A Phase 3, Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of AL001 in Individuals at Risk for or With Frontotemporal Dementia Due to Heterozygous Mutations in the Progranulin Gene
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Alector Inc.
- 入组人数
- 119
- 试验地点
- 44
- 主要终点
- Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB
研究概览
简要总结
A phase 3 double blind, placebo controlled study evaluating the efficacy and safety of AL001 in participants at risk for or with frontotemporal dementia due to heterozygous mutations in the progranulin gene.
详细描述
This is a phase 3 double blind, placebo controlled study evaluating the efficacy and safety of AL001 administered intravenously in participants at risk for or with frontotemporal dementia due to heterozygous mutations in the progranulin gene. Study completion marks the end of the open label extension period following the 96-week blinded portion of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Persons with a progranulin gene mutation and at risk of developing FTD symptoms as evidenced by a biomarker, or persons with a progranulin gene mutation and diagnosed with FTD.
- •If symptomatic, one or more of the criteria for the diagnosis of possible behavioral variant FTD, or a diagnosis of Primary Progressive Aphasia.
- •Study partner who consents to study participation and who cares for/visits the participant daily for at least 5 hours per week.
- •Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).
排除标准
- •Dementia due to a condition other than FTD including, but not limited to, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, Huntington disease, or vascular dementia.
- •Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
- •Current uncontrolled hypertension, diabetes mellitus or thyroid disease. Clinically significant heart disease, liver disease or kidney disease. History or evidence of clinically significant brain disease other than FTD.
- •Females who are pregnant or breastfeeding, or planning to conceive within the study period.
- •Any experimental vaccine or gene therapy.
- •History of cancer within the last 5 years.
- •Current use of anticoagulant medications (e.g., coumadin, heparinoids, apixaban).
- •Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care.
研究组 & 干预措施
AL001
AL001 every 4 weeks
干预措施: AL001 (Drug)
Placebo
Placebo every 4 weeks
干预措施: Placebo (Drug)
Open label - AL001
AL001 every 4 weeks
干预措施: Open label - AL001 (Drug)
结局指标
主要结局
Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB
时间窗: Through study completion, on average up to 96 weeks
The Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer's Disease Coordinating Center frontotemporal lobar degeneration Behavior \& Language Domains Sum of Boxes (CDR® plus NACC FTLD-SB) is administered by a healthcare professional and based on individual ratings of the eight domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care, language and behavior. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 8 individual domain ratings, or "box scores", were added together to give the CDR® plus NACC FTLD-SB which ranges from 0-24. Higher score indicates severe impairment.
次要结局
- Evaluation of safety and tolerability of AL001: Incidence of adverse events(Baseline to 96 weeks)
- Change in Clinical Global Impression-Severity (CGI-S) Score(Baseline to 96 weeks)
- Change in Clinical Global Impression-Improvement (CGI-I) Score(Baseline to 96 weeks)
- Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score(Baseline to 96 weeks)
- Pharmacodynamic Biomarkers(Baseline to 96 weeks)