Immunogenicity and Safety of GSK Biologicals' Influenza Vaccine Versus a Licensed Comparator in Children

Immunogenicity and Safety of GSK Biologicals' Thimerosal-free TIV Flu Vaccine Versus a Licensed Comparator in Children

The purpose of this study is to evaluate the immunogenicity and the safety of GlaxoSmithKline Biologicals' seasonal influenza vaccine, Fluarix, compared to Fluzone (a US-licensed vaccine) in children, 6 to 35 months of age.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 3317
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Pokfulam, Hong Kong
    • GSK Investigational Site
  • Shatin, Hong Kong
    • GSK Investigational Site
• Mexico
  • Mexico, Mexico, 6720
    • GSK Investigational Site
  • Mexico city, Mexico, 04530
    • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 104
    • GSK Investigational Site
  • Taipei, Taiwan
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • GSK Investigational Site
    • Birmingham, Alabama, United States, 35205
      • GSK Investigational Site
    • Dothan, Alabama, United States, 36305
      • GSK Investigational Site
  • Arkansas
    • Benton, Arkansas, United States, 72019
      • GSK Investigational Site
    • Conway, Arkansas, United States, 72034
      • GSK Investigational Site
    • Fayetteville, Arkansas, United States, 72703
      • GSK Investigational Site
    • Jonesboro, Arkansas, United States, 72401
      • GSK Investigational Site
    • Little Rock, Arkansas, United States, 72205
      • GSK Investigational Site
  • California
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
    • Long Beach, California, United States, 90806
      • GSK Investigational Site
    • Paramount, California, United States, 90723
      • GSK Investigational Site
    • Sacramento, California, United States, 95816
      • GSK Investigational Site
    • San Francisco, California, United States, 94102
      • GSK Investigational Site
    • West Covina, California, United States, 91790
      • GSK Investigational Site
  • Colorado
    • Longmont, Colorado, United States, 80501
      • GSK Investigational Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • GSK Investigational Site
  • Idaho
    • Nampa, Idaho, United States, 83686
      • GSK Investigational Site
  • Illinois
    • DeKalb, Illinois, United States, 60115
      • GSK Investigational Site
  • Indiana
    • New Albany, Indiana, United States, 47150
      • GSK Investigational Site
  • Kansas
    • Arkansas City, Kansas, United States, 67005
      • GSK Investigational Site
    • Newton, Kansas, United States, 67114
      • GSK Investigational Site
    • Wichita, Kansas, United States, 67207
      • GSK Investigational Site
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • GSK Investigational Site
    • Louisville, Kentucky, United States, 40207
      • GSK Investigational Site
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
      • GSK Investigational Site
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
  • Michigan
    • Stevensville, Michigan, United States, 49127
      • GSK Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55108
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • GSK Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89015
      • GSK Investigational Site
  • New York
    • Cortland, New York, United States, 13045
      • GSK Investigational Site
  • North Carolina
    • Boone, North Carolina, United States, 28607
      • GSK Investigational Site
    • Cary, North Carolina, United States, 27518
      • GSK Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • GSK Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • GSK Investigational Site
  • Ohio
    • Austintown, Ohio, United States, 44515
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45245
      • GSK Investigational Site
    • Cleveland, Ohio, United States, 44121
      • GSK Investigational Site
    • Dayton, Ohio, United States, 45406
      • GSK Investigational Site
  • Oregon
    • Gresham, Oregon, United States, 97030
      • GSK Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
      • GSK Investigational Site
    • Greenville, Pennsylvania, United States, 16125
      • GSK Investigational Site
    • Latrobe, Pennsylvania, United States, 15650
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15236
      • GSK Investigational Site
    • Uniontown, Pennsylvania, United States, 15401
      • GSK Investigational Site
    • Wexford, Pennsylvania, United States, 15090
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • GSK Investigational Site
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
      • GSK Investigational Site
    • Jackson, Tennessee, United States, 38305
      • GSK Investigational Site
    • Kingsport, Tennessee, United States, 37660
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76135
      • GSK Investigational Site
    • Houston, Texas, United States, 77055
      • GSK Investigational Site
    • San Angelo, Texas, United States, 76904
      • GSK Investigational Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • GSK Investigational Site
    • Layton, Utah, United States, 84041
      • GSK Investigational Site
    • Murray, Utah, United States, 84107
      • GSK Investigational Site
    • Provo, Utah, United States, 84604
      • GSK Investigational Site
    • Roy, Utah, United States, 84067
      • GSK Investigational Site
    • South Jordan, Utah, United States, 84095
      • GSK Investigational Site
  • Virginia
    • Burke, Virginia, United States, 22015
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A male or female child aged 6 to 35 months at the time of the first 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.
• Written informed consent obtained from the subject's parent/guardian.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or 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 criterion.
• 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 enrolment.
• History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine.
• Receipt of an influenza vaccine outside of this study, during current (2008-09) flu season.
• Administration of immunoglobulins and/or blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluarix Dose A Group; Subjects were administered 1 or 2 doses* of Fluarix vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children >12 months of age) or in the anterolateral thigh (children <12 months of age). * Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses.	Biological: Fluarix; One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection. Two different doses are tested.
Experimental: Fluarix Dose B Group; Subjects were administered 1 or 2 doses*, half the volume of dose A, of Fluarix vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children >12 months of age) or in the anterolateral thigh (children <12 months of age). * Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses.	Biological: Fluarix; One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection. Two different doses are tested.
Active Comparator: Fluzone Group; Subjects were administered 1 or 2 doses* of Fluzone vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children >12 months of age) or in the anterolateral thigh (children <12 months of age). * Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses.	Biological: Fluzone; One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains	GMTs and their 95% confidence interval are presented for all 3 viral strains comprised in the vaccine. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects	Day 0 (PRE), Day 28 or Day 56 (POST)
Number of Subjects Who Seroconverted	Seroconversion is defined as the number of subjects with either a pre-vaccination anti-HA 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. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects	Day 28 or Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroprotected Subjects	A seroprotected subject is a subject with a serum anti-HA titer ≥ 1:40 Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects	Day 0 (PRE), Day 28 or Day 56 (POST)
Seroconversion Factor	Seroconversion factor is defined as the fold increase in serum anti-HA GMTs post-vaccination (Day 28 or 56) compared to pre-vaccination (Day 0). Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects	Day 28 or Day 56
Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling.	During a 4-day follow-up period after vaccination
Number of Subjects Reporting Solicited General Symptoms	Solicited general symptoms assessed include drowsiness, irritability, loss of appetitie, and temperature.	During a 4-day follow-up period after vaccination
Number of Subjects Reporting Unsolicited Adverse Events (AE)	An AE 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	During a 28-day follow-up period after vaccination
Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD)	An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. NOCDs assessed include for example: diabetes, asthma, allergies, autoimmune disease, cancer, neuropathic disorders	During the entire study (Day 0 until Month 6)
Number of Subjects Reporting Rare Serious Events	Rare serious events have an occurrence rate of 1/300 (0.3%).	During the entire study (Day 0 until Month 6)

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.
• Pavia-Ruz N, Angel Rodriguez Weber M, Lau YL, Nelson EA, Kerdpanich A, Huang LM, Silas P, Qaqundah P, Blatter M, Jeanfreau R, Lei P, Jain V, El Idrissi M, Feng Y, Innis B, Peeters M, Devaster JM. A randomized controlled study to evaluate the immunogenicity of a trivalent inactivated seasonal influenza vaccine at two dosages in children 6 to 35 months of age. Hum Vaccin Immunother. 2013 Sep;9(9):1978-88. doi: 10.4161/hv.25363. Epub 2013 Jun 19.

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: October 1, 2008
• Primary Completion (Actual): March 5, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: October 1, 2008
• First Submitted That Met QC Criteria: October 1, 2008
• First Posted (Estimate): October 2, 2008

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 111751

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. Dataset Specification
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 111751
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register