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 我们避孕研究中心 (CRC) 的总体目标是开发 基于单克隆抗体 (mAb) 的创新避孕和多用途预防 技术 (MPT) 产品有可能改善全球数百万女性的生活 通过解决两个同时发生的生殖健康危机：意外发生率高得令人无法接受 发展中国家和发达国家的怀孕率以及性行为的流行 传染性感染（STI）。在 NIAID 的资助下，我们开发了一种阴道薄膜 MB-66， 含有针对 HIV-1 和 HSV-2 的单克隆抗体（我们的 MPT 产品的第一个成分）。 MB-66 是安全的，并且在 1 期临床试验中显示出良好的离体疗效。根据我们目前的 NICHD- 资助 CRC 项目，我们设计、生产并表征了 GMP 级人体 抗精子单克隆抗体“人类避孕抗体（HCA）”和 ZB-06，一种含有 HCA 用于阴道局部应用。我们获得了探索性 IND，目前正在测试 ZB- 06 在女性中进行的 1 期临床试验中具有安全性和探索性功效（性交后测试） 端点。参加临床试验的前六名女性的初步数据表明，ZB- 06 安全且高效地防止活动精子进入宫颈内膜，这是关键 避孕效果的相关性。 我们正在寻求更新我们的 CRC 项目，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- 启用研究，以及拟议的 1 期和 2a 期临床试验。 ZabBio 将归档所有 FDA 为获得临床试验 IND 所需的文件、维持 IND 和 监测临床试验。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）a ZB-06 单剂量与多剂量应用的 1 期安全性和 PK 研究，以及 2) a 期 2a ZB-06 薄膜的剂量探索研究，具有安全性和性交后测试功效终点。项目3， 总部位于波士顿大学医学院和玛吉妇女研究所，将 改进阴道薄膜设计，并进行必要的安全性研究以支持临床 试验。行政核心将为所有项目提供领导和财务管理，以及 临床试验的数据库和统计支持。到项目结束时，我们预计 ZB- 06 将由 NIH 避孕试验进行 2b 期避孕功效测试 网络。