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

Condition(s) targeted: Influenza

Intervention: Cell culture-derived influenza subunit vaccine (cTIV) (Biological); Egg derived influenza subunit vaccine (eTIV_f) (Biological); Cell culture-derived influenza subunit vaccine (cTIV) (Biological); Egg derived influenza subunit vaccine (eTIV_f) (Biological)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Novartis

Official(s) and/or principal investigator(s):
Novartis Vaccines, Study Chair, Affiliation: Novartis Vaccines

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).

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Primary outcome:

Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children

Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children

Secondary outcome:

Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents

Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents.

Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents

Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents

Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children

Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children

Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children

Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children

Number of Subjects Reporting Local* and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents.

Number of Subjects Reporting Local* and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children.

Minimum age: 3 Years. Maximum age: 17 Years. Gender(s): Both.

Criteria:

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.

Site 44:Spec. Pediatric Dispensary, Dakovo, Croatia

Site 83, Ljudevita Gaja 2, Djakovo, Croatia

Site 43: Spec. Pediatric Dispensary, Sisak, Croatia

Site 27:Institute of Public Health, Zagreb, Croatia

Site 29: Institute of Public Health, Zagreb, Croatia

Site 40:Spec. Pediatric Dispensary, Zagreb, Croatia

Site 49: Spec. Pediatric Dispensary, Zagreb, Croatia

Site 50: Spec. Pediatric Dispensary, Zagreb, Croatia

Site 86: Spec. Pediatric Dispensary, Zagreb, Croatia

Site 71: Etelä-Helsingin rokotetutkimusklinikka, Helsinki 00100, Finland

Site 72: Itä-Helsingin rokotetutkimusklinikka, Helsinki 00930, Finland

Site 76: Järvenpään rokotetutkimusklinikka, Järvenpää 04400, Finland

Site 77: Kotkan rokotetutkimusklinikka, Kotka 48600, Finland

Site 67: Lahden rokotetutkimusklinikka, Lahti 15140, Finland

Site 75: Oulun rokotetutkimusklinikka, Oulu 90100, Finland

Site 68: Porin rokotetutkimusklinikka, Pori 28120, Finland

Site 66: Tampereen rokotetutkimusklinikka, Tampere 33100, Finland

Site 69: Turun rokotetutkimusklinikka, Turku 20520, Finland

Site 73: Itä-Vantaan rokotetutkimusklinikka, Vantaa 01300, Finland

Site 74: Länsi-Vantaan rokotetutkimusklinikka, Vantaa 01600, Finland

Site 52: Ferencvárosi Gyermekorvos Kft., Budapest 1097, Hungary

Site 53: Heim Pál Gyermekkórház, Budapest 1089, Hungary

Site 54: Házi Gyermekorvosi Rendelő, Budapest 1173, Hungary

Site 56: Házi Gyermekorvosi Rendelő, Budapest 1136, Hungary

Site 57: Házi Gyermekorvosi Rendelő, Budapest 1042, Hungary

Site 51: 5053. számú Gyermekorvosi Rendelő, Miskolc 3534, Hungary

Site 55: Revamed kft., Nyíregyháza 4481, Hungary

Site 59: Vas Megyei Markusovszky Lajos, Általános, Rehabilitációs és Gyógyfürdő Kórház, Egyetemi Oktató Kórház, Szombathely 9700, Hungary

Site 42: Dipartimento di Medicina Clinica e Sperimentale - Sezione di Igiene e Medicina Preventiva, Ferrara 44100, Italy

Site 47: Dipartimento Scienze della Salute, Sezione di Igiene e Medicina Preventiva, Univesità di Genova, Genova 16132, Italy

Site 41: Ospedale Maggiore della Carità-Clinica Pediatrica, Novara 28100, Italy

Site 46: USL 2 Perugia, Distretto del perugino, Centro di Salute n. 4 (Madonna Alta) e n. 6 (Ellera di Corciano del distretto del perugino), Perugia 06070, Italy

Site 45: AUSL 7, Ragusa 97100, Italy

Site 35, Kaunas 48259, Lithuania

Site 31, Vilnius 10207, Lithuania

Site 32, Vilnius 02169, Lithuania

Site 33, Vilnius 11200, Lithuania

Site 34, Vilnius 04318, Lithuania

Site 36, Vilnius 01117, Lithuania

Site 25, Campulung Muscel, Arges 115100, Romania

Site 09, Fayetteville, Arkansas 72703, United States

Site 10, Downey, California 90241, United States

Site 21, Craiova, Dolj 200642, Romania

Site 70: Espoon rokotetutkimusklinikka, Heikintori, Espoo 02100, Finland

Site 02, Bardstown, Kentucky 40004, United States

Site 79: Kokkola Vaccine Research Clinic, Rantakatu 7, Kokkola 67100, Finland

Site 78: Kuopio Vaccine Research Clinic, Microkatu 1,Osa/Section A, 3rd floor PL1188, Kuopio 70211, Finland

Site 14, Metairie, Louisiana 70006, United States

Site 01, St. Louis, Missouri 63104, United States

Site 11, Omaha, Nebraska 68134, United States

Site 04, Edison, New Jersey 08817, United States

Site 05, Endwell, New York 13760, United States

Site 16, Fort Worth, Texas 76135, United States

Site 13, San Angelo, Texas 76904, United States

Site 12, San Antonio, Texas 78205, United States

Site 08, Bountiful, Utah 84010, United States

Site 03, Salt Lake City, Utah 84121, United States

Site 07, Salt Lake City, Utah 84109, United States

Site 06, Burke, Virginia 22105, United States

Site 15, Spokane, Washington 99202, United States

Starting date: October 2007
Last updated: January 15, 2013