Influenza, Human
Conditions
Brief summary
This is a study to assess the immune (antibody) response and safety of a Seqirus split virion, inactivated Quadrivalent Influenza Vaccine (Seqirus QIV), in comparison with a US licensed 2016/2017 Quadrivalent Influenza Vaccine (comparator QIV) in a healthy pediatric population 6 months through 59 months of age.
Interventions
BIOLOGICALSeqirus Quadrivalent Inactivated Influenza Vaccine
The Seqirus study vaccine is a sterile, thimerosal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2016/2017 influenza season). Subjects will receive one or two doses according to the recommendations of the Advisory Committee on Immunization Practices for the United States 2016-17 Influenza Season. Preferred sites for intramuscular injection are the anterolateral aspect of the thigh in infants 6 months through 11 months of age, the anterolateral aspect of the thigh (or the deltoid muscle of the arm if muscle mass is adequate) in children 12 months through 35 months of age.
BIOLOGICALComparator Quadrivalent Inactivated Influenza Vaccine
The comparator Quadrivalent Inactivated Influenza vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2016/2017 influenza season. Subjects will receive one or two doses according to the recommendations of the Advisory Committee on Immunization Practices for the United States 2016-17 Influenza Season. Preferred sites for intramuscular injection of the non-dominant arm in children 36 months through 59 months of age.
Sponsors
Seqirus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 59 Months
Healthy volunteers
Yes
Inclusion criteria
* Male or female subject 6 months through to 59 months of age at the time of first vaccination and born between 36 and 42 weeks of gestation; * Parent or legally acceptable representative able to provide written informed consent and be willing and able to adhere to all protocol requirements including blood draws. * Subject is in generally good health as per the Investigator's medical judgment
Exclusion criteria
* History of allergic reactions to egg proteins or any components of the Study Vaccines; * History of serious adverse reactions to any influenza vaccines; * History of Guillain-Barré syndrome or other demyelinating disease such as encephalomyelitis and transverse myelitis; * History of licensed or investigational influenza vaccination in the last 6 months; * Clinical signs of active infection and/or an axillary temperature of ≥ 99.5°F / (≥ 37.5 °C) on the day of vaccination or within 48 hours preceding vaccination. * Current or recent, acute or chronic medical conditions that in the opinion of the Investigator are clinically significant and/or unstable * History of any seizures, with the exception of a single febrile seizure; * Self-reported or known seropositivity suggestive of acute or chronic viral infection for human immunodeficiency virus, hepatitis B or hepatitis C; * Known or suspected congenital or acquired immunosuppressive conditions; * Current or recent immunosuppressive or immunomodulatory therapy * Current or medical history of malignant neoplasms; * Administration of immunoglobulin and/or any blood products within the previous 90 days preceding the administration of the Study Vaccine or planned administration during the study; * Participation in a clinical trial or use of an investigational compound within 28 days prior to or 28 days after receiving the Study Vaccine, or plans to enter a study during this period; * Vaccination with a licensed vaccine 21 days (for live or inactivated vaccines) prior to receiving the Study Vaccine, or plans to receive any licensed vaccine prior to the Study Exit Visit. * Medical conditions or treatment contraindicating intramuscular vaccination due to increased risk of bleeding. * Family members of the employees of the Investigator or study center with direct involvement in the study, or with other clinical studies under the direction of that Investigator or study center.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | Postvaccination (28 days after last vaccination) | Noninferiority of Seqirus QIV compared to comparator QIV was assessed by hemagglutination inhibition (HI) antibody geometric mean titer (GMT) for each viral strain included in the vaccines. The GMT ratio is defined as the geometric mean of the postvaccination HI titer for the US-licensed comparator QIV over the geometric mean of the postvaccination HI titer for Seqirus QIV. B/VIC = B/Victoria B/YAM = B/Yamagata |
| The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | Postvaccination (28 days after last vaccination) | Noninferiority of Seqirus QIV compared to comparator QIV will be assessed by seroconversion rate (SCR) for each viral strain. SCR is 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. For the SCR comparison, the difference between the SCR for each vaccine (for each strain) will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Unsolicited AEs | Postvaccination (up to 28 days after vaccination) | Frequency and severity of unsolicited AEs for at least 28 days after each vaccination dose |
| Number of Participants With Serious Adverse Events (SAE) | 180 days after the last vaccination dose. | Frequency of SAEs for 180 days after the last vaccination dose. SAE = serious adverse events, AESI = adverse event of special interest |
| Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | 28 days after last vaccination. | The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate geometric mean of HI titers prevaccination & postvaccination. |
| Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Postvaccination (up to 7 days after vaccination) | Frequency and severity of solicited local adverse reactions and systemic AEs for 7 days after each vaccination dose |
| Seroprotection Rates of Each Virus Strain | 28 days after last vaccination. | The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate the percentage of subjects with a titer ≥40 (seroprotection rates) at Day 1 and at Study Exit Visit. |
| Geometric Mean Fold Increase (GMFI) of Each Virus Strain | Prevaccination (Day 1) and Postvaccination (28 days after last vaccination) | The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate GMFIs, defined as the geometric mean fold titer change (rise) from Day 1 to Study Exit Visit. |
| Seroconversion Rates (SCRs) of Each Virus Strain | 28 days after last vaccination | The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate SCRs defined as the % 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 postvaccination titer. |
| Number of Participants With Cellulitis-like Reactions | Postvaccination (up to 28 days after each vaccination) | Frequency of cellulitis-like reactions for at least 28 days after each vaccination dose |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from 27 September 2016 to 11 August 2017 from 39 study sites in the United States of America.
Pre-assignment details
A total of 2339 subjects were screened. A total of 2250 subjects were randomized to study treatment. Due to not having valid informed consent, 3 subjects were removed from the clinical database. Therefore, overall 2247 subjects gave informed consent and were included in the analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Seqirus QIV Subjects 6 months through 59 months of age who received Seqirus Quadrivalent Inactivated Influenza Vaccine. | 1,684 |
| Comparator QIV Subjects 6 months through 59 months of age who received Comparator Quadrivalent Inactivated Influenza Vaccine. | 563 |
| Total | 2,247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Excluded due to invalid informed consent | 3 | 0 |
| Overall Study | Lost to Follow-up | 84 | 29 |
| Overall Study | Other | 4 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 26 | 10 |
Baseline characteristics
| Characteristic | Seqirus QIV | Comparator QIV | Total |
|---|---|---|---|
| Age, Continuous | 36.6 months STANDARD_DEVIATION 14.7 | 36.5 months STANDARD_DEVIATION 14.68 | 36.6 months STANDARD_DEVIATION 14.69 |
| Age, Customized 36 through 59 months | 984 Participants | 328 Participants | 1312 Participants |
| Age, Customized 6 through 35 months | 700 Participants | 235 Participants | 935 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 434 Participants | 160 Participants | 594 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1243 Participants | 400 Participants | 1643 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 3 Participants | 10 Participants |
| Prevaccination Axillary Temperature | 97.17 °F STANDARD_DEVIATION 0.963 | 97.25 °F STANDARD_DEVIATION 0.935 | 97.19 °F STANDARD_DEVIATION 0.936 |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 10 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 361 Participants | 123 Participants | 484 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 13 Participants | 3 Participants | 16 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 85 Participants | 34 Participants | 119 Participants |
| Race (NIH/OMB) White | 1205 Participants | 391 Participants | 1596 Participants |
| Region of Enrollment United States | 1684 Participants | 563 Participants | 2247 Participants |
| Sex: Female, Male Female | 820 Participants | 268 Participants | 1088 Participants |
| Sex: Female, Male Male | 864 Participants | 295 Participants | 1159 Participants |
| Vaccination against influenza 2015/2016 season | 845 Participants | 294 Participants | 1139 Participants |
| Weight | 15.36 kilograms STANDARD_DEVIATION 4.224 | 15.40 kilograms STANDARD_DEVIATION 4.149 | 15.37 kilograms STANDARD_DEVIATION 4.205 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,673 | 0 / 559 |
| other Total, other adverse events | 320 / 1,673 | 80 / 559 |
| serious Total, serious adverse events | 11 / 1,673 | 3 / 559 |
Outcome results
Primary
The Difference in Seroconversion Rate (SCR) for Each Virus Strain.
Noninferiority of Seqirus QIV compared to comparator QIV will be assessed by seroconversion rate (SCR) for each viral strain. SCR is 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. For the SCR comparison, the difference between the SCR for each vaccine (for each strain) will be determined.
Time frame: Postvaccination (28 days after last vaccination)
Population: The Per-Protocol Population comprised all subjects in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Seqirus QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | A/H1N1 | 79.1 Percentage of participants |
| Seqirus QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | A/H3N2 | 82.3 Percentage of participants |
| Seqirus QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | B/YAM | 38.9 Percentage of participants |
| Seqirus QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | B/VIC | 60.2 Percentage of participants |
| Comparator QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | B/VIC | 61.1 Percentage of participants |
| Comparator QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | A/H1N1 | 68.8 Percentage of participants |
| Comparator QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | B/YAM | 41.9 Percentage of participants |
| Comparator QIV | The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | A/H3N2 | 84.9 Percentage of participants |
Comparison: Non-inferiority of immune responses to A/H1N1 vaccine strain measured in terms of Seroconversion Rate Difference 28 days after the last vaccination95% CI: [-15.4, -5.1]
Comparison: Non-inferiority of immune responses to A/H3N2 vaccine strain measured in terms of Seroconversion Rate Difference 28 days after the last vaccination95% CI: [-2.54, 7.8]
Comparison: Non-inferiority of immune responses to B/YAM vaccine strain measured in terms of Seroconversion Rate Difference 28 days after the last vaccination95% CI: [-2.1, 8.2]
Comparison: Non-inferiority of immune responses to B/VIC vaccine strain measured in terms of Seroconversion Rate Difference 28 days after the last vaccination95% CI: [-4.2, 6.1]
Primary
The Geometric Mean Titer (GMT) Ratio of Each Virus Strain.
Noninferiority of Seqirus QIV compared to comparator QIV was assessed by hemagglutination inhibition (HI) antibody geometric mean titer (GMT) for each viral strain included in the vaccines. The GMT ratio is defined as the geometric mean of the postvaccination HI titer for the US-licensed comparator QIV over the geometric mean of the postvaccination HI titer for Seqirus QIV. B/VIC = B/Victoria B/YAM = B/Yamagata
Time frame: Postvaccination (28 days after last vaccination)
Population: The Per-Protocol Population (PPS) comprised all subjects in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Seqirus QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | A/H1N1 | 370.0 Geometric Mean Titer |
| Seqirus QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | A/H3N2 | 436.8 Geometric Mean Titer |
| Seqirus QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | B/YAM | 25.5 Geometric Mean Titer |
| Seqirus QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | B/VIC | 56.8 Geometric Mean Titer |
| Comparator QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | B/VIC | 57.9 Geometric Mean Titer |
| Comparator QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | A/H1N1 | 311.7 Geometric Mean Titer |
| Comparator QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | B/YAM | 29.7 Geometric Mean Titer |
| Comparator QIV | The Geometric Mean Titer (GMT) Ratio of Each Virus Strain. | A/H3N2 | 589.1 Geometric Mean Titer |
Comparison: Non-inferiority of immune responses to A/H1N1 vaccine strain measured in terms of Geometric Mean Titer ratios 28 days after the last vaccination95% CI: [0.72, 0.88]
Comparison: Non-inferiority of immune responses to A/H3N2 vaccine strain measured in terms of Geometric Mean Titer ratios 28 days after the last vaccination95% CI: [1.15, 1.42]
Comparison: Non-inferiority of immune responses to B/YAM vaccine strain measured in terms of Geometric Mean Titer ratios 28 days after the last vaccination95% CI: [1.01, 1.24]
Comparison: Non-inferiority of immune responses to B/VIC vaccine strain measured in terms of Geometric Mean Titer ratios 28 days after the last vaccination95% CI: [0.86, 1.09]
Secondary
Geometric Mean Fold Increase (GMFI) of Each Virus Strain
The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate GMFIs, defined as the geometric mean fold titer change (rise) from Day 1 to Study Exit Visit.
Time frame: Prevaccination (Day 1) and Postvaccination (28 days after last vaccination)
Population: The Per-Protocol Population comprised all subjects in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Seqirus QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H1N1 | 13.4 Fold Change |
| Seqirus QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H3N2 | 13.0 Fold Change |
| Seqirus QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/YAM | 2.6 Fold Change |
| Seqirus QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/VIC | 5.6 Fold Change |
| Comparator QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H3N2 | 12.5 Fold Change |
| Comparator QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/VIC | 7.5 Fold Change |
| Comparator QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H1N1 | 9.7 Fold Change |
| Comparator QIV | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/YAM | 4.5 Fold Change |
| Comparator QIV Cohort A | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/YAM | 2.8 Fold Change |
| Comparator QIV Cohort A | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/VIC | 4.6 Fold Change |
| Comparator QIV Cohort A | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H1N1 | 11.3 Fold Change |
| Comparator QIV Cohort A | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H3N2 | 15.1 Fold Change |
| Comparator QIV Cohort B | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/VIC | 8.2 Fold Change |
| Comparator QIV Cohort B | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H1N1 | 6.8 Fold Change |
| Comparator QIV Cohort B | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | A/H3N2 | 16.0 Fold Change |
| Comparator QIV Cohort B | Geometric Mean Fold Increase (GMFI) of Each Virus Strain | B/YAM | 5.3 Fold Change |
Secondary
Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain
The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate geometric mean of HI titers prevaccination & postvaccination.
Time frame: 28 days after last vaccination.
Population: The Per-Protocol Population comprised all subjects in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Prevaccination | 13.8 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Postvaccination | 184.9 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Prevaccination | 14.3 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Postvaccination | 184.9 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Prevaccination | 5.9 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Postvaccination | 15.6 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Prevaccination | 7.1 Titers |
| Seqirus QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Postvaccination | 39.8 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Postvaccination | 35.4 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Prevaccination | 7.9 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Postvaccination | 590.2 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Postvaccination | 72.1 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Prevaccination | 9.6 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Postvaccination | 778.6 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Prevaccination | 62.4 Titers |
| Comparator QIV | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Prevaccination | 60.7 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Prevaccination | 6.9 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Prevaccination | 16.4 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Postvaccination | 247.5 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Prevaccination | 5.8 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Postvaccination | 16.3 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Postvaccination | 31.9 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Prevaccination | 14.9 Titers |
| Comparator QIV Cohort A | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Postvaccination | 168.3 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Prevaccination | 65.5 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H3N2, Postvaccination | 1047 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Postvaccination | 469.2 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | A/H1N1, Prevaccination | 68.7 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Prevaccination | 8.3 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Postvaccination | 85.9 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/VIC, Prevaccination | 10.4 Titers |
| Comparator QIV Cohort B | Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain | B/YAM, Postvaccination | 44.1 Titers |
Secondary
Number of Participants With Cellulitis-like Reactions
Frequency of cellulitis-like reactions for at least 28 days after each vaccination dose
Time frame: Postvaccination (up to 28 days after each vaccination)
Population: The Solicited Safety Population comprises all subjects in the FAS who received at least one dose or partial dose of Study Vaccine and had provided any evaluable data on solicited events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seqirus QIV | Number of Participants With Cellulitis-like Reactions | 0 Participants |
| Comparator QIV | Number of Participants With Cellulitis-like Reactions | 1 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAE)
Frequency of SAEs for 180 days after the last vaccination dose. SAE = serious adverse events, AESI = adverse event of special interest
Time frame: 180 days after the last vaccination dose.
Population: The Overall Safety Population was used for the analysis of overall and unsolicited adverse event safety and comprised all subjects in the FAS who received at least one dose or partial dose of Study Vaccine and have provided any evaluable follow-up safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Seqirus QIV | Number of Participants With Serious Adverse Events (SAE) | SAEs (Day 1 to Day 28) | 4 Participants |
| Seqirus QIV | Number of Participants With Serious Adverse Events (SAE) | SAEs (Day 29 to Final Database Lock) | 7 Participants |
| Seqirus QIV | Number of Participants With Serious Adverse Events (SAE) | Related SAEs | 0 Participants |
| Seqirus QIV | Number of Participants With Serious Adverse Events (SAE) | Deaths | 0 Participants |
| Seqirus QIV | Number of Participants With Serious Adverse Events (SAE) | AESIs (Day 1 to Day 28) | 0 Participants |
| Seqirus QIV | Number of Participants With Serious Adverse Events (SAE) | AESIs (Day 29 to Final Database Lock) | 2 Participants |
| Comparator QIV | Number of Participants With Serious Adverse Events (SAE) | AESIs (Day 1 to Day 28) | 0 Participants |
| Comparator QIV | Number of Participants With Serious Adverse Events (SAE) | SAEs (Day 1 to Day 28) | 0 Participants |
| Comparator QIV | Number of Participants With Serious Adverse Events (SAE) | Deaths | 0 Participants |
| Comparator QIV | Number of Participants With Serious Adverse Events (SAE) | SAEs (Day 29 to Final Database Lock) | 3 Participants |
| Comparator QIV | Number of Participants With Serious Adverse Events (SAE) | AESIs (Day 29 to Final Database Lock) | 0 Participants |
| Comparator QIV | Number of Participants With Serious Adverse Events (SAE) | Related SAEs | 0 Participants |
Secondary
Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE)
Frequency and severity of solicited local adverse reactions and systemic AEs for 7 days after each vaccination dose
Time frame: Postvaccination (up to 7 days after vaccination)
Population: The Solicited Safety Population comprises all subjects in the Full Analysis Set (FAS) who received at least one dose or partial dose of Study Vaccine and had provided any evaluable data on solicited events.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Seqirus QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Any | 940 Participants |
| Seqirus QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Grade 1 | 592 Participants |
| Seqirus QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Grade 2 | 277 Participants |
| Seqirus QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Grade 3 | 71 Participants |
| Seqirus QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Local | 645 Participants |
| Seqirus QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Systemic | 633 Participants |
| Comparator QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Local | 208 Participants |
| Comparator QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Any | 312 Participants |
| Comparator QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Grade 3 | 39 Participants |
| Comparator QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Grade 1 | 189 Participants |
| Comparator QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Systemic | 215 Participants |
| Comparator QIV | Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE) | Solicited AEs, Grade 2 | 83 Participants |
Secondary
Number of Participants With Unsolicited AEs
Frequency and severity of unsolicited AEs for at least 28 days after each vaccination dose
Time frame: Postvaccination (up to 28 days after vaccination)
Population: The Overall Safety Population was used for the analysis of overall and unsolicited adverse event safety and comprised all subjects in the FAS who received at least one dose or partial dose of Study Vaccine and have provided any evaluable follow-up safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Seqirus QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Any | 536 Participants |
| Seqirus QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Grade 1 | 285 Participants |
| Seqirus QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Grade 2 | 206 Participants |
| Seqirus QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Grade 3 | 45 Participants |
| Comparator QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Grade 3 | 14 Participants |
| Comparator QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Any | 171 Participants |
| Comparator QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Grade 2 | 65 Participants |
| Comparator QIV | Number of Participants With Unsolicited AEs | Unsolicited AEs, Grade 1 | 92 Participants |
Secondary
Seroconversion Rates (SCRs) of Each Virus Strain
The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate SCRs defined as the % 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 postvaccination titer.
Time frame: 28 days after last vaccination
Population: The Per-Protocol Population comprised all subjects in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Seqirus QIV | Seroconversion Rates (SCRs) of Each Virus Strain | A/H1N1 | 81.9 Percentage of participants |
| Seqirus QIV | Seroconversion Rates (SCRs) of Each Virus Strain | A/H3N2 | 82.4 Percentage of participants |
| Seqirus QIV | Seroconversion Rates (SCRs) of Each Virus Strain | B/YAM | 22.5 Percentage of participants |
| Seqirus QIV | Seroconversion Rates (SCRs) of Each Virus Strain | B/VIC | 52.9 Percentage of participants |
| Comparator QIV | Seroconversion Rates (SCRs) of Each Virus Strain | A/H3N2 | 82.2 Percentage of participants |
| Comparator QIV | Seroconversion Rates (SCRs) of Each Virus Strain | B/YAM | 49.9 Percentage of participants |
| Comparator QIV | Seroconversion Rates (SCRs) of Each Virus Strain | B/VIC | 65.1 Percentage of participants |
| Comparator QIV | Seroconversion Rates (SCRs) of Each Virus Strain | A/H1N1 | 77.1 Percentage of participants |
| Comparator QIV Cohort A | Seroconversion Rates (SCRs) of Each Virus Strain | B/YAM | 26.9 Percentage of participants |
| Comparator QIV Cohort A | Seroconversion Rates (SCRs) of Each Virus Strain | A/H3N2 | 85.0 Percentage of participants |
| Comparator QIV Cohort A | Seroconversion Rates (SCRs) of Each Virus Strain | B/VIC | 49.7 Percentage of participants |
| Comparator QIV Cohort A | Seroconversion Rates (SCRs) of Each Virus Strain | A/H1N1 | 80.3 Percentage of participants |
| Comparator QIV Cohort B | Seroconversion Rates (SCRs) of Each Virus Strain | B/VIC | 68.6 Percentage of participants |
| Comparator QIV Cohort B | Seroconversion Rates (SCRs) of Each Virus Strain | A/H3N2 | 84.9 Percentage of participants |
| Comparator QIV Cohort B | Seroconversion Rates (SCRs) of Each Virus Strain | A/H1N1 | 61.2 Percentage of participants |
| Comparator QIV Cohort B | Seroconversion Rates (SCRs) of Each Virus Strain | B/YAM | 51.9 Percentage of participants |
Secondary
Seroprotection Rates of Each Virus Strain
The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate the percentage of subjects with a titer ≥40 (seroprotection rates) at Day 1 and at Study Exit Visit.
Time frame: 28 days after last vaccination.
Population: The Per-Protocol Population comprised all subjects in the Evaluable Population who did not have any protocol deviations that were medically assessed as potentially impacting on immunogenicity results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Seqirus QIV | Seroprotection Rates of Each Virus Strain | A/H1N1 | 90.1 Percentage of participants |
| Seqirus QIV | Seroprotection Rates of Each Virus Strain | A/H3N2 | 92.5 Percentage of participants |
| Seqirus QIV | Seroprotection Rates of Each Virus Strain | B/YAM | 24.7 Percentage of participants |
| Seqirus QIV | Seroprotection Rates of Each Virus Strain | B/VIC | 55.6 Percentage of participants |
| Comparator QIV | Seroprotection Rates of Each Virus Strain | A/H3N2 | 98.4 Percentage of participants |
| Comparator QIV | Seroprotection Rates of Each Virus Strain | B/YAM | 57.1 Percentage of participants |
| Comparator QIV | Seroprotection Rates of Each Virus Strain | B/VIC | 71.0 Percentage of participants |
| Comparator QIV | Seroprotection Rates of Each Virus Strain | A/H1N1 | 99.1 Percentage of participants |
| Comparator QIV Cohort A | Seroprotection Rates of Each Virus Strain | B/YAM | 29.0 Percentage of participants |
| Comparator QIV Cohort A | Seroprotection Rates of Each Virus Strain | A/H3N2 | 95.3 Percentage of participants |
| Comparator QIV Cohort A | Seroprotection Rates of Each Virus Strain | B/VIC | 52.8 Percentage of participants |
| Comparator QIV Cohort A | Seroprotection Rates of Each Virus Strain | A/H1N1 | 88.6 Percentage of participants |
| Comparator QIV Cohort B | Seroprotection Rates of Each Virus Strain | B/VIC | 75.3 Percentage of participants |
| Comparator QIV Cohort B | Seroprotection Rates of Each Virus Strain | A/H3N2 | 98.6 Percentage of participants |
| Comparator QIV Cohort B | Seroprotection Rates of Each Virus Strain | A/H1N1 | 98.3 Percentage of participants |
| Comparator QIV Cohort B | Seroprotection Rates of Each Virus Strain | B/YAM | 61.5 Percentage of participants |