Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents

A Combined Phase II/III, Observer-Blind, Randomized, Multi-center Study to Evaluate Safety, Tolerability and Immunogenicity of Trivalent Subunit Influenza Vaccines, Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs, in Healthy Children and Adolescents

The present study is the first study designed to evaluate safety, tolerability and immunogenicity of the cell culture-derived influenza vaccine in healthy children and adolescents aged 3 to 17 years. A step-down approach is utilized in which reactogenicity and safety will be assessed in children and adolescents 9 to 17 years of age (Cohort 1) prior to enrolling additional children and adolescents 9 to 17 years of age (Cohort 2) and children 3 to 8 years of age (Cohort 3).

Inclusion Criteria:

1. Subjects aged 9 to 17 years (Cohorts 1 and 2) and 3 to 8 years (Cohort 3), whose parents/legal guardians have given written informed consent prior to study entry. Assent will be obtained from subjects according to age requirements of the ECs/IRBs;

2. In good health as determined by:

   1. medical history,
   2. physical examination,
   3. clinical judgment of the Investigator;

3. Able to comply with all study procedures and available for all clinic visits and telephone calls scheduled in the study.

Exclusion Criteria:

1. Any serious disease, such as:

   1. cancer,
   2. autoimmune disease (including rheumatoid arthritis),
   3. diabetes mellitus,
   4. chronic pulmonary disease,
   5. acute or progressive hepatic disease,
   6. acute or progressive renal disease;

2. History of any anaphylaxis or serious reaction following administration of vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, polymyxin, or any other vaccine component, chemically related substance, or component of the potential packaging materials;

3. Known or suspected impairment/alteration of immune function, including:

   1. use of immunosuppressive therapy such as systemic corticosteroids known to be associated with the suppression of hypothalamic-pituitary-adrenal (HPA) axis or chronic use of inhaled high-potency corticosteroids within 60 days prior to Visit 1,
   2. cancer chemotherapy,
   3. receipt of immunostimulants within 60 days prior to Visit 1,
   4. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Visit 1 or planned during the full length of the study,
   5. known HIV infection or HIV-related disease;

4. History of Guillain-Barré syndrome;

5. Bleeding diathesis;

6. Surgery planned during the study period;

7. Receipt of another investigational agent within 90 days, or before completion of the safety follow-up period in another study, whichever is longer, prior to enrollment and unwilling to refuse participation in another clinical study through the end of the study;

8. Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1;

9. Laboratory-confirmed influenza disease within 6 months prior to Visit 1;

10. For subjects aged 3 to 8 years old, ever received two doses of an influenza vaccine in one influenza season;

11. Receipt of an influenza vaccine within 6 months prior to Visit 1;

12. Experienced a temperature 38.0°C [100.4°F]) and/or any acute illness within 3 days prior to Visit 1;

13. Pregnant or nursing mother;

14. Female of childbearing potential who is sexually active and has not used acceptable birth control measures for at least 2 months prior to study entry and who does not plan to use acceptable birth control measures during the 3 weeks following vaccination or refuses to have a urine pregnancy test prior to enrollment. Oral, injected, inserted or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device are considered acceptable forms of birth control;

15. Children of research staff or those living with research staff directly involved with the clinical study. Research staff are individuals with direct study subject contact, indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.;

16. Any condition, which in the opinion of the Investigator, might interfere with the evaluation of the study objectives.