Clinical trial NCT00645411: Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Influenza
Keywords: Influenza
Flu
Cell Culture-Derived
Egg-Derived
Healthy Children
Healthy Adolescents
Safety
Immunogenicity
Trivalent
Inactivated
Vaccination
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2008-03-27
Enrollment: 3604
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).


Eligibility 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.

Primary outcomes:
measure: Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children
timeFrame: Day 50 post vaccination
measure: 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
timeFrame: Day 50 post vaccination
Secondary outcomes:
measure: 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
timeFrame: Day 29 post vaccination
measure: 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.
timeFrame: Day 29 post vaccination
measure: 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
timeFrame: Day 29 post vaccination
measure: 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
timeFrame: Day 29 post vaccination
measure: Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children
timeFrame: Day 29 and Day 50 post vaccination
measure: Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children
timeFrame: Day 29 and Day 50 post vaccination
measure: 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
timeFrame: Day 29 and Day 50 post vaccination
measure: 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
timeFrame: Day 29 and Day 50 post vaccination
measure: 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.
timeFrame: up to 7 days after vaccination
measure: 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.
timeFrame: up to 7 days after each vaccination
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Site 09
state: Arkansas
city: Downey
country: United States
facility: Site 10
state: California
city: Bardstown
country: United States
facility: Site 02
state: Kentucky
city: Metairie
country: United States
facility: Site 14
state: Louisiana
city: St. Louis
country: United States
facility: Site 01
state: Missouri
city: Omaha
country: United States
facility: Site 11
state: Nebraska
city: Edison
country: United States
facility: Site 04
state: New Jersey
city: Endwell
country: United States
facility: Site 05
state: New York
city: Fort Worth
country: United States
facility: Site 16
state: Texas
city: San Angelo
country: United States
facility: Site 13
state: Texas
city: San Antonio
country: United States
facility: Site 12
state: Texas
city: Bountiful
country: United States
facility: Site 08
state: Utah
city: Salt Lake City
country: United States
facility: Site 07
state: Utah
city: Salt Lake City
country: United States
facility: Site 03
state: Utah
city: Burke
country: United States
facility: Site 06
state: Virginia
city: Spokane
country: United States
facility: Site 15
state: Washington
city: Dakovo
country: Croatia
facility: Site 44:Spec. Pediatric Dispensary
city: Ljudevita Gaja 2, Djakovo
country: Croatia
facility: Site 83
city: Sisak
country: Croatia
facility: Site 43: Spec. Pediatric Dispensary
city: Zagreb
country: Croatia
facility: Site 27:Institute of Public Health
city: Zagreb
country: Croatia
facility: Site 29: Institute of Public Health
city: Zagreb
country: Croatia
facility: Site 40:Spec. Pediatric Dispensary
city: Zagreb
country: Croatia
facility: Site 49: Spec. Pediatric Dispensary
city: Zagreb
country: Croatia
facility: Site 50: Spec. Pediatric Dispensary
city: Zagreb
country: Croatia
facility: Site 86: Spec. Pediatric Dispensary
city: Heikintori
country: Finland
facility: Site 70: Espoon rokotetutkimusklinikka
state: Espoo
city: Rantakatu 7
country: Finland
facility: Site 79: Kokkola Vaccine Research Clinic
state: Kokkola
city: Microkatu 1,Osa/Section A, 3rd floor PL1188
country: Finland
facility: Site 78: Kuopio Vaccine Research Clinic
state: Kuopio
city: Helsinki
country: Finland
facility: Site 71: Etelä-Helsingin rokotetutkimusklinikka
city: Helsinki
country: Finland
facility: Site 72: Itä-Helsingin rokotetutkimusklinikka
city: Järvenpää
country: Finland
facility: Site 76: Järvenpään rokotetutkimusklinikka
city: Kotka
country: Finland
facility: Site 77: Kotkan rokotetutkimusklinikka
city: Lahti
country: Finland
facility: Site 67: Lahden rokotetutkimusklinikka
city: Oulu
country: Finland
facility: Site 75: Oulun rokotetutkimusklinikka
city: Pori
country: Finland
facility: Site 68: Porin rokotetutkimusklinikka
city: Tampere
country: Finland
facility: Site 66: Tampereen rokotetutkimusklinikka
city: Turku
country: Finland
facility: Site 69: Turun rokotetutkimusklinikka
city: Vantaa
country: Finland
facility: Site 73: Itä-Vantaan rokotetutkimusklinikka
city: Vantaa
country: Finland
facility: Site 74: Länsi-Vantaan rokotetutkimusklinikka
city: Budapest
country: Hungary
facility: Site 57: Házi Gyermekorvosi Rendelő
city: Budapest
country: Hungary
facility: Site 53: Heim Pál Gyermekkórház
city: Budapest
country: Hungary
facility: Site 52: Ferencvárosi Gyermekorvos Kft.
city: Budapest
country: Hungary
facility: Site 56: Házi Gyermekorvosi Rendelő
city: Budapest
country: Hungary
facility: Site 54: Házi Gyermekorvosi Rendelő
city: Miskolc
country: Hungary
facility: Site 51: 5053. számú Gyermekorvosi Rendelő
city: Nyíregyháza
country: Hungary
facility: Site 55: Revamed kft.
city: Szombathely
country: Hungary
facility: Site 59: Vas Megyei Markusovszky Lajos, Általános, Rehabilitációs és Gyógyfürdő Kórház, Egyetemi Oktató Kórház
city: Ferrara
country: Italy
facility: Site 42: Dipartimento di Medicina Clinica e Sperimentale - Sezione di Igiene e Medicina Preventiva
city: Genova
country: Italy
facility: Site 47: Dipartimento Scienze della Salute, Sezione di Igiene e Medicina Preventiva, Univesità di Genova
city: Novara
country: Italy
facility: Site 41: Ospedale Maggiore della Carità-Clinica Pediatrica
city: Perugia
country: Italy
facility: 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)
city: Ragusa
country: Italy
facility: Site 45: AUSL 7
city: Kaunas
country: Lithuania
facility: Site 35
city: Vilnius
country: Lithuania
facility: Site 36
city: Vilnius
country: Lithuania
facility: Site 32
city: Vilnius
country: Lithuania
facility: Site 34
city: Vilnius
country: Lithuania
facility: Site 31
city: Vilnius
country: Lithuania
facility: Site 33
city: Campulung Muscel
country: Romania
facility: Site 25
state: Arges
city: Craiova
country: Romania
facility: Site 21
state: Dolj
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References:
citation: Vesikari T, Block SL, Guerra F, Lattanzi M, Holmes S, Izu A, Gaitatzis N, Hilbert AK, Groth N. Immunogenicity, safety and reactogenicity of a mammalian cell-culture-derived influenza vaccine in healthy children and adolescents three to seventeen years of age. Pediatr Infect Dis J. 2012 May;31(5):494-500. doi: 10.1097/INF.0b013e31824bb179.