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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Quadrivalent seasonal influenza vaccine GSK2282512A; Biological: FluLavalTM-VB; Biological: FluLavalTM-YB

• Study Type: Interventional
• Enrollment (Actual): 1707
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
      • GSK Investigational Site
    • Surrey, British Columbia, Canada, V3R 8P8
      • GSK Investigational Site
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4M6
      • GSK Investigational Site
• Mexico
  • Durango, Mexico, 3400
    • GSK Investigational Site
  • Estado de Mexico, Mexico, 55075
    • GSK Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico
      • GSK Investigational Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85213
      • GSK Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67207
      • GSK Investigational Site
  • Maryland
    • Elkridge, Maryland, United States, 21075
      • GSK Investigational Site
  • New York
    • Endwell, New York, United States, 13760
      • GSK Investigational Site
  • Pennsylvania
    • Jefferson Hills, Pennsylvania, United States, 15025
      • GSK Investigational Site
  • Washington
    • Wenatchee, Washington, United States, 98801
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease	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.	At Day 0 (D0) and at Day 21 (D21) post vaccination.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 0 (D0) and at Day 21 (D21) post vaccination.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 0 (D0), and at Day 21 (D21) and Day 180 (D180) post vaccination.
Number of Subjects With Medically-attended Adverse Events (MAEs)	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.	From the beginning of the study until study end (from Day 0 to Day 180)
Number of Subjects With Related Medically-attended Adverse Events (MAEs)	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.	From the beginning of the study until study end (from Day 0 to Day 180) .
Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs)	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.	From the beginning of the study until study end (from Day 0 to Day 180) .
Number of Subjects With Any and Related Serious Adverse Events (SAEs)	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.	From the beginning of the study until study end (from Day 0 to Day 180)
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 0 (D0), and at Day 21 (D21) and Day 180 (D180) post vaccination.
Number of Seroprotected Subjects Against 4 Strains of Influenza Disease	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	At Day 0 (D0) and at Day 21 (D21) after vaccination.
Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 0 (D0) and at Day 21 (D21) after vaccination.
Number of Seroprotected Subjects Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 0 (D0) and at Day 21 (D21) after vaccination
Number of Seroconverted Subjects Against 4 Strains of Influenza by Age Strata	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.	At Day 21 (D21) after vaccination.
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 21 (D21) after vaccination
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 0 (D0) and at Day 21 (D21) post vaccination.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease	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.	At Day 0 (D0), and at Day 21 (D21) and Day 180 (D180) post vaccination.
Number of Seroconverted Subjects Against 4 Strains of Influenza	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.	At Day 21 (D21) after vaccination.
Number of Seroconverted Subjects Against 4 Strains of Influenza by Age Strata	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.	At Day 21 (D21) after vaccination.
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease by Age Strata	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.	At Day 21 (D21) post vaccination.
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease	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.	At Day 21 (D21) post vaccination.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	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.	Within the 7-day (Days 0-6) follow-up period after vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	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.	Within the 7-day (Days 0-6) follow-up period after vaccination
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)	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.	Within the 21-day (Days 0-20) follow-up period after vaccination
Number of Days With Solicited Local Symptoms After Vaccination.	Solicited local symptoms were pain, redness and swelling at the injection site. Analyses of duration for solicited local symptoms were not performed.	Within the 7-day follow-up period after vaccination (Days 0-6)
Number of Days With Solicited General Symptoms After Vaccination	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.	Within the 7-day follow-up period after vaccination (Days 0-6)
Number of Days With Unsolicited Adverse Events (AEs) After Vaccination	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.	Within the 21-day (Days 0-20) follow-up period post vaccination

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Tinoco JC, Pavia-Ruz N, Cruz-Valdez A, Aranza Doniz C, Chandrasekaran V, Dewe W, Liu A, Innis BL, Jain VK. Immunogenicity, reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults aged >/=18 years: a phase III, randomized trial. Vaccine. 2014 Mar 14;32(13):1480-7. doi: 10.1016/j.vaccine.2014.01.022. Epub 2014 Jan 28.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): January 25, 2011
• Study Completion (Actual): June 24, 2011

Study Registration Dates

• First Submitted: September 7, 2010
• First Submitted That Met QC Criteria: September 8, 2010
• First Posted (Estimate): September 9, 2010

Study Record Updates

• Last Update Posted (Actual): September 21, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 112963

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 112963
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register