6A:Pharmacokinetic & Pharmacodynamic Study of an Anti-body based Vaginal Microbi

6A：药代动力学

• 批准号: 8706784
• 负责人: KENNETH H MAYER
• 金额: $ 4.43万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8706784
• 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; 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; Toxic effect; Vagina; Viral; Woman; base; cervicovaginal; cost; cytokine; digital; dosage; experience; innovation; microbicide; safety study; vaginal microbicide

This Project will be a pre-Phase 1 clinical pilot study to make preliminary assessments ofthe 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.

这项计划将是一项前期的第一期临床试验研究，以对 三价单抗的药代动力学、药效学、分布、安全性和可接受性 抗体(单抗)：局部使用的杀微生物剂，以阴道植入膜的形式传递。胶片剂量格式可使 女性要么为了方便和迅速起到保护作用而早熟使用它，要么每天使用它，这可能更多 使用方便，而且由于重复给药，可以提供更好的分布均匀性和更高的 生殖道中的持续浓度。将对三种应用策略进行评估和比较： 单剂量数字插入模拟婚前使用、每日多次数字剂量和每日多次剂量 使用Duet？的应用程序，这是一种颈部屏障设备，有望提供易于使用、低成本、可重复使用的 使用和保留杀微生物剂的手段，同时提供物理屏障以保护脆弱的宫颈。 这两种多日剂量格式将模拟非性交持续应用策略。这些将是 首先以胶片形式对这些单抗进行临床测试，并采取预防措施确保研究的安全性 参与者。为此，暴露参与者的数量和剂量将按顺序递增 频率，我们将使用可用的最敏感的方法(阴道镜，局部免疫措施 反应、阴道菌群和系统性实验室测试监测)，以检测杀菌剂的毒性。 该项目的一个创新特点是收集试验参与者的生殖道分泌物，用于 进一步的实验室研究以评估从溶解的膜中提取的单抗阻断HIV结合的效力 当与人类宫颈阴道分泌物结合时。