Baseline Characteristics from a Phase III Trial of Crenezumab in Early (Prodromal-to-Mild) Alzheimer's Disease (CREAD)

Objective: To describe the study design/methodology and baseline characteristics from the Phase III CREAD study (NCT02670083) in prodromal-to-mild Alzheimer’s disease (AD). Background: Crenezumab is a humanized anti-amyloid β (Aβ) monoclonal immunoglobulin G4 antibody in development for AD. Although Phase II co-primary endpoints were not met, exploratory analyses suggested crenezumab should be tested for efficacy at a higher dose and earlier disease stage. Data from a Phase Ib study that investigated the safety/tolerability of higher doses of crenezumab supported testing a four-fold higher dose than used in Phase II. Two global, randomized, double-blind, placebo-controlled, Phase III studies (CREAD; CREAD2, NCT03114657]) are testing the efficacy and safety of crenezumab (60 mg/kg) in prodromal-to-mild AD. Design/Methods: Patients aged 50–85 years with prodromal-to-mild AD and evidence of cerebral amyloid pathology (cerebrospinal fluid [CSF] or amyloid by positron emission tomography [PET]) were enrolled. At screening, eligible patients had a Mini-Mental State Examination score of ≥ 22, a Clinical Dementia Rating (CDR) global score of 0.5 or 1, and a Free and Cued Selective Reminding Test immediate free recall ≤ 27. Patients were randomized 1:1 to placebo or crenezumab (60 mg/kg intravenously every 4 weeks). Primary and secondary endpoints include change from baseline in CDR-Sum of Boxes, 13-item AD Assessment Scale-Cognitive Subscale and AD Cooperative Study-Activities of Daily Living scores over 105 weeks. Magnetic resonance imaging is used to monitor safety and measure volumetric changes. Results: The CREAD study has completed recruitment, with 813 patients enrolled. Baseline data will be presented. Conclusions: Building on learnings from the Phase II study, CREAD and CREAD2 Phase III trials are investigating the efficacy of a four-fold higher dose of crenezumab (versus Phase II) in prodromal-to-mild AD and testing whether clinically meaningful efficacy can be achieved without the associated safety findings described with other passive anti-amyloid immunotherapies. Disclosure: Dr. Sink has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as a full time employee of Genentech, Inc. Dr. Ostrowitzki has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech, Inc. Dr. Millar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Products Ltd. Dr. Warren has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Products Ltd. Dr. Warren holds stock and/or stock options in Roche Products Ltd. Dr. Lin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full time employee of Genentech, Inc. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Roche Products Ltd. Dr. Schneider has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of F. Hoffmann-La Roche Ltd. Dr. Fuji has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full time employee of Genentech, Inc. Dr. Quartino has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech, Inc and hold stocks in Roche. Dr. Mackey has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech and Roche. Dr. Rabbia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche/Genentech. . Dr. Yule has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman-La Roche. Dr. Fontoura has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann La-Roche Ltd. Dr. Fontoura holds stock and/or stock options in F. Hoffmann La-Roche Ltd. which sponsored research in which Dr. Fontoura was involved as an investigator. Dr. Fontoura holds stock and/or stock options in F. Hoffmann-La Roche. Dr. Doody has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech/F. Hoffman-La Roche. Dr. Doody holds stock and/or stock options in F. Hoffman-La Roche.