BioThrax Schedule Optimization for Post-Exposure Prophylaxis of Anthrax

描述（由申请人提供）：BioThrax(r)是fda批准的唯一炭疽疫苗，目前用于暴露于炭疽芽孢杆菌孢子的高风险个体的暴露前环境。已为国家战略储备购买了500万剂疫苗。这些剂量最有可能用于在炭疽发作时的暴露后预防（PEP）。BioThrax(r)目前尚未获得这一适应症的许可，然而，在这种情况下使用该疫苗可能会缩短抗菌治疗的疗程，从而降低与抗菌相关的不良事件，并降低发病率和死亡率。作为获得FDA批准BioThrax(r)用于PEP适应症的研究的一部分，EIS将进行一项临床试验，以确定优化的BioThrax(r)时间表，该时间表可快速引发并维持免疫相关保护；根据“动物规则”，免疫相关性将从兔子和非人灵长类动物功效研究中得出。这项3b期临床试验，biothrx (r)在健康成人人群中的暴露后预防的安全性、免疫原性和免疫计划研究，将评估四种biothrx方案的安全性和免疫原性。本试验旨在建立PEP的最佳疫苗接种计划，主要是为了最大限度地缩短获得保护性免疫的时间，其次是为了以最少的疫苗接种次数最大化保护性免疫的持续时间。临床试验计划的具体目标是：1)制定与研究相关的文件和程序；2)建立数据管理结构；3)对研究人员进行研究相关文件和程序的培训；4)批准供应商合同和调查员协议；5)获得研究审查委员会（IRB）和/或人类受试者保护办公室（OHRP）的批准；6)获得新药研究申请（IND）批准。这些目标将由具有所有必要专业知识的研究计划委员会完成：科学审查、法规事务、数据管理、药物警戒、研究管理、研究监测、质量保证和法律事务。首席研究员对每个委员会进行监督，并为每个委员会分配任务、主席、成员、主要可交付成果和目标完成日期。如果BLA修正案允许BioThrax(r)在炭疽攻击暴露后使用，将有利于大规模疫苗接种，并有可能减少持续时间和对抗生素的依赖，提高生存率。Emergent BioSolutions是一家生物制剂公司，专注于研究、开发和生产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及相关产品。其子公司是总部位于密歇根州兰辛市的主要制造企业biopport Corporation；以研究为重点的Emergent ImmunoSolutions公司，位于马里兰州盖瑟斯堡；研究重点是位于英国雷丁的新兴欧洲有限公司。

DESCRIPTION (provided by applicant): BioThrax(r) is the only FDA-approved anthrax vaccine and is currently indicated for use in the pre-exposure setting for individuals at high risk of exposure to Bacillus anthracis spores. Five million doses of the vaccine have been purchased for the Strategic National Stockpile. The most likely use of these doses is for postexposure prophylaxis (PEP) in the event of an anthrax attack. BioThrax(r) is not currently licensed for this indication, however, the use of the vaccine in this scenario is likely to enable a shortened course of antimicrobial therapy, which can lower antimicrobial-associated adverse events, and to reduce morbidity and mortality. As part of studies to obtain FDA approval of BioThrax(r) for the indication of PEP, EIS will conduct a clinical trial to identify an optimized BioThrax(r) schedule that quickly elicits and maintains an immune correlate of protection; the immune correlate will be derived from rabbit and nonhuman primate efficacy studies according to the "Animal Rule." This phase 3b clinical trial, Safety, Immunogenicity, and Immunization Schedule Study of Post-Exposure Prophylaxis for BioThrax(r) in a Population of Healthy Adults, will evaluate the safety and immunogenicity of four BioThrax schedules. This trial is designed to establish an optimal vaccination schedule for PEP, primarily to minimize the time to achieve protective immunity, and secondarily to maximize the duration of protective immunity with the least number of vaccinations. The Specific Aims of the clinical trial planning are to: 1) Develop study-related documents and procedures; 2) Establish data management structure; 3) Train study personnel on study-related documents and procedures; 4) Ratify vendor contracts and investigator agreements; 5) Obtain Investigational Review Board (IRB) and/or Office of Human Subjects Protection (OHRP) approval; and 6) Obtain Investigational New Drug Application (IND) approval. These aims will be accomplished by study planning committees staffed with individuals with all the necessary expertise: Scientific Review, Regulatory Affairs, Data Management, Pharmacovigilance, Study Management, Study Monitoring, Quality Assurance and Legal affairs. The Principal Investigator has oversight over each committee and has assigned each: a mission, a chairperson, membership, key deliverables, and target completion dates. A BLA amendment for the licensed use of BioThrax(r) in the post-exposure setting of an anthrax attack would facilitate mass vaccination and potentially decrease the duration and reliance on antibiotics and improve survival rates. 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.