First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.
First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.
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DOI：
10.4161/19420862.2014.976431
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发表时间：
2014
期刊：
影响因子：
5.3
通讯作者：
Gentry WB
中科院分区：
文献类型：
--
作者：
Stevens MW;Henry RL;Owens SM;Schutz R;Gentry WB
这项首次人体研究检查了ch-mAb7F9（一种抗甲基苯丙胺单克隆抗体）在健康志愿者中的安全性和药代动力学。42名受试者接受单次递增剂量的ch-mAb7F9治疗，剂量范围在0.2至20 mg/kg之间，随访147天。通过体格检查、不良事件、生命体征、心电图和临床实验室检测来衡量安全性。血清ch-mAb7F9浓度及免疫原性分析。没有严重的不良反应或因不良事件而中断研究。不良事件发生的频率、相关性或严重程度均未随剂量的增加而增加，也未在治疗组和安慰剂组之间出现变化。Ch-mAb7F9显示出预期的IgG药代动力学参数，包括3个最高剂量组的半衰期为17-19 d，分布体积为5-6 L，表明该抗体主要局限于血管腔室。在接受ch-mAb7F9治疗的32名受试者中，有4名（12.5%）在研究结束时被证实产生了人类抗嵌合抗体反应；然而，这种反应似乎与剂量无关。总体而言，没有发现明显的安全性或耐受性问题；在这项1期研究中没有达到最大耐受剂量。因此，Ch-mAb7F9似乎对人类是安全的。
This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17–19 d in the 3 highest dose groups and volume of distribution of 5–6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration.