On 19 September, researchers published the results of two Phase III trials with crenezumab in the JAMA Neurology journal. The multicenter randomised double-blind placebo-controlled parallel-group CREAD and CREAD2 clinical trials were initiated in 2016 and 2017 respectively to evaluate the efficacy and safety of crenezumab in people with early Alzheimer’s disease (AD). Crenezumab is an investigational anti-beta-amyloid drug. Both trials enrolled people aged 50 to 85 years with early AD with confirmed Aβ pathology, who received placebo or 60 mg/kg crenezumab intravenously every 4 weeks for up to 100 weeks. The CREAD study involved 94 sites in 30 countries and CREAD2 209 sites in 27 countries. Both trials were halted early based on results from a preplanned interim analysis of CREAD indicated that the study was unlikely to meet the primary end point. Overall, 173 participants completed CREAD before discontinuation and CREAD2 was discontinued before any participants completed the study. The primary outcome was change from baseline to week 105 in the CDR-SB score. Secondary efficacy measures included cognition, function and activities of daily living assessed by ADAS-Cog, MMSE, ADCS-ADL among others. Biomarker assessments were also included. Findings showed that crenezumab was well tolerated. Compared with previous trials, no new safety signals were identified, and amyloid-related imaging abnormalities were rare, mild, and transient. Following early study termination, crenezumab did not reduce clinical decline in people with early AD. Both trials did not show a beneficial effect of crenezumab on the primary and secondary endpoints. In addition, no meaningful changes in AD biomarkers were observed.
