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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。