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 *4 Variant of the Apolipoprotein E Gene (APOE4/4 or APOE3/4)

Phase 2

Recruiting

• Conditions: Alzheimer's disease; dementia; 10057167

• Registration Number: NL-OMON56257
• Lead Sponsor: Alzheon Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 42

Inclusion Criteria

1. Be between the ages of 50 and 80 years, inclusive.
2. Has a body weight >= 50 kg.
3. Has a diagnosis of Probable AD Dementia or 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].
4. Has a biomarker profile reflecting AD, according to the NIA-AA Research
Framework [Jack et al, 2018] defined as follows:
a) Positive amyloid PET scan on file prior to Screening
OR
b) CSF AD biomarker result using the Lumipulse (Fujirebio) assay at Screening
with:
i. Aβ42/Aβ40 ratio < 0.61
AND
ii. p-tau > 61 ng/L
OR
iii. If p-tau181 concentration = 50 to 61 ng/L, ratio of p-tau/Aβ42 > 0.11
OR
c) CSF AD biomarker result on file within 12 months prior to Screening that is
positive for Aβ42 (below the cut-off) AND p-tau (above the cut-off) OR a
p-tau181/Aβ42 ratio above the cut-off for that assay (amyloid AND p-tau
positive)
Note 1: Subjects without a prior CSF result must provide a new CSF sample at
the Screening - Part 2 Visit.
Note 2: Subjects with a prior positive CSF result (allowing study enrollment)
must provide 2 to 3 aliquots of CSF from their prior diagnostic assessment; and
the prior CSF result must be recorded.
5. Be willing to undergo LP for CSF testing according to the Schedule of
Assessments.
6. Has one of the following apolipoprotein E (APOE) genotypes - either APOE4/4
(homozygous) or APOE3/4 (heterozygous).
Note: For subjects with a prior (historical) APOE genotype blood test, the test
result must be provided and recorded in the CRF.
7. Has an MMSE score at Screening of 22 to 30 inclusive (> 26 for MCI; 22 to 26
for Mild AD).
8. Has a CDR Global Score at Screening of 0.5 (MCI, Mild AD) or 1 (Mild AD) and
a CDR Memory Box Score of >= 0.5.
9. Has a reliable caregiver or study partner who is willing and able to sign an
informed consent form (ICF), to accompany the subject to study visits, and
adhere to study requirements.
10. Be willing to sign an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC) approved ICF indicating that he/she understands the purpose of
the study and the procedures that are required for the study, and that he/she
is willing to participate in the study. Subjects are free to withdraw consent
at any time. If a subject is unable or deemed not competent to sign the consent
form, the subject*s legally authorized representative may sign the consent form
with the subject*s assent, except where local regulations and IRB/IEC approval
do not allow subjects who are unable or deemed not competent to sign the
consent form, to participate in the study.
Note: Subjects who participate in the PK Profile Substudy for extended PK
sampling will sign an additional consent form specific for the substudy.
11. Can complete the cognitive testing procedures. Corrected visual and
auditory acuity must be adequate to comply with the protocol.
12. Lives at home independently, in a senior living facility, or in an assisted
living facility.
13. Both subject and caregiver/study partner are fluent in, and able, to read
the local language in which study assessments are administered at the study
site.
14. Subject and caregiver/study partner agree to be compliant with study
procedures and appear to have

Exclusion Criteria

1. Has a brain MRI at screening indicative of significant abnormality,
including, but not limited to, prior hemorrhage (> 1 cm) or large infarct (> 1
cm), > 2 lacunar infarcts outside the brain stem, severe white matter changes
(Fazekas grade 3), superficial hemosiderosis > 1 cm, aneurysm, vascular
malformation, subdural hematoma, space-occupying lesion (e.g., abscess or brain
tumor such as meningioma), or ventricular enlargement consistent with normal
pressure hydrocephalus.
• Note: Ventricular enlargement consistent with AD atrophy (hydrocephalus
ex-vacuo) is not exclusionary
• Note: Subjects who have > 10 microbleeds, require approval by Sponsor Medical
Monitor
2. Has a diagnosis of neurodegenerative disorder other than AD.
3. Has a current diagnosis of Major Depressive Disorder (MDD) according to the
criteria of the Diagnostic and Statistical Manual of Mental Disorders - Fifth
Edition. Subjects who do not meet current criteria for MDD and who are on
stable doses of antidepressants or mood stabilizers may be included in the
study at the discretion of the Investigator.
4. Has a history of suicidal behavior or has ongoing suicidal ideation.
5. Has a history of seizures (excluding febrile seizures of childhood, or a
single distant seizure > 10 years). Subjects with a history of one seizure, but
without evidence of vascular or mixed dementia, or brain tumor on MRI, may be
allowed into the study at the discretion of the Medical Monitor.
6. Has a medically confirmed history of recent cerebral infarct or recent
transient ischemic attack (within 1 year prior to the Screening - Part 2 Visit).
7. Has a medically confirmed history of recent myocardial infarction or
unstable, untreated coronary artery disease, or angina pectoris (within 1 year
prior to the Screening - Part 2 Visit).
8. Has a history of cancer, diagnosed and treated within the last 3 years prior
to the Screening - Part 2 Visit, with the exception of the following: (a)
treated basal cell carcinoma of the skin, or (b) treated in situ or Stage 1
cancers of skin (squamous cell only), colon, prostate, breast, or colon
(requires approval by the Medical Monitor).
9. Has a hemoglobin level < 11 g/dL in male subjects or < 10 g/dL in female
subjects, or a hemoglobin level > 16 g/dL.
10. Has a prothrombin time as measured by INR >= 1.5 and a platelet count <= 50 x
10^9/L.
11. Has donated blood within 8 weeks prior to the Screening - Part 2 Visit.
12. Has clinically relevant abnormalities in serum thyroid-stimulating hormone
or calcium. If the subject is taking replacement therapy, corresponding
Screening test values must be clinically acceptable.
13. Has serum vitamin B12 below the lower limit of normal.
14. Has any clinical chemistry laboratory value greater than or equal to Common
Terminology Criteria for Adverse Events (CTCAE; version 4.0; National Cancer
Institute 2009) Grade 2, unless considered not clinically relevant by the
Investigator and the Medical Monitor.
15. The subject at Screening has one or more of the following:
a. Alanine aminotransferase (ALT) >= 3 × upper limit of normal (ULN), OR
b. Aspartate aminotransferase (AST) >= 3 × ULN, OR
c. Total bilirubin (TBL) >= 1.5 × ULN.
16. Has an estimated glomerular filtration rate < 40 ml/min per 1.73 m2
according to the Modification of Diet in Renal Dise

Study & Design

• Study Type: Interventional
• Study Design: Not specified