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Therapy and Prophylaxis for Genital Tract Infection

生殖道感染的治疗和预防

基本信息

批准号：
10397080
负责人：
DOMINICK AUCI
金额：
$ 91.53万
依托单位：
THERAPYX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10397080
关键词：
Acute Agreement Antibiotics Antibodies Biological Biological Sciences Cardiovascular Physiology Centers for Disease Control and Prevention (U.S.)Clinical Protocols Clinical Trials Collaborations Communicable Diseases Conscious Databases Development Development Plans Disease Dose Dose-Limiting Drug Kinetics Encapsulated Excipients Formulation Frequencies Future Generations Goals Gonorrhea Human Immune response Immunity Immunotherapeutic agent Immunotherapy Incidence Infection Interleukin-12 Intravaginal Administration Legal patent Macaca fascicularis Maximum Tolerated Dose Measures Mediating Monkeys Multi-Drug Resistance Mus NOEL Nature Neisseria gonorrhoeae No-Observed-Adverse-Effect Level Pharmaceutical Preparations Pharmacologic Substance Phase Pluronics Polyethylene Glycols Preparation Primates Process Program Development Prophylactic treatment Public Health Rattus Readiness Recombinant Interleukin-12 Recommendation Reporting Resistance Rodent Role Safety Science Serum Small Business Innovation Research Grant Toxic effect Toxicology Treatment Protocols Vaccines Vagina Woman Work base clinical development clinical toxicology comparative cytokine design drug development first-in-human immunological intervention manufacturing process manufacturing scale-up meetings mouse model nonhuman primate novel novel strategies novel therapeutics particle phase 1 study postnatal development pre-clinical profiles in patients programs public health relevance reproductive reproductive tract resistant strain respiratory response telemetering therapeutic vaccine treatment optimization vaccine development

项目摘要

PROJECT SUMMARY/ABSTRACT Genital tract infection with Neisseria gonorrhoeae does not induce a state of specific protective immunity and can be acquired repeatedly. Despite public health measures, the disease persists at an unacceptably high frequency; there is no vaccine against it, and resistance even to the latest generations of antibiotics continues to emerge. TherapyX, Inc. is advancing GneX12, a novel immune therapeutic that is designed to enhance antibiotic-mediated clearance of persistent Neisseria gonorrhoeae infection and induce long-term protection against subsequent exposure, i.e. a therapeutic vaccine. Specifically, GneX12 is the canonical type 1 cytokine interleukin-12 (IL-12) encapsulated in proprietary biodegradable sustained-release microparticles. Phase I studies in a murine model of gonoccal infection demonstrated that intra-vaginal administration of GneX12 achieved rapid disease clearance and induced the development of long-term protective immunity. Phase II work optimized treatment schedule; demonstrated the critical role of Th1 immunity in disease clearance; revealed that long-term protection was mediated by an anti-gonoccocal humoral response; that the antibodies were cross- protective; and that co-administration with antibiotics did not interfere with the induction of long-term protection. Additional Phase II work established scale-up manufacturing processes and completed a type C meeting with the FDA, garnering agency agreement with our single species primate toxicology plan to support an investigative new drug application (IND). The aims of the current Phase IIb application are based on agency recommendations communicated during that meeting. Specifically, Aim 1 studies will complete additional toxicology, including reproductive toxicology, assessment in rodents as recommend by FDA. In Aim 2, a large-batch “GMP-like” GneX12 drug product is manufactured in compliance with FDA drug substance and drug product release recommendations for use in IND-enabling, non-human primate toxicology studies. A meeting request and package, including final CMC and pre-clinical toxicology questions and finalized clinical protocols, will then be prepared and submitted for a Type B meeting with the FDA (Aim 3). Lastly, based on the FDA guidance obtained in Aim 3, initial tolerability and pK of GneX12 in non-human primates is established and IND readiness is assessed (Aim 4) in preparation for an open IND and first-in-man clinical trials. The long-term goal of this project is to develop a biologic, which when administered in conjunction with antibiotics, will not only enhance disease clearance but will also induce long-term protective immunity. No similar product currently exists.

项目总结/摘要生殖道淋病奈瑟菌感染不会诱导特异性保护性免疫状态，可以重复获得。尽管采取了公共卫生措施，频率;没有针对它的疫苗，甚至对最新一代抗生素的耐药性也在继续出现。TherapyX公司GneX 12是一种新型免疫治疗药物，旨在增强药物介导的持续性淋球菌感染的清除和诱导的长期保护预防随后的暴露，即治疗性疫苗。具体而言，GneX 12是典型的1型细胞因子白细胞介素-12（IL-12）封装在专有的可生物降解的缓释微粒中。一期在淋病感染的鼠模型中的研究表明，阴道内施用GneX 12 实现了快速的疾病清除，并诱导了长期保护性免疫的发展。二期工程优化的治疗方案;证明了Th 1免疫在疾病清除中的关键作用;揭示，长期保护作用是由抗淋球菌体液应答介导的，抗体是交叉的，保护性;与抗生素共同给药不会干扰长期保护的诱导。额外的第二阶段工作建立了规模扩大的生产工艺，并完成了C类会议， FDA，与我们的单一物种灵长类动物毒理学计划达成机构协议，以支持调查新药申请（IND）当前IIb期申请的目的是基于机构的建议在那次会议上沟通。具体而言，目标1研究将完成额外的毒理学，包括生殖毒理学，根据FDA的建议在啮齿动物中进行评估。在目标2中，大批量“类GMP” GneX 12制剂的生产符合FDA原料药和制剂放行要求建议用于IND启动的非人灵长类动物毒理学研究。会议请求和然后，将提供一个包，包括最终的CMC和临床前毒理学问题以及最终的临床方案，准备并提交给FDA的B类会议（目标3）。最后，根据获得的FDA指南，在目标3中，确定了GneX 12在非人灵长类动物中的初始耐受性和pK，并评估（目标4），为开放IND和首次人体临床试验做准备。这个项目的长期目标是是开发一种生物制剂，当与抗生素联合使用时，不仅会增加疾病，清除，但也将诱导长期的保护性免疫。目前没有类似产品。