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

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 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.