Trial to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine GSK2186877A in Adults 65 Year of Age and Older

Occurrence of PCR-confirmed influenza A and/or B infection, due to any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v). PCR-confirmed influenza (PCI) was defined as an episode of influenza-like illness (ILI) occurring after the administration of the study vaccine for which a nasal and throat swab specimen yields influenza virus A and/or B by reverse transcription polymerase chain reaction (RT-PCR) analysis.

Time frame: After the first dose during the corresponding surveillance period (from mid November 2008 to the end of April 2009 (end of influenza season))

Population: The One-Dose According-To-Protocol cohort for efficacy included eligible subjects from the One-Dose Total Vaccinated cohort (e.g. who complied with the protocol, with no elimination criteria assigned during the study), who had started their first surveillance period, who had not received a seasonal influenza vaccine not foreseen in the protocol.

Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects in the lot-to-lot subset of subjects.

Time frame: At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study

Population: The One-Dose According-To-Protocol immunogenicity cohort for the lot-to-lot consistency subset, which included all subjects from the One-Dose ATP cohort for immunogenicity included in the lot-to-lot subset.

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature.

Time frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)

Population: The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature.

Time frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)

Population: The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Solicited local symptoms assessed were ecchymosis, pain, redness and swelling

Time frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)

Population: The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Solicited local symptoms assessed were ecchymosis, pain, redness and swelling.

Time frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)

Population: The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

In the lot-to-lot subset of subject in the FluGN Group. Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Seroconversion is defined as the number of subjects with pre-vaccination HI titer (Day 0) \< 1:10 and post-vaccination titer (Day 21) ≥ 1:40 or a pre-vaccination HI titer (Day 0) ≥ 1:10 and fold-increase (post/pre) ≥ 4.

Time frame: At Day 21 of the first year (2008/2009) of the study.

Population: The One-Dose According-To-Protocol immunogenicity cohort for the lot-to-lot consistency subset included all subjects from the One-Dose ATP cohort for immunogenicity included in the lot-to-lot subset.

The influenza peak season = period during the study with the highest incidence of any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v).

Time frame: During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009)

Population: The One-Dose According-To-Protocol cohort for efficacy for peak season included all subjects from the One-Dose ATP cohort for efficacy who did not drop out from the study before the start of their first influenza peak season.

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Related = event assessed by the investigator as causally related to the study vaccination

Time frame: During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010)

Population: The Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Solicited local symptoms assessed were ecchymosis, pain, redness and swelling. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = considerable pain at rest that prevented normal everyday activities. Grade 3 ecchymosis/redness/swelling = ecchymosis/redness/swelling above 100 millimeter

Time frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)

Population: The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Solicited local symptoms assessed were ecchymosis, pain, redness and swelling. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = considerable pain at rest that prevented normal everyday activities. Grade 3 ecchymosis/redness/swelling = ecchymosis/redness/swelling above 100 millimeter

Time frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)

Population: The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature (defined as oral temperature equal to or above (≥) 38.0 degrees Celsius). Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccination. Grade 3 = general symptom which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = oral temperature ≥39.0°C - ≤ 40.0°C.

Time frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010)

Population: The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Adverse events of specific interest for safety monitoring are 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. Grade 3 = event that prevented normal everyday activities Related = event assessed by the investigator as causally related to the study vaccination

Time frame: During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010)

Population: The Total Vaccinated cohort included all subjects with at least one vaccine administration documented.

Adverse events of specific interest for safety monitoring are 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. Grade 3 = event that prevented normal everyday activities Related = event assessed by the investigator as causally related to the study vaccination

Time frame: Within 365 days after the second dose (from Dose 1 at Day 0 up to Day 365 for the Year 2009/2010)

Population: The Two-Dose Total Vaccinated cohort included all subjects with one vaccine administration documented in each year of the study

Adverse events of specific interest for safety monitoring are 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. Grade 3 = event that prevented normal everyday activities Related = event assessed by the investigator as causally related to the study vaccination

Time frame: Within 365 days after the first dose (from Dose 1 at Day 0 up to Day 365 for the Year 2008/2009)

Population: The One-Dose Total Vaccinated cohort included all subjects with one vaccine administration documented during the first year of the study.

Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature (defined as oral temperature equal to or above (≥) 38.0 degrees Celsius). Any = incidence of a particular symptom regardless of intensity grade or relationship to vaccination. Grade 3 = general symptom which prevented normal everyday activities. Related = general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = oral temperature ≥39.0°C - ≤ 40.0°C.

Time frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009)

Population: The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

An unsolicited adverse event is any adverse event (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. Grade 3 = event that prevented normal, everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.

Time frame: Within 21 days (Days 0-20) after the first dose (Year 2008/2009)

Population: The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

An unsolicited adverse event is any adverse event (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. Grade 3 = event that prevented normal, everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.

Time frame: Within 21 days (Days 0-20) after the second dose (Year 2009/2010)

Population: The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

For each solicited and unsolicited symptom the subject experienced, the subjects were asked if they received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Grade 3 = event that prevented normal everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.

Time frame: Within 180 days (Days 0-179) after the first dose (Year 2008/2009)

Population: The One-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented during the first year of the study and included in the safety subset.

For each solicited and unsolicited symptom the subject experienced, the subjects were asked if they received medical attention defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Grade 3 = event that prevented normal everyday activities. Related = event assessed by the investigator as causally related to the study vaccination.

Time frame: Within 180 days (Days 0-179) after the second dose (Year 2009/2010)

Population: The Two-Dose Total Vaccinated cohort for the safety subset included all subjects with at least one vaccine administration documented in each year of the study and included in the safety subset.

Occurrence of culture-confirmed influenza A and/or B infection, due to any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v). Culture-confirmed influenza (CCI) was defined as an episode of ILI occurring after the administration of the study vaccine for which a nasal and throat swab specimen yields influenza virus A and/or B by viral culture analysis.

Time frame: During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010)

Population: The According-To-Protocol cohort for efficacy included all eligible subjects from the Total Vaccinated cohort (e.g. who complied with the protocol, with no elimination criteria assigned during the study), who had started their first surveillance period, who had not received a seasonal influenza vaccine not foreseen in the protocol.

Respiratory disease: A diagnosis of respiratory disease included: acute respiratory infections, other diseases of upper respiratory tract, pneumonia and influenza, chronic obstructive pulmonary disease and allied conditions, pneumoconioses and other lung diseases due to external agents, other diseases of respiratory system. In case the event has a fatal outcome, the diagnosis can also be confirmed by autopsy.

Time frame: During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009)

Population: The One-Dose According-To-Protocol cohort for efficacy for peak season included all subjects from the One-Dose ATP cohort for efficacy who did not drop out from the study before the start of their first influenza peak season.

Clinical influenza= An ILI episode (with an ILI onset from the 15th of November until the end of the surveillance period) with at least simultaneously fever (oral temperature of ≥37.8 degrees Celsius) and cough. The influenza peak season = period during the study with the highest incidence of any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v).

Time frame: During the influenza peak season within the first surveillance period (the influenza peak season being defined per country, falling somewhere between mid November 2008 to end of April 2009)

Population: The One-Dose According-To-Protocol cohort for efficacy for peak season included all subjects from the One-Dose ATP cohort for efficacy who did not drop out from the study before the start of their first influenza peak season.

Occurrence of PCR-confirmed influenza A and/or B infection, due to any matching or drift influenza strain relative to the vaccine strains (i.e. not emerging novel human influenza strain like H1N1v). PCR-confirmed influenza (PCI) was defined as an episode of influenza-like illness (ILI) occurring after the administration of the study vaccine for which a nasal and throat swab specimen yields influenza virus A and/or B by reverse transcription polymerase chain reaction (RT-PCR) analysis.

Time frame: During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010)

Population: The According-To-Protocol cohort for efficacy included all eligible subjects from the Total Vaccinated cohort (e.g. who complied with the protocol, with no elimination criteria assigned during the study), who had started their first surveillance period, who had not received a seasonal influenza vaccine not foreseen in the protocol.

Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects in the immunogenicity subset of subjects.

Time frame: At Days 0 (pre-vaccination Dose 2) and 21 (post-vaccination Dose 2) of the second year (2009/2010) of the study

Population: The Two-Dose According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 21 of the second year of the study.

Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects for 600 subjects in the persistence subset only.

Time frame: At Days 0 (pre-vaccination Dose 1), 21 (post-vaccination Dose 1) and 180 (post-vaccination Dose 1) of the first year (2008/2009) of the study

Population: The One-Dose According-To-Protocol cohort for persistence included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 180 of the first year of the study.

Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects for 600 subjects in the persistence subset only.

Time frame: At Days 0 (pre-vaccination Dose 2), 21 (post-vaccination Dose 2) and 180 (post-vaccination Dose 2) of the second year (2009/2010) of the study

Population: The Two-Dose According-To-Protocol cohort for persistence included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 180 of the second year of the study.

Vaccine strains assessed were A/Brisbane/59/2077, A/Uruguay/716/2007 and B/Brisbane/3/2007. Titers were expressed as geometric mean titers calculated on all subjects in the immunogenicity subset of subjects.

Time frame: At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study

Population: The One-Dose According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available in terms of antibodies against at least one study vaccine antigen component at Day 21 of the first year of the study.