Study to Evaluate an Influenza Vaccine Candidate

Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Influenza Vaccine GSK1247446A With Various Formulations in Subjects Aged 18-64 Years

In order to find the formulation leading to a maximal increase of the immune response while maintaining an acceptable safety profile, this study is designed to evaluate the immunogenicity, safety and reactogenicity of the different formulations of GSK Biologicals' influenza vaccine administered in adults aged 18-64 years.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluarix™; Biological: Influenza Vaccine GSK1247446A - 4 different formulations

Detailed Description

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

• Study Type: Interventional
• Enrollment (Actual): 1006
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Caen cedex 4, France, 14052
    • GSK Investigational Site
  • Lagord, France, 17140
    • GSK Investigational Site
  • Lille, France, 59019
    • GSK Investigational Site
  • Paris, France, 75679
    • GSK Investigational Site
  • Paris Cedex 18, France, 75877
    • GSK Investigational Site
  • Toulouse, France, 31300
    • GSK Investigational Site
• Germany
  • Baden-Wuerttemberg
    • Tuebingen, Baden-Wuerttemberg, Germany, 72074
      • GSK Investigational Site
  • Bayern
    • Wuerzburg, Bayern, Germany, 97070
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
    • Freiberg, Sachsen, Germany, 09599
      • GSK Investigational Site
    • Schmiedeberg, Sachsen, Germany, 01762
      • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Madrid, Spain, 28035
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Only subjects who the investigator believes that they can and will comply with the requirements of the protocol .
• A male or female between, and including, 18 - 64 years of age at the time of vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must have a negative pregnancy test, practice adequate contraception for 30 days prior to vaccination, and continue such precautions 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(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first vaccine dose
• Administration of a vaccine not foreseen by the study protocol from 30 days before vaccination, up to 21 days after vaccination.
• History of hypersensitivity to a previous dose of influenza vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s)
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Confirmed influenza infection within a year preceding the study start.
• Administration of an influenza vaccine within a year preceding the study start.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
• Pregnant or lactating female.
• Concurrent participation 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 product
• Acute disease at the time of enrolment.
• History of chronic alcohol consumption and/or drug abuse.
• 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.
• History of administration of experimental/licensed vaccine containing squalene and/or tocopherol within the last 12 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK1247446A 1 Group; Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with a full dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Influenza Vaccine GSK1247446A - 4 different formulations; Single dose, Intramuscular injection
Experimental: GSK1247446A 2 Group; Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with 1/2 dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Influenza Vaccine GSK1247446A - 4 different formulations; Single dose, Intramuscular injection
Experimental: GSK1247446A 3 Group; Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with 1/4 dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Influenza Vaccine GSK1247446A - 4 different formulations; Single dose, Intramuscular injection
Experimental: GSK1247446A 4 Group; Subjects aged 18-64 years at the time of enrolment received 1 dose of GSK1247446A with 1/8 dose of AS03 adjuvant at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Influenza Vaccine GSK1247446A - 4 different formulations; Single dose, Intramuscular injection
Active Comparator: Fluarix Group; Subjects aged 18-64 years at the time of enrolment received 1 dose of FluarixTM at Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.	Biological: Fluarix™; Single dose, Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease.	Titers are presented as geometric mean titers (GMTs). The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA). The seropositivity cut-off assay was 1:10. The results for Day 0 and Day 21 are the primary efficacy variables.	At Days 0, 21 and 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconverted Subjects Against 3 Strains of Influenza Disease.	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 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA).	At Days 21 and 180
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 3 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. The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA).	At Days 21 and 180
Number of Seroprotected Subjects Against 3 Strains of Influenza Disease.	A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA).	At Days 0, 21 and 180
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease.	Titers are presented as geometric mean titers (GMTs). The 4 influenza strains assessed were A/Wisconsin (WISC), B/Malaysia (MALA), A/Brisbane (BRIS) and B/Florida (FLOR). The seropositivity cut-off assay was 1:28.	At Days 0 and 21
Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4 T-cells.	The mean was calculated for CD4 T-cells (per million CD4 T-cells) producing at least two different cytokines (All Doubles), at least CD40L, at least INF gamma (IFN-γ), at least IL2 and at least TNF alpha (TNF-α).	At Days 0, 21 and 180
Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 8 T-cells.	The mean was calculated for CD8 T-cells (per million CD8 T-cells) producing at least two different cytokines (All Doubles), at least CD40L, at least INF gamma (IFN-γ), at least IL2 and at least TNF alpha (TNF-α).	At Days 0, 21 and 180
Number of Subjects With Any and Grade 3 Solicited Local Symptoms.	Assessed solicited local symptoms were ecchymosis, pain, redness and swelling at injection site. Any = incidence of a particular symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal everyday activity. Grade 3 redness/swelling/ecchymosis = redness/swelling/ecchymosis spreading beyond 50 millimeters (mm) of the injection site.	During the 7-day (Days 0-6) post vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.	Assessed solicited general symptoms were arthralgia, fatigue, fever [oral temperature above (>) 38.0 degrees Celsius (°C)], headache, myalgia, nausea and shivering. Any = incidence of a particular symptom regardless of grade intensity or relationship with the study vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0°C. Related = symptom considered by the investigator to have a causal relationship to study vaccination.	During the 7-day (Days 0-6) post vaccination period
Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs).	MSCs were defined as conditions prompting emergency room visits or physician visits that were not related to common diseases or routine visits. Any = incidence of a particular symptom regardless of grade intensity or relationship with the study vaccination. Grade 3 = event which prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination	From Day 0 to Day 180
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 activity Related = unsolicited AE assessed by the investigator as related to the vaccination.	During the 21-day (Days 0-20) post vaccination period
Number of Subjects With 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 Day 0 to Day 180

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): October 5, 2007
• Primary Completion (Actual): May 8, 2008
• Study Completion (Actual): May 8, 2008

Study Registration Dates

• First Submitted: October 4, 2007
• First Submitted That Met QC Criteria: October 4, 2007
• First Posted (Estimate): October 5, 2007

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Influenza; Influenza Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 110794; 2007-003776-18 (EudraCT Number)

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. Dataset Specification
   Information identifier: 110794
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 110794
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 110794
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 110794
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 110794
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 110794
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register