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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00753272
First received: September 12, 2008
Last updated: September 11, 2014
Last verified: July 2013

September 12, 2008
September 11, 2014
September 2008
December 2010   (final data collection date for primary outcome measure)
  • Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection. [ 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)) ] [ Designated as safety issue: No ]
    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.
  • Serum Hemagglutination-inhibition (HI) Antibody Titers, Against Each of the 3 Vaccine Influenza Strains, in the FluNG Groups. [ Time Frame: At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study ] [ Designated as safety issue: No ]
    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.
  • Occurrence of RT-PCR confirmed influenza A and/or B infection, for any influenza strain [ Time Frame: During the influenza season ]
  • Serum haemagglutination-inhibition (HI) antibody titres, against each of the three vaccine strains, in a subset of the FLU NG groups. [ Time Frame: Day 0 and 21 ]
Complete list of historical versions of study NCT00753272 on ClinicalTrials.gov Archive Site
  • Number of Subjects Reporting Polymerase Chain Reaction (PCR)-Confirmed Influenza A and/or B Infection. [ 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) ] [ Designated as safety issue: No ]
    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.
  • Number of Subjects Reporting Culture-confirmed Influenza A and/or B Infection. [ 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) ] [ Designated as safety issue: No ]
    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.
  • Number of Subjects Reporting Pneumonia or Clinical Influenza After the First Dose of Vaccine. [ 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) ] [ Designated as safety issue: No ]

    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).

  • Number of Subjects Reporting All-cause Death After the First Dose of Vaccine. [ 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) ] [ Designated as safety issue: No ]
    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).
  • Number of Subjects Reporting Hospitalization Due to Respiratory Diseases After the First Dose of Vaccine [ 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) ] [ Designated as safety issue: No ]
    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.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID). [ Time Frame: Within 365 days after the first dose (from Dose 1 at Day 0 up to Day 365 for the Year 2008/2009) ] [ Designated as safety issue: No ]

    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

  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID). [ Time Frame: Within 365 days after the second dose (from Dose 1 at Day 0 up to Day 365 for the Year 2009/2010) ] [ Designated as safety issue: No ]

    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

  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Adverse Events (AEs) of Specific Interest Including Autoimmune Disease (AID). [ 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) ] [ Designated as safety issue: No ]

    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

  • Number of Subjects Reporting Any and Related to Vaccination Serious Adverse Events (SAEs). [ 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) ] [ Designated as safety issue: No ]

    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

  • Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ] [ Designated as safety issue: No ]
    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
  • Number of Days With Any Grade of Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were ecchymosis, pain, redness and swelling
  • Number of Subjects Reporting Any and Severe (Grade 3) Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ] [ Designated as safety issue: No ]
    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
  • Number of Days With Any Grade of Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were ecchymosis, pain, redness and swelling.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ] [ Designated as safety issue: No ]
    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.
  • Number of Days With Any Grade of Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the first year (2008/2009) ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related Solicited General Symptoms. [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ] [ Designated as safety issue: No ]
    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.
  • Number of Days With Any Grade of Solicited General Symptoms. [ Time Frame: During the 7-day (Days 0-6) post-vaccination period, the second year (2009/2010) ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and temperature.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs). [ Time Frame: Within 21 days (Days 0-20) after the first dose (Year 2008/2009) ] [ Designated as safety issue: No ]
    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.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited Adverse Events (AEs). [ Time Frame: Within 21 days (Days 0-20) after the second dose (Year 2009/2010) ] [ Designated as safety issue: No ]
    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.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit [ Time Frame: Within 180 days (Days 0-179) after the first dose (Year 2008/2009) ] [ Designated as safety issue: No ]
    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.
  • Number of Subjects Reporting Any, Severe (Grade 3) and Related to Vaccination Unsolicited AEs With Medically Attended Visit. [ Time Frame: Within 180 days (Days 0-179) after the second dose (Year 2009/2010) ] [ Designated as safety issue: No ]
    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.
  • Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains. [ Time Frame: At Days 0 (pre-vaccination Dose 1) and 21 (post-vaccination Dose 1) of the first year (2008/2009) of the study ] [ Designated as safety issue: No ]
    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.
  • Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains [ Time Frame: At Days 0 (pre-vaccination Dose 2) and 21 (post-vaccination Dose 2) of the second year (2009/2010) of the study ] [ Designated as safety issue: No ]
    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.
  • Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains. [ 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 ] [ Designated as safety issue: No ]
    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.
  • Serum Hemagglutination-inhibition (HI) Antibody Titer Against Each of the 3 Vaccine Influenza Strains. [ 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 ] [ Designated as safety issue: No ]
    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.
  • Number of Seroconverted Subjects for HI Antibodies Against Each of the 3 Vaccine Influenza Strains [ Time Frame: At Day 21 of the first year (2008/2009) of the study. ] [ Designated as safety issue: No ]
    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.
  • Occurrence of culture confirmed influenza A and/or B infection [ Time Frame: During the influenza season ]
  • Occurrence of pneumonia, clinical influenza or new onset or worsening of congestive heart failure (CHF) [ Time Frame: During the influenza peak season ]
  • Occurrence of myocardial infarction (MI) or stroke [ Time Frame: During the influenza peak season ]
  • Occurrence of all cause death [ Time Frame: During the influenza peak season ]
  • Occurrence of hospitalization due to pneumonia, influenza or new onset or worsening CHF [ Time Frame: During the influenza peak season ]
  • Occurrence of hospitalization due to respiratory diseases [ Time Frame: During the influenza peak season ]
  • Occurrence of each individual potentially influenza related complication (pneumonia, new onset or worsening CHF, MI and stroke) [ Time Frame: During the influenza peak season ]
  • Occurrence and relationship to vaccination of SAEs and AEs of specific interest including autoimmune diseases (AID) [ Time Frame: During the entire study period ]
  • Occurrence and relationship to vaccination of SAEs and AEs of specific interest including AID (in case of additional subjects recruited for the second season) [ Time Frame: During 12 months ]
  • Occurrence, intensity, duration and relationship to vaccination of solicited local and general adverse events (AEs) (in the safety/reacto subset only) [ Time Frame: During a 7-day follow-up period after each vaccination ]
  • Occurrence, intensity and relationship to vaccination of unsolicited AEs (in the safety/reacto subset only) [ Time Frame: During a 21-day follow-up period after each vaccination ]
  • Occurrence, intensity and relationship to vaccination of AEs with medically attended visit (in the safety/reacto subset only) [ Time Frame: During a 180-day follow-up period after each vaccination ]
  • Serum HI antibody titres against each of the three vaccine influenza strains (in the immuno subset only) [ Time Frame: Day 0 and 21 ]
  • Serum HI antibody titres against each of the three vaccine influenza strains (in the immuno persistency subset only) [ Time Frame: Day 180 ]
Not Provided
Not Provided
 
Trial to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine GSK2186877A in Adults 65 Year of Age and Older
Observer-blind Superior Efficacy Trial With GlaxoSmithKline Biologicals' Influenza Vaccine GSK2186877A in Elderly Subjects

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Influenza
  • Biological: GSK Bio's influenza vaccine GSK2186877A
    IM administration, two times one annual dose, 3 different lots will be tested
  • Biological: Fluarix TM
    IM administration, two times one annual dose
  • Experimental: FluNG Group
    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).
    Intervention: Biological: GSK Bio's influenza vaccine GSK2186877A
  • Active Comparator: Fluarix Group
    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).
    Intervention: Biological: Fluarix TM

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
43695
December 2010
December 2010   (final data collection date for primary outcome measure)

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).
Both
65 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Czech Republic,   United States,   Belgium,   Canada,   United Kingdom,   Estonia,   France,   Germany,   Mexico,   Netherlands,   Norway,   Poland,   Romania,   Russian Federation,   Taiwan
 
NCT00753272
106372
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP