14.2 Immunogenicity of AFLURIA QUADRIVALENT in Adults and Older Adults Administered by Needle and Syringe
Study 1 was a randomized, double-blind, active-controlled trial conducted in the U.S. in adults aged 18 years of age and older. Subjects received one dose of either AFLURIA QUADRIVALENT (N=1691) or one of two formulations of comparator trivalent influenza vaccine (AFLURIA, TIV-1 N=854 or TIV-2 N=850) each containing an influenza type B virus that corresponded to one of the two B viruses in AFLURIA QUADRIVALENT (a type B virus of the Yamagata lineage or a type B virus of the Victoria lineage, respectively).
Post-vaccination immunogenicity was evaluated on sera obtained 21 days after administration of a single dose of AFLURIA QUADRIVALENT or TIV comparator. The co-primary endpoints were HI Geometric Mean Titer (GMT) ratios (adjusted for baseline HI titers) and the difference in seroconversion rates for each vaccine strain, 21 days after vaccination. Pre-specified non-inferiority criteria required that the upper bound of the 2-sided 95% CI of the GMT ratio (TIV/AFLURIA QUADRIVALENT) did not exceed 1.5 and the upper bound of the 2-sided 95% CI of the seroconversion rate difference (TIV minus AFLURIA QUADRIVALENT) did not exceed 10.0% for each strain.
Serum HI antibody responses to AFLURIA QUADRIVALENT were non-inferior to both TIVs for all influenza strains for subjects 18 years of age and older. Additionally, non-inferiority was demonstrated for both endpoints in both age sub-groups, adults aged 18 through 64 years and 65 years and older, for all strains (Table 7). Superiority of the immune response to each of the influenza B strains contained in AFLURIA QUADRIVALENT was shown relative to the antibody response after vaccination with TIV formulations not containing that B lineage strain for subjects 18 years of age and older. Superiority against the alternate B strain was also demonstrated for each of the influenza B strains in both age sub-groups; 18 through 64 years and 65 years and older. Post-hoc 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 between races or ethnicities.
|Post-vaccination GMT||GMT Ratio b||Seroconversion % c||Difference||Met both pre-defined non-inferiority criteria? d|
|Strain||AFLURIA Quadrivalent||Pooled TIV or TIV-1(B Yamagata) or TIV-2(B Victoria)||Pooled TIV or TIV-1 or TIV-2 over AFLURIA Quadrivalent (95% CI)||AFLURIA Quadrivalent N=1691||Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria)||Pooled TIV or TIV-1 or TIV-2 minusAFLURIA Quadrivalent (95% CI)|
Abbreviations: CI, confidence interval; GMT, geometric mean titer.
b GMT ratio was computed after fitting a multi-variable model on the post-vaccination titers including sex, vaccination history, pre-vaccination HI titers and other factors.
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 Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria)/AFLURIA Quadrivalent should not exceed 1.5. NI criterion for the SCR difference: upper bound of 2-sided 95% CI on the difference between SCR Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus AFLURIA Quadrivalent should not exceed 10%.
e Pooled TIV/AFLURIA Quadrivalent
f TIV-1 (B Yamagata)/AFLURIA Quadrivalent
g TIV-2 (B Victoria)/AFLURIA Quadrivalent
h Pooled TIV – AFLURIA Quadrivalent
i TIV-1 (B Yamagata) — AFLURIA Quadrivalent
j TIV-2 (B Victoria) — AFLURIA Quadrivalent
|18 through 64 years||AFLURIA Quadrivalent N=835, Pooled TIV N=845, TIV-1 N=424, TIV-2 N=421|
|A(H1N1)||432.7||402.8||0.93 e (0.85, 1.02)||51.3||49.1||-2.1 h (-6.9, 2.7)||Yes|
|A(H3N2)||569.1||515.1||0.91 e (0.83, 0.99)||56.3||51.7||-4.6 h (-9.4, 0.2)||Yes|
|B/Massachusetts/2/2012(B Yamagata)||92.3||79.3||0.86 f (0.76, 0.97)||45.7||41.3||-4.5 i (-10.3, 1.4)||Yes|
|B/Brisbane/60/2008(B Victoria)||110.7||95.2||0.86 g (0.76, 0.98)||57.6||53.0||-4.6 j (-10.5, 1.2)||Yes|
|≥ 65 years||AFLURIA Quadrivalent N=856, Pooled TIV N=859, TIV-1 N=430, TIV-2 N=429|
|A(H1N1)||211.4||199.8||0.95 e (0.88, 1.02)||26.6||26.4||-0.2 h (-5.0, 4.5)||Yes|
|A(H3N2)||419.5||400.0||0.95 e (0.89, 1.02)||25.9||27.0||1.1 h (-3.7, 5.8)||Yes|
|B/Massachusetts/2/2012(B Yamagata)||43.3||39.1||0.90 f (0.84, 0.97)||16.6||14.4||-2.2 i (-8.0, 3.6)||Yes|
|B/Brisbane/60/2008(B Victoria)||66.1||68.4||1.03 g (0.94, 1.14)||23.5||24.7||1.2 j (-4.6, 7.0)||Yes|
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