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.

项目摘要：核心B 高度活性的抗逆转录病毒疗法（HAART），其中抗逆转录病毒（ARV）的药物结合了 成为治疗艾滋病毒/艾滋病的标准。越来越多的共识是ARV剂的组合 对于艾滋病毒的最佳有效的非疫苗生物医学预防（NBP）策略，需要进行最佳有效的非疫苗生物医学预防。 制定和交付ARV组合的难度限制了确定有效和的能力 安全的NBP产品，用于阴道局部应用。另外，难以确定局部依从性 微生物临床试验限制了这些试验测量预防HIV在人类中的功效的能力 人群。这种IPCP-MBP工作的长期目标是开发阴道内环（IVR）公式 多种ARV药物用于预防性HIV传播，强调女性的需求 发展中国家。核心B的具体目的是制定IVR库以提供ARV 由FDA批准的药物组成的组合并将这些配方提供给组件项目 IPCP：项目1-Pharmacokinetics（PK），项目2-SAVETY，项目3-效能感，项目4-（阶段I） 探索性临床试验。最佳性能候选组合的选择将通过 PK，安全性和功效的涉及迭代配方开发的新型筛查过程 结果。这种优化的公式将过渡到项目5，以开发方法和能力 在转基因生物中生产了临床CGMP最佳候选IVR的临床CMP。制定努力 在整个多方面的核心临界路径中 IPCP后I期临床试验最安全，最有效的组合。为了解决困难 在评估对治疗的依从性方面遇到了菌心试验，一种新型的依从性IVR一直是 开发使用温度测量来确定和记录IVR如果佩戴IVR。这 原型设备将被优化用于女性，并在试点临床研究中进行了评估。