RP5 MPT Study

RP5 MPT 研究

• 批准号: 10595905
• 负责人: Lisa B Hightow-Weidman
• 金额: $ 73.09万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-25 至 2029-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595905
• 关键词: AIDS prevention; Acceleration; Acquired Immunodeficiency Syndrome; Address; Adolescent; Adolescent Medicine Trials Network; Adolescent and Young Adult; Advanced Development; Age; Attitude; Benefits and Risks; Clinical Research; Contraceptive Agents; Contraceptive methods; Data; Development; Drug Delivery Systems; Drug Interactions; Drug Kinetics; Drug Targeting; Ensure; Epidemic; Evaluation; Gender; HIV; HIV Infections; HIV Seronegativity; HIV diagnosis; HIV/AIDS; Health Benefit; Healthcare Systems; In Vitro; Injectable; Injections; Intervention; Interview; Leadership; Levonorgestrel; Licensing; Licensure; Menstruation; Mission; Modality; Modeling; Oral; Ovulation Inhibition; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Pregnancy; Pregnancy in Adolescence; Prevention; Public Health; Rattus; Reporting; Reproductive Health; Risk; Safety; Sampling; Sexual Health; Sexual and Gender Minorities; Sexual and Gender Minority Youth; Signal Transduction; Site; Subcutaneous Injections; Technology; Time; United States; Youth; aged; arm; assigned female at birth; cis-female; condoms; design; experience; experimental study; first-in-human; gender affirming hormone therapy; gender minority group; health disparity; improved; innovative technologies; nonhuman primate; novel; novel therapeutics; pre-exposure prophylaxis; preclinical study; preference; pregnancy prevention; prevent; product development; reversible contraceptive; safety assessment; sex; social; success; technology development; transgender; transgender men; transmasculine; uptake

PROJECT SUMMARY Adolescents assigned female at birth (AFAB) in the United States (US) have unmet needs for pregnancy and HIV prevention; 75% of pregnancies in adolescents are unplanned and 12% of new HIV diagnoses occur in youth aged 13-24 years AFAB. Sexual and gender minority (SGM) youth may have particular vulnerabilities and yet their sexual and reproductive health needs are often overlooked or misunderstood. Multi-purpose prevention technology (MPT) products that can simultaneously prevent pregnancy, suppress menses, and prevent HIV are desirable, may bring efficiencies to both users and healthcare systems, and may serve to improve uptake of HIV prevention products among youth. Early studies suggest that adolescents AFAB would prefer an MPT that is discreet and long-lasting, with injections being a preferred delivery modality. The success of cabotegravir (CAB) as the first generally safe and highly effective long-acting systemic agent for HIV prevention opens up opportunities for the development of an injectable MPT that combines CAB with an effective contraceptive, like levonorgestrel (LNG); LNG has been widely used and has an established safety track record. CONRAD has developed a first-in-class long acting systemic MPT that consists of a bioresorbable injectable depot and that employs a novel drug delivery technology to deliver both CAB and LNG together for at least three months, and possibly longer. Pre-clinical studies in rats and non-human primates show promise. To advance the development of this injectable CAB/LNG MPT our team with complementary expertise will conduct studies to 1) assess the values and preferences for a novel MPT for pregnancy and HIV prevention in adolescent cisgender women (CW) and transgender men (TM) AFAB aged 16-24 years in the USA, using a combination of qualitative interviews and participatory attitudinal ranking approaches to inform the selection of attributes and levels for a Discrete Choice Experiment to be conducted in a sample of 200 CW and 200 TM AFAB; and 2) conduct a multi-site, phase I, single arm PK trial of the CAB/LNG injectable biodegradable depot in a sample of 16 healthy, HIV-negative adolescents and young adults AFAB, ages 18-24, to assess the safety and pharmacokinetic profile of the products in CW and TM AFAB who are receiving gender-affirming hormone therapy. Incorporation of end-user preferences for MPTs early on in product development can enhance acceptability, optimize uptake and use, and ultimately ensure public health benefit. The evaluation of the safety, acceptability and pharmacology of a first in-human CAB/LNG biodegradable depot injection in CW and TM youth will ensure that data on adolescents across genders is available for regulators should co-formulated CAB/LNG move forward for licensure. The availability of a highly effective, long-acting MPT that places a premium on safety and acceptability in adolescents AFAB across genders, has the potential to accelerate access to effective sexual and reproductive health, to potentially address disparities in health access for SGM populations, and to have a substantial impact on the HIV epidemic.

项目摘要 在美国（美国）出生时分配女性（AFAB）的青少年（美国）对怀孕有未满足的需求 和预防艾滋病毒； 75％的青少年怀孕是计划外的，发生了12％的新艾滋病毒诊断 在13-24岁的青年中。性和性别少数民族（SGM）青年可能有特殊的脆弱性 然而，他们的性和生殖健康需求经常被忽视或误解。多功能 预防技术（MPT）产品可以同时防止怀孕，抑制月经和 预防艾滋病毒是理想的，可能会给用户和医疗保健系统带来效率，并可能有助于 改善青年预防艾滋病毒预防产品的吸收。早期研究表明，青少年AFAB会 喜欢谨慎且持久的MPT，注射是首选的输送方式。成功 Cabotegravir（CAB）是艾滋病毒的第一个总体安全且高效的长效全身剂 预防为开发可注射的MPT开发的机会，将CAB与 有效的避孕药，例如左甲虫（LNG）；液化天然气已被广泛使用，并具有确定的安全性 往绩记录。康拉德（Conrad 可生物可吸收的注射仓库，并采用新型药物输送技术来交付CAB和LNG 在一起至少三个月，甚至更长。大鼠和非人类灵长类动物的临床前研究 表现出承诺。为了推动这款可注射的出租车/LNG MPT的开发，我们的团队有补充 专业知识将进行研究1）评估新型MPT怀孕和HIV的价值和偏好 青少年sisgender妇女（CW）和跨性别男性（TM）AFAB的预防，年龄16-24岁 美国，结合了定性访谈和参与式态度排名的方法来告知 在200 cw样品中进行离散选择实验的属性和水平的选择 和200 TM AFAB； 2）进行CAB/LNG的多站点I期，单臂PK试验 可生物降解的仓库在16个健康的，HIV阴性的青少年和年轻人AFAB中，年龄18-24岁， 评估正在接收的CW和TM AFAB中产品的安全性和药代动力学概况 性别表明激素疗法。早期将MPT的最终用户偏好纳入产品 开发可以增强可接受性，优化吸收和使用，并最终确保公共卫生的利益。 第一次人类驾驶室/LNG可生物降解的安全性，可接受性和药理学评估 CW和TM青年注射仓库将确保可用于跨性别的青少年数据 监管机构应共同成型的CAB/LNG向前推进许可。高效的可用性 长效的MPT将在各个性别的青少年AFAB中授予安全性和可接受性的溢价， 加速获得有效的性和生殖健康的潜力，有可能解决差异 在SGM人群的健康方面，并对HIV流行产生重大影响。