Safety and biomarker effects of Solanezumab in patients with Alzheimer's disease
Safety and biomarker effects of Solanezumab in patients with Alzheimer's disease
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DOI：
10.1016/j.jalz.2011.09.224
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发表时间：
2012-07-01
影响因子：
14
通讯作者：
Siemers, Eric R.
中科院分区：
文献类型：
--
作者：
Farlow, Martin;Amold, Steven E.;Siemers, Eric R.
目的：在轻度至中度阿尔茨海默病患者中评估每周输注12次solanezumab（一种抗β-淀粉样蛋白（A β）抗体）的安全性、耐受性、药代动力学和药效学。认知measurements were also given.Methods：在这个2期、随机、双盲、安慰剂对照的临床试验中，52例阿尔茨海默病患者接受安慰剂或抗体（每4周100 mg，每周100 mg，每4周400 mg，或每周400 mg）治疗12周。安全性和生物标志物评价持续至随机化后1年。在基线和活性治疗期后进行磁共振成像和脑脊液（CSF）检查。在血浆和CSF中的A β浓度进行了测量，和阿尔茨海默氏病评估量表的认知部分administer.Results：临床实验室值，CSF细胞计数，和磁共振成像扫描治疗不变，没有不良事件可以明确相关的抗体管理。血浆中的总A β（1-40）和A β（1-42）（结合抗体和未结合）以剂量依赖性方式增加。抗体处理类似地增加CSF中的总A β（1-40）和A β（1-42）。对于每周服用400 mg的患者，抗体治疗降低了CSF中未结合的A β（1-40）（P <0.01），但以剂量依赖性方式增加了CSF中未结合的A β（1-42）。阿尔茨海默氏病评估量表认知部分是不变的12周后antibody administration.Conclusions：抗体给药耐受性良好，剂量高达400毫克每周。未结合CSF A β（1-42）的剂量依赖性增加表明，该抗体可充分改变A β平衡，以从淀粉样斑块中动员A β（1-42）。(C)2012年，阿尔茨海默氏症协会。All rights reserved.
Objectives: To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of 12 weekly infusions of solanezumab, an anti-beta-amyloid (A beta) antibody, in patients with mild-to-moderate Alzheimer's disease. Cognitive measures were also obtained.Methods: In this phase 2, randomized, double-blind, placebo-controlled clinical trial, 52 patients with Alzheimer's disease received placebo or antibody (100 mg every 4 weeks, 100 mg weekly, 400 mg every 4 weeks, or 400 mg weekly) for 12 weeks. Safety and biomarker evaluations continued until 1 year after randomization. Both magnetic resonance imaging and cerebrospinal fluid (CSF) examinations were conducted at baseline and after the active treatment period. The A beta concentrations were measured in plasma and CSF, and the Alzheimer's Disease Assessment Scale cognitive portion was administered.Results: Clinical laboratory values, CSF cell counts, and magnetic resonance imaging scans were unchanged by treatment, and no adverse events could be clearly related to antibody administration. Total (bound to antibody and unbound) A beta(1-40) and A beta(1-42) in plasma increased in a dose-dependent manner. Antibody treatment similarly increased total A beta(1-40) and A beta(1-42) in CSF. For patients taking 400 mg weekly, antibody treatment decreased unbound A beta(1-40) in CSF (P < .01), but increased unbound A beta(1-42) in CSF in a dose-dependent manner. The Alzheimer's Disease Assessment Scale cognitive portion was unchanged after the 12-week antibody administration.Conclusions: Antibody administration was well tolerated with doses up to 400 mg weekly. The dose-dependent increase in unbound CSF A beta(1-42) suggests that this antibody may shift A beta equilibria sufficiently to mobilize A beta(1-42) from amyloid plaques. (C) 2012 The Alzheimer's Association. All rights reserved.