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

Early Alzheimer's Disease Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04693520
• Other study ID #: ALZ-801-201ADBM
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 30, 2020
• Est. completion date: August 2024

Study information

• Verified date: January 2024
• Source: Alzheon Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 84
• Est. completion date: August 2024
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Early Alzheimer's Disease

Intervention

Drug:
• ALZ-801
ALZ-801 265 mg twice daily (BID)

Locations

Country	Name	City	State
Czechia	St. Anne's University Hospital	Brno
Czechia	Motol University Hospital	Prague
Czechia	Vestra Clinics	Rychnov Nad Knežnou
Netherlands	Brain Research Center	Amsterdam
Netherlands	Brain Research Center	Den Bosch
Netherlands	Brain Research Center	Zwolle

Sponsors (1)

Lead Sponsor	Collaborator
Alzheon Inc.

Countries where clinical trial is conducted

Czechia,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognitive assessment - Rey Auditory Verbal Learning Test (RAVLT)	Change from baseline in RAVLT score	Weeks 104 and 156
Other	Cognitive Assessment - Digit Symbol Substitution Test (DSST)	Change from baseline in DSST score	Weeks 104 and 156
Other	Functional Assessment - Amsterdam Instrumental Activities of Daily Living (A-IADL)	Change from baseline in A-IADL score	Weeks 104 and 156
Other	Cognitive Assessment - Mini Mental State Examination (MMSE)	Change from baseline in MMSE score	Weeks 104 and 156
Other	Global Assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB)	Change from baseline in CDR-SB score	Weeks 104 and 156
Primary	Plasma Biomarker of Core AD Pathology	Percent change from baseline in p-tau181	Week 104
Primary	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
Primary	Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume	Change from baseline in hippocampal volume measured in mm3	Week 104
Secondary	Plasma Biomarkers of AD and Neurodegeneration	Percent changes from baseline in: Aß-40, Aß-42,p-tau217 and plasma glial fibrillary acidic protein (GFAP),NfL	Weeks 104 and 156
Secondary	vMRI Biomarker - Ventricular volume and Cortical Thickness	Change from baseline in cortical thickness measured in mm3	Weeks 104 and 156
Secondary	Additional CSF Biomarkers of AD Pathology and Neurodegeneration	Percent changes from baseline for: p-tau217,Aß-40, Aß-42, NfL, t-tau, sTREM2, YKL-40 and neurogranin	Weeks 104 and 156
Secondary	Plasma Biomarker of Core AD Pathology	Percent change from baseline in p-tau181	Week 156
Secondary	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
Secondary	Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume	Change from baseline in hippocampal volume measured in mm3	Week 156