AMD11070 IN HIV-POSITIVE SUBJECTS (A5210)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 A5210是一项AMD 11070的剂量递增、开放标签、安全性和活性研究。起始剂量基于A5191的结果。受试者在给药期入住一般临床研究中心（GCRC）。治疗将连续进行10天。允许受试者在第4、6、7、8和9天离开GCRC。 从AMD 11070末次给药开始，将获得稳态时的36小时药代动力学（PK）曲线（强化24小时PK和30-38小时的谷浓度），并将包括终末PK消除曲线。根据治疗组，将在第6天或第7天采集PK谷值，以评估CXCR 4受体饱和度并表征药物蓄积。将采集外周血单核细胞，用于未来分析X4结合和/或受体表达随时间的变化。 将在第0、1、2、5、7、10、14、17、30和90天评估HIV-1 RNA水平。将在第0、5、10、17、30和90天获得安全性实验室检查结果。还将在第21天评估未重新开始抗逆转录病毒药物治疗的受试者的安全性和疗效。 受试者可在第17天访视后开始其他抗逆转录病毒治疗（研究未提供），使用筛选HIV-1基因型的结果帮助选择适当的药物。 主要目的： 1.确定携带嗜X4病毒的HIV感染受试者接受10天内几种剂量水平的AMD 11070（起始剂量由A5191的结果确定）给药的安全性。 2.确定每个队列中在AMD 11070治疗10天内或治疗终止后7天内X4嗜性病毒降低>1 log 10 rlu的受试者比例，以及 描述从基线至第10天对应于X4嗜性病毒的log 10 rlu的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A5210 is a dose escalating, open-label, safety and activity study of AMD11070. The starting dose is based on the results from A5191. Subjects are admitted to the general clinical research center (GCRC) for the dosing period. Treatment will continue for 10 consecutive days. Subjects will be allowed daytime passes away from the GCRC on days 4,6,7,8, and 9. Thirty-six-hour pharmacokinetic (PK) profiles (intensive 24-hour PK and a trough level at Hour 30-38) will be obtained at steady state, beginning with the last dose of AMD11070, and will include terminal PK elimination profiles. Trough PK collections will be drawn on day 6 or 7, depending on the treatment group, to assess CXCR4 receptor saturation and characterize drug accumulation. Peripheral blood mononuclear cells will be collected for future analyses of X4 binding and/or receptor expression over time. HIV-1 RNA levels will be assessed on Days 0, 1, 2, 5, 7, 10, 14, 17, 30 and 90. Safety labs will bevobtained at Days 0, 5, 10, 17, 30, and 90. Subjects who have not restarted antiretroviral medications will also be assessed for safety and efficacy on Day 21. Subjects may begin other antiretroviral therapy (not supplied by the study) after the Day 17 visit using the results of the screening HIV-1 genotype to help select the appropriate drugs. Primary Objectives: 1. To determine the safety of several dose levels of AMD11070 (with the starting dose determined by the results of A5191) administered over 10 days to HIV-infected subjects who harbor X4-tropic virus. 2. To determine the proportion of subjects per cohort who have a >1 log10 rlu reduction in X4-tropic virus during 10 days of AMD11070 treatment or in the 7 days following treatment discontinuation, and to describe changes from baseline to Day 10 in log10 rlu corresponding to X4-tropic virus.