BASELINE CHARACTERISTICS FROM CREAD2: A PHASE III TRIAL OF CRENEZUMAB IN EARLY (PRODROMAL-TO-MILD) ALZHEIMER'S DISEASE

Crenezumab is a humanized anti-amyloid-beta (Aβ) monoclonal IgG4 antibody currently in development for the treatment of Alzheimer's disease (AD). Crenezumab binds to monomeric and aggregated forms of Aβ, with high affinity for oligomers, protecting neurons from oligomer-induced toxicity. It is associated with a low risk of amyloid-related imaging abnormalities (ARIA). Whilst Phase II co-primary endpoints were not met, exploratory analyses suggested that crenezumab should be investigated for clinically meaningful efficacy at a higher dose and earlier stage of disease. Based on learnings from Phase II, two, global, randomized, double-blind, placebo-controlled, parallel-group Phase III studies (CREAD [NCT02670083];1 CREAD2 [NCT03114657]) are investigating the efficacy and safety of crenezumab (60 mg/kg, a 4-fold higher dose than that used in the Phase II trials) in patients with early (prodromal-to-mild) AD. CREAD baseline data have previously been presented.1 Patients aged 50–85 years with prodromal-to-mild AD and confirmed evidence of cerebral amyloid pathology (CSF or amyloid PET) were enrolled. At screening, patients had an MMSE score of ≥22, a CDR-global score of 0.5 or 1, Free and Cued Selective Reminding Test (FCSRT) immediate free recall ≤27 and cueing index ≤0.67 (to enrich for patients with greater likelihood of progression over 105 weeks), and were randomized 1:1 to placebo or crenezumab (60 mg/kg q4w IV). Randomization was stratified by dementia and APOE status, baseline anti-dementia medications, and geographic region. Primary and secondary endpoints include change from baseline in CDR-SB, ADAS-Cog-13, ADCS-ADL, and FAQ scores over 105 weeks. Exploratory objectives include assessing treatment effects on CSF biomarkers and amyloid- and tau-PET. MRI examinations are used to monitor safety and measure volumetric changes. CREAD2 has completed global recruitment, enrolling 784 patients. Enrollment in a China extension continues. Baseline characteristics for the global enrollment population in CREAD2 are similar to those of CREAD (data to be presented and compared with CREAD). The CREAD and CREAD2 Phase III trials are investigating the efficacy and safety of a 4-fold higher dose of crenezumab (vs. Phase II) in prodromal-to-mild AD. Both studies have completed global recruitment, enrolling similar populations. 1. Lin et al. AAIC 2018.