Comparison of Flu Vaccine Doses in Children

Influenza is an important cause of morbidity and mortality among both children and adults.
Influenza A and/or B viruses cause yearly epidemics in the United States with an average of
36,000 deaths and 114,000 hospitalizations annually. Children have the highest rates of
infection. Influenza is also associated with substantial numbers of hospitalizations among
young infants. Because of the limited data available and the variability of reported
seroresponses to doses of 0.25 ml in children 6-35 months of age, investigators hypothesize
that a higher dose will be more consistently immunogenic. In addition, since currently
licensed trivalent inactivated influenza (TIV) vaccines are well tolerated with minimal
systemic and local adverse events, investigators hypothesize that administering a higher
dose of 0.5 ml to this age group will be well-tolerated. Therefore, investigators propose to
compare the safety and immunogenicity of 0.25 ml doses of TIV to that of 0.5 ml doses of TIV
when administered to children 6-35 months of age. The proposed study is a phase I, two-arm,
1:2 randomized, double-blinded trial comparing the safety and immunogenicity of increased
dose(s) (0.5 ml) with standard dose (0.25 ml) of TIV in children 6-35 months of age with and
without a history of previous TIV vaccination. The population will include a Naïve Cohort:
90 healthy male and female children who are 6-35 months of age and have never received an
influenza vaccination; and a Fully Primed Cohort: 60 healthy male and female children who
are 12-35 months of age and have received two doses of 2009-2010 H1N1 and two doses of TIV
at anytime in the past as defined for purposes of this study. Either a standard pediatric
dose (0.25 ml) or a larger dose (0.5 ml) of TIV will be administered intramuscularly in the
anterolateral thigh with a 25 gauge 1" needle. The primary objective is to evaluate the
safety of administering an increased dose(s) (0.5 ml) of TIV to children 6-35 months of age
as compared to standard dose(s) (0.25 ml) of TIV. The secondary objective is to compare the
humoral immune responses to TIV antigens in children 6-35 months of age who receive the
increased dose(s) of TIV to those who receive the standard dose(s) of TIV.

Inclusion Criteria:

All Subjects

- Healthy children 6-35 months of age (naïve cohort) or 12-35 months of age (fully
primed cohort)

- Free of obvious health problems as established by medical history and clinical
examination before entering the study

- Parent/legal guardian willing and capable of signing written informed consent

- Parent/legal guardian expected to be available for entire study

- Parent/legal guardian can be reached by telephone

Fully Primed Cohort

-Have received two doses of 2009-2010 H1N1 and two doses of trivalent inactivated
influenza vaccine (TIV) at anytime in the past as defined for the purpose of this study.

Exclusion Criteria:

All Subjects:

- Have known allergy to eggs or other components of the vaccine. *Refer to the Fluzone
package insert for a list of vaccine components.

- Known or suspected latex allergy.

- Former premature infants (<32 weeks).

- History of bronchodilator use more than 2 times per week within 28 days of
vaccination.

- Significant underlying chronic illness (e.g., congenital heart disease,
bronchopulmonary dysplasia).

- Immunodeficiency disease or use of immunosuppressive therapy by the participant,
including perinatal exposure to or infection with human immunodeficiency virus (HIV),
or known infection with hepatitis B or hepatitis C.

- Any other condition that, in the clinical judgment of the investigator, may interfere
with vaccine evaluation. Children receiving antibiotics are eligible for enrollment.

- Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled
steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the
preceding 6 months. (Nasal and topical steroids are allowed.)

- Previous, exposure to an investigational drug or investigational vaccine within 28
days prior to vaccination in this trial.

- Plans for participation in another clinical trial with an investigational drug or
investigational vaccine for the duration of this study.

- History of Guillain-Barré syndrome or any other neuromuscular disease.

- History of seizures (including febrile seizures).

Naïve Cohort:

- Any prior influenza vaccination.

- History of documented laboratory-confirmed influenza infection.

Fully primed Cohort:

- Have not received two doses of 2009-2010 H1N1 and two doses of trivalent inactivated
influenza vaccine (TIV) at anytime in the past as defined for the purpose of this
study.

- Allergic response to prior receipt of influenza vaccine.

Criteria for temporarily delaying vaccine administration for both groups:

The following conditions are temporary or self-limiting and a subject may be included in
the study once the condition(s) has/have resolved, provided that the subject is otherwise
eligible:

- Receipt of blood products in the previous 90 days

- Fever (axillary temperature > 100.0 degrees Fahrenheit/37.8 degrees Celsius), or an
acute illness within 48 hours of enrollment.

- Receipt of any live vaccines within four weeks or any inactivated vaccines within two
weeks of study vaccination.