A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington's Disease
Study Details
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 (Direct Rollover) 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
Oral softgel lipid capsules
|
| Experimental: Cohort 2 (Gap Rollover) 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
Oral softgel lipid capsules
|
| Experimental: Cohort 3 (De Novo) 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
Oral softgel lipid capsules
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Severity of TEAEs [Up to 13 months]
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) [Up to 13 months]
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 [Up to 13 months]
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 [Up to 13 months]
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.
Eligibility Criteria
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.
Additional inclusion criteria for 718-CIH-201/202 completers who enroll after a gap of >7 days since completion of the parent study (Cohort 2)
- No significant decline in functional status since last visit in 718-CIH-201 or 718-CIH-202, in the opinion of the investigator.
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.
-
UHDRS-Total Functional Capacity (TFC)=13 or Montreal Cognitive Assessment (MoCA) >25 score at Screening.
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.
Additional exclusion criteria for the de novo cohort (Cohort 3):
- Have participated in a previous clinical study of SAGE-718, have participated in a previous gene therapy study, or have participated in any other drug, biologic, or device trial within 30 days or 5 half-lives (whichever is longer), unless the patient participated solely in the placebo arm of the study. Additionally, participants who have received treatment with antisense oligonucleotides or an mRNA splicing modifier will 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sage Investigational Site | Englewood | Colorado | United States | 80113 |
| 2 | Sage Investigational Site | Memphis | Tennessee | United States | 38157 |
| 3 | Sage Investigational Site | Spokane | Washington | United States | 99202 |
Sponsors and Collaborators
- Sage Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 718-CIH-301