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

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Huntington Disease

Intervention / Treatment
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* Drug: SAGE-718


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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): 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. Either Unified Huntington's Disease Rating Scale (UHDRS) -Total Functional Capacity (TFC)=13 or Montreal Cognitive Assessment (MoCA) >25 score at Screening (one or the other; not both) Exclusion Criteria: 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): 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 ongoing serious adverse events 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Direct Rollover)<br>Participants from studies 718-CIH-201 (NCT05107128)/202 (NCT05358821) who will sign the informed consent for study 718-CIH-301 ≤7 days after the last day of the corresponding parent study. Participants will receive Sage-718 from Day 1 up to Day 365. | Drug: SAGE-718<br>* Oral softgel lipid capsules<br>|
| Experimental: Cohort 2 (Gap Rollover)<br>Participants from studies 718-CIH-201 (NCT05107128)/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. Participants will receive Sage-718 from Day 1 up to Day 365. | Drug: SAGE-718<br>* Oral softgel lipid capsules<br>|
| Experimental: Cohort 3 (De Novo)<br>Participants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 up to Day 365. | Drug: SAGE-718<br>* Oral softgel lipid capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Severity of 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 Investigational Product (IP), or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Severity will be graded as mild (barely noticeable to the participant/does not make participant uncomfortable); moderate (discomfort sufficient to cause interference with normal activities); severe (incapacitating, with significant impact to perform normal activities). | Up to 13 months | 
| Number of Participants Who Withdrew Due to Adverse Events (AEs) | 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 AE can therefore be any unfavourable 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. | Up to 13 months | 
| Percentage of Participants with Change From Baseline in Vital Signs, Clinical Laboratory Parameters and Electrocardiograms (ECGs) Parameters | Vital signs will include body temperature, respiratory rate, heart rate and blood pressure. Laboratory parameters will include haematology, biochemistry, coagulation, and urinalysis. ECG parameters such as heart rate, PR, QRS, QT, and QT corrected according to Fridericia's formula [QTcF] will be recorded. | Up to 13 months | 
| Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Responses | The C-SSRS scale consists of baseline evaluation that assesses lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and postbaseline evaluation that focused 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]. C-SSRS SI items involve (a) wish to be dead, (b) non-specific active suicidal thoughts, (c) active SI with any methods (not plan) without intent to act, (d) active SI with some intent to act, without specific plan and (e) active SI with specific plan and intent. C-SSRS SB items involves (a) actual attempt, (b) engaged in non-suicidal self-injurious behavior, (c) interrupted attempt, (d) aborted attempt, (e) preparatory acts or behavior, (f) suicidal behavior. | Up to 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington Disease, SAGE-718