H5 Vaccine Alone or With Aluminum Hydroxide in Elderly Adults

This is a double-blind, randomized, controlled, dose-ranging, Phase I-II study in healthy ambulatory elderly adults. The primary objectives are to: determine the dose-related safety of subvirion-inactivated H5N1 vaccine adjuvanted with aluminum hydroxide in healthy elderly adults (65 years of age and older); determine the potential for aluminum hydroxide to enhance the immune response to subvirion inactivated H5N1 vaccine in healthy elderly adults approximately 1 month following receipt of 2 doses of vaccine; and provide information for the selection of the best dosage level for further studies. A secondary objective is to evaluate dose-related immunogenicity and the percent of subjects responding approximately 1 and 7 months after the first vaccination. Approximately 600 elderly subjects are planned for enrollment. Subjects will be screened for health status by history and targeted physical examination. Subjects who meet the entry criteria for the study will be randomized into 8 groups to receive 2 doses of nonadjuvanted or aluminum hydroxide-adjuvanted influenza A/H5N1 vaccine containing 3.75, 7.5, 15, or 45 micrograms of hemagglutinin (HA) by intramuscular injection. The first vaccination will occur on Day 0. Symptoms and signs will be assessed 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 adverse events (AEs) for 7 days after each immunization. Subjects will be encouraged to take their temperature around the same time each day. All subjects will return to the clinic on Days 2 and 8 after each vaccination for assessment of AEs and concomitant medications, as well as a targeted physical examination if indicated. Memory aids will be reviewed at each visit. At approximately Day 28 after the first vaccination, subjects will return to the clinic for blood sample collection and safety follow-up, followed by a second vaccination. Safety follow-up will be identical to that performed after the first vaccination. Approximately 56 days after first immunization (or about 28 days after the second vaccination), subjects will return to the clinic for immunogenicity blood sample collection, AE and concomitant medication assessments, and targeted physical examinations (if indicated). At approximately Day 208 (7 months after the first vaccination), subjects will return to the clinic for a final immunogenicity blood sample collection and for follow-up, which includes a targeted physical examination if indicated. The duration of the study treatment for each subject will be about 7 months. The primary study endpoints include: AE or serious adverse event (SAE) information; proportion of subjects in each dose group achieving a serum neutralizing antibody titer of greater than or equal to 1:40 against influenza A/H5N1 virus 28 days after receipt of the second dose of vaccine; proportion of subjects in each dose group achieving a serum hemagglutination inhibition (HAI) antibody titer of greater than or equal to 1:40 against the influenza A/H5N1 virus 28 days after receipt of the second dose of vaccine; geometric mean titer (GMT) and frequency of 4-fold or greater increases in neutralizing antibody titers in each group 28 days after receipt of the second dose of vaccine; and GMT and frequency of 4-fold or greater increases in serum HAI antibody titers in each group 28 days after receipt of the second dose of vaccine. The secondary endpoints include: GMT and frequency of 4-fold or greater increases in neutralizing antibody titers in each group 1 month and 7 months after receipt of the first dose of vaccine; GMT and frequency of 4-fold or greater increases i