Antibody-based Contraceptive MPTs: Preclinical and Clinical Research

CRC综述：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， 局部使用强效抗精子单克隆抗体（mAb）。我们建议制造第一个 第二代HCA避孕产品由HCA人mAb组成，按照GMP标准在 创新的具有成本效益的mAb平台（Nicotiana），并配制成与 阴道粘膜提供短期（按需）避孕。将在体外测试HCA薄膜的有效性 将进行IND使能研究，并在向FDA提交IND申请后， 将在两项1期临床试验中进行安全性和有效性测试。HCA阴道环（IVR）原型将 还应制定旨在提供长期（>30天）避孕保护的计划。HCA-IVR将 在体外和非人灵长类动物（NHP）模型中进行检测，以初步评估PK/PD、抗体 分配和安全。该计划还将生产和测试HCA多价变体， 用于第二代HCA避孕产品的精子捕获能力。在未来，HCA可以 单独用于避孕膜或IVRs，或与mAb或其他杀微生物化合物联合使用 针对性传播感染病原体，以提高多用途 预防技术（MPT）产品。

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.