14.3 Immunogenicity of AFLURIA (trivalent formulation) Administered by PharmaJet Stratis Needle-Free Injection System
Study 2 was a randomized, comparator-controlled, non-inferiority study that enrolled 1,250 subjects 18 through 64 years of age. This study compared the immune response following administration of AFLURIA (trivalent formulation) when delivered intramuscularly using either the PharmaJet Stratis Needle-Free Injection System or needle and syringe. Immunogenicity assessments were performed prior to vaccination and at 28 days after vaccination in the immunogenicity population (1130 subjects, 562 PharmaJet Stratis Needle-Free Injection System group, 568 needle and syringe group). The co-primary endpoints were HI GMT ratios for each vaccine strain and the absolute difference in seroconversion rates for each vaccine strain 28 days after vaccination. As shown in Table 8, non-inferiority of administration of AFLURIA (trivalent formulation) by the PharmaJet Stratis Needle-Free Injection System compared to administration of AFLURIA (trivalent formulation) by needle and syringe was demonstrated in the immunogenicity population for all strains. Post-hoc analyses of immunogenicity by age showed that younger subjects (18 through 49 years) elicited higher immunological responses than older subjects (50 through 64 years). Post-hoc analyses of immunogenicity according to sex and body mass index did not reveal significant influences of these variables on immune responses. The study population was not sufficiently diverse to assess immunogenicity by race or ethnicity.
|Baseline GMT||Post-vaccination GMT||GMT Ratio b||Seroconversion % c||Difference||Met both pre-defined non-inferiority criteria? d|
|Strain||Needle and Syringe N=568||PharmaJet Stratis Needle-Free Injection System N=562||Needle and Syringe N=568||PharmaJet Stratis Needle-Free Injection System N=562||Needle and Syringe over PharmaJet Stratis Needle-Free Injection System (95% CI)||Needle and Syringe N=568||PharmaJet Stratis Needle-Free Injection System N=562||Needle and Syringe minus PharmaJet Stratis Needle-Free Injection System (95% CI)|
Abbreviations: CI, confidence interval; GMT, geometric mean titer.
b GMT ratio is defined as post-vaccination GMT for Needle and Syringe/PharmaJet Stratis Needle-Free Injection System.
c Seroconversion rate is defined as a 4-fold increase in post-vaccination HI antibody titer from pre-vaccination titer ≥ 1:10 or an increase in titer from < 1:10 to ≥ 1:40.
d Non-inferiority (NI) criterion for the GMT ratio: upper bound of 2-sided 95% CI on the GMT ratio of Needle and Syringe/PharmaJet Stratis Needle-Free Injection System should not exceed 1.5. NI criterion for the seroconversion rate (SCR) difference: upper bound of 2-sided 95% CI on the difference between SCR Needle and Syringe – SCR PharmaJet Stratis Needle-Free Injection System should not exceed 10%.
|A(H1N1)||79.5||83.7||280.6||282.9||0.99 (0.88, 1.12)||38.4||37.5||0.8 (-4.8, 6.5)||Yes|
|A(H3N2)||75.4||68.1||265.9||247.3||1.08 (0.96, 1.21)||45.1||43.8||1.3 (-4.5, 7.1)||Yes|
|B||12.6||13.5||39.7||42.5||0.94 (0.83, 1.06)||35.2||34.9||0.3 (-5.2, 5.9)||Yes|
14.4 Immunogenicity of AFLURIA QUADRIVALENT in Children 5 through 17 Years Administered by Needle and Syringe
Study 3 was a randomized, observer-blinded, comparator-controlled trial conducted in the U.S. in children 5 through 17 years of age. A total of 2278 subjects were randomized 3:1 to receive one or two doses of AFLURIA QUADRIVALENT (N=1709) or a U.S.-licensed comparator quadrivalent influenza vaccine (N=569). Subjects 5 through 8 years of age were eligible to receive a second dose at least 28 days after the first dose depending on their influenza vaccination history, consistent with the 2015-2016 recommendations of the Advisory Committee on Immunization Practices (ACIP) for Prevention and Control of Seasonal Influenza with Vaccines. Approximately 25% of subjects in each treatment group in the 5 through 8 years of age sub-group received two vaccine doses.
Baseline serology for HI assessment was collected prior to vaccination. Post-vaccination 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=1605, Comparator n=528) 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/AFLURIA QUADRIVALENT) did not exceed 1.5 and the upper bound of the 2-sided 95% CI of the seroconversion rate difference (Comparator 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 9). 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=1605||Comparator N=528||Comparator over AFLURIA Quadrivalent (95% CI)||AFLURIA Quadrivalent N=1605(95% CI)||Comparator N=528 (95% CI)||Comparator minus AFLURIA Quadrivalent (95% CI)|
Abbreviations: CI, confidence interval; Comparator, Comparator quadrivalent influenza vaccine (Fluarix® Quadrivalent [GlaxoSmithKline Biologicals]); GMT (adjusted), geometric mean titer; SCR, seroconversion rate.
b The Per-Protocol Population comprised all subjects 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 Strata [5-8, 9-17] + Gender + Vaccination History [y/n] + Log-transformed Pre-Vaccination HI Titer + Site + Number of Doses (1 vs 2) + Age Strata*Vaccine. The Age Strata*Vaccine interaction term was excluded from the model fit for the strains B/Yamagata and B/Victoria 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 Non-inferiority (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 8400394-0046 was excluded from the Per-Protocol Population for the adjusted GMT analysis for the GMT ratio since the subject did not have information on all covariates (unknown prevaccination history).
|A(H1N1)||952.6 (n=1604 g)||958.8||1.01 (0.93, 1.09)||66.4(64.0, 68.7)||63.3(59.0, 67.4)||-3.1(-8.0, 1.8)||Yes|
|A(H3N2)||886.4 (n=1604 g)||930.6||1.05 (0.96, 1.15)||82.9(81.0, 84.7)||83.3(79.9, 86.4)||0.4(-4.5, 5.3)||Yes|
|B/Phuket/3073/2013(B Yamagata)||60.9 (n=1604 g)||54.3||0.89 (0.81, 0.98)||58.5(56.0, 60.9)||55.1(50.8, 59.4)||-3.4(-8.3, 1.5)||Yes|
|B/Brisbane/60/2008(B Victoria)||145.0 (n=1604 g)||133.4||0.92 (0.83, 1.02)||72.1(69.8, 74.3)||70.1(66.0, 74.0)||-2.0(-6.9, 2.9)||Yes|
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