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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项I期、随机、安慰剂对照、双盲序贯队列剂量递增研究，对接受有效ART治疗的HIV-1感染者进行单剂量皮下注射rhIL-7， CD4+计数为100个细胞/mm3，病毒载量为5万拷贝/ml。该研究将着眼于生物活性剂量的IL-7的安全性，并将研究rhIL-7 （CD127， IL-7受体α链）对CD4和CD8 t细胞的生物学效应，t细胞内bcI-2的表达以及IL-7抗体的产生。它还将研究rhIL-7在HIV-1感染受试者中的药代动力学特征。剂量将从3-100ug/kg逐步增加。对于活性rhIL-7药物或安慰剂的每一剂量（3,10,30,60和100ug/kg），受试者将在进入时分层（病毒载量< 50拷贝/mL或病毒载量50-50,000拷贝/mL）。在每个阶层中，受试者将按3:1的比例随机分配（每组正好有3名受试者接受rhIL-7治疗，另一组正好有1名受试者接受安慰剂治疗）。主要终点是安全性：对于每个地层，将报告rhIL-7的最大毒性剂量（MTD）。对于每个层和剂量，剂量限制性毒性（DLT）的频率将通过治疗组和构成DLT的特定ae和/或实验室评估来描述。次要终点包括CD8/CD127比率和药代动力学。在全国40-50名受试者中，MHMC将招募2-3名受试者。将有一个预筛选，筛选和12小时的PK参赛参观。入院后，患者将在8周的随访期间接受约7次检查。

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.