Project 3: Film Formulation, PK/PD and Safety Studies of ZB-06

项目3：ZB-06的成膜、PK/PD及安全性研究

• 批准号: 10532094
• 负责人: Deborah J Anderson
• 金额: $ 45.11万
• 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/10532094
• 关键词: Antibodies; Atopobium vaginae; Biological Assay; Blood; Boston; CCR5 gene; Cells; Cellular Immunity; Clinical; Clinical Trials; Conduct Clinical Trials; Contraceptive Agents; Contraceptive methods; Data; Development; Dose; Enrollment; Enzyme-Linked Immunosorbent Assay; Epithelial; Film; Formulation; Gene Expression; Generations; Health; Human; Immunity; Inflammation; Inflammatory; Intravaginal Administration; Laboratories; Laboratory Study; Measures; Monoclonal Antibodies; Pathway interactions; Patient Preferences; Phase; Phase I/II Clinical Trial; Production; Reporting; Research Institute; Research Project Grants; Safety; Sampling; Sperm Agglutination; Surveys; System; Technology Transfer; Testing; Time; Universities; Vagina; Woman; Work; base; commercialization; cytokine; design; experimental study; improved; inflammatory marker; innovation; pathogen; pharmacokinetics and pharmacodynamics; research and development; safety study; sexual HIV transmission; sperm cell; vaginal microbiome; vaginal microbiota

PROJECT 3 - ABSTRACT The primary objectives of Project 3 are to optimize the vaginal film delivery system for the Human Contraception Antibody (HCA) and to perform assays to assess PK/PD and safety endpoints in vaginal samples from women in the clinical trials. Vaginal film optimization will be conducted by Dr. Rohan at the University of Pittsburgh. The first step will be to optimize the immediate-release film that will be used in the clinical trials; Dr. Rohan will oversee transfer of film production to KBio, the company that will manufacture the GMP HCA film. The next step will be the development of an extended-release film that will deliver contraceptive antibody for > 3 days. Antibody studies for the film optimization work and for the clinical PK/PD trial will be conducted in Dr. Anderson’s laboratory. Both HCA antibody concentration and activity will be assessed. In addition, Dr. Anderson’s laboratory will evaluate safety endpoints in women enrolled in the clinical trials. The Specific Aims of Project 3 are: 1) Develop improved vaginal film formulations for immediate and extended HCA release. 2) Evaluate exploratory PK/PD endpoints using innovative assays that measure HCA concentrations and activity in vaginal samples before and after film use. 3) Assess exploratory safety endpoints (vaginal inflammation, changes in the vaginal microbiome and gene expression pathways, de novo development of antisperm immunity) in women before and after HCA film use. We expect that data from these experiments will guide decisions concerning critical parameters of product format, safety and dose that will be invaluable for the progression of ZB-06 through clinical trials and commercialization.

项目3 -摘要