Immunogenicity and Safety Study of GSK Biologicals' Influenza Vaccine When Administered in Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01196988
First received: September 7, 2010
Last updated: April 25, 2013
Last verified: February 2013
  Purpose

This study is designed to assess the safety and immunogenicity of GlaxoSmithKline (GSK) Biologicals' investigational vaccine GSK2321138A in children aged 3 to 17 years, and to describe safety and immunogenicity of the GSK Biologicals' investigational vaccine GSK2321138A in children aged 6 to 35 months.


Condition Intervention Phase
Influenza Vaccines
Biological: Influenza vaccine GSK2321138A
Biological: FluarixTM
Biological: Influenza vaccine GSK2604409A
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety Study of GSK Biologicals' Influenza Vaccine GSK2321138A When Administered in Children

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

  • Number of Seroconverted Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥1:40, or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).


Secondary Outcome Measures:
  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]

    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

    Subjects were assessed according to 2 age strata: 3-8 years and 9-17 years.


  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]

    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

    Subjects were assessed according to 2 age strata: 6-17 months and 18-35 months.


  • Number of Seroconverted Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥1:40, or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 3-8 years and 9-17 years.

  • Number of Seroconverted Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥1:40, or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 6-17 months and 18-35 months.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 3-8 years and 9-17 years.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 6-17 months and 18-35 months.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:80. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:80. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 3-8 years and 9-17 years.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:80. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 6-17 months and 18-35 months.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:120. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:120. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 3-8 years and 9-17 years.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as as a vaccinated subject who had a serum HI titer ≥ 1:120. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 6 -17 months and 18-35 months.

  • Mean Geometric Increase (MGI) Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) ] [ Designated as safety issue: No ]
    MGI is defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata).

  • Mean Geometric Increase (MGI) Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) ] [ Designated as safety issue: No ]
    MGI is defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 3-8 years and 9-17 years.

  • Mean Geometric Increase (MGI) Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. [ Time Frame: At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) ] [ Designated as safety issue: No ]
    MGI is defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. The 4 influenza strains assessed were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (Victoria) and FLU B/Brisbane/3/07 (Yamagata). Subjects were assessed according to 2 age strata: 6 -17 months and 18-35 months.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination. ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling at the injection site. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful (Child <6 years) or pain that prevented normal activity (Child >6 years). Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of the injection site.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects Younger Than 6 Years Old. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination. ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = temperature >39.0°C.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects Aged 6 Years or Older. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination. ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = temperature >39.0°C.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: During the 28-day (Days 0-27) follow-up period after any 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 = any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 = unsolicited AE that prevented normal activity Related = unsolicited AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Any, Grade 3 and Related Medically Attended Adverse Events (MAEs). [ Time Frame: During the entire study period (Day 0 - Day 180) ] [ Designated as safety issue: No ]
    MAEs were defined as AEs that resulted in medical attention (defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason). Any = any MAE regardless of intensity or relationship to vaccination. Grade 3 MAE = MAE which prevented normal, everyday activities. Related = MAE assessed by the investigator as related to the vaccination. Assessment of intensity for MAEs was not performed.

  • Number of Subjects With Any and Related Potential Immune-Mediated Diseases (pIMDs). [ Time Frame: During the entire study period (Day 0 - Day 180) ] [ Designated as safety issue: No ]
    pIMDs were defined as a subset of AEs that included both clearly autoimmune diseases (AID) and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.

  • Number of Subjects With Any and Related Serious Adverse Events (SAEs). [ Time Frame: During the entire study period (Day 0 - Day 180) ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include 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 Days With Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) follow-up period after vaccination. ] [ Designated as safety issue: No ]
    The number of days with any grade of local symptoms after Dose 1 and Dose 2 vaccination respectively was tabulated. Assessed solicited local symptoms for duration were pain, redness and swelling at the injection site.

  • Number of Days With Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) follow-up period after vaccination. ] [ Designated as safety issue: No ]
    The number of days with any grade of local symptoms after Dose 1 and Dose 2 vaccination respectively was tabulated. Assessed solicited general symptoms for duration were drowsiness, fatigue, gastrointestinal symptoms (Gastro.), headache, irritability, loss of appetite, muscle aches, shivering and temperature [axillary temperature equal to or above 37.5 degrees Celsius (°C)].


Enrollment: 3027
Study Start Date: October 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2321138A 1 Group
Subjects aged 3-17 years received if primed, 1 dose of GSK2321138A at Day 0 and if unprimed, 2 doses of GSK2321138A at Day 0 and Day 28. The vaccine was administered intramuscularly into the deltoid for subjects aged 12 months or above or into the anterolateral region of the thigh for subjects below 12 month of age. The vaccine was administered in the non-dominant side of the body at Day 0 and in the opposite side at Day 28.
Biological: Influenza vaccine GSK2321138A
intramuscular injections
Active Comparator: Fluarix Group
Subjects aged 3-17 years received if primed, 1 dose of Fluarix at Day 0 and if unprimed, 2 doses of Fluarix at Day 0 and Day 28. The vaccine was administered intramuscularly into the deltoid for subjects aged 12 months or above or into the anterolateral region of the thigh for subjects below 12 month of age. The vaccine was administered in the non-dominant side of the body at Day 0 and in the opposite side at Day 28.
Biological: FluarixTM
intramuscular injections
Active Comparator: GSK2604409A Group
Subjects aged 3-17 years received if primed, 1 dose of GSK2604409A at Day 0 and if unprimed, 2 doses of GSK2604409A at Day 0 and Day 28. The vaccine was administered intramuscularly into the deltoid for subjects aged 12 months or above or into the anterolateral region of the thigh for subjects below 12 month of age. The vaccine was administered in the non-dominant side of the body at Day 0 and in the opposite side at Day 28.
Biological: Influenza vaccine GSK2604409A
intramuscular injections
Experimental: GSK2321138A 2 Group
Subjects aged 6-35 months received if primed, 1 dose of GSK2321138A at Day 0 and if unprimed, 2 doses of GSK2321138A at Day 0 and Day 28. The vaccine was administered intramuscularly into the deltoid for subjects aged 12 months or above or into the anterolateral region of the thigh for subjects below 12 month of age. The vaccine was administered in the non-dominant side of the body at Day 0 and in the opposite side at Day 28.
Biological: Influenza vaccine GSK2321138A
intramuscular injections

  Eligibility

Ages Eligible for Study:   6 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
  • For non US countries:
  • - Children, male or female, aged between 6 months and 17 years at the time of the first study vaccination.

For US :

  • Children, male or female, aged between 3 and 17 years at the time of the first study vaccination
  • Written informed consent obtained from the subject parent(s) or LAR(s) of the subject. Assent obtained from the subject when applicable.
  • Subjects in stable health as determined by investigator's clinical examination and assessment of subjects' medical history.
  • Written informed assent obtained from the subject if/as required by local regulations.
  • Female subjects of non-childbearing potential may be enrolled in the study.
  • Female subjects of childbearing potential may be enrolled in the study, if the subject:
  • - has practiced adequate contraception for 30 days prior to vaccination,
  • - and has a negative urine pregnancy test on the day of vaccination,
  • - and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series

Exclusion Criteria:

  • 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. Routine registered childhood vaccinations are permitted.
  • Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration.
  • Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination.
  • Prior receipt of any seasonal or pandemic influenza vaccine (registered or investigational) within 6 months preceding the first dose of study vaccine, or planned use during the study period.
  • 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.
  • Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned during the study.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
  • History of seizures or progressive neurological disease.
  • History of Guillain-Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine.
  • Concurrently participating in another clinical study, at any time during the study period in which the subject has been or will be exposed to an investigational or a non-investigational product .
  • History of hypersensitivity to a previous dose of influenza vaccine, history of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines
  • Acute disease and/or fever at the time of enrolment
  • Ongoing aspirin therapy
  • Pregnant or lactating female
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.
  • Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study
  • Child in Care.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196988

Locations
Philippines
GSK Investigational Site
Dasmariñas, Cavite, Philippines, 4114
GSK Investigational Site
Quezon City, Philippines, 1113
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01196988     History of Changes
Other Study ID Numbers: 113275
Study First Received: September 7, 2010
Results First Received: December 17, 2012
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
GSK Biologicals influenza vaccine GSK2321138A
influenza infection

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

ClinicalTrials.gov processed this record on October 22, 2014