Study Comparing the Immune Response and Safety of Fluarix and Fluzone Influenza Vaccines in Children

A Phase III, Single-blind, Randomized Study to Evaluate the Immunogenicity and Safety of Fluarix® (GSK Biologicals') Compared With Fluzone® (Aventis Pasteur/Sanofi) Administered Intramuscularly in Children (6 Months and Older)

The purpose of this study is to compare two influenza vaccines (Fluzone and Fluarix) in terms of the immune response elicited and safety with a six month follow-up after first vaccination. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluarix™; Biological: Fluzone

• Study Type: Interventional
• Enrollment (Actual): 3327
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Antioch, California, United States, 94509
      • GSK Investigational Site
    • Fairfield, California, United States, 94533
      • GSK Investigational Site
    • Fresno, California, United States, 93710
      • GSK Investigational Site
    • Pleasanton, California, United States, 94588
      • GSK Investigational Site
    • Redwood City, California, United States, 94063
      • GSK Investigational Site
    • Richmond, California, United States, 94801
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
    • Sacramento, California, United States, 95815
      • GSK Investigational Site
    • San Francisco, California, United States, 94115
      • GSK Investigational Site
    • San Francisco, California, United States, 94102
      • GSK Investigational Site
    • Santa Clara, California, United States, 95051
      • GSK Investigational Site
    • Santa Rosa, California, United States, 95403
      • GSK Investigational Site
    • Vacaville, California, United States, 95688
      • GSK Investigational Site
    • Vallejo, California, United States, 94589
      • GSK Investigational Site
    • Walnut Creek, California, United States, 94596
      • GSK Investigational Site
  • Colorado
    • Englewood, Colorado, United States, 80112
      • GSK Investigational Site
    • Lakewood, Colorado, United States, 80401
      • GSK Investigational Site
  • Georgia
    • Tifton, Georgia, United States, 31794
      • GSK Investigational Site
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • GSK Investigational Site
    • Lexington, Kentucky, United States, 40509
      • GSK Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • GSK Investigational Site
  • New Jersey
    • Whitehouse Station, New Jersey, United States, 08889
      • GSK Investigational Site
  • New York
    • Fishkill, New York, United States, 12524
      • GSK Investigational Site
    • Hopewell Junction, New York, United States, 12533
      • GSK Investigational Site
    • Poughkeepsie, New York, United States, 12603
      • GSK Investigational Site
    • Rochester, New York, United States, 14609
      • GSK Investigational Site
    • Rochester, New York, United States, 14620
      • GSK Investigational Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • GSK Investigational Site
    • Sylva, North Carolina, United States, 28779
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44118
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • GSK Investigational Site
    • Uniontown, Pennsylvania, United States, 15401
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78728
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76135
      • GSK Investigational Site
    • San Angelo, Texas, United States, 76904
      • GSK Investigational Site
  • Utah
    • Layton, Utah, United States, 84041
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • GSK Investigational Site
    • South Jordan, Utah, United States, 84095
      • GSK Investigational Site
    • West Jordan, Utah, United States, 84084
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A male or female child age 6 months to < 18 years at the time of the vaccination; children who may or may not have had previous administration of influenza vaccine in a previous season are acceptable.
• Subjects having a parent/guardian who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study.
• Written informed consent obtained from the subject's parent/guardian; assent obtained in subjects > 10 years.
• Female subjects of childbearing potential must agree to take a pregnancy test.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine, other than the study vaccine) within 30 days preceding the administration of the study vaccine, or planned use during the study period. Routine, registered childhood vaccinations are not an exclusion.
• History of hypersensitivity to any vaccine.
• History of allergy or reactions likely to be exacerbated by any component of the vaccine.
• Acute disease at the time of enrollment.
• History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine.
• Pregnant or lactating female.
• Receipt of an influenza vaccine outside of this study, during current (2006-07) flu season.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluarix Group; Subjects in this group received Fluarix™ and will be further stratified by 3 age groups; 1:1 in 6 months to < 36 months; 1:1 in 3 to < 5 years; 3:1 in 5 to < 18 years	Biological: Fluarix™; Subjects were administered 1 or 2 doses* intramuscularly, into the non-dominant upper arm for children > 12 months of age, in the anterolateral thigh for children < 12 months. *Only those subjects between the age of 6 months and < 9 years, who had no history of prior influenza vaccination, received 2 doses at months 0 & 1.
Active Comparator: Fluzone Group; Subjects in this group received Fluzone and will be further stratified by 3 age groups; 1:1 in 6 months to < 36 months; 1:1 in 3 to < 5 years; 3:1 in 5 to < 18 years	Biological: Fluzone; Subjects were administered 1 or 2 doses* intramuscularly, into the non-dominant upper arm for children > 12 months of age, in the anterolateral thigh for children < 12 months. *Only those subjects between the age of 6 months and < 9 years, who had no history of prior influenza vaccination, received 2 doses at months 0 & 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titer (GMT) of Serum Haemagglutination-inhibition (HI) Antibodies	GMTs and their 95% confidence interval are presented for all 3 viral strains comprised in the vaccine.	21 or 28 days after last vaccine dose
Number of Seroconverted Subjects	Seroconverted subjects are defined as subjects with either a pre-vaccination HI titer <1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a minimum 4-fold increase at post-vaccination titer. Data are presented for all 3 viral strains comprised in the vaccine.	21 or 28 days after last vaccine dose
Number of Subjects Reporting Rare Serious Events	Rare serious event is defined as any untoward medical event with an occurrence rate of ≥1/300 that: resulted in death,; was life-threatening,; required hospitalization or prolongation of existing hospitalization,; resulted in disability/incapacity, or; was a congenital anomaly/birth defect in the offspring of a study subject.	Up to 6 months after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects	Seroprotected subjects are defined as vaccinees with a serum HI titer ≥ 1:40. Data are presented for all 3 viral strains comprised in the vaccine.	Before (PRE) and 21 or 28 days after (POST) the last vaccine dose
Number of Initially Unprotected Subjects With at Least a 4 Fold Increase in HI Titer	Initially unprotected subjects are subjects with a baseline HI titer < 1:40. Data are presented for all 3 viral strains comprised in the vaccine.	21 or 28 days after last vaccine dose
Number of Subjects Reporting Solicited Local and General Symptoms	Solicited local symptoms assessed include pain, redness, and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability, loss of appetite, arthralgia, fatigue, headache, muscle aches, and shivering. Data across doses are presented. Any = at least one symptom irrespective of intensity/relationship to vaccination; Grade 3: symptom that prevented normal everyday activities; Related: considered by the investigator as related to the study vaccination.	During a 4-day follow-up period after each vaccination
Number of Subjects Reporting Unsolicited Adverse Events	An Adverse Event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any = at least one symptom irrespective of intensity and relationship to vaccination; Grade 3 = preventing normal activity; Related = considered by the investigator to be causally related to the study vaccination.	Within 28 days following vaccination
Number of Subjects Reporting New Onset Chronic Illnesses and/or Serious Adverse Events (SAE)	SAE: any untoward medical occurrence that; resulted in death,; was life-threatening,; required hospitalization or prolongation of existing hospitalization,; resulted in disability/incapacity, or; was a congenital anomaly/birth defect in the offspring of a study subject. Examples of possible new onset chronic illnesses include but are not limited to diabetes, asthma, allergies, autoimmune disease, cancer, neuropathic disorders.	Up to 6 months after vaccination

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Li-Kim-Moy J, Wood N, Jones C, Macartney K, Booy R. Impact of Fever and Antipyretic Use on Influenza Vaccine Immune Reponses in Children. Pediatr Infect Dis J. 2018 Oct;37(10):971-975. doi: 10.1097/INF.0000000000001949.
• Baxter R, Jeanfreau R, Block SL, Blatter M, Pichichero M, Jain VK, Dewe W, Innis BL. A Phase III evaluation of immunogenicity and safety of two trivalent inactivated seasonal influenza vaccines in US children. Pediatr Infect Dis J. 2010 Oct;29(10):924-30. doi: 10.1097/INF.0b013e3181e075be.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: November 2, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 19, 2007

Study Registration Dates

• First Submitted: September 29, 2006
• First Submitted That Met QC Criteria: September 29, 2006
• First Posted (Estimate): October 2, 2006

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 8, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Influenza; Fluarix
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 104858

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 104858
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register