Immunogenicity & Safety of GSK's Influenza Vaccine 1557484A Given to Adults Aged ≥18 Years

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00616928
First received: January 28, 2008
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The purpose of this Phase 3, observer-blind, placebo-controlled, multi-center study is to characterize the immunogenicity & safety of the investigation vaccination regimen of GSK 1557484A vaccine given to adults aged ≥18 years.


Condition Intervention Phase
Influenza
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Trial to Evaluate the Safety and Immunogenicity of an Investigational Vaccination Regimen in Adults Aged ≥18 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) [ Time Frame: At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer < 1:10 and a post-vaccination (Day 42) reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination reciprocal titer against A/Indonesia/5/05 virus 21 days after the second dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.

  • Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) [ Time Frame: At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40.

  • Number of Subjects With Any Solicited Local Symptoms. [ Time Frame: During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.

  • Number of Subjects With Any Solicited General Symptoms. [ Time Frame: During a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after each vaccine administration ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were fatigue, headache, joint pain at other locations, muscle aches, shivering, sweating and temperature[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade.

  • Number of Subjects With Any Unsolicited Adverse Events (AEs). [ Time Frame: During a 21-day follow-up period for each vaccine administration, as well as overall (Day 0 through Day 84) ] [ Designated as safety issue: No ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From Day 0 through Day 182 and through Day 379. ] [ 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 or result in disability/incapacity.

  • Number of Subjects With Medically Attended Events (MAEs) [ Time Frame: From Day 0 through Day 182 and through Day 364. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Subjects With Serum Reciprocal HI Antibodies Against A/Indonesia/5/2005 Equal to or Above (≥) 1:10 [ Time Frame: At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) ] [ Designated as safety issue: No ]
  • Number of Subjects With A/Indonesia/5/05 Antibody Titers ≥ 1:10 [ Time Frame: At Month 6 (Day 182) post Dose 1 ] [ Designated as safety issue: No ]
  • Number of Seroconverted Subjects Against A/Indonesia/5/2005 (H5N1) [ Time Frame: At Month 6 (Day 182) after Dose 1 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer < 1:10 and a post-vaccination (Day 42) reciprocal titer ≥ 1:40, or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a 4-fold increase in post-vaccination reciprocal titer against A/Indonesia/5/05 virus 21 days after the second dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted.

  • Number of Seroprotected Subjects Against A/Indonesia/5/2005 (H5N1) [ Time Frame: At Month 6 (Day 182) after Dose 1 ] [ Designated as safety issue: No ]
  • Titers for Serum HI Antibodies Against A/Indonesia/5/05 (H5N1) [ Time Frame: At Month 6 (Day 182) after Dose 1 ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10.

  • Number of Subjects With a Vaccine Response to the Vaccine-homologous Virus and Drift Variant H5N1 Virus, as Assessed by Microneutralization Assays. [ Time Frame: At Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) ] [ Designated as safety issue: No ]
    Virus antibody response rates were defined as the number of subjects with antibody titers at Day 42 ≥ 4-fold the pre-vaccination antibody titers. The 2 strains assessed were Flu A/Indonesia/5/05 and Flu A/Vietnam/1194/04.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1) as Assessed by Microneutralization Assays [ Time Frame: At Day 0 and Day 42 post Dose 1 (Day 42 post Dose 1 = Day 21 post Dose 2) ] [ Designated as safety issue: No ]
    Titers were expressed as Geometric Mean Titers (GMTs).


Enrollment: 4561
Study Start Date: January 2008
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Influenza A (H5N1) 18-64Y Group
Subjects aged 18-64 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine formulations A. B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Two intramuscular injections at Days 0 and 21.
Placebo Comparator: Placebo 18-64Y Group
Subjects aged 18-64 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Placebo
Two intramuscular injections at Days 0 and 21.
Experimental: Influenza A (H5N1) >64Y Group
Subjects aged > 64 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine formulations A. B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Two intramuscular injections at Days 0 and 21.
Placebo Comparator: Placebo >64Y Group
Subjects aged > 64 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Placebo
Two intramuscular injections at Days 0 and 21.
Experimental: Influenza A (H5N1) Group
Pooled group of subjects aged >18 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine formulations A. B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Two intramuscular injections at Days 0 and 21.
Placebo Comparator: Placebo Group
Pooled group of subjects aged >18 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Placebo
Two intramuscular injections at Days 0 and 21.
Experimental: Influenza A (H5N1) 18-60Y Group
Subjects aged 18-60 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine formulations A. B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Two intramuscular injections at Days 0 and 21.
Placebo Comparator: Placebo 18-60Y Group
Subjects aged 18-60 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Placebo
Two intramuscular injections at Days 0 and 21.
Experimental: Influenza A (H5N1) >60Y Group
Subjects aged >60 years, who received 2 doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted vaccine formulations A. B, or C in approximately equal proportions, at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Two intramuscular injections at Days 0 and 21.
Placebo Comparator: Placebo >60Y Group
Subjects aged > 60 years, who received 2 doses of placebo at Days 0 and 21. The first dose was administered in the deltoid region of the non-dominant arm. The second dose was administered in the deltoid region of the dominant arm.
Biological: Placebo
Two intramuscular injections at Days 0 and 21.

  Eligibility

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

Inclusion Criteria:

  • A male or female 18 years of age or greater at the time of the first vaccination.
  • Written informed consent obtained from the subject.
  • Among 18 to 49 year old subjects, good general health as established by medical history and clinical examination before entering into the study.
  • Among subjects > 49 years of age, stable health status within 1 month prior to enrollment.
  • Access to a consistent means of telephone contact.
  • Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of short- and long-term safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits.

Exclusion Criteria:

  • Evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the investigator to render the potential subjectunable/unlikely to provide accurate safety reports.
  • Diagnosed with cancer, or treatment for cancer, within 3 years.
  • An oral temperature ≥37.8º C, or acute symptoms greater than "mild" severity on the scheduled date of first vaccination.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus infection.
  • Receipt of systemic glucocorticoids within 1 month of study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment.
  • Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin.
  • Administration of any vaccines within 30 days before study enrollment.
  • Previous administration of any H5N1 vaccine.
  • Use of any investigational or non-registered product or planned participation in another investigational study within 30 days prior to study enrollment, or during the 364 days following the first test article dose. 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 test result prior to either 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 treatments.
  • Known use of an analgesic or antipyretic medication within 12 hours prior to first treatment.
  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: NCT00616928

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Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Langley J et al. AS03-adjuvanted A/Indonesia/5/05 H5N1 pre pandemic vaccine consistently induces strong, broad and persistent immunity in young adults and the elderly. Abstract presented at Infectious Diseases Society of America (IDSA). Philadelphia, Pennsylvania, 29 October-1 November 2009.
Langley JM et al. (2011) Dose-sparing H5N1 A/Indonesia/05/2005 pre-pandemic influenza vaccine in adults and elderly adults: a phase III, placebo-controlled, randomized study. J Infect Dis. 203(12):1729-1738.

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00616928     History of Changes
Other Study ID Numbers: 110464
Study First Received: January 28, 2008
Results First Received: December 19, 2013
Last Updated: March 13, 2014
Health Authority: Canada: Health Products and Foods Branch, Health Canada
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
vaccines
immunogenicity
human
safety
influenza

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 September 18, 2014