CLINICAL TRIAL: INFLUENZA VACCINE ALONE OR WITH ALUMINUM HYDROXIDE TO HEALTHY YO

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究的目的是确定一种禽流感疫苗的安全性和有效性，无论是否有佐剂，佐剂是一种用于增强免疫反应的物质。 这些信息将用于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、分期、随机化、双盲、安慰剂对照、剂量范围研究，旨在评估Vero细胞生长的灭活全病毒甲型H5 N1流感疫苗（含或不含氢氧化铝佐剂）通过肌内（IM）途径2次给药方案（第0天和第28天）的安全性、反应原性和初步免疫原性。 5个研究中心将入组约300名健康年轻成人（18 - 40岁，含）。 受试者将在2-3个月内入组。 斯坦福大学研究中心预计共入组约60例受试者-第1阶段15-20例受试者，第2阶段40-45例受试者。 每例受试者将被随机分配接受2剂生理盐水安慰剂，或7.5或15？g含或不含氢氧化铝的A/H5 N1流感病毒疫苗，或45？g不含氢氧化铝的甲型流感/H5 N1病毒疫苗（N=50/剂量组）IM注射。 疫苗制备和接种将由非盲态疫苗接种人员进行，该人员将不参与后续研究程序。 所有研究评估将由设盲的研究人员进行，受试者将尽可能对治疗分配保持盲态。 本研究将分2个阶段（1和2）进行。在第1阶段，90例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 mg（含或不含氢氧化铝）、15 mg（含或不含氢氧化铝）或45 mg（不含氢氧化铝）（6组;每组N=15）。 将在筛选时、每次疫苗接种前和接种后1周从第1阶段队列的所有受试者中采集用于安全性评价的血液（包括总白色血细胞计数[WBC]、血红蛋白[Hgb]、血小板计数、丙氨酸氨基转移酶[ALT]和血清肌酐）。 安全性监查委员会（SMC）将在第1阶段受试者入组和完成首次疫苗接种后约10天举行会议，以审查可用的临床和实验室安全性数据。 如果在第1阶段接种首剂疫苗后一周内未观察到临床或实验室安全性相关问题或剂量限制性毒性，则所有第1阶段受试者将接受第二次疫苗接种。 此外，在第2阶段每个疫苗组开始额外入组210例受试者之前，SMC将开会审查第1阶段的完整临床和实验室安全性数据包（每组总计N=50例）。

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 a 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 years 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 ?g of the influenza A/H5N1 virus vaccine with or without aluminum hydroxide, or 45 ?g 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 mg (with or without aluminum hydroxide), 15 mg (with or without aluminum hydroxide), or 45 mg (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).