Safety and Immunogenicity of the 2015-2016 Formulation of Fluzone® Quadrivalent (Influenza Vaccine) Among Healthy Children

Study Overview
=================
Brief Summary
-----------------
The study will evaluate the safety and immunogenicity of the 2015-2016 formulation of Fluzone Quadrivalent vaccine, administered in a 1- or 2-dose schedule, in accordance with the Advisory Committee on Immunization Practices (ACIP) recommendations, in children 6 months to < 9 years of age. Objective: To describe the safety of the 2015-2016 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. Observational objectives: To describe the immunogenicity of the 2015-2016 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 available sera from each subject to 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 FDA to support formulation recommendations for subsequent influenza vaccines.

Detailed Description
-----------------
Study 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. Participants aged 6 months to < 36 months will receive a 0.25 mL dose of Fluzone Quadrivalent vaccine and those aged 3 years to < 9 years will receive a 0.5 mL dose of Fluzone Quadrivalent vaccine. Participants, for whom 2 doses of influenza vaccine are recommended per ACIP guidance, will receive a second dose of Fluzone Quadrivalent vaccine during Visit 2 (28 days after Visit 1). 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 (SAE) information will be collected from Visit 1 to Visit 2 or Visit 3, as appropriate. 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 (HAI) technique. For each influenza vaccine strain, pre- and post-vaccination geometric mean titers (GMTs) will be calculated.

Official Title
-----------------
Safety and Immunogenicity of the 2015-2016 Formulation of Fluzone® Quadrivalent (Influenza Vaccine) Among Healthy Children

Conditions
-----------------
Influenza

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is 6 months to < 9 years of age on the day of first study vaccination (study product administration) Subject and parent/guardian 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 guardian for subjects 6 months to < 9 years of age 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 2015-2016 influenza vaccine 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 Thrombocytopenia, which may be a contraindication for intramuscular 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, 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
-----------------
Minimum Age: 6 Months
Maximum Age: 8 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: Study Group 1<br>Participants at 6 months to < 36 months age at enrollment | Biological: Fluzone® Quadrivalent Influenza Vaccine, No Preservative<br>* 0.25 mL, Intramuscular (Pediatric Dose, 2015 2016 formulation)<br>* Other names: Fluzone® Quadrivalent, No Preservative;|
| Experimental: Study Group 2<br>Participants at 3 years to < 9 years age at enrollment | Biological: Fluzone® Quadrivalent Influenza Vaccine, No Preservative<br>* 0.5 mL, Intramuscular (2015 2016 formulation)<br>* Other names: Fluzone® Quadrivalent, No Preservative;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. | Solicited injection-site reactions for 6 to < 36 months: Tenderness, Erythema, and Swelling. For 3 to < 9 years: Pain, Erythema, and Swelling. Solicited systemic reactions for 6 to < 36 months: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. For 3 to < 9 years: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 for 6 to < 36 months: Tenderness, Cries when injected limb is moved; Erythema and Swelling, ≥ 50 mm; Vomiting, 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability, Inconsolable. Grade 3 for 3 to < 9 years: Pain, Incapacitating; Erythema and Swelling, ≥ 50 mm; Fever, ≥ 39.0°C; Headache, Malaise, and Myalgia, prevents daily activity. | Day 0 up to Day 7 post any vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. | Day 0 (pre-vaccination) and 28 days post-last vaccination | 
| Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Seroprotection was defined as a pre-vaccination or post-vaccination influenza antibody titer of ≥ 1:40 (1/dilutions). | Day 0 (pre-vaccination) and 28 days post-last vaccination | 
| Number of Participants Who Achieved Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-final vaccination titer. | 28 days post-last vaccination | 
| Geometric Mean Titer Ratios of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Geometric mean of titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer ratios | Day 0 (pre-vaccination) and 28 days post-last vaccination | 

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