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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Early Alzheimer's Disease
• Intervention / Treatment: Drug: ALZ-801

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • St. Anne's University Hospital
  • Prague, Czechia
    • Motol University Hospital
  • Rychnov Nad Kněžnou, Czechia
    • Vestra Clinics
• Netherlands
  • Amsterdam, Netherlands
    • Brain Research Center
  • Den Bosch, Netherlands
    • Brain Research Center
  • Zwolle, Netherlands
    • Brain Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age between 50 and 80 years, inclusive.
2. 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].
3. One of the following apolipoprotein E (APOE) genotypes - either APOE4/4 (homozygous) or APOE3/4 (heterozygous).
4. 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.
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.
6. Stable doses of acetylcholinesterase for the duration of the study are allowed.

Exclusion Criteria

1. Brain MRI at screening indicative of significant abnormality
2. Diagnosis of neurodegenerative disorder other than AD
3. Current diagnosis of Major Depressive Disorder (MDD)
4. Concomitant treatment with memantine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Plasma Biomarker of Core AD Pathology	Percent change from baseline in p-tau181	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	Weeks 104 and 156
vMRI Biomarker - Ventricular volume and Cortical Thickness	Change from baseline in cortical thickness measured in mm3	Weeks 104 and 156
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	Weeks 104 and 156
Plasma Biomarker of Core AD Pathology	Percent change from baseline in p-tau181	Week 156
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 160
Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume	Change from baseline in hippocampal volume measured in mm3	Week 156

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive assessment - Rey Auditory Verbal Learning Test (RAVLT)	Change from baseline in RAVLT score	Weeks 104 and 156
Cognitive Assessment - Digit Symbol Substitution Test (DSST)	Change from baseline in DSST score	Weeks 104 and 156
Functional Assessment - Amsterdam Instrumental Activities of Daily Living (A-IADL)	Change from baseline in A-IADL score	Weeks 104 and 156
Cognitive Assessment - Mini Mental State Examination (MMSE)	Change from baseline in MMSE score	Weeks 104 and 156
Global Assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB)	Change from baseline in CDR-SB score	Weeks 104 and 156

Collaborators and Investigators

• Sponsor: Alzheon Inc.
• Investigators: Study Director: John Hey, PhD, Alzheon Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): August 31, 2023
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: December 28, 2020
• First Submitted That Met QC Criteria: December 31, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: ALZ-801-201ADBM

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No