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: 10493305
• 负责人: Lisa Blake Haddad
• 金额: $ 233.5万
• 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/10493305
• 关键词: AIDS prevention; Adherence; Advanced Development; Advisory Committees; Anti-Bacterial Agents; Bacterial Vaginosis; Basic Science; Behavioral Sciences; Biomedical Research; Characteristics; 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; Grant; HIV; HIV Infections; HIV-1; Health; Hormones; Human; Human Herpesvirus 2; In Vitro; Industry; Infertility; Investigational Drugs; Investments; Lactic acid; Lead; Macaca mulatta; 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; TimeLine; Toxic effect; Vagina; Vaginal Ring; Woman; Women' s Health; Work; Zinc; Zinc Acetate; antimicrobial; career; chronic pelvic pain; collaborative environment; combat; community engagement; contraceptive efficacy; design; experience; experimental study; health goals; improved; in vivo; innovation; interest; novel; preclinical study; prevent; product development; prototype; public health priorities; research and development; safety study; sensor; sperm cell; success; technology development; 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 – 摘要 人口理事会 (PC) P50 提案的总体目标是开发一种创新的非激素药物 多用途预防技术 (MPT) 阴道环 (IVR) 有可能改善患者的生活 通过对抗意外怀孕和性行为的重叠负担，全球数以百万计的妇女 传播感染 (STI)，包括艾滋病毒。新数据表明，女性绝大多数更喜欢产品 预防怀孕和性传播感染/艾滋病毒的药物优于仅预防怀孕或仅预防性传播感染/艾滋病毒的药物。我们的“CZL-IVR”是 用户控制的 30 天 IVR，包含三种活性药物成分 (API)、铜 (C)、醋酸锌 (Z) 和丙交酯 (L)（乳酸前药）共同具有非激素避孕和抗 STI/HIV 活性 包括衣原体 (CT)、淋病 (GC)、HSV-2 和 HIV-1。丙交酯可维持最佳阴道 pH 值并提供 抗菌、抗病毒和抗细菌性阴道病（BV）作用。我们将推进CZL-IVR的开发 通过实施三个综合研究项目。在项目 1 中，我们的目标是配制和制造 CZL-IVR 可实现 30 天的 API 交付、制造并表征药物的体外机械性能 具有不同尺寸和聚合物的 IVR，并选择具有一系列机械性能的四个候选者 在最终用户研究中评估的特征，并建立良好生产规范 (GMP) 生产 用于项目 3 中进行的研究的非药物环。在项目 2 中，我们的目标是定义最佳 API 三种 API 单独和组合的给药剂量，并确认原型的有效性和安全性 CZL-IVR 通过进行重要的临床前研究，包括体外和体内避孕功效和 API 以及人体大小和恒河猴大小的原型 CZL- 的抗菌功效和毒性研究 IVR。在项目 3 中，我们将通过最终用户研究更广泛地为 CZL-IVR 开发和该领域提供信息 采用新颖的混合方法方法，包括对四种选定的方法进行受控设置交叉研究 具有不同机械特性的候选非药物 IVR，一项针对非药物的 30 天连续使用研究 带有嵌入式温度传感器的药物原型 IVR，以及带有 离散选择实验（DCE）和潜在类别分析（LCA）。行政核心将支持和 协同我们的跨学科合作研究，提供科学、管理和运营专业知识 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目标 通过严格的科学来实现目标。我们的 P50 中心将成为培养早期研究人员和 通过奖学金和试点项目资助激励 MPT 产品开发。借鉴我们的世界一流水平 生物医学研究中心以数十年成功的避孕产品开发为基础， PC 的 P50 中心将利用丰富、协作和跨学科的环境以及广阔的 PC 和我们的合作伙伴的经验推动了创新 MPT 产品的开发。