Antibody-based Contraceptive MPTs: Advancing the Human Contraceptive Antibody (HCA) through Clinical Trials

CRC概述-摘要 我们避孕研究中心的首要目标是发展 创新的单抗避孕药和多用途预防 有潜力改善全球数百万女性生活的科技(MPT)产品 通过解决两个同时发生的生殖健康危机：不可接受的高意外生育率 发展中国家和发达国家的怀孕以及性传播疾病 可传播感染(STI)。在NIAID的资助下，我们开发了一种阴道薄膜MB-66， 含有抗HIV-1和HSV-2的单抗[我们MPT产品的第一个成分]。MB-66 是安全的，在一期临床试验中显示出良好的体外疗效。在我们目前的NICHD下- 资助的CRC计划，我们设计、生产并表征了一个GMP级人类 抗精子单抗“人类避孕抗体(HCA)”，以及ZB-06，一种含有 用于阴道局部应用的HCA。我们获得了一个探索性的IND，目前正在测试ZB- 06在女性的一期临床试验中，具有安全性和探索性疗效(性交后试验) 终端。参加临床试验的前六名女性的初步数据表明，ZB- 06在防止可活动的精子进入子宫内膜方面是安全和高效的，这是一个关键 避孕药效的相关性。 我们正在寻求更新我们的CRC计划，以通过进一步的临床试验来推进ZB-06。 在项目1中，ZabBio将改进和扩大ZB-06的生产，以用于工业- 启动研究，以及拟议的第1阶段和2a阶段临床试验。ZabBio将提交所有 FDA为临床试验获得IND所需的文书工作，维护IND和 监督临床试验。项目2，将在东弗吉尼亚医学院和 德克萨斯大学圣安东尼奥分校将负责进行两项临床试验：1) ZB-06单剂与多剂应用的1期安全性和PK研究2)a期 2ZB-06药膜安全性和性交后疗效终点的剂量发现研究。项目3， Will在波士顿大学医学院和Magee妇女研究所工作 改进阴道膜设计，并进行必要的安全性研究，以支持临床 审判。行政核心将为所有项目提供领导和财务管理，以及 为临床试验提供数据库和统计支持。到项目结束时，我们预计ZB- 06将用于NIH避孕药试验的2b期避孕药效测试 网络。

CRC OVERALL – ABSTRACT The overarching goal of our Contraception Research Center (CRC) is to develop innovative monoclonal antibody (mAb)-based contraceptive and multipurpose prevention technology (MPT) products with the potential to improve the lives of millions of women globally by addressing two concurrent reproductive health crises: an unacceptably high rate of unintended pregnancies in both developing and developed countries, and an epidemic of sexually transmissible infections (STIs). With funding from NIAID we developed a vaginal film, MB-66, containing mAbs against HIV-1 and HSV-2 [the first components of our MPT product]. MB-66 was safe and showed good ex vivo efficacy in a Phase 1 Clinical Trial. Under our current NICHD- funded CRC program we engineered, produced and characterized a GMP-grade human antisperm mAb “Human Contraception Antibody (HCA)”, and ZB-06, a vaginal film containing HCA for topical vaginal application. We obtained an exploratory IND, and are currently testing ZB- 06 in a Phase 1 Clinical Trial in women with safety and exploratory efficacy (postcoital test) endpoints. Preliminary data from the first six women enrolled in the clinical trial indicate that ZB- 06 is safe and highly effective at preventing motile sperm from entering the endocervix, a key correlate of contraceptive efficacy. We are seeking to renew our CRC program to advance ZB-06 through further clinical trials. In Project 1, ZabBio will improve upon and scale up the production of ZB-06 for use in IND- enabling studies, and in the proposed Phase 1 and Phase 2a clinical trials. ZabBio will file all paperwork required by the FDA to obtain an IND for the clinical trials, maintain the IND and monitor the clinical trials. Project 2, to be conducted at Eastern Virginia Medical School and the University of Texas San Antonio, will be responsible for the conduct of the two clinical trials: 1) a Phase 1 safety and PK study of single dose vs. multiple dose application of ZB-06, and 2) a Phase 2a dose-finding study of ZB-06 film with safety and postcoital test efficacy endpoints. Project 3, based at Boston University School of Medicine and Magee-Women’s Research Institute, will improve upon the vaginal film design, and conduct essential safety studies to support the clinical trials. An Administrative Core will provide leadership and fiscal management for all projects, and database and statistical support for the clinical trials. By the end of the project we expect that ZB- 06 will be positioned for Phase 2b contraceptive efficacy testing by the NIH Contraceptive Trials Network.