Trial to Evaluate the Safety and the Immunogenicity of GSK Biologicals' Influenza Vaccine GSK2186877A in Healthy Children

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' influenza vaccine GSK2186877A in healthy children 6 to 35 months of age. This Protocol Posting has been updated following Amendment 1 of the Protocol, Jun 2010. The impacted sections are study design, outcome measures, intervention sections and number of subjects.

Official Title
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Safety and Immunogenicity of GSK2186877A Candidate Seasonal Influenza Vaccine in Healthy Children 6 to 35 Months of Age.

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza vaccine GSK2186877A formulation 1
* Biological: Influenza vaccine GSK2186877A formulation 2
* Biological: Fluarix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must satisfy ALL the following criteria at study entry: Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol. Children, male or female between, and including, 6 and 35 months of age at the time of the first vaccination. Written informed consent obtained from the parent(s)/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Age appropriate scheduled childhood vaccinations completed to the best of parent(s)/LAR(s) knowledge. Exclusion Criteria: The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study: Child in care Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Prior receipt of any influenza vaccination (seasonal or pandemic) or planned administration during the study period. Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone >0.5 mg/kg of body weight, or equivalent. Inhaled and topical steroids are allowed. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). A family history of congenital or hereditary immunodeficiency. Any known or suspected allergy to any constituent of influenza or routine paediatric vaccines, a history of severe adverse reaction to any previous vaccination; or a history of anaphylactic-type reaction to consumption of egg proteins. History of any neurological disorders or seizures (including febrile convulsion). Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history or physical examination. Acute disease and/or fever at the time of enrolment: Fever is defined as temperature >= 37.5°C on oral, axillary or tympanic setting, or >=38.0°C on rectal setting. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever might be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the 3 month preceding the first dose of study vaccine or planned administration during the study period. Any condition which, in the opinion of the investigator, render the subject unfit for participation in the study.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza vaccine GSK2186877A formulation 1 Group<br>Subjects received 2 doses of influenza vaccine GSK2186877A formulation 1 at Day 0 and Day 21 and 1 dose of Fluarix vaccine at Month 6. | Biological: Influenza vaccine GSK2186877A formulation 1<br>* Intramuscular administration, 2 doses<br>Biological: Fluarix<br>* Intramuscular administration, 1 dose<br>|
| Experimental: Influenza vaccine GSK2186877A formulation 2 Group<br>Subjects received 1 dose of influenza vaccine GSK2186877A formulation 2 at Day 0 and 1 dose of Fluarix vaccine at Month 6. | Biological: Influenza vaccine GSK2186877A formulation 2<br>* Intramuscular administration, 1 dose<br>Biological: Fluarix<br>* Intramuscular administration, 1 dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Fever Grade 2 or Higher | Fever grade greater than or equal to 2 i.e. ≥ 2 was defined as axillary temperature >38 degree centigrade (°C). | Within 7 days following any vaccination with New generation influenza vaccine GSK2186877A | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers | Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains included Flu A/CAL/7/09 H1N1, Flu A/Uru/716/07 H3N2 and FluB/Bri/60/08 Victoria antigens. | At Day 0 and Day 42 | 
| The Number of Subjects Seropositive to HI Antibodies | A seropositive subject was defined as a subject with antibody titer greater than or equal to 1:10. The vaccine strains included Flu A/CAL/7/09 H1N1, Flu A/Uru/716/07 H3N2 and FluB/Bri/60/08 Victoria antigens. | At Day 0 and Day 42 | 
| The Number of Subjects Seroprotected to HI Antibodies | A seroprotected subject was defined as a subject with a serum HI titre greater than or equal to 1:40 that usually is accepted as indicating protection. The vaccine strains included Flu A/CAL/7/09 H1N1, Flu A/Uru/716/07 H3N2 and FluB/Bri/60/08 Victoria antigens. | At Day 0 and Day 42 | 
| The Number of Subjects Seroconverted to HI Antibodies | A seroconverted subject was defined as a subject who had either a pre-vaccination 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. The vaccine strains included Flu A/CAL/7/09 H1N1, Flu A/Uru/716/07 H3N2 and FluB/Bri/60/08 Victoria antigens. | Day 42 | 
| HI Antibody Geometric Mean Fold Rise (GMFR) | GMFR was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The vaccine strains included Flu A/CAL/7/09 H1N1, Flu A/Uru/716/07 H3N2 and FluB/Bri/60/08 Victoria antigens. | Day 42 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) | Grade 3 redness and swelling was > 50 millimeter (mm) and grade 3 pain was subjects crying when limb was moved/spontaneously painful. Any was occurrence of any local symptom regardless of their intensity grade. | Within 7 days following any vaccination with New generation influenza vaccine GSK2186877A | 
| Duration of Solicited Local AEs | Duration was defined as number of days with any grade of local symptoms following each dose of New generation influenza vaccine GSK2186877A. Dose 1 application of vaccine involved Influenza vaccine GSK2186877A formulation 1 Group and Influenza vaccine GSK2186877A formulation 2 Group while Dose 2 involved only Influenza vaccine GSK2186877A formulation 1 Group. | Within 7 days following any vaccination with New generation influenza vaccine GSK2186877A | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Any temperature was defined as axillary temperature ≥37.5°C, grade 3 temperature was axillary temperature >39.0°C. For other symptoms, any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination. Grade 3 drowsiness was defined as general symptom that prevented normal activity, grade 3 irritability was crying that cannot be comforted/prevented normal activity, grade 3 loss of appetite was not eating at all and grade 3 vomiting was defined as ≥3 episode of vomiting/day. Related was symptom assessed by the investigator as causally related to vaccination. | Within 7 days following any vaccination with New generation influenza vaccine GSK2186877A | 
| Duration of Solicited General AEs | Duration was defined as number of days with any grade of local symptoms following each dose of New generation influenza vaccine GSK2186877A. Dose 1 application of vaccine involved subjects in Influenza vaccine GSK2186877A formulation 1 Group and Influenza vaccine GSK2186877A formulation 2 Group while Dose 2 application of vaccine involved only subjects in the Influenza vaccine GSK2186877A formulation 1 Group. | Within 7 days following any vaccination with New generation influenza vaccine GSK2186877A | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited 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 was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was event that prevented normal activities and Related was defined as unsolicited AE assessed by the investigator to be causally related to the study vaccination. | Within 21 days after any vaccination with New generation influenza vaccine GSK2186877A | 
| Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit (MAEs) | For each solicited and unsolicited AE the subject experienced, the subject was asked if they had received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination, grade 3 was defined as symptom that prevented normal activity and related was symptom assessed by the investigator as causally related to the study vaccination. | Day 0 up to Month 7 | 
| Number of Subjects Reporting Any Potential Immune-Mediated-Diseases (pIMDs) | pIMDs are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. | Day 0 up to Month 7 | 
| Number of Subjects Reporting 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 was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was event assessed by the investigator as causally related to the study vaccination. | Day 0 up to Month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Influenza, Safety, Immunogenicity, Vaccine