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

NCT03722589 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 7179
• Study Type: interventional
• Target: 944
• Locations: 1 country
• Sites: 2

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.

Conditions

Influenza

Outcome Measures

Primary Outcomes (2)

• Microneutralization (MN) Assay Response to Cell-grown Influenza A/H3N2 - Seroconversion Rate (SCR)

  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

  28 days post-vaccination during year 1

• Microneutralization (MN) Assay Response to Cell-grown Influenza A/H3N2 - Seroconversion Rate (SCR)

  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

  28 days post-vaccination during year 2

Study Arms (5)

Flublok (Recombinant)

ACTIVE COMPARATOR

Flublok® Quadrivalent by Sanofi Pasteur, 45µg of HA per strain

Biological: Flublok

Flucelvax (Cell-based)

ACTIVE COMPARATOR

Flucelvax™ Quadrivalent by Seqirus, Inc., 15µg of HA per strain

Biological: Flucelvax

Fluarix (Egg-based)

ACTIVE COMPARATOR

Fluarix® Quadrivalent by GlaxoSmithKlein, 15µg of HA per strain

Biological: Fluarix

Fluzone (Egg-based)

ACTIVE COMPARATOR

Fluzone® Quadrivalent by Sanofi Pasteur, 15µg of HA per strain

Biological: Fluzone

Fluzone (Egg-based) High-Dose

ACTIVE COMPARATOR

Fluzone® Trivalent High-Dose by Sanofi Pasteur, 60µg of HA per strain

Biological: Fluzone High-Dose

Interventions

Flublok BIOLOGICAL

0.5 mL intramuscular dose of Flublok

Flublok (Recombinant)

Flucelvax BIOLOGICAL

0.5 mL intramuscular dose of Flucelvax

Flucelvax (Cell-based)

Fluarix BIOLOGICAL

0.5 mL intramuscular dose of Fluarix

Fluarix (Egg-based)

Fluzone BIOLOGICAL

0.5 mL intramuscular dose of Fluzone

Fluzone (Egg-based)

Fluzone High-Dose BIOLOGICAL

0.5 mL intramuscular dose of Fluzone

Fluzone (Egg-based) High-Dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Baylor Scott and White Health: collaborator
• Kaiser Permanente: collaborator
• Abt Associates: collaborator

Study Sites (2)

Kaiser Permanente Northwest

Portland, Oregon, 97227, United States

Location

Baylor Scott and White Health

Temple, Texas, 76543, United States

Location

Related Publications (3)

• Liu F, Gross FL, Joshi S, Gaglani M, Naleway AL, Murthy K, Groom HC, Wesley MG, Edwards LJ, Grant L, Kim SS, Sambhara S, Gangappa S, Tumpey T, Thompson MG, Fry AM, Flannery B, Dawood FS, Levine MZ. Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines. Nat Commun. 2024 Jan 4;15(1):254. doi: 10.1038/s41467-023-44551-x.

  PMID: 38177116 DERIVED

• Gaglani M, Kim SS, Naleway AL, Levine MZ, Edwards L, Murthy K, Dunnigan K, Zunie T, Groom H, Ball S, Jeddy Z, Hunt D, Wesley MG, Sambhara S, Gangappa S, Grant L, Cao W, Gross FL, Mishina M, Fry AM, Thompson MG, Dawood FS, Flannery B. Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial. Clin Infect Dis. 2023 Feb 8;76(3):e1168-e1176. doi: 10.1093/cid/ciac683.

  PMID: 36031405 DERIVED

• Dawood FS, Naleway AL, Flannery B, Levine MZ, Murthy K, Sambhara S, Gangappa S, Edwards L, Ball S, Grant L, Belongia E, Bounds K, Cao W, Gross FL, Groom H, Fry AM, Rentz Hunt D, Jeddy Z, Mishina M, Kim SS, Wesley MG, Spencer S, Thompson MG, Gaglani M. Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized Open-Label Trial. Clin Infect Dis. 2021 Dec 6;73(11):1973-1981. doi: 10.1093/cid/ciab566.

  PMID: 34245243 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

FluBlok; Influenza Vaccines; fluarix; Fluzone High-Dose

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Fatimah Dawood, Medical Officer
• Organization: Centers for Disease Control and Prevention

hgj0@cdc.gov

404-639-0431

Study Officials

• Fatimah Dawood, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

• Brendan Flannery, PhD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 29, 2018
• Study Start: September 12, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: July 22, 2024
• Results First Posted: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study period

Locations

US (2)