Study of GSK Biologicals' Pandemic Influenza (H1N1) Candidate Vaccine in Children Aged 10 to Less Than 18 Years

Study Overview
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Brief Summary
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The purpose of this study is to show that vaccination with a single dose of GSK Biologicals' pandemic H1N1 vaccine results in an immune response that meets or exceeds European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP) guidance criteria for a pandemic influenza vaccine.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza (H1N1) Candidate Vaccine (GSK2340274A) in Children Aged 10 to Less Than 18 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A
* Biological: GSK Biologicals' Influenza investigational vaccine GSK2340273A
* Biological: Placebo (saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female children 10 to < 18 years of age at the time of the first vaccination. Less than 18 years of age implies inclusion of adolescents who have not reached their 18th birthday as of Day 0, the day of the first vaccine dose under this protocol. Written informed consent obtained from the subject's parent/legally acceptable representative (LAR); written informed assent obtained from the subject if appropriate. Good general health as established by medical history and clinical examination before entering into the study. Parent/LAR access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device. Subjects who the investigator believes that they and/or their parent(s)/LAR can and will comply with the requirements of the protocol. Exclusion Criteria: Medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus. Previous vaccination at any time with an A/California/7/2009 (H1N1)v-like virus vaccine. Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject or parent(s)/ LAR(s) unable/unlikely to provide accurate safety reports. Presence of a temperature >= 38.0ºC by any route or method, or acute symptoms greater than mild severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied. Diagnosed with cancer, or treatment for cancer, within 3 years. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Receipt of systemic glucocorticoids within 1 month prior to study enrollment (first dose of study vaccine), or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Topical, intra-articular or inhaled glucocorticoids are allowed. Receipt of any immunoglobulins and/or any blood products within 6 months of study enrollment or planned administration of any of these products during the study period. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin are eligible if no such doses are given in the 24 hours before a study vaccination. Persons receiving prophylactic antiplatelet medications, e.g., low-dose acetylsalicylic acid, and without a clinically-apparent bleeding tendency, are eligible. An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine. Administration of any licensed vaccine within 30 days before the first dose of study vaccine, with the exception of seasonal influenza vaccine (which may be given within 2 weeks before the first dose of study vaccine). Planned administration of any A/California H1N1v-like vaccine other than the study vaccine between Day 0 and the Day 189 phlebotomy. Planned administration of any other vaccine not foreseen by the study protocol between Day 0 and Day 42 after the first vaccine dose, including seasonal influenza vaccine. Routine childhood vaccinations are exempted if they cannot be delayed, but they must not be administered on the same day as the H1N1 vaccine candidate. 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. Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Child in care.

Ages Eligible for Study
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Minimum Age: 10 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AREPANRIX-ADJUVANTED F1 2D GROUP<br>Subjects received 2 doses of Arepanrix ™ formulation 1 adjuvanted vaccine on Day 0 and Day 182 (booster) and one dose of saline placebo on Day 21. | Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A<br>* One or two doses administered intramuscularly<br>Biological: Placebo (saline)<br>* One dose intramuscularly<br>|
| Experimental: AREPANRIX-ADJUVANTED F2 2D GROUP<br>Subjects received 2 doses of Arepanrix ™ formulation 2 adjuvanted vaccine on Day 0 and Day 182 (booster) and one dose of saline placebo on Day 21. | Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A<br>* One or two doses administered intramuscularly<br>Biological: Placebo (saline)<br>* One dose intramuscularly<br>|
| Experimental: AREPANRIX-ADJUVANTED F2 3D GROUP<br>Subjects received 3 doses of Arepanrix ™ formulation 2 adjuvanted vaccine on Day 0, Day 21 and Day 182 (booster). | Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A<br>* One or two doses administered intramuscularly<br>|
| Experimental: AREPANRIX-UNADJUVANTED F2 2D GROUP<br>Subjects received 2 doses of Arepanrix ™ unadjuvanted vaccine on Day 0 and Day 182 (booster) and one dose of saline placebo on Day 21. | Biological: GSK Biologicals' Influenza investigational vaccine GSK2340273A<br>* Two doses intramuscularly<br>Biological: Placebo (saline)<br>* One dose intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | Seroconversion defined as: - For initially seronegative subjects, antibody titre ≥ 1:40 after vaccination - For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre | At Day 21 | 
| Number of Subjects Seroprotected for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | 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. | At Day 0 and Day 21 | 
| HI Antibody Seroconversion Factors Against Flu A/CAL/7/09 H1N1 Strain | Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain | Antibody titres were expressed as Geometric mean titers (GMTs). | At Day 0 and Day 42 | 
| HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain | Antibody titres were expressed as GMTs. | At Day 0 and Day 182 | 
| HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain | Antibody titres were expressed as Geometric mean titers (GMTs). | At Days 0, 182 and 189 | 
| Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | A seroconverted subject was defined as a subject who had either a pre-vaccination titre below 1:10 and a post-vaccination titre greater than or equal to 1:40 or a pre-vaccination titre greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titre. | At Day 42 | 
| HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain | Antibody titers were expressed as GMTs. | At Day 0 and Day 21 | 
| Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | A seroconverted subject was defined as a subject who had either a pre-vaccination titre below 1:10 and a post-vaccination titre greater than or equal to 1:40 or a pre-vaccination titre greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titre. | At Day 182 | 
| Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | A seroconverted subject was defined as a subject who had either a pre-vaccination titre below 1:10 and a post-vaccination titre greater than or equal to 1:40 or a pre-vaccination titre greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titre. Day 0 was used as reference activity. | At Day 189 | 
| Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | 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. Day 182 was used as reference activity. | At Day 189 | 
| The Number of Subjects Seroprotected for HI Antibodies Against Flu A/CAL/7/09 H1N1 | 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. | At Day 0 and Day 42 | 
| Number of Subjects Seroprotected to HI Antibodies Against Flu A/CAL/7/09 H1N1 | 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. | At Day 0 and Day 182 | 
| Number of Subjects Seroprotected to HI Antibodies Against Flu A/CAL/7/09 H1N1 | 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. | At Day 0, Day 182 and Day 189 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 H1N1 | GMFR (also known as the seroconversion factor, SCF) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. | At Day 42 | 
| GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 | GMFR (also known as the seroconversion factor, SCF) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. | At Day 182 | 
| GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 Using Day 0 as Reference Activity | GMFR (also known as the seroconversion factor, SCF) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. | At Day 189 | 
| GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 Using Day 182 as Reference Activity | GMFR (also known as the seroconversion factor, SCF) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. | At Day 189 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) | Any was defined as occurrence of any local symptom regardless of their intensity grade.Grade 3 redness and swelling was > 100 millimeter (mm) and grade 3 pain was defined as pain that prevented normal activity. | During the 7-day (Days 0-6) post-vaccination period following each dose | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local AEs | Any was defined as occurrence of any local symptom regardless of their intensity grade.Grade 3 redness and swelling was > 100 millimeter (mm) and grade 3 pain was defined as pain that prevented normal activity | During the 7-day (Days 0-6) post-vaccination period following booster dose | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering, sweating and fever (Fever = axillary temperature equal to or above 38.0 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature equal to or above (≥) 39.0°C. | During the 7-day (Days 0-6) post-vaccination period following each dose | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering, sweating and fever (Fever = axillary temperature equal to or above 38.0 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature equal to or above (≥) 39.0°C. | During the 7-day (Days 0-6) post-vaccination period following booster dose | 
| Number of Subjects Reporting Any Medically Attended Events (MAEs) | MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. | During the entire study period (Days 0-364) following the first vaccination | 
| Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs) | pIMDs were defined as a subset of AEs that included 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 (Days 0-364) following first vaccination | 
| Number of Subjects With Normal and Abnormal Hematological and Biochemical Parameters Assessed With Respect to Normal Laboratory Ranges | Subjects were categorized according to their results at pre-vaccination (PRE), Day 21, Day 42, Day 182 and Day 189 which were within normal, above normal, below the normal ranges or unknown. The laboratory parameters assessed were Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT), Total Bilirubin, Creatinine, Hematocrit, Hemoglobin, Platelets, Blood urea nitrogen (BUN) and White blood cells (WBCs). | At Days 0, 21, 42, 182 and 189 | 
| Number of Subjects Reporting Any 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 any symptom regardless of intensity or relationship to vaccination. | During the 42-day (Days 0-41) follow up period after first vaccination. | 
| Number of Subjects Reporting Any 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 any symptom regardless of intensity or relationship to vaccination. | During the 21-day (Days 0-20) follow-up period after booster vaccination. | 
| 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. | During the entire study period (Day 0 to Day 364) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pandemic influenza, Clinical trial, H1N1, children