Abstract Details

Title INVOKE-2 - A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AL002 in Participants with Early Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P17 - Poster Session 17 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-005

Objective

INVOKE-2 is a randomized, double-blind, dose-ranging, placebo-controlled study evaluating the efficacy and safety of AL002 in participants with early AD (NCT04592874).

Background Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in the brain predominantly by microglia. Mutations in TREM2 cause an increased risk of developing Alzheimer’s Disease (AD). E.g., the R47H coding variant confers similar risk for AD as does one copy of APOE4. AL002 is a humanized monoclonal IgG1 antibody (mAb) that activates the TREM2 signaling pathway to increase the ability of microglia to clear pathology and protect neurons. AL002 is believed to be the first anti-TREM2 mAb in clinical development for the treatment of AD. AL002 was generally well tolerated in a Phase 1 study and has demonstrated proof of target engagement and proof of mechanism. These results have supported progressing AL002 to the INVOKE-2 Phase 2 study of AL002 in patients with early AD.

Design/Methods This study will enroll approximately 265 participants in North America, Australia, New Zealand, Europe, and South America. Participants will be randomized to receive one of 3 doses of AL002 or placebo, via IV infusion every 4 weeks, for up to 96 weeks. All participants require a diagnosis of early AD, evidence of cerebral amyloidosis, clinical severity consistent with Stage 2 to early Stage 4 (2018 Research Framework), a CDR-GS of 0.5 or 1, MMSE from 22 to 30, and RBANS DMI of 85 or lower.

Results

Efficacy will be measured with clinical outcome assessments and fluid and imaging biomarkers. Safety will be assessed through monitoring of AEs, suicidality assessments, changes in laboratory and vital signs, ECG and MRI. PK in serum and CSF will be assessed.

Conclusions INVOKE-2 is designed to investigate the efficacy and safety of AL002, representing a novel, first-in-class neuro-immunological approach for treating AD. Enrollment is ongoing.

Authors/Disclosures
PRESENTER	No disclosure on file
Robert Paul, MD, PhD	Dr. Paul has received personal compensation for serving as an employee of Alector. Dr. Paul has received stock or an ownership interest from Alector.
	No disclosure on file
	No disclosure on file
Glenn Morrison, PhD (Annexon Biosciences)	Dr. Morrison has received personal compensation for serving as an employee of Alector. Dr. Morrison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG . Dr. Morrison has stock in Alector. Dr. Morrison has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Michael Ward	Michael Ward has received personal compensation for serving as an employee of Alector. Michael Ward has stock in Alector. Michael Ward has received intellectual property interests from a discovery or technology relating to health care. Michael Ward has a non-compensated relationship as a Reviewer with ADDF that is relevant to AAN interests or activities.

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