Contraception development research center to advance a novel intravaginal ring as a non-hormonal multipurpose prevention technology

避孕开发研究中心将开发新型阴道环作为非激素多用途预防技术

• 批准号: 10700065
• 负责人: Lisa Blake Haddad
• 金额: $ 211.63万
• 依托单位: POPULATION COUNCIL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700065
• 关键词: AIDS prevention; Adherence; Advanced Development; Advisory Committees; Anti-Bacterial Agents; Bacterial Vaginosis; Basic Science; Behavioral Sciences; Biomedical Research; Characteristics; Child Health; Chlamydia; Clinical Trials; Contraceptive Agents; Contraceptive methods; Copper; Cross-Over Studies; Cross-Sectional Studies; Data; Development; Development Plans; Dimensions; Dose; Drug Delivery Systems; Drug Kinetics; Ensure; Evaluation; Failure; Fellowship; Formulation; Fostering; Funding; Goals; Gonorrhea; Good Manufacturing Process; Grant; HIV; HIV-1; Health; Hormones; Human; Human Herpesvirus 2; In Vitro; Industry; Infertility; Institution; Investigational Drugs; Investments; Lactic acid; Lead; Macaca mulatta; Marketing; Maternal Mortality; Maternal and Child Health; Mechanics; Medical; Menstruation; Methods; National Institute of Child Health and Human Development; Pathway interactions; Performance; Persons; Pharmacologic Actions; Pharmacologic Substance; Pilot Projects; Polymers; Population; Pregnancy; Premature Birth; Prevention; Prevention Research; Prodrugs; Production; Property; Regulatory Affairs; Reproductive Health; Research; Research Personnel; Research Project Grants; Risk; Safety; Science; Sexually Transmitted Diseases; Sheep; Side; Social Sciences; Technology; Temperature; Testing; Toxic effect; Vagina; Vaginal Ring; Viral; Woman; Women' s Health; Work; Zinc; Zinc Acetate; antimicrobial; candidate selection; career; chronic pelvic pain; collaborative environment; combat; community engagement; contraceptive efficacy; design; experience; experimental study; health goals; improved; in vivo; innovation; interest; manufacture; novel; preclinical study; prevent; product development; prototype; public health priorities; research and development; safety study; sensor; sperm cell; success; synergism; technology development; timeline; unintended pregnancy

OVERALL – ABSTRACT The overarching goal of the Population Council’s (PC) P50 proposal is to develop an innovative non-hormonal multipurpose prevention technology (MPT) intravaginal ring (IVR) with the potential to improve the lives of millions of women globally by combatting the overlapping burdens of unintended pregnancy and sexually transmitted infections (STIs), including HIV. Emerging data indicate that women overwhelmingly prefer products that prevent pregnancy and STIs/HIV over ones that prevent only pregnancy or only STI/HIVs. Our ‘CZL-IVR’ is a user-controlled 30-day IVR containing three active pharmaceutical ingredients (APIs), copper (C), zinc acetate (Z), and lactide (L) (a lactic acid prodrug) that together have non-hormonal contraceptive and anti-STI/HIV activity including chlamydia (CT), gonorrhea (GC), HSV-2, and HIV-1. Lactide maintains optimal vaginal pH and provides antibacterial, antiviral, and anti-bacterial vaginosis (BV) effects. We will advance development of our CZL-IVR through implementation of three integrated research projects. In Project 1 we aim to formulate and manufacture CZL-IVRs that achieve 30-day API delivery, manufacture and characterize in vitro mechanical performance of IVRs with varying dimensions and polymers with the selection of four candidates with a range of mechanical characteristics to evaluate in end-user research, and establish Good Manufacturing Practice (GMP) production for non-medicated rings for research conducted in Project 3. In Project 2 we aim to define the optimal API delivery doses of the three APIs alone and in combination, and to confirm the efficacy and safety of the prototype CZL-IVR by conducting essential preclinical studies including in-vitro and in-vivo contraceptive efficacy and antimicrobial efficacy and toxicity studies of APIs and of prototype human-sized and rhesus macaque-sized CZL- IVRs. In Project 3 we will inform CZL-IVR development and the field more broadly through end-user research employing novel mixed method approaches including a controlled setting cross-over study of the four selected candidate non-medicated IVRs of varying mechanical characteristics, a 30-day continuous use study of a non- medicated prototype IVR with an embedded temperature sensor, and a national cross-sectional survey with a discrete choice experiment (DCE) and latent class analysis (LCA). The Administrative Core will support and synergize our interdisciplinary collaborative research, provide scientific, administrative, and operational expertise and oversight, and manage advisory committees to ensure adherence to timelines and success in achieving our aims through rigorous science. Our P50 Center will be a hub fostering careers of early stage investigators and inspiring MPT product development through fellowships and pilot project grants. Drawing from our world-class Center for Biomedical Research and building on decades of successful contraceptive product development, the PC’s P50 Center will capitalize on the rich, collaborative, and interdisciplinary environment and the vast experience of the PC and our partners to advance development of an innovative MPT product.

总体 - 抽象 人口委员会（PC）P50提案的总体目标是开发一种创新的非激素 多功能预防技术（MPT）弹性静脉环（IVR）有可能改善生命 通过比较意外怀孕和性行为的重叠伯伦斯，全球数百万妇女 传播感染（ETI），包括艾滋病毒。新兴数据表明女性压倒性地更喜欢产品 这可以防止仅防止怀孕或仅仅阻止性病/艾滋病毒的怀孕和性传播感染/艾滋病毒。我们的“ CZL-IVR”是 用户控制的30天IVR，其中包含三种活性药物成分（API），铜（C），乙酸锌 （Z）和乳酸（L）（乳酸前药），具有非激素避孕药和抗STI/HIV活性 包括衣原体（CT），淋病（GC），HSV-2和HIV-1。乳酸保持最佳的阴道pH，并提供 抗菌，抗病毒和抗菌阴道（BV）作用。我们将提高CZL-IVR的发展 通过实施三个综合研究项目。在项目1中，我们旨在制定和制造 CZL-IVR可实现30天的API递送，制造和表征的体外机械性能 具有不同尺寸和聚合物的IVR，选择了四个具有一系列机械的候选者 在最终用户研究中评估并建立良好的制造实践（GMP）生产的特征 对于项目3中进行的研究的非物种环。在项目2中，我们旨在定义最佳API 单独和组合三个API的递送剂量，并确认原型的效率和安全性 CZL-IVR通过进行基本的临床前研究，包括体外和体内避孕效率以及 API的抗菌效率和毒性研究以及原型人级和恒河猴大小的CZL- IVR。在项目3中，我们将通过最终用户研究更广泛地告知CZL-IVR开发和该领域 采用新颖的混合方法方法，包括对四个选定的受控设置的交叉研究 候选的非机械特征的非药物IVR，这是一项30天的连续使用研究 带有嵌入式温度传感器的药物原型IVR，以及一项国家横截面调查 离散选择实验（DCE）和潜在类别分析（LCA）。行政核心将支持并 协同我们的跨学科合作研究，提供科学，行政和运营专业知识 和监督，并管理咨询委员会，以确保遵守时间表，并成功实现我们的成功 通过严格的科学目标。我们的P50中心将是枢纽促进早期调查人员的职业和 通过奖学金和试点项目赠款激发了MPT产品开发。从我们的世界一流的 生物医学研究中心和建筑中心数十年来，成功的避孕产品开发， PC的P50中心将利用富裕，协作和跨学科环境和疫苗 PC和我们的合作伙伴的经验可以推进创新的MPT产品的开发。