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，旨在支持整个使命 我们的CRC计划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，以确定的效力，特异性，安全性和作用机制 GMP HCA抗体用于HCA-薄膜临床试验。我们亦会支持 1期临床试验，通过测试妇女在使用HCA膜前后的阴道分泌物， 促炎细胞因子和抗精子抗体。此外，我们还将确定以下药物的PK/PD： 非人灵长类动物中原型HCA阴道环（IVR）和HCA抗体分布 模型，并将设计新的多价HCA结构，旨在增强精子 凝集活性，可用于第二代HCA避孕产品。 我们的具体目标是： SA 1：在体外人精子功能试验中检测GMP HCA，以确定浓度， 持续时间和HCA避孕效果的作用机制。 SA 2：GMP HCA和HCA膜的体外特异性和安全性试验。 SA 3：NHP模型中HCA-IVR PK/PD和HCA成像以及精子分布。 SA 4：检测临床试验中女性阴道分泌物的细胞因子和HCA抗精子剂 活动 SA 5：生产经工程改造以增强活性的HCA多价变体（第2代 HCA）;精子功能和安全性试验。