FLUZONE HIGH-DOSE QUADRIVALENT Rx

Immunogenicity of Fluzone High-Dose Quadrivalent in Adults 65 Years of Age and Older

• Study 1 (NCT03282240, see http://clinicaltrials.gov) was a randomized, active-controlled, modified double-blind trial which compared the safety and immunogenicity of Fluzone High-Dose Quadrivalent to Fluzone High-Dose in 2670 adults 65 years of age and older conducted in the US. 

• Patients were randomly assigned 4:1:1 to receive 1 dose of either Fluzone High-Dose Quadrivalent or 1 of 2 formulations of Fluzone High-Dose (one formulation contained a B strain of the Victoria lineage [TIV-HD1] while the other contained a B strain of the Yamagata lineage [TIV-HD2]). The objective was to demonstrate noninferiority of Fluzone High-Dose Quadrivalent to Fluzone High-Dose, as assessed by HAI geometric mean antibody titers (GMTs) at Day 28 and seroconversion rates.

• Fluzone High-Dose Quadrivalent was as immunogenic as Fluzone High-Dose for GMTs and seroconversion rates for the common influenza strains. Fluzone High-Dose Quadrivalent induced a superior immune response, based on a pre-specified superiority criterion, with respect to the additional B strain than the immune response induced by Fluzone High-Dose formulation that did not contain the additional B strain.

Efficacy of Fluzone High-Dose in Adults 65 Years of Age and Older

• The efficacy of Fluzone High-Dose (trivalent formulation) is relevant to Fluzone High-Dose Quadrivalent.

• Study 2 (NCT01427309) was a multi-center, double-blind, post-licensure efficacy trial conducted in the U.S. and Canada in which adults 65 years of age and older were randomized (1:1) to receive either Fluzone High-Dose or Fluzone.

• The primary endpoint of the study was the occurrence of laboratory-confirmed influenza (as determined by culture or polymerase chain reaction) caused by any influenza viral type/subtype in association with influenza-like illness (ILI), defined as the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrent with at least one of the following systemic signs or symptoms: temperature >99.0°F, chills, tiredness, headaches or myalgia.

• The relative efficacy of Fluzone High-Dose against laboratory-confirmed influenza regardless of similarity to the vaccine components was as followed:

• Any type/subtype: 24.2% (95% CI, 9.7-36.5)

• Influenza A: 23.6% (95% CI, 7.4-37.1)

• A (H1N1): 11% (95% CI, -159.9, 70.1)

• A (H3N2): 22.9% (95% CI, 5.4-37.2)

• Influenza B: 27.4% (95% CI, -13.1, 53.8)

• The efficacy of Fluzone High-Dose relative to Fluzone was 51.1% (95% CI: 16.8; 72.0) for the secondary endpoint, which was the occurrence of culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations in associated with a modified CDC-defined ILI.