一个随机、双盲、2 b概念验证期临床试验与lecanemab早期阿尔茨海默病,一个anti-Abeta原纤丝抗体。

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Swanson CJ,张Y, Dhadda年代,王J, Kaplow J,赖昌星RYK, Lannfelt L,布拉德利H,瑞芭M,小山,Reyderman L,贝瑞哒,浆果,戈登R,克莱默LD,卡明斯杰

一个随机、双盲、2 b概念验证期临床试验与lecanemab早期阿尔茨海默病,一个anti-Abeta原纤丝抗体。

老年痴呆症Res。2021年4月17日,13 (1):80。doi: 10.1186 / s13195 - 021 - 00813 - 8。

PubMed ID
33865446 (在PubMed
]
文摘

背景:Lecanemab (BAN2401),一个IgG1单克隆抗体,优先目标可溶性聚合β淀粉样蛋白(β淀粉状蛋白质),在低聚物与活动,原纤丝和不溶性纤维。ban2401 - g000 - 201,随机双盲临床试验,利用贝叶斯设计response-adaptive随机评估3跨2方案lecanemab剂量和安慰剂在阿尔茨海默病早期,轻度认知障碍由于阿尔茨海默病(AD)和轻度AD痴呆。方法:ban2401 - g000 - 201旨在建立有效剂量90% (ED90),定义为最简单的剂量,达到> / = 90%的最大的治疗效果。主要终点是贝叶斯分析12个月的临床变化对阿尔茨海默病的综合得分(美国爱琴)ED90剂量,这需要一个80%的概率> / =临床减少下降25%和安慰剂。关键二级端点包括18个月的贝叶斯和频率论的分析脑淀粉样蛋白的减少使用正电子发射断层扫描;临床下降美国爱琴,临床痴呆Rating-Sum-of-Boxes (CDR-SB)和阿尔茨海默氏症评估Scale-Cognitive次生氧化皮(ADAS-Cog14);CSF改变核心生物标志物;海马体积和总使用体积磁共振成像(高压)。结果:共有854名随机受试者治疗(lecanemab, 609;安慰剂,245)。 At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (-0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. CONCLUSIONS: BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer's disease is underway. TRIAL REGISTRATION: Clinical Trials.gov NCT01767311 .

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药物
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药物 目标 类 生物 药理作用 行动
Lecanemab β淀粉样蛋白A4蛋白 蛋白质 人类
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