An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects

Study Overview
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Brief Summary
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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
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This is a multi-center, double-blind study that will evaluate 265 mg 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.

Official Title
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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

Conditions
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Early Alzheimer's Disease

Intervention / Treatment
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* Drug: Experimental: ALZ-801
* Drug: Placebo Comparator: Placebo


Participation Criteria
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Eligibility Criteria
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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 ≥ 0.5. RBANS delayed memory index score ≤ 85. 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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multi-center Phase 3, randomized, double-blind, placebo-controlled, parallel-group study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALZ-801<br>ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. | Drug: Experimental: ALZ-801<br>* ALZ-801 tablet 265 mg BID<br>|
| Placebo Comparator: Placebo<br>Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study | Drug: Placebo Comparator: Placebo<br>* Placebo tablet BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary cognitive efficacy endpoint | Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks | Week 78 | 
| Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE) | Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAE, and TEAE leading to withdrawal. | Week 78 | 
| Primary fluid biomarker endpoint 1 | Change from baseline in cerebrospinal fluid p-tau181 levels in sub-study | Week 78 | 
| Primary fluid biomarker endpoint 2 | Change from baseline in plasma p-tau181 levels | Week 78 | 
| Primary imaging biomarker endpoint | Change from baseline in total hippocampal volume (mm3) as measured by Magnetic Resonance Imaging (MRI) | Week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional assessment 1 | Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores | Week 78 | 
| Global assessment | Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores | Week 78 | 
| Functional assessment 2 | Change from baseline in Disability Assessment for Dementia (DAD)scores | Week 78 |