BAN2401 In Early Alzheimer's Disease: A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With An Open-Label Extension Phase To Confirm Safety And Efficacy (1567)

Objective: To describe the study design for the ongoing CLARITY AD study. Background: BAN2401 is a humanized immunoglobulin G1 monoclonal antibody that selectively binds to soluble Aβ aggregate species, while demonstrating low affinity for Aβ monomer. An 18-month phase 2 proof-of-concept study (BAN2401-G000-201;NCT01767311) using Bayesian adaptive design was recently conducted in 856 patients with early Alzheimer’s disease (AD). Although the primary Bayesian analysis at 12 months was not met, pre-specified 18-month frequentist analyses showed BAN2401 treatment (10mg/kg-biweekly) produced clinically meaningful reductions in clinical decline and brain amyloid burden in patients with early AD. Based on these encouraging results, a phase 3 study (BAN2401-G000-301 [CLARITY AD], NCT03887455) was designed to confirm the efficacy and safety of BAN2401 in early AD. Design/Methods: CLARITY AD is an 18-month treatment (core study), multicenter, double-blind, placebo-controlled, study with open-label extension (OLE) in patients with early AD. Eligibility criteria include age 50–90 years old, MCI due to AD with intermediate likelihood or mild AD dementia with amyloid pathology confirmed by amyloid positron emission tomography (PET) or CSF assessment of t-tau/Aβ(1–42) ratio. Patients are required to have objective impairment in episodic memory (≥1 standard deviation below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II (WMS-IV LMII)). 1566 patients will be randomized across 2 treatment groups (placebo and BAN2401 10mg/kg-biweekly; 1:1 randomization). At end of core study, patients who qualify may participate in OLE phase for up to 2 years. Results: The primary efficacy endpoint in core study is change in CDR-SB from baseline at 18 months. The OLE phase will evaluate long-term safety and tolerability of BAN2401 10mg/kg-biweekly in patients with early AD. Conclusions: Building on positive findings from the phase 2 study, the phase 3 CLARITY AD study is designed to confirm clinical efficacy and safety of BAN2401 in patients with early AD. Disclosure: Dr. Lynch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.Dr. Irizarry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc. Dr. Dhadda has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.Dr. Zhang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.. Dr. Bogoslovsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc. Dr. Reyderman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee at Eisai Inc.. Dr. Kaplow has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.. Dr. Kaplow has received personal compensation in an editorial capacity for Eisai Inc.. Dr. Bradley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.Dr. Rabe has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.. Dr. Totsuka has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Co., Ltd.. Dr. Kramer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.. Dr. Hampel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.Dr. Swanson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc.