Early Alzheimer's Disease
Conditions
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.
Detailed description
The LTE year 1 & 2 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 LTE study are to continue longitudinal assessment of the efficacy and safety/tolerability of ALZ-801 over a total period of 4 years (2-year Core study plus 2 years of LTE). Core study: ALZ-801 265 mg twice daily (BID) in the Core Study, Weeks 0-104 LTE year 1: ALZ-801 265 mg BID in the Core Study and the Long-Term Extension (LTE, Weeks 104-208) LTE year 2: ALZ-801 265mg BID in the Core Study and LTE Year 1 (Weeks 104-156), and LTE Year 2 (Weeks 156-208)
Interventions
DRUGALZ-801
ALZ-801 265 mg twice daily (BID)
Sponsors
Alzheon Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Biomarker of Core AD Pathology | Week 104 | Percent change from baseline in p-tau181 |
| Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume | Weeks 104 | Change from baseline in hippocampal volume measured in mm3 |
| Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE) | Week 108 | Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAE, and TEAE leading to withdrawal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| vMRI Biomarker - Ventricular volume and Cortical Thickness | Weeks 104, 156 and 208 | Change from baseline in cortical thickness measured in mm3 |
| Plasma Biomarkers of AD and Neurodegeneration | Weeks 104 | Percent changes from baseline in: Aβ-40, Aβ-42,p-tau217 and plasma glial fibrillary acidic protein (GFAP),NfL |
| Additional CSF Biomarkers of AD Pathology and Neurodegeneration | Weeks 104 | Percent changes from baseline for: p-tau217,Aβ-40, Aβ-42, NfL, t-tau, sTREM2, YKL-40 and neurogranin |
| Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE) | Week 160 and week 212 | 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 | Week 156 and week 208 | Change from baseline in hippocampal volume measured in mm3 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Functional Assessment - Amsterdam Instrumental Activities of Daily Living (A-IADL) | Weeks 104, Week 156 and Week 208 | Change from baseline in A-IADL score |
| Global Assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB) | Weeks 104, Week 156 and Week 208 | Change from baseline in CDR-SB score |
| Cognitive Assessment - Digit Symbol Substitution Test (DSST) | Weeks 104, Week 156 and Week 208 | Change from baseline in DSST score |
| Cognitive assessment - Rey Auditory Verbal Learning Test (RAVLT) | Weeks 104, week 156 and week 208 | Change from baseline in RAVLT score |
| Cognitive Assessment - Mini Mental State Examination (MMSE) | Weeks 104, Week 156 and Week 208 | Change from baseline in MMSE score |
Countries
Czechia, Netherlands
Outcome results
None listed