AMD11070 IN HIV-POSITIVE SUBJECTS (A5210)

AMD11070 在 HIV 阳性受试者中的应用 (A5210)

• 批准号: 7603209
• 负责人: Michael S. Saag
• 金额: $ 3.14万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603209
• 关键词: Anti-Retroviral Agents; Binding; CXCR4 Receptors; Clinical Research; Collection; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Kinetics; Funding; Future; Genotype; Grant; HIV Seropositivity; HIV-1; Hour; Institution; Label; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; RNA; Research; Research Personnel; Resources; Restart; Safety; Screening Result; Source; Time; United States National Institutes of Health; Virus; Visit; antiretroviral therapy; base; cohort; day; receptor expression

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 A5210是AMD11070的剂量升级，开放标签，安全性和活动研究。起始剂量基于A5191的结果。在给药期间，受试者被接受为一般临床研究中心（GCRC）。治疗将连续10天持续。在第4,6,7,8天和9天，将允许受试者从GCRC中脱离GCRC，而36小时的药代动力学（PK）配置文件（密集的24小时PK和30-38小时下的槽水平）将在稳定状态下获得，从最后一个剂量开始，并将包括AMD11070的最后一个剂量，并将包括AMD11070的最后一个终端PK emimininer pk Eliminitional Pefiles。根据治疗组的不同，将在第6或第7天绘制槽PK收集，以评估CXCR4受体饱和度并表征药物积累。将收集外周血单核细胞，以将来对X4结合和/或受体表达的未来分析。 HIV-1 RNA水平将在第0、1、2、5、7、10、14、17、30和90天进行评估。安全实验室将在第0、5、10、17、30和90天进行。 第17天访问后，受试者可以使用筛查HIV-1基因型的结果开始其他抗逆转录病毒疗法（未由研究提供），以帮助选择适当的药物。 主要目标： 1。确定AMD11070的几个剂量水平的安全性（由A5191结果确定的起始剂量）在10天内施用了携带X4循环病毒的HIV感染受试者。 2。确定在AMD11070治疗的10天或在治疗后的7天中，X4-纤维病毒降低> 1 log10 ru降低的受试者的比例 描述从基线到log10 rlu中第10天的变化，对应于X4-循环病毒。