HARBOR: ABBV-916 In Subjects With Early Alzheimer’s Disease Combined Multiple-Ascending Dose/Proof-Of-Concept Study Design (P7-6.008)

Abstract

<h3>Objective:</h3> This study evaluates safety, tolerability, pharmacokinetics, immunogenicity, and amyloid reduction associated with ABBV-916, a recombinant humanized immunoglobulin G1 monoclonal antibody, in subjects with early AD. <h3>Background:</h3> Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. <h3>Design/Methods:</h3> Approximately 163 subjects will be enrolled in this Phase 1b/2 multicenter, randomized, placebo-controlled, double-blind, dose-finding study (NCT05291234), which consists of 2 stages: multiple-ascending dose (MAD; Phase 1b; Stage A) and proof-of-concept (POC; Phase 2; Stage B). Each stage has a 60-day screening period, 24-week double-blind period (ABBV-916 or placebo administered intravenously once every 4 weeks) and a 16-week safety follow-up period, with the option of a 2-year open-label extension. Subjects must meet the following inclusion criteria: be between 50 and 90 years of age, diagnosis of Stage 3 or 4 AD, as defined by the 2018 NIA-AA Research Framework, a Mini-Mental State Examination score between 20 and 28, a positive Precivity AD-Aβ blood test, and an amyloid PET scan consistent with amyloid pathology. <h3>Results:</h3> Safety evaluations include adverse events reports, clinical laboratory tests, MRI, vital signs, electrocardiograms, and the Columbia-Suicide Severity Rating Scale. Cerebrospinal fluid collection is required for subjects in Stage A and optional for subjects in Stage B. Change from baseline in brain amyloid plaque deposition is measured by amyloid PET scan in Stage B. <h3>Conclusions:</h3> This study tests the hypothesis that ABBV-916 will lead to rapid and robust removal of amyloid plaques from the brain of subjects with AD. <b>Disclosure:</b> Dr. Watson has nothing to disclose. Shau Yu Lynch has received personal compensation for serving as an employee of AbbVie. Shau Yu Lynch has received personal compensation for serving as an employee of Eisai. Shau Yu Lynch has stock in AbbVie. Hana Florian has received personal compensation for serving as an employee of AbbVie. Hana Florian has stock in AbbVie. Dr. Wang has received personal compensation for serving as an employee of AbbVie Inc.. Dr. Wang has stock in AbbVie Inc.. Mr. Bachhav has received personal compensation for serving as an employee of AbbVie Inc, USA. Mr. Bachhav has stock in AbbVie Inc. USA. Dr. Boiser has received personal compensation for serving as an employee of AbbVie. Dr. Boiser has stock in AbbVie. Dr. Bannon has received personal compensation for serving as an employee of AbbVie. Dr. Bannon has stock in AbbVie. Dr. Stage has received personal compensation for serving as an employee of AbbVie. Dr. Stage has stock in AbbVie.. Dr. Graff has received personal compensation for serving as an employee of AbbVie. Dr. Graff has stock in AbbVie.