Immunogenicity and Safety Study of FluarixTM Vaccine in Children Who Have Previously Been Vaccinated With PandemrixTM

Study Overview
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Brief Summary
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This study is designed to assess the immunogenicity, reactogenicity and safety following vaccination with GSK Biologicals' FluarixTM vaccine in children who have previously been vaccinated with one dose of PandemrixTM at the age of 10-17 years.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Seasonal (2010-2011) Influenza Vaccine FluarixTM in Adolescents Previously Vaccinated With GSK Biologicals' H1N1 Vaccine PandemrixTM

Conditions
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Influenza

Intervention / Treatment
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* Biological: FluarixTM
* Biological: HavrixTM Junior (in subjects of 15 years old or below) or HavrixTM (in subjects above 15 years old)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects having previously been immunized with only one single dose of Pandemrix at the age of 10-17 years inclusive. Subjects having received Pandemrix at least six months prior to study enrolment. Subjects who the investigator believes that subject and/or parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol Written informed consent obtained from the subject/ the parent(s)/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Subjects or Parent(s)/LAR(s) with access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device Exclusion Criteria: Active participation in other clinical trials. 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. Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration. 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. Acute disease and/or fever at the time of enrolment: Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination. Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned use during the study. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine. History of seizures or progressive neurological disease. Subjects having received an H1N1v pandemic vaccine other than Pandemrix or having received the 2010/2011 seasonal influenza vaccine. If the subject is female and if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Child in care.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluarix Group<br>Subjects previously vaccinated with Pandemrix vaccine received 1 dose of Fluarix vaccine. All vaccines were administered in the deltoid region of the non-dominant arm on Day 0. | Biological: FluarixTM<br>* One Intramuscular injection<br>|
| Active Comparator: Havrix Group<br>Subjects previously vaccinated with Pandemrix vaccine received 1 first dose of Havrix vaccine (subjects aged above 15 years) or Havrix-Junior vaccine (subjects aged 15 years and below). A second dose was given outside the study setting, at Month 6. All vaccines were administered in the deltoid region of the non-dominant arm on Day 0. | Biological: HavrixTM Junior (in subjects of 15 years old or below) or HavrixTM (in subjects above 15 years old)<br>* Two Intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Antibody Titres for Haemagglutination Inhibition (HI) Antibodies Against Fluarix Vaccine Containing H1N1 Strain. | Fluarix vaccine strain was Flu A/California/7/2009 (H1N1). Day 28 data were presented only for the Fluarix Group. Titres were expressed as geometric mean antibody titre. | At Day 0 and Day 28 | 
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies Against Fluarix Vaccine Containing H1N1 Strain. | Fluarix vaccine strain was Flu A/California/7/2009 (H1N1). Seropositivity was assessed for subjects with an antibody titre assay cut-off value equal to or above 1:10. Day 28 data was presented only for the Fluarix Group. | At Day 0 and Day 28 | 
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against Fluarix Vaccine Containing H1N1 Strain. | Fluarix vaccine strain was Flu A/California/7/2009 (H1N1). A seroconverted subject was a subject who had either a pre-vaccination (Day 0) titre less than (< ) 1:10 and a post-vaccination titre greater than or equal to ( ≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. Day 28 data were presented for the Fluarix Group only. | At Day 28 | 
| Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against Fluarix Vaccine Containing H1N1 Strain. | Fluarix vaccine strain was Flu A/California/7/2009 (H1N1). A seroprotected subject was a subject with a serum HI titre ≥ 1:40 that usually is accepted as indicating protection. Day 28 data were presented for the Fluarix Group only. | At Day 0 and Day 28 | 
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibodies Against Fluarix Vaccine Containing H1N1 Strain. | Fluarix vaccine strain was Flu A/California/7/2009 (H1N1). MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titre to the pre-vaccination (Day 0) reciprocal HI titre. Day 28 data were presented for the Fluarix Group only. | At Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Antibody Titres for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. Day 28 data were presented for the Fluarix Group only. Titres were expressed as geometric mean antibody titres (GMTs). | At Day 0 and Day 28 | 
| Geometric Mean Antibody Titres for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. Only data for the Flu A/California/7/2009 (H1N1) strain were presented for the Havrix Group. Titres were expressed as geometric mean antibody titres (GMTs). | At Day 0 and at Month 6 | 
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. Seropositivity was assessed for subjects with an antibody titre assay cut-off value equal to or above 1:10. Day 28 data were presented for the Fluarix Group only. | At Day 0 and Day 28 | 
| Number of Seropositive Subjects for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. Seropositivity was assessed for subjects with an antibody titre assay cut-off equal to or above 1:10. Only data for the Flu A/California/7/2009 (H1N1) strain were presented for the Havrix Group. | At Day 0 and at Month 6 | 
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. A seroconverted subject was a subject who had either a pre-vaccination (Day 0) titre less than (< ) 1:10 and a post-vaccination titre greater than or equal to ( ≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. Day 28 data were presented for the Fluarix Group only. | At Day 28 | 
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. A seroconverted subject was a subject who had either a pre-vaccination (Day 0) titre < 1:10 and a post-vaccination titre ≥ 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. Only data for the Flu A/California/7/2009 (H1N1) strain were presented for the Havrix Group. | At Month 6 | 
| Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. A seroprotected subject was a subject with a serum HI titre ≥ 1:40 that usually is accepted as indicating protection. Day 28 data were presented for the Fluarix Group only. | At Day 0 and Day 28 | 
| Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. A seroprotected subject was a subject with a serum HI titre ≥ 1:40 that usually is accepted as indicating protection. Only data for the Flu A/California/7/2009 (H1N1) strain were presented for the Havrix Group. | At Day 0 and Month 6 | 
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titre to the pre-vaccination (Day 0) reciprocal HI titre. Day 28 data were presented for the Fluarix Group only. | At Day 28 | 
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2) and B/Brisbane/60/2008. MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titre to the pre-vaccination (Day 0) reciprocal HI titre. Only data for the Flu A/California/7/2009 (H1N1) strain were presented for the Havrix Group. | At Month 6 | 
| Geometric Mean Antibody Titres for Neutralising Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Perth/16/09(H3N2) and B/Brisbane/60/2008. Day 28 data were presented for the Fluarix Group only. Titres were expressed as geometric mean antibody titres (GMTs). | At Day 0 and at Day 28 | 
| Geometric Mean Antibody Titres for Neutralising Antibodies Against All Fluarix Vaccine Strains. | Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Perth/16/09 (H3N2) and B/Brisbane/60/2008. Titres were expressed as geometric mean antibody titres (GMTs). | At Day 0 and at Month 6 | 
| Number of Seroconverted Subjects for Neutralising Antibodies Against All Fluarix Vaccine Strains. | A seroconverted subject for neutralising antibodies was a subject with a minimum 4-fold increase in titre at post-vaccination. Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Perth/16/09 (H3N2) and B/Brisbane/60/2008. Day 28 data were presented for the Fluarix Group only. | At Day 28 | 
| Number of Seroconverted Subjects for Neutralising Antibodies Against All Fluarix Vaccine Strains. | A seroconverted subject for neutralising antibodies was a subject with a minimum 4-fold increase in titre at post-vaccination. Fluarix vaccine strains were Flu A/California/7/2009 (H1N1), A/Perth/16/09 (H3N2) and B/Brisbane/60/2008. At Month 6, only data for the Flu A/California/7/2009 (H1N1) strain were presented for the Havrix Group. | At Month 6 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any solicited local symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling above 50 millimetres. | Within 7 days (Day 0 - Day 6) after vaccination | 
| Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, sweating, temperature (temperature = axillary temperature equal to or above 37.5 degrees Celsius). Any = occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = general symptom that prevented normal activity. Grade 3 temperature = axillary temperature above 39.0 degrees Celsius. | Within 7 days (Day 0 - Day 6) after vaccination | 
| Number of Days With Any Solicited Local Symptoms. | Solicited local symptoms assessed were pain, redness and swelling. Inter-quartile range assessed was the 25th percentile and the 75th percentile. | Within 7 days (Day 0 - Day 6) after vaccination | 
| Number of Days With Grade 3 Solicited Local Symptoms. | Solicited local symptoms assessed were pain and swelling. Grade 3 redness/swelling = redness/swelling above 50 millimetres. Inter-quartile range assessed was the 25th percentile and the 75th percentile. | Within 7 days (Day 0 - Day 6) after vaccination | 
| Number of Days With Any Solicited General Symptoms. | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, sweating, temperature (temperature = axillary temperature equal to or above 37.5 degrees Celsius). Inter-quartile range assessed was the 25th percentile and the 75th percentile. | Within 7 days (Day 0 - Day 6) after vaccination | 
| Number of Days With Grade 3 Solicited General Symptoms. | Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and myalgia. Grade 3 symptom = general symptom that prevented normal activity. Inter-quartile range assessed was the 25th percentile and the 75th percentile. | Within 7 days (Day 0 - Day 6) after vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. Grade 3 = event that prevented normal, everyday activities. Related = event assessed by the investigator as causally related to the study vaccination. | Within 28 days (Day 0 - Day 27) after vaccination | 
| Number of Subjects Reporting Medically-attended Events (MAEs). | For each solicited and unsolicited symptom the subject experienced, the subject was asked if they received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason. | Within the 28-day (Days 0-27) post-vaccination period | 
| Number of Subjects Reporting Medically-attended Events (MAEs). | For each solicited and unsolicited symptom the subject experienced, the subject was asked if they received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason. | During the entire study period (Up to Month 6) | 
| Number of Subjects Reporting Adverse Events of Specific Interest (AESIs)/Potential Immune Mediated Diseases (pIMDs). | Potential Immune-Mediated Diseases (pIMDs) or Adverse events of specific interest (AESI), 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. | During the entire study period (Up to Month 6) | 
| Number of Subjects Reporting Adverse Events of Special Interest. | Adverse events of special interest for safety monitoring includes both convulsion and anaphylaxis. | During the entire study period (Up to Month 6) | 
| Number of Subjects Reporting Serious Adverse Events (SAEs). | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | Within the 28-day (Days 0-27) post-vaccination period | 
| Number of Subjects Reporting Serious Adverse Events (SAEs). | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | During the entire study period (Up to Month 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Pandemrix, H1N1, Fluarix