A Pharmacokinetic and Pharmacodynamic Study of an Antibody-based Vaginal Microbi

基于抗体的阴道微生物的药代动力学和药效学研究

• 批准号: 8329761
• 负责人: KENNETH H MAYER
• 金额: $ 6.74万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8329761
• 关键词: AIDS prevention; Antibodies; Binding; Blood; Cervical; Cervix Uteri; Clinical; Clinical Investigator; Coagulation Process; Collection; Colposcopy; Devices; Dose; Drug Kinetics; Film; Frequencies; Genital system; HIV; Hepatic; Human; Immune; Immune response; Instruction; Kidney; Laboratories; Laboratory Study; Local Microbicides; Measurement; Measures; Methods; Modeling; Monitor; Monoclonal Antibodies; Mucous body substance; Participant; Pharmacodynamics; Phase; Pilot Projects; Property; Safety; Sampling; Scientist; Site; Specimen; Testing; Time; Toxic effect; Vagina; Viral; Woman; base; cost; cytokine; digital; dosage; experience; innovation; microbicide; residence; safety study; vaginal microbicide

PROJECT SUMMARY (See instructions): This Project will be a pre-Phase 1 clinical pilot study to make preliminary assessments of the pharmacokinetics, pharmacodynamics, distribution, safety, and acceptability of a trivalent monoclonal antibody (mAb) topical microbicide delivered as a vaginally-inserted film. The film dosage format may enable women to use it either precoitally, for convenience and rapid onset of protection, or daily, which may be more convenient, and due to repeated dosing, could provide superior evenness of distribution and higher sustained concentrations in the genital tract. Three application strategies will be assessed and compared: single-dose digital insertion modeling precoital use, multiple-daily-dose digital, and multiple-daily-dose application using Duet¿, a cervical barrier device expected to provide an easy to use, low cost, reusable means to apply and retain microbicides, while providing a physical barrier to protect the vulnerable cervix. The two multiple daily dose formats will model non-coital continual application strategies. These will be the first clinical tests of these Mabs in film format, and precautions will be taken to assure the safety of study participants. To this end, there will be sequential escalation of the number of exposed participants and dose frequency, and we will employ the most sensitive methods available (colposcopy, measures of local immune response, vaginal flora, and systemic laboratory test monitoring) to detect microbicide toxicities. An innovative feature of this project will be the collection of genital tract secretions from trial participants for further laboratory studies to assess the potency of mAbs from the dissolved film in blocking HIV binding when combined with human cervicovaginal secretions.

项目摘要（请参阅说明）： 该项目将是一项前1次临床试验研究，旨在对三价单克隆抗体（MAB）局部菌糖的药代动力学，药效学，分布，安全性和可接受性进行初步评估。膜剂量格式可能使女性能够在妇女的情况下使用它，以便于方便和快速发作，或者每天都更方便，并且由于反复的给药，可以在生殖道中提供较高的分布和更高的持续浓度。将评估和比较三种应用程序策略：单剂量数字插入建模前使用前使用剂量的剂量数字，以及使用二重奏的多天剂量应用，这是一种预期的颈椎屏障设备，可提供易于使用，低成本，可重复使用的方法，以应用和保留微生物，同时提供可保护易受弱点的子宫的物理障碍。 两种多个每日剂量格式将建模非核心连续应用策略。这些将是这些mAB的第一个临床测试，并采取预防措施，以实现研究参与者的安全性。为此，暴露的参与者和剂量频率的数量将依次升级，我们将采用最敏感的方法（角阴Soscopicy，局部免疫反应的测量，阴道菌群和全身实验室测试监测）来检测微生物剂的毒性。 该项目的创新特征将是从试验参与者中收集进一步实验室研究的生殖道分泌物，以评估溶解膜中mAb的效力，以阻止与人宫颈阴道分泌物结合使用时阻断艾滋病毒结合。