Clinical trial NCT04693520: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Early Alzheimer's Disease
Lead sponsor: Alzheon Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-05
Enrollment: 84
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Plasma Biomarker of Core AD Pathology
timeFrame: Week 104
measure: Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE)
timeFrame: Week 108
measure: Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume
timeFrame: Week 104
Secondary outcomes:
measure: Plasma Biomarkers of AD and Neurodegeneration
timeFrame: Weeks 104 and 156
measure: vMRI Biomarker - Ventricular volume and Cortical Thickness
timeFrame: Weeks 104 and 156
measure: Additional CSF Biomarkers of AD Pathology and Neurodegeneration
timeFrame: Weeks 104 and 156
measure: Plasma Biomarker of Core AD Pathology
timeFrame: Week 156
measure: Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE)
timeFrame: Week 160
measure: Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume
timeFrame: Week 156
Other outcomes:
measure: Cognitive assessment - Rey Auditory Verbal Learning Test (RAVLT)
timeFrame: Weeks 104 and 156
measure: Cognitive Assessment - Digit Symbol Substitution Test (DSST)
timeFrame: Weeks 104 and 156
measure: Functional Assessment - Amsterdam Instrumental Activities of Daily Living (A-IADL)
timeFrame: Weeks 104 and 156
measure: Cognitive Assessment - Mini Mental State Examination (MMSE)
timeFrame: Weeks 104 and 156
measure: Global Assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB)
timeFrame: Weeks 104 and 156
Locations:
city: Brno
country: Czechia
facility: St. Anne's University Hospital
city: Prague
country: Czechia
facility: Motol University Hospital
city: Rychnov Nad Kněžnou
country: Czechia
facility: Vestra Clinics
city: Amsterdam
country: Netherlands
facility: Brain Research Center
city: Den Bosch
country: Netherlands
facility: Brain Research Center
city: Zwolle
country: Netherlands
facility: Brain Research Center
Study officials:
affiliation: Alzheon Inc.
name: John Hey, PhD
role: STUDY_DIRECTOR
References: