A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety and Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease and APOE4/4 Genotype
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Alzheon Inc.
- 入组人数
- 325
- 试验地点
- 186
- 主要终点
- Primary Cognitive Efficacy Endpoint (ADAS-Cog13)
研究概览
简要总结
This study is being conducted to evaluate the safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is a double-blind, randomized trial with one dose of ALZ-801 compared to placebo.
详细描述
This is a multi-center, double-blind study that will evaluate 265 mg twice daily (BID) of ALZ-801, an oral tablet, over 78 weeks as a treatment for subjects (50-80 years old) with Early AD who are homozygous for the ε4 allele of the apolipoprotein gene (APOE4 homozygous or APOE4/4). The primary efficacy outcome assessment is a measure of cognition (ADAS-cog 13). Additional measures of global and functional impairments will also be assessed. Imaging and soluble biomarkers of AD and neurodegeneration will be measured and a sub-study to evaluate cerebrospinal fluid (CSF) biomarkers is also included.
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
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of MCI or Mild Dementia due to AD consistent with the National Institute on Aging-Alzheimer's Association (NIA-AA) Working Group Criteria.
- •Homozygous for the ε4 allele of the apolipoprotein E gene (APOE4/4).
- •MMSE score at Screening of 22 to 30 (inclusive).
- •CDR - Global score of 0.5 or 1 and CDR Memory Box Score of ≥ 0.
- •RBANS delayed memory index score ≤
- •Evidence of progressive memory loss over the last 12 months per investigator assessment
排除标准
- •Brain magnetic resonance imaging (MRI) indicative of significant abnormality per central reader, other than AD related atrophy. Computed tomography (CT) scan acceptable for subjects who cannot undergo MRI.
- •Diagnosis of neurodegenerative disorder other than AD.
- •Diagnosis of major depressive disorder (MDD) within one year prior to screening.
- •Currently taking memantine or has taken memantine within 12 weeks prior to the Baseline Visit.
- •History of suicidal behavior within one year prior to screening or has ongoing suicidal ideation.
- •History of seizures, excluding febrile seizures of childhood or a single distant seizure (> 5 years).
- •Medically confirmed history of recent cerebral infarct or transient ischemic attack within one year prior to screening.
结局指标
主要结局
Primary Cognitive Efficacy Endpoint (ADAS-Cog13)
时间窗: Baseline to Week 78
Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog13) scores. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity.
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE)
时间窗: Entire study: approximately 82 weeks. (first dose of study drug until end of Safety Follow-up Visit at 28 +/- 7 days after the last dose (ie, 78-week treatment period plus 4-weeks follow-up after last dose up to total of 82 weeks)
Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAEs, and TEAEs leading to withdrawal.
次要结局
- Key Secondary Endpoint (A-IADL-W)(Baseline to Week 78)
- Key Secondary Endpoint (CDR-SB)(Baseline to Week 78)
- Functional Assessment (DAD)(Baseline to Week 78)
- Global Cognition Assessment (MMSE)(Baseline to Week 78)