A novel intravaginal ring technology featuring the sustained release of natural progesterone for the prevention of preterm birth in at-risk women

一种新型阴道环技术，可持续释放天然黄体酮，用于预防高危女性早产

• 批准号: 10004392
• 负责人: DAVID R FRIEND
• 金额: $ 29.97万
• 依托单位: DARE BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-18 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004392
• 关键词: Advanced Development; Affect; American College of Obstetricians and Gynecologists; Biological Sciences; Brain; Centers for Disease Control and Prevention (U.S.); Cervix Uteri; Child; Clinic Visits; Clinical Research; Collaborations; Country; Data; Devices; Diagnosis; Disease; Dose; Drug Kinetics; Economic Burden; Ensure; Epithelial; Epithelium; Face; Female; Foundations; Gel; Gold; Health; Health Sciences; Hearing; High Risk Woman; Hormones; In Vitro; Infant Mortality; Infection; Inflammation; Intramuscular Injections; Laboratories; Length of Stay; Lung; Maternal-fetal medicine; Measures; Medical; Methods; Necrotizing Enterocolitis; Oregon; Outcome; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Postmenopause; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Premature Infant; Prevention; Production; Progesterone; Property; Property Leasing; Quality Control; Reporting; Risk; Risk Factors; Safety; Second Pregnancy Trimester; Self Administration; Societies; Supplementation; Survivors; System; Technology; Testing; United States; United States National Institutes of Health; Universities; Vagina; Vaginal Gel; Vaginal Ring; Vision; Woman; World Health Organization; capsule; clinical risk; comparative; cost; first-in-human; healthy pregnancy; high risk; improved; in vivo; liquid chromatography mass spectrometry; meetings; neonatal outcome; novel; off-label use; open label; phase III trial; pre-clinical; preclinical study; premature; prevent; primary endpoint; respiratory distress syndrome; skills; social; stability testing; standard care

In the United States, one in ten babies is born prematurely. The earlier in pregnancy a baby is born, the more likely s/he will have an extended hospital stay, as well as serious health complications such as respiratory distress syndrome, necrotizing enterocolitis, vision problems and infection. Women who have had a previous premature birth and women diagnosed with a short cervix in mid pregnancy are at high risk for preterm birth, and are typically prescribed a progesterone product to reduce this risk. There are currently only two general progesterone products available to women at risk for pre-term birth, each having drawbacks associated with variable efficacy and ease of use. Moreover, none of the available progesterone products have received approval from the Federal Drug Administration for use in pregnant women diagnosed with a short cervix. To improve treatment options for women having one or both clinical risk factors for a preterm birth, Daré Bioscience is advancing the development of a novel intravaginal ring, called DARE-FRT1. DARE-FRT1 offers women a patient-friendly, extended-release progesterone product that delivers a relatively constant level of the drug in close proximity to the cervix, where progesterone action regulates inflammation, contractility, and other activities associated with labor. An in vivo preclinical study demonstrated that DARE-FRT1 slowly releases bioidentical progesterone over at least 14 days. Building on these strong foundational studies we aim to (i) complete IND- enabling in vitro DARE-FRT1 product stability studies to ensure consistent and product and (ii) evaluate the comparative pharmacokinetics of different DARE-FRT1 doses in a first-in-human clinical study. Thus, DARE- FRT1 holds promise to be the first simple, safe, and convenient method to extend the term of gestation in women at high risk for preterm birth, improving overall health outcomes, and reducing infant mortality.

在美国，十分之一的婴儿早产。怀孕期间出生的婴儿越早。 他/她可能会延长住院时间，并出现严重的健康并发症，例如呼吸道疾病 曾患过窘迫综合征、坏死性小肠结肠炎、视力问题和感染的女性。 早产和在怀孕中期诊断出子宫颈短的妇女早产的风险很高，并且 通常会开出黄体酮产品来降低这种风险，目前一般只有两种。 有早产风险的女性可以使用黄体酮产品，每种产品都有与 此外，现有的黄体酮产品尚未获得批准。 来自联邦药物管理局的用于诊断患有短子宫颈的孕妇的使用。 对于具有一种或两种早产临床危险因素的女性，Dare Bioscience 提供治疗选择 推进新型阴道环的开发，称为 DARE-FRT1，为女性提供了一种新的方法。 对患者友好的缓释黄体酮产品，可在体内提供相对恒定的药物水平 靠近子宫颈，黄体酮的作用可调节炎症、收缩性和其他活动 一项体内临床前研究表明，DARE-FRT1 缓慢释放生物同质性。 在这些强有力的基础研究的基础上，我们的目标是 (i) 完成 IND- 至少 14 天。 进行体外 DARE-FRT1 产品稳定性研究，以确保产品的一致性，并且 (ii) 评估 在首次人体临床研究中比较不同 DARE-FRT1 剂量的药代动力学。 FRT1有望成为第一个简单、安全、方便的延长女性妊娠期限的方法 早产的高风险，改善整体健康结果，并降低婴儿死亡率。