Study to Evaluate the Immunogenicity and Safety of an Investigational Influenza Vaccine (H1N1) in Children

Study Overview
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Brief Summary
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The objective of this study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A in children aged between 3 and 17 years.

Detailed Description
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This Protocol Posting has been updated following Protocol amendment 1, October 2009. The impacted section are the study design section, the outcomes measures section and the intervention section.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (GSK2340272A) in Children Aged 3 to 17 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK investigational vaccine GSK2340272A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol. Children, male or female, aged between 3 and 17 years at the time of the first study vaccination. Written informed consent obtained from the subject parent(s) or LAR(s) of the subject. Assent obtained from the subject when applicable. Healthy children as established by medical history and clinical examination when 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: 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. Clinically or virologically confirmed influenza infection within six months preceding the study start. 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. Previous administration of any H1N1 A/California-like vaccine. Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned during the study. 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. 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. Known use of an analgesic or antipyretic medication within 12 hours prior to first vaccination. Child in Care.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Subjects receiving alternative dose of GSK23440272A vaccine | Biological: GSK investigational vaccine GSK2340272A<br>* Three intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against the Flu A/California/7/2009 (H1N1) Vaccine Strain | Antibody titers were expressed as Geometric mean titers (GMTs). | At Day 0, Day 21 and Day 42 | 
| Number of Seroconverted Subjects for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination 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. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years. | At Day 42 | 
| Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years. | At Day 42 | 
| HI Antibody Geometric Mean Fold Rise (GMFR) Against the Flu A/California/7/2009 (H1N1) Virus Strain | GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The CHMP criterion was fulfilled if the point estimate for GMFR was greater than (>) 2.5 in children aged 3 to 17 years | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against the Flu A/California/7/2009 (H1N1) Vaccine Strain | Antibody titers were expressed as geometric mean titers (GMTs) | At Month 6 | 
| Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against the Flu A/California/7/2009 (H1N1) Vaccine Strain | Antibody titers were expressed as geometric mean titers (GMTs) | At Month 12 | 
| Number of Seroconverted Subjects for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination 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. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years. | At Month 6 | 
| Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years. | At Month 6 | 
| Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years. | At Month 12 | 
| HI Antibody Geometric Mean Fold Rise (GMFR) Against the Flu A/California/7/2009 (H1N1) Virus Strain | GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The CHMP criterion was fulfilled if the point estimate for GMFR was greater than (>) 2.5 in children aged 3 to 17 years | At Month 6 | 
| Humoral Immune Response in Terms of Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Vaccine Strain | Antibody titers were expressed as Geometric mean titers (GMTs). | At Day 0, Day 21, Day 42 and Month 6 | 
| Humoral Immune Response in Terms of Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Vaccine Strain | Antibody titers were expressed as Geometric mean titers (GMTs). | At Month 12 | 
| Number of Seroconverted Subjects for Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Virus Strain | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination 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. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years. | At Day 21 and Day 42 | 
| Number of Seroconverted Subjects for Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Virus Strain | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination 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. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years. | At Month 6 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities as assessed by inability to attend/do work or school or cried when limb was moved/spontaneously painful. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. > 50mm. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed were arthralgia, diarrhoea, drowsiness, fatigue, gastro-intestinal symptoms, headache, irritability, loss of appetite, myalgia, shivering, sweating and fever [axillary temperature above 37.5 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 above 39.0°C. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs) | MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination. | During the entire study period (Day 0 to Month 12) | 
| Number of Subjects Reporting Any Adverse Events of Specific Interest (AESI)/Potential Immune-mediated Diseases (pIMDs) | Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune etiology. Any pIMD was defined as at least one pIMD experienced by the study subject. | During the entire study period (Day 0 to Month 12) | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | An unsolicited AE was defined as any AE (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. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. | Within the 84-day after the first vaccination or from 63-day follow-up period after the second vaccination | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. | During the entire study period (Day 0 to Month 12) | 
| Number of Subjects With Normal and Abnormal Haematological and Biochemistry Parameters With Respect to Alanine Aminotransferase (ALAT), Aspartate Aminotransferase (ASAT), Total Bilirubin, Bilirubin Conjugated/ Direct,Creatine and Blood Urea Nitrogen(BUN) | Subjects were categorized by age and according to their results at pre-vaccination (Day 0), Day 21, Day 42 and Month 6 which were below, within and above the normal ranges or unknown as measured by validated assay according to international standards. | At Day 0, Day 21, Day 42 and Month 6 (M6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK Bio's influenza vaccine GSK2340272A, influenza infection