Influenza
Conditions
Keywords
avian flu, seasonal influenza vaccine, influenza vaccine, prepandemic vaccine, virus strain with the potential to cause pandemic, tetravalent vaccine, Prophylaxis of influenza
Brief summary
Evaluate the immune response and reactogenicity of H5N1 vaccination in adults aged 18 years and above (as part of a tetravalent vaccine)
Interventions
BIOLOGICALMF59-eTIV-H5N1+ placebo /pandemic influenza vaccine
Tetravalent influenza vaccine (MF59-eTIV-H5N1)and placebo on day 1 followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1+V3.
BIOLOGICALPandemic influenza vaccine + placebo /MF59-eTIV-H5N1
Pandemic influenza vaccine plus placebo on day 1 followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1+V3.
BIOLOGICALPandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine
Pandemic influenza vaccine plus seasonal influenza vaccine, 3-5 weeks later pandemic influenza vaccine , including serology blood draw at V1+V3.
BIOLOGICALPandemic influenza vaccine + placebo / MF59-eTIV-H5N1
Pandemic influenza vaccine plus placebo followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1, V2 and V3.
BIOLOGICALPandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine
Pandemic influenza vaccine plus seasonal influenza vaccine followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.
BIOLOGICALMF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine
Tetravalent influenza vaccine (MF59-eTIV-H5N1)plus placebo followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects (aged 18 years and above) who have signed an informed consent form
Exclusion criteria
* Any acute or chronic illness * Receipt of seasonal influenza vaccine for the current season 2007/2008 * Known or suspected impairment/alteration of immune function * Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination * Any serious disease * Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein,neomycin or kanamycin or any other component of the study vaccine * Receipt of blood, blood products or immunoglobulins 3 months prior to vaccination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | up to day 43 | The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence. The statistical analysis was done based on the GMRs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Up to 7 days after 1st vaccination | Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently. |
| Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Up to 7 days after 2nd vaccination | Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. |
| Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | 7 days after 1st and 2nd vaccinations each | Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. |
| Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | Up to 43 days | Measurement of immunogenicity in terms of percentage of subjects achieving a titre ≥ 40/area ≥ 25mm\^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay. |
| Antibody Response Determined by HI and MN Assay. | Up to 43 days | Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay. |
| Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43) | The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects. Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC. |
| Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | Three weeks after 1st vaccination (day 22) and three weeks after 2nd vaccination (day 43) | Frequency and functionality of vaccine antigen-specific CD4+ (cluster of differentiation 4) T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb \[monoclonal antibody (aCD3)\]. The change in frequency of T-cells was measured. |
| Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | up to day 43 | Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion. Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (≥ 10) for HI or a 50% increase in area for SRH. Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer ≥40 for HI (area ≥25 mm2 for SRH) |
Countries
Germany
Participant flow
Recruitment details
Participants were enrolled at 2 sites in Germany
Pre-assignment details
All subjects were included in the trial. The data entered is for the overall study.
Participants by arm
| Arm | Count |
|---|---|
| T/P-A one dose of the tetravalent (T) influenza vaccine administered concomitantly, in a different arm, with one dose of the placebo (P) control, on study day 1, followed by Aflunov, on study day 22 | 199 |
| A/P-T one dose of the Aflunov (A; A/H5N1) avian influenza vaccine administered concomitantly, in a different arm, with one dose of the placebo (P) control, on study day 1, followed by the tetravalent (T) influenza vaccine, on study day 22 | 203 |
| A/S-A one dose of the Aflunov (A; A/H5N1) avian influenza vaccine administered concomitantly, in a different arm, one dose of licensed seasonal(S) vaccine, on study day 1, followed by Aflunov (A), on study day 22 | 199 |
| Total | 601 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 |
| Overall Study | Inappropriate enrolment | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 6 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | T/P-A | Total | A/S-A | A/P-T |
|---|---|---|---|---|
| Age, Customized ≤60 years | 196 participants 8 | 596 participants | 198 participants 9.6 | 202 participants 9.8 |
| Age, Customized ≥ 61 Years | 3 participants 1 | 4 participants | 0 participants | 1 participants 0 |
| Sex/Gender, Customized Female (≤60 years of age) | 126 participants | 369 participants | 114 participants | 129 participants |
| Sex/Gender, Customized Female (≥61 years of age) | 1 participants | 2 participants | 0 participants | 1 participants |
| Sex/Gender, Customized Male (≤60 years of age) | 70 participants | 227 participants | 84 participants | 73 participants |
| Sex/Gender, Customized Male (≥61 years of age) | 2 participants | 2 participants | 0 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 190 / 199 | 185 / 203 | 183 / 198 |
| serious Total, serious adverse events | 2 / 199 | 3 / 203 | 4 / 198 |
Outcome results
Primary
To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43.
The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence. The statistical analysis was done based on the GMRs.
Time frame: up to day 43
Population: The analysis was done on Per Protocol Set (PPS)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| T/P-A | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 22 (N= 31, 31, 30) | 14 Area (mm^2) |
| T/P-A | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 1 | 4.64 Area (mm^2) |
| T/P-A | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 43 (N=181, 189, 189) | 41 Area (mm^2) |
| A/P-T | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 22 (N= 31, 31, 30) | 12 Area (mm^2) |
| A/P-T | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 1 | 4.10 Area (mm^2) |
| A/P-T | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 43 (N=181, 189, 189) | 35 Area (mm^2) |
| A/S-A | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 1 | 4.61 Area (mm^2) |
| A/S-A | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 43 (N=181, 189, 189) | 39 Area (mm^2) |
| A/S-A | To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. | Day 22 (N= 31, 31, 30) | 16 Area (mm^2) |
Comparison: (On day 1) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [1.02, 1.25]ANOVA
Comparison: (On day 1) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.91, 1.12]ANOVA
Comparison: (On day 1)Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.8, 0.99]ANOVA
Comparison: (On day 22) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.74, 1.93]ANOVA
Comparison: (On day 22) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.52, 1.38]ANOVA
Comparison: (On day 22) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.44, 1.15]ANOVA
Comparison: (On day 43) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [1.01, 1.3]ANOVA
Comparison: (On day 43) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.93, 1.19]ANOVA
Comparison: (On day 43) Null hypothesis representing non-equivalence was rejected if the two-sided (1-2α)\*100% CI on one GMA ratio is completely within the equivalence range \[0.5, 2.0\].96.67% CI: [0.81, 1.04]ANOVA
Secondary
Antibody Response Determined by HI and MN Assay.
Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay.
Time frame: Up to 43 days
Population: The population was analyzed on Per protocol set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| T/P-A | Antibody Response Determined by HI and MN Assay. | HI-Day 22 (N=31,31,30) | 8.36 titers |
| T/P-A | Antibody Response Determined by HI and MN Assay. | HI-Day 1 | 5.93 titers |
| T/P-A | Antibody Response Determined by HI and MN Assay. | HI-Day 43 (N=181,187,186) | 46 titers |
| T/P-A | Antibody Response Determined by HI and MN Assay. | MN-Day 1 (N=194,202,198) | 10 titers |
| T/P-A | Antibody Response Determined by HI and MN Assay. | MN-Day 22 (N=31,31,30) | 14 titers |
| T/P-A | Antibody Response Determined by HI and MN Assay. | MN-Day 43 (N=181,189,189) | 141 titers |
| A/P-T | Antibody Response Determined by HI and MN Assay. | MN-Day 43 (N=181,189,189) | 111 titers |
| A/P-T | Antibody Response Determined by HI and MN Assay. | HI-Day 1 | 5.58 titers |
| A/P-T | Antibody Response Determined by HI and MN Assay. | MN-Day 1 (N=194,202,198) | 10 titers |
| A/P-T | Antibody Response Determined by HI and MN Assay. | MN-Day 22 (N=31,31,30) | 16 titers |
| A/P-T | Antibody Response Determined by HI and MN Assay. | HI-Day 22 (N=31,31,30) | 6.76 titers |
| A/P-T | Antibody Response Determined by HI and MN Assay. | HI-Day 43 (N=181,187,186) | 33 titers |
| A/S-A | Antibody Response Determined by HI and MN Assay. | HI-Day 22 (N=31,31,30) | 9.66 titers |
| A/S-A | Antibody Response Determined by HI and MN Assay. | HI-Day 43 (N=181,187,186) | 49 titers |
| A/S-A | Antibody Response Determined by HI and MN Assay. | MN-Day 1 (N=194,202,198) | 10 titers |
| A/S-A | Antibody Response Determined by HI and MN Assay. | MN-Day 43 (N=181,189,189) | 133 titers |
| A/S-A | Antibody Response Determined by HI and MN Assay. | HI-Day 1 | 5.85 titers |
| A/S-A | Antibody Response Determined by HI and MN Assay. | MN-Day 22 (N=31,31,30) | 17 titers |
Secondary
Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit
Frequency and functionality of vaccine antigen-specific CD4+ (cluster of differentiation 4) T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb \[monoclonal antibody (aCD3)\]. The change in frequency of T-cells was measured.
Time frame: Three weeks after 1st vaccination (day 22) and three weeks after 2nd vaccination (day 43)
Population: Analysis was done on full analysis set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 43 (N=31, 31, 30) | 784 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 43 (N=31, 31, 30) | 311 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 1 (N=30, 31, 30) | 275 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 1 (N=31, 31, 30) | 329 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 22 (N=31, 31, 30) | 273 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 43 (N=31, 31, 30) | 910 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 22 (N=31, 31, 30) | 1050 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 1 (N=30, 31, 30) | 162 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 1 (N=31, 31, 30) | 38714 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 1 (N=31, 31, 30) | 136 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 43 (N=31, 31, 30) | 31001 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 43 (N=30, 30, 29) | 930 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 22 (N=31, 31, 30) | 604 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 22 (N=31, 31, 30) | 29134 Mean cells per million total cells |
| T/P-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 22 (N=30, 30, 30) | 998 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 22 (N=31, 31, 30) | 616 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 1 (N=30, 31, 30) | 175 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 22 (N=31, 31, 30) | 358 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 43 (N=31, 31, 30) | 328 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 1 (N=31, 31, 30) | 180 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 22 (N=31, 31, 30) | 711 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 43 (N=31, 31, 30) | 813 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 1 (N=31, 31, 30) | 344 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 43 (N=31, 31, 30) | 1034 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 1 (N=30, 31, 30) | 427 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 22 (N=30, 30, 30) | 729 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 43 (N=30, 30, 29) | 973 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 1 (N=31, 31, 30) | 32703 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 22 (N=31, 31, 30) | 27324 Mean cells per million total cells |
| A/P-T | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 43 (N=31, 31, 30) | 29327 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 22 (N=31, 31, 30) | 938 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 43 (N=31, 31, 30) | 34680 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 22 (N=30, 30, 30) | 1040 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 1 (N=31, 31, 30) | 155 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 22 (N=31, 31, 30) | 32324 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 43 (N=30, 30, 29) | 792 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 43 (N=31, 31, 30) | 290 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 1 (N=30, 31, 30) | 167 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 22 (N=31, 31, 30) | 1129 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 1 (N=31, 31, 30) | 349 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | aCD3 Day 1 (N=31, 31, 30) | 27824 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H3N2 Wisconsin Day 43 (N=31, 31, 30) | 814 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5N1 Vietnam Day 43 (N=31, 31, 30) | 750 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H5 Pool of 70 Vietnam Day 22 (N=31, 31, 30) | 365 Mean cells per million total cells |
| A/S-A | Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit | H1N1 Solomon Islands Day 1 (N=30, 31, 30) | 331 Mean cells per million total cells |
Secondary
Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination
Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently.
Time frame: Up to 7 days after 1st vaccination
Population: The analysis was performed on Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Ecchymosis | 2 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Induration | 22 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Erythema | 10 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Pain | 164 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Swelling | 19 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Induration | 1 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Ecchymosis | 1 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Erythema | 0 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Pain | 30 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Swelling | 1 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Induration | 5 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Ecchymosis | 2 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Pain | 138 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Swelling | 6 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Erythema | 5 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Swelling | 0 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Erythema | 0 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Induration | 0 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Ecchymosis | 0 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Pain | 32 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Ecchymosis | 2 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Erythema | 6 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Pain | 131 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Induration | 9 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Swelling | 7 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Erythema | 5 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Ecchymosis | 1 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Induration | 3 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Pain | 80 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination | Swelling | 3 Participants |
Secondary
Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination
Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.
Time frame: Up to 7 days after 2nd vaccination
Population: The analysis was performed on Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/P-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Ecchymosis | 3 Participants |
| T/P-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Swelling | 5 Participants |
| T/P-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Erythema (N=188,192,191) | 2 Participants |
| T/P-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Induration | 7 Participants |
| T/P-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Pain | 98 Participants |
| A/P-T | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Swelling | 8 Participants |
| A/P-T | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Erythema (N=188,192,191) | 7 Participants |
| A/P-T | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Induration | 10 Participants |
| A/P-T | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Ecchymosis | 3 Participants |
| A/P-T | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Pain | 136 Participants |
| A/S-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Pain | 91 Participants |
| A/S-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Ecchymosis | 2 Participants |
| A/S-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Erythema (N=188,192,191) | 5 Participants |
| A/S-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Swelling | 6 Participants |
| A/S-A | Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination | Induration | 7 Participants |
Secondary
Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations.
Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.
Time frame: 7 days after 1st and 2nd vaccinations each
Population: The analysis was performed on Per Protocol Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Body Temp. (< 38C)[N=195,201,195,188,192,192] | 187 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Nausea (N=195,201,196,187,192,192) | 24 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Myalgia (N=195,201,196,187,192,192) | 68 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Chills (N=195,201,196,187,192,192) | 24 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Malaise (N=195,201,196,187,192,192) | 62 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Stayed home due to reactions | 8 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fever (>= 38 C) [N=195,201,195,188,192,192] | 8 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fatigue (N=195,201,196,187,192,192) | 79 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Arthralgia (N=195,201,196,187,192,192) | 34 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Sweating (N=195,201,196,187,192,192) | 13 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Coughing (N=195,201,196,187,192,192) | 14 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Headache (N=195, 201, 196, 187, 192, 192) | 70 Participants |
| T/P-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Analgesic, Antipyretic Medicines Used | 27 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Headache (N=195, 201, 196, 187, 192, 192) | 52 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Malaise (N=195,201,196,187,192,192) | 29 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Sweating (N=195,201,196,187,192,192) | 16 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fever (>= 38 C) [N=195,201,195,188,192,192] | 1 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fatigue (N=195,201,196,187,192,192) | 58 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Nausea (N=195,201,196,187,192,192) | 16 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Stayed home due to reactions | 7 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Myalgia (N=195,201,196,187,192,192) | 47 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Coughing (N=195,201,196,187,192,192) | 16 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Analgesic, Antipyretic Medicines Used | 21 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Body Temp. (< 38C)[N=195,201,195,188,192,192] | 200 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Arthralgia (N=195,201,196,187,192,192) | 14 Participants |
| A/P-T | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Chills (N=195,201,196,187,192,192) | 8 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fatigue (N=195,201,196,187,192,192) | 52 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Coughing (N=195,201,196,187,192,192) | 16 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Nausea (N=195,201,196,187,192,192) | 8 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Malaise (N=195,201,196,187,192,192) | 28 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Stayed home due to reactions | 2 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Myalgia (N=195,201,196,187,192,192) | 42 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Body Temp. (< 38C)[N=195,201,195,188,192,192] | 192 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Arthralgia (N=195,201,196,187,192,192) | 12 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Headache (N=195, 201, 196, 187, 192, 192) | 43 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Chills (N=195,201,196,187,192,192) | 9 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fever (>= 38 C) [N=195,201,195,188,192,192] | 3 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Sweating (N=195,201,196,187,192,192) | 10 Participants |
| A/S-A | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Analgesic, Antipyretic Medicines Used | 15 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Myalgia (N=195,201,196,187,192,192) | 22 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Chills (N=195,201,196,187,192,192) | 6 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Malaise (N=195,201,196,187,192,192) | 15 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Arthralgia (N=195,201,196,187,192,192) | 6 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Headache (N=195, 201, 196, 187, 192, 192) | 33 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Sweating (N=195,201,196,187,192,192) | 6 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fatigue (N=195,201,196,187,192,192) | 32 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Nausea (N=195,201,196,187,192,192) | 7 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Coughing (N=195,201,196,187,192,192) | 13 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fever (>= 38 C) [N=195,201,195,188,192,192] | 2 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Body Temp. (< 38C)[N=195,201,195,188,192,192] | 186 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Stayed home due to reactions | 1 Participants |
| A/P-T: In Arm Receiving Placebo (P) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Analgesic, Antipyretic Medicines Used | 6 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Coughing (N=195,201,196,187,192,192) | 12 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Sweating (N=195,201,196,187,192,192) | 13 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fever (>= 38 C) [N=195,201,195,188,192,192] | 5 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Headache (N=195, 201, 196, 187, 192, 192) | 50 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Myalgia (N=195,201,196,187,192,192) | 53 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Body Temp. (< 38C)[N=195,201,195,188,192,192] | 187 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Arthralgia (N=195,201,196,187,192,192) | 15 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Malaise (N=195,201,196,187,192,192) | 38 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Analgesic, Antipyretic Medicines Used | 16 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Stayed home due to reactions | 8 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Nausea (N=195,201,196,187,192,192) | 16 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fatigue (N=195,201,196,187,192,192) | 60 Participants |
| A/S-A: In Arm Receiving Aflunov (A) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Chills (N=195,201,196,187,192,192) | 11 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Body Temp. (< 38C)[N=195,201,195,188,192,192] | 192 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Coughing (N=195,201,196,187,192,192) | 13 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Sweating (N=195,201,196,187,192,192) | 7 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Stayed home due to reactions | 1 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Headache (N=195, 201, 196, 187, 192, 192) | 27 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Arthralgia (N=195,201,196,187,192,192) | 6 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Malaise (N=195,201,196,187,192,192) | 15 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fever (>= 38 C) [N=195,201,195,188,192,192] | 0 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Chills (N=195,201,196,187,192,192) | 3 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Myalgia (N=195,201,196,187,192,192) | 27 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Nausea (N=195,201,196,187,192,192) | 6 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Analgesic, Antipyretic Medicines Used | 6 Participants |
| A/S-A: In Arm Receiving Seasonal Influenza Vaccine (S) | Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. | Fatigue (N=195,201,196,187,192,192) | 35 Participants |
Secondary
Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination.
The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects. Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC.
Time frame: Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43)
Population: The analysis was done on Full analysis set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| T/P-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 1 (N=30, 30, 29) | 0.7 Percentages of B-cell antibodies |
| T/P-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 22 (N=30, 30, 28) | 5.39 Percentages of B-cell antibodies |
| T/P-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 43 (N=30, 30, 29) | 6.67 Percentages of B-cell antibodies |
| T/P-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 1 (N=30, 30, 29) | 2.35 Percentages of B-cell antibodies |
| T/P-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 22 (N=30, 30, 28) | 13 Percentages of B-cell antibodies |
| T/P-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 43 (N=30, 30, 29) | 12 Percentages of B-cell antibodies |
| A/P-T | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 43 (N=30, 30, 29) | 16 Percentages of B-cell antibodies |
| A/P-T | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 1 (N=30, 30, 29) | 0.42 Percentages of B-cell antibodies |
| A/P-T | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 1 (N=30, 30, 29) | 2.64 Percentages of B-cell antibodies |
| A/P-T | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 22 (N=30, 30, 28) | 8.55 Percentages of B-cell antibodies |
| A/P-T | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 22 (N=30, 30, 28) | 6.08 Percentages of B-cell antibodies |
| A/P-T | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 43 (N=30, 30, 29) | 7.21 Percentages of B-cell antibodies |
| A/S-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 22 (N=30, 30, 28) | 7.58 Percentages of B-cell antibodies |
| A/S-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 43 (N=30, 30, 29) | 6.84 Percentages of B-cell antibodies |
| A/S-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 43 (N=30, 30, 29) | 15 Percentages of B-cell antibodies |
| A/S-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 1 (N=30, 30, 29) | 1.61 Percentages of B-cell antibodies |
| A/S-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H5N1-IgG MBC - Day 1 (N=30, 30, 29) | 0.53 Percentages of B-cell antibodies |
| A/S-A | Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. | H1N1-IgG MBC - Day 22 (N=30, 30, 28) | 15 Percentages of B-cell antibodies |
Secondary
Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2
Measurement of immunogenicity in terms of percentage of subjects achieving a titre ≥ 40/area ≥ 25mm\^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay.
Time frame: Up to 43 days
Population: The analysis was done on Per Protocol Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/P-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | SRH-Day 1 (N=194,202,198) | 4 Percentages of subjects |
| T/P-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | SRH-Day 43 (N=181,189,189) | 93 Percentages of subjects |
| T/P-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | HI-Day 1 (N=192,198,193) | 2 Percentages of subjects |
| T/P-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | HI-Day 43 (N=181,187,186) | 70 Percentages of subjects |
| T/P-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | MN-Day 1 (N=194,202,198) | 1 Percentages of subjects |
| T/P-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | MN-Day 43 (N=181,189,189) | 90 Percentages of subjects |
| A/P-T | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | MN-Day 43 (N=181,189,189) | 87 Percentages of subjects |
| A/P-T | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | SRH-Day 1 (N=194,202,198) | 0 Percentages of subjects |
| A/P-T | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | HI-Day 43 (N=181,187,186) | 66 Percentages of subjects |
| A/P-T | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | MN-Day 1 (N=194,202,198) | 3 Percentages of subjects |
| A/P-T | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | SRH-Day 43 (N=181,189,189) | 86 Percentages of subjects |
| A/P-T | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | HI-Day 1 (N=192,198,193) | 0 Percentages of subjects |
| A/S-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | SRH-Day 43 (N=181,189,189) | 89 Percentages of subjects |
| A/S-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | HI-Day 1 (N=192,198,193) | 2 Percentages of subjects |
| A/S-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | MN-Day 43 (N=181,189,189) | 89 Percentages of subjects |
| A/S-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | HI-Day 43 (N=181,187,186) | 74 Percentages of subjects |
| A/S-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | SRH-Day 1 (N=194,202,198) | 4 Percentages of subjects |
| A/S-A | Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 | MN-Day 1 (N=194,202,198) | 3 Percentages of subjects |
Secondary
Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain
Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion. Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (≥ 10) for HI or a 50% increase in area for SRH. Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer ≥40 for HI (area ≥25 mm2 for SRH)
Time frame: up to day 43
Population: The population was analyzed on per protocol set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T/P-A | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Seroconversion/significant rise HI (N=180,186,184) | 69 Percentage of subjects |
| T/P-A | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Seroconversion/significant rise SRH(N=181,189,189) | 90 Percentage of subjects |
| T/P-A | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Four fold increase MN (N=181,189,189) | 90 Percentage of subjects |
| A/P-T | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Seroconversion/significant rise HI (N=180,186,184) | 67 Percentage of subjects |
| A/P-T | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Seroconversion/significant rise SRH(N=181,189,189) | 86 Percentage of subjects |
| A/P-T | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Four fold increase MN (N=181,189,189) | 86 Percentage of subjects |
| A/S-A | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Seroconversion/significant rise SRH(N=181,189,189) | 86 Percentage of subjects |
| A/S-A | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Four fold increase MN (N=181,189,189) | 89 Percentage of subjects |
| A/S-A | Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain | Seroconversion/significant rise HI (N=180,186,184) | 75 Percentage of subjects |