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

基本信息

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
项目类别：
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&apos 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

项目摘要

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包括艾滋病毒在内的传播感染（STI）的新数据表明，女性绝大多数更喜欢产品。与仅预防怀孕或仅预防性传播感染/艾滋病毒的药物相比，我们的“CZL-IVR”是预防怀孕和性传播感染/艾滋病毒的。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 和丙交酯，可维持最佳阴道 pH 值并提供。我们将推进 CZL-IVR 的抗菌、抗病毒和抗细菌性阴道病 (BV) 作用。通过实施三个综合研究项目，我们的目标是制定和制造。 CZL-IVR 可实现 30 天的 API 交付、制造和表征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）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我们的 P50 中心将成为培养早期研究人员职业生涯的中心。通过奖学金和试点项目资助来激励 MPT 产品开发。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。