Immunogenicity and Safety Study to Evaluate Different Formulations of GSK Biologicals' Influenza Vaccine GSK576389A

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00540592
First received: October 5, 2007
Last updated: November 8, 2012
Last verified: November 2012
  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 65 years and older compared to Fluarix.


Condition Intervention Phase
Influenza
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Biological: Fluarix
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Observer Blind Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Influenza Vaccine GSK576389A With Various Formulations in Adults Aged 65 Years and Above

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Haemagglutination Inhibition (HI) Antibody Titers [ Time Frame: At Day 21 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs) against each of the 3 vaccine strains in greater than or equal to 65 years age groups only. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.


Secondary Outcome Measures:
  • HI Antibody Titers at Day 0 and Day 21 [ Time Frame: At Day 0 and 21 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs in all the vaccine groups. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • HI Antibody Titers at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs in all the vaccine groups. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The Number of Subjects Seroconverted to HI Antibodies at Day 21 [ Time Frame: At Day 21 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 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.

  • The Number of Subjects Seroconverted to HI Antibodies at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 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 at Day 21 [ Time Frame: At Day 21 ] [ Designated as safety issue: No ]
    Seroconversion factors were 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.

  • HI Antibody Seroconversion Factors at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    Seroconversion factors were 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 at Day 0 and 21 [ Time Frame: At Day 0 and 21 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • 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 greater than or equal to 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 Influenza-specific CD4 T-cells Per Million CD4+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Days 0 and 21 [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    The markers assessed were Cluster of Differentiation 4-All doubles i.e. CD4-All doubles, CD4-CD40Ligand(L), CD4-interferon gamma (CD4-IFNγ), CD4-interleukin 2 (CD4-IL2) and CD4-tumor necrosis factor alpha (CD4-TNFα). The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The GM Number of Influenza-specific CD4 T-cells Per Million CD4+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    The markers assessed were CD4-All doubles, CD4-CD40L, CD4-IFNγ, CD4-IL2 and CD4-TNFα. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The GM Number of Influenza-specific CD8 T-cells Per Million CD8+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Days 0 and 21 [ Time Frame: At Days 0 and 21 ] [ Designated as safety issue: No ]
    The markers assessed were Cluster of Differentiation 8-All doubles i.e. CD8-All doubles, CD8-CD40L, CD8-IFNγ, CD8-IL2 and CD8-TNFα. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • The GM Number of Influenza-specific CD8 T-cells Per Million CD8+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Day 180 [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
    The markers assessed were CD8-All doubles, CD8-CD40L, CD8-IFNγ, CD8-IL2 and CD8-TNFα. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ] [ Designated as safety issue: No ]
    Grade 3 ecchymosis, pain, redness and swelling was greater than 100 millimeter (mm) 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. Any for ecchymosis, redness and swelling was >20mm.

  • Duration of Solicited Local AEs [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ] [ 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: During a 7-day follow-up period (Day 0-6) after vaccination ] [ Designated as safety issue: No ]
    Any Fever was defined as axillary temperature greater than or equal to 38.0 degree centigrade i.e.≥ 38.0°C, grade 3 fever was axillary temperature >40°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 a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination.

  • Duration of Solicited General AEs [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ] [ 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: During a 21-day follow-up period (Day 0-20) after vaccination ] [ 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 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.

  • Number of Subjects Reporting Any, Grade 3 and Related Adverse Events Resulting in Medically Attended Visit Between Day 0 and Day 20 [ Time Frame: Between Day 0 and Day 20 after vaccination ] [ 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 or relation to vaccination and grade 3 was defined as a symptom that prevented normal activity. Related was a symptom assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any, Grade 3 and Related Adverse Events Resulting in Medically Attended Visit Between Day 21 and Day 179 [ Time Frame: Between Day 21 and Day 179 after vaccination ] [ 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 or relation to vaccination and grade 3 was defined as a symptom that prevented normal activity. Related was a symptom assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) Between Day 0 and Day 20 [ Time Frame: Between Day 0 and Day 20 after vaccination ] [ 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 or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) Between Day 21 and Day 179 [ Time Frame: Between Day 21 and Day 179 after vaccination ] [ 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 or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.


Enrollment: 2007
Study Start Date: October 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Influenza vaccine GSK576389A formulation 1 Group
Subjects aged ≥65 years received one dose of formulation 1 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 2 Group
Subjects aged ≥65 years received one dose of formulation 2 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 3 Group
Subjects aged ≥65 years received one dose of formulation 3 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 4 Group
Subjects aged ≥65 years received one dose of formulation 4 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 5 Group
Subjects aged ≥65 years received one dose of formulation 5 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 6 Group
Subjects aged ≥65 years received one dose of formulation 6 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 7 Group
Subjects aged ≥65 years received one dose of formulation 7 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 8 Group
Subjects aged ≥65 years received one dose of formulation 8 of the adjuvanted influenza vaccine GSK576389A.
Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A
Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Active Comparator: Fluarix elderly Group
Subjects aged ≥65 years received one dose of Fluarix vaccine.
Biological: Fluarix
Single dose, Intramuscular injection
Active Comparator: Fluarix young Group
Subjects aged 18-40 years received one dose of Fluarix vaccine.
Biological: Fluarix
Single dose, Intramuscular injection

Detailed Description:

There are 10 parallel groups: 9 observer blinded groups with subjects 65 years and older receiving an investigational vaccine or Fluarix, and 1 open group with subjects between 18 and 40 years old receiving Fluarix. CMI response will be determined for a subset only.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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 18-40 years old or 65 years or 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 (medical history and medical history directed 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 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 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 a vaccine not foreseen by the study protocol during the entire study period.
  • Planned administration of an influenza vaccine other than the study vaccines during the entire study period.
  • Vaccination against influenza since January 2007 (with 2007/2008 or 2006/2007 influenza vaccine).
  • Administration of more than 14 days of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
  • Hypersensitivity to a previous dose of influenza vaccine.
  • Allergy to any component of the vaccine.
  • Acute (active) clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
  • 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 diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. axillary temperature<37.5ºC (99.5ºF).
  • 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 IM injections are contraindicated.
  • Lactating female or female planning to become pregnant or 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: NCT00540592

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, 13359
GSK Investigational Site
Berlin, Germany, 13347
GSK Investigational Site
Berlin, Germany, 10435
GSK Investigational Site
Hamburg, Germany, 22335
GSK Investigational Site
Hamburg, Germany, 22415
Netherlands
GSK Investigational Site
Rotterdam, Netherlands, 3015 GE
GSK Investigational Site
Rotterdam, Netherlands, 3011 EN
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
United Kingdom
GSK Investigational Site
Reading, Berkshire, United Kingdom, RG2 0TG
GSK Investigational Site
Buckshaw Village, Chorley, Lancashire, United Kingdom, PR7 7NA
GSK Investigational Site
Clydebank, Glasgow, United Kingdom, G81 2DR
GSK Investigational Site
Edgbaston, Birmingham, United Kingdom, B15 2SQ
GSK Investigational Site
Waterloo, Liverpool, United Kingdom, L22 0LG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00540592     History of Changes
Other Study ID Numbers: 110847
Study First Received: October 5, 2007
Results First Received: April 26, 2012
Last Updated: November 8, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
Influenza vaccine GSK576389A
Influenza infection
Fluarix

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 23, 2014