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
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Early Alzheimer's Disease
- Sponsor
- Alzheon Inc.
- Enrollment
- 325
- Locations
- 91
- Primary Endpoint
- Primary Cognitive Efficacy Endpoint (ADAS-Cog13)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Primary Cognitive Efficacy Endpoint (ADAS-Cog13)
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- 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)