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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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
排除标准
- •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 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.
研究组 & 干预措施
Cohort 1 (Direct Rollover)
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.
干预措施: SAGE-718 (Drug)
Cohort 2 (Gap Rollover)
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.
干预措施: SAGE-718 (Drug)
Cohort 3 (De Novo)
Participants who were not previously included in any SAGE-718 clinical study. Participants will receive Sage-718 from Day 1 onwards.
干预措施: SAGE-718 (Drug)
结局指标
主要结局
Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to 24 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 IP, or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study.
Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Bicarbonate, Calcium, Chloride, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Phosphate, Potassium, Sodium, Triglycerides, Urea Nitrogen
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Albumin and Protein
时间窗: Baseline; Last value on study (up to 24 months)
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.
Number of Participants With at Least One TEAE by Severity
时间窗: Up to 24 months
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.
Number of Participants Who Withdrew From Study Due to TEAEs
时间窗: Up to 24 months
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.
Change From Baseline in Vital Signs: Blood Pressure
时间窗: Baseline; Last Value on Study (up to 24 months)
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.
Change From Baseline in Vital Signs: Heart Rate
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Vital Signs: Respiratory Rate
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Vital Signs: Temperature
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Hematology - Basophils, Eosinophils, Erythrocytes, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Hematology- Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Hematology- Erythrocytes (Ery.) Mean Corpuscular Hemoglobin (HGB) Concentration, Hemoglobin
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Hematology - Erythrocytes Mean Corpuscular Hemoglobin
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Hematology - Erythrocytes Mean Corpuscular Volume
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Hematology - Hematocrit
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Biochemistry- Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase
时间窗: Baseline, Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Bilirubin, Creatinine, Direct Bilirubin, Indirect Bilirubin
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Thyrotropin
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Biochemistry - Thyroxine Free, Triiodothyronine Free
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Urinalysis- Erythrocytes in Urine, Leukocytes in Urine, Renal Epithelial Casts, Squamous Epithelial Cells, Transitional Epithelial Cells
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Urinalysis- Hyaline Casts
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Urinalysis- pH
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Coagulation- Activated Partial Thromboplastin Time, Prothrombin Time
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Clinical Laboratory Parameters: Coagulation- Prothrombin International (Intl) Normalized Ratio
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in Electrocardiograms (ECGs) Parameters: Mean Heart Rate
时间窗: Baseline; Last value on study (up to 24 months)
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.
Change From Baseline in ECG Parameters - PR Interval Aggregate, QRS Duration Aggregate, QT Interval Aggregate and QTcF Interval Aggregate
时间窗: Baseline; Last value on study (up to 24 months)
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.
Number of Participants With Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Responses
时间窗: Day 30, Day 60, Day 90, Day 365, Day 395, Safety Follow-up (up to 24 months)
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.
次要结局
未报告次要终点