Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: Safety and antiviral activity
Clinical evaluation (Phase I) of a human monoclonal antibody against hepatitis C virus: Safety and antiviral activity
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DOI：
10.1016/j.jhep.2006.08.019
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发表时间：
2007-01-01
影响因子：
25.7
通讯作者：
Dagan, Shlomo
中科院分区：
文献类型：
--
作者：
Galun, Eithan;Terrault, Norah A.;Dagan, Shlomo
背景/目标：HCV-AB 68是一种抗丙型肝炎病毒（HCV）包膜蛋白的人单克隆抗体，可中和细胞培养物和HCV-Trimera小鼠模型中的HCV。一项1期临床试验的目的是测试HCV-AB 68的安全性，耐受性，和抗病毒活性的患者与慢性HCV-infection.Methods/结果：单剂量的HCV-AB 68，0.25-40毫克，给药15例患者耐受良好，没有中度或严重的不良事件（SAE）的报道。在6例患者中，HCV-RNA水平在输注后立即短暂下降2- 100倍，并在24-48小时内反弹至基线水平。对25名患者给予多剂量的HCV-AB 68，10-120 mg。每周给药一次，持续3周，然后在第四周每周给药3次，之后随访患者3个月。未报告药物相关SAE，也无明显的特定不良事件模式。八个25例患者至少有1个对数减少，17个至少有0.75个对数减少HCV-RNA水平从基线在一个或多个时间点后HCV-AB 68 infination.Conclusions：这些数据支持调查HCV-AB 68在预防复发HCV感染的患者接受肝移植终末期肝病。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: HCV-AB68, a human monoclonal antibody against the envelope protein of hepatitis C virus (HCV), neutralizes HCV in cell-culture and in the HCV-Trimera mouse model. A Phase 1 clinical trial was designed to test safety, tolerability, and antiviral activity of HCV-AB68 in patients with chronic HCV-infection.Methods/Results: Single doses of HCV-AB68, 0.25-40 mg, administered to 15 patients were well tolerated with no moderate or serious adverse events (SAEs) reported. In six patients, HCV-RNA levels transiently decreased by 2- to 100-fold immediately following infusion and rebound to baseline in 24-48 h. Multiple doses of HCV-AB68, 10-120 mg, were administered to 25 patients. Doses were given weekly for 3 weeks, then 3x a week during the fourth week, after which patients were followed for 3 months. No drug-related SAEs were reported and no specific pattern of adverse events was evident. Eight out of 25 patients had at least a 1-log reduction and 17 had at least a 0.75-log reduction in HCV-RNA levels from baseline at one or more time points following HCV-AB68 infusion.Conclusions: These data support the investigation of HCV-AB68 in the prevention of recurrent HCV-infection in patients who had received hepatic allografts for end-stage liver disease. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.