A Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Seasonal Influenza Vaccine in Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01196975
First received: September 7, 2010
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

This study is designed to test the immunogenicity and safety of an investigational influenza vaccine, in adults compared to two other influenza vaccines.

This study will also evaluate the lot-to-lot consistency of three vaccine lots.


Condition Intervention Phase
Influenza
Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
Biological: FluLavalTM-VB
Biological: FluLavalTM-YB
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Immunogenicity, Reactogenicity and Safety of GSK Biologicals' Quadrivalent Influenza Vaccine FLU Q-QIV (GSK2282512A) When Administered Intramuscularly to Adults 18 Years of Age and Older

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease [ Time Frame: At Day 0 (D0) and at Day 21 (D21) post vaccination. ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. Antibodies assessed were antibodies against the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Results for Day 21 for the subjects in the GSK2282512A Group are the results specific to this primary outcome measure.


Secondary Outcome Measures:
  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 0 (D0) and at Day 21 (D21) post vaccination. ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. Antibodies assessed were antibodies against the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 flu strains. Subjects were assessed according to 2 age categories, 18-64Y and ≥ 65Y.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 0 (D0), and at Day 21 (D21) and Day 180 (D180) post vaccination. ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. Antibodies assessed were antibodies against the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 flu strains. Subjects were assessed according to 2 age categories, 18-60Y and ≥ 61Y.

  • Number of Subjects With Medically-attended Adverse Events (MAEs) [ Time Frame: From the beginning of the study until study end (from Day 0 to Day 180) ] [ Designated as safety issue: No ]
    Medically-attended adverse events (MAEs) were non-serious and serious events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. If a medically-attended adverse event was leading to hospitalization (or met any other serious adverse event [SAE] criterion), it was reported as SAE.

  • Number of Subjects With Related Medically-attended Adverse Events (MAEs) [ Time Frame: From the beginning of the study until study end (from Day 0 to Day 180) . ] [ Designated as safety issue: No ]
    Medically-attended adverse events (MAEs) were non-serious and serious events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. If a medically-attended adverse event was leading to hospitalization (or met any other serious adverse event [SAE] criterion), it was reported as SAE. Related MAE = MAE assessed by the investigator to be causally related to vaccination. Relationship to vaccination was not computed for MAEs.

  • Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs) [ Time Frame: From the beginning of the study until study end (from Day 0 to Day 180) . ] [ Designated as safety issue: No ]
    Potential immune-mediated diseases (pIMDs) are a subset of adverse events that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Related pIMD = pIMD assessed by the investigator to be causally related to vaccination.

  • Number of Subjects With Any and Related Serious Adverse Events (SAEs) [ Time Frame: From the beginning of the study until study end (from Day 0 to Day 180) ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 0 (D0), and at Day 21 (D21) and Day 180 (D180) post vaccination. ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. Antibodies assessed were antibodies against the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 flu strains. Subjects were assessed according to 2 age categories, 18-64Y and ≥ 65Y.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease [ Time Frame: At Day 0 (D0) and at Day 21 (D21) after vaccination. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 0 (D0) and at Day 21 (D21) after vaccination. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Subjects were assessed according to 2 age categories, 18-60Y and ≥ 61Y.

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 0 (D0) and at Day 21 (D21) after vaccination ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition titer ≥ 1:40. The 4 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Subjects were assessed according to 2 age categories, 18-64Y and ≥ 65Y.

  • Number of Seroconverted Subjects Against 4 Strains of Influenza by Age Strata [ Time Frame: At Day 21 (D21) after vaccination. ] [ Designated as safety issue: No ]
    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 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Subjects were assessed according to 2 age categories, 18-64Y and ≥ 65Y.

  • Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 21 (D21) after vaccination ] [ Designated as safety issue: No ]
    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 (i.e. the geometric mean of the within-subject ratios of the Day 21 reciprocal HI titer to the Day 0 reciprocal HI titer). The 4 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Subjects were assessed according to 2 age categories, 18-64Y and ≥ 65Y.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 0 (D0) and at Day 21 (D21) post vaccination. ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. Antibodies assessed were antibodies against the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 flu strains. Subjects were assessed according to 2 age categories, 18-60Y and ≥ 61Y.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease [ Time Frame: At Day 0 (D0), and at Day 21 (D21) and Day 180 (D180) post vaccination. ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was 1:10. Antibodies assessed were antibodies against the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N2), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 flu strains.

  • Number of Seroconverted Subjects Against 4 Strains of Influenza [ Time Frame: At Day 21 (D21) after vaccination. ] [ Designated as safety issue: No ]
    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 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains.

  • Number of Seroconverted Subjects Against 4 Strains of Influenza by Age Strata [ Time Frame: At Day 21 (D21) after vaccination. ] [ Designated as safety issue: No ]
    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 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Subjects were assessed according to 2 age categories, 18-60Y and ≥ 61Y.

  • Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata [ Time Frame: At Day 21 (D21) post vaccination. ] [ Designated as safety issue: No ]
    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 (i.e. the geometric mean of the within-subject ratios of the Day 21 reciprocal HI titer to the Day 0 reciprocal HI titer). The 4 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains. Subjects were assessed according to 2 age categories, 18-60Y and ≥ 61Y.

  • Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease [ Time Frame: At Day 21 (D21) post vaccination. ] [ Designated as safety issue: No ]
    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 (i.e. the geometric mean of the within-subject ratios of the Day 21 reciprocal HI titer to the Day 0 reciprocal HI titer). The 4 assessed influenza strains were the FLU A/California/7/09 (H1N1), FLU A/Victoria/210/09 (H3N1), FLU B/Brisbane/60/08 (BRI) and FLU B/Florida/4/06 (FLO) flu strains.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: Within the 7-day (Days 0-6) follow-up period after vaccination ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling at the injection site. Grade 3 pain = significant pain at rest/pain that prevented normal everyday activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: Within the 7-day (Days 0-6) follow-up period after vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (Gastr. Symptoms), headache, muscle ache, shivering, temperature - oral temperature equal to or above (≥) 38.0 degrees Celsius (°C) - and joint pain at location other than the injection site (Joint Pain). Grade 3 temperature = temperature ≥ 39.0 °C. Grade 3 symptom = symptom that prevented normal everyday activity. Related symptom = symptom assessed by the investigator as causally related to study vaccination. Joint pain data were collected for subjects in Canada and Mexico only.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: Within the 21-day (Days 0-20) follow-up period after vaccination ] [ Designated as safety issue: No ]
    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 everyday activity Related: unsolicited AE assessed by the investigator as related to the vaccination.

  • Number of Days With Solicited Local Symptoms After Vaccination. [ Time Frame: Within the 7-day follow-up period after vaccination (Days 0-6) ] [ Designated as safety issue: No ]
    Solicited local symptoms were pain, redness and swelling at the injection site. Analyses of duration for solicited local symptoms were not performed.

  • Number of Days With Solicited General Symptoms After Vaccination [ Time Frame: Within the 7-day follow-up period after vaccination (Days 0-6) ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (Gastr.), headache, muscle ache, shivering, temperature (defined as oral temperature equal to or above 38.0 degrees Celsius) and joint pain at location other than the injection site (Joint Pain). Joint pain data were collected for subjects in Canada and Mexico only. Analyses of duration for solicited general symptoms were not performed.

  • Number of Days With Unsolicited Adverse Events (AEs) After Vaccination [ Time Frame: Within the 21-day (Days 0-20) follow-up period post vaccination ] [ Designated as safety issue: No ]
    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 everyday activity. Analyses of duration for unsolicited AEs were not performed.


Enrollment: 1707
Study Start Date: October 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2282512A 1 Group
Subjects received at Day 0 one dose of the GSK2282512A vaccine, Lot 1. The GSK2282512A vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
Single intramuscular dose
Other Name: GSK2282512A
Experimental: GSK2282512A 2 Group
Subjects received at Day 0 one dose of the GSK2282512A vaccine, Lot 2. The GSK2282512A vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
Single intramuscular dose
Other Name: GSK2282512A
Experimental: GSK2282512A 3 Group
Subjects received at Day 0 one dose of the GSK2282512A vaccine, Lot 3. The GSK2282512A vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
Single intramuscular dose
Other Name: GSK2282512A
Active Comparator: Victoria Strain FluLaval Group
Subjects received at Day 0 one dose of FluLaval®-VB vaccine containing the Victoria B flu strain. The FluLaval®-VB vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: FluLavalTM-VB
Single intramuscular dose
Other Names:
  • FluLavalTM containing the Victoria B flu strain
  • FluLaval®-VB
  • Victoria Strain FluLaval vaccine
Active Comparator: Yamagata Strain FluLaval Group
Subjects received at Day 0 one dose of FluLaval®-YB vaccine containing the Yamagata B flu strain. The FluLaval®-YB vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: FluLavalTM-YB
Single intramuscular dose
Other Names:
  • FluLavalTM containing the Yamagata B flu strain
  • FluLaval®-YB

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes can and will comply with the requirements of the protocol
  • A male or female 18 years of age or older, in stable health, as established by medical history and physical examination before entering into the study.
  • Written informed consent obtained from the subject.
  • Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device.
  • Female subjects of non-childbearing potential may be enrolled in the study.
  • Female subjects of childbearing potential may be enrolled in the study, if the subject:
  • - has practiced adequate contraception for 30 days prior to vaccination, and
  • - has a negative pregnancy test on the day of vaccination, and
  • - has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

  • Use of an investigational / non-registered product other than the study vaccines within 30 days before study vaccination or planned use during study period.
  • Planned administration or administration of a licensed vaccine within 30 days before study vaccination.
  • Prior receipt of 2010/2011 influenza vaccine.
  • Receipt of any investigational or approved influenza vaccine within six months of the first study visit.
  • Any known or suspected allergy to any constituent of influenza vaccines ; a history of anaphylactic-type reaction to constituent of vaccine; or a history of severe adverse reaction to a previous influenza vaccine.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • History of Guillain-Barre syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine.
  • Presence or evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the investigator to render the potential subject unable / unlikely to provide accurate safety reports.
  • Acute, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, based on history and physical examination.
  • Presence of significant uncontrolled chronic medical or neuropsychiatric illness, based on history and physical examination
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin
  • Chronic administration of immunosuppressants or other immune-modifying drugs within 3 months prior to the first vaccine/product dose.
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
  • Pregnant or lactating female.
  • Fever at the time of enrolment.
  • Acute disease at the time of enrolment
  • Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196975

Locations
United States, Arizona
GSK Investigational Site
Mesa, Arizona, United States, 85213
United States, Kansas
GSK Investigational Site
Wichita, Kansas, United States, 67207
United States, Maryland
GSK Investigational Site
Elkridge, Maryland, United States, 21075
United States, New York
GSK Investigational Site
Endwell, New York, United States, 13760
United States, Pennsylvania
GSK Investigational Site
Jefferson Hills, Pennsylvania, United States, 15025
United States, Washington
GSK Investigational Site
Wenatchee, Washington, United States, 98801
Canada, British Columbia
GSK Investigational Site
Coquitlam, British Columbia, Canada, V3K 3P4
GSK Investigational Site
Surrey, British Columbia, Canada, V3R 8P8
Canada, Quebec
GSK Investigational Site
Quebec City, Quebec, Canada, G1V 4M6
Mexico
GSK Investigational Site
Cuernavaca, Morelos, Mexico
GSK Investigational Site
Durango, Mexico, 3400
GSK Investigational Site
Estado de Mexico, Mexico, 55075
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01196975     History of Changes
Other Study ID Numbers: 112963
Study First Received: September 7, 2010
Results First Received: November 21, 2012
Last Updated: November 21, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by GlaxoSmithKline:
Influenza

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 23, 2014