Safety and Immunogenicity of Trivalent Subunit Inactivated Flu Vaccine Administered to Healthy Children and Adolescents 3 to 17 Years of Age

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity in healthy children and adolescents after one or two IM dose(s) of trivalent subunit inactivated flu vaccine.

Official Title
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A Multi-center, Phase III, Randomized, Observer Blind Study to Evaluate the Safety, Tolerability and Immunogenicity of a Trivalent Subunit Inactivated Flu Vaccine in Healthy Children and Adolescents 3 to 17 Years of Age

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: TIV
* Biological: TIVf
* Biological: Comparator TIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 3 to 17 years, in good health as determined by medical history, physical examination and clinical judgment of the investigator Documented consent provided by parents or legal guardians For individuals 8 years of age and older, informed assent to participate in the study after the nature of the study had been explained to them in terms they could understand Individuals and parents/guardians who were able to comply with all study procedures and were available for all clinic visits scheduled in the study Exclusion Criteria: Parents or legal guardians and individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study Parents or legal guardians and individuals providing assent who do not consent to the retention of the subject's serum samples after study completion Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may have interfered with the subject's ability to participate in the study Individuals with history or any illness that, in the opinion of the investigator, might have interfered with the results of the study or posed additional risk to the subjects due to participation in the study History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, latex, to any excipients, and to eggs (including ovalbumin), chicken protein, influenza viral protein, kanamycin, neomycin sulphate, cetyltrimethylammonium bromide (CTAB), polysorbate 80, neomycin, polymixin, formaldehyde, thimerosal, beta propiolactone, or nonoxynol-9 History of any serious disease, such as: cancer history of serious chronic, rheumatologic, neurologic and hematologic diseases history of underlying medical condition such as inborn errors of metabolism Known or suspected impairment/alteration of immune function, including: chronic use of oral steroids within 60 days prior to Visit 1 (use of inhaled, intranasal, or topical corticosteroids is allowed) receipt of immunostimulants within 60 days prior to Visit 1 receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study HIV infection or HIV-related disease Pregnant or breast-feeding female and any positive or indeterminate pregnancy test Received an influenza vaccine within 6 months prior to Visit 1 Laboratory-confirmed or suspected influenza disease within 6 months prior to Visit 1 Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study Experienced a fever and/or any acute illness within 3 days prior to each study vaccination

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TIV (3-8 years)<br>Non-Naive subjects received one dose and naive subjects received two doses, administered 4 weeks apart, of investigational trivalent influenza vaccine (TIV) | Biological: TIV<br>* Investigational egg-derived trivalent subunit influenza vaccine.<br>|
| Active Comparator: Control TIV (3-8 years)<br>Non-Naive subjects received one dose and Naive subjects received two doses, administered 4 weeks apart, of control vaccine. Subjects aged 3 to <4 years and subjects aged 4 to 8 years received different control TIV. | Biological: TIVf<br>* US licensed trivalent inactivated subunit influenza vaccine -Fluvirin (Novartis Vaccines and Diagnostics) is approved for use in subjects ≥4 years.<br>Biological: Comparator TIV<br>* US licensed trivalent subunit inactivated influenza vaccine- Fluzone (Sanofi Pasteur) is approved for use in children <4 years.<br>|
| Experimental: TIV ( 9-17 years)<br>All subjects received one dose of investigational TIV. The subjects in this cohort were included only for safety analysis. | Biological: TIV<br>* Investigational egg-derived trivalent subunit influenza vaccine.<br>|
| Active Comparator: Control TIV ( (9-17 years)<br>All subjects received one dose of the control vaccine. The subjects from this cohort were included only for safety analysis. | Biological: TIVf<br>* US licensed trivalent inactivated subunit influenza vaccine -Fluvirin (Novartis Vaccines and Diagnostics) is approved for use in subjects ≥4 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination. Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer <1:10 and post-vaccination HI titer ≥1:40 or as a pre-vaccination HI titer ≥1:10 and at minimum four-fold rise in post-vaccination antibody titer | Day 22 for non-naive/Day 50 for naive subjects | 
| Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children. | Day 22 for non-naive/Day 50 for naive subjects | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | The percentages of 3 to 8 year old subjects achieving HI titers ≥40 after receiving either one or two doses of investigational TIV or control vaccine, 21 days after last vaccination, are reported. This criterion according to the US (CBER)guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40, is ≥70%. | Day 22 for non-naive/Day 50 for naive subjects | 
| Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | The percentages of 3 to 8 years-old subjects achieving seroconversion in HI antibody titers after receiving either one or two doses of investigational TIV or control vaccine, at 21 days after last vaccination, are reported. This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 22 and day 50 (21 days after last vaccination) is ≥40. | Day 22 for non-naive/Day 50 for naive | 
| Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | The percentage of 3 to 8 years-old vaccine-naive subjects achieving HI titers ≥40, after receiving two doses of investigational TIV or control vaccine. The time frame of evaluation was 28 days after first (Day 29) and 21 days after second vaccine dose (Day 50). This criterion according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%, for each vaccine strain. | Day 1, Day 29, and Day 50 | 
| Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | The percentages of 3 to 8 years-old vaccine naive children achieving seroconversion or significant increase in HI antibody titers after receiving two doses of investigational TIV or control vaccine, are reported. The time frame of evaluation was 28 days after first (Day 29) and 21 days after the second dose (Day 50). This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 29 and day 50 is ≥40, for each vaccine strain. | Day 29 and Day 50 | 
| Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | The number of 3-17 year old children with solicited local and systemic adverse events and other adverse events, after receiving either one or two doses of investigational TIV as compared to control vaccine are reported. | Day 1 to 7 after vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | The number of 3-17 year old children reporting any unsolicited adverse event and any serious adverse event (SAE) after receiving either one or two doses of investigational TIV and control vaccine are reported. | Day 1 to 180 (non-naive )/Day 1 to 209 (naive) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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seasonal influenza, vaccine