CLINICAL TRIAL: INTRAMUSCULAR INACTIVATED INFLUENZA A/H5N1 VACCINE IN HEALTHY AD

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这是一项在18至64岁（含）健康成人中开展的随机、安慰剂对照、剂量范围探索、I/II期研究。 本研究的目的是研究研究甲型H5 N1流感病毒灭活疫苗单独或与佐剂氢氧化铝或MF 59联合给药时的安全性、反应原性和剂量相关免疫原性。 第二个目标是确定疫苗和佐剂的最佳剂量水平，其产生可接受的免疫原性应答，同时保持足够的安全性。 该剂量优化将在后续研究中应用于年轻和老年受试者人群。 本研究将有4家临床试验机构入组受试者。 这项多中心、随机化、安慰剂对照、剂量范围探索临床试验将在2-4周期间入组约270名18至64岁（含）的健康成人。符合研究入选标准的受试者将被随机分为9组，分别接受两剂生理盐水安慰剂或60、30或15 mg甲型流感/H5 N1疫苗;或15或7.5 mg甲型流感/H5 N1疫苗与MF 59;或以近似相等的比例通过IM注射30、15或7.5 mg氢氧化铝的甲型流感/H5 N1疫苗（N=30/疫苗剂量组总共270）。首次免疫前将采集用于实验室安全性特征的血液。 受试者将接受2次给药，间隔约28天。 疫苗接种将由未设盲的疫苗接种人员进行，该人员将不参与后续评估。 接种后将在门诊观察受试者至少15分钟，每次免疫后7天内，受试者将保持记忆辅助记录口腔温度以及全身和局部AE。 接种后1 - 3天（约第2天）通过电话联系受试者，以评估AE的发生情况，受试者将在第7天返回诊所进行AE和合并用药评估、有针对性的体格检查（如有指征）、安全性实验室检查和记忆辅助检查。 每次接种后，将进行电话访问以评估AE。将在首次免疫前和首次免疫后约7天以及第二次免疫后7天获得用于安全性实验室检查的血清。将在免疫前、首次免疫后约1个月以及第二次免疫后约1个月和6个月获得用于免疫原性评价的血清。 在开始第二剂疫苗接种前，SMC将审查疫苗首次接种后7天的所有可用安全性数据。

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. This is a randomized, placebo-controlled, dose-ranging, Phase I/II study in healthy adults, 18 to 64 years old, inclusive. This study is designed to investigate the safety, reactogenicity, and dose-related immunogenicity of an investigational inactivated influenza A/H5N1 virus vaccine when given alone or combined with the adjuvants aluminum hydroxide or MF59. A secondary goal is to identify an optimal dose level of the vaccine and the adjuvant that generates an acceptable immunogenic response while maintaining an adequate safety profile. This dose optimization will be applied to both younger and older subject populations in subsequent studies. Four sites will enroll subjects in this study. Approximately 270 healthy adults, 18 to 64 years old, inclusive, will be enrolled over a 2-4 week period into this multicenter, randomized, placebo-controlled, dose-ranging clinical trial. Subjects who meet the entry criteria for the study will be randomized into 9 groups to receive two doses of saline placebo or influenza A/H5N1 vaccine at 60, 30, or 15 mg; or influenza A/H5N1 vaccine at 15 or 7.5 mg with MF59; or influenza A/H5N1 vaccine with aluminum hydroxide at 30, 15, or 7.5 mg by IM injection in an approximate equal ratio (N=30/vaccine dose group total 270). Blood for a laboratory safety profile will be drawn prior to the first immunization. Subjects will receive 2 doses separated by approximately 28 days. Vaccine administration will be performed by an unblinded vaccine administrator, who will not be involved in subsequent assessments. Subjects will be observed in the clinic for at least 15 minutes after inoculation, and subjects will maintain a memory aid to record oral temperature and systemic and local AEs for 7 days after each immunization. Subjects will be contacted by telephone 1 to 3 days after vaccination (approximately Day 2) to assess for the occurrence of AEs, and they will return to the clinic on Day 7 for AE and concomitant medication assessment, a targeted physical examination (if indicated), safety laboratory tests and a review of the memory aid. Telephone calls to assess AEs will be performed following each vaccination. Serum for safety laboratory tests will be obtained prior to and approximately 7 days following first immunization and 7 days following second immunization. Serum for Immunogenicity evaluations will be obtained prior to immunization, approximately 1 month after first immunization and approximately 1 month and 6 months after second immunization. All available 7 day safety data following the first dose of the vaccine will be reviewed by a SMC prior to initiation of administration of the second dose of vaccine.