Immunogenicity & Safety of GSK's Avian Flu Vaccine 1557484A Given to Adults Aged 18-64 Years

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00771615
First received: October 10, 2008
Last updated: September 4, 2014
Last verified: August 2014
  Purpose

The purpose of this observer-blind study is to determine whether GSK's avian flu vaccine GSK 1557484A is immunogenic when given to adults aged 18-64 years.


Condition Intervention Phase
Influenza
Biological: GSK A/turkey H5N1 Influenza vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Trial to Evaluate the Safety & Immunogenicity of Investigational Influenza Vaccine GSK1557484A in Adults 18-64 Yrs of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain. [ Time Frame: At Day 10 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) titer less than (<) 1:10 for HI and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40, or a pre-vaccination reciprocal titer ≥ 1:10 for HI and at least a 4-fold increase in post-vaccination reciprocal titer.

  • Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain [ Time Frame: At Day 10 ] [ Designated as safety issue: No ]
    A seroprotected subject against the A/turkey virus strain was defined as a subject with serum HI antibody reciprocal titer ≥ 1:40 post-vaccination, a level of HI antibodies that may correlate with benefit in protection against influenza.

  • Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain. [ Time Frame: At Day 10 ] [ Designated as safety issue: No ]
    HI antibody titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of ≥ 1:10.


Secondary Outcome Measures:
  • Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strains. [ Time Frame: At Day 0 to Day 42 and at Day 0 to Day 182 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) titer less than (<) 1:10 for HI and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40, or a pre-vaccination reciprocal titer ≥ 1:10 for HI and at least a 4-fold increase in post-vaccination reciprocal titer.

  • Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 Virus Strain. [ Time Frame: At Day 0, Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of ≥ 1:10

  • HI Antibody Geometric Mean Fold Rise (GMFR) Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain. [ Time Frame: At Day 0 to Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    GMFR were defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer.

  • HI Antibody Titers Against the A/Indonesia/5/2005 (A/Indo) Virus Strain. [ Time Frame: At Day 0, Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of ≥ 1:10

  • Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (A/Indo) and A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strains. [ Time Frame: At Day 0, Day 10, Day 42 and Day 182 for A/Indo and at Day 0, Day 42 and Day 182 for A/turkey virus strains. ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with serum HI antibody reciprocal titer ≥ 1:40 post-vaccination, a level of HI antibodies that may correlate with benefit in protection against influenza.

  • Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (A/Indo) Virus Strains. [ Time Frame: At Day 0 to Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer.

  • HI Antibody Geometric Mean Fold Rise (GMFR) Against the A/Indonesia/5/2005 (A/Indo) Virus Strains. [ Time Frame: At Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    GMFR were defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer.

  • Microneutralization (MN) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey), A/Indonesia/5/2005 (A/Indo) and A/Vietnam/1194/2004 (A/Vie) Virus Strains. [ Time Frame: At Day 0, Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    MN antibody titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of ≥ 1:28.

  • Number of Subjects Seropositive for MN Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey), A/Indonesia/5/2005 (A/Indo) and A/Vietnam/1194/2004 (A/Vie) Virus Strains. [ Time Frame: At Day 0, Day 10, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    A seropositive subject was defined as a vaccinated subject who had a MN antibody titer ≥ the cut-off value of 1:28.

  • Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey), A/Indonesia/5/2005 (A/Indo) and A/Vietnam/1194/2004 (A/Vie) Virus Strains. [ Time Frame: At Day 10 ] [ Designated as safety issue: No ]
    VRR was defined as a 4-fold rise from a detectable baseline titer or a rise from undetectable (< 1:28, recorded 1:14 if < 1:28) to ≥ 1:56 in the subjects.

  • Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey), A/Indonesia/5/2005 (A/Indo) and A/Vietnam/1194/2004 (A/Vie) Virus Strains [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    VRR was defined as a 4-fold rise from a detectable baseline titer or a rise from undetectable (< 1:28, recorded 1:14 if < 1:28) to ≥ 1:56 in the subjects.

  • Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey), A/Indonesia/5/2005 (A/Indo) and A/Vietnam/1194/2004 (A/Vie) Virus Strains. [ Time Frame: At Day 182 ] [ Designated as safety issue: No ]
    VRR was defined as a 4-fold rise from a detectable baseline titer or a rise from undetectable (< 1:28, recorded 1:14 if < 1:28) to ≥ 1:56 in the subjects.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. [ Time Frame: Within the 7-day (Days 0-6) post vaccination period. ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptoms regardless of their intensity grade.

  • Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms. [ Time Frame: Within the 7-day (Days 0-6) post vaccination period. ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were fatigue, headache, joint pain at other location (joint pain), muscle aches, shivering, sweating and fever. Any =occurrence of any solicited general symptoms reported irrespective of intensity grade and relationship to vaccination. Any fever = oral temperature ≥ 38.0 degrees Celsius (°C).

  • Number of Subjects With Medically-attended Adverse Events (MAEs). [ Time Frame: From Day 0 to Day 378 ] [ Designated as safety issue: No ]
    MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s).

  • Number of Subjects Reporting Any Unsolicited Adverse Events (AEs). [ Time Frame: From Day 0 to Day 42 ] [ Designated as safety issue: No ]
    An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs). [ Time Frame: From Day 0 to Day 378 ] [ Designated as safety issue: No ]
    A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was 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.


Enrollment: 469
Study Start Date: October 2008
Study Completion Date: December 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A/turkey H5N1 influenza Formulation A Group
Subjects previously primed in NCT00510874 study with formulation 1 of Influenza A (Q-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation A of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation B1 Group
Subjects previously primed in NCT00510874 study with formulation 2 of Influenza A (Q-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation B1 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation B2 Group
Subjects previously primed in NCT00510874 study with formulation 2 of Influenza A (Q-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation B2 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation C1 Group
Subjects previously primed in NCT00510874 study with formulation 3 of Influenza A (Q-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation C1 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation C2 Group
Subjects previously primed in NCT00510874 study with formulation 3 of Influenza A (Q-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation C2 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation D1 Group
Subjects previously primed in NCT00510874 study with formulation 2 of Influenza A (D-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation D1 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation D2 Group
Subjects previously primed in NCT00510874 study with formulation 2 of Influenza A (D-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation D2 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation E1 Group
Subjects previously primed in NCT00510874 study with formulation 3 of Influenza A (D-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation E1 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.
Experimental: A/turkey H5N1 influenza Formulation E2 Group
Subjects previously primed in NCT00510874 study with formulation 3 of Influenza A (D-Pan H5N1) virus monovalent vaccine (A/Indonesia) were boosted with a single dose of formulation E2 of GSK A/turkey H5N1 Influenza vaccine in this study. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: GSK A/turkey H5N1 Influenza vaccine
One dose administered intramuscularly (IM) in the deltoid region. Different formulations are tested.

Detailed Description:

All enrolled subjects will receive 1 dose of study vaccine. All subjects will attend formal study center visits for safety and immunogenicity assessments on Days 0, 10, 42, 84, and 182 with a telephone safety contact on Day 364.

This Protocol Posting has been updated according to Protocol amendment, 8 Dec 08

  Eligibility

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

Inclusion Criteria:

  • Male and female adults 18 to 64 years of age at time of first vaccination, inclusive.
  • Written informed consent obtained from the subject.
  • Stable health status as defined by absence of a health event satisfying the definition of a SAE, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrollment.
  • Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device.
  • Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
  • Subjects who the investigator believes can and will comply with the requirements of the protocol.

Exclusion Criteria:

  • Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
  • Diagnosed with cancer, or treatment for cancer, within 3 years.
  • Presence of an oral temperature >= 37.8ºC, or acute symptoms greater than "mild" severity on the scheduled date of vaccination.
  • Any confirmed or suspected immunosuppressive or immunodeficiency condition including history of human immunodeficiency virus (HIV) infection.
  • Receipt of systemic glucocorticoids (prednisone >= 10 mg/day for more than 14 consecutive days) within 1 month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment.
  • An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine.
  • Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin.
  • Administration of any vaccines within 30 days before the first study vaccine dose.
  • Previous administration of any H5N1 vaccine.
  • Use of any investigational or non-registered product (drug or vaccine) or planned participation in another investigational study within 30 days prior to study enrollment, or during the 12 months following test article administration. Use of any investigational or non-registered product with immunosuppressive properties is exclusionary at any time during the trial.
  • Receipt of any immunoglobulins and/or any blood products within 3 months of study enrollment or planned administration of any of these products during the study period.
  • Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
  • Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result prior to vaccination.
  • Lactating or nursing.
  • Women of child bearing potential (who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to vaccination.
  • Known receipt of analgesic or antipyretic medication with the specific intent of prophylaxis of vaccine reactogenicity on the day of vaccination. Subjects on stable chronic regimens of potentially analgesic or anti-pyretic medications for pre-existing diagnoses are not required to discontinue them.
  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: NCT00771615

Locations
United States, Alabama
GSK Investigational Site
Huntsville, Alabama, United States, 35802
United States, California
GSK Investigational Site
Anaheim, California, United States, 92801
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33143
United States, Georgia
GSK Investigational Site
Stockbridge, Georgia, United States, 30281
United States, Kansas
GSK Investigational Site
Lenexa, Kansas, United States, 66219
United States, Montana
GSK Investigational Site
Missoula, Montana, United States, 59801
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89130
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3K 6R8
GSK Investigational Site
Truro, Nova Scotia, Canada, B2N 1L2
Canada, Quebec
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1H 4J6
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: NCT00771615     History of Changes
Other Study ID Numbers: 111729
Study First Received: October 10, 2008
Results First Received: December 19, 2013
Last Updated: September 4, 2014
Health Authority: Canada: Biologics and Genetics Therapeutic Directorate (B>D)
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
human
Avian
safety
vaccines
influenza
pandemic
immunogenicity
H5N1

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
Respiratory Tract Diseases
Respiratory Tract Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 30, 2014