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
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo as Measured by the CDR® Plus NACC FTLD-SB in Symptomatic Patients
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, unless in remission or stable/adequately controlled.
- •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
Part 2 (OLE Treatment) - Placebo Switched to AL001
Participants who received placebo during the double-blind treatment period and enroll in the optional open-label extension receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks.
干预措施: Part 2 (OLE Treatment) - Placebo Switched to AL001 (Drug)
Part 1 Blinded - AL001
Participants receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period.
干预措施: Part 1 Blinded - AL001 (Drug)
Part 1 Blinded - Placebo
Participants receive placebo administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period.
干预措施: Part 1 Blinded - Placebo (Drug)
Part 2 (OLE Treatment) - AL001
Participants who received AL001 during the double-blind treatment period and enroll in the optional open-label extension receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks.
干预措施: Part 2 (OLE Treatment) - AL001 (Drug)
结局指标
主要结局
Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo as Measured by the CDR® Plus NACC FTLD-SB in Symptomatic Patients
时间窗: Through study completion, on average up to 96 weeks
Part 1 Primary Endpoint - Change from baseline to Weeks 48, 72, and 96 in the CDR® plus NACC FTLD-SB. 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.
Part 1 Double Blind (Co-Primary US Endpoint) - Evaluation of the Treatment Effect of AL001 Compared With Placebo as Measured by Pharmacodynamic and Disease Pathology Biomarkers in Symptomatic Patients
时间窗: Baseline to 96 weeks
Geometric Mean Fold Change from baseline to Week 96 in PGRN concentrations in plasma
Part 2 OLE - To Assess the Long-term Safety and Tolerability of AL001 in Participants Who Have Completed Part 1 of the Study
时间窗: 96 weeks
Part 2 OLE Primary Endpoint - Incidence, nature, and severity of AEs and SAEs in Part 2 OLE
次要结局
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-S(Baseline to 96 weeks)
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-I(Baseline to 96 weeks)
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score(Baseline to 96 weeks)
- Part 1 Double Blind - Evaluation of the Safety and Tolerability of AL001 Compared With Placebo as Measured by Safety Assessments(Baseline to 96 weeks)
- Part 1 Double Blind: Clinical Progression as Measured by Frontotemporal Dementia Rating Scale (FRS) Logit Score in Symptomatic Participants(baseline to 96 weeks)