Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study |
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| Institution: | 1. University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, United States;2. Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia;3. Pharmacovigilance and Risk Management, Seqirus Pty Ltd, Parkville, Victoria, Australia;4. Medical Affairs, Seqirus Pty Ltd, Parkville, Victoria, Australia |
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| Abstract: | BackgroundVaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014–2015 trivalent inactivated influenza vaccine (IIV3-Yamagata IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18 years.MethodsParticipants (n = 3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n = 1741), IIV3-YAM (n = 871), or IIV3-VIC (n = 872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval CI] ≤ 1.5) and seroconversion rate (SCR) difference (IIV3 – IIV4; upper bound of two-sided 95% CI ≤ 10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7 days postvaccination, AEs recorded for 28 days postvaccination, and serious AEs for 6 months postvaccination.ResultsIIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were ?1.1 (?4.5, 2.3), ?1.7 (?5.0, 1.7), ?3.2 (IIV3-YAM; ?7.4, 0.9), and ?1.6 (IIV3-VIC; ?5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%).ConclusionsIIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains not contained in IIV3 comparators. Safety/tolerability profiles were similar across vaccine groups.Funding: Seqirus; Clinicaltrials.gov: NCT02214225. |
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| Keywords: | Immunogenicity Inactivated Influenza vaccine Noninferiority Quadrivalent Safety AE"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"adverse event CI"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"confidence interval DSMB"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"Data and Safety Monitoring Board FAS"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"full analysis set GMFI"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"geometric mean fold increase GMT"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"geometric mean titer HI"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"hemagglutination inhibition IIV3"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"trivalent inactivated influenza vaccine IIV4"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"quadrivalent inactivated influenza vaccine LS"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"least square SAE"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"serious adverse event SCR"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"seroconversion rate SD"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"standard deviation SPR"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"seroprotection rate US"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"United States VIC"} {"#name":"keyword" "$":{"id":"k0190"} "$$":[{"#name":"text" "_":"Victoria YAM"} {"#name":"keyword" "$":{"id":"k0200"} "$$":[{"#name":"text" "_":"Yamagata |
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