Immunogenicity and Safety of GSK Biologicals' (Pre-) Pandemic Influenza Candidate Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00742885
First received: August 27, 2008
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

This trial will assess the immunogenicity and safety elicited by the adjuvanted GSK Biologicals' (pre-) pandemic influenza candidate vaccine in healthy Japanese adults.


Condition Intervention Phase
Influenza
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety of GSK Biologicals' (Pre-) Pandemic Influenza Candidate Vaccine GSK 1557484A.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Haemagglutination Inhibition (HI) Antibody Titers for the H5N1 Vaccine Strain [ Time Frame: At Day 0 and Day 42 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Indonesia/05/2005 antigen (A/Indonesia).

  • Number of Subjects Seroconverted for H5N1 HI Antibodies [ Time Frame: At Day 42 ] [ 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 H5N1 vaccine strain included A/Indonesia antigen.

  • HI Antibody Seroconversion Factors for H5N1 HI Antibodies [ Time Frame: At Day 0 and Day 42 ] [ Designated as safety issue: No ]
    Seroconversion factors (SCF) were defined as the fold increase in serum H5N1 HI antibody GMTs post-vaccination compared to Day 0, at Day 42. The H5N1 vaccine strain included A/Indonesia antigen.

  • Number of Subjects Seroprotected for H5N1 HI Antibodies [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum H5N1 HI antibody titer greater than or equal to 1:40, at Day 42. The H5N1 vaccine strain included A/Indonesia antigen.

  • Haemagglutination Inhibition (HI) Antibody Titers for the H5N1 Vaccine Strain [ Time Frame: At Day 0, Day 21 and Day 182 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Indonesia antigen.


Secondary Outcome Measures:
  • Number of Subjects Seroconverted for H5N1 HI Antibodies [ Time Frame: At Day 21 and Day 182 ] [ 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, at Days 21 and 182. The H5N1 vaccine strain included A/Indonesia antigen.

  • Seroconversion Factors for H5N1 HI Antibodies [ Time Frame: At Day 21 and Day 182 ] [ Designated as safety issue: No ]
    Seroconversion factors (SCF) were defined as the fold increase in serum H5N1 HI antibody GMTs post-vaccination compared to Day 0, at Days 21 and 182. The H5N1 vaccine strain included A/Indonesia antigen.

  • Number of Subjects Seroprotected for H5N1 HI Antibodies [ Time Frame: At Day 0, Day 21 and Day 182 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with a serum H5N1 HI antibody titer greater than or equal to 1:40, at Days 21 and 182. The H5N1 vaccine strain included A/Indonesia antigen.

  • Antibody Titers for Serum Anti-H5N1 Neutralising Antibodies [ Time Frame: At Day 0, Day 42 and Day 182 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs). The H5N1 vaccine strain included A/Indonesia antigen.

  • Number of Subjects Seroconverted for Serum Anti-H5N1 Neutralising Antibodies [ Time Frame: At Day 42 and Day 182 ] [ Designated as safety issue: No ]

    A seroconverted subject was defined as a subject with a minimum 4 fold increase in titer at post-vaccination for neutralising antibody response at Days 42 and 182.

    The H5N1 vaccine strain included A/Indonesia antigen.


  • Number of Subjects With Any Biochemical and Haematological Laboratory Abnormalities [ Time Frame: At Day 0, Day 7 and Day 42 ] [ Designated as safety issue: No ]
    Biochemical and haematological parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS) and blood urea nitrogen (BUN ). Categories = unknown, below, within, or above the normal ranges.

  • Number of Subjects With Any Biochemical and Haematological Laboratory Abnormalities [ Time Frame: At Day 0, Day 7 and Day 42 ] [ Designated as safety issue: No ]

    Biochemical and haematological parameters assessed in blood samples include creatinine (CREA), eosinophils (EOS), hemoglobin (HB) and hematocrit (HC).

    Categories = unknown, below, within, or above the normal ranges.


  • Number of Subjects With Any Biochemical and Haematological Laboratory Abnormalities [ Time Frame: At Day 0, Day 7 and Day 42 ] [ Designated as safety issue: No ]

    Biochemical and haematological parameters assessed in blood samples include lymphocytes (LYM), monocytes (MON) and neutrophils (NEU).

    Categories = unknown, below, within, or above the normal ranges.


  • Number of Subjects With Any Normal or Abnormal Urine Values [ Time Frame: At Day 0, Day 7 and Day 42 ] [ Designated as safety issue: No ]
    Urine parameters assessed were blood, glucose, protein and urobilinogen. Categories = negative, positive

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day post vaccination period (Days 0-6) after any vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling/induration. Any=any solicited local symptom reported regardless of their intensity. Grade 3 pain= significant pain at rest that prevented normal activities as assessed by inability to attend/do work or school. Grade 3 redness and swelling/induration=redness and swelling/induration above 100 millimetres (mm).

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day post vaccination period (Days 0-6) after any vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were fatigue, headache, joint pain, muscle aches, shivering, increase sweating and fever. Any=any solicited general symptom reported regardless of their intensity grade or their relationship to vaccination. Any fever was ≥ 38.0 degrees celsius (°C). Grade 3 = general symptom that prevented normal everyday activities as assessed by inability to attend/do work or school, or required intervention of a physician/healthcare provider. Grade 3 fever was≥ 39.0°C. Related= general symptom assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During the 21-day (Days 0-20) following vaccination ] [ Designated as safety issue: No ]
    Unsolicited AE is 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 AE 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 Unsolicited AEs [ Time Frame: From Day 0 to Day 83 following vaccination ] [ Designated as safety issue: No ]
    Unsolicited AE is 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 AE 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 Medically-significant Conditions (MSCs) [ Time Frame: During the 182-day (Days 0-181) post-vaccination period ] [ Designated as safety issue: No ]
    MSCs were defined as AEs with a medically-attended visit (s) i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0 to Day 181) ] [ 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.


Enrollment: 100
Study Start Date: September 2008
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Influenza A (H5N1) 20-40 Years Group
Subjects aged between 20 and 40 years inclusive received 2 doses of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted at Days 0 and 21 administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
All subjects will receive 2 doses administered as an intramuscular (IM) injection.
Other Name: PumarixTM
Experimental: Influenza A (H5N1) 41-64 Years Group
Subjects aged between 41 and 64 years inclusive received 2 doses of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted at Days 0 and 21 administered intramuscularly in the deltoid region of the non-dominant arm.
Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
All subjects will receive 2 doses administered as an intramuscular (IM) injection.
Other Name: PumarixTM

  Eligibility

Ages Eligible for Study:   20 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Japanese male and female adults 20 to 64 years of age at time of the first vaccination, inclusive.
  • Good general health as assessed by medical history and physical examination.
  • 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.
  • Written informed consent obtained from the subject.
  • Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.

Exclusion Criteria:

  • Presence of significant acute or chronic, uncontrolled medical or psychiatric illness.
  • Presence or evidence of substance abuse or of neurological or psychiatric diagnoses which, although 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 axillary temperature >= 37.5 °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 (HIV) infection.
  • Receipt of systemic glucocorticoids within 1 month of study enrolment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrolment.
  • Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin.
  • Administration of any registered vaccine within 30 days before study enrolment or planned administration within the first vaccination up to blood sampling at Day 42 and within 30 days prior to blood sampling at Day 182.
  • Use of any investigational or non-registered product within 30 days prior to study enrolment or planned use during the study period.
  • History of previous H5N1 vaccination, or history of H5N1 influenza infection.
  • Receipt of any immunoglobulins and/or any blood products within 6 months of study enrolment or planned administration of any of these products during the study period.
  • Any known or suspected allergy to any constituent of influenza vaccines or component used in the manufacturing process of the study vaccine, 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 the time of first 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; all women will have urine pregnancy tests regardless of their status.
  • Known receipt of analgesic or antipyretic medication on the day of treatment (Day 0).
  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: NCT00742885

Locations
Japan
GSK Investigational Site
Fukuoka, Japan, 813-8588
GSK Investigational Site
Tokyo, Japan, 204-8585
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: NCT00742885     History of Changes
Other Study ID Numbers: 111756
Study First Received: August 27, 2008
Results First Received: December 20, 2013
Last Updated: April 24, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by GlaxoSmithKline:
Immunogenicity
Safety
Pandemic 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 16, 2014