A PHASE I, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING CLINICAL

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。 这是一项由美国国立卫生研究院赞助的、多中心随机、部分盲法(调查者、安全数据收集者)、安慰剂对照、剂量范围不等的甲型H5N1流感疫苗研究，对象为大约300名18至40岁的健康成年人。在该网站，预计将有75-90名成年人参与这项研究。每名受试者的参与时间约为7个月。 受试者将被随机分配到六个研究组(每组50人)，并将接受2剂疫苗：1)生理盐水安慰剂，2)7.5微克A/H5N1流感疫苗加佐剂(氢氧化铝)，3)无佐剂的7.5mcg疫苗，4)15微克疫苗加佐剂，5)15mcg疫苗无佐剂，或6)45mcg无佐剂。疫苗将在上臂肌肉注射，两次注射间隔约28天。对于有生育潜力的受试者，在接种每剂疫苗之前，尿液妊娠试验必须是阴性的。 接种后将在诊所评估症状和体征15-30分钟，受试者将在每次接种后7天内保持记忆辅助器，记录口腔温度和全身和局部不良事件(AEs)。受试者将在接种疫苗后1-3天到诊所就诊，研究人员将评估伴随的药物和不良反应。如有需要，将进行有针对性的体检。这将在第7天他们返回诊所采集血样时报告。第二次接种将在大约第28天进行，同样的接种后程序和访问将进行。在大约第208天(第二次接种疫苗后6个月)，受试者将返回诊所进行后续检查，其中包括最终血样和有针对性的体检(如果有指示)。血凝和中和抗体反应测试将在中心实验室进行。 研究将分两个阶段进行。在第一阶段，将招收90名受试者(每个研究组15名)。用于安全性评估的血液样本(WBC、HGB、血小板计数、ALT、血清肌酐、血清妊娠)将在研究前筛查访问以及每次接种疫苗前和接种后一周内采集。安全监测委员会(SMC)将在第一阶段的科目登记后大约10天举行会议，审查临床和实验室数据的安全数据。如果在第一阶段接种每剂疫苗后的一周内没有发现与临床或实验室安全有关的问题或剂量限制毒性，则在第二阶段每组疫苗将额外招募210名受试者。在第二阶段受试者将不会收集额外的血液进行安全实验室测试。 对于处于第一阶段的受试者，NIH将提供接种常规许可流感疫苗的选项。当参与者前来参观第7天(第56天)时，他们将免费获得疫苗。第二阶段的受试者将被鼓励在参与研究之前接种他们的流感疫苗(灭活流感疫苗为两周)。第二阶段预计将在所有第一阶段参与者接种疫苗后进行，因此第二阶段的登记将在2007年1月左右进行。

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 NIH-sponsored, multicenter randomized, partially-blinded (investigator, safety data collectors), placebo-controlled, dose-ranging study of A/H5N1 influenza vaccine in approximately 300 healthy adults, 18 to 40 years of age. At this site, it is anticipated that 75-90 adults may take part in the study. Each subject's participation will last about 7 months. Subjects will be randomly assigned to one of six study groups (50 subjects per group) and will receive 2 doses of either: 1) saline placebo, 2) 7.5 mcg A/H5N1 influenza vaccine with adjuvant (aluminum hydroxide), 3) 7.5mcg vaccine without adjuvant, 4) 15 mcg vaccine with adjuvant, 5) 15mcg vaccine without adjuvant, or 6) 45mcg without adjuvant. The vaccine will be given intramuscularly in the upper arm with the doses administered ~28 days apart. For subjects of child-bearing potential, a urine pregnancy test must be negative prior to administration of each vaccine dose. Symptoms and signs will be assessed in the clinic for 15-30 minutes after inoculation, and the subjects will maintain a memory aid to record oral temperature and systemic and local adverse events (AEs) for 7 days after each immunization. Subjects will visit the clinic 1 to 3 days after vaccination and study personnel will assess concomitant medication and AEs. A targeted physical examination will be performed if indicated. This will be reported on Day 7 when they return to the clinic for a blood sample. The second vaccination will occur at approximately day 28 and the same post vaccination procedures and visits will take place. At approximately day 208 (6 months after the second vaccination), subjects will return to the clinic for follow-up which includes a final blood sample and a targeted physical examination if indicated. The HA and neutralizing antibody response assays will be performed in a central laboratory. The study will be conducted in 2 stages. In stage 1, 90 subjects will be enrolled (15 per study group). Blood samples for safety evaluations (WBC, Hgb, platelet count, ALT, serum creatinine, serum pregnancy) will be obtained at a pre-study screening visit and before and one week after each vaccination. The Safety Monitoring Committee (SMC) will meet approximately 10 days after the enrollment of subjects in stage 1 to review clinical and laboratory data safety data. If no clinical or laboratory safety-related issues or dose-limiting toxicity are noted during the week after administration of each dose of vaccine during stage 1, then 210 additional subjects will be enrolled into each vaccine group during stage 2. The additional blood for safety laboratory tests will not be collected for subjects in stage 2. For subjects in Stage 1, NIH will provide an option to receive the regular licensed flu vaccine. Participants will be offered the vaccine at no cost when they come for Visit 7 (day 56). Subjects in Stage 2 will be encouraged to receive their flu vaccine prior to study participation (2 weeks for inactivated flu vaccine). Stage 2 is expected to take place after all Stage 1 participants have received their vaccines, so enrollment for Stage 2 will occur around January 2007.