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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Quadrivalent Influenza Vaccine (QIV) | Experimental | 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). |
|
| Trivalent Influenza Vaccine (TIV-1) | Active Comparator | 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). |
|
| Trivalent Influenza Vaccine (TIV-2) | Active Comparator | 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 alternate B strain for the Northern Hemisphere 2014/2015 influenza season). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Quadrivalent Influenza Vaccine (QIV) | Biological | One 0.5 mL intramuscular dose into the deltoid muscle |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 21 days after vaccination. |
| 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. | 21 days after vaccination. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| bioCSL Pty Ltd Clinical Program Director | Seqirus | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site 296 | Huntsville | Alabama | 35802 | United States | ||
| Site 286 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28302411 | Derived | Treanor JT, Albano FR, Sawlwin DC, Graves Jones A, Airey J, Formica N, Matassa V, Leong J. Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study. Vaccine. 2017 Apr 4;35(15):1856-1864. doi: 10.1016/j.vaccine.2017.02.066. Epub 2017 Mar 13. |
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Number of subjects screened: 3673. Number of subjects randomized: 3484.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Quadrivalent Influenza Vaccine (QIV) | The 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). Quadrivalent Influenza Vaccine (QIV): One 0.5 mL intramuscular dose into the deltoid muscle |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Trivalent Influenza Vaccine (TIV-1) | Biological | One 0.5 mL intramuscular dose into the deltoid muscle. |
|
| Trivalent Influenza Vaccine (TIV-2) | Biological | One 0.5 mL intramuscular dose into the deltoid muscle. |
|
| 21 days after vaccination. |
| 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. | 21 days after vaccination. |
| 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.) | 21 days after vaccination. |
| 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. | 21 days after vaccination. |
| 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). | 21 days after vaccination. |
| 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). | 21 days after vaccination. |
| 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). | 21 days after vaccination. |
| 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). | 21 days after vaccination. |
| 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. | For 7 days following vaccination. |
| The Frequency of Cellulitis-like Reaction and Cellulitis. | The number of subjects experiencing at least one episode of each event. | For 28 days following vaccination. |
| 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. | For 28 days following vaccination. |
| 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. | For 6 months following vaccination. |
| Los Angeles |
| California |
| 90036 |
| United States |
| Site 315 | San Diego | California | 92108 | United States |
| Site 301 | Milford | Connecticut | 06460 | United States |
| Site 297 | Jacksonville | Florida | 32207 | United States |
| Site 293 | Melbourne | Florida | 32935 | United States |
| Site 292 | Savannah | Georgia | 31406 | United States |
| Site 289 | Meridian | Idaho | 83642 | United States |
| Site 294 | Peoria | Illinois | 61614 | United States |
| Site 295 | Mishawaka | Indiana | 46545 | United States |
| Site 317 | Witchita | Kansas | 67207 | United States |
| Site 291 | Rockville | Maryland | 20850 | United States |
| Site 310 | Methuen | Massachusetts | 01844 | United States |
| Site 287 | St Louis | Missouri | 63141 | United States |
| Site 316 | Bellevue | Nebraska | 68005 | United States |
| Site 298 | Las Vegas | Nevada | 89104 | United States |
| Site 285 | Binghamton | New York | 13901 | United States |
| Site 313 | Rochester | New York | 14642 | United States |
| Site 302 | Charlotte | North Carolina | 28209 | United States |
| Site 306 | Raleigh | North Carolina | 27609 | United States |
| Site 309 | Wilmington | North Carolina | 28401 | United States |
| Site 305 | Winston-Salem | North Carolina | 27103 | United States |
| Site 299 | Oklahoma City | Oklahoma | 73112 | United States |
| Site 307 | Mt. Pleasant | South Carolina | 29464 | United States |
| Site 308 | Bristol | Tennessee | 37620 | United States |
| Site 311 | Jefferson City | Tennessee | 37760 | United States |
| Site 312 | Knoxville | Tennessee | 37912 | United States |
| Site 304 | Knoxville | Tennessee | 37938 | United States |
| Site 283 | Austin | Texas | 78705 | United States |
| Site 282 | Forth Worth | Texas | 76135 | United States |
| Site 288 | San Angelo | Texas | 76904 | United States |
| Site 300 | Salt Lake City | Utah | 84124 | United States |
| Site 303 | Charlottesville | Virginia | 22911 | United States |
| FG001 |
| Trivalent Influenza Vaccine (TIV-1) |
The 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). Trivalent Influenza Vaccine (TIV-1): One 0.5 mL intramuscular dose into the deltoid muscle. |
| FG002 | Trivalent Influenza Vaccine (TIV-2) | The 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). Trivalent Influenza Vaccine (TIV-2): One 0.5 mL intramuscular dose into the deltoid muscle. |
| COMPLETED |
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| NOT COMPLETED |
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The Full Analysis Set (FAS) was used for analysis of subject characteristics and comprised all subjects who gave informed consent and who were randomized to treatment. Screening failures were not included in the FAS.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number of participants allocated within each age subset category for each arm. | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Geometric Mean | Full Range | Titer | 21 days after vaccination. |
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| 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. | 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. | Posted | Number | percentage of participants | 21 days after vaccination. |
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| 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. | 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. | Posted | Geometric Mean | Full Range | Titer | 21 days after vaccination. |
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| 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. | 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. | Posted | Number | percentage of participants analyzed | 21 days after vaccination. |
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| 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.) | 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. | Posted | Geometric Mean | Full Range | Titer | 21 days after vaccination. |
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| 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. | 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. | Posted | Number | percentage of participants analyzed | 21 days after vaccination. |
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| 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). | 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. | Posted | Geometric Mean | 95% Confidence Interval | Titer | 21 days after vaccination. |
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| 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). | 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. | Posted | Geometric Mean | 95% Confidence Interval | Fold Change Titer (GMFI) | 21 days after vaccination. |
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| 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 21 days after vaccination. |
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| 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 21 days after vaccination. |
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| 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. | 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. | Posted | Number | participants | For 7 days following vaccination. |
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| Secondary | The Frequency of Cellulitis-like Reaction and Cellulitis. | The number of subjects experiencing at least one episode of each event. | 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. | Posted | Number | participants | For 28 days following vaccination. |
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| 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. | 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. | Posted | Number | participants | For 28 days following vaccination. |
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| 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. | 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. | Posted | Number | participants | For 6 months following vaccination. |
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Local and systemic solicited AEs collected from Day 1 to Day 7. Unsolicited AEs collected for 28 days after vaccination. SAEs collected for 6 months after vaccination.
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Quadrivalent Influenza Vaccine (QIV) | The 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). Quadrivalent Influenza Vaccine (QIV): One 0.5 mL intramuscular dose into the deltoid muscle | 39 | 1,721 | 872 | 1,721 | ||
| EG001 | Trivalent Influenza Vaccine (TIV-1) | The 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). Trivalent Influenza Vaccine (TIV-1): One 0.5 mL intramuscular dose into the deltoid muscle. | 14 | 864 | 445 | 864 | ||
| EG002 | Trivalent Influenza Vaccine (TIV-2) | The 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). Trivalent Influenza Vaccine (TIV-2): One 0.5 mL intramuscular dose into the deltoid muscle. | 13 | 864 | 397 | 864 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Atypical pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Cellulitis | Infections and infestations | Systematic Assessment |
| ||
| Diverticulitis | Infections and infestations | Systematic Assessment |
| ||
| Pelvic inflammatory disease | Infections and infestations | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Parathyroid tumor benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Bipolar I disorder | Psychiatric disorders | Systematic Assessment |
| ||
| Bipolar disorder | Psychiatric disorders | Systematic Assessment |
| ||
| Cerebrovascular accident | Nervous system disorders | Systematic Assessment |
| ||
| Transient ischemic attack | Nervous system disorders | Systematic Assessment |
| ||
| Carotid artery disease | Nervous system disorders | Systematic Assessment |
| ||
| Carotid artery stenosis | Nervous system disorders | Systematic Assessment |
| ||
| Hemorrhage intracranial | Nervous system disorders | Systematic Assessment |
| ||
| Ischemic stroke | Nervous system disorders | Systematic Assessment |
| ||
| Posterior reversible encephalopathy syndrome | Nervous system disorders | Systematic Assessment |
| ||
| Spasmodic dysphonia | Nervous system disorders | Systematic Assessment |
| ||
| Syncope | Nervous system disorders | Systematic Assessment |
| ||
| Thalamic infarction | Nervous system disorders | Systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Cardiac failure congestive | Cardiac disorders | Systematic Assessment |
| ||
| Acute myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Atrioventricular block second degree | Cardiac disorders | Systematic Assessment |
| ||
| Bundle branch block left | Cardiac disorders | Systematic Assessment |
| ||
| Cardiac failure | Cardiac disorders | Systematic Assessment |
| ||
| Coronary artery disease | Cardiac disorders | Systematic Assessment |
| ||
| Sick sinus syndrome | Cardiac disorders | Systematic Assessment |
| ||
| Ventricular arrhythmia | Cardiac disorders | Systematic Assessment |
| ||
| Osteoarthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Joint swelling | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Hydronephrosis | Renal and urinary disorders | Systematic Assessment |
| ||
| Renal failure | Renal and urinary disorders | Systematic Assessment |
| ||
| Renal failure acute | Renal and urinary disorders | Systematic Assessment |
| ||
| Renal impairment | Renal and urinary disorders | Systematic Assessment |
| ||
| Chest pain | General disorders | Systematic Assessment |
| ||
| Asthenia | General disorders | Systematic Assessment |
| ||
| Pyrexia | General disorders | Systematic Assessment |
| ||
| Oxygen saturation decreased | Investigations | Systematic Assessment |
| ||
| Esophageal injury | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Postprocedural hematuria | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Road traffic accident | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Upper limb fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Accelerated hypertension | Vascular disorders | Systematic Assessment |
| ||
| Deep vein thrombosis | Vascular disorders | Systematic Assessment |
| ||
| Granulomatosis with polyangiitis | Vascular disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Abominable pain upper | Gastrointestinal disorders | Systematic Assessment |
| ||
| Colitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diverticulum intestinal | Gastrointestinal disorders | Systematic Assessment |
| ||
| Pancreatitis acute | Gastrointestinal disorders | Systematic Assessment |
| ||
| Small intestinal obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diabetic foot | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain | General disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Malaise | Nervous system disorders | Systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
bioCSL agreements and restrictions on publishing may vary with individual investigators; however, bioCSL will not prohibit any investigator from publishing. bioCSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
(Note: bioCSL was previously known as CSL Biotherapies; bioCSL QIV & TIV were called CSL QIV & TIV in the original protocol)
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Seqirus Clinical Trial Disclosure Lead | Seqirus | Seqirus.ClinicalTrials@Seqirus.com |
| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
Not provided
Not provided
| 50 to 64 years |
|
| 65 to 74 years |
|
| => 75 years |
|
| Male |
|
| B/Yamagata |
|
| B/Victoria |
|
| 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. | GMT ratio (A/H3N2) | 0.93 | 2-Sided | 95 | 0.88 | 0.98 | Non-Inferiority or Equivalence | The non-inferiority criterion for the GMT ratio was that the upper bound of two-sided 95% CI on the ratio of Pooled TIV (for A strains) or TIV-1 (B Yamagata) or TIV-2 (B Victoria)/ bioCSL QIV should not exceed 1.5. |
| 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. | GMT ratio (B/YAM) | 0.87 | 2-Sided | 95 | 0.81 | 0.93 | Non-Inferiority or Equivalence | The non-inferiority criterion for the GMT ratio was that the upper bound of two-sided 95% CI on the ratio of Pooled TIV (for A strains) or TIV-1 (B Yamagata) or TIV-2 (B Victoria)/ bioCSL QIV should not exceed 1.5. |
| 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. | GMT ratio (B/VIC) | 0.94 | 2-Sided | 95 | 0.86 | 1.01 | Non-Inferiority or Equivalence | The non-inferiority criterion for the GMT ratio was that the upper bound of two-sided 95% CI on the ratio of Pooled TIV (for A strains) or TIV-1 (B Yamagata) or TIV-2 (B Victoria)/ bioCSL QIV should not exceed 1.5. |
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
| OG002 | GMT: bioCSL QIV (≥ 65 Years) | Postvaccination GMT. bioCSL QIV, n=856. |
| OG003 | GMT: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | Postvaccination GMT. Pooled TIV (A strains), n=859 TIV-1 (B/YAM), n=430. TIV-2 (B/VIC), n=429. |
|
|
|
| OG002 | SCR: bioCSL QIV (≥ 65 Years) | bioCSL TIV-1 and bioCSL TIV-2 are pooled for analysis of the A strains. For B/Yamagata TIV=TIV-1, for B/Victoria TIV=TIV-2. bioCSL QIV, n=856. Pooled TIV (A strains), n=859. TIV-1 (B Yamagata), n=430. TIV-2 (B Victoria), n=429. |
| OG003 | SCR: Pooled TIV (A Strains) or TIV-1 or TIV-2 (≥ 65 Years) | bioCSL TIV-1 and bioCSL TIV-2 are pooled for analysis of the A strains. For B/Yamagata TIV=TIV-1, for B/Victoria TIV=TIV-2. bioCSL QIV, n=856. Pooled TIV (A strains), n=859. TIV-1 (B Yamagata), n=430. TIV-2 (B Victoria), n=429. |
|
|
|
|
|
|
For B/Yamagata TIV=TIV-1, for B/Victoria TIV=TIV-2. B/Yamagata serology for TIV-2 (B Victoria), Adults 18 years and older, n=850. B/Victoria serology for TIV-1 (B Yamagata), Adults 18 years and older, n=854. B/Yamagata serology for TIV-2 (B Victoria), Adults 18 to <65 years, n=421. B/Victoria serology for TIV-1 (B Yamagata), Adults 18 years to <65 years, n=424. B/Yamagata serology for TIV-2 (B Victoria), Adults 65 years and older, n=429. B/Victoria serology for TIV-1 (B Yamagata), Adults 65 years and older, n=430. |
|
|
|
| OG005 |
| bioCSL TIV-2 (B/VIC) (≥ 65 Years) |
|
|
| OG005 | bioCSL TIV-1 (B/VIC) (≥ 65 Years) |
|
|
| OG005 | bioCSL TIV-1 (B/VIC) (≥ 65 Years) |
|
|
| OG005 | bioCSL TIV-1 (B/VIC) (≥ 65 Years) |
|
|
| OG002 | 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). Trivalent Influenza Vaccine (TIV-2): One 0.5 mL intramuscular dose into the deltoid muscle. |
|
|
| 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). Trivalent Influenza Vaccine (TIV-2): One 0.5 mL intramuscular dose into the deltoid muscle. |
|
|
| OG002 | 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). Trivalent Influenza Vaccine (TIV-2): One 0.5 mL intramuscular dose into the deltoid muscle. |
|
|
| OG002 |
| 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). Trivalent Influenza Vaccine (TIV-2): One 0.5 mL intramuscular dose into the deltoid muscle. |
|
|