Ferrero James, Williams Leslie, Stella Heather, Leitermann Kate, Mikulskis Alvydas, O'Gorman John, Sevigny Jeff
Biogen, Cambridge, MA, USA.
Alzheimers Dement (N Y). 2016 Jun 20;2(3):169-176. doi: 10.1016/j.trci.2016.06.002. eCollection 2016 Sep.
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).
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.
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, AUC, and AUC increased in a dose-proportional manner.
In this single-dose study, aducanumab demonstrated an acceptable safety and tolerability profile and linear PK at doses ≤30 mg/kg (clinicaltrials.govNCT01397539).
阿杜卡单抗（BIIB037）是一种对聚集形式的β淀粉样蛋白具有选择性的人源单克隆抗体，正作为阿尔茨海默病（AD）的疾病修饰治疗药物进行研究。
这项随机、双盲、安慰剂对照的单剂量递增研究调查了阿杜卡单抗在轻至中度AD患者中的安全性、耐受性和药代动力学（PK）。符合条件的患者按6:2顺序随机分为阿杜卡单抗组（0.3、1、3、10、20、30和60mg/kg）或安慰剂组。
主要结局是安全性和耐受性。剂量≤30mg/kg通常耐受性良好，无严重或重大不良事件（SAE）。接受60mg/kg阿杜卡单抗的所有三名患者均出现了有症状的淀粉样蛋白相关成像异常的SAE，这些异常在第8 - 15周完全消退。阿杜卡单抗的Cmax、AUC和AUC以剂量比例方式增加。
在这项单剂量研究中，阿杜卡单抗在剂量≤30mg/kg时显示出可接受的安全性和耐受性概况以及线性PK（clinicaltrials.govNCT01397539）。
