Immunogenicity and Safety of Fluzone® Quadrivalent, Southern Hemisphere 2015 Formulation (Intramuscular Route)

Study Overview
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Brief Summary
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The aim of the study was to assess the immunogenicity and safety of Fluzone Quadrivalent influenza vaccine Southern Hemisphere (SH) 2015 formulation in participants aged 18 to 60 years as well as in participants 61 years or older. The objectives were: To evaluate the compliance, in terms of immunogenicity, of the Fluzone Quadrivalent influenza vaccine SH 2015 formulation with the requirements of the European Medicines Agency (EMA) Note for guidance (NfG) CPMP/BWP/214/96 To describe the immunogenicity of the Fluzone Quadrivalent influenza vaccine SH 2015 formulation To describe the safety of the Fluzone Quadrivalent influenza vaccine SH 2015 formulation

Detailed Description
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All participants received 1 intramuscular dose of Fluzone Quadrivalent vaccine at the first visit. Immunogenicity and safety were assessed in all participants. Adverse events (AE) defined in EMA NfG CPMP/BWP/214/96 were collected for 3 days after vaccination, solicited AE pre-listed in the diary card were collected for 7 days after vaccination, unsolicited AEs were collected for 21 days after vaccination, and serious adverse event (SAE) information was collected throughout the study.

Official Title
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Immunogenicity and Safety of Fluzone® Quadrivalent, Southern Hemisphere 2015 Formulation (Intramuscular Route)

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluzone Quadrivalent Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants were >= 18 years of age on the day of inclusion . Informed consent form had been signed and dated. Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: History of serious adverse reaction to any influenza vaccine. Receipt of any vaccine within 30 days before receiving study vaccine, or plans to receive another vaccine before Visit 2. Participation in another interventional clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 30 days preceding the first study vaccination or during the course of the study. Self-reported thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator. Vaccination against influenza in the previous 12 months if administered in the context of a clinical trial or a flu vaccination campaign. Known systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to the vaccine or to a vaccine containing any of the same substances (the complete list of vaccine components is included in the Prescribing Information) . Receipt of immune globulins, blood, or blood-derived products in the past 3 months. Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator. Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 3 weeks after vaccination). Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine. Personal history of Guillain-Barré syndrome. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion . Known seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, as reported by the participant. (No screening procedures were implemented.) Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. Current alcohol or drug addiction that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures. Moderate or severe acute illness/infection (according to Investigator judgment) or febrile illness (temperature ≥ 38°C) on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. Identified as an Investigator or employee of an Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e. parent, spouse, natural or adopted child) of an Investigator or employee with direct involvement in the proposed study.

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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants were enrolled in two age groups: participants aged 18 to 60 years and participants aged 61 years or older.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years<br>Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0. | Biological: Fluzone Quadrivalent Influenza Vaccine<br>* 0.5-mL, Intramuscular, SH 2015 formulation<br>* Other names: Fluzone® Quadrivalent Influenza Vaccine;|
| Experimental: Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older<br>Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0. | Biological: Fluzone Quadrivalent Influenza Vaccine<br>* 0.5-mL, Intramuscular, SH 2015 formulation<br>* Other names: Fluzone® Quadrivalent Influenza Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) | Anti-influenza antibodies were measured using hemagglutination-inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. Seroprotection was defined as an antibody titer >=40 (1/dilution [dil]) at pre-vaccination and post-vaccination. | Day 0 (pre-vaccination) and Day 21 (post-vaccination) | 
| Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) | Anti-influenza antibodies were measured using a HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. | Day 0 (pre-vaccination) and Day 21 (post-vaccination) | 
| Geometric Mean Titer Ratio (GMTR) of Influenza Vaccine Antibodies | Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. Geometric mean titer ratio was calculated as geometric mean titer at Day 21 divided by geometric mean titer at day 0 for each specified group. | Day 0 (pre-vaccination), Day 21 (Post-vaccination) | 
| Number of Participants With Seroconversion or Significant Increase to Influenza Vaccine Antigens | Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. Seroconversion was defined as participants with a pre-vaccination titer <10 (1/dil) and a post-vaccination titer >= 40 (1/dil). Significant increase was defined as a pre-vaccination titer >= 10 (1/dil) and >= 4-fold increase in post vaccination titer. Number of participants with seroconversion or significant increase to Influenza vaccine antigens were reported. | 21 days post-vaccination | 
| Number of Participants Reporting Solicited Injection Site and Systemic Reactions | A solicited reaction is an adverse event (AE) that is pre-listed in the electronic case report form (eCRF) and considered to be related to vaccination. Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significantly prevent daily activity), erythema, swelling, induration, and ecchymosis (Grade 1: >=25 mm to <= 50 mm, Grade 2: >=51 to <=100 mm, Grade 3: > 100 mm). Solicited systemic reactions: Fever (Grade 1: >=38.0 degree Celsius (°C) to <=38.4°C, Grade 2: >=38.5°C to <=38.9 °C, Grade 3: >= 39°C), headache, malaise, myalgia, and shivering (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significantly prevent daily activity). Number of participants with any of the Grade 1, 2 or 3 solicited injection-site and systemic reactions and Grade 3 solicited injection-site and systemic reactions were reported. | Within 7 days after vaccination | 
| Number of Participants Reporting Solicited Reactions Listed in the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance | Solicited reactions listed in the CHMP note for guidance included: injection site induration >= 50 mm for at least 4 consecutive days , injection site ecchymosis, temperature > 38.0°C for at least one day, malaise, and shivering. | Within 3 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Influenza virus vaccine, Fluzone® Quadrivalent Influenza Vaccine (No Preservative)