Today, the leading contender for the next influenza pandemic is H5N1, a strain of avian virus found primarily in domestic and wild birds. Experts warn that the next influenza pandemic is imminent and could be severe. Prevention and control will depend on the rapid production and worldwide distribution of specific pandemic vaccines. Candidate 'pandemic-like' vaccines must be developed and tested in clinical trials to determine the best formulation and vaccination schedule. The purpose of this study is to assess the immune response of a candidate pandemic vaccine. The protocol posting deals with objectives \& outcome measures of the secondary phase of this study. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = 00449670).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
845
IM administration
GSK Investigational Site
Hong Kong, Hong Kong
GSK Investigational Site
Singapore, Singapore
GSK Investigational Site
Singapore, Singapore
GSK Investigational Site
Taipei, Taiwan
GSK Investigational Site
Taipei, Taiwan
GSK Investigational Site
Bangkok, Thailand
Number of Subjects Boosted at Month 12 With Haemagglutinin-inhibition (HI) Antibody Concentrations Above the Cut-off Value
Seropositivity cut-off values assessed were equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 12 + 21 days
Titers for Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12
Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 12 + 21 days
Number of Subjects Boosted at Month 36 With HI Antibody Concentrations Above the Cut-off Value
Seropositivity cut-off values assessed were equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 36 + 21 days
Titers for Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36
Titers are presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 36 + 21 days
Booster Vaccine Response for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12
Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4-fold the pre-booster antibody titer. The Flu strain assessed was A/Indonesia/05/2005 (H5N1).
Time frame: At Month 12 + 21 days
Booster Vaccine Response for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36
Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4-fold the pre-booster antibody titer. The Flu strain assessed was A/Indonesia/05/2005 (H5N1).
Time frame: At Month 36 + 21 Days
Geometric Mean Fold Rise (GMFR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 12
GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 12 + 21 days
Geometric Mean Fold Rise (GMFR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease for Subjects Boosted at Month 36
GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 36 +21 days
Number of Subjects Boosted at Month 12 Seroprotected (SPR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease
Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 12 + 21 days
Number of Subjects Boosted at Month 36 Seroprotected (SPR) for HI Antibodies Against A/Indonesia/05/2005 Strain of Influenza Disease
Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005.
Time frame: At Month 36 + 21 days
Number of Seropositive Subjects for H5N1 HI Antibodies
Seropositivity was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:10 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 18, 24, 30 and 36
Number of Seropositive Subjects for H5N1 HI Antibodies
Seropositivity was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:10 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 42 and 48
Booster Vaccine Response for H5N1 HI Antibodies for Subjects Boosted at Month 6 and Month 12
Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4 fold the pre-booster antibody titer. The Flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 18, 24 and 30
Number of Subjects Boosted at Month 36 Seroconverted for H5N1 HI Antibodies
Seroconversion was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer \< 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 18, 24 and 30
Booster Vaccine Response for H5N1 HI Antibodies
Booster vaccine response was defined as: antibody titer after booster vaccination ≥ 4-fold the pre-booster antibody titer. The Flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 36, 42 and 48
Geometric Mean Fold Rise (GMFR) for H5N1 HI Antibodies
GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
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Time frame: At Months 18, 24, 30
Geometric Mean Fold Rise (GMFR) for H5N1 HI Antibodies
GMFR, also known as seroconversion factor (SCF), was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 36, 42 and 48
Number of Seroprotected (SPR) Subjects for H5N1 HI Antibodies
Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 18, 24 and 30
Number of Seroprotected (SPR) Subjects for H5N1 HI Antibodies
Seroprotection (SPR) was defined as the proportion of subjects with H5N1 reciprocal HI titers equal to or above (≥) 1:40 against the tested vaccine virus. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 36, 42 and 48
Titers for Serum Neutralizing Antibodies
Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:28. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 6/12, 6/12 + 21 days, 24, 36 and 48
Booster Vaccine Response for Neutralizing Antibodies
Booster vaccine response was defined as: for pre-booster antibody titer \< 1:28, antibody titer ≥ 1:56 post-booster; for pre-booster, antibody titer ≥ 1:28, post-booster ≥ 4-fold the pre-booster antibody titer. The flu strains assessed were A/Indonesia/05/2005 and A/Vietnam/1194/2004.
Time frame: At Months 6/12/36 + 21 days, 12, 24, 36 and 48
Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value
Seropositivity cut-off values assessed were equal to or above (≥) 1:28, ≥ 1:56 and ≥ 1:112 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/Indonesia/05/2005.
Time frame: At Months 6/12/36 + 21 days, 12, 24, 36 and 48
Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off
Seropositivity cut-off values assessed were equal to or above (≥) 1:28, ≥ 1:56 and ≥ 1:112 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/Vietnam/1194/2004.
Time frame: At Months 6/12/36 + 21 days, 12, 24, 36 and 48
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Time frame: During the 7-day (Days 0-6) post-vaccination period - subjects boosted at Month 12 and Month 36
Number of Subjects With Any, Grade 3 and Related Solicited General Symptom
Assessed solicited general symptoms were arthralgia, fatigue, headache, myalgia, shivering, sweating and fever \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Time frame: During the 7-day (Days 0-6) post-vaccination period - subjects boosted at Month 12 and 36
Number of Subjects With Adverse Events of Specific Interest (AESIs)
An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.
Time frame: During the entire study period (From Month 12 to Month 48)
Frequency of Antigen-specific CD4 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Indonesia/05/2005 Strain)
Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Indonesia/05/2005.
Time frame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
Frequency of Antigen-specific CD4 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Vietnam/1194/2004 Strain)
Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Vietnam/1194/2004.
Time frame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
Frequency of Antigen-specific CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Indonesia/05/2005 Strain)
Among cytokines expressed after background reduction were cluster of differentiation 8 all doubles (CD8 all doubles), cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Indonesia/05/2005.
Time frame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
Frequency of Antigen-specific CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines (for A/Vietnam/1194/2004 Strain)
Among cytokines expressed after background reduction were cluster of differentiation 8 all doubles (CD8 all doubles), cluster of differentiation 40-ligand (CD40-L), interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α). The flu strain assessed was H5N1 A/Vietnam/1194/2004.
Time frame: At Months 6, 12, 18, 24, 30, 36, 42 and 48 and at Months 6/12/36 + 21 days
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Time frame: During the 30-day (Days 0-29) follow-up period after vaccination
Number of Subjects With Serious Adverse Events (SAEs)
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.
Time frame: During the entire study period (From Month 12 up to Month 48)