CLINICAL DEVELOPMENT OF SA-IGIV FOR S AUREUS INFECTIONS

SA-IGIV 用于金黄色葡萄球菌感染的临床开发

• 批准号: 6283771
• 负责人: Joseph M. Patti
• 金额: $ 2.6万
• 依托单位: INHIBITEX, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-05 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6283771
• 关键词: Staphylococcus aureus; bacterial disease; clinical research; human subject; immunoglobulin G; immunotherapy; passive immunization

Multi-drug resistant Staphylococcus aureus is a significant cause of both nosocomial and community-acquired infections. In the past, powerful antibiotic drugs have provided effective treatments for staphylococcal infections. However, each antibiotic introduced has been met by the emergence of drug resistant staphylococcal strains. Importantly, with the global emergence of S. aureus strains with reduced susceptibility to vancomycin, it is anticipated that fully resistant strains may be detected in the near future. This disconcerting scenario, coupled with the lack of new therapeutics against S. aureus in clinical trials mandate the need to support the development of novel strategies to prevent S. aureus related infections. Inhibitex, Inc. is developing a novel Immune Globulin Intravenous (Human) (abbreviated as SA-IGIV) targeted against multi-drug resistant S. aureus. SA-IGIV is a purified immunoglobulin G product derived from pooled adult human plasma selected for high titers of antibody to S. aureus adhesins, specifically, Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMTM) proteins. The MSCRAMMTM specific IgG in SA-IGIV binds to MSCRAMM proteins on the surface of S. aureus and inhibits the adhesion of the organism to extracellular matrix molecules, prevents colonization, and enhances the phagocytosis by the immune system. The focus of this proposal is the clinical development of SA-IGIV that would be used to treat patients with persistent S. aureus bacteremia. Specifically, the Phase II Challenge Grant will be used to (I) evaluate in a pilot study the safety and tolerability of SA-IGIV administered as a single dose in a Phase 1/Phase 2 clinical trial under the clinical condition of persistent S. aureus bacteremia due to left-sided endocarditis, (2) evaluate the efficacy and pharmacokinetics of SA-IGIV at a single dose under the clinical condition of persistent S. aureus bacteremia due to left-sided endocarditis, and (3) pending positive data from the first clinical trial, determine the efficacy of SA-IGIV in additional high morbidity and mortality S. aureus mediated infections.

金黄色葡萄球菌具有多药抗性葡萄球菌是医院和社区获得感染的重要原因。过去，强大的抗生素药物为葡萄球菌感染提供了有效的治疗方法。然而，通过耐药葡萄球菌菌株的出现，引入了每种抗生素。重要的是，随着金黄色葡萄球菌菌株的全球出现，对万古霉素的敏感性降低，预计在不久的将来可能会发现完全抗性的菌株。这种令人不安的情况，加上在临床试验中缺乏针对金黄色葡萄球菌的新疗法，要求需要支持新型策略的发展，以防止金黄色葡萄球菌相关的感染。 Inphitex，Inc。正在开发一种新型免疫球蛋白静脉（人）（人）（缩写为Sa-Igiv），其针对多药抗性金黄色葡萄球菌。 SA-IGIV是一种纯化的免疫球蛋白G产物，该产物源自选择用于金黄色葡萄球菌蛋白抗体的高滴度的合并成人人血浆，特别是识别粘性基质基质分子（MSCRAMPTM）蛋白的微生物表面成分。 SA-IGIV中的MSCrammTM特异性IgG与金黄色葡萄球菌表面上的MSCRAMM蛋白结合，并抑制生物体对细胞外基质分子的粘附，防止定殖并通过免疫系统增强吞噬细胞增多。该提案的重点是SA-IGIV的临床发育，该临床发育将用于治疗持续性金黄色葡萄球菌菌血症患者。具体而言，II期挑战赠款将用于（i）在试点研究中评估SA-IGIV的安全性和耐受性，该SA-IGIV在持续的金黄色葡萄球菌细菌的临床状态下，在1阶段/第2阶段临床试验中作为单剂量给药，这是由于左侧内膜炎引起的，（2）评估SA-S. S. S. S. S. S. S. S. S. S. S. S. S. S. S. S. S. persistion S.由于左侧心内膜炎引起的菌血症，以及（3）在第一次临床试验的阳性数据中，确定了SA-IGIV在额外的高发病率和死亡率S.金黄色葡萄球菌介导的感染中的疗效。