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: 8172717
• 负责人: Robert E LANFORD
• 金额: $ 3.09万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172717
• 关键词: Adverse event; Agonist; Animals; Blood Chemical Analysis; Blood specimen; Callithrix; Chronic; Clinical Trials; Complete Blood Count; Computer Retrieval of Information on Scientific Projects Database; Dose; Funding; Grant; Hepatitis B Virus; Hepatitis C virus; Immune; Immune response; Institution; Interferons; Liver; Macaca fascicularis; Monitor; Oral; Pan Genus; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Research; Research Personnel; Resources; Serum; Source; Time; Transcript; United States National Institutes of Health; Virus Diseases; 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. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究被设计为黑猩猩中的PK/PD研究，用于新型免疫调节剂，预计将诱导包括IFN在内的先天免疫反应。该药物是针对包括HBV和HCV在内的慢性病毒感染开发的。该化合物已经过测试，以确保和诱导cynomolgus猴子和果酱中的先天免疫反应。在进行临床试验之前，需要在黑猩猩中进行剂量升级研究，以找到具有先天免疫反应的适当诱导水平的安全剂量。在四个黑猩猩中使用口服给药进行了四轮给药。在每一轮比赛中，动物都会通过饲料给单一口服剂量。几次采集血液样本，并评估了PBMC和肝脏中先天免疫转录本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，包括完整的血液计数和血液化学。