The goals of this study are to assess the safety, reactogenicity, and immunogenicity of 45-microgram dosage level of monovalent subvirion influenza A/H5N1 virus vaccine administered by intramuscular (IM) route to healthy children. The primary goal of this study is to determine if this dosage level of H5N1 will result in an acceptable proportion of children achieving a potentially protective post vaccination antibody titer (provisionally assigned as a serum neutralizing titer of 1:40, based on studies conducted in Hong Kong during the 1997 H5N1 outbreak). Approximately 130 healthy children, aged 2 through 9 years, will be enrolled in this multicenter, randomized, double-blinded, placebo-controlled, clinical trial to receive at least 2 and up to 3 doses of an inactivated influenza A/H5N1 vaccine at a 45-microgram dose. One hundred subjects will be enrolled and randomly assigned into the influenza A/H5N1 vaccine dose group and 20 subjects into the placebo group (in 5:1 ratio). Subjects will be stratified into 2 age groups (2 to 5 years old and 6 to 9 years old). Vaccine or placebo will be administered into the deltoid. Subjects randomized to receive vaccine will receive 2 doses of the vaccine approximately 28 days apart. At approximately month 5, subjects' parent(s) or guardian(s) will be called to remind them of the 6-month follow-up visit. At the 6-month visit, subjects will be assessed for serious adverse events (SAEs) and the randomization assignment, ie, to vaccine or placebo, will be unmasked to the subject and parent(s) or guardian(s). Should data evaluating a third dose of the influenza A/H5N1 vaccine in adults show enhanced immunogenicity, parents or guardians of subjects who received vaccine will be offered a third dose, with an additional blood draw immediately prior to the third dose and 28 days and 6 months thereafter. The 6-month post-Dose 3 blood draw is optional. For subjects assigned to placebo, the parents or guardians will be offered the opportunity to enroll the subject into a separate open-label protocol if the 2 dose regimen administered to the vaccine recipients is found to be safe and immunogenic. The primary endpoints of the study include: adverse event (AE) and SAE information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments, as indicated); proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus 28 days after receipt of second dose of vaccine (approximately Day 56); and geometric mean titer (GMT) and the frequency of 4-fold or greater increases in hemagglutination inhibition and neutralizing antibody titers 28 days after receipt of second dose of vaccine (approximately Day 56). The secondary endpoints of the study include: proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus 1 and 6 months after receipt of first and third doses (if third dose will be administered \[see study design\]) of vaccine; GMT and the frequency of 4-fold or greater increases in serum hemagglutination inhibition antibody titer 1 and 6 months after receipt of first and third (if third dose will be administered \[see study design\]) doses of vaccine; and development of serum antibody responses against antigenically drifted variants of influenza H5N1 virus. This study is linked to protocol 06-0072.
