O4‐11‐06: A RANDOMIZED, DOUBLE‐BLIND, PLACEBO‐CONTROLLED PHASE 2 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CRENEZUMAB IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE

Abstract

Crenezumab is a humanized anti-abeta monoclonal antibody in development for the treatment of Alzheimer disease (AD). Crenezumab has been evaluated in a phase 2 clinical study designed to assess its efficacy and safety in patients with mild to moderate AD. The study was conducted in patients 50−80 years of age who were diagnosed with mild to moderate AD with a screening MMSE score of 18 - 26 points.A total of 433 patients were randomized at a 2:1 ratio (active to placebo) to receive either crenezumab or matching placebo for 68 weeks. 184 patients received 300 mg of study drug as a SC injection every 2 weeks and 247 patients received 15mg/kg of study drug as an IV infusion every 4 weeks. Randomization was stratified by ApoE4 status (carrier vs. non-carrier), MMSE score (≤ 21 vs. > 21), and study site. The co-primary efficacy outcome measures were the changes in the ADAS-Cog12 and CDR-SOB scores from baseline to Week 73. The secondary efficacy outcome measure was the change in the ADCS-ADL score from baseline to Week 73. A mixed model for repeated measures analysis was used for statistical analysis of treatment differences at study endpoints. Safety was assessed by monitoring adverse events (AEs), clinical laboratory evaluations, MRI evaluations (ARIA-E and ARIA-H events) and immunogenicity. The ADAS-Cog12, CDR-SOB, and ADCS-ADL endpoints as well as safety data will be presented and discussed This clinical trial was designed to provide an evaluation of the efficacy and safety of crenezumab in AD patients with mild to moderate dementia.