14.5 Immunogenicity of Afluria Quadrivalent in Children 6 Months Through 59 Months Administered by Needle and Syringe
Study 4 was a randomized, observer-blind, comparator-controlled trial conducted in the U.S. in children 6 months through 59 months of age. A total of 2247 subjects were randomized 3:1 to receive AFLURIA QUADRIVALENT (N=1684) or a U.S.-licensed comparator quadrivalent influenza vaccine (N=563). Children 6 months through 35 months received one or two 0.25 mL doses and children 36 months through 59 months received one or two 0.5 mL doses. Subjects were eligible to receive a second dose at least 28 days after the first dose depending on their influenza vaccination history, consistent with the 2016-2017 recommendations of the Advisory Committee on Immunization Practices (ACIP) for Prevention and Control of Seasonal Influenza with Vaccines. Approximately 40% of subjects in each treatment group received two vaccine doses.
Baseline serology for HI assessment was collected prior to vaccination. Postvaccination immunogenicity was evaluated by HI assay on sera obtained 28 days after the last vaccination dose.
The primary objective was to demonstrate that vaccination with AFLURIA QUADRIVALENT elicits an immune response that is not inferior to that of a comparator vaccine containing the same recommended virus strains. The Per Protocol Population (AFLURIA QUADRIVALENT n=1456, Comparator QIV n=484) was used for the primary endpoint analyses. The co-primary endpoints were HI Geometric Mean Titer (GMT) ratios (adjusted for baseline HI titers and other covariates) and seroconversion rates for each vaccine strain, 28 days after the last vaccination. Pre-specified non-inferiority criteria required that the upper bound of the 2-sided 95% CI of the GMT ratio (Comparator QIV/AFLURIA QUADRIVALENT) did not exceed 1.5 and the upper bound of the 2-sided 95% CI of the seroconversion rate difference (Comparator QIV minus AFLURIA QUADRIVALENT) did not exceed 10.0% for each strain. Serum HI antibody responses to AFLURIA QUADRIVALENT were non-inferior for both GMT ratio and seroconversion rates relative to the comparator vaccine for all influenza strains (Table 10). Analyses of immunogenicity endpoints by gender did not demonstrate meaningful differences between males and females. The study population was not sufficiently diverse to assess differences among races or ethnicities.
|Post-vaccination GMT||GMT Ratio c||Seroconversion % d||SCR Difference e||Met both pre-defined non-inferiority criteria? f|
|Strain||AFLURIA Quadrivalent N=1456||Comparator N=484||Comparator over AFLURIA Quadrivalent (95% CI)||AFLURIA Quadrivalent N=1456(95% CI)||Comparator N=484(95% CI)||Comparator minus AFLURIA Quadrivalent (95% CI)|
Abbreviations: CI, confidence interval; Comparator, Comparator quadrivalent influenza vaccine (Fluzone Quadrivalent [Sanofi Aventis]); GMT (adjusted), geometric mean titer; SCR, seroconversion rate.
b The Per-Protocol Population comprised all subjects (6 through 35 months of age receiving one or two 0.25 mL doses and 36 through 59 months of age receiving one or two 0.5 mL doses) in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
c GMT Ratio = Comparator / AFLURIA QUADRIVALENT. Adjusted analysis model: Log-transformed Post-Vaccination HI Titer=Vaccine + Age Cohort [6 through 35 months or 36 through 59 months] + Gender + Vaccination History [y/n] + Log-transformed Pre-Vaccination HI Titer + Site + Number of Doses (1 vs 2) + Age Cohort*Vaccine. The Age Cohort*Vaccine interaction term was excluded from the model fit for the strains A(H1N1), A(H3N2) and B/Yamagata as the interaction result was non-significant (p>0.05). Least square means were back transformed.
d Seroconversion rate was defined as the percentage of subjects with either a prevaccination HI titer < 1:10 and a postvaccination HI titer ≥ 1:40 or a prevaccination HI titer ≥ 1:10 and a 4-fold increase in postvaccination HI titer.
e Seroconversion rate difference = Comparator SCR percentage minus AFLURIA QUADRIVALENT SCR percentage.
f Noninferiority (NI) criterion for the GMT ratio: upper bound of two-sided 95% CI on the GMT ratio of Comparator / AFLURIA QUADRIVALENT should not exceed 1.5. NI criterion for the SCR difference: upper bound of two-sided 95% CI on the difference between SCR Comparator – AFLURIA QUADRIVALENT should not exceed 10%.
g Subject 8400402-0073 was excluded from the Per-Protocol Population for the adjusted GMT analysis for the GMT ratio because the subject did not have information on all covariates (unknown prevaccination history).
h Subject 8400427-0070 had missing B/Victoria Antigen pre-vaccination titer.
i Subject 8400402-0074 had missing A/H3N2 post-vaccination titer.
|A(H1N1)||353.5 (n=1455 g)||281.0(n=484)||0.79 (0.72, 0.88)||79.1(76.9, 81.1)(n=1456)||68.8(64.5, 72.9)(n=484)||-10.3(-15.4, - 5.1)||Yes|
|A(H3N2)||393.0(n=1454 gi)||500.5(n=484)||1.27 (1.15, 1.42)||82.3(80.2, 84.2)(n=1455i)||84.9(81.4, 88.0)(n=484)||2.6(-2.5, 7.8)||Yes|
|B/Phuket/3073/2013(B Yamagata)||23.7 (n=1455 g)||26.5(n=484)||1.12 (1.01, 1.24)||38.9(36.4, 41.4)(n=1456)||41.9(37.5, 46.5)(n=484)||3.1(-2.1, 8.2)||Yes|
|B/Brisbane/60/2008(B Victoria)||54.6 (n=1455 g)||52.9(n=483h)||0.97 (0.86, 1.09)||60.2(57.6, 62.7)(n=1456)||61.1(56.6, 65.4)(n=483h)||0.9(-4.2, 6.1)||Yes|
- Centers for Disease Control and Prevention. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010;59 (RR-8):1-62.
- Hannoun C, Megas F, Piercy J. Immunogenicity and Protective Efficacy of Influenza Vaccination. Virus Res 2004;103:133-138.
- Hobson D, Curry RL, Beare AS, et al. The Role of Serum Hemagglutination-Inhibiting Antibody in Protection against Challenge Infection with Influenza A2 and B Viruses. J Hyg Camb 1972;70:767-777.
Each product presentation includes a package insert and the following components:
|Presentation||Carton NDC Number||Components|
|Pre-Filled Syringe||33332-219-20|| |
|Pre-Filled Syringe||33332-319-01|| |
|Multi-Dose Vial||33332-419-10|| |
VxLabels.com provides trustworthy package insert and label information about marketed drugs and vaccines as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by VxLabels.com. Every individual vaccine label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.