ANALYSIS OF CHIMPANZEE PK FOR GILEAD TLR AGONIST

吉利德 TLR 激动剂在黑猩猩中的 PK 分析

• 批准号: 8357690
• 负责人: Robert E LANFORD
• 金额: $ 2.41万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357690
• 关键词: Adverse event; Agonist; Animals; Blood Chemical Analysis; Blood specimen; Callithrix; Chronic; Clinical Trials; Complete Blood Count; Dose; Funding; Grant; Hepatitis B Virus; Hepatitis C virus; Immune; Immune response; Interferons; Liver; Macaca fascicularis; Monitor; National Center for Research Resources; Oral; Pan Genus; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Serum; Source; Time; Transcript; United States National Institutes of Health; Virus Diseases; cost; cytokine; design; novel; safety testing

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 本研究旨在对黑猩猩进行 PK/PD 研究，寻找一种新型免疫调节剂，该调节剂有望诱导包括 IFN 在内的先天免疫反应。该药物正在开发用于治疗慢性病毒感染，包括乙型肝炎病毒和丙型肝炎病毒。该化合物已在食蟹猴和狨猴中进行了安全性测试和诱导先天免疫反应的测试。在进入临床试验之前，需要在黑猩猩中进行剂量递增研究，以找到具有适当诱导先天免疫反应水平的安全剂量。对四只黑猩猩进行四轮口服给药。在每一轮中，通过管饲法给动物单次口服剂量。多次采集血样并评估 PBMC 和肝脏中先天免疫转录物的诱导以及血清中的细胞因子水平。密切监测动物的不良事件，包括全血细胞计数和血液化学。