HARBOR: ABBV-916 In Subjects With Early Alzheimer’s Disease Combined Multiple-Ascending Dose/Proof-Of-Concept Study Design
David Watson1, Shau Yu Lynch2, Hana Florian2, Deli Wang3, Sagar Bachhav4, Joey Boiser5, Anthony Bannon6, Edwin Stage7, Ole Graff2
1Alzheimer's Research and Treatment Center, 2Neuroscience Clinical Development, AbbVie Inc., 3Statistics, AbbVie Inc., 4Clinical Pharmacology, AbbVie Inc., 5Pharmacovigilance and Patient Safety, AbbVie Inc., 6Precision Medicine, AbbVie Inc., 7Discovery, AbbVie Inc.
Objective:
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.
Background:
Alzheimer’s disease (AD) is the most common cause of dementia in the elderly.
Design/Methods:
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.
Results:
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.
Conclusions:
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.