ANALYSIS OF CHIMPANZEE PK FOR GILEAD TLR AGONIST

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究被设计为在黑猩猩身上进行PK/PD研究，以寻找一种新的免疫调节剂，有望诱导包括干扰素在内的先天免疫反应。该药物正在开发中，用于治疗包括乙肝病毒和丙型肝炎病毒在内的慢性病毒感染。该化合物已经在食蟹猴和绒猴身上进行了安全性和诱导先天免疫反应的测试。在进行临床试验之前，需要在黑猩猩身上进行剂量递增研究，以找到诱导天然免疫反应的适当水平的安全剂量。在四只黑猩猩身上进行了四轮口服给药。在每一轮中，这些动物都被给予单一剂量的口服。多次采集血液样本，评估PBMC和肝脏中天然免疫转录本的诱导以及血清中细胞因子的水平。这些动物被密切监测不良事件，包括完整的血细胞计数和血液化学。

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 study was designed as a PK/PD study in chimpanzees for a novel immune modulator that is expected to induce an innate immune response including IFN. The drug is being developed for chronic viral infections including HBV and HCV. The compound has been tested for safety and induction of the innate immune response in cynomolgus monkeys and marmosets. Prior to progressing to clinical trials, dose escalating studies need to be conducted in chimpanzees to find a safe dose with the appropriate level of induction of the innate immune response. Four rounds of dosing were conducted using oral dosing in four chimpanzees. In each round, the animals were given a single oral dose by gavage. Blood samples were taken at several times and evaluated for induction of innate immune transcripts in PBMC and the liver and for cytokine levels in the serum. The animals were monitored closely for adverse events including complete blood counts and blood chemistries.