Acceptable Multi-user Biodegradable Extended Release (AMBER) Implant System for HIV Prevention

用于预防艾滋病毒的可接受的多用户可生物降解缓释 (AMBER) 植入系统

基本信息

批准号：
10663830
负责人：
Leah Johnson
金额：
$ 92.15万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-20 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10663830
关键词：
AIDS prevention Address Adherence Adverse reactions African American Alabama Animal Model Anti-Retroviral Agents Antiviral Agents Area Behavioral Research Biodegradation Bypass California Centers for Disease Control and Prevention (U.S.)Characteristics Development Devices Dose Drug Delivery Systems Drug Formulations Drug Kinetics Engineering Epidemic Ethnic Origin Excision Exposure to Focus Groups Formulation Future Gender Geographic Locations Geography Goals HIV Implant In Vitro Injectable Integrase Inhibitors International Intervention Interview Kinetics Latino Lead Mechanics Medical Medicine Modeling Modification Mucous Membrane Nucleosides Online Systems Pattern Pharmaceutical Preparations Pharmacologic Substance Polymers Population Property Public Health RNA-Directed DNA Polymerase Rectum Research Research Institute Risk Safety San Francisco Science Sex Orientation Social Behavior Surveys System Tail Technology Toxic effect Trocars United States United States National Institutes of Health Universities Vagina Woman biodegradable polymer cis-female clinical translation copolymer design dosage drug release kinetics efficacy evaluation experimental study exposure route fabrication forgetting gender diversity improved in vivo in vivo Model industry partner informant inhibitor innovation insight manufacturing process mechanical properties men who have sex with men multidisciplinary nonhuman primate novel penis pre-exposure prophylaxis preclinical study preference product development programs prototype racial minority population rectal safety study subcutaneous success technology development transgender women young men who have sex with men

AIDS prevention Address Adherence Adverse reactions African American Alabama Animal Model Anti-Retroviral Agents Antiviral Agents Area Behavioral Research Biodegradation Bypass California Centers for Disease Control and Prevention (U.S.)Characteristics Development Devices Dose Drug Delivery Systems Drug Formulations Drug Kinetics Engineering Epidemic Ethnic Origin Excision Exposure to Focus Groups Formulation Future Gender Geographic Locations Geography Goals HIV Implant In Vitro Injectable Integrase Inhibitors International Intervention Interview Kinetics Latino Lead Mechanics Medical Medicine Modeling Modification Mucous Membrane Nucleosides Online Systems Pattern Pharmaceutical Preparations Pharmacologic Substance Polymers Population Property Public Health RNA-Directed DNA Polymerase Rectum Research Research Institute Risk Safety San Francisco Science Sex Orientation Social Behavior Surveys System Tail Technology Toxic effect Trocars United States United States National Institutes of Health Universities Vagina Woman biodegradable polymer cis-female clinical translation copolymer design dosage drug release kinetics efficacy evaluation experimental study exposure route fabrication forgetting gender diversity improved in vivo in vivo Model industry partner informant inhibitor innovation insight manufacturing process mechanical properties men who have sex with men multidisciplinary nonhuman primate novel penis pre-exposure prophylaxis preclinical study preference product development programs prototype racial minority population rectal safety study subcutaneous success technology development transgender women young men who have sex with men

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项目摘要

PROJECT SUMMARY/ABSTRACT The overarching goal of this proposed program is to develop an innovative, end-user informed HIV pre- exposure prophylaxis (PrEP) product as an Acceptable Multi-user Biodegradable Extended Release (AMBER) implant. The implant technology addresses multiple challenges with current PrEP drug delivery systems (DDS) by offering beneficial attributes: user-independence and discretion of use, zero-order (sustained) release, long-term protection (≤1 year), retrievability and biodegradation of the polymeric implant. We propose to engineer the implant to be retrievable throughout the drug delivery period, in the case of adverse reactions or an end-user’s wish to discontinue. Otherwise, the AMBER implant will remain in-place and biodegrade after drug depletion. Uniquely, the AMBER implant decouples drug delivery features from biodegradation properties, which enables zero-order kinetics of drug release. The AMBER program addresses the goals of this National Institutes of Health (NIH) opportunity (RFA-AI-19-063) for the development of new and innovative sustained/extended release (SER) DDS for HIV PrEP with novel (non- tenofovir based) antivirals (ARV). We will inform implant development by eliciting preference insights from diverse gender, sexual orientation, and ethnic/racial minority populations in two priority geographical areas under “Ending the HIV Epidemic” initiative in the United States. We propose three specific aims: (1) develop the AMBER implant with polymers optimized for high durability and bioerosion profiles; (2) formulate selected ARVs and evaluate safety, pharmacokinetics, and efficacy of lead AMBER implants in preclinical studies; (3) identify Preferred User Characteristics (PUCs), inform technology development and future deployment of AMBER into practice by conducting iterative socio-behavioral research with Young MSM, cis- and trans- gender women in California and Alabama. We will strive to align PUC and key modifiable attributes during product development: sustained (≤1 year) delivery of novel ARV, polymers designed to optimize biodegradation timescales, incorporation of end-user acceptability information into a Target Product Profile (TPP), and evaluation of efficacy in nonhuman primate model. The AMBER program is milestone-driven and provides defined deliverables to product development efforts to support future needs in clinical translation.

项目摘要/摘要该提议的计划的总体目标是开发创新的，最终用户的知情艾滋病毒暴露预防（PREP）产品作为可接受的多用户可生物降解延长释放（琥珀）植入物。植入物技术通过当前的准备药物提供了多个挑战通过提供有益属性的系统（DDS）：用户独立和使用的使用，零订单（持续的）释放，长期保护（≤1年），聚合物的可检索性和生物降解性我们建议设计植入物在整个药物输送期间都可以检索不良反应或最终用户希望中断的情况。否则，琥珀植入物将保留药物耗竭后的原位和生物降解。独特的是，琥珀色植入物将药物输送功能脱离从生物降解特性，可以使药物释放的零级动力学。琥珀色计划解决该国卫生研究院（NIH）的目标（RFA-AI-19-063）的目标新的和创新的持续/扩展释放（SER）DDS用于HIV PREP的新型（非 - 基于Tenofovir）抗病毒药（ARV）。我们将通过引起偏好见解来告知植入物开发在两个优先地理领域的各种性别，性取向和种族/种族少数群体在美国的“结束艾滋病毒流行病”倡议下。我们提出了三个具体目标：（1）发展具有优化聚合物的琥珀色植入物，可针对高耐用性和生物膜剖面；（2）选择的公式 ARV并评估临床前研究中琥珀铅的安全性，药代动力学和有效性；（3）确定首选用户特征（PUC），为技术开发和未来部署提供信息通过使用年轻的MSM，顺式和跨性别的MSM进行迭代社会行为研究来实践琥珀色加利福尼亚和阿拉巴马州的性别妇女。我们将努力将PUC和关键修改属性对齐产品开发：新型ARV的持续（≤1年）旨在优化的聚合物生物降解时间尺度，将最终用户可接受性信息纳入目标产品概况（TPP），以及非人类私人模型中效率的评估。琥珀色计划是里程碑驱动的，为产品开发工作提供定义的可交付成果，以支持临床翻译中的未来需求。