An Etonogestrel/Ethinyl Estradiol/QGriffithsin (ETG/EE/QGRFT) IVR to Prevent Pregnancy and HIV

用于预防怀孕和艾滋病毒的依托孕烯/乙炔雌二醇/QGriffithsin (ETG/EE/QGRFT) IVR

基本信息

批准号：
10394426
负责人：
Nina R. Derby
金额：
$ 98.7万
依托单位：
POPULATION COUNCIL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-06 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10394426
关键词：
Adherence Adverse event Anti-Retroviral Agents Antiretroviral resistance Antiviral Agents Biological Assay Biological Response Modifiers Caliber Collaborations Colposcopy Computer Assisted Contraceptive Agents Contraceptive Usage Contraceptive methods Counseling Couples Cross-Over Studies Development Plans Dose Drug Delivery Systems Drug Kinetics Estrogens Ethinyl Estradiol Etonogestrel Excision Fibroins Formulation Frequencies Future HIV HIV Infections HIV drug resistance HIV resistance Hemorrhage High Pressure Liquid Chromatography High Risk Woman Human In Vitro Infectious Pregnancy Complications Institutes Instruction Interview Lead Lectin Levonorgestrel Macaca mulatta Measurement Measures Menstruation Methodology Pharmacodynamics Pilot Projects Placebos Plasma Population Pregnancy Prevention Process Progestins Questionnaires Reporting Research Design Resistance Resistance development Risk Safety Science Self Assessment Serious Adverse Event Sex Behavior Silicones Silk Technology Testing Text Messaging Tissues Vagina Vaginal Ring Viremia Virus Shedding Woman Women&apos s Health Work anti-viral efficacy base demographics design diaries efficacy study experimental study improved in vivo innovation non-drug novel parity preference prevent product development reproductive tract safety assessment sex side effect simian human immunodeficiency virus social technology development tool transcriptome transcriptome sequencing transmission process unintended pregnancy vaginal fluid

项目摘要

An Etonogestrel/Ethinyl Estradiol/QGriffithsin (EEQ) IVR to Prevent Pregnancy and HIV Several multipurpose prevention technologies (MPTs) have been advanced to prevent unintended pregnancy and HIV. The current MPT development pipeline is dominated by antiretroviral (ARV) products with progestin- only contraception using levonorgestrel. The Population Council, in collaboration with Oak Crest Institute of Science (OCIS), proposes to develop a 90d pod-type IVR containing the progestin etonogestrel (ETG), the estrogen ethinyl estradiol (EE), and the anti-HIV lectin QGriffithsin (QGRFT), hereafter referred to as the EEQ IVR, to prevent unintended pregnancy and HIV. This product offers a highly effective contraceptive combination (used in NuvaRing®) with the extremely potent and stable non-ARV anti-HIV lectin QGRFT. The EEQ IVR offers significant advantages over ARV/progestin-only contraceptive products. It could reduce both the emergence of drug-resistant HIV and the concern of potential increased risk of HIV transmission as well as common irregular bleeding complaints associated with use of a progestin-only contraceptive. Aim 1: The proposed product development plan for the EEQ IVR includes innovative formulation work involving pod IVR designs and the use of silk fibroin to achieve QGRFT release for 90d. We will develop a scalable process to manufacture an EEQ IVR. Aim 2: Two lead EEQ IVRs will be tested in safety/pharmacokinetics/pharmacodynamics studies in rhesus macaques (RMs). We intend that the EEQ IVR will be safe, deliver target API doses for 90d in vivo and demonstrate in vitro efficacy against HIV/SHIV AD8. Based on these studies, the lead RM IVR will be selected and advanced to in vivo efficacy studies in RMs. We postulate that the EEQ IVR will be efficacious against SHIV AD8 in vivo and will not drive resistance. Aim 3: We will conduct a pilot study among 24 US couples to compare adherence, preference and acceptability of 3 placebo silicone IVRs of different external diameters (46mm, 56mm and 66mm) to inform the design of the EEQ IVR. Using a 3-way crossover study design, we will identify the external IVR diameter associated with greatest adherence and preference to inform the final EEQ IVR design. The EEQ IVR has the potential to significantly improve women’s health and advance the MPT and drug delivery fields. The EEQ IVR would be the first non-ARV MPT for women at high risk for both unintended pregnancy and HIV acquisition.

用于预防怀孕和艾滋病毒的依托孕烯/乙炔雌二醇/QGriffithsin (EEQ) IVR 多项多用途预防技术 (MPT) 已取得进展，可预防意外怀孕目前的 MPT 开发管线以含有孕激素的抗逆转录病毒 (ARV) 产品为主。人口委员会与 Oak Crest 研究所合作，仅使用左炔诺孕酮进行避孕。 Science (OCIS) 提议开发一种含有孕激素依托孕烯 (ETG) 的 90 天荚式 IVR，雌激素乙炔雌二醇 (EE) 和抗 HIV 凝集素 QGriffithsin (QGRFT)，以下简称 EEQ IVR，防止意外怀孕和艾滋病毒。该产品提供高效的避孕措施。与极其有效且稳定的非 ARV 抗 HIV 凝集素 QGRFT 的组合（用于 NuvaRing®）。 EEQ IVR 比仅使用 ARV/孕激素的避孕产品具有显着优势，它可以减少这两种情况。耐药艾滋病毒的出现以及对艾滋病毒传播风险潜在增加的担忧以及与使用纯孕激素避孕药相关的常见不规则出血症状目标 1：拟议的 EEQ IVR 产品开发计划包括涉及 pod IVR 的创新配方工作我们将开发一种可扩展的工艺来实现 90 天的 QGRFT 释放。目标 2：将测试两个主要 EEQ IVR。我们打算在恒河猴 (RM) 中进行安全性/药代动力学/药效学研究。将是安全的，可在体内提供 90 天的目标 API 剂量，并在体外展示针对 HIV/SHIV AD8 的功效。基于这些研究，将选择主要的 RM IVR 并将其推进到 RM 的体内疗效研究。假设 EEQ IVR 在体内对 SHIV AD8 有效并且不会产生耐药性目标 3：我们将对 24 对美国夫妇进行一项试点研究，以比较 3 对夫妇的依从性、偏好和可接受性不同外径（46 毫米、56 毫米和 66 毫米）的安慰剂硅胶 IVR 可为设计提供信息 EEQ IVR。使用三路交叉研究设计，我们将确定与相关的外部 IVR 直径。最大的坚持和偏好为最终的 EEQ IVR 设计提供信息 EEQ IVR 有潜力 EEQ IVR 将显着改善女性健康并推进 MPT 和药物输送领域。首个针对意外怀孕和艾滋病毒感染高风险女性的非抗逆转录病毒 MPT。