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

James Ferrero; Leslie Williams; Heather Stella; Kate Leitermann; Alvydas Mikulskis; John O'Gorman; Jeff Sevigny

doi:10.1016/j.trci.2016.06.002

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

Alzheimers Dement (N Y). 2016 Jun 20;2(3):169-176. doi: 10.1016/j.trci.2016.06.002. eCollection 2016 Sep.

Authors

James Ferrero¹, Leslie Williams¹, Heather Stella¹, Kate Leitermann¹, Alvydas Mikulskis¹, John O'Gorman¹, Jeff Sevigny¹

Affiliation

¹ Biogen, Cambridge, MA, USA.

Abstract

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.govNCT01397539).

Keywords: Adverse events; Alzheimer's disease; Clinical trial; Monoclonal antibody; Pharmacokinetics.

Associated data

ClinicalTrials.gov/NCT01397539