Evaluation of Safety and Immunogenicity of GSK Bio's Influenza Vaccine GSK576389A After Repeated Vaccination in Elderly Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00538213
First received: October 1, 2007
Last updated: August 2, 2012
Last verified: May 2012
  Purpose

Since influenza vaccines are administered every year because of the frequent change in their antigenic composition, the safety and immunogenicity profile of GSK Biologicals' influenza vaccine GSK576389A will be re-evaluated after repeated vaccine administration. In this study, the subjects previously enrolled in study 104887 will receive a dose with the 2007-2008 season's formulations of Fluarix or GSK576389A. Only subjects who were previously enrolled in study 104887 are eligible for participation in this study.


Condition Intervention Phase
Influenza
Influenza Vaccines
Biological: Fluarix™
Biological: GSK Bio's Influenza Vaccine GSK576389A
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Reactogenicity and Immunogenicity of GSK Biologicals' Influenza Vaccine GSK576389A in Elderly Adults (≥66 Years) Previously Vaccinated With the Same Candidate Vaccine. Fluarix™ Will be Used as Reference

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [ Time Frame: Day 0-6 ] [ Designated as safety issue: No ]
    Grade 3 ecchymosis, redness and swelling was greater than 100 millimeter i.e. >100 mm and grade 3 pain was considerable pain at rest that prevented normal everyday activities. Any was occurrence of any local symptom regardless of their intensity grade.

  • Duration of Solicited Local AEs [ Time Frame: Day 0-6 ] [ Designated as safety issue: No ]
    Duration was defined as number of days with any grade of local symptoms.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs [ Time Frame: Day 0-6 ] [ Designated as safety issue: No ]
    Any temperature was defined as axillary temperature ≥38.0 degree centigrade (°C), grade 3 temperature was axillary temperature ≥39.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 was defined as general symptom that prevented normal activity. Related was general symptom assessed by the investigator as causally related to the study vaccination.

  • Duration of Solicited General AEs [ Time Frame: Day 0-6 ] [ Designated as safety issue: No ]
    Duration was defined as number of days with any grade of general symptoms.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs [ Time Frame: Day 0-20 ] [ 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 was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was event that prevented normal activities and related was defined as unsolicited AE assessed by the investigator to be causally related to the study vaccination.

  • Number of Subjects Reporting at Least One, Grade 3 and Related Medically Significant Conditions (MSCs) [ Time Frame: Day 0-20 ] [ Designated as safety issue: No ]
    MSCs 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. At least one MSC was defined as at least one MSC experienced. Grade 3 was MSC that prevented normal activities and Related was defined as MSC assessed by the investigator to be causally related to the study vaccination.

  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) [ Time Frame: Day 0-20 ] [ Designated as safety issue: No ]
    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. Any was defined as occurrence of any symptom regardless of intensity grade and related was event assessed by the investigator as causally related to the study vaccination.


Secondary Outcome Measures:
  • Haemagglutination Inhibition (HI) Antibody Titers [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The Number of Subjects Seropositive to HI Antibodies [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e. ≥ 1:10. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The Number of Subjects Seroconverted to HI Antibodies [ Time Frame: At Day 21 ] [ Designated as safety issue: No ]
    Seroconversion was defined as 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 4-fold increase in post-vaccination titer. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • HI Antibody Seroconversion Factors (SCF) [ Time Frame: At Day 21 ] [ Designated as safety issue: No ]
    SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The Number of Subjects Seroprotected to HI Antibodies [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    Seroprotection was defined as serum HI titer ≥1:40 that usually is accepted as indicating protection. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The Geometric Mean (GM) Number of CD4 T-cells Per Million CD4+ T-cells for Each Vaccine Strain and for Pooled Vaccine Strains Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    The vaccine strains included A/Solomon Islands, A/Wisconsin, B/Malaysia and Pool FLU antigens and the markers assessed were Cluster of Differentiation 4-All doubles i.e. CD4-All doubles, CD40 Ligand (CD40L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α).

  • The GM Number of CD8 T-cells Per Million CD8+ T-cells for Each Vaccine Strain and for Pooled Vaccine Strains Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    The vaccine strains included A/Solomon Islands, A/Wisconsin, B/Malaysia and Pool FLU antigens and the markers assessed were CD8-All doubles, CD40L, IFN-γ, IL-2 and TNF-α.


Enrollment: 133
Study Start Date: October 2007
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjuvanted influenza vaccine GSK576389A Group
Subjects aged ≥ 66 years who previously received 1 dose of adjuvanted influenza vaccine GSK576389A in NCT00318149 and NCT00386698 studies were administered 1 dose of adjuvanted influenza vaccine GSK576389A.
Biological: GSK Bio's Influenza Vaccine GSK576389A
Single dose, Intramuscular injection
Active Comparator: Fluarix young Group
Subjects aged 19-42 years who previously received 1 dose of Fluarix vaccine in NCT00318149 and NCT00386698 studies were administered 1 dose of Fluarix vaccine.
Biological: Fluarix™
Single dose, Intramuscular injection
Active Comparator: Fluarix elderly Group
Subjects aged ≥ 66 years who previously received 1 dose of Fluarix vaccine in NCT00318149 and NCT00386698 studies were administered 1 dose of Fluarix vaccine.
Biological: Fluarix™
Single dose, Intramuscular injection

Detailed Description:

This study is a year 2 revaccination study. First year revaccination was done in study 104887 (NCT00386698). Primary study was study 104886 (NCT00318149). This study involves 2 age groups (based on primary study):

Subjects enrolled in the ≥ 65 years age group in the primary study. Subjects enrolled in the 18-40 years age group in the primary study.

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

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who were previously vaccinated with GlaxoSmithKline Biologicals Fluarix™ or GSK576389A investigational vaccines in the 104887 study (NCT00386698).
  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
  • A male or female aged between 19 and 42 years or 66 years and older at the time of the vaccination.
  • Written informed consent obtained from the subject.
  • Free of an acute aggravation of the health status as established by clinical evaluation 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 practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test 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 vaccines within 30 days prior to vaccination, or planned use during the study period.
  • Administration of other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study. Planned administration of a vaccine not foreseen by the study protocol up to 21 days after vaccination.
  • Planned administration of an influenza vaccine other than the study vaccines during the entire study period.
  • Vaccination against influenza since January 2007 with the Northern Hemisphere 2007/2008 influenza vaccine or 2006/2007 influenza vaccine.
  • History of confirmed influenza infection since the date of previous vaccination.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the administration of the study vaccine. (For corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of hypersensitivity to a previous dose of influenza vaccine.
  • History of allergy or reactions likely to be exacerbated by any component of the vaccine(s)
  • Acute (active) clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by clinical evaluation (medical history and medical history directed physical examination) or pre-existing laboratory screening tests.
  • Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Axillary temperature <37.5°C / Oral temperature of <37.5°C).
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the study vaccine or planned administration during the study.
  • Any medical conditions in which intramuscular injections are contraindicated.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538213

Locations
Belgium
GSK Investigational Site
Gent, Belgium, 9000
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00538213     History of Changes
Other Study ID Numbers: 110263
Study First Received: October 1, 2007
Results First Received: April 5, 2012
Last Updated: August 2, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by GlaxoSmithKline:
Influenza vaccine GSK576389A
Fluarix
Influenza infection

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 August 21, 2014