Immunogenicity Trial of Recombinant Influenza Vaccine Among HCP in Israel

Study Overview
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Brief Summary
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This randomized, open-label, active-controlled trial will assess humoral immune responses to a single dose of 2019-20 recombinant hemagglutinin quadrivalent influenza vaccines (RIV4) compared with standard egg-based unadjuvanted quadrivalent influenza vaccines (IIV4) among healthcare personnel (HCP) vaccinated during the previous 2018-19 season with IIV4. The trial will be conducted at two hospital sites in Israel during the 2019-20 influenza season among HCP who were enrolled in the Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI).

Detailed Description
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This is a randomized, open-label study design. Starting in July 2019, approximately 550 to 700 HCP from two hospitals (275-350 per hospital site) in Israel will be enrolled. Following completion of a written consent form, participants will complete an enrollment survey and grant permission for review of information collected during the SHIRI study, including vaccination status and immune response during the SHIRI study years. Participants will complete an enrollment survey and grant permission to include and integrate information collected during the SHIRI study into the current study's data, including health history, influenza vaccination history, and immune response to vaccination during the SHIRI study years. HCP will be randomly assigned 1:1 to receive a single dose of IIV4 licensed in Israel (expected to be Vaxigrip® Quadrivalent, 15µg of HA per strain) or RIV4 (Flublok® Quadrivalent by Sanofi Pasteur, 45µg of HA per strain) during August-October of 2019. Adverse events following vaccination will be monitored and documented. Blood specimens will be collected prior to vaccination and approximately 28 days after to evaluate immune responses to vaccination. Eligible HCP who were already vaccinated with Vaxigrip, the vaccine that is routinely available in Israel, at the time they are approached to join the study, will be invited to join the study as part of the Vaxigrip arm. Like randomized participants, participants who were vaccinated with Vaxigrip outside the study will complete a written consent form, an enrollment survey and grant permission for review of information collected during the SHIRI study, including vaccination status and immune response during the SHIRI study years. As part of the consent form, participants will record the estimated date that they received the vaccine, and the location, and will authorize study staff to verify the date of current-year Vaxigrip vaccination in the Clalit EMR and with the hospital vaccination staff. Participants will complete an enrollment survey and grant permission to include and integrate information collected during the SHIRI study into the current study's data, including health history, influenza vaccination history, and immune response to vaccination during the SHIRI study years. Blood specimens will be collected approximately 28 days after to evaluate immune responses to vaccination.

Official Title
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Randomized Comparison of the Immunogenicity of Recombinant and Egg-based Influenza Vaccines Among Healthcare Personnel in Israel

Conditions
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Influenza

Intervention / Treatment
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* Biological: Flublok™ Quadrivalent by Sanofi, Inc.
* Biological: VaxigripTetra™ by Sanofi, Inc.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 Current member of Clalit Health Services Consent to randomized receipt of influenza vaccination with either RIV4 or IIV4, or, if already vaccinated in the current year outside of the study, consent to receive a post-vaccination blood draw Participated in the SHIRI study and received influenza vaccination during the 2018-19 influenza season (Group 1) Participated in any year of the SHIRI study, not vaccinated in 2018-2019, but vaccinated in at least one study year (Group 1 supplemental) Participated in the SHIRI study during all three years, regardless of vaccination status (Group 1 supplemental) Participated in any year of the SHIRI study and had PCR-confirmed influenza virus infection during any of the three study years (Group 2) Exclusion Criteria: Already received an influenza vaccine during the current influenza season Not willing or able to get the flu vaccines being used in this study; Previous hypersensitivity reaction to the study vaccines, or any vaccine, as reported by the subject Received any non-influenza vaccine (e.g., Hepatitis B or other vaccine recommended for HCP) in the 4 weeks prior to the first study visit or plans to receive a vaccine 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 or employment status that the potential participant or local study site principle investigator (PI) believes may interfere with successful completion of the study prior to December 2019, including being currently pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RIV4 (Flublok Quadrivalent)<br>Flublok® Quadrivalent by Sanofi Pasteur, 45µg of HA per strain | Biological: Flublok™ Quadrivalent by Sanofi, Inc.<br>* 0.5 mL intramuscular dose of Flublok<br>|
| Active Comparator: IIV4 (Vaxigrip Quadrivalent)<br>VaxigripTetra™ by Sanofi, Inc., 15µg of HA per strain, egg-based | Biological: VaxigripTetra™ by Sanofi, Inc.<br>* 0.5 mL intramuscular dose of Vaxigrip<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-vaccination Geometric Mean Titer Against Influenza Virus A/H1N1 | The geometric mean of antibody titers following a single dose of RIV4 or IIV4 as measured by hemagglutination inhibition (HI) for influenza virus A/H1N1 | Day 28 days after vaccination | 
| Geometric Mean Titer Ratio (GMR) Against Influenza Virus A/H1N1 | The ratio of the pre- vs. post-vaccination titer against influenza virus A/H1N1 following a single dose of RIV4 versus IIV4. | 0 to 28 days after vaccination | 
| Post-vaccination Geometric Mean Titer Against Egg-grown Influenza Virus A/H3N2 | The geometric mean of antibody titers following a single dose of RIV4 or IIV4 as measured by hemagglutination inhibition (HI) for egg-grown influenza virus A/H3N2 | Day 28 days after vaccination | 
| Geometric Mean Titer Ratio (GMR) Against Egg-grown Influenza Virus A/H3N2 | The ratio of the pre- vs. post-vaccination titer against egg-grown influenza virus A/H3N2 following a single dose of RIV4 versus IIV4. | 0 to 28 days after vaccination | 
| Post-vaccination GMT Against Cell-grown Influenza Virus A/H3N2 | The geometric mean of antibody titers following a single dose of RIV4 or IIV4 as measured by hemagglutination inhibition (HI) for cell-grown influenza virus A/H3N2 | Day 28 days after vaccination | 
| Geometric Mean Titer Ratio (GMR) Against Cell-grown Influenza Virus A/H3N2 | The ratio of the pre- vs. post-vaccination titer against cell-grown influenza virus A/H3N2 following a single dose of RIV4 versus IIV4. | 0 to 28 days after vaccination | 
| Post-vaccination Geometric Mean Titer Against Influenza B(Victoria) | The geometric mean of antibody titers following a single dose of RIV4 or IIV4 as measured by hemagglutination inhibition (HI) for Influenza B(Victoria) | Day 28 days after vaccination | 
| Geometric Mean Titer Ratio (GMR) Against Influenza B(Victoria) | The ratio of the pre- vs. post-vaccination titer against Influenza B(Victoria) following a single dose of RIV4 versus IIV4. | 0 to 28 days after vaccination | 
| Post-vaccination Geometric Mean Titer Against Influenza B(Yamagata) | The geometric mean of antibody titers following a single dose of RIV4 or IIV4 as measured by hemagglutination inhibition (HI) for Influenza B(Yamagata) | Day 28 days after vaccination | 
| Geometric Mean Titer Ratio (GMR) Against Influenza B(Yamagata) | The ratio of the pre- vs. post-vaccination titer against Influenza B(Yamagata) following a single dose of RIV4 versus IIV4. | 0 to 28 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Healthcare personnel, Immunogenicity, Repeat vaccination