A Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Seasonal Influenza Vaccine in Children

Study Overview
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Brief Summary
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This study is designed to test the immunogenicity and safety of an investigational influenza vaccine, in children compared to two other influenza vaccines.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) When Administered in Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
* Biological: Fluarix™ VB
* Biological: Fluarix™ YB
* Biological: Quadrivalent seasonal influenza vaccine GSK2282512A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they and/or their parent(s) or legally acceptable representative(s) can and will comply with the requirements of the protocol. A male or female child aged between 6 months and 17 years inclusive at the time of the first vaccination; children are eligible regardless of history of administration of influenza vaccine in a previous season. Written informed consent obtained from the subject/from the parent(s)/legally acceptable representative(s) of the subject. Written informed assent obtained from the subject if/as required by local regulations. Subjects in stable health as determined by investigator's clinical examination and assessment of subjects' medical history. 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 pregnancy urine 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: Child in care Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.Prior receipt of any seasonal or pandemic influenza vaccine 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 six months prior to the first vaccine dose. Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. History of Guillain-Barré syndrome within 6 weeks of receipt of prior influenza vaccine. Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Fever at the time of enrolment. Acute disease at the time of enrolment. Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Ongoing aspirin therapy. Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2282512A 1 Group<br>Subjects, 3 to 17 years old, received 1 dose of GSK2282512A vaccine at Day 0 or 2 doses of GSK2282512A vaccine at Day 0 and Day 28. The GSK2282512A vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Quadrivalent seasonal influenza vaccine GSK2282512A<br>* For subject 3 to 8 years of age, single intramuscular dose for primed subjects, two doses for unprimed subjects. For subjects 9 to 17 years of age, single intramuscular dose.<br>|
| Active Comparator: Victoria strain Fluarix Group<br>Subjects, 3 to 17 years old, received 1 dose of Fluarix™ VB vaccine containing the Victoria lineage B flu strain at Day 0 or 2 doses of Fluarix™ VB vaccine at Day 0 and Day 28. The Fluarix™ VB vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix™ VB<br>* For subject 3 to 8 years of age, single intramuscular dose for primed subjects, two doses for unprimed subjects. For subjects of 9 to 17 years of age, single intramuscular dose.<br>|
| Active Comparator: Yamagata strain Fluarix Group<br>Subjects, 3 to 17 years old, received 1 dose of Fluarix™ YB vaccine containing the Yamagata lineage B flu strain at Day 0 or 2 doses of Fluarix™ YB vaccine at Day 0 and Day 28. The Fluarix™ YB vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluarix™ YB<br>* For subject 3 to 8 years of age, single intramuscular dose for primed subjects, two doses for unprimed subjects. For subjects of 9 to 17 years of age, single intramuscular dose<br>|
| Experimental: GSK2282512A 2 Group<br>Subjects, 6 to 35 months old, received 1 dose of GSK2282512A vaccine at Day 0 or 2 doses of GSK2282512A vaccine at Day 0 and Day 28. The GSK2282512A vaccine was administered intramuscularly in the deltoid region of the non-dominant arm for subjects ≥12 months of age and into the antero-lateral region of the left thigh for infants <12 months of age. | Biological: Quadrivalent seasonal influenza vaccine GSK2282512A<br>* Single intramuscular dose for primed subjects, two doses for unprimed subjects.<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 the seropositivity cut-off of 1:10. Antibodies assessed were antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains. | At 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Number of Subjects Seroconverted 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 vaccine strains assessed were the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains. | At 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 

Secondary 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 the seropositivity cut-off of 1:10. Antibodies assessed were antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains. | At Day 0 and at 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Number of Subjects Seroprotected Against 4 Strains of Influenza Disease | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition titer ≥ 1:40. The 4 assessed influenza strains were the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 flu strains. | At Day 0 and at 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination (at Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects (POST)) compared to Day 0 (i.e. the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer). The 4 assessed influenza strains were the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains | At 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at 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 the seropositivity cut-off of 1:10. Antibodies assessed were antibodies against the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains. Subjects were assessed according to 3 age categories, 3-8 years, 9-17 years and 6-35 months. | At Day 0 and at 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Number of Subjects Seroconverted 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 vaccine strains assessed were A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains. Subjects were assessed according to 3 age categories, 3-8 years, 9-17 years and 6-35 months. | At 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Number of Subjects Seroprotected Against 4 Strains of Influenza Disease - By Age Strata | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition titer ≥ 1:40. The 4 assessed influenza strains were the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 flu strains. Subjects were assessed according to 3 age categories, 3-8 years, 9-17 years and 6-35 months. | At Day 0 and at 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Seroconversion Factor for Hemagglutination Inhibition Antibodies Against 4 Strains of Influenza Disease - By Age Strata | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0 (i.e. the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer). The 4 assessed influenza strains were the A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Florida/4/2006 (Yamagata) flu strains. Subjects were assessed according to 3 age categories, 3-8 years, 9-17 years and 6-35 months. | At 28 days after administration of the last vaccine dose (Day 28 for Primed Subjects and at Day 56 for Unprimed Subjects) (POST) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Vaccination | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity grade. Grade 3 pain for subjects < 5 years of age = Cried when limb was moved/spontaneously painful; Grade 3 pain for subjects ≥ 5 years of age = Significant pain at rest, pain that preventeded normal everyday activities. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeters (mm). | During the 7-day follow-up period (Days 0-6) after vaccination | 
| Number of Days With Solicited Local Symptoms After Vaccination | Duration was assessed via tabulation of the number of days with local symptoms of any grade after vaccination with Dose 1 and Dose 2 respectively. Solicited local symptoms assessed for duration were pain, redness and swelling. | During the 7-day follow-up period (Days 0-6) after vaccination | 
| Number of Subjects Below 5 Years of Age With Any, Grade 3 and Related Solicited General Symptoms | Symptoms assessed were drowsiness, irritability, loss of appetite and temperature. Any = Incidence of a particular symptom regardless of intensity grade or relationship to vaccination. Any temperature = Axillary temperature ≥ 38.0 degrees Celsius (°C). Grade 3 temperature = Axillary temperature ≥ 39.0°C. Grade 3 irritability = Crying that could not be comforted/ preventing normal activity. Grade 3 drowsiness = Drowsiness preventing normal activity. Grade 3 loss of appetite = Not eating at all. Related = A general symptom assessed by the investigator as causally related to vaccination. | During the 7-day follow-up period (Days 0-6) after vaccination | 
| Number of Subjects 5 Years of Age and Above With Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering and temperature. Any = Incidence of a particular symptom regardless of intensity grade or relationship to vaccination. Any temperature = axillary temperature ≥ 38.0 °C. Grade 3 temperature = axillary temperature ≥ 39.0°C. Grade 3 symptom = Symptom that prevented normal activity. Related = A general symptom assessed by the investigator as causally related to vaccination. | During the 7-day follow-up period (Days 0-6) after vaccination | 
| Number of Days With Solicited General Symptoms After Vaccination in Subjects Below 5 Years of Age | Duration was assessed via tabulation of the number of days with local symptoms of any grade after vaccination with Dose 1 and Dose 2, respectively. Solicited general symptoms assessed for duration in subjects below 5 years of age were drowsiness, irritability and loss of appetite. | During the 7-day follow-up period (Days 0-6) after vaccination | 
| Number of Days With Solicited General Symptoms After Vaccination in Subjects 5 Years of Age and Above | Duration was assessed via tabulation of the number of days with local symptoms of any grade after vaccination with Dose 1 and Dose 2, respectively. Solicited general symptoms assessed for duration in subjects 5 years of age and above were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches and shivering. | During the 7-day follow-up period (Days 0-6) after vaccination | 
| Number of Days With Fever in All Subjects Regardless of Their Age After Vaccination | Duration for fever was assessed via tabulation of the number of days with local symptoms of fever (axillary temperature ≥ 38°C) after vaccination with Dose 1 and Dose 2, respectively. | During the 7-day follow-up period (Days 0-6) after 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 unsolicited AE(s) = Occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 unsolicited AE = Occurrence of any unsolicited AE that prevented normal activities. Related unsolicited AE(s) = Occurrence of an unsolicited AE assessed by the investigator to be causally related to vaccination. | During the 28-day follow-up period (Day 0-27) after vaccination | 
| Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs) After Vaccination | Potential immune-mediated diseases (pIMDs) are a subset of adverse events that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Any pIMD(s) = Occurrence of any pIMD(s) regardless of intensity grade or relation to vaccination. Related pIMD(s) = pIMD assessed by the investigator as causally related to the study vaccination. | During the entire study period (from Day 0 to Day 180) | 
| Number of Subjects With Any and Related Medically-attended Adverse Events (MAEs) After Vaccination | Medically-attended adverse events (MAEs) were non-serious and serious events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. If a medically-attended adverse event was leading to hospitalization (or met any other criterion for serious adverse event (SAE)), it was reported as SAE. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination.Relationship to vaccination was not assessed for MAEs. | During the entire study period (from Day 0 to Day 180) | 
| Number of Subjects With Any and Related Serious Adverse Events (SAEs) | 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. Any SAE(s) = Occurrence of any SAE(s) regardless of intensity grade or relation to vaccination. Related SAE(s)= Occurrence of any SAE(s) assessed by the investigator as causally related to vaccination. | During the entire study period (from Day 0 to Day 180) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza