A Clinical Trial to evaluate AL002 in Participants with early Alzheimer's Disease
- Conditions
- Early Alzheimer’s DiseaseMedDRA version: 20.0Level: SOCClassification code 10029205Term: Nervous system disordersSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2019-001476-11-DE
- Lead Sponsor
- Alector Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 328
Key clinical inclusion criteria for the study:
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 PrecivityADTM Aß 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 PrecivityADTM 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/Aß42
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/Aß42 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 longitudinal Amyloid PET imaging assessment only - Inclusion criteria for participants participating in the optional at-home and/or in-clinic WLSA only.
Are the trial subjects
Central nervous system (CNS) disorders-related exclusion criteria:
1.Participant has any evidence of a condition other than AD that may affect cognition 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 area of leptomeningeal hemosiderosis based on central read.
15. Participant has presence of significant cerebral vascular pathology as assessed by the M
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method