Landen Jaren W, Andreasen Niels, Cronenberger Carol L, Schwartz Pamela F, Börjesson-Hanson Anne, Östlund Henrik, Sattler Catherine A, Binneman Brendon, Bednar Martin M
Pfizer Inc., Groton, CT, USA.
Karolinska University Hospital, Stockholm, Sweden.
Alzheimers Dement (N Y). 2017 Jun 8;3(3):393-401. doi: 10.1016/j.trci.2017.05.003. eCollection 2017 Sep.
The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year.
Subjects were aged ≥50 years with Mini-Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg ( = 12) or placebo ( = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg ( = 12) or placebo ( = 6), respectively.
Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected.
Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.
在接受治疗1年的轻至中度阿尔茨海默病患者中，对多剂量抗淀粉样蛋白β（Aβ）单克隆抗体泊奈单抗的安全性、药代动力学以及对外周和中枢Aβ的影响进行了研究。
受试者年龄≥50岁，简易精神状态检查表评分在16至26分之间。队列Q被随机分为每季度接受10mg/kg泊奈单抗（n = 12）或安慰剂（n = 6）。队列M被随机分为接受10mg/kg泊奈单抗或安慰剂的负荷剂量，随后分别每月接受7.5mg/kg泊奈单抗（n = 12）或安慰剂（n = 6）。
泊奈单抗总体耐受性良好。血浆浓度呈剂量依赖性增加，但脑脊液（CSF）渗透率较低。血浆Aβ随泊奈单抗剂量依赖性增加，但脑脊液生物标志物、脑淀粉样蛋白负荷、认知和功能均未受影响。
两种泊奈单抗给药方案总体上安全且耐受性良好，但未改变脑脊液生物标志物、脑淀粉样蛋白负荷或临床结局。
