Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine in Healthy Children

Study Overview
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Brief Summary
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The purpose of the present study is to assess the immunogenicity and safety of vaccine GSK2321138A in children.

Official Title
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Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine GSK2321138A in Healthy Children

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza vaccine GSK2321138A
* Biological: Fluarix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all subjects: Subjects who the investigator believes that they and/or their Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol. Written informed consent obtained from the subject/from the LAR(s). For unprimed subjects: A male or female child aged 18 to 47 months at the time of the first vaccination. Children who did not have influenza vaccine in a previous season. For primed subjects from study NCT00764790: • Children who received Fluarix™ in the 111751 study NCT00764790. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. History of hypersensitivity to any vaccine. History of allergy or reactions likely to be exacerbated by any component of the vaccine. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before and ending 28 days after each dose of vaccine(s). Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination. Acute disease at the time of enrolment. History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. Receipt of another seasonal influenza vaccine outside of this study, during current (2009-2010) flu season. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccination Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or blood products within the 3 month preceding the first dose of study vaccine or planned administration during the study period. 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.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 47 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2321138A Group<br>Subjects aged between 18 and 47 months received the GSK2321138A. Primed subjects (subjects who had received a 2-dose priming immunization with Fluarix™ vaccine in study NCT00764790 - or the GSK2321138A-Primed Group) received 1 dose of GSK2321138A vaccine at Day 0. Unprimed subject (subjects who had not received any 2-dose priming influenza immunization in any previous year - or the the GSK2321138A-Unprimed Group) received 2 doses of GSK2321138A vaccine at Days 0 and 28. The GSK2321138A vaccine was administered intramuscularly in the deltoid of the right arm. | Biological: Influenza vaccine GSK2321138A<br>* Intramuscular injection<br>|
| Active Comparator: Fluarix Group<br>Subjects aged between 18 and 47 months received the Fluarix™ vaccine. Primed subjects (subjects who had received a 2-dose priming immunization with Fluarix™ vaccine in study NCT00764790 - or the Fluarix-Primed Group) received 1 dose of Fluarix™ vaccine at Day 0. Unprimed subject (subjects who had not received any 2-dose priming influenza immunization in any previous year - or the the Fluarix-Unprimed Group) received 2 doses of Fluarix™ vaccine at Days 0 and 28. The Fluarix™ vaccine was administered intramuscularly in the deltoid of the right arm. | Biological: Fluarix™<br>* Intramuscular injection<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 the 3 Fluarix Vaccine Strains. | Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. The 3 influenza strains assessed were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2) and Flu B/Brisbane/60/08 Victoria (VICT).The POST results were the primary outcome variables. | At Day 0 [PRE] and at 28 days post last vaccination (Day 28 or Day 56) [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 1:10. The 4 influenza strains assessed were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups. | At Days 0 and 28. | 
| 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/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups. | At Days 0, 28 and Day 56 | 
| Number of Seropositive Subjects Against 4 Strains of Influenza Disease. | A seropositive subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:10. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups. | At Days 0 and 28 | 
| Number of Seropositive Subjects Against 4 Strains of Influenza Disease. | A seropositive subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:10. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups. | At Days 0, 28 and 56 | 
| 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 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups. | At Day 28 | 
| 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 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups. | At Days 28 and 56 | 
| 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 compared to Day 0. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups. | At Day 28 | 
| 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 compared to Day 0. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups. | At Days 28 and 56 | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the primed groups. | At Days 0 and 28 | 
| Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), Flu B/Brisbane/60/08 Victoria (VICT) and Flu B/Brisbane/3/07 Yamagata (YAMA). This outcome only covers the results for the unprimed groups. | At Days 0, 28 and 56 | 
| 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 = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. | During the 7-day follow-up period (Days 0 to 6) after any vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature (defined as axillary temperature equal to or above 37.5 degrees Celsius). For other symptoms: Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms assessed by the investigator as related to vaccination. Grade 3 drowsiness = prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 irritability= crying that could not be comforted/prevented normal activity. Grade 3 temperature: ≥ 39.0°C. | During the 7-day follow-up period (Days 0 to 6) after any vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited AE covers any untoward medical occurrence in a subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 = occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to vaccination. | During the 28-day follow-up period (Days 0 to 27) after vaccination | 
| 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 or result in disability/incapacity. Any was defined as occurrence of any symptom regardless of intensity grade and related was an event assessed by the investigator as causally related to the study vaccination. | From Day 0 to Day 180 (study conclusion) | 
| Number of Subjects With Any Adverse Events of Specific Interest (AESIs). | An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration. | From Day 0 to Day 180 (study conclusion) | 

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