INTRAMUSCULAR INACTIVATED INFLUENZA A/H5N1 VACCINE WITH DIFFERENT ADJUVANTS

点击翻译按钮获取中文摘要

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, 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 (see table) to receive two doses of saline placebo or influenza A/H5N1 vaccine at 60, 30, or 15 >g; or influenza A/H5N1 vaccine at 15 or 7.5 >g with MF59; or influenza A/H5N1 vaccine with aluminum hydroxide at 30, 15, or 7.5 >g 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.