Novel pre-coital, non-hormonal multipurpose prevention technology (MPT)

新型性交前非激素多用途预防技术 (MPT)

• 批准号: 10569037
• 负责人: Pavimol Angsantikul
• 金额: $ 90.89万
• 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: 2020-03-20 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569037
• 关键词: Acceleration; Acids; Animal Model; Anti-Infective Agents; Anti-Retroviral Agents; Antimicrobial Effect; Antiretroviral resistance; Atopobium vaginae; Bacteria; Bacterial Vaginosis; Biological Assay; Biological Sciences; Breast Feeding; Breastfed infant; Buffers; Chlamydia; Clinical; Contraceptive Agents; Contraceptive methods; Data; Dose; Enrollment; Evaluation; Event; Excipients; Female; Female Adolescents; Formulation; Freeze Drying; Gel; Genitourinary system; Goals; Gonorrhea; HIV; HIV antiretroviral; HIV resistance; HIV risk; HIV/STD; Health; High Pressure Liquid Chromatography; Human Herpesvirus 2; Human papilloma virus infection; Infection; Infection prevention; Intravaginal Administration; Lead; Lectin; Literature; Macaca; Macaca mulatta; Methods; Modeling; Mus; Normal Range; Oral; Oryctolagus cuniculus; Partner in relationship; Pharmaceutical Preparations; Pharmacodynamics; Phase; Predisposition; Pregnancy; Prevention; Prevention trial; Property; Protocols documentation; Rattus; Risk; Risk Reduction; Safety; Seminal fluid; Series; Technology; Testing; Toxic effect; Toxicology; Tube; Vagina; Vaginal Gel; Viral; Viral Physiology; Virus; Virus Diseases; Woman; Women' s Health; Work; analog; contraceptive efficacy; cytotoxicity; efficacy study; efficacy testing; efficacy trial; hormonal contraception; improved; in vitro Assay; in vivo; innovation; irritation; male; manufacture; manufacturing process; meetings; mouse model; novel; pharmacokinetics and pharmacodynamics; phase I trial; pill; pre-Investigational New Drug meeting; preclinical development; prevent; prototype; relapse prevention; sex; side effect; simian human immunodeficiency virus; sperm cell; systemic toxicity; technology development; vaginal fluid; young woman

ABSTRACT Emerging evidence indicates that women are more likely to use a multipurpose prevention technology (MPT) for pregnancy and HIV/STI infection prevention than a product for pregnancy or HIV/STI infection prevention. The MPT development space is dominated by products that contain one or more hormonal contraceptives, which many women, including breastfeeding women, cannot or will not use. Amphora gel is an exception. Ampphora is a non-hormonal, vaginally-acting contraceptive product for women being developed by Evofem Biosciences Inc. It works by maintaining a low vaginal pH that is hostile to sperm, bacteria, and viruses. Evofem recently completed a Phase 3 contraceptive efficacy trial of Amphora that indicated typical use efficacy of 86.0% and per protocol efficacy (perfect use) of 98.7%, comparable to the efficacy of the most commonly used forms of hormonal contraception, oral pills. Amphora is currently being tested in Phase 2b trials for prevention of urogenital chlamydia and gonorrhea in women and preparing for trials for prevention of recurrent bacterial vaginosis (BV), which has completed enrollment. QGRFT is a stable analog of the non-antiretroviral (non-ARV) anti-HIV lectin griffithsin (GRFT). We completed a Phase 1 trial of a vaginally administered GRFT gel, and with PATH developed a novel vaginally administered GRFT fast dissolving insert (FDI) that significantly prevented simian human immunodeficiency virus (SHIV) infection in macaques and HSV-2 and HPV infection in mice. Our long term goal is to develop an Amphora/QGRFT FDI for adolescent girls and a wide range of women, including breastfeeding women, which provides non-hormonal contraception and reduces the risk of acquiring a broad range of viral and bacterial STIs. Herein we will evaluate the feasibility, safety, and in vivo efficacy of two innovative MPT prototypes: an Amphora/QGRFT FDI that could have contraceptive and anti-HIV/STI/BV properties and an Amphora-only FDI that could have contraceptive and anti-STI/BV properties. The prototypes will be manufactured and then evaluated in a series of in vitro assays, physiochemical property/stability evaluations, and in vivo studies to demonstrate FDI disintegration, drug retention in the vagina, safety, anti-HIV activity (pharmacodynamics studies in a macaque model and in vivo efficacy in macaques) and anti-HSV-2 activity (murine model). The Amphora/QGFRT FDI may offer more potent anti-HSV-2 activity than Amphora alone due to QGRFT’s anti-HSV-2 activity. Using data obtained in these studies, we will select one FDI to advance into contraceptive efficacy testing in rabbits and IND-enabling toxicology studies in rats. The novel non-hormonal FDI proposed here could (i) eliminate side effects associated with hormonal contraceptives, (ii) meet the needs of women who have infrequent sex or who are breastfeeding, and (iii) reduce the sexual acquitision of HIV/STIs and the emergence of ARV-resistant HIV. This woman-initiated FDI has the potential to improve women’s health and advance the MPT field. When approved, the FDI would be the first non-hormonal, on-demand and event-driven MPT with both contraceptive and broad spectrum anti/HIV/STI properties.

抽象的 新兴的证据表明，女性更有可能使用多功能预防技术（MPT） 预防妊娠和HIV/STI感染的预防产品预防怀孕或HIV/STI感染。这 MPT开发空间由包含一种或多种激素避孕药的产品主导 许多妇女，包括母乳喂养的妇女，无法或不会使用。 Amphora Gel是一个例外。安福拉 是一种非激素，阴道作用的避孕产品，用于由Evofem Biosciences开发的女性 Inc.它通过维持对精子，细菌和病毒敌对的低阴道pH值的起作用。最近 完成了三阶段的Amphora避孕效率试验，该试验表明典型的使用有效性为86.0％＆per 协议有效性（完美使用）为98.7％，可与最常用形式的效率相当 荷尔蒙避孕药，口服药丸。目前正在2阶段试验中对Amphora进行测试以预防 女性泌尿生殖道衣原体和淋病，并准备预防复发细菌的试验 阴道（BV），已完成入学。 QGRFT是非抗抗病毒（非ARV）的稳定类似物 抗HIV凝集素Griffithsin（GRFT）。我们完成了一项阴道施用的GRFT凝胶的1期试验，然后 随着路径的发展，一种新型的阴道施用的GRFT快速溶解插入物（FDI）显着 在猕猴中预防猿猴免疫缺陷病毒（SHIV）感染，HSV-2和HPV感染 老鼠。我们的长期目标是为青少年女孩和众多女性开发Amphora/QGRFT FDI， 包括母乳喂养的妇女，提供非荷尔蒙违规行为并降低获得A的风险 广泛的病毒和细菌性传播感染。在此，我们将评估两个的可行性，安全性和体内效率 创新的MPT原型：一种可能具有避孕药和抗HIV/STI/BV的Amphora/QGRFT FDI 可能具有避孕/抗STI/BV特性的性质和仅使用两栖动物的外国直接投资。 原型将制造然后在一系列体外测定中进行评估 财产/稳定性评估和体内研究，以证明FDI崩解，阴道中的药物保留， 安全性，抗HIV活性（猕猴模型中的药效学研究和猕猴中的体内效率）和 抗HSV-2活性（鼠模型）。 Amphora/QGFRT FDI可能会提供更多的潜在抗HSV-2活动 仅由于QGRFT的抗HSV-2活性，仅两侧。使用这些研究获得的数据，我们将选择一个FDI 在兔子和大鼠的毒理学研究中进展进行避孕效率测试。小说 这里提出的非激素外国直接投资可以（i）消除与激素避孕药相关的副作用，（ii） 满足不经常性或母乳喂养的妇女的需求，（iii）减少性 艾滋病毒/性传播疾病的无罪释放和抗ARV抗艾滋病毒的出现。这个女性发起的外国直接投资有可能 改善妇女的健康并提高MPT领域。批准后，外国直接投资将是第一个非激素， 按需和事件驱动的MPT具有避孕和广谱抗/HIV/STI特性。