Formulation development and testing of a novel non-hormonal intravaginal ring to prevent pregnancy and sexually transmitted infections

用于预防怀孕和性传播感染的新型非激素阴道环的配方开发和测试

• 批准号: 10493312
• 负责人: BRUCE F VARIANO
• 金额: $ 44.64万
• 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/10493312
• 关键词: AIDS prevention; Address; Adherence; Advanced Development; Anti-Bacterial Agents; Bacterial Vaginosis; Biological Assay; Characteristics; Chlamydia; Collaborations; Contraceptive Agents; Contraceptive methods; Copper; Data; Development; Dimensions; Documentation; Dose; Evaluation; Failure; Formulation; Geometry; Goals; Gonorrhea; HIV; HIV/STD; Health; Healthcare; Human; Human Herpesvirus 2; In Vitro; Infection; Ions; Lactic acid; Lead; Macaca mulatta; Manufactured Supplies; Measures; Mechanics; Methods; Modeling; Molds; Pathway interactions; Performance; Pharmacologic Substance; Polymers; Population; Positioning Attribute; Pregnancy; Prevention; Prodrugs; Property; Quality Control; Regimen; Reproductive Health; Research; Research Project Grants; Residual state; Role; Salts; Scientist; Self Care; Sexual Transmission; Sexually Transmitted Diseases; Sheep; Silicone Elastomers; Source; Technology; Technology Transfer; Temperature; Testing; Universities; Vagina; Vaginal Ring; Woman; Zinc; analytical method; clinical efficacy; cost efficient; design; expectation; experience; flexibility; health goals; in vitro testing; lead candidate; manufacturing process; manufacturing scale-up; medical schools; meetings; metallicity; multidisciplinary; new technology; novel; pre-clinical; preference; prevent; prototype; public health intervention; quality assurance; reproductive; research and development; research clinical testing; safety testing; scale up; sensor; social; stability testing; tool; vaginal infection

PROJECT I – ABSTRACT Despite extensive choice and increasing availability, current contraceptive options are not meeting the needs of many women, as is evident by high levels of typical-use failure, method non-use, switching, and discontinuation. Approximately half of all pregnancies (121 million) around the world are unintended and 218 million women have an unmet need for effective contraception. New technologies having attributes more closely aligned with users’ needs and expectations are urgently needed to fill this critical gap in sexual and reproductive healthcare. The overall goal of this P50 center is to bring together some of the leading research organizations in the world with unrivalled expertise and know-how around design, manufacture and testing of intravaginal ring (IVR) technology – including Population Council (PC), Queen's University Belfast (QUB), and Weill Cornell Medical College (WCMC) – in a concerted effort to develop a new, practical, easy-to-use, long-acting, multipurpose prevention technology (MPT) IVR offering both spermicidal activity and broad antibacterial/antiviral activity against various common sexually transmitted/vaginal infections, including chlamydia, gonorrhea, bacterial vaginosis (BV), and infection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV). Unlike other marketed and experimental contraceptive IVR products, we are committed here to the development of a non- hormonal contraceptive strategy, referred to as the CZL-IVR, in which copper ions or copper salts (C), zinc ions or zinc salts (Z), and lactide (L) are simultaneously administered to the vagina in a sustained/controlled manner over at least 30 days. The overarching goal of Project 2, which involves a strategic and highly integrated partnership between Queen's University Belfast (QUB) and Population Council (PC), is to provide formulation support for the P50 project. Specifically, this will involve all aspects of CZL-IVR product design, formulation, manufacture and in vitro testing, according to three key aims: In Aim 1, we will develop a CZL-IVR that releases copper, zinc and lactide for at least 30 days in quantities sufficient for clinical efficacy; in Aim 2, we will design, manufacture and characterize non-medicated IVRs and sensor- embedded IVRs for end-user testing; and in Aim 3, we will complete technology transfer between QUB and PC and GMP manufacture the IVRs for clinical evaluation for Project 3. Project 1 will be closely coordinated with Projects 2 and 3 to inform IVR loading and selection of the lead IVR. Our multidisciplinary collaborative team is uniquely qualified to advance the development of this novel MPT IVR. The CZL-IVR will address a critical gap in the non-hormonal contraceptive landscape, fill a niche that users want and deliver an important public health intervention.

项目I - 摘要 尽管选择了广泛的选择和可用性的增加，但当前的避孕方法仍未满足 许多女性，正如高水平的典型使用故障，方法不使用，切换和中断所证明的那样。 世界上大约一半的怀孕（1.21亿）是意想不到的，有2.18亿妇女 未满足有效避孕的需求。具有与用户更加紧密匹配的新技术 迫切需要需求和期望，以填补性和生殖医疗保健方面的这一关键差距。 这个P50中心的总体目标是将世界上一些领先的研究组织与 无与伦比的专业知识和专业知识，围绕着阴道圈（IVR）技术的设计，制造和测试 - 包括人口委员会（PC），贝尔法斯特皇后大学（QUB）和威尔·康奈尔医学院 （WCMC） - 一致努力开发一种新的，实用的，易于使用，长效，预防多功能 技术（MPT）IVR提供杀精性活性和广泛的抗菌/抗病毒活性 常见的性传播/阴道感染，包括衣原体，淋病，阴道细菌（BV）和 用单纯疱疹病毒2型（HSV-2）和人类免疫缺陷病毒（HIV）感染。与其他不同 销售和实验性的避孕IVR产品，我们在这里致力于开发非 - 激素避孕策略，称为CZL-IVR，其中铜离子或铜盐（C），锌离子 或以持续/控制的方式将锌盐（Z）和乳酸（L）简单地给予阴道 至少30天。项目2的总体目标，涉及战略性且高度融合 贝尔法斯特皇后大学（QUB）与人口委员会（PC）之间的伙伴关系将提供 P50项目的编队支持。具体而言，这将涉及CZL-IVR产品的所有方面 根据三个关键目的，设计，配方，制造和体外测试：在AIM 1中，我们将 开发一种CZL-IVR，该CZL-IVR释放铜，锌和乳酸至少30天的数量足以 临床效率；在AIM 2中，我们将设计，制造和表征非药物IVR和传感器 - 用于最终用户测试的嵌入式IVR；在AIM 3中，我们将完成QUB之间的技术转移 PC和GMP制造了用于项目3的临床评估的IVR。项目1将紧密 与项目2和3协调，以告知IVR加载和选择铅IVR。我们的多学科 协作团队具有独特的资格，可以推进这部小说MPT IVR的发展。 CZL-IVR会 解决非荷尔蒙避孕景观中的关键差距，填补用户想要并提供的利基市场 重要的公共卫生干预。