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

Huntington Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05655520
• Other study ID #: 718-CIH-301
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2022
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Sage Therapeutics
• Contact: Grant Rutledge, PhD
• Phone: 339-368-8432
• Email: grant.rutledge[@]sagerx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• SAGE-718
Oral softgel lipid capsules

Locations

Country	Name	City	State
Canada	Sage Investigational Site	Toronto	Ontario
United States	Sage Investigational Site	Boca Raton	Florida
United States	Sage Investigational Site	Charleston	South Carolina
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Cincinnati	Ohio
United States	Sage Investigational Site	Englewood	Colorado
United States	Sage Investigational Site	Iowa City	Iowa
United States	Sage Investigational Site	La Jolla	California
United States	Sage Investigational Site	Los Alamitos	California
United States	Sage Investigational Site	Los Angeles	California
United States	Sage Investigational Site	Memphis	Tennessee
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Richmond	Virginia
United States	Sage Investigational Site	Spokane	Washington
United States	Sage Investigational Site	Tampa	Florida
United States	Sage Investigational Site	Toledo	Ohio
United States	Sage Investigational Site	Washington	District of Columbia
United States	Sage Investigational Site	Williamsville	New York

Sponsors (1)

Lead Sponsor	Collaborator
Sage Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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