Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine, Fluarix/Influsplit Tetra® (2013/2014 Season), in Adults 18 Years of Age and Older

Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine (GSK2321138A) Fluarix/Influsplit Tetra® (2013/2014 Season) in Adults 18 Years of Age and Older

The purpose of this study is to assess, in adults 18 years of age and above, the immunogenicity and reactogenicity of the seasonal influenza vaccine, Fluarix/Influsplit Tetra containing the four influenza strains (two A strains and two B strains) for the 2013/2014 season.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluarix/Influsplit Tetra® (2013-2014 season)

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Sachsen
    • Dresden, Sachsen, Germany, 01309
      • GSK Investigational Site
    • Dresden, Sachsen, Germany, 01097
      • GSK Investigational Site
    • Dresden, Sachsen, Germany, 01099
      • GSK Investigational Site
    • Dresden, Sachsen, Germany, 01129
      • 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 aged 18 years or above at the time of vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects or subjects with well-controlled chronic diseases as established by medical history and clinical examination before entering the study.

• Female subjects of non-childbearing potential may be enrolled in the study.

  • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• 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 vaccination.

Exclusion Criteria:

• Participation in previous year's Fluarix registration study (116663).
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within the six months prior to vaccination. Inhaled and topical steroids are allowed.
• Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period.
• Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned administration during the study period.
• Administration of an influenza vaccine within the twelve months preceding the study vaccination.
• Receipt of a vaccine other than the study vaccine within 30 days before study vaccination and/or plan to receive any vaccine other than the study vaccine during the entire study period.
• Clinically or virologically confirmed influenza infection within the six months preceding the study vaccination.

• Acute disease and/or fever at the time of enrollment.

  • Fever is defined as temperature ≥ 37.5°C/99.5°F on oral, axillary or tympanic setting, or ≥ 38.0°C/100.4°F on rectal setting. The preferred route for recording temperature in this study will be axillary.
  • Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Acute, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Chronic underlying disease (such as cancer, chronic obstructive pulmonary disease under oxygen therapy, insulin-dependent diabetes mellitus), not stabilized or clinically serious.
• History of chronic alcohol consumption and/or drug abuse.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of Guillain-Barré syndrome.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine including latex.
• Anaphylaxis following the administration of vaccine(s).
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• Any condition which, in the opinion of the investigator, prevents the subject from participating in the study or would make intramuscular injection unsafe.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fluarix/Influsplit Tetra® Adult Group; Subjects 18-60 years of age receiving Fluarix/Influsplit Tetra® 2013-2014, administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Fluarix/Influsplit Tetra® (2013-2014 season); 1 dose administered intramuscularly in the deltoid region of non-dominant arm
EXPERIMENTAL: Fluarix/Influsplit Tetra® Elderly Group; Subjects >60 years of age receiving Fluarix/Influsplit Tetra® 2013-2014, administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Fluarix/Influsplit Tetra® (2013-2014 season); 1 dose administered intramuscularly in the deltoid region of non-dominant arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-HI Antibody Titers Against 4 Strains of Influenza Disease	The strains assessed were: Flu A/Christchurch/16/2010 H1N1 HI, Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata) ,Flu B/Brisbane/60/2008 Victoria HI. Titers are presented as geometric mean titers (GMTs).	At Days 0 and 21
Number of Seroprotected Subjects Against 4 Strains of Influenza Disease	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI,(referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. A seroprotected subject is defined as a subject with serum HI titre ≥ 1:40.	At Day 21
Number of Seroconverted Subjects Against 4 Strains of Influenza Disease	The strains are: Flu A/Christchurch/16/2010 H1N1 HI,(referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. A seroconverted subject is defined as a subject with either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least 4-fold increase in post-vaccination titer.	At Day 21
Mean Geometric Increase (MGI) for HI Antibody Titer Against the 4 Flu Strains of Influenza Disease	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, (referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata) Flu B/Brisbane/60/2008 Victoria HI. MGI was defined as the fold increase in serum HI geometric mean titers post-vaccination compared to Day 0.	At Day 21
Seroprotection Powers (SPP) for HI Antibody Titer Against the 4 Flu Strains of Influenza Disease	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, (referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. SPP is defined as the percentage of subjects who had a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:40.	During a 4-day follow-up period after vaccination (i.e. day of vaccination and 3 subsequent days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = ecchymosis/induration/redness/swelling spreading beyond 100 millimeters (mm) of injection site.	During a 21-day follow-up period after vaccination (i.e. day of vaccination and 20 subsequent days)
Number of Days of Solicited Local Symptoms	Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. The number of days is expressed as a mean value.	During the entire study period (Days 0 to 21)
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, sweating and temperature [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)],. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During a 4-day follow-up period after vaccination (i.e. day of vaccination and 3 subsequent days)
Number of Days of Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, sweating and temperature [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)],. Any = occurrence of the symptom regardless of intensity grade. The number of days is expressed as a mean value.	During a 4-day follow-up period after vaccination (i.e. day of vaccination and 3 subsequent days)
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs).	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During a 4-day follow-up period after vaccination (i.e. day of vaccination and 3 subsequent days)
Number of Subjects With Any, Grade 3 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 or result in disability/incapacity.	At Days 0 and 21
Anti-HI Antibody Titers Against 4 Strains of Influenza Virus by Vaccination Status	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, (referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. Titers are presented as geometric mean titers (GMTs). Vaccination status is presented as Y = vaccinated or N = not vaccinated during the 2012-2013 season.	At Days 0 and 21
Number of Seroprotected Subjects Against 4 Strains of Influenza Virus by Vaccination Status	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, (referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. A seroprotected subject is defined as a subject with serum HI titre ≥ 1:40. Vaccination status is presented as Y = vaccinated or N = not vaccinated during the 2012-2013 season.	At Day 21
Number of Seroconverted Subjects Against 4 Strains of Influenza Virus by Vaccination Status	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, (referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. A seroconverted subject is defined as a subject with either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least 4-fold increase in post-vaccination titer. Vaccination status is presented as Y = vaccinated or N = not vaccinated during the 2012-2013 season.	At Day 21
Mean Geometric Increase (MGI) for HI Antibody Titer Against the 4 Flu Strains of Influenza Virus by Vaccination Status	The strains are: Flu A/Christchurch/16/2010 H1N1 HI, (referred to as Flu A/Christch/16/2010 H1N1), Flu A/Texas/50/2012 H3N2 HI, Flu B/Massachusetts/2/2012 Yamagata HI, (referred to as Flu B/Mass/2/2012 Yamagata), Flu B/Brisbane/60/2008 Victoria HI. MGI was defined as the fold increase in serum HI geometric mean titers post-vaccination compared to Day 0. Vaccination status is presented as Y = vaccinated or N = not vaccinated during the 2012-2013 season.	At Day 21

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• IPD for this study will be made available via the Clinical Study Data Request site.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 11, 2013
• Primary Completion (ACTUAL): August 5, 2013
• Study Completion (ACTUAL): August 5, 2013

Study Registration Dates

• First Submitted: June 13, 2013
• First Submitted That Met QC Criteria: June 14, 2013
• First Posted (ESTIMATE): June 17, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 7, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Elderly; Safety; Influenza; Adults; Immunogenicity
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 200188; 2013-001094-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR