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-摘要 我们的避孕研究中心（CRC）的首要目标是开发 创新性单克隆抗体避孕和多用途预防 技术（MPT）产品，有可能改善全球数百万妇女的生活 解决两个同时发生的生殖健康危机： 在发展中国家和发达国家， 传染性疾病（STI）。在NIAID的资助下，我们开发了一种阴道膜，MB-66， 含有抗HIV-1和HSV-2的mAb [我们MPT产品的第一个组分]。MB-66 是安全的，并在1期临床试验中显示出良好的离体功效。根据我们目前的NICHD- 我们资助的CRC项目设计，生产和表征了一个GMP级的人类 抗精子mAb“人避孕抗体（HCA）"和ZB-06，一种阴道膜，含有 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在女性中进行的I期临床试验，具有安全性和探索性疗效（性交后试验） 端点。最初参加临床试验的6名妇女的初步数据表明，ZB- 06是安全和高效的，在防止活动精子进入宫颈内膜，一个关键 与避孕效果相关。 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推进ZB-06。 在项目1中，ZabBio将改进并扩大ZB-06的生产，用于IND- 使能研究，以及拟议的1期和2a期临床试验。ZabBio将提交所有 FDA要求的文件，以获得临床试验的IND，维护IND， 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开展两项临床试验：1）a ZB-06的单剂量与多剂量应用的I期安全性和PK研究，和2）I期 2a ZB-06膜的剂量探索研究，包括安全性和性交后试验有效性终点。项目三， 总部设在波士顿大学医学院和马吉妇女研究所， 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政管理， 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将进入NIH避孕试验的2b期避孕功效测试 网络