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

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

James Ferrero  1 , Leslie Williams  1 , Heather Stella  1 , Kate Leitermann  1 , Alvydas Mikulskis  1 , John O'Gorman  1 , Jeff Sevigny  1
Affiliations

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

James Ferrero et al. Alzheimers Dement (N Y). .

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 Cmax, AUC0-last, and AUCinf 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.

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Figures

Fig. 1
Fig. 1
Serum concentration (mean ± SE) of aducanumab (logarithmic scale) over time after a single dose. aOne patient in the 10 mg/kg group had a measurable concentration of aducanumab at the pre-dose sample (0) time. Abbreviation: SE, standard error.
Fig. 2
Fig. 2
Mean (SE) Aβ40 and Aβ42 plasma levels (extracted) after a single dose of aducanumab or placebo. an = 13 at W3 and W6; bn = 5 at W3. Abbreviations: D, day; H, hour; SE, standard error; W, week.
Fig. 3
Fig. 3
Change from baseline in ADAS-Cog 13 Score (Mean ± SE) after a single dose of aducanumab at weeks 3 and 24. Abbreviations: ADAS-Cog 13, Alzheimer's Disease Assessment Scale-Cognitive Subscale; SE, standard error.
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