Study to Evaluate an Influenza Vaccine Candidate

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00540228
First received: October 4, 2007
Last updated: May 9, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Influenza
Influenza Vaccines
Biological: Influenza Vaccine GSK1247446A - 4 different formulations
Biological: Fluarix™
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Influenza Vaccine GSK1247446A With Various Formulations in Subjects Aged 18-64 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease. [ Time Frame: At Days 0, 21 and 180 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. [ Time Frame: At Days 21 and 180 ] [ 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 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA).

  • Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 3 Strains of Influenza Disease. [ Time Frame: At Days 21 and 180 ] [ 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. The 3 influenza strains assessed were A/Solomon Islands (SOLO), A/Wisconsin (WISC) and B/Malaysia (MALA).

  • Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. [ Time Frame: At Days 0, 21 and 180 ] [ Designated as safety issue: No ]
    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).

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 4 T-cells. [ Time Frame: At Days 0, 21 and 180 ] [ Designated as safety issue: No ]
    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).

  • Geometric Mean of Influenza-specific Cluster of Differentiation (CD) 8 T-cells. [ Time Frame: At Days 0, 21 and 180 ] [ Designated as safety issue: No ]
    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).

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) post vaccination period ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 7-day (Days 0-6) post vaccination period ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs). [ Time Frame: From Day 0 to Day 180 ] [ Designated as safety issue: No ]
    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

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: During the 21-day (Days 0-20) post vaccination period ] [ 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 activity Related = unsolicited AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: 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.


Enrollment: 1006
Study Start Date: October 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00540228

Locations
France
GSK Investigational Site
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
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00540228     History of Changes
Other Study ID Numbers: 110794
Study First Received: October 4, 2007
Results First Received: March 14, 2013
Last Updated: May 9, 2013
Health Authority: Spain:Agencia Espanola de Medicamentos y Productos Sanitarios

Keywords provided by GlaxoSmithKline:
Influenza
Influenza Vaccine

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 April 17, 2014