ANALYSIS OF CHIMPANZEE PK FOR GILEAD TLR AGONIST

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究设计为在黑猩猩中进行的一项PK/PD研究，旨在研究一种新型免疫调节剂，该免疫调节剂预期可诱导先天性免疫应答，包括IFN。该药物正在开发用于慢性病毒感染，包括HBV和HCV。已在食蟹猴和绒猴中测试了该化合物的安全性和先天免疫应答的诱导。在进行临床试验之前，需要在黑猩猩中进行剂量递增研究，以找到诱导先天免疫应答的适当水平的安全剂量。在4只黑猩猩中采用经口给药进行了4轮给药。在每轮中，通过灌胃对动物进行单次经口给药。多次采集血液样品，并评价PBMC和肝脏中先天免疫转录物的诱导以及血清中细胞因子水平。密切监测动物的不良事件，包括全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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.