Influenza, Human
Conditions
Brief summary
This is a study to assess the immune (antibody) response and safety of a bioCSL split virion, inactivated quadrivalent influenza vaccine, in comparison with a US licensed 2014/2015 trivalent influenza vaccine (bioCSL TIV-1), and a trivalent influenza vaccine containing the alternate B strain (bioCSL TIV-2), in healthy adult volunteers aged 18 years and above.
Detailed description
This multicenter, randomized, double-blinded study was conducted during the 2014-2015 Northern Hemisphere influenza immunization season to evaluate the non-inferior immune response of bioCSL QIV to that of bioCSL TIV-1 and bioCSL TIV-2 along with safety in healthy male and female adults aged ≥ 18 years. Each vaccinated subject had a maximum 25 day on-study period with a six month safety follow-up.
Interventions
BIOLOGICALQuadrivalent Influenza Vaccine (QIV)
One 0.5 mL intramuscular dose into the deltoid muscle
BIOLOGICALTrivalent Influenza Vaccine (TIV-1)
One 0.5 mL intramuscular dose into the deltoid muscle.
BIOLOGICALTrivalent Influenza Vaccine (TIV-2)
One 0.5 mL intramuscular dose into the deltoid muscle.
Sponsors
Seqirus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Males or non-pregnant females aged ≥ 18 years at the time of vaccination. * Females of child-bearing potential (i.e., ovulating, pre-menopausal, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen for the duration of the On-study period. Females of child-bearing potential must return a negative urine pregnancy test result prior to vaccination with the vaccine.
Exclusion criteria
* Known hypersensitivity to a previous dose of influenza vaccine or allergy to eggs, chicken protein, neomycin, polymyxin, or any components of bioCSL influenza vaccines. * Vaccination against influenza in the previous 6 months. * Known history of Guillain-Barré Syndrome or other demyelinating disease. * Clinical signs of active infection and/or an oral temperature of ≥ 100.4°F (38.0°C). * A clinically significant medical condition. * Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | 21 days after vaccination. | Immunogenicity was assessed by measuring HI titers to the four virus strains. Postvaccination GMTs were determined. (GMT dispersion values are based on unadjusted GMT values.) The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was then determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains. |
| The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | 21 days after vaccination. | SCR (defined as the percentage of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40 or a prevaccination HI titer ≥ 1:10 and a 4-fold increase in postvaccination HI titer) was determined for each virus strain included in the vaccines: bioCSL TIV-1 and bioCSL TIV-2 SCRs were pooled for analysis of the A strains. The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | 21 days after vaccination. | Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses. (GMT dispersion values are based on unadjusted GMT values.) |
| Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | 21 days after vaccination. | Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The SCR difference was calculated as bioCSL QIV SCR minus bioCSL TIV SCR, which is the reverse of how it was calculated for the non-inferiority analyses. For the SCR comparison superiority was demonstrated if the lower limit of the two-sided 95% CI of the difference of the seroconversion rates was greater than 0 for each B strain in QIV compared with the corresponding B strain not contained in each TIV. |
| Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | 21 days after vaccination. | The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 was assessed in terms of geometric mean HI titers (GMT) prevaccination (Day 1) and postvaccination (Day 21), in age cohorts (per protocol population). |
| Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | 21 days after vaccination. | The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 assessed in terms of Geometric Mean Fold Increase (GMFI, defined as the geometric mean of the fold increases of postvaccination antibody titer over the prevaccination antibody titer) by Age Cohort (Per Protocol Population). |
| Seroprotection Rates Prevaccination and Postvaccination. | 21 days after vaccination. | The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 was assessed in terms of percentage of subjects with a HI titer ≥40 (seroprotection rates) prevaccination (Day 1) and postvaccination (Day 21), in age cohorts (per protocol population). |
| Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | 21 days after vaccination. | Immunogenicity was assessed by measuring HI titers to the four virus strains. Postvaccination GMTs were determined. (GMT dispersion values are based on unadjusted GMT values.) The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was then determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains. Non-inferiority of bioCSL QIV compared to bioCSL TIV-1, and to bioCSL TIV-2 was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age) through assessment of GMT ratios as described for the primary endpoint. |
| The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | For 7 days following vaccination. | The overall number of subjects experiencing at least one event of a local and systemic solicited AE, and the overall number of subjects with at least one severe (grade 3) local and systemic solicited AE. |
| The Frequency of Cellulitis-like Reaction and Cellulitis. | For 28 days following vaccination. | The number of subjects experiencing at least one episode of each event. |
| The Frequency and Severity of Unsolicited AEs. | For 28 days following vaccination. | The overall number of subjects experiencing at least one event of an unsolicited AE, and the overall number of subjects with at least one severe (grade 3) unsolicited AE. |
| The Frequency of Serious Adverse Events (SAEs) for 6 Months Following Vaccination. | For 6 months following vaccination. | The number of participants reporting Serious Adverse Events for 6 months following vaccination. |
| Seroconversion Rates | 21 days after vaccination. | The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bio CSL TIV-2 was assessed in terms of the seroconversion rate, ie, percentage of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40, or a prevaccination titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination titer. Data presented in age cohorts (per protocol population). |
| The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | 21 days after vaccination. | Non-inferiority of bioCSL QIV compared to bioCSL TIV-1, and to bioCSL TIV-2 was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age) through assessment of SCR differences as described for the primary endpoint. |
Countries
United States
Participant flow
Recruitment details
First Patient In: 15-AUG-2014, Last Patient Last Visit: 20-APR-2015. Number of activated sites that enrolled subjects: 31 (all based in USA).
Pre-assignment details
Number of subjects screened: 3673. Number of subjects randomized: 3484.
Participants by arm
| Arm | Count |
|---|---|
| Quadrivalent Influenza Vaccine (QIV) The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season).
QIV dose: One 0.5 mL intramuscular dose into the deltoid muscle. | 1,741 |
| Trivalent Influenza Vaccine (TIV-1) The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season).
TIV-1 dose: One 0.5 mL intramuscular dose into the deltoid muscle. | 871 |
| Trivalent Influenza Vaccine (TIV-2) The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the recommended influenza A (H1N1-, H3N2-like) strains and the alternative B strain for the Northern Hemisphere 2014/2015 influenza season).
TIV-2 dose: One 0.5 mL intramuscular dose into the deltoid muscle. | 872 |
| Total | 3,484 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 5 | 0 | 1 |
| Overall Study | Lost to Follow-up | 46 | 18 | 18 |
| Overall Study | randomized in error, not vaccinated | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Quadrivalent Influenza Vaccine (QIV) | Trivalent Influenza Vaccine (TIV-1) | Trivalent Influenza Vaccine (TIV-2) | Total |
|---|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 18.1 | 58.2 years STANDARD_DEVIATION 18.1 | 58.3 years STANDARD_DEVIATION 17.89 | 58.3 years STANDARD_DEVIATION 18.04 |
| Age, Customized 18 to 49 years | 510 participants | 255 participants | 255 participants | 1020 participants |
| Age, Customized 50 to 64 years | 361 participants | 179 participants | 181 participants | 721 participants |
| Age, Customized 65 to 74 years | 541 participants | 271 participants | 270 participants | 1082 participants |
| Age, Customized => 75 years | 329 participants | 166 participants | 166 participants | 661 participants |
| Region of Enrollment United States | 1741 participants | 871 participants | 872 participants | 3484 participants |
| Sex: Female, Male Female | 971 Participants | 511 Participants | 510 Participants | 1992 Participants |
| Sex: Female, Male Male | 770 Participants | 360 Participants | 362 Participants | 1492 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 | 872 / 1,721 | 445 / 864 | 397 / 864 |
| serious Total, serious adverse events | 39 / 1,721 | 14 / 864 | 13 / 864 |
Outcome results
Primary
Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population).
Immunogenicity was assessed by measuring HI titers to the four virus strains. Postvaccination GMTs were determined. (GMT dispersion values are based on unadjusted GMT values.) The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was then determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GMT: bioCSL QIV | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | A/H1N1 | 303.0 Titer |
| GMT: bioCSL QIV | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | B/Yamagata | 64.3 Titer |
| GMT: bioCSL QIV | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | A/H3N2 | 488.7 Titer |
| GMT: bioCSL QIV | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | B/Victoria | 87.9 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | B/Victoria | 82.2 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | A/H1N1 | 280.2 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | A/H3N2 | 454.2 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). | B/Yamagata | 55.7 Titer |
Comparison: For A/H1N1 strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.87, 0.98]
Comparison: For A/H3N2 strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.88, 0.98]
Comparison: For B/Yamagata strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.81, 0.93]
Comparison: For B/Victoria strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.86, 1.01]
Primary
The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years.
SCR (defined as the percentage of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40 or a prevaccination HI titer ≥ 1:10 and a 4-fold increase in postvaccination HI titer) was determined for each virus strain included in the vaccines: bioCSL TIV-1 and bioCSL TIV-2 SCRs were pooled for analysis of the A strains. The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | A/H1N1 | 38.8 percentage of participants |
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | A/H3N2 | 40.9 percentage of participants |
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | B/Yamagata | 31.0 percentage of participants |
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | B/Victoria | 40.3 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | B/Victoria | 38.7 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | A/H1N1 | 37.7 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | B/Yamagata | 27.8 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. | A/H3N2 | 39.3 percentage of participants |
95% CI: [-4.4, 2.2]
95% CI: [-5, 1.6]
95% CI: [-7, 0.5]
95% CI: [-5.6, 2.4]
Secondary
Geometric Mean Fold Titer Change From Prevaccination to Postvaccination.
The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 assessed in terms of Geometric Mean Fold Increase (GMFI, defined as the geometric mean of the fold increases of postvaccination antibody titer over the prevaccination antibody titer) by Age Cohort (Per Protocol Population).
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GMT: bioCSL QIV | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Yamagata | 4.1 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Victoria | 5.5 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H3N2 | 5.5 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H1N1 | 5.5 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Victoria | 2.7 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H1N1 | 5.3 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H3N2 | 5.2 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Yamagata | 3.4 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H1N1 | 5.2 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H3N2 | 5.0 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Yamagata | 2.3 Fold Change Titer (GMFI) |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Victoria | 4.8 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Victoria | 2.2 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H1N1 | 2.3 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H3N2 | 2.3 Fold Change Titer (GMFI) |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Yamagata | 1.9 Fold Change Titer (GMFI) |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H1N1 | 2.4 Fold Change Titer (GMFI) |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Victoria | 1.7 Fold Change Titer (GMFI) |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Yamagata | 1.8 Fold Change Titer (GMFI) |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H3N2 | 2.4 Fold Change Titer (GMFI) |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Victoria | 2.3 Fold Change Titer (GMFI) |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H1N1 | 2.3 Fold Change Titer (GMFI) |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | A/H3N2 | 2.3 Fold Change Titer (GMFI) |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. | B/Yamagata | 1.5 Fold Change Titer (GMFI) |
Secondary
Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination.
The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 was assessed in terms of geometric mean HI titers (GMT) prevaccination (Day 1) and postvaccination (Day 21), in age cohorts (per protocol population).
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 533.3 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 111.9 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination) | 23.7 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 97.4 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 97.4 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 429.9 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 20.4 Titer |
| GMT: bioCSL QIV | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 78.1 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 432.8 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 20.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 82.3 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 84.6 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 55.5 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 499.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination) | 24.7 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 96.1 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 532.5 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 103.0 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 53.5 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 21.7 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 82.8 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 433.9 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 105.7 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination) | 23.7 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 38.1 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 54.0 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 153.0 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 75.7 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 356.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination) | 20.3 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 24.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 175.9 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 72.0 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination) | 18.6 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 33.2 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 336.6 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 169.3 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 139.0 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 38.7 Titer |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 23.4 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 57.4 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 69.2 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 142.7 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 158.7 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination) | 19.6 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 25.1 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 330.3 Titer |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 28.6 Titer |
Secondary
Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population)
Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The SCR difference was calculated as bioCSL QIV SCR minus bioCSL TIV SCR, which is the reverse of how it was calculated for the non-inferiority analyses. For the SCR comparison superiority was demonstrated if the lower limit of the two-sided 95% CI of the difference of the seroconversion rates was greater than 0 for each B strain in QIV compared with the corresponding B strain not contained in each TIV.
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Victoria (≥65 years) | 23.5 percentage of participants analyzed |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Yamagata (overall, ≥18 years) | 31.0 percentage of participants analyzed |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Victoria (overall, ≥18 years) | 40.3 percentage of participants analyzed |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Yamagata (18 to <65 years) | 45.7 percentage of participants analyzed |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Victoria (18 to <65 years) | 57.6 percentage of participants analyzed |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Yamagata (≥65 years) | 16.6 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Victoria (18 to <65 years) | 29.0 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Victoria (≥65 years) | 11.6 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Yamagata (18 to <65 years) | 22.8 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Yamagata (overall, ≥18 years) | 15.6 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Yamagata (≥65 years) | 8.6 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) | B/Victoria (overall, ≥18 years) | 20.3 percentage of participants analyzed |
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. Seroconversion rate difference = bioCSL QIV SCR percentage - bioCSL TIV-1 or TIV-2 SCR percentage95% CI: [12.1, 18.6]
Comparison: Seroconversion rate difference = bioCSL QIV SCR percentage - bioCSL TIV-1 or TIV-2 SCR percentage95% CI: [16.5, 23.6]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. Seroconversion rate difference = bioCSL QIV SCR percentage - bioCSL TIV-1 or TIV-2 SCR percentage95% CI: [17.7, 28.2]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. Seroconversion rate difference = bioCSL QIV SCR percentage - bioCSL TIV-1 or TIV-2 SCR percentage95% CI: [23.1, 34.1]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. Seroconversion rate difference = bioCSL QIV SCR percentage - bioCSL TIV-1 or TIV-2 SCR percentage95% CI: [4.3, 11.6]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. Seroconversion rate difference = bioCSL QIV SCR percentage - bioCSL TIV-1 or TIV-2 SCR percentage.95% CI: [7.7, 16]
Secondary
Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population).
Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses. (GMT dispersion values are based on unadjusted GMT values.)
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Yamagata (overall, ≥18 years) | 62.9 Titer |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Victoria (overall, ≥18 years) | 86.9 Titer |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Yamagata (18 to <65 years) | 89.9 Titer |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Victoria (18 to <65 years) | 113.5 Titer |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Yamagata (≥65 years) | 43.8 Titer |
| GMT: bioCSL QIV | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Victoria (≥65 years) | 64.1 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Yamagata (≥65 years) | 33.6 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Yamagata (overall, ≥18 years) | 42.7 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Victoria (18 to <65 years) | 64.3 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Victoria (overall, ≥18 years) | 55.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Victoria (≥65 years) | 46.3 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). | B/Yamagata (18 to <65 years) | 53.8 Titer |
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.95% CI: [1.38, 1.57]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.95% CI: [1.45, 1.7]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.95% CI: [1.5, 1.87]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.95% CI: [1.55, 2.01]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.95% CI: [1.21, 1.4]
Comparison: Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.95% CI: [1.27, 1.51]
Secondary
Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population).
Immunogenicity was assessed by measuring HI titers to the four virus strains. Postvaccination GMTs were determined. (GMT dispersion values are based on unadjusted GMT values.) The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was then determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains. Non-inferiority of bioCSL QIV compared to bioCSL TIV-1, and to bioCSL TIV-2 was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age) through assessment of GMT ratios as described for the primary endpoint.
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GMT: bioCSL QIV | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H1N1 | 432.7 Titer |
| GMT: bioCSL QIV | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H3N2 | 569.1 Titer |
| GMT: bioCSL QIV | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Yamagata | 92.3 Titer |
| GMT: bioCSL QIV | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Victoria | 110.7 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H3N2 | 515.1 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Yamagata | 79.3 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Victoria | 95.2 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H1N1 | 402.8 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Yamagata | 43.3 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H3N2 | 419.5 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Victoria | 66.1 Titer |
| GMT: bioCSL QIV (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H1N1 | 211.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Victoria | 68.4 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H3N2 | 400.0 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | A/H1N1 | 199.8 Titer |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). | B/Yamagata | 39.1 Titer |
Comparison: For A/H1N1 strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.85, 1.02]
Comparison: For A/H3N2 strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.83, 0.99]
Comparison: For B/YAM strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.76, 0.97]
Comparison: For B/VIC strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.76, 0.98]
Comparison: For A/H1N1 strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.88, 1.02]
Comparison: For A/H3N2 strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.89, 1.02]
Comparison: For B/YAM strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.84, 0.97]
Comparison: For B/VIC strain. The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.95% CI: [0.94, 1.14]
Secondary
Seroconversion Rates
The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bio CSL TIV-2 was assessed in terms of the seroconversion rate, ie, percentage of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40, or a prevaccination titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination titer. Data presented in age cohorts (per protocol population).
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | Seroconversion Rates | A/H1N1 | 51.3 percentage of participants |
| GMT: bioCSL QIV | Seroconversion Rates | A/H3N2 | 56.3 percentage of participants |
| GMT: bioCSL QIV | Seroconversion Rates | B/Yamagata | 45.7 percentage of participants |
| GMT: bioCSL QIV | Seroconversion Rates | B/Victoria | 57.6 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroconversion Rates | B/Yamagata | 41.3 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroconversion Rates | A/H3N2 | 52.8 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroconversion Rates | A/H1N1 | 50.5 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroconversion Rates | B/Victoria | 29.0 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroconversion Rates | B/Victoria | 53.0 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroconversion Rates | B/Yamagata | 22.8 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroconversion Rates | A/H3N2 | 50.6 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroconversion Rates | A/H1N1 | 47.7 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroconversion Rates | A/H1N1 | 26.6 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroconversion Rates | B/Victoria | 23.5 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroconversion Rates | A/H3N2 | 25.9 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroconversion Rates | B/Yamagata | 16.6 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroconversion Rates | B/Yamagata | 14.4 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroconversion Rates | B/Victoria | 11.6 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroconversion Rates | A/H3N2 | 28.6 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroconversion Rates | A/H1N1 | 27.4 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroconversion Rates | A/H3N2 | 25.4 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroconversion Rates | B/Yamagata | 8.6 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroconversion Rates | B/Victoria | 24.7 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroconversion Rates | A/H1N1 | 25.4 percentage of participants |
Secondary
Seroprotection Rates Prevaccination and Postvaccination.
The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 was assessed in terms of percentage of subjects with a HI titer ≥40 (seroprotection rates) prevaccination (Day 1) and postvaccination (Day 21), in age cohorts (per protocol population).
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination | 39.9 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 78.3 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 73.2 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 33.5 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 99.0 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 99.0 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 84.3 percentage of participants |
| GMT: bioCSL QIV | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 86.7 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 32.8 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 68.2 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 76.9 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 81.4 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 98.8 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination | 39.9 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 77.1 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 100.0 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 81.5 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination | 40.9 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 35.9 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 86.2 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 99.0 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 98.8 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 68.4 percentage of participants |
| GMT: bioCSL QIV (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 75.5 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 57.5 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 99.8 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 94.6 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 78.5 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination | 33.2 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 38.7 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 68.3 percentage of participants |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 92.9 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 54.4 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 80.0 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 95.8 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 99.1 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 54.2 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 90.9 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination | 29.1 percentage of participants |
| bioCSL TIV-1 (B/YAM) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 36.3 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (post-vaccination) | 68.3 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (post-vaccination) | 95.3 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (pre-vaccination | 31.2 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Victoria (pre-vaccination) | 40.1 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (post-vaccination) | 98.1 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H3N2 (pre-vaccination) | 88.8 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | B/Yamagata (post-vaccination) | 46.2 percentage of participants |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) | Seroprotection Rates Prevaccination and Postvaccination. | A/H1N1 (pre-vaccination) | 77.4 percentage of participants |
Secondary
The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs).
The overall number of subjects experiencing at least one event of a local and systemic solicited AE, and the overall number of subjects with at least one severe (grade 3) local and systemic solicited AE.
Time frame: For 7 days following vaccination.
Population: The Safety Population was used for the analysis of safety and comprised all subjects in the Full Analysis Set (FAS) who received the study vaccine and provided follow-up safety data. A statement that they were no AEs constituted follow-up safety data. A total of 31 subjects were assessed as having no follow-up safety data post-vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | Frequency of solicited AEs | 803 participants |
| GMT: bioCSL QIV | The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | Severe (grade 3) solicited AEs | 42 participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | Frequency of solicited AEs | 391 participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | Severe (grade 3) solicited AEs | 15 participants |
| GMT: bioCSL QIV (≥ 65 Years) | The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | Frequency of solicited AEs | 397 participants |
| GMT: bioCSL QIV (≥ 65 Years) | The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). | Severe (grade 3) solicited AEs | 24 participants |
Secondary
The Frequency and Severity of Unsolicited AEs.
The overall number of subjects experiencing at least one event of an unsolicited AE, and the overall number of subjects with at least one severe (grade 3) unsolicited AE.
Time frame: For 28 days following vaccination.
Population: The Safety Population was used for the analysis of safety and comprised all subjects in the Full Analysis Set (FAS) who received the study vaccine and provided follow-up safety data. A statement that they were no AEs constituted follow-up safety data. A total of 31 subjects were assessed as having no follow-up safety data post-vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | The Frequency and Severity of Unsolicited AEs. | At least one unsolicited AE | 351 participants |
| GMT: bioCSL QIV | The Frequency and Severity of Unsolicited AEs. | Severe (grade 3) unsolicited AE | 73 participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Frequency and Severity of Unsolicited AEs. | At least one unsolicited AE | 191 participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Frequency and Severity of Unsolicited AEs. | Severe (grade 3) unsolicited AE | 29 participants |
| GMT: bioCSL QIV (≥ 65 Years) | The Frequency and Severity of Unsolicited AEs. | At least one unsolicited AE | 176 participants |
| GMT: bioCSL QIV (≥ 65 Years) | The Frequency and Severity of Unsolicited AEs. | Severe (grade 3) unsolicited AE | 33 participants |
Secondary
The Frequency of Cellulitis-like Reaction and Cellulitis.
The number of subjects experiencing at least one episode of each event.
Time frame: For 28 days following vaccination.
Population: The Safety Population was used for the analysis of safety and comprised all subjects in the Full Analysis Set (FAS) who received the study vaccine and provided follow-up safety data. A statement that they were no AEs constituted follow-up safety data. A total of 31 subjects were assessed as having no follow-up safety data post-vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GMT: bioCSL QIV | The Frequency of Cellulitis-like Reaction and Cellulitis. | 0 participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Frequency of Cellulitis-like Reaction and Cellulitis. | 0 participants |
| GMT: bioCSL QIV (≥ 65 Years) | The Frequency of Cellulitis-like Reaction and Cellulitis. | 0 participants |
Secondary
The Frequency of Serious Adverse Events (SAEs) for 6 Months Following Vaccination.
The number of participants reporting Serious Adverse Events for 6 months following vaccination.
Time frame: For 6 months following vaccination.
Population: The Safety Population was used for the analysis of safety and comprised all subjects in the Full Analysis Set (FAS) who received the study vaccine and provided follow-up safety data. A statement that they were no AEs constituted follow-up safety data. A total of 31 subjects were assessed as having no follow-up safety data post-vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GMT: bioCSL QIV | The Frequency of Serious Adverse Events (SAEs) for 6 Months Following Vaccination. | 39 participants |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Frequency of Serious Adverse Events (SAEs) for 6 Months Following Vaccination. | 14 participants |
| GMT: bioCSL QIV (≥ 65 Years) | The Frequency of Serious Adverse Events (SAEs) for 6 Months Following Vaccination. | 13 participants |
Secondary
The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population).
Non-inferiority of bioCSL QIV compared to bioCSL TIV-1, and to bioCSL TIV-2 was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age) through assessment of SCR differences as described for the primary endpoint.
Time frame: 21 days after vaccination.
Population: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H1N1 | 51.3 percentage of participants analyzed |
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H3N2 | 56.3 percentage of participants analyzed |
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Yamagata | 45.7 percentage of participants analyzed |
| GMT: bioCSL QIV | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Victoria | 57.6 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H3N2 | 51.7 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Yamagata | 41.3 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Victoria | 53.0 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 (B/YAM) or TIV-2 (B/VIC) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H1N1 | 49.1 percentage of participants analyzed |
| GMT: bioCSL QIV (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Yamagata | 16.6 percentage of participants analyzed |
| GMT: bioCSL QIV (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H3N2 | 25.9 percentage of participants analyzed |
| GMT: bioCSL QIV (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Victoria | 23.5 percentage of participants analyzed |
| GMT: bioCSL QIV (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H1N1 | 26.6 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Victoria | 24.7 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H3N2 | 27.0 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | A/H1N1 | 26.4 percentage of participants analyzed |
| GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). | B/Yamagata | 14.4 percentage of participants analyzed |
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-6.9, 2.6]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-9.3, 0.2]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-10.3, 1.3]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-10.5, 1.2]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-4.4, 4]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-3.1, 5.2]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-6.3, 2]
Comparison: The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.95% CI: [-3.7, 6.2]