Anthrax Immune Globulin to Prevent & Treat Anthrax: Clinical Development

炭疽免疫球蛋白预防

• 批准号: 7132591
• 负责人: ROBERT Jay HOPKINS
• 金额: $ 11.18万
• 依托单位: EMERGENT PRODUCT DEVELOPMENT GAITHERSBUR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7132591
• 关键词: globulins; pharmacokinetics

DESCRIPTION (provided by applicant): The licensed anthrax vaccine, BioThrax(r), elicits protective immunity consisting of multiple antibodies that protect against anthrax. In purified form, these anthrax immune globulins can be administered to victims of inhalational anthrax to provide immediate protective immunity against drug-sensitive, and importantly, drug- resistant strains of B. anthracis. Proposed herein is the clinical development of Anthrax Immune Globulin for intravenous administration (AIGIV) for the intended indication of the "Treatment of inhalational anthrax due to antibiotic-susceptible and antibiotic-resistant B. anthracis in persons 18-65 years of age." An additional indication will be sought for the prophylaxis of inhalational anthrax for individuals at risk for having contact with, or who have contacted, either antibiotic-resistant and/or antibiotic-susceptible B. anthracis (pre- exposure and post-exposure prophylaxis). Proposed herein is a single, dose-ranging, placebo-controlled clinical trial to test the tolerability and pharmacokinetics of AIGIV (anti-PA IgG and Toxin Neutralizing Activity, TNA). Outside the scope of this application Emergent ImmunoSolutions will manufacture and release one cGMP lot of AIGIV and conduct "Animal Rule" efficacy studies in rabbit and NHP models. Emergent ImmunoSolutions has collected plasma from BioThrax(r)-immunized individuals for the manufacture of AIGIV using an FDA-approved process for immune globulin purification. The first clinical lot of AIGIV will be used for "Animal Rule" studies to determine the doses providing preventative and therapeutic protection against aerosolized B. anthracis spore challenge. This information together with data from the proposed dose- ranging, safety and pharmacokinetic trial of AIGIV will be used to derive the human dose of AIGIV. The coupling of an FDA-approved anthrax vaccine to generate Source Plasma and an FDA-approved process for the production of AIGIV provides a low-risk path to the timely delivery of an efficacious, licensable anthrax therapeutic to fulfill the vital need to supply the Strategic National Stockpile. The targeting of multiple epitopes by polyclonal antibodies has potential advantages over a single monoclonal antibody for the treatment and prevention of inhalational anthrax. Emergent BioSolutions is a biologics company focused on the research, development and manufacture of novel vaccines and related products for prophylactic and therapeutic use against common diseases and biological weapons of mass destruction. Its subsidiaries are BioPort Corporation, the primary manufacturing operation, headquartered in Lansing, Michigan; research-focused Emergent ImmunoSolutions, located in Gaithersburg, Maryland; and research- focused Emergent Europe Limited, located in Reading, England. More information about Emergent BioSolutions and its subsidiaries can be found at www.ebsi.com.

描述（由申请人提供）：已获得许可的炭疽疫苗biothrx (r)，可引起由多种抗体组成的保护性免疫，以防止炭疽。纯化后的炭疽免疫球蛋白可用于吸入性炭疽患者，以提供对药物敏感的、重要的是耐药的炭疽杆菌株的即时保护性免疫。本文建议临床开发用于静脉给药的炭疽免疫球蛋白（AIGIV），用于“治疗18-65岁人群中因抗生素敏感和耐药炭疽杆菌引起的吸入性炭疽”。对于有接触或接触过抗生素耐药和/或抗生素敏感炭疽杆菌风险的个体，将寻求预防吸入性炭疽的额外适应症（暴露前和暴露后预防）。本文提出了一个单一的、剂量范围的、安慰剂对照的临床试验，以测试AIGIV（抗pa IgG和毒素中和活性，TNA）的耐受性和药代动力学。在此申请范围之外，Emergent ImmunoSolutions将生产和发布一个cGMP批次的AIGIV，并在兔和NHP模型中进行“动物规则”功效研究。Emergent ImmunoSolutions已经从BioThrax(r)免疫个体中收集血浆，使用fda批准的免疫球蛋白纯化工艺生产AIGIV。第一批临床批次的AIGIV将用于“动物规则”研究，以确定提供预防和治疗性保护的剂量，以抵御雾化炭疽芽孢杆菌的攻击。这些信息与拟议的剂量范围、安全性和药代动力学试验的数据将用于确定AIGIV的人剂量。将fda批准的炭疽疫苗用于产生源血浆和fda批准的AIGIV生产工艺结合起来，为及时提供有效的、可获得许可的炭疽治疗药物提供了低风险途径，以满足供应国家战略储备的重要需求。多克隆抗体靶向多个表位在治疗和预防吸入性炭疽方面比单一单克隆抗体具有潜在的优势。