Anthrax Immune Globulin to Prevent & Treat Anthrax: Clinical Development

描述(由申请人提供)：获得许可的炭疽疫苗BioThrax(R)可引起保护性免疫，由多种抗体组成，可预防炭疽病。以纯化的形式，这些炭疽免疫球蛋白可用于吸入性炭疽的受害者，以提供对药物敏感的炭疽杆菌的即时保护性免疫，更重要的是，提供抗药性炭疽菌株。在此提出了用于静脉注射的炭疽免疫球蛋白(AIGIV)的临床开发，旨在用于“治疗18-65岁的人因对抗生素敏感和耐药的炭疽杆菌引起的吸入性炭疽病”。对于接触过或接触过耐抗生素和/或对抗生素敏感的炭疽杆菌的风险人群(暴露前和暴露后的预防)，将寻求另一种预防吸入性炭疽的适应症。本文提出了一项单一、剂量范围、安慰剂对照的临床试验，以测试AIGIV的耐受性和药代动力学(抗PA抗体和毒素中和活性，TNA)。在这一应用范围之外，Emerent免疫解决方案公司将生产和释放一批cGMP AIGIV，并在兔和NHP模型上进行“动物法则”疗效研究。Emerent免疫解决方案公司使用FDA批准的免疫球蛋白提纯工艺，从BioThrax(R)免疫的个体中收集血浆，用于制造AIGIV。AIGIV的第一批临床试验将用于“动物规则”研究，以确定对炭疽芽胞雾化攻击提供预防和治疗保护的剂量。这些信息将与拟议的AIGIV剂量范围、安全性和药代动力学试验的数据一起用于得出AIGIV的人体剂量。FDA批准的用于产生来源血浆的炭疽疫苗和FDA批准的生产AIGIV的工艺相结合，为及时提供有效的、可许可的炭疽治疗药物提供了一条低风险途径，以满足供应国家战略储备的关键需求。在治疗和预防吸入性炭疽病方面，多克隆抗体靶向多个表位比单一单抗具有潜在的优势。 Emerent BioSolutions是一家生物制药公司，专注于研究、开发和制造用于预防和治疗常见疾病和大规模杀伤性生物武器的新型疫苗和相关产品。它的子公司包括总部设在密歇根州兰辛的主要制造业务BioPort Corporation、位于马里兰州盖瑟斯堡的专注于研究的Emergent免疫解决方案公司以及位于英国雷丁的专注于研究的Emergent Europe Limited。欲了解更多有关艾默生生物解决方案公司及其子公司的信息，请访问www.ebsi.com。

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.