Immunogenicity and Safety Study of Fluarix™ Vaccine in Children Who Have Previously Been Vaccinated With Pandemrix™

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' Fluarix vaccine in children who have previously been vaccinated with two doses of Pandemrix at the age of 6 months-9 years.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Seasonal (2010-2011) Influenza Vaccine Fluarix™ in Children Previously Vaccinated With GSK Biologicals' H1N1 Vaccine Pandemrix™

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluarix™
* Biological: Havrix™ Junior


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects having previously been immunized with two 0.25 mL doses of Pandemrix, given at least 21 days apart, at the age of 6 months to 9 years inclusive at the time of first vaccination. Subjects having received the last dose of Pandemrix at least six months prior to study enrolment. Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol. Written informed consent obtained from the parent(s)/LAR(s) of the subjects. Healthy subjects as established by medical history and clinical examination before entering into the study. Parent/LAR 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. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. 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 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. Child in care.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 10 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 6-11 months Group<br>Subjects previously vaccinated with Pandemrix vaccine, will receive one or two doses of Fluarix vaccine | Biological: Fluarix™<br>* One or two intramuscular injections<br>|
| Experimental: Fluarix 12-35 months Group<br>Subjects previously vaccinated with Pandemrix vaccine, will receive one or two doses of Fluarix vaccine | Biological: Fluarix™<br>* One or two intramuscular injections<br>|
| Experimental: Fluarix 3-9 years Group<br>Subjects previously vaccinated with Pandemrix vaccine, will receive one or two doses of Fluarix vaccine | Biological: Fluarix™<br>* One or two intramuscular injections<br>|
| Active Comparator: Havrix Junior 6-11 months Group<br>Subjects previously vaccinated with Pandemrix vaccine will receive two doses of Havrix Junior vaccine | Biological: Havrix™ Junior<br>* Two intramuscular injections<br>|
| Active Comparator: Havrix Junior 12-35 months Group<br>Subjects previously vaccinated with Pandemrix vaccine will receive two doses of Havrix Junior vaccine | Biological: Havrix™ Junior<br>* Two intramuscular injections<br>|
| Active Comparator: Havrix Junior 3-9 years Group<br>Subjects previously vaccinated with Pandemrix vaccine will receive two doses of Havrix Junior vaccine | Biological: Havrix™ Junior<br>* Two intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers Against H1N1 in All Subjects Receiving Fluarix Vaccine | Antibody titers were expressed as Geometric mean titers (GMTs). | Day 0 and 28 | 
| Number of Subjects Seropositive for HI Antibodies Against H1N1 in All Subjects Receiving Fluarix Vaccine | Seropositivity was defined as antibody titers greater than or equal to 1:10. | Day 0-28 | 
| Number of Subjects Seroprotected for HI Antibodies Against H1N1 in All Subjects Receiving Fluarix Vaccine | A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. | Day 0-28 | 
| Number of Subjects Seroconverted for HI Antibodies Against H1N1 in All Subjects Receiving Fluarix Vaccine | A seroconverted subject was defined as a subject that had either a prevaccination (Day 0) 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. | Day 28 | 
| Mean Geometric Increase (MGI) in HI Antibody Titers Against H1N1 in All Subjects Receiving Fluarix Vaccine | MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 28) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI Antibody Titers Against All Fluarix Vaccine Strains | Antibody titers were expressed as GMTs. Vaccine strains included in the analysis were Flu A/CAL/7/09 H1N1 , FluB/Bri/60/08 Victoria, and Flu A/Vic/210/09 H3N2, further in this summary denoted as H1N1, Victoria and H3N2 strains, respectively. | Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) | 
| HI Antibody Titers Against H1N1 in Subjects Receiving Havrix Junior Vaccine | Antibody titers were expressed as GMTs. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Day 0 and Month 6 | 
| Number of Subjects Seropositive for HI Antibodies Against All Fluarix Vaccine Strains | Seropositivity was defined as antibody titers greater than or equal to 1:10. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains. | Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) | 
| Number of Subjects Seropositive for HI Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine | Seropositivity was defined as antibody titers greater than or equal to 1:10. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Day 0 and Month 6 | 
| Number of Subjects Seroconverted for HI Antibodies Against All Fluarix Vaccine Strains in All Subjects Receiving Fluarix Vaccine | A seroconverted subject was defined as a subject that had either a pre-vaccination (Day 0) 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. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains. | Day 28 | 
| Number of Subjects Seroconverted for HI Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine | A seroconverted subject was defined as a subject that had either a pre-vaccination (Day 0) 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. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Month 6 | 
| Number of Subjects Seroprotected for HI Antibodies Against All Fluarix Vaccine Strains | A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains. | Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) | 
| Number of Subjects Seroprotected for HI Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine | A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Day 0 and Month 6 | 
| Mean Geometric Increase (MGI) in HI Antibody Titers Against All Fluarix Vaccine Strains in All Subjects Receiving Fluarix Vaccine | MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination (Day 28) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains. | Day 28 | 
| Mean Geometric Increase (MGI) in HI Antibody Titers Against H1N1 in Subjects Receiving Havrix Junior Vaccine | MGI is defined as the geometric mean of the within-subject ratios of the post-vaccination (Month 6) reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Month 6 | 
| Serum Neutralising Antibody Titers Against All Fluarix Vaccine Strains | Antibody titers were expressed as Geometric Mean Titers (GMTs). | Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) | 
| Serum Neutralising Antibody Titers Against H1N1 in Subjects Receiving Havrix Junior Vaccine | Antibody titers were expressed as GMTs.] Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Day 0 and Month 6 | 
| Number of Subjects Seropositive for Serum Neutralising Antibodies Against All Fluarix Vaccine Strains | Seropositivity was defined as antibody titers greater than or equal to 1:28. | Day 0 (for all groups) and Day 28 (for groups receiving Fluarix only) | 
| Number of Subjects Seropositive for Serum Neutralising Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine | Seropositivity was defined as antibody titers greater than or equal to 1:28. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Day 0 and Month 6 | 
| Number of Subjects Seroconverted for Serum Neutralising Antibodies Against All Fluarix Vaccine Strains in Subjects Receiving Fluarix | Seroconverted subject was a subject with a minimum 4-fold increase in titer at post-vaccination for neutralizing antibody response. | Day 28 | 
| Number of Subjects Seroconverted for Serum Neutralising Antibodies Against H1N1 in Subjects Receiving Havrix Junior Vaccine | Seroconverted subject was a subject with a minimum 4-fold increase in titer at post-vaccination for neutralizing antibody response. Vaccine strains included in the analysis were H1N1, Victoria and H3N2 strains for subjects in groups receiving Fluarix vaccine and H1N1 strain for subjects in groups receiving Havrix Junior Vaccine. | Month 6 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed include: pain, redness and swelling. Any is any symptom regardless of intensity. Grade 3 was defined as a symptom that prevented normal activity.above 50 millimeter. | During the 7 days (Day 0 - 6) after vaccination | 
| Duration of Any Solicited Local Symptom | Duration was expressed as median number of days the symptom persisted. Solicited local symptoms assessed include: pain, redness and swelling. | During the 7 days (Days 0 - 6) after vaccination | 
| Number of Subjects Less Than 6 Years Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed include diarrhoea, drowsiness, irritability, loss of appetite and fever. Any was defined as any symptom regardless of intensity; any fever was axillary temperature greater than or equal to 37.5 degrees celsius. Grade 3 was a symptom preventing normal everyday activity; grade 3 loss of appetite was not eating at all; grade 3 fever was axillary temperature above 39 degrees celsius. Related was any symptom assessed by the investigator as causally related to the study vaccination. | During the 7 days (Days 0-6) after vaccination | 
| Duration of Any Solicited General Symptom Experienced by Subjects Less Than 6 Years Old | Duration was expressed as median number of days the symptom persisted. Solicited general symptoms assessed include diarrhoea, drowsiness, irritability, loss of appetite and fever. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Number of Subjects Above 6 Years Reported Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, sweating and fever. Any was defined as any symptom regardless of intensity; any fever was axillary temperature greater than or equal to 37.5 degrees celsius. Grade 3 was a symptom preventing normal everyday activity; grade 3 fever was axillary temperature above 39 degrees celsius. Related was any symptom assessed by the investigator as causally related to the study vaccination. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Duration of Any Solicited General Symptom Experienced by Subjects Above 6 Years Old | Duration was expressed as median number of days the symptom persisted. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever. | During a 7-day follow-up period (Day 0-6) after vaccination | 
| Number of Subjects Reporting 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 was defined as any symptom regardless of intensity or relationship to vaccination. Grade 3 was a symptom preventing normal everyday activity. Related was any symptom assessed by the investigator as causally related to the study vaccination. | During a 28 day follow-up period (Day 0-27) after vaccination | 
| Number of Subjects Reporting Medically-Attended Events (MAEs), Adverse Events of Specific Interest (AESIs)/ Potential Immune Mediated Diseases (pIMDs) and Adverse Events (AEs) of Special Interest | MAEs: subject received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. AESIs/pIMD: includes both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Adverse events of special interest include both convulsion and anaphylaxis. | During the entire study period (up to Month 6) | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | SAEs: 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. | Up to Day 28 | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | SAEs: 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. | Up to Month 6 | 

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