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

Primary Purpose

Huntington Disease

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SAGE-718
Sponsored by
Sage Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington Disease focused on measuring Huntington Disease, SAGE-718

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting
  • Sage Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1 (Direct Rollover)

Cohort 2 (Gap Rollover)

Cohort 3 (De Novo)

Arm Description

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.

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.

Participants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 up to Day 365.

Outcomes

Primary Outcome Measures

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).
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
December 9, 2022
Last Updated
September 29, 2023
Sponsor
Sage Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05655520
Brief Title
A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sage Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
Keywords
Huntington Disease, SAGE-718

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 (Direct Rollover)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2 (Gap Rollover)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3 (De Novo)
Arm Type
Experimental
Arm Description
Participants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 up to Day 365.
Intervention Type
Drug
Intervention Name(s)
SAGE-718
Intervention Description
Oral softgel lipid capsules
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Severity of TEAEs
Description
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).
Time Frame
Up to 13 months
Title
Number of Participants Who Withdrew Due to Adverse Events (AEs)
Description
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.
Time Frame
Up to 13 months
Title
Percentage of Participants with Change From Baseline in Vital Signs, Clinical Laboratory Parameters and Electrocardiograms (ECGs) Parameters
Description
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.
Time Frame
Up to 13 months
Title
Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Responses
Description
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.
Time Frame
Up to 13 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Grant Rutledge, PhD
Phone
339-368-8432
Email
grant.rutledge@sagerx.com
Facility Information:
Facility Name
Sage Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Los Alamitos
State/Province
California
ZIP/Postal Code
90720
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33431
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Williamsville
State/Province
New York
ZIP/Postal Code
14221
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38157
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com
Facility Name
Sage Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M2K 1E1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
Email
clinicaltrialsinquiry@sagerx.com

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data sharing will be consistent with the results submission policy of ClinicalTrials.gov

Learn more about this trial

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

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