Immunogenicity and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra (2015 Season Southern Hemisphere) in Adults 18 Years of Age and Above

A Phase III Study for the Evaluation of the Immunogenicity and Reactogenicity of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra (2015 Season Southern Hemisphere) in Adults 18 Years of Age and Above

The purpose of this study is to evaluate the safety and immunogenicity of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra (2015 Southern hemisphere) in adults (18 to 60 years of age) and in the elderly (over 60 years of age).

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluarix Tetra

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 04266-010
    • GSK Investigational Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure.
• A male or female aged 18 years or above at the time of vaccination.
• Healthy subjects with well-controlled chronic diseases as established by medical history and clinical examination before entering into the study.
• 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 any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the dose of study vaccine (Day -29 to Day 0), or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs (e.g. rituximab, infliximab, etc.) within 6 months before study start, or planned administration during the study.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the study vaccination and during the entire study period.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
• Administration of an influenza vaccine within the 6 months preceding the study start or planned use of such vaccines during the study period..
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
• Clinically or virologically confirmed influenza infection within the six months preceding the study vaccination.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).

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

  • Fever is defined as temperature ≥ 38.0°C/100.4°F, measured by any means.
  • 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 or chronic, 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 stabilised or clinically serious.
• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
• History of Guillain-Barré syndrome.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine, including latex.
• History of severe adverse reaction to a previous influenza vaccination.
• Anaphylaxis following the administration of vaccine(s).
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluarix Tetra (Southern Hemisphere) Adult Group; Subjects aged 18-60 years received 1 dose of Fluarix™ Tetra (Southern Hemisphere) vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm.	Biological: Fluarix Tetra; One dose of the Fluarix™ Tetra vaccine was administered to all subjects on Day 0 (Visit 1) intramuscularly into the deltoid of the non-dominant arm.; Other Names: FLU D-QIV (GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra); Influsplit™ Tetra
Experimental: Fluarix Tetra (Southern Hemisphere) Elderly Group; Subjects aged >60 years received 1 dose of Fluarix™ Tetra (Southern Hemisphere) vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm.	Biological: Fluarix Tetra; One dose of the Fluarix™ Tetra vaccine was administered to all subjects on Day 0 (Visit 1) intramuscularly into the deltoid of the non-dominant arm.; Other Names: FLU D-QIV (GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra); Influsplit™ Tetra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral Immune Response for Each Vaccine Strain in Terms of Haemagglutination Inhibition (HI) Antibody Titers.	Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Days 0 and 21.
Number of Seropositive Subjects for HI Antibodies Against Each of the 4 Vaccine Strains.	A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cutoff value of 1:10. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Days 0 and 21
Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the 4 Vaccine Influenza Strains.	A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Days 0 and 21
Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the 4 Vaccine Influenza Strains.	A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination HI titer less than (<) 1:10 and a post-vaccination HI titer ≥1:40 or pre-vaccination HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination HI titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Day 21.
Number of Subjects With Seroprotection Power (SPP) for HI Antibody Titer Against Each of the 4 Vaccine Influenza Strains Above the Cut-off Value.	SPP was defined as the number of vaccinated subjects with a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:40. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Day 21
Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the 4 Vaccine Influenza Strains.	MGI also known as the seroconversion factor [SCF] was defined as the fold increase in serum HI GMTs post vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seropositive Subjects for HI Antibodies Against Each of the 4 Vaccine Strains.	A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cutoff value of 1:10. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Days 0 and 21
Humoral Immune Response for Each Vaccine Strain in Terms of HI Antibodies.	Antibody titers were expressed as GMTs. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Days 0 and 21
Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the 4 Vaccine Influenza Strains.	A seroprotected subject was defined as a vaccinated subject with a serum HI titer ≥ 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Days 0 and 21
MGI for HI Antibody Titer Against Each of the 4 Vaccine Influenza Strains.	MGI also known as the seroconversion factor [SCF] was defined as the fold increase in serum HI GMTs post vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Day 21
Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the 4 Vaccine Influenza Strains.	A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination HI titer less than (<) 1:10 and a post-vaccination HI titer ≥1:40 or pre-vaccination HI titer ≥1:10 and at least a 4-fold increase in post-vaccination HI titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Day 21.
Number of Subjects With Seroprotection Power (SPP) for HI Antibody Titer Against Each of the 4 Vaccine Influenza Strains Above the Cut-off Value.	SPP was defined as the number of vaccinated subjects with a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:40. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).	At Day 21
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 redness and swelling was greater than 100 millimeters (mm) i.e. >100mm.	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.	Solicited general symptoms assessed were Arthralgia, Fatigue, Gastrointestinal symptoms, Headache, Myalgia, Shivering, Sweating and Temperature (Oral). Any was defined as any general symptom reported irrespective of intensity or relationship to vaccination. Grade 3 was defined as symptoms that prevented normal activity. Related was defined as general symptom assessed by the investigator to have a causal relationship to vaccination.	During the 4-day (Days 0-3) post-vaccination period
Duration of Solicited Local Symptoms	Duration was defined as number of days with any grade of local symptoms.	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects Reporting Any, Grade 3 and Related Medically Attended Adverse Events (MAEs).	MAEs were defined as AEs with a medically-attended visit i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. Any MAE was defined as at least one MAE experienced. Grade 3 was defined as MAEs that prevented normal activities and related was defined as MAEs assessed by the investigator to be causally related to the study vaccination.	During the entire study period (approximately 21 days for each subject).
Duration of Solicited General Symptoms	Duration was defined as number of days with any grade of general symptoms.	During the 4-day (Days 0-3) post-vaccination period
Number of Subjects Reporting 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 was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination.	During the 21-day (Days 0-20) post-vaccination period.
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)	A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.	During the entire study period (approximately 21 days for each subject)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

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 (Actual): April 29, 2015
• Primary Completion (Actual): June 3, 2015
• Study Completion (Actual): June 3, 2015

Study Registration Dates

• First Submitted: February 16, 2015
• First Submitted That Met QC Criteria: February 16, 2015
• First Posted (Estimate): February 23, 2015

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Elderly; Influenza; Adults; Immunogenicity; Reactogenicity; Southern Hemisphere influenza vaccine; Seasonal flu; Fluarix Tetra
• 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: 201959

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. Annotated Case Report Form
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 201959
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No