A Study to Evaluate the Safety and Immunogenicity of a Prime-boost Schedule of GSK Biologicals' Influenza Vaccine in Children

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of a prime-boost schedule of GSK Biologicals' influenza vaccine in children aged 3 to 17 years.

Detailed Description
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In this study Influenza vaccine GSK1562902A is the primary study vaccine and Havrix™ will be administered as the active comparator and not co-administered along with the study vaccine.Therefore, there exist no relation between the vaccines administered in this study. As the study will be carried out in Philippines, Havrix™ vaccine will be used as an active comparator instead of saline placebo to offer an advantage to the subjects.

Official Title
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Safety and Immunogenicity Study of a Prime-boost Schedule of GSK Biologicals' Influenza Vaccine GSK1562902A in Children Aged 3 to 17 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza vaccine GSK1562902A Formulation 1
* Biological: Influenza vaccine GSK1562902A Formulation 2
* Biological: Havrix™
* Biological: Havrix™ Junior


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 for whom the investigator believes that the parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol . A male or female child 3 to 17 years of age inclusive, at the time of the first vaccination. Written informed consent obtained from the subject's parent or guardian. Assent obtained from the subject when applicable. Good general health as established by medical history and clinical examination before entering into the study. Comprehension by the subject's parent or guardian of the study requirements, ability to comprehend and comply with procedures for collection of short- and long-term safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits. 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 (i.e., a common-use phone serving multiple rooms or apartments). 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 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: 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 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 21 days after any study vaccine administration. Active participation in other clinical trials. Receipt of systemic glucocorticoids within 1 month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Topical, intra-articular or inhaled glucocorticoids are allowed. 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 (no laboratory testing required). Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination. An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine. Receipt of any immunoglobulins and/or any blood products within 9 months of study enrolment or planned administration of any of these products during the study period. Any known or suspected allergy to any constituent of influenza vaccines ; a history of anaphylactic-type reaction to vaccine components or a history of severe adverse reaction to a previous influenza vaccine. History of seizures or progressive neurological disease. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. Diagnosed with cancer or any chronic severe disease. Previous administration of any H5N1 vaccine.

Ages Eligible for Study
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Minimum Age: 3 Years
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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group<br>Subjects in this group received 2 primary vaccination doses of Influenza vaccine GSK1562902A Formulation 1, a booster vaccination dose of Influenza vaccine GSK1562902A Formulation 2 and 1 dose of Havrix™ or Havrix™ Junior vaccine, administered intramuscularly in the deltoid region. | Biological: Influenza vaccine GSK1562902A Formulation 1<br>* Intramuscular injection, two doses each in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group<br>Biological: Influenza vaccine GSK1562902A Formulation 2<br>* Intramuscular injection, one dose each in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group<br>Biological: Havrix™<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>Biological: Havrix™ Junior<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group,GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>|
| Experimental: GSK1562902A Formulation 1 - Havrix / Havrix Jr Group<br>Subjects in this group received 2 primary vaccination doses of Influenza vaccine GSK1562902A Formulation 1 and 2 doses of Havrix™ or Havrix™ Junior vaccine, administered intramuscularly in the deltoid region. | Biological: Influenza vaccine GSK1562902A Formulation 1<br>* Intramuscular injection, two doses each in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group<br>Biological: Havrix™<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>Biological: Havrix™ Junior<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group,GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>|
| Active Comparator: GSK1562902A Formulation 2 - Havrix / Havrix Jr Group<br>Subjects in this group received 1 dose of Influenza vaccine GSK1562902A Formulation 2 and 2 doses of Havrix™ or Havrix™ Junior vaccine, administered intramuscularly in the deltoid region. | Biological: Influenza vaccine GSK1562902A Formulation 2<br>* Intramuscular injection, one dose each in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group<br>Biological: Havrix™<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>Biological: Havrix™ Junior<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group,GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>|
| Active Comparator: Havrix / Havrix Jr Group<br>Subjects in this group received 2 doses of Havrix™ or Havrix™ Junior vaccine, administered intramuscularly in the deltoid region. | Biological: Havrix™<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>Biological: Havrix™ Junior<br>* Intramuscular injection, one dose in GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and two doses each in GSK1562902A Formulation 1 - Havrix / Havrix Jr Group,GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and Havrix / Havrix Jr Group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers for the A/Turkey/Turkey/01/2005 (H5N1) Vaccine Strain. | Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Turkey/Turkey/01/2005 antigen. The A/Turkey/Turkey/01/2005 (A/TURK) vaccine strain was administered to groups receiving the adjuvanted Influenza vaccine GSK1562902A. This outcome concerns solely subjects in the GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group as required by the protocol. | At Day 192. | 
| Number of Subjects With Any Medically Attended Adverse Events (MAEs) | Any = occurrence of the symptom regardless of intensity grade. This outcome concerns solely subjects in the GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group as required by the protocol. | From Day 0 to Day 182 | 
| Number of Subjects With Any Medically Attended Adverse Events (MAEs) | Any = occurrence of the symptom regardless of intensity grade. | From Day 0 to Day 364. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| H5N1 HI Antibody Titres Against the A/Indonesia/5/2005 and A/Turkey/Turkey/01/2005 (H5N1 Virus) Strains | The antibody titres were given as Geometric Mean Titer (GMT). A/Indonesia/5/2005 = A/INDO and A/Turkey/Turkey/01/2005 = A/TURK. | At Days 0, 42, 182, 192, 364 | 
| H5N1 HI Neutralizing Antibody Titres Against the A/Indonesia/5/2005 and A/Turkey/Turkey/01/2005 (H5N1 Virus) Strains | Antibody titers were given as GMTs. A/Indonesia/5/2005 = A/INDO and A/Turkey/Turkey/01/2005 = A/TURK. | At Days 0, 42, 182, 192, 364 | 
| Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms. | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Relationship analysis was not performed. | During a 7-day (Day 0-6) follow-up period after each vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were diarrhea/vomiting, drowsiness, irritability/fussiness, loss of appetite and temperature [defined as axillary temperature equal to or above 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. The symptoms were assessed for subjects aged less than 6 years. | During a 7-day (Day 0-6) follow-up period after each vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. | Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia and temperature[defined as axillary temperature equal to or above 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. The symptoms were assessed for subjects aged 6 years or more. | During a 7-day (Day 0-6) follow-up period after vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited AE covers any untoward medical occurrence in a clinical investigation 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During a 21-day (Days 0 - 20) follow-up period after vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited AE covers any untoward medical occurrence in a clinical investigation 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During Day 0 to Telephone Contact (TC) Day 84 overall. | 
| Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs) |  | During the entire study period (Day 0 to 364) | 
| Number of Subjects With 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. | During the entire study period (Day 0 to 364) | 
| Number of Subjects With Anti-H5N1 Antibodies Above the Cut Off Values ≥1:10 | Seropositivity rates against the A/Indonesia/5/2005 (H5N1 virus) strain, were tabulated on Days 0,42,182 for all subjects, 192 for GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and 364 for GSK1562902A Formulation 1 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group. Seropositivity rates against the A/turkey/Turkey/01/2005 (H5N1 virus) strain, were tabulated on Days 182, 192 and 364. | At Days 0, 42, 182, 192 and 364 | 
| Number of Seroconverted Subjects Against the A/Indonesia/05/2005 Strains of H5N1 Influenza Disease | A seroconverted subject was defined as a vaccinee with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. Seroconversion rates against the A/Indonesia/05/2005 (H5N1 VIRUS) strain were tabulated on Days 0,42,182 for all subjects, 192 for GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and 364 for GSK1562902A Formulation 1 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group. | At Days 42, 182, 192 and 364 | 
| Number of Seroprotected Subjects Against the A/Indonesia/05/2005 and A/Turkey/Turkey/01/2005 Strains of H5N1 Influenza Disease | 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. Seroprotection rates against the A/Indonesia/5/2005 (H5N1 virus) strain, were tabulated 95% CI on Days 0,42,182 for all subjects, 192 for GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 -Havrix / Havrix Jr Group and 364 for GSK1562902A Formulation 1 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group. Seroprotection rates against the A/turkey/Turkey/01/2005 (H5N1 virus) strain, were tabulated on Days 182 and 192. | At Days 0,42, 182, 192 and 364 | 
| Mean Geometric Increase for Anti-H5N1 Antibody Titers | MGI against the A/Indonesia/05/2005 (H5N1 VIRUS) strain were tabulated on Days 0,42,182 for all subjects, 192 for GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and 364 for GSK1562902A Formulation 1 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group. MGI against the A/turkey/Turkey/01/2005 (H5N1 virus) strain were tabulated on Days 42, 182 and 364. | At Days 42, 182, 192 and 364 | 
| Number of Seroconverted Subjects Against the A/Turkey/Turkey/01/2005 Strains of H5N1 Influenza Disease | Booster seroconversion rates against the A/turkey/Turkey/01/2005 (H5N1 VIRUS) strain were tabulated on Days 192 and 364. This outcome concerns solely subjects in the GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group as required by the protocol. | At Days 192 and 364 | 
| Booster Factor for Hemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/01/2005 Strain of H5N1 Influenza Disease | Boooster factor against the A/turkey/Turkey/01/2005 (H5N1 VIRUS) strain were tabulated 95% CI on Days 192,364. This outcome concerns solely subjects in the GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group as required by the protocol. | At Days 192 and 364 | 
| Number of Subjects With Neutralizing Anti-H5N1 Antibody Titers | Seropositivity rates against the A/Indonesia/5/2005 (H5N1 virus) strain, were tabulated on Days 0,42,182 for all subjects, 192 for GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group, GSK1562902A Formulation 2 - Havrix / Havrix Jr Group and 364 for GSK1562902A Formulation 1 - Havrix / Havrix Jr Group and GSK1562902A Formulation 1 - Havrix / Havrix Jr Group. Seropositivity rates against the A/turkey/Turkey/01/2005 (H5N1 virus) strain, were tabulated on Days 0, 42,182, 192 and 364. | At Days 0, 42, 182 192 and 364 | 
| Number of Subjects With Vaccine Response Rates (VRR) for H5N1 Neutralizing Antibodies |  | At Days 42, 182 192 and 364 | 
| Number of Subjects With Booster Vaccine Response for H5N1 Neutralizing Antibodies | This outcome concerns solely subjects in the GSK1562902A Formulation 1 and 2 - Havrix / Havrix Jr Group and GSK1562902A Formulation 2 - Havrix / Havrix Jr Group as required by the protocol. | At Days 192 and 364 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, H5N1, vaccine, children