摘要
背景:洗礼是一种人源化的抗淀粉样β-β(Aβ)单克隆抗体,旨在降低阿尔茨海默病(AD)患者脑Aβ沉积。 目的:本阶段为开放标签扩展(OLE)研究,旨在评价洗礼治疗轻度至中度AD患者的长期安全性和有效性。 方法:患者(58-78岁),完成两项随机、安慰剂对照、双盲研究(皮下[SC]单剂量递增,或静脉(Iv)多次上升剂量)。进入了奥莱。对三组患者进行了评估:在OLE(洗礼SC/洗礼IV)、研究201和OLE(洗礼/洗礼)中的洗礼(IV)和试验201 a中的洗礼/洗礼(IV),以及研究201 a中的安慰剂(IV)。在OLE(安慰剂/洗礼)中进行第四次洗礼。 结果:194例患者中158例退出OLE,主要原因为受试者(n=85)和AE(n=30)。平均施洗量为2.9(1.90)年。无显着性d受洗/洗礼组与安慰剂/洗礼组的疗效终点(AD评估量表-认知子量表[ADAS-Cog]、痴呆残疾评估[DAD]和MMSE评分)的差异。帕蒂Ents(94.8%,184/194)报告了OLE的≥1治疗-紧急不良事件(TEAES)。22例(11.3%)患者发生与淀粉样蛋白相关的积液或水肿(ARIA-E)异常.最普通的通讯TEAE组(>20%)为跌倒、躁动、尿路感染,与安慰剂/洗礼组相似。 结论:早期治疗组与延迟治疗组认知功能下降差异无显着性(P>0.05)。没有出现新的安全问题。ARIA-E发生率较高。IRST暴露在OLE和以前的洗礼中。没有明确的病因导致死亡事件。
关键词: 阿尔茨海默病,洗礼,MRI,脑淀粉样蛋白相关影像学异常,AD评估量表,痴呆残疾评估。
Current Alzheimer Research
Title:Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study
Volume: 15 Issue: 13
关键词: 阿尔茨海默病,洗礼,MRI,脑淀粉样蛋白相关影像学异常,AD评估量表,痴呆残疾评估。
摘要: Background: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibody directed at lowering the cerebral Aβ deposit in Alzheimer’s disease (AD).
Objective:This phase 2, open-label extension (OLE) study evaluated long-term safety and efficacy of bapineuzumab in patients with the mild-to-moderate AD.
Methods: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblind studies (subcutaneous [SC] single-dose-escalation, or intravenous (IV) multiple-ascending-dose)) entered the OLE. Three groups were assessed: bapineuzumab or placebo SC, and bapineuzumab (IV) in OLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study 201 and bapineuzumab IV in OLE (placebo/bapi).
Results: Of 194 patients enrolled, 158 withdrew from OLE; primarily due to withdrawal by subject (n=85) and AE (n=30). Mean (SD) bapineuzumab exposure was 2.9 (1.90) years. There were no significant differences for efficacy endpoints (AD Assessment Scale–cognitive subscale [ADAS-Cog], Disability Assessment for Dementia [DAD] and MMSE scores) between the bapi/bapi and placebo/bapi groups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) in OLE. Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) occurred in 22 (11.3%) patients. The most common TEAEs (>20% patients) were fall, agitation and urinary tract infection with similar incidences between bapi/bapi and placebo/bapi groups.
Conclusion: No significant difference was seen in cognitive and functional decline between early and delayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patients first exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributed to death events.
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Cite this article as:
Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study, Current Alzheimer Research 2018; 15 (13) . https://dx.doi.org/10.2174/1567205015666180821114813
DOI https://dx.doi.org/10.2174/1567205015666180821114813 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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