title: Immunologic non-inferiority of a newly licensed inactivated trivalent influenza vaccine versus an established vaccine: a randomized study in US adults.
abstract: A trivalent inactivated influenza vaccine (Fluarix (™) , GlaxoSmithKline Biologicals) was licensed under US accelerated approval regulations. We performed a randomized, observer-blind, post-approval study to demonstrate its immunological non-inferiority versus an established US-licensed vaccine (primary endpoint). Adult (including elderly) subjects received a single injection of newly-licensed vaccine (n = 923) or established vaccine (n = 922). Serum hemagglutination-inhibition titers were determined pre-vaccination and 21-28 days after vaccination. Non-inferiority was assessed by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI] ≤ 1.5) and difference in seroconversion rate (upper 95% CI ≤ 0.1) for all three vaccine strains. Safety was monitored for 6 months. The newly-licensed vaccine was non-inferior to the established vaccine in all subjects (≥ 18 years) and in elderly subjects (≥ 65 years). Adjusted GMT ratios (established/newly-licensed) against the H1N1, H3N2 and B strains were 0.65 (95% CI: 0.58, 0.73), 0.93 (0.83, 1.04) and 1.13 (1.03, 1.25) for all subjects and 0.75 (0.67, 0.85), 0.95 (0.82, 1.09) and 1.13 (1.00, 1.27) for elderly subjects. Corresponding values for the differences in seroconversion rate (established minus newly-licensed) were -0.12 (-0.16, -0.07), -0.02 (-0.06, 0.03) and 0.01 (-0.04, 0.06) for all subjects and -0.11 (-0.16, -0.05), -0.02 (-0.07, 0.04) and 0.02 (-0.04, 0.08) for elderly subjects. The most common adverse events with both vaccines were injection site pain, fatigue and headache, and no serious adverse events or deaths were considered related; there were no clinically relevant differences between the vaccines. In conclusion, the newly-licensed vaccine was well tolerated and immunologically non-inferior to the established vaccine for all three vaccine strains in the whole population and the elderly.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA. campbellj@ug.cdc.gov
authors.forename: James D
authors.initials: JD
authors.lastname: Campbell
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Chambers
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Brady
authors.forename: Michael C
authors.initials: MC
authors.lastname: Caldwell
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Bennett
authors.forename: Marc A
authors.initials: MA
authors.lastname: Fourneau
authors.forename: Varsha K
authors.initials: VK
authors.lastname: Jain
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014481:United States; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C510903:fluarix