Preclinical Testing of Human Contraceptive Antibody (HCA) and HCA products

人类避孕抗体（HCA）和HCA产品的临床前测试

• 批准号: 10159120
• 负责人: Deborah J Anderson
• 金额: $ 39.97万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-14 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159120
• 关键词: Acrosome Reaction; Adult; Antibodies; Biological Assay; Cervix Mucus; Clinical Research; Clinical Trials; Complement; Contraceptive Agents; Contraceptive methods; Engineering; Female; Film; Generations; Human; Imaging Techniques; Immobilization; In Vitro; Inflammation; Macaca nemestrina; Measures; Mission; Modeling; Monitor; Penetration; Phase; Phase I Clinical Trials; Preclinical Testing; Quality Control; Research Project Grants; Safety; Specificity; Sperm Agglutination; Sperm Motility; Testing; Time; Translational Research; Vagina; Vaginal Ring; Variant; Western Blotting; Woman; antibody test; base; cytokine; design; design and construction; efficacy testing; human imaging; in vitro Assay; in vivo imaging; innovation; irritation; nonhuman primate; novel; pharmacokinetics and pharmacodynamics; pre-clinical research; preclinical study; programs; prototype; reproductive tract; sperm cell; sperm function

PROJECT 2: ABSTRACT Project 2 is a contraceptive translational research project designed to support the overall mission of our CRC program which is to develop a new contraceptive method based on the vaginal use of a potent sperm agglutinating antibody, Human Contraceptive Antibody (HCA). Preclinical studies will be performed to establish the potency, specificity, safety and mechanism of action of the GMP HCA antibody manufactured for the HCA-film clinical trial. We will also support the Phase 1 clinical trials by testing vaginal secretions from women before and after HCA-film use for proinflammatory cytokines and antisperm antibodies. In addition, we will determine the PK/PD of a prototype HCA intravaginal ring (IVR) and HCA antibody distribution in a nonhuman primate model, and will engineer novel multivalent HCA constructs that are designed for enhanced sperm agglutination activity and may be used for second generation HCA contraceptive products. Our specific aims are: SA1: Test GMP HCA in in vitro assays of human sperm function to determine concentration(s), duration, and mechanism(s) of action of HCA contraceptive effects. SA2: Test specificity and safety of GMP HCA and HCA-film in vitro. SA3: HCA-IVR PK/PD and imaging of HCA and sperm distribution in NHP model. SA4: Test vaginal secretions from women in clinical trials for cytokines and HCA antisperm activity. SA5: Manufacture HCA multivalent variants engineered for enhanced activity (2nd generation HCA); test in sperm function and safety assays.

项目 2：摘要 项目 2 是一个避孕转化研究项目，旨在支持总体使命 我们的 CRC 计划的目的是开发一种基于阴道使用的新避孕方法 一种有效的精子凝集抗体，人类避孕抗体（HCA）。临床前 将进行研究以确定其效力、特异性、安全性和作用机制 为 HCA 胶片临床试验生产的 GMP HCA 抗体。我们也将支持 第一阶段临床试验通过测试 HCA 胶片使用前后女性的阴道分泌物 促炎细胞因子和抗精子抗体。此外，我们将确定 PK/PD 原型 HCA 阴道环 (IVR) 和 HCA 抗体在非人灵长类动物中的分布 模型，并将设计专为增强精子而设计的新型多价 HCA 结构 凝集活性，可用于第二代 HCA 避孕产品。 我们的具体目标是： SA1：在人类精子功能体外测定中测试 GMP HCA 以确定浓度， HCA 避孕效果的持续时间和作用机制。 SA2：体外测试 GMP HCA 和 HCA-film 的特异性和安全性。 SA3：NHP 模型中 HCA-IVR PK/PD 以及 HCA 和精子分布的成像。 SA4：在临床试验中测试女性阴道分泌物的细胞因子和 HCA 抗精子活性 活动。 SA5：制造专为增强活性而设计的 HCA 多价变体（第二代 HCA）；精子功能和安全性测定测试。