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.

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

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.

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.

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).

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).

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).

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.