INFLUENZA A/H5N1 VACCINE GIVEN ALONE OR WITH ALUMINUM HYDROXIDE TO YOUNG ADULTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是确定使用或不使用佐剂的禽流感疫苗的安全性和有效性，佐剂是一种用于增强免疫反应的物质。这些信息将被用来设计一种禽流感疫苗，这种疫苗可以在最低有效剂量下产生有效的免疫反应。 这是一项I期、多中心、分阶段、随机、双盲、安慰剂对照、剂量范围的研究，研究的是使用或不使用铝的Vero细胞培养、灭活、全病毒甲型H5N1流感疫苗的安全性、反应性和初步免疫原性。 氢氧化物佐剂通过肌肉注射(IM)途径，作为2剂方案(第0天和第28天)。 五个地点将招收大约300名健康的年轻人(年龄在18岁到40岁之间)。这些科目将在2-3个月内注册。斯坦福网站预计总共招募约60名受试者：第一阶段15-20名受试者，第二阶段40-45名受试者。每名受试者将被随机分配到IM注射2剂生理盐水安慰剂，或7.5或15微克含或不含氢氧化铝的甲型H5N1流感病毒疫苗，或45微克不含氢氧化铝的甲型H5N1流感疫苗(N=50/剂量组)。疫苗的制备和给药将由一名非盲目的疫苗管理员执行，他不会参与后续的研究程序。所有的研究评估都将由盲人研究人员进行，受试者将对治疗任务尽可能地失明。 这项研究将分两个阶段(1和2)进行。在第一阶段，90名符合研究入选标准的受试者将随机接受生理盐水安慰剂或7.5微克(含或不含氢氧化铝)、15微克(含或不含氢氧化铝)或45微克(不含氢氧化铝)(6组，每组15个)的治疗。用于安全性评估的血液(包括白细胞总数[WBC]、血红蛋白[HGB]、血小板计数、丙氨酸氨基转移酶[ALT]和血肌酐)将在筛查时、每次接种前和接种后一周从阶段1队列中的所有受试者中获取。安全监测委员会(SMC)将在第一阶段受试者登记和完成第一次疫苗接种后约10天举行会议，审查现有的临床和实验室安全数据。如果在第一阶段接种第一剂疫苗后的一周内没有发现与临床或实验室安全相关的问题或剂量限制毒性，则所有第一阶段的受试者将接受第二次接种。此外，SMC将开会审查第一阶段的完整临床和实验室安全数据包，然后在第二阶段开始为每个疫苗组招募210名额外的受试者(每组总共50名)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to determine the safety and effectiveness of an avian flu vaccine given with or without an adjuvant, a substance used to boost the immune response. The information will be used to design an avian flu vaccine which could produce an effective immune response at the lowest effective dose. This is a Phase I, multicenter, staged, randomized, double-blind, placebo-controlled, dosage ranging study of the safety, reactogenicity, and preliminary immunogenicity of a Vero cell-grown, inactivated, whole virus influenza A/H5N1 vaccine administered with or without aluminum hydroxide adjuvant by the intramuscular (IM) route as a 2-dose regimen (Day 0 and Day 28). Approximately 300 healthy young adults (aged 18 to 40 yrs inclusive) will be enrolled by five sites. Subjects will be enrolled over a 2-3 month period. The Stanford site expects to enroll a total of about 60 subjects: 15-20 subjects in Stage 1 and 40-45 subjects in Stage 2. Each subject will be randomly assigned to receive 2 doses of either saline placebo, or 7.5 or 15 mcg of the influenza A/H5N1 virus vaccine with or without aluminum hydroxide, or 45 mcg of the influenza A/H5N1 virus vaccine without aluminum hydroxide (N=50/dose group) by IM injection. Vaccine preparation and administration will be performed by an unblinded vaccine administrator, who will not be involved in subsequent study procedures. All study assessments will be performed by blinded study personnel and subjects will be blinded as much as practical to treatment assignment. The study will be conducted in 2 stages (1 and 2). During Stage 1, 90 subjects who meet the entry criteria for the study will be randomized to receive saline placebo or 7.5 mcg (with or without aluminum hydroxide), 15 mcg (with or without aluminum hydroxide), or 45 mcg (without aluminum hydroxide) (6 groups; N=15 per group). Blood for safety evaluations (including total white blood cell count [WBC], hemoglobin [Hgb], platelet count, alanine aminotransferase [ALT], and serum creatinine) will be obtained from all subjects in Stage 1 cohort at screening, and before and 1 week after each vaccination. The Safety Monitoring Committee (SMC) will meet approximately 10 days after enrollment and completion of first vaccination of subjects in Stage 1 to review available clinical and laboratory safety data. If no clinical or laboratory safety-related issues or dose-limiting toxicities are noted during the week after administration of the first dose of vaccine during Stage 1, then all Stage 1 subjects will receive second vaccination. Furthermore, the SMC will meet to review a complete clinical and laboratory safety data package for Stage 1 prior to initiation of the enrollment of 210 additional subjects into each vaccine group during Stage 2 (N=50 per group total).