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

Study Overview
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Brief Summary
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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.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Influenza Vaccine GSK2321138A When Administered in Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza vaccine GSK2321138A
* Biological: FluarixTM
* Biological: Influenza vaccine GSK2604409A


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2321138A 1 Group<br>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<br>* intramuscular injections<br>|
| Active Comparator: Fluarix Group<br>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<br>* intramuscular injections<br>|
| Active Comparator: GSK2604409A Group<br>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<br>* intramuscular injections<br>|
| Experimental: GSK2321138A 2 Group<br>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<br>* intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. | 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). | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroconverted Subjects Against 4 Strains of Influenza Disease. | 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). | At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroconverted Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) | 
| Number of Seroconverted Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease | 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). | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza. | 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). | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. | 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). | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST] | 
| Mean Geometric Increase (MGI) Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. | 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). | At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) | 
| Mean Geometric Increase (MGI) Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) | 
| Mean Geometric Increase (MGI) Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata. | 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. | At Day 28 (for primed subjects) and Day 56 (for unprimed subjects) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms. | 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. | During the 7-day (Days 0-6) follow-up period after any vaccination. | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects Younger Than 6 Years Old. | 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. | During the 7-day (Days 0-6) follow-up period after any vaccination. | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects Aged 6 Years or Older. | 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. | During the 7-day (Days 0-6) follow-up period after any vaccination. | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | 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. | During the 28-day (Days 0-27) follow-up period after any vaccination. | 
| Number of Subjects With Any, Grade 3 and Related Medically Attended Adverse Events (MAEs). | 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. | During the entire study period (Day 0 - Day 180) | 
| Number of Subjects With Any and Related Potential Immune-Mediated Diseases (pIMDs). | 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. | During the entire study period (Day 0 - Day 180) | 
| Number of Subjects With Any and Related Serious Adverse Events (SAEs). | 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. | During the entire study period (Day 0 - Day 180) | 
| Number of Days With Solicited Local Symptoms. | 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. | During the 7-day (Days 0-6) follow-up period after vaccination. | 
| Number of Days With Solicited General Symptoms | 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)]. | During the 7-day (Days 0-6) follow-up period after vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK Biologicals influenza vaccine GSK2321138A, influenza infection