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