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

Phase 4

Completed

Conditions: Influenza

Interventions: Biological: Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative

Registration Number: NCT01946425

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Age 6 Months to <36 Months (Study Group 1)	Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative	Participants at 6 months to \< 36 months of age at enrollment
Age 3 Years to <9 Years Group (Study Group 2)	Fluzone® Quadrivalent Influenza Virus Vaccine, No Preservative	Participants at 3 years to \< 9 years of age at enrollment

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine	Day 0 up to Day 7 post-vaccination	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine	Day 0 (pre-vaccination) and Day 28 after final vaccination	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.
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine	Day 0 (pre-vaccination) and Day 28 after final vaccination	Influenza virus antibodies were measured using an HAI assay. Seroprotection was defined as a titer ≥40 (1/dilution).
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine	Day 0 (pre-vaccination) and Day 28 after final vaccination	Influenza virus antibodies were measured using a hemagglutination inhibition (HAI) assay.
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine	Day 0 (pre-vaccination) and Day 28 after final vaccination	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.