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

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

Time frame: At Day 42

Population: This measure was assessed on the ATP cohort for immunogenicity on subjects with assay results available for Day 0, Day 21 and Day 42. As no pre-vaccination (Day 0 and Day 21) blood samples were planned for the Flu BS2 Groups, GMFR at Day 42 could not be computed for those groups.

Antibody titers were expressed as Geometric mean titers (GMTs).

Time frame: At Day 0, Day 21 and Day 42

Population: The ATP cohort for immunogenicity included all subjects for whom 2 doses were administrated and assay results were available for the blood samples taken before the first vaccination (Day 0), before the second vaccination (Day 21) and after the second vaccine dose (Day 42). No blood samples were planned at Day 0 and Day 21 for Flu BS2 Groups.

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.

Time frame: At Day 42

Population: This measure was assessed on the ATP cohort for immunogenicity on subjects with assay results available for Day 0, Day 21 and Day 42. As no pre-vaccination (Day 0 and Day 21) blood samples were planned for the Flu BS2 Groups, seroconversion at Day 42 could not be computed for those groups.

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.

Time frame: At Day 42

Population: The ATP cohort for immunogenicity included all evaluable subjects for whom 2 doses were administrated and assay results were available for antibodies against H1N1 antigen for the blood sample taken after the second vaccine dose (Day 42).

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

Time frame: At Month 6

Population: The ATP cohort for antibody persistence at Month 6 including all subjects for whom assay results were available for antibodies against the study vaccine antigen component pre-vaccination (Day 0 and Day 21) and at Month 6. As no pre-vaccination blood samples were planned for the Flu BS2 Groups, GMFR at Month 6 could not be computed for those groups.

Antibody titers were expressed as geometric mean titers (GMTs)

Time frame: At Month 6

Population: The ATP cohort for antibody persistence at Month 6 included all evaluable subjects for whom data concerning immunogenicity outcome measures were available for antibodies against the study vaccine antigen component at Month 6.

Antibody titers were expressed as geometric mean titers (GMTs)

Time frame: At Month 12

Population: The ATP cohort for antibody persistence at Month 12 including all evaluable subjects for whom assay results were available for antibodies against the study vaccine antigen component at Month 12. As no blood samples were planned at Month 12 for the Flu BS1 Groups, GMTs could not be computed for those groups.

Antibody titers were expressed as Geometric mean titers (GMTs).

Time frame: At Day 0, Day 21, Day 42 and Month 6

Population: The ATP cohort for immunogenicity including all evaluable subjects for whom assay results were available at the considered time points. No blood samples were taken at Day 0 and Day 21 and hence no GMTs computed for the Flu BS2 Groups. This analysis was conducted on a randomly selected subset of one third of the subjects.

Antibody titers were expressed as Geometric mean titers (GMTs).

Time frame: At Month 12

Population: The ATP cohort for immunogenicity including all evaluable subjects for whom assay results were available at Month 12. No blood samples were planned at Month 12 the Flu BS1 Groups and hence no GMTs computed for these Groups. This analysis was conducted on a randomly selected subset of one third of the subjects.

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.

Time frame: At Month 6

Population: The ATP cohort for antibody persistence at Month 6 including all evaluable subjects for whom assay results were available at pre-vaccination time points (Day 0 and Day 21) and post-vaccination time point (Month 6). No pre-vaccination blood samples were taken from Flu BS2 Groups and hence seroconversion could not be assessed for these groups.

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.

Time frame: At Day 21 and Day 42

Population: The ATP cohort for immunogenicity including subjects with assay results available for Day 0, Day 21 and Day 42. As no pre-vaccination (Day 0 and Day 21) blood samples were planned for the Flu BS2 Groups, seroconversion could not be computed for those groups. This analysis was conducted on a randomly selected subset of one third of the subjects.

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.

Time frame: At Month 6

Population: The ATP cohort for antibody persistence at Month 6 including subjects with assay results available for Day 0, Day 21 and Month 6. As no pre-vaccination (Day 0/21) blood samples were planned for the Flu BS2 Groups, seroconversion could not be computed for those groups. This analysis was done on a randomly selected subset of a third of the subjects.

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.

Time frame: During the entire study period (Day 0 to Month 12)

Population: The Total Vaccinated cohort included all vaccinated subjects.

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.

Time frame: During the 7-day (Days 0-6) post-vaccination period

Population: The Total Vaccinated cohort including all vaccinated subjects who returned their symptom sheet.

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.

Time frame: During the entire study period (Day 0 to Month 12)

Population: The Total Vaccinated cohort included all vaccinated subjects.

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.

Time frame: During the 7-day (Days 0-6) post-vaccination period

Population: The Total Vaccinated cohort including all vaccinated subjects who returned their symptom sheet.

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.

Time frame: Within the 84-day after the first vaccination or from 63-day follow-up period after the second vaccination

Population: The Total Vaccinated cohort included all vaccinated subjects.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination.

Time frame: During the entire study period (Day 0 to Month 12)

Population: The Total Vaccinated cohort included all vaccinated subjects.

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.

Time frame: At Month 12

Population: The ATP cohort for antibody persistence at Month 12 including all evaluable subjects for whom assay results were available for antibodies against the study vaccine antigen component at Month 12. As no blood samples were planned at Month 12 for the Flu BS1 Groups, no data were computed for these groups.

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.

Time frame: At Month 6

Population: The ATP cohort for antibody persistence at Month 6 including all evaluable subjects for whom assay results were available for antibodies against the study vaccine antigen component at Month 6.

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.

Time frame: At Day 0, Day 21, Day 42 and Month 6 (M6)

Population: The Total Vaccinated cohort including all vaccinated subjects with data available for the respective assays at the considered timepoints. Note that for Flu BS2 Groups, no blood samples were taken at Day 0 and Day 21 and hence no data for these timepoints are reported for the Flu BS2 Groups.