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

Influenza Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01992107
• Other study ID #: V130_03
• Status: Completed
• Phase: Phase 3
• First received: November 7, 2013
• Last updated: November 2, 2015
• Start date: November 2013
• Est. completion date: August 2014

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2333
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 4 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Male or female aged 4 years to less than 18 years of age.

2. 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.

3. 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:

1. Individuals recently vaccinated against influenza

2. Subjects with contraindications to receive influenza vaccine

Study Design

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• QIVc
Novartis Investigational Quadrivalent Vaccine
• TIV1c
Licensed Influenza Vaccine
• TIV2c
Novartis Investigational Vaccine

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	Yes
Secondary	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	Yes