Immunogenicity Trial of Egg- Versus Non-Egg-Based Influenza Vaccines Among HCP

Phase 4

Completed

Conditions: Influenza

Interventions: Biological: Flucelvax
Biological: Fluarix
Biological: Flublok
Biological: Fluzone High-Dose
Biological: Fluzone

Registration Number: NCT03722589

Lead Sponsor: Centers for Disease Control and Prevention

Brief Summary: This randomized, open-label trial will assess humoral and cell-mediated immune responses to cell culture-based and recombinant unadjuvanted quadrivalent influenza vaccines compared to conventional egg-based unadjuvanted quadrivalent standard dose (15µg of HA per strain) influenza vaccines among persons aged 18-64 years. The trial will be conducted at two sites in the United States during two influenza seasons (2018-19 and 2019-20). Stratified enrollment procedures will be used to enroll a mix of participants based on age.

Detailed Description: In year 1 of the trial (the 2018-19 Northern Hemisphere influenza season), eligible participants at each site will be randomized 2:2:1:1 to receive a single dose of cell culture-based vaccine (Flucelvax™ Quadrivalent by Seqirus, Inc., 15µg of HA per strain) versus recombinant vaccine (Flublok® Quadrivalent by Sanofi Pasteur, 45µg of HA per strain) versus one of two standard dose egg-based vaccines (Fluzone® Quadrivalent by Sanofi Pasteur, 15µg of HA per strain and Fluarix® Quadrivalent by GlaxoSmithKlein, 15µg of HA per strain) during August-September of 2018. All study vaccines are licensed for use in adults aged \>18 years in the United States. Participants will have blood collected just prior to vaccination and at approximately 28 days and 6 months post-vaccination (or at the end of influenza virus circulation as determined by available surveillance data) to evaluate humoral immune responses to vaccination.

In year 1, sites will aim to enroll 864 participants (432 per site) at the start of the 2018-19 season, including up to 200 participants (up to 100 per site) who will contribute additional blood at all study visits to evaluate cell-mediated immune responses to vaccination. Efforts will be made to retain participants enrolled in the first year of the study for both years of the study. Sites will also enroll additional participants at the start of the 2019-20 season to make up for participants who withdraw or are lost to follow-up prior to the start of the 2019-20 season. Both participants and study investigators will be aware of study arm assignments with the exception of laboratory investigators who will be blinded to study arm assignment until testing is completed, as appropriate.

In year 1 , relative efficacy of single doses of study vaccines will be assessed by comparing immunologic responses to vaccination among participants between study arms using Fluzone® Quadrivalent and Fluarix® Quadrivalent as the comparator groups for participants in the Flucelvax™ Quadrivalent or Flublok® Quadrivalent arms. In addition, the effect of frequency of prior vaccination during the preceding five years on immunologic responses to vaccine will be evaluated in subgroup analysis. Both humoral (influenza antibody) and cell-mediated (influenza- specific CD4 and CD8 T cell) immune responses will be evaluated.

In year 2 of the trial, (the 2019-20 Northern Hemisphere influenza season), participants from the first year of the trial who received Flucelvax™ Quadrivalent or Flublok® Quadrivalent will be randomized 1:1 to receive Flucelvax™ Quadrivalent or Flublok® Quadrivalent, and participants who received an egg-based standard-dose vaccine in year one (Fluzone® Quadrivalent or Fluarix Quadrivalent) will be randomized 1:1:1 to receive Flucelvax™ Quadrivalent , Flublok® Quadrivalent , or Fluzone® Quadrivalent. In addition, both sites will enroll additional participants in year 2 to achieve a total of 150 participants per site (including participants who continue from year one plus additional newly enrolled participants) who received egg-based standard dose influenza vaccine during the 2018-2019 influenza season and who will be randomized 1:1:1 to receive Flucelvax™ Quadrivalent, Flublok® Quadrivalent, or Fluzone® Quadrivalent in year two. The Kaiser Permanente Northwest site site will also enroll up to 80 new participants for a non-randomized study arm that will receive Fluzone® High-Dose. All study vaccines except Fluzone High-Dose are licensed for use in adults aged \>=18 years in the United States. Fluzone High-Dose is licensed for use in adults aged \>=64 years in the United States and will be used off-label in this trial. Participants will have blood collected just prior to vaccination and at approximately 28 days post-vaccination (or at the end of influenza virus circulation as determined by available surveillance data) to evaluate humoral immune responses to vaccination. Additional blood will be collected from a subset of participants pre-vaccination and at approximately 7 and 28 days post-vaccination to evaluate cell-mediated immune responses to vaccination.

In year 2, sites will aim to retain from year 1 or newly enroll 750 participants.

Deaths and/or adverse events were not monitored/assessed in any arms for any flu seasons

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 944

Inclusion Criteria

Healthcare personnel (HCP) who have direct contact with patients, including dentists and other dental health personnel
Enrolled in Scott & White Healthcare or Kaiser Permanente health network for at least one month
Aged 18-64 years for newly enrolled participants
Aged 18-65 years for participants who were originally enrolled in year one of the study and return for year 2
Available and willing to participate in study follow-up through the end of the 2019-2020 influenza season (i.e. at least approximately 18 months if enrolled during season 1 or 6 months if enrolled during season 2)
Received an egg-based standard dose influenza vaccine during the 2018-2019 influenza season (for participants enrolled for the first-time during year two)

Exclusion Criteria

Already received an influenza vaccine during the current influenza season
Previous hypersensitivity reaction to the study vaccines as reported by the subject
Received any vaccine in the 4 weeks prior to the first study visit or plans to receive a vaccine (other than influenza vaccine provided through the study protocol) in the 4 weeks following the first study visit
Currently participating in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication), or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive an experimental agent during participation in this study
Any condition that the principle investigator (PI) believes may interfere with successful completion of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Flucelvax (Cell-based)	Flucelvax	Flucelvax™ Quadrivalent by Seqirus, Inc., 15µg of HA per strain
Fluarix (Egg-based)	Fluarix	Fluarix® Quadrivalent by GlaxoSmithKlein, 15µg of HA per strain
Flublok (Recombinant)	Flublok	Flublok® Quadrivalent by Sanofi Pasteur, 45µg of HA per strain
Fluzone (Egg-based) High-Dose	Fluzone High-Dose	Fluzone® Trivalent High-Dose by Sanofi Pasteur, 60µg of HA per strain
Fluzone (Egg-based)	Fluzone	Fluzone® Quadrivalent by Sanofi Pasteur, 15µg of HA per strain

Primary Outcome Measures

Name	Time	Method
Microneutralization (MN) Assay Response to Cell-grown Influenza A/H3N2 - Seroconversion Rate (SCR)	28 days post-vaccination during year 2	MN responses to the cell-grown influenza A/H3N2 vaccine reference viruses for each study season at approximately 28 days post-vaccination, including by assessing SCR in the various vaccine arms defined as the proportion of participants with paired samples that achieved ≥ 4 fold rises comparing post- versus pre-vaccination titers, and post vaccination titers ≥ 40

Secondary Outcome Measures