Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease
Primary Purpose
Early Alzheimer's Disease
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALZ-801
Sponsored by
About this trial
This is an interventional treatment trial for Early Alzheimer's Disease
Eligibility Criteria
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.
Sites / Locations
- St. Anne's University Hospital
- Motol University Hospital
- Vestra Clinics
- Brain Research Center
- Brain Research Center
- Brain Research Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Active treatment
Arm Description
ALZ-801 265 mg tablets once daily for two weeks and twice daily thereafter
Outcomes
Primary Outcome Measures
Plasma Biomarker of Core AD Pathology
Percent change from baseline in p-tau181
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.
Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume
Change from baseline in hippocampal volume measured in mm3
Secondary Outcome Measures
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
vMRI Biomarker - Ventricular volume and Cortical Thickness
Change from baseline in cortical thickness measured in mm3
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04693520
Brief Title
Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 30, 2020 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alzheon Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early Alzheimer's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
84 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active treatment
Arm Type
Experimental
Arm Description
ALZ-801 265 mg tablets once daily for two weeks and twice daily thereafter
Intervention Type
Drug
Intervention Name(s)
ALZ-801
Intervention Description
ALZ-801 265 mg twice daily (BID)
Primary Outcome Measure Information:
Title
Plasma Biomarker of Core AD Pathology
Description
Percent change from baseline in p-tau181
Time Frame
Week 104
Title
Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE)
Description
Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAE, and TEAE leading to withdrawal.
Time Frame
Week 108
Title
Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume
Description
Change from baseline in hippocampal volume measured in mm3
Time Frame
Week 104
Secondary Outcome Measure Information:
Title
Plasma Biomarkers of AD and Neurodegeneration
Description
Percent changes from baseline in: Aβ-40, Aβ-42,p-tau217 and plasma glial fibrillary acidic protein (GFAP),NfL
Time Frame
Week 104
Title
vMRI Biomarker - Ventricular volume and Cortical Thickness
Description
Change from baseline in cortical thickness measured in mm3
Time Frame
Week 104
Title
Additional CSF Biomarkers of AD Pathology and Neurodegeneration
Description
Percent changes from baseline for: p-tau217,Aβ-40, Aβ-42, NfL, t-tau, sTREM2, YKL-40 and neurogranin
Time Frame
Week 104
Other Pre-specified Outcome Measures:
Title
Cognitive assessment - Rey Auditory Verbal Learning Test (RAVLT)
Description
Change from baseline in RAVLT score
Time Frame
104 weeks
Title
Cognitive Assessment - Digit Symbol Substitution Test (DSST)
Description
Change from baseline in DSST score
Time Frame
104 weeks
Title
Functional Assessment - Amsterdam Instrumental Activities of Daily Living (A-IADL)
Description
Change from baseline in A-IADL score
Time Frame
104 weeks
Title
Cognitive Assessment - Mini Mental State Examination (MMSE)
Description
Change from baseline in MMSE score
Time Frame
104 weeks
Title
Global Assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB)
Description
Change from baseline in CDR-SB score
Time Frame
104 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Hey, PhD
Organizational Affiliation
Alzheon Inc.
Official's Role
Study Director
Facility Information:
Facility Name
St. Anne's University Hospital
City
Brno
Country
Czechia
Facility Name
Motol University Hospital
City
Prague
Country
Czechia
Facility Name
Vestra Clinics
City
Rychnov Nad Kněžnou
Country
Czechia
Facility Name
Brain Research Center
City
Amsterdam
Country
Netherlands
Facility Name
Brain Research Center
City
Den Bosch
Country
Netherlands
Facility Name
Brain Research Center
City
Zwolle
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease
We'll reach out to this number within 24 hrs