A Phase 2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in Heterozygous Carriers of Granulin or C9orf72 Mutations Causative of Frontotemporal Dementia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Alector Inc.
- 入组人数
- 33
- 试验地点
- 12
- 主要终点
- Severity of TEAEs
研究概览
简要总结
A Phase 2 open label study evaluating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AL001 in participants with a Granulin mutation or C9orf72 mutation causative of frontotemporal dementia.
详细描述
This is a Phase 2, multicenter, open label study evaluating the safety, tolerability, PK and PD of AL001 administered intravenously in participants with a Granulin mutation or C9orf72 mutation causative of frontotemporal dementia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At screening, female participants must be nonpregnant and nonlactating
- •In good physical health on the basis of no clinically significant findings from medical history, physical examinations (PEs), laboratory tests, ECGs, and vital signs.
- •Participant is a carrier of a loss of function progranulin gene (GRN) mutation or carrier of a hexanucleotide repeat expansion C9orf72 mutation
排除标准
- •Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
- •History of alcohol abuse or substance abuse
- •Participant resides in a skilled nursing facility, convalescent home, or long term care facility
研究组 & 干预措施
Granulin and C9orf72
IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]
干预措施: AL001 (Drug)
结局指标
主要结局
Severity of TEAEs
时间窗: 197 weeks
Number of TEAEs categorized by severity
Severity of Treatment-Related TEAEs
时间窗: 197 weeks
Number of treatment-related TEAEs categorized by severity
Any TEAE Leading to Study Drug Discontinuation
时间窗: 197 weeks
Number of TEAEs leading to study drug discontinuation
Immunogenicity Antidrug Antibodies (ADA) Titer
时间窗: 97 weeks
Titer values of antidrug antibodies (ADAs) in participants receiving latozinemab at week 97/Part 1 end of study
Confirmatory Immunogenicity Antidrug Antibodies (ADA) Responses
时间窗: 97 weeks
Presence of confirmatory antidrug antibodies (ADAs) in participants who test positive for ADA at week 97 (Part 1 End of Study).
Change From Baseline in Sheehan Suicidality Tracking Scale
时间窗: 197 weeks
The Sheehan Suicidality Tracking Scale (S-STS) is a structured assessment tool used to evaluate the presence, severity, and frequency of suicidal ideation and behavior. It includes items that address passive thoughts of death, active suicidal ideation, intent, planning, suicide attempts, and non-suicidal self-injury. The S-STS total score ranges from 0 to 64, based on 16 items each rated from 0 (not at all) to 4 (extremely), with higher scores indicating greater severity of suicidal ideation, intent, or behavior. The total score provides a quantitative measure of suicidality severity and is sensitive to change over time, making it suitable for clinical monitoring and research use.
次要结局
- Longitudinal Percent Change From Baseline of CSF PGRN(97 weeks)
- Latozinemab Concentration in Serum(97 weeks)
- Cmax of Latozinemab at Specified Timepoints(97 weeks)
- Longitudinal Levels of Sortilin in WBCs(97 weeks)
- Ctrough of Latozinemab at Specified Timepoints(97 weeks)
- ARCmax of Latozinemab(61 weeks)
- Longitudinal Percent Change From Baseline in Plasma PGRN(97 weeks)