A Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of AL002 in Participants with Early Alzheimer*s Disease

Phase 2

• Conditions: Alzheimers Disease - Neurodegenerative disease - Dementia; 10012303

• Registration Number: NL-OMON56389
• Lead Sponsor: Alector Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

1. Participant must be in the AD continuum as defined by the 2018 NIAAA
Research Framework; this requires evidence of cerebral amyloidosis (A+). This
evidence requirement can be satisfied by any one of the following 3 pathways:
a. Historical Amyloid PET may be allowed to fulfill this criterion if it meets
all of the following:
i. Must utilize either [18F]florbetaben, [18F]florbetapir, or [18F]flutametamol.
ii. Must have adequate scan parameters and image quality as determined by the
central imaging reader.
iii. Must have the raw data available to send to the core PET laboratory.
iv. Must have been read as positive (elevated amyloid) by the core PET
laboratory.
b. Historical CSF measurements may be allowed to fulfill this criterion after
review by the Medical Monitor. At a minimum, documentation of historical CSF
testing must contain the following details:
i. Identification of which laboratory did the testing.
ii. Identity of the type of assay used.
iii. Reference ranges for the values reported.
c. If historical testing is not available, the participant must undergo a
2-step verification of amyloid positivity:
i. As an initial screen for cerebral amyloidosis, the participant must have a
high or intermediate APS as measured by the PrecivityAD Aβ blood test.
Participants with a low APS are not eligible for study participation. (Note:
Historical studies that do not meet the full criteria in a. or b. may still be
considered sufficient, after consultation with the Medical Monitor, to allow a
participant to forego PrecivityAD screening and thus allow the participant to
proceed to steps outlined in 1.c.ii - amyloid
confirmation.).
ii. Participants need confirmation of amyloid positivity with either:
o New positive Amyloid PET scan
o New positive CSF pTau/Aβ42
o Participants who do not have confirmation of amyloid pathology based on an
initial Amyloid PET scan may opt to have a second assessment with CSF.
Participants who do not have confirmation of amyloid pathology on an initial
CSF pTau/Aβ42 measurement may opt to have a second assessment with an Amyloid
PET scan.
2. Participant has evidence of episodic memory impairment as demonstrated by
the RBANS-Update DMI score: i. If the DMI score is <= 85, the participant meets
this requirement without additional evidence needed. ii. If the DMI >85 and
<=95, the participant may still be considered for participation if they have a
history of cognitive and functional decline consistent with diagnosis of Early
AD. Agreement between the Investigator and the Medical Monitor that the
participant meets criteria for clinical severity consistent with mild cognitive
impairment or mild dementia due to Early AD must be documented prior to
randomization.
3. If Participant is receiving symptomatic AD medications, the dosing regimen
must have been stable for 60days prior to screening not expected to change
during study, and must not be initiated, modified, or stopped within 90 days
prior to screening start.

Bullets 4 to 19 (pages 69 to 70) in the protocol for the following:
- General inclusion criteria for the study
- Inclusion criteria for participants participating in the optional Tau PET
imaging assessment with [18F]MK-6240 only
- Inclusion criteria for participants participating in the optional
longitudin

Exclusion Criteria

Central nervous system (CNS) disorders-related exclusion criteria:
1. Participant has any evidence of a condition other than AD that may affect
cognition, including but not limited to, frontotemporal dementia, dementia with
Lewy bodies, vascular dementia, Parkinson's disease, corticobasal degeneration,
Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal
degeneration, Huntington disease, normal pressure hydrocephalus, hypoxic
injury, seizure disorder, static encephalopathy, closed brain injury, or
developmental disability.
2. Participant has history or presence of vascular disease that has the
potential to affect cognitive function (eg, clinically significant carotid,
vertebral stenosis, or plaque; aortic aneurysm; intracranial aneurysm;
macro-hemorrhage; arteriovenous malformation).
3. Participant has a history or presence of cerebrovascular accident within the
past 2 years, or recent transient ischemic attack within 180 days before
screening, or has radiologic evidence of any cortical stroke regardless of age.
4. Participant has history of severe, clinically significant (persistent
neurologic deficit or structural brain damage) CNS trauma (eg, cerebral
contusion).
5. Participant has history or presence of intracranial tumor (eg, glioma,
except for benign brain tumors that, in the opinion of the Investigator, are
not likely to impair cognition).
6. Participant has ongoing infections that may affect brain function (eg, human
immunodeficiency virus [HIV], syphilis, neuroborreliosis, viral or bacterial
meningitis/encephalitis), or history of infections that resulted in neurologic
sequelae.
7. Participant currently has or has had an acute illness that requires or
required IV antibiotics within 30 days prior to first study drug administration.
8. Participant has history or presence of systemic autoimmune disorders that
potentially cause progressive neurologic disease with associated cognitive
deficits (eg, multiple sclerosis, lupus erythematosus, antiphospholipid
antibody syndrome, Behçet disease).
9. Participant has any of the following eye conditions: a history or presence
of uveitis, a serious chronic inflammatory condition of the eye, a current eye
infection, or any ongoing eye disorder requiring anticipated invasive eye
procedures or injectable medical therapy (eg, ranibizumab or aflibercept for
macular degeneration or diabetic eye disease) during the study period.
10. Participant has any history of schizophrenia, schizoaffective disorder,
major depression, or bipolar disorder.
a. A history of major depression is acceptable if no episode has been reported
within the previous 2 years. Treatment with antidepressant medications is
allowed.
11. Participant is at risk of suicide in the Investigator's opinion.
12. Participant has history of alcohol and/or moderate to severe substance use
disorder (according to the Diagnostic and Statistical Manual of Mental
Disorders, 5th Edition) within the past 2 years.
a. Nicotine use is allowed.
Imaging-related exclusion criteria:
13. Participant has MRI evidence of
a. >2 lacunar infarcts.
b. Any territorial infarct >1 cm3.
c. White matter hyperintense lesions on the FLAIR sequence that correspond to
an overall Fazekas score of 3.
14. Participant has presence on MRI of >5 microbleeds and/or >1 ar

Study & Design

• Study Type: Interventional
• Study Design: Not specified