Clinical Trial to Evaluate the Immunogenicity of an Adjuvanted Influenza Vaccine Among HCP

Study Overview
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Brief Summary
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This randomized, double-blinded trial will assess humoral immune responses to adjuvanted, egg-based quadrivalent influenza vaccines compared to standard dose, egg-based quadrivalent influenza vaccines among healthcare personnel (HCP). The trial will be conducted at two sites in Lima, Peru during 2022 and 2023.

Detailed Description
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The trial will be conducted at two hospital sites in Lima, Peru during 2022-2023 among HCP who were previously enrolled in the Cohort study of Influenza and other Respiratory Viruses among HCP in Peru (cohort size: approximately 1500 participants). The minimum number of participants to be enrolled is 248 in total (142 subjects per vaccine group), and the aim is to enroll approximately 800 participants (400 subjects per vaccine group). The study design is a randomized, double-blind vaccine trial. Eligible HCP at each site who consent to participate will be randomized 1:1 to receive either a single dose of adjuvanted egg-based quadrivalent influenza vaccine (AD, FLUAD Quadrivalent by Seqirus, 15 µg of hemagglutinin [HA] from each strain) or standard dose, egg-based quadrivalent influenza vaccine (SD, FluQuadri by Sanofi-Pasteur, 15 µg of HA from each strain). Participants will be invited to come to the study site to be screened for eligibility to participate in the clinical trial. After they consent to participate and sign informed consent form, participants will visit the site for medical assessment and vaccination. Additional brief medical adverse event assessments will be performed on days 3 and 7. Participants will be followed up to twice per week via SMS or phone calls to assess if they become sick with a respiratory event. In the event they become sick, they will be asked questions about their illness through an acute illness survey and a mid-turbinate nasal swab specimen will be collected and tested for influenza virus. Additional surveys will be administered on day 28 post-vaccination as well as at the end of the influenza season. Participants will have blood collected just prior to vaccination (Day 0) and at approximately 28 days and 6 months post-vaccination (or at the end of influenza virus circulation as determined by active surveillance data) to evaluate humoral immune responses to vaccination. After these specimens are tested, differences in seroconversion and seroprotection between AD and SD vaccination groups will be assessed. In addition, we multivariable modelling will be used to assess risk factors for poor immunogenicity and to assess possible effects of repeated vaccination. As an optional sub-study, indicators of cell-mediated immune (CMI) responses to influenza vaccination will be examined. This part of the study, which is optional to participants, will require collection of additional blood samples at prior to vaccination (Day 0) and at 7 and 28 days post-vaccination.

Official Title
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Randomized Controlled Trial, Double Blind, Phase III, to Evaluate the Immunogenicity of an Adjuvanted Influenza Vaccine Among Health Care Personnel (EDUCATE)

Conditions
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Influenza

Intervention / Treatment
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* Biological: FLUAD Quadrivalent
* Biological: FluQuadri


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old; Have participated in the healthcare personnel cohort study at Hospital Nacional Cayetano Heredia or Hospital Nacional Arzobispo Loayza during 2016-2021; Work at the facility full-time (≥30 hours per week); Have routine, direct, hands-on or face-to-face contact with patients (≤1 meter) as part of a typical work shift, including, but not limited to, physicians, nurses, respiratory therapists, physical therapists, unit clerks, radiograph technicians, medical assistants, and transporters; Work at the facility for ≥1 year prior to enrollment and planning to continue working at the facility for one year after enrollment; Willing to receive influenza vaccination (adjuvanted or standard dose); Women of childbearing age must complete the following criteria to be eligible: Have a negative urine pregnancy test performed by the study staff ≤24 hours preceding receipt of the vaccine; Be willing to use a reliable form of contraception approved by the Investigator for ≤2 months after receiving the vaccine. If they are not currently using an approved contraceptive, study staff will provide access to contraceptives; Must not be breastfeeding. Exclusion Criteria: Have received a vaccine against influenza during the 2022 influenza season (season of clinical trial); Have a severe, life-threatening allergy to influenza vaccines, eggs, or influenza vaccine components; Have a history of Guillain-Barre Syndrome or other autoimmune diseases; Received blood or blood products within 3 months of enrollment; Be pregnant, confirmed by rapid pregnancy test.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLUAD Quadrivalent<br>Participants administered a single dose of adjuvanted egg-based quadrivalent influenza vaccine (FLUAD Quadrivalent by Seqirus, 15 µg of HA from each strain). | Biological: FLUAD Quadrivalent<br>* 0.5 mL intramuscular dose of FLUAD Quadrivalent<br>|
| Active Comparator: FluQuadri<br>Participants administered a single dose of standard dose egg-based quadrivalent influenza vaccine (FluQuadri by Sanofi-Pasteur, 15 µg of HA from each strain). | Biological: FluQuadri<br>* 0.5 mL intramuscular dose of FluQuadri<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination inhibition (HI) geometric mean titers (GMT) pre- (Day 0) and post-vaccination (Day 28) of each vaccine reference virus | The geometric mean of antibody titers before and after a single dose of FLUAD Quadrivalent (adjuvanted dose, AD) vs. FluQuadri (standard dose, SD) as measured by HI assay for egg-grown influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata and cell-grown influenza B/Victoria vaccine reference viruses at approximately 28 days post-vaccination | 28 days post-vaccination | 
| HI GMT pre- (Day 0) and post-vaccination (6 months) | The geometric mean of antibody titers before and after a single dose of AD vs SD vaccine as measured by HI assay for egg-grown influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata and cell-grown influenza B/Victoria vaccine reference viruses at approximately 6 months post-vaccination | 6 months post-vaccination | 
| Geometric Mean Fold Rise (MFR) of each vaccine reference virus post-vaccination | The ratio of the post-vaccination (approximately 28 days) titer value to the pre-vaccination titer value for each vaccine reference virus (egg-grown influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata and cell-grown influenza B/Victoria viruses) following a single dose of AD vs. SD vaccine. | 28 days post-vaccination | 
| MFR of each vaccine reference virus post-vaccination | The ratio of the post-vaccination (approximately 6 months) titer value to the pre-vaccination titer value for each vaccine reference virus (egg-grown influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata and cell-grown influenza B/Victoria viruses) following a single dose of AD vs. SD vaccine. | 6 months post-vaccination | 
| Seroconversion rate (SCR) of each vaccine reference virus post-vaccination | The proportion of participants with paired samples that achieved ≥4-fold rises comparing post- (approximately 28 days) versus pre-vaccination titers, and post vaccination titers ≥40 for each vaccine reference virus (egg-grown influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata and cell-grown influenza B/Victoria viruses) following a single dose of AD vs. SD vaccine. | 28 days post-vaccination | 
| SCR of each vaccine reference virus post-vaccination | The proportion of participants with paired samples that achieved ≥4-fold rises comparing post- (approximately 6 months) versus pre-vaccination titers, and post-vaccination titers ≥40 for each vaccine reference virus (egg-grown influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata and cell-grown influenza B/Victoria viruses) following a single dose of AD vs. SD vaccine. | 6 months post-vaccination |