Influenza
Conditions
Keywords
Elderly, Influenza, Immunogenicity, Safety, Adjuvant, Adjuvanted, Adjuvants, Vaccines
Brief summary
The present phase III study aims to evaluate the safety and immunogenicity of MF59-adjuvanted subunit seasonal influenza vaccine and to evaluate the consistency in the manufacturing process of three consecutive lots of MF59-adjuvanted subunit seasonal influenza vaccine with respect to immunogenicity in subjects aged 65 years and older. The active comparator non-adjuvanted seasonal influenza vaccine is approved for use in this age group in the United States and will be used to provide a comparative assessment for immunogenicity and safety.
Interventions
BIOLOGICALMF59 adjuvanted trivalent subunit influenza vaccine (aTIV)
one dose 0.5 mL administered IM in the deltoid muscle of (preferably) the non-dominant arm
BIOLOGICALNon-adjuvanted trivalent subunit influenza vaccine (TIV)
one 0.5 mL dose administered IM in the deltoid muscle of (preferably) the non-dominant arm
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Males and females subjects aged ≥65 years at day of vaccination who are willing and able to comply to study procedures.
Exclusion criteria
1. Individuals with behavioral or cognitive impairment or a psychiatric condition or with a history of any illness that,in the opinion of the investigator, would have interfered with the subject's ability to participate in the study. 2. Individuals who were not able to comprehend and/or follow all required study procedures for the whole period of the study. 3. Known or suspected impairment/alteration of immune function. 4. Individuals with a known bleeding diathesis. 5. History of Guillain-Barré syndrome. 6. Individuals with history of allergy to vaccine components and/or a history of any anaphylaxis, serious vaccine reactions or hypersensitivity to influenza viral proteins, egg proteins (including ovalbumin), polymyxin, neomycin, betapropiolactone, thimerosal/ sodium ethylmercurothiosalicylate/ mercury and nonylphenolethoxylate/ nonoxynol-9 (spermicide). 7. Receipt of another investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study. 8. Individuals who had received any other vaccines within 2 weeks for inactivated vaccines or 4 weeks for live vaccines prior to enrollment in this study or who had planned to receive any vaccine within 3 weeks from the study vaccine. 9. Individuals who had received vaccination against seasonal influenza in the previous 6 months. 10. Individuals with oral temperature ≥38.0°C (≥100.4°F) on day of study vaccination. 11. Individuals with history of substance or alcohol abuse within the past 2 years. 12. Individuals providing consent who did not consent to the retention of their serum samples after study completion. 13. Elective surgery or hospitalization planned to occur during the treatment phase or during the follow-up phase that, according to the opinion of the investigator, might have poses additional risk to the subject. 14. Subjects from whom blood could not be drawn at visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | Day 22 post vaccination | Immunologic equivalence of 3 consecutive production lots of aTIV (Lot 1, Lot 2 and Lot 3), was assessed in terms of Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) in subjects, at three weeks after vaccination, against each vaccine strain. |
| Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | Day 22 post vaccination | The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains. |
| Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | Day 22 post vaccination | The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | Day 22 post vaccination | The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains. |
| Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | Day 22 post vaccination | The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | Day 22 post vaccination | The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV. |
| Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | Day 22 post vaccination | The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | Day 22 post vaccination | The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV. |
| Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | Day 22 post vaccination | The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV. |
| Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | Day 22 post vaccination | The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV. |
| Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | Day 22 post vaccination | The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups | Day 1 through Day 366 post vaccination | The number of high risk subjects reporting exacerbation of preexisting chronic conditions (i.e.congestive heart failure, Chronic Obstructive Pulmonary disease (COPD), asthma, hepatic disease, renal insufficiency, and neurological/neuromuscular or metabolic disorders including diabetes mellitus) in aTIV group compared to TIV group. |
| Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups | Day 1 through Day 366 post vaccination | The number of subjects with emergency room visits, unscheduled physician visits, and hospitalizations due to community acquired influenza or pneumonia, cardiopulmonary disease, cardiac disease, respiratory or pulmonary disease,in aTIV group compared to TIV group. |
| Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | Day 22 post vaccination | The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains. |
| Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Day 1 through Day 7 post vaccination | The number of subjects reporting solicited local and systemic adverse events and other adverse events in aTIV group compared to TIV group. |
| All Cause Mortality Rate, Across Vaccine Groups | Day 1 through Day 366 post vaccination | The all-cause mortality rate (excluding injury)reported in aTIV group compared to TIV group, by country. |
| Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | Day 22 post vaccination | The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | Day 22 post vaccination | The superiority of HI antibody responses of aTIV compared to TIV, in subjects with predefined co-morbidities (high risk group) assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains. |
| Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | Day 22 postvaccination | The superiority of HI antibody responses of aTIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | Day 22 post vaccination | The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination . |
| Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | Day 22 post vaccination | The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination. |
| Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | Day 22 postvaccination | The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous strains, in overall group and in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | Day 22 post vaccination | The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of percentage of subjects achieving seroconversion, at three weeks after vaccination. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Persistence of GMTs Against Homologous and Heterologous Strains | Day 181, Day 366 post vaccination | The GMTs against homologous and heterologous strains, persisting in subjects at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV. |
| Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | Day 181, Day 366 post vaccination | The percentage of subjects demonstrating seroconversion in HI titers against homologous and heterologous strains, at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10. |
| Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Day 22 through Day 366 post vaccination | The number of subjects reporting ILI from three weeks after vaccination to up to one year in aTIV group compared to TIV group, by country. |
Countries
Colombia, Panama, Philippines, United States
Participant flow
Recruitment details
Subjects were enrolled from 4 sites in Columbia, 2 sites in Panama, 11 sites in Philippines, 21 sites in USA.
Pre-assignment details
Five enrolled subjects were not randomized and did not receive study vaccination, hence were discontinued.
Participants by arm
| Arm | Count |
|---|---|
| aTIV (Pooled) Subjects received one dose of MF59-adjuvanted trivalent subunit influenza vaccine (aTIV) from one of three consecutive lots (Lot 1, Lot 2 or Lot 3). | 3,545 |
| Licensed TIV Subjects received one dose of non-adjuvanted trivalent subunit influenza vaccine (TIV). | 3,537 |
| Total | 7,082 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason | 1 | 1 |
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 51 | 46 |
| Overall Study | Inappropriate enrollment | 5 | 4 |
| Overall Study | Lost to Follow-up | 73 | 91 |
| Overall Study | Missing primary reason | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Unable to classify | 3 | 7 |
| Overall Study | Withdrawal by Subject | 52 | 43 |
Baseline characteristics
| Characteristic | aTIV (Pooled) | Licensed TIV | Total |
|---|---|---|---|
| Age, Continuous | 72.0 years STANDARD_DEVIATION 5.3 | 71.8 years STANDARD_DEVIATION 5.3 | 71.9 years STANDARD_DEVIATION 5.3 |
| Sex: Female, Male Female | 2272 Participants | 2342 Participants | 4614 Participants |
| Sex: Female, Male Male | 1273 Participants | 1195 Participants | 2468 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,678 / 3,545 | 1,257 / 3,537 |
| serious Total, serious adverse events | 264 / 3,545 | 243 / 3,537 |
Outcome results
Primary
Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS
The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Time frame: Day 22 post vaccination
Population: Analysis was done on PPS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | H1N1 strain (N=3225,3257) | 198 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | H3N2 strain (N=3225,3256) | 544 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | B strain | 55 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | H1N1 strain (N=3225,3257) | 141 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | H3N2 strain (N=3225,3256) | 337 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS | B strain | 48 Titers |
95% CI: [1.32, 1.49]
95% CI: [1.52, 1.7]
95% CI: [1.08, 1.21]
Primary
Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS)
The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Time frame: Day 22 post vaccination
Population: Analysis was done on FAS i.e all randomized subjects who received a study vaccination and provided evaluable serum samples both at day 1 and at day 22
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | H1N1 strain (N=3477,3480) | 196 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | H3N2 strain (N=3477,3479) | 534 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | B strain | 54 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | H1N1 strain (N=3477,3480) | 142 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | H3N2 strain (N=3477,3479) | 334 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) | B strain | 48 Titers |
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 homologous strains was \>1.5.95% CI: [1.29, 1.46]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 homologous strains was \>1.5.95% CI: [1.51, 1.68]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 homologous strains was \>1.5.95% CI: [1.08, 1.2]
Primary
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS
The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 post vaccination
Population: Analysis was done on FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H1N1 strain (N=3477, 3480) | 77.3 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H3N2 strain (N=3477,3479) | 73.7 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | B strain | 46.9 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H1N1 strain (N=3477, 3480) | 67.8 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H3N2 strain (N=3477,3479) | 60.6 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | B strain | 41.5 Percentage of subjects |
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 homologous strains was \>10%.95% CI: [6.9, 10.9]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 homologous strains was \>10%.95% CI: [10.6, 14.8]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 homologous strains was \>10%.95% CI: [2.9, 7.2]
Primary
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS
The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 post vaccination
Population: Analysis was done on PPS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H1N1 strain (N=3225,3257) | 77.4 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H3N2 strain (N=3225,3256) | 74.0 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | B strain | 47.0 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H1N1 strain (N=3225,3257) | 67.6 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H3N2 strain (N=3225,3256) | 60.7 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | B strain | 41.2 Percentage of subjects |
95% CI: [7.1, 11.3]
95% CI: [10.5, 14.9]
95% CI: [3, 7.4]
Primary
Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains
The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Time frame: Day 22 post vaccination
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Brisbane strain (N=887,880), overall | 5.76 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Wisconsin strain, overall | 4.95 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | B strain (N=887,880), overall | 5.76 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Brisbane strain (N=330,333), high risk group | 5.42 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Wisconsin strain (N=330,333), high risk group | 4.67 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | B strain (N=330,333), high risk group | 5.41 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Wisconsin strain (N=330,333), high risk group | 3.73 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Brisbane strain (N=887,880), overall | 3.87 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Brisbane strain (N=330,333), high risk group | 4.15 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | H3N2/Wisconsin strain, overall | 3.54 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | B strain (N=330,333), high risk group | 4.77 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains | B strain (N=887,880), overall | 5.28 Ratio |
Primary
Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains
The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Time frame: Day 22 post vaccination
Population: Analysis was done on the FAS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H1N1 strain (N=1299, 1273), high risk group | 12 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H3N2 strain (N=3477, 3479), overall | 10 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H3N2 strain (N=1299, 1273), high risk group | 9.26 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H1N1 strain (N=3477, 3480), overall | 13 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | B strain (N=1300, 1273), high risk group | 4.48 Ratio |
| aTIV_Lot 1 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | B strain , overall | 4.85 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | B strain (N=1300, 1273), high risk group | 3.99 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H1N1 strain (N=3477, 3480), overall | 9.77 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H3N2 strain (N=3477, 3479), overall | 6.54 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H1N1 strain (N=1299, 1273), high risk group | 9.17 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | H3N2 strain (N=1299, 1273), high risk group | 6.24 Ratio |
| aTIV_Lot 2 | Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains | B strain , overall | 4.27 Ratio |
Primary
Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV
Immunologic equivalence of 3 consecutive production lots of aTIV (Lot 1, Lot 2 and Lot 3), was assessed in terms of Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) in subjects, at three weeks after vaccination, against each vaccine strain.
Time frame: Day 22 post vaccination
Population: Analysis was done on the per protocol set population (PPS) i.e all randomised subjects who received the correct vaccine, provided evaluable serum samples, and had no major protocol deviation prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | H3N2 strain (N=1072,1078,1075) | 548 Titers |
| aTIV_Lot 1 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | H1N1 strain (N=1072,1078,1075) | 209 Titers |
| aTIV_Lot 1 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | B strain | 56 Titers |
| aTIV_Lot 2 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | H3N2 strain (N=1072,1078,1075) | 542 Titers |
| aTIV_Lot 2 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | H1N1 strain (N=1072,1078,1075) | 187 Titers |
| aTIV_Lot 2 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | B strain | 56 Titers |
| aTIV_Lot 3 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | H1N1 strain (N=1072,1078,1075) | 199 Titers |
| aTIV_Lot 3 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | B strain | 58 Titers |
| aTIV_Lot 3 | Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV | H3N2 strain (N=1072,1078,1075) | 556 Titers |
95% CI: [1, 1.24]
95% CI: [0.95, 1.17]
95% CI: [0.85, 1.05]
95% CI: [0.92, 1.11]
95% CI: [0.9, 1.08]
95% CI: [0.89, 1.07]
95% CI: [0.91, 1.1]
95% CI: [0.87, 1.05]
95% CI: [0.87, 1.05]
Primary
Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains
The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 post vaccination
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Brisbane, overall (N=887, 880) | 60.4 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Wisconsin, overall | 57.5 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | B strain, overall (N=887, 880) | 53.3 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Brisbane (N= 330,333), high risk group | 54.2 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Wisconsin ( N= 330,333), high risk group | 52.1 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | B strain (N= 330, 333), high risk group | 46.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Wisconsin ( N= 330,333), high risk group | 38.7 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Brisbane, overall (N=887, 880) | 48.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Brisbane (N= 330,333), high risk group | 41.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | H3N2/Wisconsin, overall | 45.5 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | B strain (N= 330, 333), high risk group | 41.7 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains | B strain, overall (N=887, 880) | 49.8 Percentage of subjects |
Primary
Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains
The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 post vaccination
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H1N1 strain ( N= 3477,3480), overall | 77.3 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H3N2 strain ( N= 3477,3479), overall | 73.7 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | B strain, overall | 46.9 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H1N1 strain ( N= 1299,1273), high risk group | 72.6 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H3N2 strain ( N= 1299,1273), high risk group | 68.9 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | B strain (N= 1299,1273), high risk group | 40.0 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H3N2 strain ( N= 1299,1273), high risk group | 55.2 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H1N1 strain ( N= 3477,3480), overall | 67.8 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H1N1 strain ( N= 1299,1273), high risk group | 62.0 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | H3N2 strain ( N= 3477,3479), overall | 60.6 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | B strain (N= 1299,1273), high risk group | 34.3 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains | B strain, overall | 41.5 Percentage of subjects |
Primary
Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains
The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Time frame: Day 22 post vaccination
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Brisbane strain(N=887,880), overall | 95.8 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Wisconsin strain, overall | 99.6 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | B strain (N=887,880), overall | 76.2 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Brisbane (N=330, 333), high risk group | 94.9 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Wisconsin (N=330, 333), high risk group | 99.7 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | B strain (N=330, 333), high risk group | 83.3 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Wisconsin (N=330, 333), high risk group | 98.5 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Brisbane strain(N=887,880), overall | 94.0 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Brisbane (N=330, 333), high risk group | 94.0 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | H3N2/Wisconsin strain, overall | 98.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | B strain (N=330, 333), high risk group | 78.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains | B strain (N=887,880), overall | 72.4 Percentage of subjects |
Primary
Percentage of Subjects With HI Titers ≥40 Against Homologous Strains
The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Time frame: Day 22 post vaccination
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H3N2 strain (N=3477,3479) overall | 99.0 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H1N1 strain (N=3477,3480) overall | 91.1 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | B strain, overall | 64.6 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H1N1 strain (N=1299,1273), high risk group | 91.9 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H3N2 strain (N=1299,1273), high risk group | 98.7 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | B strain (N=1300,1273), high risk group | 66.3 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H3N2 strain (N=1299,1273), high risk group | 96.7 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H1N1 strain (N=1299,1273), high risk group | 85.8 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H1N1 strain (N=3477,3480) overall | 84.5 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | H3N2 strain (N=3477,3479) overall | 97.0 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | B strain (N=1300,1273), high risk group | 61.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With HI Titers ≥40 Against Homologous Strains | B strain, overall | 58.9 Percentage of subjects |
Secondary
All Cause Mortality Rate, Across Vaccine Groups
The all-cause mortality rate (excluding injury)reported in aTIV group compared to TIV group, by country.
Time frame: Day 1 through Day 366 post vaccination
Population: Analysis was done on the mFAS (effectiveness).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | All Cause Mortality Rate, Across Vaccine Groups | Columbia (N=519, 509) | 7 participants |
| aTIV_Lot 1 | All Cause Mortality Rate, Across Vaccine Groups | Panama (N=109, 105) | 0 participants |
| aTIV_Lot 1 | All Cause Mortality Rate, Across Vaccine Groups | Philippines (N=1873,1867) | 39 participants |
| aTIV_Lot 1 | All Cause Mortality Rate, Across Vaccine Groups | United states (N=1039,1060) | 6 participants |
| aTIV_Lot 2 | All Cause Mortality Rate, Across Vaccine Groups | United states (N=1039,1060) | 5 participants |
| aTIV_Lot 2 | All Cause Mortality Rate, Across Vaccine Groups | Columbia (N=519, 509) | 7 participants |
| aTIV_Lot 2 | All Cause Mortality Rate, Across Vaccine Groups | Philippines (N=1873,1867) | 34 participants |
| aTIV_Lot 2 | All Cause Mortality Rate, Across Vaccine Groups | Panama (N=109, 105) | 0 participants |
Secondary
Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS
The superiority of HI antibody responses of aTIV compared to TIV, in subjects with predefined co-morbidities (high risk group) assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Time frame: Day 22 post vaccination
Population: Analysis was done on FAS population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | H1N1 strain (N=1299,1273) | 212 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | H3N2 strain (N=1299,1273) | 499 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | B strain | 60 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | H1N1 strain (N=1299,1273) | 160 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | H3N2 strain (N=1299,1273) | 324 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS | B strain | 54 Titers |
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 homologous strains was \>1.5.95% CI: [1.2, 1.45]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 homologous strains was \>1.5.95% CI: [1.42, 1.68]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 homologous strains was \>1.5.95% CI: [1.03, 1.21]
Secondary
Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS
The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Time frame: Day 22 post vaccination
Population: Analysis was done on PPS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | H1N1 strain (1194, 1190) | 221 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | H3N2 strain (1194, 1190) | 519 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | B strain | 61 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | H1N1 strain (1194, 1190) | 161 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | H3N2 strain (1194, 1190) | 331 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS | B strain | 54 Titers |
95% CI: [1.25, 1.52]
95% CI: [1.44, 1.72]
95% CI: [1.03, 1.21]
Secondary
Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS
The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination.
Time frame: Day 22 post vaccination
Population: Analysis was done on FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Brisbane (overall) (N=887,880) | 362 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Wisconsin (overall) | 1016 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | B strain (overall) (N=887,880) | 87 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Brisbane (high risk) (N=302,307) | 364 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Wisconsin (high risk) (N=302,307) | 927 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | B strain (high risk) (N=302,307) | 112 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Wisconsin (high risk) (N=302,307) | 724 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Brisbane (overall) (N=887,880) | 243 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Brisbane (high risk) (N=302,307) | 267 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | H3N2/Wisconsin (overall) | 738 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | B strain (high risk) (N=302,307) | 99 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS | B strain (overall) (N=887,880) | 80 Titers |
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 heterologous strains was \>1.5.95% CI: [1.33, 1.67]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 heterologous strains was \>1.5.95% CI: [1.25, 1.52]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 heterologous strains was \>1.5.95% CI: [0.99, 1.21]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 heterologous strains was \>1.5.95% CI: [1.15, 1.61]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 heterologous strains was \>1.5.95% CI: [1.1, 1.48]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 vaccine group GMT ratios for at least 2 heterologous strains was \>1.5.95% CI: [0.97, 1.31]
Secondary
Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS
The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination .
Time frame: Day 22 post vaccination
Population: Analysis was done on PPS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Brisbane (overall) (N=834,814) | 369 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Wisconsin (overall) | 1037 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | B strain (overall) (N=834,814) | 89 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Brisbane (high risk) (N=302,307) | 377 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Wisconsin (high risk) (N=302,307) | 965 Titers |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | B strain (high risk) (N=302,307) | 117 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Wisconsin (high risk) (N=302,307) | 751 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Brisbane (overall) (N=834,814) | 255 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Brisbane (high risk) (N=302,307) | 279 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | H3N2/Wisconsin (overall) | 764 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | B strain (high risk) (N=302,307) | 105 Titers |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS | B strain (overall) (N=834,814) | 82 Titers |
95% CI: [1.29, 1.63]
95% CI: [1.23, 1.5]
95% CI: [0.98, 1.21]
95% CI: [1.13, 1.61]
95% CI: [1.1, 1.5]
95% CI: [0.95, 1.3]
Secondary
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS
The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of percentage of subjects achieving seroconversion, at three weeks after vaccination. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 post vaccination
Population: Analysis was done on FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Brisbane (overall) (N=887,880) | 60.4 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Wisconsin (overall) | 57.5 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | B strain (overall) (N=887,880) | 53.3 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Brisbane (high risk) (N=330, 333) | 54.2 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Wisconsin (high risk) (N=330,333) | 52.1 Percentage of subjects |
| aTIV_Lot 1 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | B strain (high risk) (N=330, 333) | 46.4 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Wisconsin (high risk) (N=330,333) | 38.7 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Brisbane (overall) (N=887,880) | 48.4 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Brisbane (high risk) (N=330, 333) | 41.4 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | H3N2/Wisconsin (overall) | 45.5 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | B strain (high risk) (N=330, 333) | 41.7 Percentage of subjects |
| aTIV_Lot 2 | Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS | B strain (overall) (N=887,880) | 49.8 Percentage of subjects |
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 heterologous strains was \>10%.95% CI: [8.1, 16.9]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 heterologous strains was \>10%.95% CI: [8.1, 17.1]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 heterologous strains was \>10%.95% CI: [0.4, 8.8]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 heterologous strains was \>10%.95% CI: [5.2, 19.6]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 heterologous strains was \>10%.95% CI: [5.8, 20.3]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 heterologous strains was \>10%.95% CI: [-1.6, 11.8]
Secondary
Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS
The superiority of HI antibody responses of aTIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 postvaccination
Population: Analysis was done on FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H1N1 strain (N=1299,1273) | 72.6 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H3N2 strain (N=1299,1273) | 68.9 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | B strain | 40.0 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H1N1 strain (N=1299,1273) | 62.0 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | H3N2 strain (N=1299,1273) | 55.2 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS | B strain | 34.3 Percentage of subjects |
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 homologous strains was \>10%.95% CI: [6.4, 13.3]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 homologous strains was \>10%.95% CI: [9.5, 16.6]
Comparison: Superiority was established if the lower bound of the 95% CI for the day 22 differences in seroconversion rates for at least 2 homologous strains was \>10%.95% CI: [1.5, 8.3]
Secondary
Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS
The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 post vaccination
Population: Analysis was done on PPS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H1N1 strain (N=1194, 1190) | 73.6 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H3N2 strain (N=1194, 1190) | 69.1 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | B strain | 40.0 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H1N1 strain (N=1194, 1190) | 61.7 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | H3N2 strain (N=1194, 1190) | 54.8 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS | B strain | 34.0 Percentage of subjects |
95% CI: [7.5, 14.6]
95% CI: [9.8, 17.2]
95% CI: [1.4, 8.5]
Secondary
Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS
The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous strains, in overall group and in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 22 postvaccination
Population: Analysis was done on PPS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Brisbane (overall) (N=834,814) | 60.0 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Wisconsin (overall) | 57.0 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | B strain (overall) (N=834,814) | 52.8 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Brisbane (high risk) (N=302,307) | 54.3 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Wisconsin (high risk) (N=302,307) | 51.7 Percentage of subjects |
| aTIV_Lot 1 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | B strain (high risk) (N=302,307) | 45.7 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Wisconsin (high risk) (N=302,307) | 38.8 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Brisbane (overall) (N=834,814) | 49.1 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Brisbane (high risk) (N=302,307) | 41.7 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | H3N2/Wisconsin (overall) | 45.9 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | B strain (high risk) (N=302,307) | 41.4 Percentage of subjects |
| aTIV_Lot 2 | Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS | B strain (overall) (N=834,814) | 49.3 Percentage of subjects |
95% CI: [6.7, 15.9]
95% CI: [7.3, 16.6]
95% CI: [-0.4, 8.4]
95% CI: [4.8, 19.9]
95% CI: [5, 20.2]
95% CI: [-2.1, 11.8]
Secondary
Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups
The number of high risk subjects reporting exacerbation of preexisting chronic conditions (i.e.congestive heart failure, Chronic Obstructive Pulmonary disease (COPD), asthma, hepatic disease, renal insufficiency, and neurological/neuromuscular or metabolic disorders including diabetes mellitus) in aTIV group compared to TIV group.
Time frame: Day 1 through Day 366 post vaccination
Population: Analysis was done on the mFAS (effectiveness) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| aTIV_Lot 1 | Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups | 55 participants |
| aTIV_Lot 2 | Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups | 48 participants |
Secondary
Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups
The number of subjects with emergency room visits, unscheduled physician visits, and hospitalizations due to community acquired influenza or pneumonia, cardiopulmonary disease, cardiac disease, respiratory or pulmonary disease,in aTIV group compared to TIV group.
Time frame: Day 1 through Day 366 post vaccination
Population: Analysis was done on the mFAS (effectiveness).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| aTIV_Lot 1 | Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups | 275 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups | 289 participants |
Secondary
Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups
The number of subjects reporting ILI from three weeks after vaccination to up to one year in aTIV group compared to TIV group, by country.
Time frame: Day 22 through Day 366 post vaccination
Population: Analysis was done on the modified full analysis set (mFAS; effectiveness) population i.e all subjects in the randomized population who received a study vaccination but excluding those who received a non-study vaccine during the follow-up phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Columbia (N=516, 506) | 119 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Panama (N=108, 102) | 20 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Philippines (N=1836,1835) | 102 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | United states (N=1037,1055) | 72 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | United states (N=1037,1055) | 76 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Columbia (N=516, 506) | 97 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Philippines (N=1836,1835) | 113 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups | Panama (N=108, 102) | 21 participants |
Secondary
Number of Subjects Reporting Solicited Adverse Events Following Vaccination
The number of subjects reporting solicited local and systemic adverse events and other adverse events in aTIV group compared to TIV group.
Time frame: Day 1 through Day 7 post vaccination
Population: Analysis was done on the safety set i.e all randomized subjects who received a study vaccination and provided postvaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Arthralgia (N=3492,3486) | 296 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Any Local | 1137 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Headache (N= 3495,3486) | 463 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site pain (N=3495,3485) | 875 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Fatigue (N= 3494, 3484) | 466 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site induration (N=3494, 3488) | 45 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Nausea (N=3492,3482) | 101 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Any sytemic | 1120 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Vomiting (N=3494,3483) | 48 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site tenderness (N=3495,3483) | 739 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Diarrhea (N=3494,3485) | 168 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Chills (N=3495,3485) | 235 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Fever (≥ 38°C) | 122 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site erythema (N=3492, 3485) | 43 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Any other | 210 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Oral Temperature (≥ 40°C) | 3 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Myalgia (N=3496,3487) | 515 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Analgesic/Antipyretic used | 158 participants |
| aTIV_Lot 1 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site swelling (N=3495,3488) | 43 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Analgesic/Antipyretic used | 122 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site induration (N=3494, 3488) | 17 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Any Local | 593 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site erythema (N=3492, 3485) | 18 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site tenderness (N=3495,3483) | 391 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site swelling (N=3495,3488) | 15 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Injection site pain (N=3495,3485) | 425 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Any sytemic | 902 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Chills (N=3495,3485) | 163 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Myalgia (N=3496,3487) | 339 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Arthralgia (N=3492,3486) | 272 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Headache (N= 3495,3486) | 391 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Fatigue (N= 3494, 3484) | 361 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Nausea (N=3492,3482) | 98 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Vomiting (N=3494,3483) | 59 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Diarrhea (N=3494,3485) | 158 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Fever (≥ 38°C) | 116 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Oral Temperature (≥ 40°C) | 0 participants |
| aTIV_Lot 2 | Number of Subjects Reporting Solicited Adverse Events Following Vaccination | Any other | 165 participants |
Secondary
Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains
The percentage of subjects demonstrating seroconversion in HI titers against homologous and heterologous strains, at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Time frame: Day 181, Day 366 post vaccination
Population: The analysis was done on the FAS (persistence) subset.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H1N1 (homologous) Day 181 | 28.6 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H1N1 (homologous) Day 366 | 18.5 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2 (homologous) Day 181 | 36.0 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2 (homologous) Day 366 | 16.9 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (homologous) Day 181 | 3.7 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (homologous) Day 366 | 2.1 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (heterologous) Day 181 | 2.65 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (heterologous) Day 366 | 4.23 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Brisbane (heterologous) Day 181 | 15.34 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Brisbane(heterologous) Day 366 | 7.94 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 181 | 12.17 Percentage of subjects |
| aTIV_Lot 1 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 366 | 8.99 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 181 | 8.90 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H1N1 (homologous) Day 181 | 26.2 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (heterologous) Day 181 | 3.14 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H1N1 (homologous) Day 366 | 19.4 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Brisbane(heterologous) Day 366 | 5.24 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2 (homologous) Day 181 | 24.6 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (heterologous) Day 366 | 3.14 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2 (homologous) Day 366 | 12.6 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 366 | 6.28 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (homologous) Day 181 | 2.6 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | H3N2/Brisbane (heterologous) Day 181 | 8.38 Percentage of subjects |
| aTIV_Lot 2 | Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains | B (homologous) Day 366 | 3.1 Percentage of subjects |
Secondary
Persistence of GMTs Against Homologous and Heterologous Strains
The GMTs against homologous and heterologous strains, persisting in subjects at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV.
Time frame: Day 181, Day 366 post vaccination
Population: The analysis was done on the FAS (persistence) subset population i.e all randomized population only from US sites who received a study vaccination, provided evaluable blood samples at day 1, day 22, day 181, and day 366.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | B (heterologous) Day 181 | 39 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Brisbane(heterologous) Day 366 | 75 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H1N1 (homologous) Day 181 | 71 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H1N1 (homologous) Day 366 | 49 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2 (homologous) Day 181 | 123 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2 (homologous) Day 366 | 70 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | B (homologous) Day 181 | 25 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | B (homologous) Day 366 | 21 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | B (heterologous) Day 366 | 38 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Brisbane (heterologous) Day 181 | 100 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 181 | 228 Titers |
| aTIV_Lot 1 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 366 | 190 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Brisbane(heterologous) Day 366 | 72 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | B (homologous) Day 366 | 20 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | B (heterologous) Day 181 | 38 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H1N1 (homologous) Day 181 | 68 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 366 | 182 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H1N1 (homologous) Day 366 | 52 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | B (heterologous) Day 366 | 40 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2 (homologous) Day 181 | 91 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Wisconsin (heterologous) Day 181 | 194 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2 (homologous) Day 366 | 54 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | H3N2/Brisbane (heterologous) Day 181 | 81 Titers |
| aTIV_Lot 2 | Persistence of GMTs Against Homologous and Heterologous Strains | B (homologous) Day 181 | 22 Titers |