A5214: SQ SINGLE DOSE INTERLEUKIN-7 IN HIV-1 INFECTED SUBJECTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项第一阶段的随机、安慰剂对照、双盲序贯队列剂量递增研究，在接受有效抗逆转录病毒疗法的HIV-1感染者中，单次皮下注射rhIL-7，其CD4计数和病毒载量分别为100个/mm~3和50,000个拷贝/毫升。该研究将考察IL-7生物活性剂量的安全性，并将研究rhIL-7(CD127，IL-7受体的阿尔法链)对CD4和CD8 T细胞的生物学影响、T细胞内BCI-2的表达以及IL-7抗体的产生。它还将研究重组人白介素7在HIV-1感染者中的药代动力学特征。剂量将从3-100微克/公斤递增。对于每个剂量(3、10、30、60和100ug/kg)的活性rhIL-7药物或安慰剂，受试者将在进入时进行分层(病毒载量50拷贝/毫升或病毒载量50-50,000拷贝/毫升)。在每一组中，受试者将被随机分为3：1(每组中恰好有三名受试者接受重组人白细胞介素7，而安慰剂组中恰好有一名受试者)。主要终点是安全性：对于每一层，将报告重组人IL-7的最大中毒剂量(MTD)。对于每一层和剂量，剂量限制毒性(DLT)的频率将通过治疗臂和特定的AEs和/或构成DLT的实验室评估来描述。次要终点包括CD8/CD127比值和药代动力学。在全国40-50名受试者中，MHMC将招募2-3名受试者。将有预映、放映和12小时的PK入境参观。进入后，患者将在八周的随访中被看到大约七次。

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. This is a phase I, randomized, placebo-controlled, double-blind sequential cohort dose-escalation study of single dose subcutaneous injection of rhIL-7 in HIV-1 infected subjects receiving potent ART with CD4+ counts > 100 cells/mm3 and viral load > 50,000 copies/ml. The study will look at the safety of biologically active doses of IL-7 and will study the biologic effect of rhIL-7 (CD127, alpha chain of the IL-7 receptor) on CD4 and CD8 T-cells, expression of intracellular bcI-2 in T-cells and development of IL-7 antibodies. It will also study the pharmacokinetic profile of rhIL-7 in HIV-1 infected subjects. Doses will be escalated from 3-100ug/kg. For each dose (3, 10, 30, 60 and 100ug/kg) of active rhIL-7 drug or placebo, subjects will be stratified at entry (viral load < 50 copies/mL or viral load 50-50,000 copies/mL). Within each stratum, subjects will be randomized 3:1 (exactly three subjects in each arm receiving rhIL-7 and exactly one subject in the arm receiving placebo). The primary endpoint is safety: for each stratum, the maximum toxic dosage (MTD) of rhIL-7 will be reported. For each stratum and dose, the frequency of dose-limiting toxicity (DLT) will be described by treatment arm and specific AEs and/or laboratory evaluations that constituted the DLT. Secondary endpoints include CD8/CD127 ratio and pharmacokinetics. Of 40-50 subjects nationally, 2-3 subjects will be recruited at MHMC. There will be a pre-screening, a screening and a 12-hour PK entry visit. Post entry, patients will be seen about seven times during eight weeks of follow-up.