Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children

Study Overview
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Brief Summary
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The aim of the study was to describe the safety and immunogenicity of a 0.5-mL dose (15 μg hemagglutinin [HA] per strain) of Fluzone Quadrivalent vaccine in children 6 to <36 months of age. Primary objective: To compare the rate of any fever (temperature ≥100.4 degrees Fahrenheit [38.0 degrees Celsius) following a 0.5-mL dose of Fluzone Quadrivalent vaccine to that following a 0.25-mL dose of Fluzone Quadrivalent vaccine during the 7 days after either vaccination (Dose 1 and Dose 2 combined) in participants 6 to < 36 months of age. Secondary objective: To compare antibody responses induced by a 0.5-mL dose of Fluzone Quadrivalent vaccine to those induced by a 0.25-mL dose of Fluzone Quadrivalent vaccine as assessed by geometric mean titer (GMT) ratios and seroconversion rate differences after the final vaccination in participants 6 to < 36 months of age. Other objectives: To describe the safety of 2 different dose levels of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in participants 6 to < 36 months of age. To describe the immunogenicity of 2 different dose levels of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in participants 6 months to < 36 months of age. To submit available sera from approximately 30 participants to the Center for Biologics Evaluation and Research for further analysis by the World Health Organization, the Centers for Disease Control and Prevention, and the FDA to support formulation recommendations for subsequent influenza vaccines.

Detailed Description
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All participants received 1 intramuscular dose of Fluzone Quadrivalent vaccine during Visit 1. For participants, for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of Fluzone Quadrivalent vaccine (of the same volume as the first dose) was administered during Visit 2 (28 days after Visit 1). Solicited adverse event (AE) information was collected for 7 days after each vaccination, unsolicited AE information was collected from Visit 1 to Visit 2 or to Visit 3 for participants receiving 2 doses of study vaccine. Serious adverse event (SAE) information was collected for 28 days after each vaccination. Immunogenicity was evaluated in a planned subset of 1600 randomly selected participants prior to vaccination on Day 0 (Visit 1) and at Day 28 after the final vaccination.

Official Title
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Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children 6 to < 36 Months of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluzone Quadrivalent vaccine, No Preservative
* Biological: Fluzone Quadrivalent vaccine, No Preservative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 6 to < 36 months of age on the day of first study vaccination (study product administration). Born at full term of pregnancy (≥37 weeks) and/or with a birth weight ≥2.5 kg. Note: This inclusion criterion only applies to participants 6 to <12 months of age on the day of the first study visit. Informed consent form has been signed and dated by the parent(s) or guardian(s). Participant and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Participation at the time of study enrollment (or in the 30 days preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. Receipt of any vaccine in the 30 days preceding the first trial vaccination, or planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine. Previous vaccination against influenza (in the 2016-2017 season) with either the trial vaccine or another vaccine. Receipt of immune globulins, blood, or blood-derived products in the past 3 months. 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). Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances. Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion. Moderate or severe acute illness/infection (according to Investigator judgment) on the day of planned vaccination or febrile illness (temperature ≥100.4 degrees Fahrenheit [38.0 degrees Celsius]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. Identified as a natural or adopted child of either the Investigator or an employee with direct involvement in the proposed study. History of serious adverse reactions to any influenza vaccine. Personal history of Guillain-Barré syndrome. 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 clinically significant developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder. Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fluzone Quadrivalent Vaccine, 0.25-mL<br>Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28. | Biological: Fluzone Quadrivalent vaccine, No Preservative<br>* 0.25-mL (Pediatric Dose), Intramuscular (2016-2017 formulation)<br>* Other names: Fluzone® Quadrivalent Influenza Vaccine;|
| Experimental: Fluzone Quadrivalent Vaccine, 0.5-mL<br>Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28. | Biological: Fluzone Quadrivalent vaccine, No Preservative<br>* 0.5-mL, Intramuscular (2016-2017 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 |
| --- | --- | --- |
| Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine | Fever rate was defined as percentage of participants with fever (temperature >=100.4 degrees Fahrenheit [38.0 degrees Celsius]) following vaccination with Fluzone Quadrivalent vaccine. | Within 7 days after any vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. | 28 days post-final vaccination | 
| Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) 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. SCR was defined as percentage of participants with either a pre-vaccination titer <10 (1/dil) and a post-final vaccination titer >=40 (1/dil), or a pre-vaccination titer >=10 (1/dil) and at least a four-fold increase in post-final vaccination titer. | 28 days post-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)