Core B: Antiretroviral Intravaginal Ring Formulation

核心B：抗逆转录病毒阴道环制剂

• 批准号: 8910626
• 负责人: John A Moss
• 金额: $ 37.58万
• 依托单位: OAK CREST INSTITUTE OF SCIENCE
• 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/8910626
• 关键词: AIDS prevention; AIDS/HIV problem; Address; Adherence; Adverse effects; Anti-Retroviral Agents; Characteristics; Clinical; Clinical Research; Clinical Trials; Consensus; Critical Pathways; Cyclic GMP; Development; Devices; Drug Combinations; Drug Controls; Drug Formulations; Drug Kinetics; Drug Targeting; Environment; FDA approved; Failure; Future; Goals; HIV; HIV Infections; Highly Active Antiretroviral Therapy; Human; In Vitro; Individual; Integrase Inhibitors; Investments; Lead; Libraries; Local Microbicides; Macaca; Measurement; Measures; Methods; Monitor; Mus; Nucleosides; Oral; Pharmaceutical Preparations; Pharmacodynamics; Phase; Phase I Clinical Trials; Population; Prevention; Prevention strategy; Process; Prophylactic treatment; Protease Inhibitor; Regimen; Research; Resistance; Reverse Transcriptase Inhibitors; Route; Safety; Sheep; Staging; Technology; Temperature; Tenofovir disoproxil fumarate; Testing; Topical application; Toxic effect; Vaccines; Vagina; Vaginal Ring; Vaginal delivery procedure; Viral; Woman; Work; base; chemical property; clinical lot; data modeling; design; emtricitabine; improved; in vivo; men; microbicide; non-nucleoside reverse transcriptase inhibitors; novel; prevent; programs; prototype; research clinical testing; screening; sex; sexual HIV transmission; tool; transgender women; transmission process

PROJECT SUMMARY: CORE B Highly Active Antiretroviral Therapy (HAART), where antiretroviral (ARV) drugs are given in combination, has become the standard in treatment of HIV/AIDS. There is growing consensus that combinations of ARV agents are going to be needed for an optimally effective non-vaccine biomedical prevention (nBP) strategy for HIV. Difficulty in formulation and delivery of ARV combinations has limited the ability to determine efficacious and safe nBP products for vaginal topical application. Additionally, difficulty in determining adherence in topical microbicide clinical trials has limited the ability of these trials to measure efficacy of HIV prevention in human populations. The long-term goal of this IPCP-MBP effort is to develop intravaginal ring (IVR) formulations of multiple ARV drugs for prevention of sexual HIV transmission, emphasizing the needs of women in the developing world. The specific objective of Core B is to formulate a library of IVRs for delivering ARV combinations consisting of FDA-approved drugs and to provide these formulations to the component projects of the IPCP: Project 1-pharmacokinetics (PK), Project 2-safety, Project 3-efficacy, Project 4-(pre-Phase I) Exploratory Clinical Trial. Selection of the best performing candidate combination will be accomplished through a novel screening process involving iterative formulation development informed by PK, safety, and efficacy results. This optimized formulation will be transitioned into Project 5 to develop methods and capacity to manufacture clinical cGMP lots of the best performing candidate IVR at GMOs. The formulation efforts throughout this multi-faceted IND-enabling critical path will enable advancement of the lead formulation of the safest and most efficacious combination into post-IPCP Phase I clinical trials. In order to address the difficulty microbicide trials have encountered in assessing adherence to treatment, a novel adherence IVR has been developed that uses temperature measurement to determine and record hourly if an IVR is being worn. The prototype device will be optimized for use in women and evaluated in a pilot clinical study.

项目总结：核心B 高效抗逆转录病毒疗法（HAART）是将抗逆转录病毒（ARV）药物联合使用， 成为艾滋病治疗的标准。越来越多的人认为， 将需要一个最有效的非疫苗生物医学预防（nBP）艾滋病毒的战略。 抗逆转录病毒药物组合制剂和递送的困难限制了确定有效和有效的抗逆转录病毒药物的能力。 用于阴道局部应用的安全nBP产品。此外，难以确定局部用药的依从性 杀微生物剂临床试验限制了这些试验测量人类HIV预防效果的能力 人口。这项IPCP-MBP努力的长期目标是开发阴道环（IVR）制剂， 预防艾滋病毒性传播的多种抗逆转录病毒药物，强调妇女在 发展中国家的团结合作核心B的具体目标是制定一个用于提供抗逆转录病毒药物的IVR库 由FDA批准的药物组成的组合，并将这些制剂提供给组成项目 IPCP：项目1-药代动力学（PK），项目2-安全性，项目3-疗效，项目4-（I期前） 探索性临床试验。最佳表现候选组合的选择将通过以下方式完成： 一种新的筛选过程，涉及根据PK、安全性和疗效进行迭代制剂开发 结果这一优化配方将过渡到项目5，以开发方法和能力， 在GMO生产临床cGMP批次的最佳性能候选IVR。制定工作 在这条多方面的IND实现关键路径中， 最安全和最有效的组合进入IPCP后I期临床试验。为了解决 杀微生物剂试验在评估治疗依从性时遇到， 开发了一种使用温度测量来确定和记录每小时是否佩戴IVR的方法。的 原型装置将优化用于女性，并在试点临床研究中进行评估。