To describe the study design/methodology and baseline characteristics from the Phase III CREAD study (NCT02670083) in prodromal-to-mild Alzheimer’s disease (AD).

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.

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.

The CREAD study has completed recruitment, with 813 patients enrolled. Baseline data will be presented.

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.