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

• 批准号: 9926449
• 负责人: Nina R. Derby
• 金额: $ 106.89万
• 依托单位: POPULATION COUNCIL
• 依托单位国家: 美国
• 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/9926449
• 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' 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

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.

依托孕烯/乙炔雌二醇/QGriffithsin（EEQ）IVR预防妊娠和HIV 为防止意外怀孕，已经开发了几种多用途预防技术（MPT） 和艾滋病病毒。目前的MPT开发管道主要是抗逆转录病毒（ARV）产品， 仅使用左炔诺孕酮避孕。人口理事会与Oak Crest研究所合作， 科学（OCIS），建议开发一种90天的豆荚型IVR含有依托孕烯（ETG）， 雌激素炔雌醇（EE）和抗HIV凝集素QGriffithsin（QGRFT），以下简称EEQ IVR，以防止意外怀孕和艾滋病毒。本产品是一种高效的避孕药 与极其有效且稳定的非ARV抗HIV凝集素QGRFT组合（用于NuvaRing®）。的 EEQ IVR比ARV/仅孕激素避孕产品具有显著优势。它可以减少两者 艾滋病毒抗药性的出现和对艾滋病毒传播风险可能增加的关切，以及 与使用仅含孕激素的避孕药相关的常见不规则出血投诉。目标1： EEQ IVR的拟议产品开发计划包括涉及pod IVR的创新配方工作 设计并使用丝素蛋白实现QGRFT释放90天。我们将开发一个可扩展的流程， 制作一个EEQ IVR。目标2：将对两种电极导线EEQ IVR进行测试， 恒河猴（RM）的安全性/药代动力学/药效学研究。我们希望EEQ IVR 将是安全的，在体内递送目标API剂量达90天，并在体外证明对HIV/SHIV AD 8的功效。 根据这些研究，将选择主要RM IVR并推进至RM体内疗效研究。我们 假设EEQ IVR将在体内有效对抗SHIV AD 8，并且不会引起耐药性。目标三： 我们将在24对美国夫妇中进行一项试点研究，以比较3种药物的依从性、偏好和可接受性。 不同外径（46 mm、56 mm和66 mm）的安慰剂硅胶IVR，以告知 EEQ IVR。使用3向交叉研究设计，我们将确定与以下因素相关的IVR外径： 最大程度的遵守和偏好，以告知最终的EEQ IVR设计。EEQ IVR有可能 显著改善妇女的健康，推进MPT和药物输送领域。EEQ IVR将是 第一个非ARV MPT用于意外怀孕和艾滋病毒感染高风险的妇女。