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: 10324914
• 负责人: Lisa Blake Haddad
• 金额: $ 200万
• 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/10324914
• 关键词: AIDS prevention; Adherence; Advanced Development; Advisory Committees; Anti-Bacterial Agents; Antiviral 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; 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提案的首要目标是开发一种创新的非激素 多用途预防技术(MPT)阴道内环(IVR)有可能改善患者的生活 通过应对意外怀孕和性行为的重叠负担，全球数百万妇女 传播感染(STI)，包括艾滋病毒。最新数据显示，绝大多数女性更喜欢产品 与仅预防怀孕或仅预防性传播感染/艾滋病毒相比，预防怀孕和性传播感染/艾滋病毒。我们的‘CZL-IVR’ 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)(一种乳酸前体药物)，它们一起具有非激素避孕和抗性传播感染/艾滋病毒活性 包括衣原体(CT)、淋病(GC)、HSV-2和HIV-1。丙交酯维持最佳阴道酸碱度，并提供 抗菌、抗病毒和抗细菌性阴道病(BV)的效果。我们将推进我们的CZL-IVR的发展 通过实施三个综合研究项目。在项目1中，我们的目标是制定和制造 实现30天原料药递送的CZL-IVRS、制造和表征体外力学性能 IVRS具有不同的尺寸和聚合物，可选择四个候选的机械范围 在最终用户研究中评估特性，并建立良好的制造规范(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原料药 三种原料药单独和联合给药的剂量，并确认原型的有效性和安全性 CZL-IVR通过进行基本的临床前研究，包括体外和体内避孕效果和 原料药、人体大小和猕猴大小的原型CZL的抗菌效果和毒性研究 IVRS。在项目3中，我们将通过终端用户研究向CZL-IVR的开发和更广泛的领域提供信息 采用新的混合方法，包括对选定的四个项目进行受控设置交叉研究 机械特性不同的候选非药物IVR，一项非药物连续使用30天的研究 带有嵌入式温度传感器的医用原型IVR，以及一项具有 离散选择实验(DCE)和潜在类分析(LCA)。行政核心将支持和 协同我们的跨学科协作研究，提供科学、管理和运营方面的专业知识 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 以严谨的科学为目标。我们的P50中心将成为促进早期调查人员和 通过奖学金和试点项目赠款激励MPT产品开发。取材于我们世界级的 生物医学研究中心在几十年成功的避孕产品开发的基础上， PC的P50中心将利用丰富、协作和跨学科的环境以及 PC和我们的合作伙伴的经验，以推动创新的MPT产品的开发。