Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent Influenza Virus Vaccine

Study Overview
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Brief Summary
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The aim of this study is to evaluate the safety and immunogenicity of Fluzone® Quadrivalent vaccine in participants aged 6 months to < 9 years at enrollment, divided into 2 age strata (6 months to < 36 months and 3 years to < 9 years) Primary Objective: To describe the safety of the 2013-2014 formulation of Fluzone Quadrivalent vaccine, administered in a 1- or 2-dose schedule, in accordance with Advisory Committee on Immunization Practices (ACIP) recommendations, in children 6 months to < 9 years of age. Observational Objectives: To describe the immunogenicity of the 2013-2014 formulation of Fluzone Quadrivalent vaccine, administered in a 1- or 2-dose schedule in accordance with ACIP recommendations, in children 6 months to < 9 years of age. To submit sera from subjects to the Center for Biologics Evaluation and Research (CBER) for further analysis by the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) to support formulation recommendations for subsequent influenza vaccines.

Detailed Description
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Participants will be assigned to the appropriate age group (6 months to < 36 months of age or 3 years to < 9 years of age) based on the subject's age at the time of enrollment. Solicited adverse event (AE) information will be collected for 7 days after each vaccination, unsolicited AE information will be collected from Visit 1 to Visit 2, or to Visit 3 for those subjects receiving 2 doses. Serious adverse event information will be collected from Visit 1 to Visit 2, or Visit 3 for those subjects receiving 2 doses. Immunogenicity will be evaluated in all subjects prior to vaccination on Day 0 (Visit 1) and at Day 28 after the final vaccination using the hemagglutination inhibition technique. For each influenza vaccine strain, pre- and post-vaccination geometric mean titers will be calculated.

Official Title
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Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent Influenza Virus Vaccine (2013-2014 Formulation)

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative
* Biological: Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is 6 months to < 9 years of age on the day of first study vaccination (study product administration) Subject and parent/legally acceptable representative are willing and able to attend scheduled visits and to comply with the study procedures during the entire duration of the study Assent form has been signed and dated by subjects 7 to < 9 years of age, and informed consent form has been signed and dated by parent(s) or another legally acceptable representative For subjects 6 months to < 12 months of age, born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg (5.5 lbs.) Exclusion Criteria: Known systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone Quadrivalent vaccine or to a vaccine containing any of the same substances (the complete list of vaccine components is included in the Prescribing Information) 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 for subjects receiving 1 dose of influenza vaccine or Visit 3 for subjects receiving 2 doses of influenza vaccine 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 unless no intervention for the other study occurred within the 30 days prior to the first study vaccination and none are planned before the subject would complete safety surveillance for the present study Prior vaccination with any formulation of 2013-2014 influenza vaccine Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for intramuscular (IM) vaccination, at the discretion of the Investigator Thrombocytopenia, which may be a contraindication for IM vaccination, at the discretion of the Investigator Any condition that in the opinion of the Investigator would pose a health risk to the subject 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) Personal history of clinically significant developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder 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 Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 100.4°F]). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided Receipt of immune globulins, blood, or blood-derived products in the past 3 months Identified as a natural or adopted child of the Investigator or an employee with direct involvement in the proposed study

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 8 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Age 6 Months to <36 Months (Study Group 1)<br>Participants at 6 months to < 36 months of age at enrollment | Biological: Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative<br>* 0.25 mL, Intramuscular (Pediatric Dose, 2013-2014 formulation)<br>* Other names: Fluzone® Quadrivalent, No Preservative;|
| Experimental: Age 3 Years to <9 Years Group (Study Group 2)<br>Participants at 3 years to < 9 years of age at enrollment | Biological: Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative<br>* 0.5 mL, Intramuscular (2013-2014 formulation)<br>* Other names: Fluzone® Quadrivalent, No Preservative;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine | Solicited injection-site reactions (6 months to <36 months of age): Tenderness, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite loss, and Irritability. Grade 3: Tenderness, Cries if limb is moved; Erythema and Swelling, ≥50 mm; Fever, >103.1ºF; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Drowsiness, Sleeping most of the time; Appetite lost, Refuses ≥3 feeds/meals or refuses most feeds/meals; Irritability, Inconsolable. Solicited injection-site reactions (3 years to < 9 years of age): Pain, Erythema, and Swelling. Systemic Reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥50 mm; Fever, ≥102.1ºF; Headache, Malaise, and Myalgia, Significant, prevents daily activity. | Day 0 up to Day 7 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine | Influenza virus antibodies were measured using a hemagglutination inhibition (HAI) assay. | Day 0 (pre-vaccination) and Day 28 after final vaccination | 
| Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine | Influenza virus antibodies were measured using an HAI assay. Seroprotection was defined as a titer ≥40 (1/dilution). | Day 0 (pre-vaccination) and Day 28 after final vaccination | 
| Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine | Influenza virus antibodies were measured using an HAI assay. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination titer. | Day 0 (pre-vaccination) and Day 28 after final vaccination | 
| Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine | Influenza virus antibodies were measured using an HAI assay. Geometric mean titer ratios are the geometric means of the individual post-vaccination/pre-vaccination titer ratios for each hemagglutinin antigen contained in the vaccine. | Day 0 (pre-vaccination) and Day 28 after final 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)