Safety and Immunogenicity of Three Influenza Vaccines in Children Aged 4 Years Old to Less Than 18 Years Old

Study Overview
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Brief Summary
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Evaluate safety and immunogenicity of three influenza vaccines in children ages greater than 4 years old to less than 18 years old.

Official Title
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A Phase III, Stratified, Randomized, Double-Blind, Multicenter, Non-Inferiority Study to Evaluate Safety and Immunogenicity of Cell-Based Quadrivalent Subunit Influenza Virus Vaccine and Cell-Based Trivalent Subunit Influenza Virus Vaccines in Subjects Ages ≥4 Years to < 18 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: QIVc
* Biological: TIV1c
* Biological: TIV2c


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 4 years to less than 18 years of age. Individual who had a parent or guardian who could give written informed consent after understanding the nature of the study and comply with study procedures and were available for follow-up. If the individual was of an age where, according to local regulations, informed assent is required, that individual had provided assent to participate in the study. Exclusion Criteria: Individuals recently vaccinated against influenza Subjects with contraindications to receive influenza vaccine

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QIVc (≥4 to <18 years)<br>Subjects received one or two doses of QIVc-Quadrivalent Cell-based Influenza Vaccine recommended for 2013-2014 season | Biological: QIVc<br>* Novartis Investigational Quadrivalent Vaccine<br>|
| Active Comparator: TIV1c (≥4 to <18 years)<br>Subjects received one or two doses of TIV1c (Trivalent Inactivated Cell-based Influenza Vaccine containing one strain from B lineage (B1 strain) recommended for 2013-2014 season | Biological: TIV1c<br>* Licensed Influenza Vaccine<br>|
| Active Comparator: TIV2c (≥4 to <18 years)<br>Subjects received one or two doses of TIV2c (Trivalent Inactivated Cell-based Influenza Vaccine containing B strain from the alternate lineage (B2 strain) recommended for 2013-2014 | Biological: TIV2c<br>* Novartis Investigational Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c | Immunogenicity of QIVc to comparator TIV1c (For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c) was assessed in terms of GMT in subjects (Previously vaccinated and Not previously vaccinated) measured by hemagglutination inhibition (HI) assay, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c. Non-inferiority was established if the upper bound of the two-sided 95% confidence interval (CI) for the ratio of GMTs (GMT TIV1c or TIV2c /GMT QIVc) for HI antibody does not exceed the non-inferiority margin of 1.5. | Day 1,Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c | Immunogenicity of QIVc to comparator TIVc (For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c) was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase (at least a 4-fold increase in HI titer in subjects seropositive at baseline [i.e., HI titer ≥1:10 at Day 1] ) in HI antibody titers, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c Seroconversion was defined in subjects seronegative at baseline (i.e., HI titer <1:10 at Day 1) as postvaccination HI titer ≥1:40, and defined in subjects seropositive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer. | Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years | Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c Seroconversion was defined in subjects seronegative at baseline (i.e., HI titer <1:10 at Day 1) as postvaccination HI titer ≥1:40, and defined in subjects seropositive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer. The Center for Biologics Evaluation, Research, and Review (CBER) criterion for an adult population is that the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40% | Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years | Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing HI titer ≥1:40, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c. The CBER criterion for adult population was that the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70% | Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years | Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c Seroconversion was defined in subjects seronegative at baseline (i.e., HI titer <1:10 at Day 1) as postvaccination HI titer ≥1:40, and defined in subjects seropositive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer. | Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years | Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing HI titer ≥1:40, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c The Committee for Medicinal Products for Human Use (CHMP) criterion for an adult population was that the percentage of subjects achieving an HI titer ≥1:40 is >70% | Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Geometric Mean Ratios (GMR) in Subjects After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years Age | Immunogenicity was measured in subjects (Previously vaccinated and Not previously vaccinated) as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c .For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c The CHMP criterion for GMR in adult population is >2.5 | Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| GMT in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c Against B2 Strain | Immunogenicity of QIVc to comparator TIV1c was assessed in terms of GMT in subjects (Previously vaccinated and Not previously vaccinated) measured by HI assay, three weeks after last vaccination with one or two doses of either QIVc or TIV1c. Superiority was established if the upper bound of the two-sided 95% CI for the ratio of GMTs (GMT TIV1c /GMT QIVc) for HI antibody did not exceed the superiority margin of 1 | Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Percentages of Subjects Achieving Seroconversion Against B2 Strain After One or Two Doses of Either QIVc or TIV1c | Immunogenicity of QIVc to comparator TIV1c in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, against influenza strain B2, three weeks after last vaccination with QIVc or TIV1c. Superiority criterion was established if the upper bound of the two-sided 95% CI for the difference between seroconversion rates (% seroconversion TIV1c - % seroconversion QIVc) for HI antibody does not exceed the margin of 0 points | Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| GMT in Subjects After Receiving One or Two Doses of Either QIVc,TIV2c Against B1 Strain | Immunogenicity of QIVc to comparator TIV2c was assessed in terms of GMT in subjects (Previously vaccinated and Not previously vaccinated) measured by HI assay, three weeks after last vaccination with one or two doses of either QIVc or TIV2c. Superiority was established if the upper bound of the two-sided 95% CI for the ratio of GMTs (GMT TIV2c /GMT QIVc) for HI antibody does not exceed the superiority margin of 1 | Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc or TIV2c | Immunogenicity of QIVc to comparator TIV2c in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, against influenza strain B1, three weeks after last vaccination with QIVc or TIV2c. Superiority was established if the upper bound of the two-sided 95% CI for the difference between seroconversion rates (% seroconversion TIV2c - % seroconversion QIVc) for HI antibody does not exceed the margin of 0 points | Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects) | 
| Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata | Safety was assessed in terms of number of subjects (Previously vaccinated and Not previously vaccinated) reporting solicited local and systemic reactions, day 1 to 7 after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c.For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison is between QIVc and TIV2c. | Day 1 to 7 after last vaccination | 
| Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group | Safety was assessed in terms of number of subjects (Previously vaccinated and Not previously vaccinated) reporting unsolicited AEs (day 1 to 22 for Previously vaccinated and day 1 to day 50 for Not previously vaccinated subjects), serious adverse events (SAEs), medically attended AEs, AEs leading to withdrawal from the study, new onset of chronic diseases (NOCDs), and concomitant medications (day 1 to day 181 for Previously vaccinated and day 1 to day 210 for Not previously vaccinated subjects) after receiving one or two doses of either QIVc, TIV1c or TIV2c. For A/H1N1, A/H3N2 and B1 strain, the comparison is between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c. | Day 1 to 210 post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Influenza vaccine, Novartis, children