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 项目3的主要目标是优化人类阴道膜递送系统 避孕抗体（HCA），并进行试验以评估PK/PD和安全性终点， 临床试验中女性的阴道样本阴道胶片优化将由 博士匹兹堡大学的罗汉。第一步将是优化即时发布 将用于临床试验的薄膜;罗汉博士将监督将薄膜生产转移到KBio， 生产GMP HCA薄膜的公司。下一步将是开发 一种缓释膜，可释放避孕抗体超过3天。抗体研究 薄膜优化工作和临床PK/PD试验将在安德森博士的 实验室将评估HCA抗体浓度和活性。此外，博士。 安德森的实验室将评估参加临床试验的妇女的安全性终点。的 项目3的具体目标是： 1)开发改进的阴道膜配方，用于立即和延长HCA释放。 2)使用测量HCA的创新试验评价探索性PK/PD终点 在使用薄膜之前和之后阴道样品中的浓度和活性。 3)评估探索性安全性终点（阴道炎症、阴道炎的变化、 微生物组和基因表达途径，抗精子免疫的从头发展） 在使用HCA膜之前和之后的女性中。 我们期望这些实验的数据将指导有关关键参数的决策 产品的形式，安全性和剂量，这将是非常宝贵的ZB-06的进展， 临床试验和商业化。