HIV Monoclonal Antibody Studies

该疫苗研究中心（VRC）临床试验计划（CTP）项目用于与针对HIV的被动免疫（单克隆抗体）相关的临床试验，在健康志愿者和HIV感染志愿者中进行评估。以下是迄今为止每项研究的简要摘要。 VRC 601（13-I-0189）是在HIV感染的志愿者中进行的第一项I期剂量递增研究，该研究使用的是一种人单克隆抗体，鉴定为VRC-HIVMAB 060 -00-VP（VRC 01），具有广泛的HIV-1中和活性，由VRC/NIAID/NIH开发。Sci Transl Med.2015年12月23日;7（319）：319 ra 206。 VRC 602（14-I-0019）是一项对健康成人静脉或皮下给予人单克隆抗体VRC 01的安全性和药代动力学进行的I期剂量递增研究。该研究始于FY 14。临床实验免疫学2015年12月;182（3）：289-301。 VRC 606（16-I-0018）是对靶向HIV-1 CD 4结合位点的新一代高效和广泛中和HIV-1人单克隆抗体（VRC 01 LS）的首次研究。该研究检查了安全性、耐受性和药代动力学。VRC 01 LS通过静脉和皮下途径给予健康成人。该研究于2016财年启动，并于2017财年完成招募。PLoS Med. 2018 Jan 24;15. VRC 607（16-I-0147）是第一个I期单次给药研究的安全性和病毒学效应的单克隆抗体VRC 01 LS静脉注射给药的艾滋病毒感染的成年人。VRC 01 LS是VRC开发的新一代单克隆抗体，用于延长抗体半衰期。分析正在进行中。 VRC 605（17-I-0030）是一项对健康成人静脉或皮下给予人单克隆抗体VRC 07 - 523 LS的安全性和药代动力学进行的I期剂量递增研究。本研究于2017财年启动并完成招募。Lancet HIV. 2019年10月;6（10）：e667-e679。 VRC 603（18-I-0030）是首项关于表达VRC 07 HIV-1中和抗体的AAV 8-VRC 07（VRC-HIVAAV 070 -00-GT）重组AAV载体在经抗逆转录病毒治疗的HIV-1感染且病毒血症得到控制的成人中的安全性的I期剂量递增研究。应计正在进行中。 VRC 609（18-I-0105）是一项I期剂量递增研究，旨在评估健康成人静脉或皮下注射人单克隆抗体N6 LS的安全性和药代动力学。该研究于2018财年启动，数据分析正在进行中。 VRC 610（18-I-0113）是一项I期安全性和药代动力学研究，旨在评价健康成人中人单克隆抗体10 E8 VLS单独或与MAB VRC 07 - 523 LS同时皮下注射给药的安全性和药代动力学。该研究于2018财年启动，分析正在进行中。

This Vaccine Research Center (VRC) Clinical Trials Program (CTP) project is for clinical trials related to passive immunity (monoclonal antibodies) directed against HIV, evaluated in healthy volunteers and HIV-infected volunteers. A brief summary of each study to date follows. VRC 601 (13-I-0189) is the first Phase I dose-escalation study in HIV-infected volunteers of a human monoclonal antibody, identified as VRC-HIVMAB060-00-VP (VRC01), which has broad HIV-1 neutralizing activity and was developed by the VRC/NIAID/NIH. Sci Transl Med. 2015 Dec 23;7(319):319ra206. VRC 602 (14-I-0019) was a Phase 1 dose-escalation study of the safety and pharmacokinetics of human monoclonal antibody VRC01, administered intravenously or subcutaneously to healthy adults. The study initiated in FY14. Clin Exp Immunol. 2015 Dec;182(3):289-301. VRC 606 (16-I-0018) wds the first study of a new generation of highly potent and broadly neutralizing HIV-1 human MAb, VRC01LS, targeted against the HIV-1 CD4 binding site. The study examined safety, tolerability and pharmacokinetics. VRC01LS was being administered to healthy adults by the intravenous and subcutaneous routes. The study was initiated in FY16 and accrual completed in FY17. PLoS Med. 2018 Jan 24;15. VRC 607 (16-I-0147) is the first Phase I single dose study of the safety and virologic effect of monoclonal antibody VRC01LS administered intravenously to HIV-infected adults. VRC01LS is a next generation MAb developed by the VRC to extend the antibody half-life. Analysis is ongoing. VRC 605 (17-I-0030) was a Phase 1 dose-escalation study of the safety and pharmacokinetics of human monoclonal antibody VRC07-523LS administered intravenously or subcutaneously to healthy adults. The study was initiated and accrual completed in FY17. Lancet HIV. 2019 Oct;6(10):e667-e679. VRC 603 (18-I-0030) is the first Phase I dose-escalation study of the safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) recombinant AAV vector expressing VRC07 HIV-1 neutralizing antibody in antiretroviral treated, HIV-1 infected adults with controlled viremia. Accrual is ongoing. VRC 609 (18-I-0105) is a Phase I dose-escalation study of the safety and pharmacokinetics of human monoclonal antibody, N6LS, administered intravenously or subcutaneously to healthy adults. The study was initiated in FY18 and data analysis is ongoing. VRC 610 (18-I-0113) is a phase I safety and pharmacokinetics study to evaluate human monoclonal antibody 10E8VLS administered alone or concurrently with MAB VRC07-523LS via subcutaneous injection in healthy adults. The study was initiated in FY18 and analysis is ongoing.