First‐in‐human, double‐blind, placebo‐controlled, single‐dose escalation study of aducanumab (BIIB037) in mild‐to‐moderate Alzheimer's disease

Introduction Aducanumab (BIIB037), a human monoclonal antibody selective for aggregated forms of amyloid beta, is being investigated as a disease‐modifying treatment for Alzheimer's disease (AD). Methods This randomized, double‐blind, placebo‐controlled single ascending‐dose study investigated the safety, tolerability, and pharmacokinetics (PK) of aducanumab in patients with mild‐to‐moderate AD. Eligible patients were sequentially randomized 6:2 to aducanumab (0.3, 1, 3, 10, 20, 30, and 60 mg/kg) or placebo. Results The primary outcome was safety and tolerability. Doses ≤30 mg/kg were generally well tolerated with no severe or serious adverse events (SAEs). All three patients who received 60 mg/kg aducanumab developed SAEs of symptomatic amyloid‐related imaging abnormalities, which completely resolved by weeks 8–15. Aducanumab C max , AUC 0–last , and AUC inf increased in a dose‐proportional manner. Discussion In this single‐dose study, aducanumab demonstrated an acceptable safety and tolerability profile and linear PK at doses ≤30 mg/kg ( clinicaltrials.gov NCT01397539 ).