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

A5214：SQ 单剂量白介素 7 用于 HIV-1 感染者

• 批准号: 7378025
• 负责人: ROBERT C KALAYJIAN
• 金额: $ 0.9万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378025
• 关键词: A5214; SQ; SINGLE; DOSE; INTERLEUKIN

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，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 且 CD4+ 计数 > 100 个细胞/mm3 和病毒载量的 HIV-1 感染受试者进行单剂量皮下注射 rhIL-7 > 50,000 份/毫升。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 受体的 α 链）对 CD4 和 CD8 T 细胞的生物效应、细胞内 bcI- 的表达。 2 T 细胞和 IL-7 抗体的开发。它还将研究 HIV-1 感染受试者中 rhIL-7 的药代动力学特征。剂量将从 3-100ug/kg 逐步增加。对于每个剂量（3、10、30、60 和 100ug/kg）的活性 rhIL-7 药物或安慰剂，受试者在进入时将被分层（病毒载量 < 50 拷贝/mL 或病毒载量 50-50,000 拷贝/mL）。在每个层中，受试者将以 3:1 的比例随机分配（每组中恰好有 3 名受试者接受 rhIL-7，而每组中正好有 1 名受试者接受安慰剂）。主要终点是安全性：对于每个层，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。全国 40-50 名受试者中，MHMC 将招募 2-3 名受试者。将会有预审、筛选和12小时的PK入场参观。入院后，患者将在八周的随访期间约见七次。