Antibody-based Contraceptive MPTs: Preclinical and Clinical Research

基于抗体的避孕 MPT：临床前和临床研究

• 批准号: 10159117
• 负责人: Deborah J Anderson
• 金额: $ 181.36万
• 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/10159117
• 关键词: Antibodies; Antigens; Biological Assay; CDW52 gene; Cells; Cervix Mucus; Clinical; Clinical Research; Clinical Trials; Contraceptive Agents; Contraceptive methods; Data; Database Management Systems; Development; Dose; Engineering; Film; Future; Generations; Goals; Grant; Human; Immobilization; In Vitro; Industrialization; Infertility; Leadership; Methods; Modeling; Monoclonal Antibodies; Nicotiana; Pharmaceutical Preparations; Phase I Clinical Trials; Phase Ia Clinical Trial; Phase Ib Clinical Trial; Preclinical Testing; Prevention; Research; Research Project Grants; Safety; Seminal fluid; Specificity; Sperm Motility; Standardization; Technology; Testing; Tissues; Translational Research; Tubal Ligation; Vagina; Vaginal Ring; Variant; Woman; aged; antibody test; base; cost; cost effective; cytokine; human imaging; human monoclonal antibodies; in vitro Assay; in vitro testing; innovation; male; microbicide; nonhuman primate; pathogen; pharmacokinetics and pharmacodynamics; pre-clinical research; preclinical study; prevent; programs; prototype; reproductive; reproductive tract; safety testing; sexually active; sperm cell; sperm function; statistics; vaginal mucosa

CRC OVERVIEW: ABSTRACT We propose to establish a Contraceptive Research Center (CRC) to develop a new contraception method based on the topical use of a potent antisperm monoclonal antibody (mAb). We propose to manufacture a first generation HCA contraceptive product comprised of HCA human mAb, produced to GMP standards in an innovative cost-effective mAb platform (Nicotiana), and formulated into a film that dissolves on contact with the vaginal mucosa to deliver short-term (on-demand) contraception. The HCA film will be tested in vitro for efficacy and safety, IND-enabling studies will be performed, and after filing an IND application with the FDA the HCA film will be tested for safety and efficacy in two Phase 1 clinical trials. A prototype HCA-intravaginal ring (IVR) will also be developed with the goal to provide long-term (>30 day) contraceptive protection. The HCA-IVR will undergo testing in vitro and in a nonhuman primate (NHP) model for preliminary assessment of PK/PD, antibody distribution and safety. The program will also produce and test HCA multivalent variants with potential enhanced sperm trapping capabilities for use in second generation HCA contraception products. In the future HCA could be used alone in films or IVRs for contraception, or in combination with mAbs or other microbicidal compounds directed against STI pathogens, to enhance the acceptability, efficacy and marketability of Multipurpose Prevention Technology (MPT) products.

CRC 概述：摘要 我们建议建立一个避孕研究中心（CRC），以开发一种新的避孕方法 关于局部使用强效抗精子单克隆抗体（mAb）。我们建议制造第一个 第一代 HCA 避孕产品由 HCA 人单克隆抗体组成，按照 GMP 标准在 创新的具有成本效益的单克隆抗体平台（Nicotiana），并配制成薄膜，与物质接触后溶解 阴道粘膜提供短期（按需）避孕。 HCA薄膜将在体外进行功效测试 将进行安全性、IND 启用研究，并向 FDA 提交 IND 申请后，HCA 薄膜 将在两项 1 期临床试验中测试其安全性和有效性。 HCA 阴道环 (IVR) 原型将 开发的目的还在于提供长期（> 30 天）避孕保护。 HCA-IVR 将 在体外和非人灵长类动物 (NHP) 模型中进行测试，以初步评估 PK/PD、抗体 分布和安全。该计划还将生产和测试具有潜在增强功能的 HCA 多价变体 用于第二代 HCA 避孕产品的精子捕获功能。未来 HCA 可以 单独用于避孕膜或 IVR 中，或与单克隆抗体或其他杀菌化合物结合使用 针对 STI 病原体，提高多用途的可接受性、有效性和适销性 预防技术（MPT）产品。