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），以开发基于新的避孕方法 关于局部使用有效的抗体单克隆抗体（MAB）。我们建议制造第一个 HCA避孕产物由HCA人MAB组成，在GMP标准中生产 创新的具有成本效益的MAB平台（Nicotiana），并制作成一部溶解在接触时的电影 阴道粘膜可提供短期（按需）避孕。 HCA膜将在体外测试以获得功效 和安全性，将进行辅助研究，并在向FDA提交IND申请后，HCA膜 将在两阶段1临床试验中测试安全性和功效。原型HCA内膜环（IVR）将 还可以开发出长期（> 30天）避孕药的目标。 HCA-IVR会 在体外和非人类灵长类动物（NHP）中进行测试，以评估PK/PD，抗体 分配和安全。该程序还将生产和测试具有潜在增强的HCA多价变体 精子捕获功能用于第二代HCA避孕产品。将来HCA可以 单独在膜或IVR中用于避孕，或与MAB或其他杀菌化合物结合使用 针对STI病原体，以增强多功能的可接受性，功效和销售性 预防技术（MPT）产品。