Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals' Influenza Vaccine in Elderly People

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00992784
First received: October 1, 2009
Last updated: July 19, 2012
Last verified: March 2012
  Purpose

The purpose of the study is to evaluate the safety of GSK Biologicals' influenza vaccine. Elderly subjects were randomized in the primary study (NCT00760617) and will now receive the same vaccine for the third time. For this study the masking is "observer-blind" for elderly subjects and "open" for young adult subjects.


Condition Intervention Phase
Influenza Infection
Biological: GSK investigational vaccine 2186877A
Biological: FluarixTM
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Observer-blind Safety and Immunogenicity Study of GlaxoSmithKline Biologicals' Influenza Vaccine GSK2186877A When Administered to Elderly Subjects

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 ≥ 100 millimeter (mm) and grade 3 pain was considerable pain at rest, that prevented normal everyday activities.

  • 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 fever was defined as oral temperature ≥ 38.0 degree centigrade (°C), grade 3 fever was oral temperature ≥ 39.0°C-≤ 40.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade, grade 3 was defined as general symptom that prevented normal activity and 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, grade 3 was unsolicited symptom that prevented normal activity and related was event assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit [ Time Frame: Day 0-179 ] [ Designated as safety issue: No ]
    For each solicited and unsolicited AE the subject experienced, the subject was asked if they had received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting AEs of Specific Interest (AESI) [ Time Frame: Day 0-179 ] [ Designated as safety issue: No ]
    AESI for safety monitoring are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) up to Day 180 [ Time Frame: Up to Day 180 ] [ 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.

  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) After Day 180 [ Time Frame: After Day 180 ] [ 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 at Days 0 and 21 [ Time Frame: Day 0 and Day 21 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs) against separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens.

  • HI Antibody Titers at Day 180 [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs against separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens.

  • The Number of Subjects Seropositive to HI Antibodies at Days 0 and 21 [ Time Frame: Day 0 and Day 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 Number of Subjects Seropositive to HI Antibodies at Day 180 [ Time Frame: Day 180 ] [ 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 Number of Subjects Seroconverted to HI Antibodies at Day 21 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a 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 4-fold increase in post-vaccination titer.

  • The Number of Subjects Seroconverted to HI Antibodies at Day 180 [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a 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 4-fold increase in post-vaccination titer.

  • HI Antibody Seroconversion Factors (SCF) at Day 21 [ 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.

  • HI Antibody SCF at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.

  • The Number of Subjects Seroprotected to HI Antibodies at Days 0 and 21 [ Time Frame: At Day 0 and Day 21 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum HI titer ≥ to 1:40 that usually is accepted as indicating protection.

  • The Number of Subjects Seroprotected to HI Antibodies at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum HI titer ≥ 1:40 that usually is accepted as indicating protection.

  • The Geometric Mean (GM) Number of Influenza Specific Cluster of Differentiation 4 (CD4) T-cells Per Million CD4 T-cells for Each Vaccine Strains Expressing at Least Two Different Markers or Expressing Different Combinations of Markers at Days 0 and 21 [ Time Frame: At Day 0 and Day 21 ] [ Designated as safety issue: No ]
    The markers assessed were Cluster of Differentiation 40 Ligand (CD40L), interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) and vaccine strains tested included A/Brisbane, A/Uruguay and B/Brisbane antigens.

  • The GM Number of Influenza Specific Cluster of Differentiation 4 (CD4) T-cells Per Million CD4 T-cells for Each Vaccine Strain Expressing at Least Two Different Markers or Expressing Different Combinations of Markers at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    The markers assessed were CD40L, IL-2, TNF-α and IFN-γ and vaccine strains tested included A/Brisbane, A/Uruguay and B/Brisbane antigens.


Enrollment: 370
Study Start Date: October 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: New generation influenza vaccine GSK2186877A Group
Subjects aged ≥ 66 years receiving 1 dose of New generation influenza vaccine GSK2186877A
Biological: GSK investigational vaccine 2186877A
Single dose, intramuscular injection
Active Comparator: Fluarix elderly Group
Subjects aged ≥ 66 years receiving 1 dose of Fluarix vaccine
Biological: FluarixTM
Single dose, intramuscular injection
Active Comparator: Fluarix young Group
Subjects aged 19-43 years receiving 1 dose of Fluarix vaccine
Biological: FluarixTM
Single dose, intramuscular injection

  Eligibility

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

Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. Specific attention should be given to the compliance potential of subjects with suspected drug or alcohol abuse.
  • A male or female aged 19-43 years or >=66 years at the time of the vaccination and who participated in the study NCT00760617 and completed the 6-month follow-up.
  • 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.
  • 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 for 2 months after the vaccination.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:

  • Use of any investigational or non-registered product other than the study vaccine(s) 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 an influenza vaccine other than the study vaccines or of a vaccine not foreseen in the study protocol during the entire study period.
  • Vaccination against influenza since January 2009 with a seasonal influenza vaccine.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the administration of the study vaccine.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • History of hypersensivity to a previous dose of influenza vaccine.
  • History of allergy or reactions likely to be exacerbated by any component of the vaccine(s).
  • Acute clinically significant pulmonary, cardiovascular, hepatic, renal, neurological and psychiatric disorders, as determined by clinical evaluation or pre-existing laboratory screening tests.
  • Acute disease and/or fever at the time of enrolment.

    • Fever is defined as temperature >=37.5°C on oral setting.
    • Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  • 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.
  • Any medical conditions in which IM 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: NCT00992784

Locations
Germany
GSK Investigational Site
Gueglingen, Baden-Wuerttemberg, Germany, 74363
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68161
GSK Investigational Site
Rudersberg, Baden-Wuerttemberg, Germany, 73635
GSK Investigational Site
Weinheim, Baden-Wuerttemberg, Germany, 69469
GSK Investigational Site
Augsburg, Bayern, Germany, 86150
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45359
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Rhaunen, Rheinland-Pfalz, Germany, 55624
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
GSK Investigational Site
Wolmirstedt, Sachsen-Anhalt, Germany, 39326
GSK Investigational Site
Dresden, Sachsen, Germany, 01067
GSK Investigational Site
Freital, Sachsen, Germany, 01705
GSK Investigational Site
Leipzig, Sachsen, Germany, 04103
GSK Investigational Site
Berlin, Germany, 12627
GSK Investigational Site
Berlin, Germany, 10435
GSK Investigational Site
Berlin, Germany, 13347
GSK Investigational Site
Hamburg, Germany, 22415
GSK Investigational Site
Hamburg, Germany, 22335
Netherlands
GSK Investigational Site
Rotterdam, Netherlands, 3011 EN
GSK Investigational Site
Rotterdam, Netherlands, 3011 AA
Sweden
GSK Investigational Site
Eskilstuna, Sweden, SE-631 88
GSK Investigational Site
Karlskrona, Sweden, SE-371 41
GSK Investigational Site
Uppsala, Sweden, SE-751 85
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00992784     History of Changes
Other Study ID Numbers: 113094
Study First Received: October 1, 2009
Results First Received: March 8, 2012
Last Updated: July 19, 2012
Health Authority: Netherlands: Ministry of Health, Welfare and Sports
Germany: Paul-Ehrlich-Institut
Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
Influenza Vaccines
GSK Bio's influenza vaccine GSK2186877A
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 July 29, 2014