Open-Label Study of H5 Vaccine in Participants of Protocol 04-077

Overview

This study may provide safety information on a flu vaccine given to children and may provide immunogenicity information to add to what was collected in a previous flu vaccine study. Participants will include 55 healthy children, ages 2-10, who participated in 04-077 and received a placebo injection instead of the flu vaccine or were incompletely immunized. The study has 2 purposes: to make sure there are no serious side effects in children and to see how the immune systems react to the vaccine. Study procedures include up to 4 study visits, up to 9 follow-up phone calls, 2 blood samples to be collected during visits 1 and 3, and up to 3 vaccine injections in the arm or thigh muscle. Parents will be given a memory aid card to record side effects, temperatures, and medications. Parents will have the option for the child to receive a 3rd dose of vaccine if offered, at month 6. This booster shot will require a 6-month visit and participation for an additional 6 months.

The recent emergence of novel influenza virus strains in human populations has encouraged efforts to develop vaccines for a potential pandemic. The objectives of this study are to evaluate the safety of intramuscular (IM) subvirion inactivated H5N1 vaccine in healthy children aged 2 through 10 years and to determine the immunogenicity profile of IM subvirion inactivated H5N1 vaccine in healthy children approximately 1 month following receipt of the second of 2 doses of vaccine. Study endpoints include: adverse event (AE) and serious adverse event (SAE) information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments, as indicated); proportion of subjects achieving a serum hemagglutination inhibition antibody titer of 1:40 against the influenza A/H5N1 virus 28 days after receipt of second dose of vaccine (approximately Day 56); geometric mean titer and the frequency of 4-fold or greater increases in hemagglutination inhibition antibody titers 28 days after receipt of second dose of vaccine (approximately Day 56); and development of serum antibody responses against antigenically drifted variants of influenza H5N1 virus. This study is linked to DMID protocol 06-0072. Up to 55 healthy children, aged 2 through 10 years, who previously participated in DMID 04-077, will be eligible for enrollment in this multimember, open-label, phase I/II clinical trial to receive at least 2 and up to 3 doses of an inactivated influenza A/H5N1 vaccine at a 45-micrograms dose. The vaccine dosage level that will be used in this study was chosen based upon safety and immunogenicity data collected previously in adults and children. The injection volume of the 90-micrograms dose is 1 mL for the vaccine being used in this study, but this is considered unacceptable in this age group. Therefore, the 45-micrograms dose (0.5 ml volume) has been selected. Twenty three subjects who were previously enrolled and assigned to placebo in the DMID 04-077 study (A Randomized, Double-Blinded, Placebo-Controlled, Phase I/II, Study of the Safety, Reactogenicity, and Immunogenicity of Intramuscular Inactivated Influenza A/H5N1 Vaccine in Healthy Children Aged 2 Years Through 9 Years) along with up to 32 subjects from a single site who were incompletely immunized are eligible for enrollment in this study. Vaccine will be administered into the deltoid or (if age appropriate) thigh muscle. All subjects will receive 2 doses of the vaccine approximately 28 days apart. At month 6, subjects' parent(s) or guardian(s) will be called to assess the subjects for serious adverse events. Blood collection for immunogenicity studies will be at the discretion of the parent(s) or legal guardian(s). Should data evaluating a third dose of the influenza A/H5N1 vaccine show enhanced immunogenicity in pediatric subjects participating in DMID 04-077, parents/guardians of subjects who received vaccine will be offered the possibility of a third dose for their participating children.