A Study to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine in Children

To confirm influenza A and/or B disease, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.

Time frame: From Day 14 to Day 180

Population: The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.

HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Victoria/210/09 (H3N2), Flu B/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: On Day 0 and at least 6 months after first vaccination (Month 6)

Population: The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer \< 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]

Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.

A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At least 6 months after first vaccination (Month 6)

Population: The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At Day 0 [PRE] and 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]

Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.

A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At Day 0 and at least 6 months after first vaccination (Month 6)

Population: The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

To confirm influenza A and/or B disease due to antigenically matched strain, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.

Time frame: From Day 14 to Day 180

Population: The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.

To confirm influenza A and/or B disease due to any strain, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.

Time frame: From Day 14 to Day 180

Population: The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.

To confirm influenza A and/or B disease moderate to severe cases, a positive RT-PCR result for influenza A or B virus from a nose and throat swab obtained concurrently with an ILI was required. Moderate to severe influenza was defined as RT-PCR-confirmed ILI with: * Fever \>39°C, and/or at least one of the following manifestations, * Physician-verified shortness of breath, pulmonary congestion, pneumonia, bronchiolitis, bronchitis, wheezing, croup, or acute otitis media, and/or one of the following, * Physician-diagnosed serious extra-pulmonary complication of influenza, including myositis, encephalitis, seizure, or myocarditis

Time frame: From Day 14 to Day 180

Population: The analysis was performed on the According-To-Protocol cohort for efficacy - Time to event, which included all eligible subjects who met all inclusion criteria and no exclusion criteria, followed their study treatment assignment and were successfully contacted at least once after the first vaccination.

MAEs were defined as AEs that resulted in medical attention (defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason). Any = Any MAE regardless of intensity or relationship to vaccination. Related = MAE assessed by the investigator as causally related to the vaccination.

Time frame: During the entire study period (Day 0 - Day 180)

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

pIMDs were defined as a subset of AEs that included both clearly autoimmune diseases (AID) and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Any = Any pIMD(s) regardless of intensity or relationship to vaccination. Related = pIMDs assessed by the investigator as causally related to the vaccination.

Time frame: During the entire study period (Day 0 - Day 180)

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

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. Any = Any SAE(s) regardless of intensity or relationship to vaccination. Related = SAEs assessed by the investigator as causally related to the vaccination.

Time frame: During the entire study period (Day 0 - Day 180)

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature. Any = Occurrence of any solicited general symptom regardless of intensity grade and relation to vaccination. Any temperature = Axillary temperature ≥ 38.0 °C. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = not eating at all. Related = General symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = Axillary temperature ≥ 39.0°C.

Time frame: During the 7-day (Days 0-6) follow-up period after any vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented and with the symptom sheet completed.

Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (Gastro.), headache, joint pain at other location (Joint pain), muscle aches, shivering and temperature. Any = Occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Any temperature = Axillary temperature ≥ 38.0 °C. Grade 3 symptom = Symptom that prevented normal activity. Related = Symptom assessed by the investigator as causally related to the vaccination. Grade 3 temperature = Axillary temperature ≥ 39.0°C.

Time frame: During the 7-day (Days 0-6) follow-up period after any vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented and with the symptom sheet completed.

Assessed solicited local symptoms were pain, redness and swelling at the injection site. Any = Incidence of a particular symptom regardless of intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful for subjects \< 5 years of age or significant pain at rest that prevented normal, everyday activities for subjects ≥ 5 years of age. Grade 3 redness/swelling = Redness/swelling above 100 millimeters (mm) of the injection site. All solicited local symptoms were considered related to vaccination.

Time frame: During the 7-day (Days 0-6) follow-up period after any vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented and with the symptom sheet completed.

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 = Any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 = Unsolicited AE that prevented normal activity. Related = Unsolicited AE assessed by the investigator as causally related to the vaccination.

Time frame: During the 28-day (Days 0-27) follow-up period after vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented.

The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]

Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.

Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At least 6 months after first vaccination (Month 6)

Population: The ATP Cohort for persistence included, in terms of antibody response measured by the HI assay, all evaluable subjects for whom data concerning immunogenicity outcome measure were available and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

Titers are presented as geometric mean titers (GMTs). The reference cut-off value was the seropositivity cut-off of 1:10. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

Time frame: At Day 0 [PRE] and 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST]

Population: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects (those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome measure were available.