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

基于抗体的避孕 MPT：通过临床试验推进人类避孕抗体 (HCA)

• 批准号: 10532090
• 负责人: Deborah J Anderson
• 金额: $ 171.54万
• 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 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10532090
• 关键词: Address; Affect; Antibodies; Antigens; Atopobium vaginae; Biological Assay; Boston; CDW52 gene; Cells; Cellular Immunity; Cervix Mucus; Child Mortality; Clinical; Clinical Research; Clinical Trials; Contraceptive Agents; Contraceptive methods; Couples; Data; Database Management Systems; Databases; Developed Countries; Developing Countries; Development; Dose; Double-Blind Method; Endocervix; Engineering; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemic; Film; Formulation; Funding; Gene Expression; Goals; Good Clinical Practice; Grant; HIV-1; Health; Human; Human Herpesvirus 2; Immobilization; Industrialization; Infection; Infertility; Leadership; Manuals; Maternal Mortality; Measures; Methods; Monitoring Clinical Trials; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; National Institute of Child Health and Human Development; Nicotiana; Oryctolagus cuniculus; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Placebo Control; Positioning Attribute; Poverty; Prevention; Production; Protocols documentation; Randomized; Rattus; Regimen; Reproductive Health; Research; Research Institute; Research Project Grants; Safety; Seminal fluid; Sexual Transmission; Single-Blind Study; Site; Specificity; Sperm Agglutination; Sperm Motility; Technology; Testing; Texas; Tissues; Toxicology; Training; United States National Institutes of Health; Universities; Vagina; Vaginal Route of Drug Administration; Virginia; Woman; base; cervicovaginal; clinical lot; contraceptive efficacy; cost effective; cytokine; design; drug testing; efficacy testing; efficacy trial; human male; human monoclonal antibodies; human subject; improved; innovation; intergenerational; irritation; male; manufacturing process; medical schools; microbicide; minimal risk; operation; pathogen; pharmacokinetics and pharmacodynamics; pre-clinical; preclinical study; prevent; programs; reproductive; reproductive tract; research and development; safety study; scale up; sperm cell; stability testing; statistics; unintended pregnancy; vaginal microbiome; young woman; zygote

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.

CRC总体 - 抽象 避孕研究中心（CRC）的总体目标是发展 基于创新的单克隆抗体（MAB）的避孕和多功能预防 技术（MPT）产品有可能改善全球数百万妇女的生活 通过解决两个并发的复制健康危机：不可接受的意外率很高 发展中国家和发达国家的怀孕，以及性行为 可传播感染（STIS）。通过Niaid的资助，我们开发了一部阴道膜MB-66， 含有针对HIV-1和HSV-2的mAb [我们MPT产品的第一个组成部分]。 MB-66 是安全的，在1期临床试验中显示出良好的离体效率。在我们目前的Nichd- 我们设计，生产和特征的GMP级人类资助的CRC计划 Antisperm mAb“人类避孕抗体（HCA）”和ZB-06，一种阴道膜 HCA用于局部阴道应用。我们获得了探索性IND，目前正在测试ZB- 06在1阶段的临床试验中，具有安全性和探索性效率的妇女（涂料后测试） 端点。前六名妇女的初步数据参加了ZB-的临床试验指标 06是安全且非常有效的，可防止运动精子进入内聚物，这是一个钥匙 避孕效率的相关性。 我们正在寻求通过进一步的临床试验更新我们的CRC计划来推进ZB-06。 在项目1中，Zabbio将改进并扩大ZB-06的生产 在拟议的第1阶段和2A阶段临床试验中启用研究。 Zabbio将提交全部 FDA要求获得临床试验的IND，维护IND和 监视临床试验。项目2，将在东弗吉尼亚医学院和 得克萨斯大学圣安东尼奥大学将负责这两个临床试验的行为：1）a 单剂量与ZB-06的多剂量应用的1阶段安全性和PK研究，2）阶段 2a ZB-06膜具有安全性和外约生后测试效率终点的剂量调查研究。项目3， 位于波士顿大学医学院和Magee-Women的研究所，将 改进阴道膜设计，并进行基本的安全研究以支持临床 试验。行政核心将为所有项目提供领导和财政管理，以及 临床试验的数据库和统计支持。到项目结束时，我们期望ZB- 06将通过NIH避孕试验对2B期避孕效率测试定位 网络。