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

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

The study will evaluate the safety and immunogenicity of the 2014-2015 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 2014-2015 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 2014-2015 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 WHO, the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) to support formulation recommendations for subsequent influenza vaccines.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Fluzone® Quadrivalent Influenza Vaccine, No Preservative	Phase 4

Detailed Description:

Participants will be assigned to the appropriate age group based on the age at the time of enrollment. Participants will receive a dose of Fluzone Quadrivalent vaccine, those for whom 2 doses of influenza vaccine are recommended per ACIP guidance, will receive a second dose 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 the study. Immunogenicity will be evaluated in all participants prior to vaccination and at Day 28 after the final vaccination.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent, Influenza Vaccine (2014-2015 Formulation)
• Study Start Date: August 2014
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fluzone Study Group 1; Participants at 6 months to < 36 months age at enrollment	Biological: Fluzone® Quadrivalent Influenza Vaccine, No Preservative; 0.25 mL, Intramuscular (Pediatric Dose, 2014-2015 formulation); Other Name: Fluzone® Quadrivalent, No Preservative
Experimental: Fluzone Study Group 2; Participants at 3 years to < 9 years of age at enrollment	Biological: Fluzone® Quadrivalent Influenza Vaccine, No Preservative; 0.5 mL, Intramuscular (2014-2015 formulation); Other Name: Fluzone® Quadrivalent, No Preservative

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Influenza Vaccine [ Time Frame: Day 0 up to Day 7 post-any injection ]

   Solicited Injection-site: 6 to < 36 months - Tenderness, Erythema, and Swelling; 3 to < 9 years - Pain, Erythema, and Swelling. Solicited systemic reactions: 6 to < 36 months - Fever (Temperature), Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability; 3 to < 9 years - Fever, Headache, Malaise, and Myalgia.

   Grade 3: Fever, > 39.5˚C (6 to < 36 months), ≥ 39.0˚C (3 to < 9 years); Vomiting, ≥ 6 episodes/24 hours or requires parenteral hydration; Crying abnormal, > 3 hours; Drowsiness, Sleeping often/difficult to wake; Appetite lost, Refuses ≥ 3 or most meals; Irritability, Inconsolable; Headache, Malaise, and Myalgia, Significant, prevents daily activity.

Secondary Outcome Measures :

1. Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Post Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Influenza Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-final vaccination ]
   Geometric titers of influenza antibodies were assessed using the hemagglutination inhibition (HAI) assay.
2. Number of Participants With Seroprotection Before and Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-final vaccination ]
   Influenza antibodies were assessed using the hemagglutination inhibition (HAI) assay. Seroprotection was defined as a titer ≥ 40 (l/dil) at pre-vaccination and at 28 days after the final vaccination.
3. Percentage of Participants With Seroconversion Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Vaccine [ Time Frame: Day 28 post-final vaccination ]
   Influenza antibodies were assessed using the hemagglutination inhibition (HAI) assay. Seroconversion is 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.
4. Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Vaccine [ Time Frame: Day 28 post-final vaccination ]
   Geometric titer ratios of influenza antibodies were assessed using the hemagglutination inhibition (HAI) assay.

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 8 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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/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 < 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 2014-2015 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.

Contacts and Locations

Locations

United States, Kentucky

Bardstown, Kentucky, United States, 40040

United States, Utah

Salt Lake City, Utah, United States, 84121

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Additional Information:

Related Info  Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02222870 History of Changes
• Other Study ID Numbers: GRC56; U1111-1143-8966 ( Other Identifier: WHO )
• First Posted: August 21, 2014
• Results First Posted: October 19, 2015
• Last Update Posted: October 19, 2015
• Last Verified: September 2015

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Influenza; Influenza virus vaccine; Quadrivalent Influenza Virus Vaccine (No Preservative); Fluzone®

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs