A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED, PHASE I/II, DOSE-RANGING STUDY

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， 因此可以在其他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。 本提案描述了一项在约240名65岁及以上健康成人中进行的A/H5 N1流感疫苗的多中心、随机、双盲、安慰剂对照、剂量范围研究。(240最多可从4个美国研究中心招募260名成人）。在该研究中心，预计最多有65名成人参与研究。 受试者将被随机分配接受3剂生理盐水安慰剂（N=40）、45 μ g甲型流感/H5 N1疫苗（N = 100）或90 μ g甲型流感/H5 N1病毒疫苗（N=100），通过上臂肌肉注射。除非盲护士接种员外，所有研究工作人员均为盲态。 所有志愿者将在第0、28和180（约6个月）天接受疫苗或安慰剂注射，随后是7天的安全性评估期。 接种后15-30分钟在门诊评估症状和体征，每次免疫后7天，受试者将保持记忆辅助记录口腔温度和全身和局部不良事件（AE）。 所有受试者将在每次接种后1-3天和14-18天接受安全性电话随访，以获取任何AE信息。 受试者将在第8天返回诊所，以审查记忆辅助、评估AE和合并用药，并进行有针对性的体格检查（如有指征）。 在每次疫苗接种前（约第0、28和6个月）和第三次疫苗接种后第28天（约7个月），将采集血样，以测量疫苗产生的抗体。抗体检测将在中心实验室进行。 主要结局指标将是每个剂量组中AE的频率和严重程度以及达到预定水平的A/H5 N1流感保护性抗体的受试者比例。

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. This proposal describes a multicenter randomized, double-blinded, placebo-controlled, dose-ranging study of A/H5N1 influenza vaccine in approximately 240 healthy adults 65 years of age and older. (240 and up to 260 adults may be enrolled from 4 U.S. study sites). At this site, it is anticipated that up to 65 adults may take part in the study. Participants will be randomly assigned to receive 3 doses of saline placebo (N=40), 45 ¿g of the influenza A/H5N1 vaccine (N = 100) or 90 ¿g of the influenza A/H5N1 virus vaccine (N=100) by intramuscular injection in the upper arm. All study staff will be blinded except the unblinded nurse vaccinator. All volunteers will receive the vaccine or placebo injection at 0, 28, and 180 (~6 months) days followed by a 7-day safety assessment period. 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 (AE) for 7 days after each immunization. All subjects will receive a safety follow-up telephone call at 1-3 days and 14-18 days after each vaccination to elicit any AE information. Subjects will return to the clinic on day 8 for review of the memory aid, assessment of AEs and concomitant medications, and a targeted physical examination (if indicated). Just prior to each vaccination (approximately days 0, 28 and 6 months) and on day 28 following the third vaccination (approximately 7 months), a blood sample will be obtained to measure the antibodies produced by the vaccine. The antibody tests will be performed in a central laboratory. The primary outcome measures will be the frequency and severity of AEs in each dose group and the proportions of subjects who achieve a predefined level of protective antibody against A/H5N1 flu.