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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of GlaxoSmithKline Biologicals' influenza vaccine GSK2186877A in adults 65 year of age and older. The study design is divided in two surveillance phases: one passive phase along the study during the influenza season and one active surveillance phase during the influenza peak season.

Detailed Description
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This Protocol Posting has been updated according to Protocol Amendment 3, Sep 2009. After the analyses for this study were completed, questions arose regarding the integrity of study data from a single study site in Romania, which enrolled 102 subjects in the trial. Because evaluation of data from this site did not reveal irregularities when compared with overall study data and because GSK has no current plans to use the data from the study in support of any regulatory filings, they were not excluded from the analyses reflected in this results summary.

Official Title
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Observer-blind Superior Efficacy Trial With GlaxoSmithKline Biologicals' Influenza Vaccine GSK2186877A in Elderly Subjects

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Bio's influenza vaccine GSK2186877A
* Biological: Fluarix TM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol. A man or woman aged 65 years or older at the time of the vaccination. Written informed consent obtained from the subject. Subjects with residence status allowing free mixing with general community. Exclusion Criteria: Bedridden subjects Previous vaccination against influenza since February 2008. Previous vaccination in the last three years with an investigational adjuvanted candidate seasonal or pandemic influenza vaccine. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Any contra-indication to intramuscular administration of the influenza vaccines. History of hypersensitivity to a previous dose of influenza vaccine. History of allergy or reactions likely to be exacerbated by any component of the vaccine including egg and chicken protein. Acute disease at the time of enrolment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature <37.5°C (99.5°F).

Ages Eligible for Study
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Minimum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FluNG Group<br>subjects received 2 doses (1 dose per season) of FluNG vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1). | Biological: GSK Bio's influenza vaccine GSK2186877A<br>* IM administration, two times one annual dose, 3 different lots will be tested<br>|
| Active Comparator: Fluarix Group<br>subjects received 2 doses (1 dose per season) of Fluarix™ vaccine during the Northern Hemisphere (NH) vaccination periods. One dose at Day 0 of the Year 1 and one dose at Day 0 of the Year 2 (= Day 365 Year 1). | Biological: Fluarix TM<br>* IM administration, two times one annual dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection. | 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. | After the first dose during the corresponding surveillance period (from mid November 2008 to the end of April 2009 (end of influenza season)) | 
| Serum Hemagglutination-inhibition (HI) Antibody Titers, Against Each of the 3 Vaccine Influenza Strains, in the FluNG Groups. | 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. | At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection. | 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. | During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010) | 
| Number of Subjects Reporting Culture-confirmed Influenza A and/or B Infection. | 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. | During the whole surveillance period (from mid November 2008 to end of April 2009 and from mid November 2009 to end of April 2010) | 
| Number of Subjects Reporting Pneumonia or Clinical Influenza After the First Dose of Vaccine. | 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). | 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) | 
| Number of Subjects Reporting All-cause Death After the First Dose of Vaccine. | 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). | 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) | 
| Number of Subjects Reporting Hospitalization Due to Respiratory Diseases After the First Dose of Vaccine | 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. | 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) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID). | 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 | Within 365 days after the first dose (from Dose 1 at Day 0 up to Day 365 for the Year 2008/2009) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID). | 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 | Within 365 days after the second dose (from Dose 1 at Day 0 up to Day 365 for the Year 2009/2010) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID). | 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 | During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010) | 
| Number of Subjects Reporting Any and Related to Vaccination Serious Adverse Events (SAEs). | 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 | During the entire study period (during the 365 days of follow-up after each vaccination at Year 2008/2009 and Year 2009/2010) | 
| Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms. | 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 | During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) | 
| Number of Days With Any Grade of Solicited Local Symptoms | Solicited local symptoms assessed were ecchymosis, pain, redness and swelling | During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) | 
| Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms | 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 | During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) | 
| Number of Days With Any Grade of Solicited Local Symptoms. | Solicited local symptoms assessed were ecchymosis, pain, redness and swelling. | During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Symptoms | 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. | During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) | 
| Number of Days With Any Grade of Solicited General Symptoms | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature. | During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms. | 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. | During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) | 
| Number of Days With Any Grade of Solicited General Symptoms. | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature. | During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs). | 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. | Within 21 days (Days 0-20) after the first dose (Year 2008/2009) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs). | 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. | Within 21 days (Days 0-20) after the second dose (Year 2009/2010) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit | 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. | Within 180 days (Days 0-179) after the first dose (Year 2008/2009) | 
| Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit. | 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. | Within 180 days (Days 0-179) after the second dose (Year 2009/2010) | 
| Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains. | 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. | At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study | 
| Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains | 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. | At Days 0 (pre-vaccination Dose 2) and 21 (post-vaccination Dose 2) of the second year (2009/2010) of the study | 
| Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains. | 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. | 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 | 
| Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains. | 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. | 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 | 
| Number of Seroconverted Subjects for HI Antibodies Against Each of the 3 Vaccine Influenza Strains | 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. | At Day 21 of the first year (2008/2009) of the study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efficacy, Influenza Vaccines, Influenza, Vaccine, Elderly