Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease

Study Overview
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Brief Summary
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The study will investigate the effects of oral ALZ-801, in subjects with Early AD who have the APOE4/4 or APOE3/4 genotype, on the biomarkers of core AD pathology. The objectives of this study include determining the efficacy and safety/tolerability of ALZ-801. In addition, the study will evaluate the extended PK profile over 8 hours in 16 subjects after 65 weeks of treatment.

Official Title
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A Phase 2, Single-arm Study of the Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease Who Are Carriers of the ε4 Variant of the Apolipoprotein E Gene (APOE4/4 or APOE3/4)

Conditions
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Early Alzheimer's Disease

Intervention / Treatment
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* Drug: ALZ-801


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age between 50 and 80 years, inclusive. Early Alzheimer's Disease (AD): a diagnosis of Probable AD Dementia or Mild Cognitive Impairment (MCI) due to AD in accordance with the National Institute on Aging-Alzheimer's Association (NIA-AA) Working Group Criteria [Albert et al, 2011; McKhann et al, 2011]. One of the following apolipoprotein E (APOE) genotypes - either APOE4/4 (homozygous) or APOE3/4 (heterozygous). MMSE score 22 to 30 inclusive; Clinical Dementia Rating (CDR)-Global Score of 0.5 or 1.0, and CDR Memory Box Score of ≥ 0.5. Documented confirmation of AD diagnosis by either positive amyloid positron emission tomography (PET) or positive CSF AD signature. Subjects without documented positive AD biomarker status must have a positive CSF biomarker result from a sample provided at screening. Stable doses of acetylcholinesterase for the duration of the study are allowed. Exclusion Criteria Brain MRI at screening indicative of significant abnormality Diagnosis of neurodegenerative disorder other than AD Current diagnosis of Major Depressive Disorder (MDD) Concomitant treatment with memantine.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment<br>ALZ-801 265 mg tablets once daily for two weeks and twice daily thereafter | Drug: ALZ-801<br>* ALZ-801 265 mg twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Biomarker of Core AD Pathology | Percent change from baseline in p-tau181 | Week 104 | 
| 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 108 | 
| Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume | Change from baseline in hippocampal volume measured in mm3 | Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Biomarkers of AD and Neurodegeneration | Percent changes from baseline in: Aβ-40, Aβ-42,p-tau217 and plasma glial fibrillary acidic protein (GFAP),NfL | Week 104 | 
| vMRI Biomarker - Ventricular volume and Cortical Thickness | Change from baseline in cortical thickness measured in mm3 | Week 104 | 
| Additional CSF Biomarkers of AD Pathology and Neurodegeneration | Percent changes from baseline for: p-tau217,Aβ-40, Aβ-42, NfL, t-tau, sTREM2, YKL-40 and neurogranin | Week 104 |