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Immunogenicity and Safety Study of Fluarix™ Vaccine in Children Who Have Previously Been Vaccinated With Pandemrix™

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01196026
First received: September 3, 2010
Last updated: January 31, 2013
Last verified: October 2012
History of Changes
  Purpose

This study is designed to assess the immunogenicity, reactogenicity and safety following vaccination with GSK Biologicals' Fluarix vaccine in children who have previously been vaccinated with two doses of Pandemrix at the age of 6 months-9 years.


Condition Intervention Phase
Influenza Infection
 Biological: Fluarix™
Biological: Havrix™ Junior
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety Study of GSK Biologicals' Seasonal (2010-2011) Influenza Vaccine Fluarix™ in Children Previously Vaccinated With GSK Biologicals' H1N1 Vaccine Pandemrix™

Resource links provided by NLM:

MedlinePlus related topics: Flu
U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Haemagglutination Inhibition (HI) Antibody Titers Against H1N1 in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 0 and 28 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs).

  • Number of Subjects Seropositive for HI Antibodies Against H1N1 in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 0-28 ] [ Designated as safety issue: No ]
    Seropositivity was defined as antibody titers greater than or equal to 1:10.

  • Number of Subjects Seroprotected for HI Antibodies Against H1N1 in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 0-28 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection.

  • Number of Subjects Seroconverted for HI Antibodies Against H1N1 in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject that had either a prevaccination (Day 0) titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer.

  • Mean Geometric Increase (MGI) in HI Antibody Titers Against H1N1 in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 28) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer.


Secondary Outcome Measures:
  • HI Antibody Titers Against All Fluarix Vaccine Strains [ Time Frame: Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs. Vaccine strains included in the analysis were Flu A/CAL/7/09 H1N1 , FluB/Bri/60/08 Victoria, and Flu A/Vic/210/09 H3N2, further in this summary denoted as H1N1, Victoria and H3N2 strains, respectively.

  • HI Antibody Titers Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Day 0 and Month 6 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.

  • Number of Subjects Seropositive for HI Antibodies Against All Fluarix Vaccine Strains [ Time Frame: Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) ] [ Designated as safety issue: No ]
    Seropositivity was defined as antibody titers greater than or equal to 1:10. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains.

  • Number of Subjects Seropositive for HI Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Day 0 and Month 6 ] [ Designated as safety issue: No ]
    Seropositivity was defined as antibody titers greater than or equal to 1:10. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.

  • Number of Subjects Seroconverted for HI Antibodies Against All Fluarix Vaccine Strains in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

    A seroconverted subject was defined as a subject that had either a pre-vaccination (Day 0) titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer.

    Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains.


  • Number of Subjects Seroconverted for HI Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Month 6 ] [ Designated as safety issue: No ]

    A seroconverted subject was defined as a subject that had either a pre-vaccination (Day 0) titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer.

    Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.


  • Number of Subjects Seroprotected for HI Antibodies Against All Fluarix Vaccine Strains [ Time Frame: Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains.

  • Number of Subjects Seroprotected for HI Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Day 0 and Month 6 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.

  • Mean Geometric Increase (MGI) in HI Antibody Titers Against All Fluarix Vaccine Strains in All Subjects Receiving Fluarix Vaccine [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 28) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains.

  • Mean Geometric Increase (MGI) in HI Antibody Titers Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Month 6 ] [ Designated as safety issue: No ]

    MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination (Month 6) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer.

    Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.


  • Serum Neutralising Antibody Titers Against All Fluarix Vaccine Strains [ Time Frame: Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric Mean Titers (GMTs).

  • Serum Neutralising Antibody Titers Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Day 0 and Month 6 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs.] Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.

  • Number of Subjects Seropositive for Serum Neutralising Antibodies Against All Fluarix Vaccine Strains [ Time Frame: Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) ] [ Designated as safety issue: No ]
    Seropositivity was defined as antibody titers greater than or equal to 1:28.

  • Number of Subjects Seropositive for Serum Neutralising Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Day 0 and Month 6 ] [ Designated as safety issue: No ]
    Seropositivity was defined as antibody titers greater than or equal to 1:28. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.

  • Number of Subjects Seroconverted for Serum Neutralising Antibodies Against All Fluarix Vaccine Strains in Subjects Receiving Fluarix [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Seroconverted subject was a subject with a minimum 4-fold increase in titer at post-vaccination for neutralizing antibody response.

  • Number of Subjects Seroconverted for Serum Neutralising Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine [ Time Frame: Month 6 ] [ Designated as safety issue: No ]

    Seroconverted subject was a subject with a minimum 4-fold increase in titer at post-vaccination for neutralizing antibody response.

    Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine.


  • Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7 days (Day 0 - 6) after vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed include: pain, redness and swelling. Any is any symptom regardless of intensity. Grade 3 was defined as a symptom that prevented normal activity.above 50 millimeter.

  • Duration of Any Solicited Local Symptom [ Time Frame: During the 7 days (Days 0 - 6) after vaccination ] [ Designated as safety issue: No ]
    Duration was expressed as median number of days the symptom persisted. Solicited local symptoms assessed include: pain, redness and swelling.

  • Number of Subjects Less Than 6 Years Reporting Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7 days (Days 0-6) after vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed include diarrhoea, drowsiness, irritability, loss of appetite and fever. Any was defined as any symptom regardless of intensity; any fever was axillary temperature greater than or equal to 37.5 degrees celsius. Grade 3 was a symptom preventing normal everyday activity; grade 3 loss of appetite was not eating at all; grade 3 fever was axillary temperature above 39 degrees celsius. Related was any symptom assessed by the investigator as causally related to the study vaccination.

  • Duration of Any Solicited General Symptom Experienced by Subjects Less Than 6 Years Old [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ] [ Designated as safety issue: No ]
    Duration was expressed as median number of days the symptom persisted. Solicited general symptoms assessed include diarrhoea, drowsiness, irritability, loss of appetite and fever.

  • Number of Subjects Above 6 Years Reported Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, sweating and fever. Any was defined as any symptom regardless of intensity; any fever was axillary temperature greater than or equal to 37.5 degrees celsius. Grade 3 was a symptom preventing normal everyday activity; grade 3 fever was axillary temperature above 39 degrees celsius. Related was any symptom assessed by the investigator as causally related to the study vaccination.

  • Duration of Any Solicited General Symptom Experienced by Subjects Above 6 Years Old [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ] [ Designated as safety issue: No ]
    Duration was expressed as median number of days the symptom persisted. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During a 28 day follow-up period (Day 0-27) after vaccination ] [ Designated as safety issue: No ]

    Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

    Any was defined as any symptom regardless of intensity or relationship to vaccination. Grade 3 was a symptom preventing normal everyday activity. Related was any symptom assessed by the investigator as causally related to the study vaccination.


  • Number of Subjects Reporting Medically-Attended Events (MAEs), Adverse Events of Specific Interest (AESIs)/ Potential Immune Mediated Diseases (pIMDs) and Adverse Events (AEs) of Special Interest [ Time Frame: During the entire study period (up to Month 6) ] [ Designated as safety issue: No ]

    MAEs: subject received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason.

    AESIs/pIMD: includes both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Adverse events of special interest include both convulsion and anaphylaxis.


  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    SAEs: medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: Up to Month 6 ] [ Designated as safety issue: No ]
    SAEs: medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.


Enrollment: 162
Study Start Date: September 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluarix 6-11 months Group
Subjects previously vaccinated with Pandemrix vaccine, will receive one or two doses of Fluarix vaccine
 Biological: Fluarix™
One or two intramuscular injections
Experimental: Fluarix 12-35 months Group
Subjects previously vaccinated with Pandemrix vaccine, will receive one or two doses of Fluarix vaccine
 Biological: Fluarix™
One or two intramuscular injections
Experimental: Fluarix 3-9 years Group
Subjects previously vaccinated with Pandemrix vaccine, will receive one or two doses of Fluarix vaccine
 Biological: Fluarix™
One or two intramuscular injections
Active Comparator: Havrix Junior 6-11 months Group
Subjects previously vaccinated with Pandemrix vaccine will receive two doses of Havrix Junior vaccine
 Biological: Havrix™ Junior
Two intramuscular injections
Active Comparator: Havrix Junior 12-35 months Group
Subjects previously vaccinated with Pandemrix vaccine will receive two doses of Havrix Junior vaccine
 Biological: Havrix™ Junior
Two intramuscular injections
Active Comparator: Havrix Junior 3-9 years Group
Subjects previously vaccinated with Pandemrix vaccine will receive two doses of Havrix Junior vaccine
 Biological: Havrix™ Junior
Two intramuscular injections

  Eligibility

Ages Eligible for Study:   1 Year to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects having previously been immunized with two 0.25 mL doses of Pandemrix, given at least 21 days apart, at the age of 6 months to 9 years inclusive at the time of first vaccination.
  • Subjects having received the last dose of Pandemrix at least six months prior to study enrolment.
  • Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol.
  • Written informed consent obtained from the parent(s)/LAR(s) of the subjects.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Parent/LAR with access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device.

Exclusion Criteria:

  • Active participation in other clinical trials.
  • Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period.
  • Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to enrolment in this study or planned administration during the study period.
  • Acute disease and/or fever at the time of enrolment.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
  • Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination.
  • Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned use during the study.
  • Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.
  • History of seizures or progressive neurological disease.
  • Subjects having received an H1N1v pandemic vaccine other than Pandemrix or having received the 2010/2011 seasonal influenza vaccine.
  • Child in care.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01196026

Locations
Netherlands
GSK Investigational Site
Rotterdam, Netherlands, 3011 EN
Sweden
GSK Investigational Site
Karlskrona, Sweden, SE-371 41
GSK Investigational Site
Malmö, Sweden, SE-205 02
GSK Investigational Site
Skellefteå, Sweden, SE-931 86
GSK Investigational Site
Stockholm, Sweden, SE-118 83
GSK Investigational Site
Umeå, Sweden, SE-901 85
GSK Investigational Site
Örebro, Sweden, SE-702 11
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01196026     History of Changes
Other Study ID Numbers: 114451
Study First Received: September 3, 2010
Results First Received: March 12, 2012
Last Updated: January 31, 2013
Health Authority: Sweden: Läkemedelsverket
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by GlaxoSmithKline:
Influenza
H1N1
Fluarix
Pandemrix

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
 Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 23, 2013