Rollover); Cohort 3 (De Novo)

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (43)

Sage Investigational Site

Birmingham, Alabama, 35233, United States

Location

Sage Investigational Site

Little Rock, Arkansas, 72205, United States

Location

Sage Investigational Site

La Jolla, California, 92037, United States

Location

Sage Investigational Site

Los Alamitos, California, 90720, United States

Location

Sage Investigational Site

Los Angeles, California, 90095, United States

Location

Sage Investigational Site

Sacramento, California, 95817, United States

Location

Sage Investigational Site

Englewood, Colorado, 80113, United States

Location

Sage Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

Sage Investigational Site

Boca Raton, Florida, 33431, United States

Location

Sage Investigational Site

Tampa, Florida, 33612, United States

Location

Sage Investigational Site

Chicago, Illinois, 60611, United States

Location

Sage Investigational Site

Chicago, Illinois, 60612, United States

Location

Sage Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Sage Investigational Site

Iowa City, Iowa, 52242, United States

Location

Sage Investigational Site

Kansas City, Kansas, 66103, United States

Location

Sage Investigational Site

Baltimore, Maryland, 21287, United States

Location

Sage Investigational Site

Boston, Massachusetts, 02215, United States

Location

Sage Investigational Site

New York, New York, 10032, United States

Location

Sage Investigational Site

Williamsville, New York, 14221, United States

Location

Sage Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

Sage Investigational Site

Durham, North Carolina, 27705, United States

Location

Sage Investigational Site

Cincinnati, Ohio, 45219, United States

Location

Sage Investigational Site

Toledo, Ohio, 43614, United States

Location

Sage Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

Sage Investigational Site

Charleston, South Carolina, 29425, United States

Location

Sage Investigational Site

Memphis, Tennessee, 38157, United States

Location

Sage Investigational Site

Houston, Texas, 77030, United States

Location

Sage Investigational Site

Richmond, Virginia, 23298, United States

Location

Sage Investigational Site

Spokane, Washington, 99202, United States

Location

Sage Investigational Site

Westmead, New South Wales, 2145, Australia

Location

Sage Investigational Site

Caulfield South, Victoria, 3162, Australia

Location

Sage Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

Sage Investigational Site

Halifax, Nova Scotia, B3S1N2, Canada

Location

Sage Investigational Site

Toronto, Ontario, M2K 1E1, Canada

Location

Sage Investigational Site

Montreal, Quebec, H2X1R9, Canada

Location

Sage Investigational Site

Plymouth, Derriford, PL6 8BT, United Kingdom

Location

Sage Investigational Site

Southampton, England, SO16 6YD, United Kingdom

Location

Sage Investigational Site

Tooting, London, SW17 0QT, United Kingdom

Location

Sage Investigational Site

Aberdeen, Scotland, AB25 2ZA, United Kingdom

Location

Sage Investigational Site

Newcastle, Upon Tyne, NE6 4QD, United Kingdom

Location

Sage Investigational Site

Cardiff, Wales, CF144XW, United Kingdom

Location

Sage Investigational Site

Birmingham, West Midlands, B15 2FG, United Kingdom

Location

Sage Investigational Site

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Gianpiera Ceresoli-Borroni PhD
• Organization: Supernus Pharmaceuticals, Inc.

gceresoliborroni@supernus.com

3018382521

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: December 19, 2022
• Study Start: December 14, 2022
• Primary Completion: January 20, 2025
• Study Completion: January 20, 2025
• Last Updated: December 17, 2025
• Results First Posted: December 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (8); CA (3); US (29); AU (3)