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 美国出生时被指定为女性的青少年（AFAB）的妊娠需求未得到满足 预防艾滋病毒; 75%的青少年怀孕是计划外的，12%的新艾滋病毒诊断是在 在13-24岁的青年AFAB。性少数和性别少数（SGM）青年可能特别脆弱 然而，他们的性健康和生殖健康需求往往被忽视或误解。多用途 预防技术（MPT）产品，可以同时防止怀孕，抑制月经， 预防HIV是期望的，可以为用户和医疗保健系统带来效率，并且可以用于 提高青年对艾滋病毒预防产品的接受程度。早期的研究表明，青少年AFAB 更喜欢谨慎和持久的MPT，注射是首选的输送方式。成功 cabotegravir（CAB）作为第一种普遍安全和高效的长效系统性HIV药物 预防为开发一种将CAB与 有效的避孕药，如左炔诺孕酮（LNG）; LNG已被广泛使用，并具有既定的安全性 业绩记录CONRAD开发了一流的长效系统MPT，由以下组成： 生物可吸收的可注射贮库，并采用新的药物输送技术来输送CAB和LNG 在一起至少三个月，甚至更长。大鼠和非人灵长类动物的临床前研究 表现出承诺。为了推进这种可注射CAB/LNG MPT的开发，我们的团队与互补的 专家将进行研究，以1）评估价值和偏好的一种新的MPT怀孕和艾滋病毒 预防青少年顺性别妇女（CW）和变性男子（TM）AFAB年龄在16-24岁， 美国，使用定性访谈和参与性态度排名方法相结合，以告知 在200个CW样本中进行离散选择实验的属性和水平选择 和200 TM AFAB;和2）进行CAB/LNG注射剂的多中心、I期、单臂PK试验 在16名健康的HIV阴性青少年和年轻成人AFAB的样品中，年龄为18-24岁， 评估CW和TM AFAB患者接受本品的安全性和药代动力学特征 性别确认激素疗法将最终用户对MPT的偏好尽早纳入产品 发展可以提高可接受性，优化吸收和使用，并最终确保公共健康利益。 第一个人体可生物降解CAB/LNG的安全性、可接受性和药理学评价 在CW和TM青少年中进行长效注射将确保可获得不同性别青少年的数据， 监管机构应共同制定CAB/LNG推进许可证。一种高效， 长效MPT重视青少年AFAB的安全性和可接受性， 加速获得有效的性健康和生殖健康的可能性， 在SGM人群的健康获取方面，并对艾滋病毒的流行产生重大影响。