Human, Influenza, Virus Diseases
Conditions
Keywords
Influenza, RNA Virus, WHO Strains
Brief summary
This phase 3 clinical study is a randomized, observer-blind, comparator-controlled, multicenter study of QIVc versus a US-licensed comparator QIV in children 6 months through 47 months of age. The purpose of this study is to demonstrate that vaccination with QIVc elicits an immune response that is noninferior to that of a US-licensed comparator QIV containing the same virus strains, in children 6 months through 47 months of age.
Interventions
BIOLOGICALQIVc
Previously vaccinated subjects received a 0.5 mL intramuscular dose of QIVc on Day 1; not previously vaccinated subjects received a 0.5 mL intramuscular dose of QIVc on Day 1 and Day 29.
BIOLOGICALComparator QIV
Previously vaccinated subjects received a dose of Comparator QIV on Day 1; not previously vaccinated subjects received a dose of Comparator QIV on Day 1 and Day 29. Subjects 6 months through 35 months of age received a 0.25 mL intramuscular dose of Comparator QIV; subjects 36 months through 47 months of age received a 0.5 mL intramuscular dose of Comparator QIV.
Sponsors
Seqirus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The trial is designed as an observer-blind study. During the treatment period of the study designated unblinded nurse(s), physician(s), or other qualified health care professional will be responsible for administering the study vaccine to the subjects.
Eligibility
Sex/Gender
ALL
Age
6 Months to 47 Months
Healthy volunteers
Yes
Inclusion criteria
* Individuals of 6 through 47 months of age on the day of informed consent. * Individuals whose parent(s)/Legally Acceptable Representative (LAR) have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. * Individuals who can comply with study procedures including follow-up * Individual is in generally good health as per the Investigator's medical judgement
Exclusion criteria
* Acute (severe) febrile illness * History of any anaphylaxis, serious vaccine reactions or hypersensitivity, including allergic reactions, to any component of vaccine or medical equipment whose use is foreseen in this study * A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis * Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study * Received influenza vaccination or has had documented influenza disease in the last 6 months prior to informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | Day 29 for previously vaccinated subjects; Day 57 for not previously vaccinated subjects | The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) HAI titer for the Comparator QIV divided by the geometric mean of the postvaccination HAI titer for QIVc. |
| Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | The SCR is defined as the percentage of subjects with either a prevaccination HAI titer \<1:10 and a postvaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in postvaccination HAI titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR. |
| Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by Microneutralization (MN) Assay Using Cell-derived Target Viruses | Day 29 for previously vaccinated subjects; Day 57 for not previously vaccinated subjects | The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) MN titer for the Comparator QIV divided by the geometric mean of the postvaccination MN titer for QIVc. |
| Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | The SCR is defined as the percentage of subjects with either a prevaccination MN titer \<1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | GMR is defined as the geometric mean of the (within-subject) fold increase in serum HAI GMT postvaccination (Day 29/57) compared to prevaccination (Day 1). |
| Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | GMR is defined as the geometric mean of the (within-subject) fold increase in serum MN GMT postvaccination (Day 29/57) compared to prevaccination (Day 1). |
| Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | GMR is defined as the geometric mean of the (within-subject) fold increase in serum MN GMT postvaccination (Day 29/57) compared to prevaccination (Day 1). |
| Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects | The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) HAI titer for the Comparator QIV divided by the geometric mean of the postvaccination HAI titer for QIVc. |
| Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | The percentage of subjects with at least one unsolicited AE from Day 1 to Day 29 for previously vaccinated subjects and from Day 1 to Day 57 for not previously vaccinated subjects. Related AEs = considered at least possibly related to study vaccination by the investigator; Severity = based on the greatest severity associated with a preferred term for a reported AE. |
| Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | Day 1 to Day 181 for previously vaccinated subjects; Day 1 to Day 209 for not previously vaccinated subjects | The percentage of subjects with any SAE, NOCD or AE leading to withdrawal during the study period from Day 1 to Day 181 for previously vaccinated subjects or from Day 1 to Day 209 for not previously vaccinated subjects. Definitions: SAEs = AEs defined as any untoward medical occurrence that at any dose resulted in one or more of the following: 1. Death, 2. Life-threatening 3. Required/prolonged hospitalization 4. Persistent or significant disability/incapacity 5. congenital anomaly/or birth defect 6. An important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based on appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above |
| Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Day 1 to Day 7 after each vaccination (Day 1 to Day 7 for previously vaccinated subjects; Day 1 to Day 7 and Day 29 to Day 35 for not previously vaccinated subjects) | The percentage of subjects with at least one solicited AE Day 1 through Day 7 after any study vaccination. |
| Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | The SCR is defined as the percentage of subjects with either a prevaccination HAI titer \<1:10 and a postvaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in postvaccination HAI titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR. |
| Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects | The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) MN titer for the Comparator QIV divided by the geometric mean of the postvaccination MN titer for QIVc. |
| Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects | The SCR is defined as the percentage of subjects with either a prevaccination MN titer \<1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled in the 2019/2020 Northern Hemisphere influenza season from 47 centers in the United States.
Pre-assignment details
In total, 2414 subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| QIVc Cell-derived Quadrivalent Influenza Vaccine containing 2 influenza type A strains and 2 influenza type B strains | 1,597 |
| Comparator QIV Comparator Quadrivalent Influenza Vaccine containing 2 influenza type A strains and 2 influenza type B strains | 805 |
| Total | 2,402 |
Baseline characteristics
| Characteristic | QIVc | Comparator QIV | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1597 Participants | 805 Participants | 2402 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 28.1 months STANDARD_DEVIATION 11.54 | 28.2 months STANDARD_DEVIATION 11.63 | 28.1 months STANDARD_DEVIATION 11.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 434 Participants | 226 Participants | 660 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1160 Participants | 575 Participants | 1735 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 8 Participants | 21 Participants |
| Race/Ethnicity, Customized Black or African American | 455 Participants | 209 Participants | 664 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 71 Participants | 32 Participants | 103 Participants |
| Race/Ethnicity, Customized White | 1039 Participants | 539 Participants | 1578 Participants |
| Region of Enrollment United States | 1597 Participants | 805 Participants | 2402 Participants |
| Sex: Female, Male Female | 794 Participants | 399 Participants | 1193 Participants |
| Sex: Female, Male Male | 803 Participants | 406 Participants | 1209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 1,597 | 0 / 805 |
| other Total, other adverse events | 926 / 1,597 | 490 / 805 |
| serious Total, serious adverse events | 15 / 1,597 | 7 / 805 |
Outcome results
Primary
Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses
The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) HAI titer for the Comparator QIV divided by the geometric mean of the postvaccination HAI titer for QIVc.
Time frame: Day 29 for previously vaccinated subjects; Day 57 for not previously vaccinated subjects
Population: Per Protocol Set (PPS): All subjects in the FAS who received vaccine on Day 1, provided serology specimens which yielded valid serology assay results from both Day 1 and Day 29 (previously vaccinated subjects) or Day 1 and Day 57 (not previously vaccinated subjects) and for whom there was no protocol deviation that was medically assessed as having potential to impact the immunogenicity results.~1092 and 575 subjects in the QIVc and Comparator QIV groups had HAI assay data for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | A/H1N1 | 78.0 Titer |
| QIVc | Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | B/Yamagata | 35.6 Titer |
| QIVc | Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | B/Victoria | 22.4 Titer |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | A/H1N1 | 57.3 Titer |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | B/Yamagata | 26.0 Titer |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses | B/Victoria | 19.6 Titer |
Comparison: Non-inferiority, A/H1N1, GMT ratio, Day 29/57~Non-inferiority of the Day 29/57 immune response to the A/H1N1 vaccine strain calculated by GMT ratio (Comparator QIV GMT divided by QIVc GMT)95% CI: [0.645, 0.836]
Comparison: Non-inferiority, B/Yamagata, GMT ratio, Day 29/57~Non-inferiority of the Day 29/57 immune response to the B/Yamagata vaccine strain calculated by GMT ratio (Comparator QIV GMT divided by QIVc GMT)95% CI: [0.656, 0.809]
Comparison: Non-inferiority, B/Victoria, GMT ratio, Day 29/57~Non-inferiority of the Day 29/57 immune response to the B/Victoria vaccine strain calculated by GMT ratio (Comparator QIV GMT divided by QIVc GMT)95% CI: [0.791, 0.972]
Primary
Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by Microneutralization (MN) Assay Using Cell-derived Target Viruses
The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) MN titer for the Comparator QIV divided by the geometric mean of the postvaccination MN titer for QIVc.
Time frame: Day 29 for previously vaccinated subjects; Day 57 for not previously vaccinated subjects
Population: PPS (1078 and 572 subjects in the QIVc and Comparator QIV groups, respectively, had MN assay data for this outcome)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by Microneutralization (MN) Assay Using Cell-derived Target Viruses | 23.1 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by Microneutralization (MN) Assay Using Cell-derived Target Viruses | 23.9 Titer |
Comparison: Non-inferiority, A/H3N2, GMT ratio, Day 29/57~Non-inferiority of the Day 29/57 immune response to the A/H3N2 vaccine strain calculated by GMT ratio (Comparator QIV GMT divided by QIVc GMT)95% CI: [0.927, 1.16]
Primary
Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived Target Viruses
The SCR is defined as the percentage of subjects with either a prevaccination MN titer \<1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (1078 and 572 subjects in the QIVc and Comparator QIV groups, respectively, had MN assay data for this outcome)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QIVc | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived Target Viruses | 27.64 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived Target Viruses | 30.77 Percentage of participants |
Comparison: Non-inferiority, A/H3N2, SCR difference, Day 29/57~Non-inferiority of the immune response to the A/H3N2 vaccine strain by SCR difference (Comparator QIV SCR minus QIVc SCR)95% CI: [-1.443, 7.812]
Primary
Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses
The SCR is defined as the percentage of subjects with either a prevaccination HAI titer \<1:10 and a postvaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in postvaccination HAI titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (1092 and 575 subjects in the QIVc and Comparator QIV groups, respectively, had HAI assay data for this outcome)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | A/H1N1 | 58.24 Percentage of participants |
| QIVc | Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | B/Yamagata | 46.52 Percentage of participants |
| QIVc | Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | B/Victoria | 30.31 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | A/H1N1 | 46.78 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | B/Yamagata | 31.65 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses | B/Victoria | 24.35 Percentage of participants |
Comparison: Non-inferiority, A/H1N1, SCR difference, Day 29/57~Non-inferiority of the immune response to the A/H1N1 vaccine strain by SCR difference (Comparator QIV SCR minus QIVc SCR)95% CI: [-16.447, -6.423]
Comparison: Non-inferiority, B/Yamagata, SCR difference, Day 29/57~Non-inferiority of the immune response to the B/Yamagata vaccine strain by SCR difference (Comparator QIV SCR minus QIVc SCR)95% CI: [-19.61, -9.983]
Comparison: Non-inferiority, B/Victoria, SCR difference, Day 29/57~Non-inferiority of the immune response to the B/Victoria vaccine strain by SCR difference (Comparator QIV SCR minus QIVc SCR)95% CI: [-10.327, -1.44]
Secondary
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses
GMR is defined as the geometric mean of the (within-subject) fold increase in serum HAI GMT postvaccination (Day 29/57) compared to prevaccination (Day 1).
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (1092 and 575 subjects in the QIVc and Comparator QIV groups, respectively, had HAI assay data for this outcome)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | A/H1N1 (cell) HAI GMR | 5.34 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Yamagata (cell) HAI GMR | 4.12 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Victoria (cell) HAI GMR | 2.65 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | A/H1N1 (egg) HAI GMR | 5.67 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Yamagata (egg) HAI GMR | 3.04 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Victoria (egg) HAI GMR | 2.14 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Yamagata (egg) HAI GMR | 3.27 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | A/H1N1 (cell) HAI GMR | 3.97 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | A/H1N1 (egg) HAI GMR | 5.11 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Yamagata (cell) HAI GMR | 3.03 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Victoria (egg) HAI GMR | 2.33 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses | B/Victoria (cell) HAI GMR | 2.31 Geometric mean ratio |
Secondary
Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses
GMR is defined as the geometric mean of the (within-subject) fold increase in serum MN GMT postvaccination (Day 29/57) compared to prevaccination (Day 1).
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (A randomly selected subset of subjects; 195 and 122 subjects in the QIVc and Comparator QIV groups, respectively, had MN assay data for this outcome) The MN assays for A/H1N1, B/Yamagata, and B/Victoria strains were only evaluated for cell-derived target viruses. Data were not collected for egg-derived target viruses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | A/H1N1 (cell) MN GMR | 5.74 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | B/Yamagata (cell) MN GMR | 3.14 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | B/Victoria (cell) MN GMR | 1.88 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | B/Victoria (cell) MN GMR | 1.63 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | A/H1N1 (cell) MN GMR | 4.29 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses | B/Yamagata (cell) MN GMR | 2.86 Geometric mean ratio |
Secondary
Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses
GMR is defined as the geometric mean of the (within-subject) fold increase in serum MN GMT postvaccination (Day 29/57) compared to prevaccination (Day 1).
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (1078 and 572 subjects in the QIVc and Comparator QIV groups, respectively, had MN assay data for the outcome of GMR against the A/H3N2 vaccine strain by MN assay using cell-derived target viruses; 1079 and 572 subjects in the QIVc and Comparator QIV groups, respectively, had data for the outcome of GMR against the A/H3N2 vaccine strain by MN assay using egg-derived target viruses)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses | A/H3N2 (cell) MN GMR | 2.11 Geometric mean ratio |
| QIVc | Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses | A/H3N2 (egg) MN GMR | 3.13 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses | A/H3N2 (cell) MN GMR | 2.19 Geometric mean ratio |
| Comparator QIV | Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses | A/H3N2 (egg) MN GMR | 3.22 Geometric mean ratio |
Secondary
Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses
The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) HAI titer for the Comparator QIV divided by the geometric mean of the postvaccination HAI titer for QIVc.
Time frame: Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects
Population: PPS (1092 and 575 subjects in the QIVc and Comparator QIV groups, respectively, had HAI assay data for this outcome)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | A/H1N1 Day 1 HAI GMT | 14.0 Titer |
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | A/H1N1 Day 29/57 HAI GMT | 92.2 Titer |
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Yamagata Day 1 HAI GMT | 6.7 Titer |
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Yamagata Day 29/57 HAI GMT | 23.0 Titer |
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Victoria Day 1 HAI GMT | 6.1 Titer |
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Victoria Day 29/57 HAI GMT | 13.6 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Victoria Day 1 HAI GMT | 6.0 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | A/H1N1 Day 1 HAI GMT | 13.9 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Yamagata Day 29/57 HAI GMT | 24.7 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | A/H1N1 Day 29/57 HAI GMT | 82.9 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Victoria Day 29/57 HAI GMT | 14.8 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Yamagata Day 1 HAI GMT | 6.7 Titer |
Comparison: A/H1N1, GMT ratio, Day 29/5795% CI: [0.79, 1.024]
Comparison: B/Yamagata, GMT ratio, Day 29/5795% CI: [0.968, 1.195]
Comparison: B/Victoria, GMT ratio, Day 29/5795% CI: [0.986, 1.202]
Secondary
Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses
The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) MN titer for the Comparator QIV divided by the geometric mean of the postvaccination MN titer for QIVc.
Time frame: Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects
Population: PPS (1079 and 572 subjects in the QIVc and Comparator QIV groups, respectively, had MN assay data for this outcome)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | A/H3N2 Day 1 MN GMT | 12.9 Titer |
| QIVc | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | A/H3N2 Day 29/57 MN GMT | 43.4 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | A/H3N2 Day 1 MN GMT | 12.6 Titer |
| Comparator QIV | Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | A/H3N2 Day 29/57 MN GMT | 44.7 Titer |
Comparison: A/H3N2, GMT ratio, Day 29/5795% CI: [0.914, 1.165]
Secondary
Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses
The SCR is defined as the percentage of subjects with either a prevaccination HAI titer \<1:10 and a postvaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in postvaccination HAI titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (1092 and 575 subjects in the QIVc and Comparator QIV groups, respectively, had HAI assay data for this outcome)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QIVc | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | A/H1N1 HAI SCR | 58.52 Percentage of participants |
| QIVc | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Yamagata HAI SCR | 38.64 Percentage of participants |
| QIVc | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Victoria HAI SCR | 19.69 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | A/H1N1 HAI SCR | 56.00 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Yamagata HAI SCR | 38.61 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses | B/Victoria HAI SCR | 20.87 Percentage of participants |
Comparison: A/H1N1, SCR difference, Day 29/5795% CI: [-7.526, 2.461]
Comparison: B/Yamagata, SCR difference, Day 29/5795% CI: [-4.912, 4.911]
Comparison: B/Victoria, SCR difference, Day 29/5795% CI: [-2.805, 5.353]
Secondary
Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses
The SCR is defined as the percentage of subjects with either a prevaccination MN titer \<1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: PPS (1079 and 572 subjects in the QIVc and Comparator QIV groups, respectively, had MN assay data for this outcome)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QIVc | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | 37.44 Percentage of participants |
| Comparator QIV | Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses | 39.34 Percentage of participants |
Comparison: A/H3N2, SCR difference, Day 29/5795% CI: [-3.006, 6.856]
Secondary
Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period
The percentage of subjects with any SAE, NOCD or AE leading to withdrawal during the study period from Day 1 to Day 181 for previously vaccinated subjects or from Day 1 to Day 209 for not previously vaccinated subjects. Definitions: SAEs = AEs defined as any untoward medical occurrence that at any dose resulted in one or more of the following: 1. Death, 2. Life-threatening 3. Required/prolonged hospitalization 4. Persistent or significant disability/incapacity 5. congenital anomaly/or birth defect 6. An important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based on appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above
Time frame: Day 1 to Day 181 for previously vaccinated subjects; Day 1 to Day 209 for not previously vaccinated subjects
Population: Unsolicited Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QIVc | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | Death | 2 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | Related SAE | 0 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | AE leading to study withdrawal | 3 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | NOCD | 22 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | SAE | 15 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | Related SAE | 0 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | SAE | 7 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | NOCD | 13 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | Death | 0 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period | AE leading to study withdrawal | 0 Participants |
Secondary
Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs
The percentage of subjects with at least one unsolicited AE from Day 1 to Day 29 for previously vaccinated subjects and from Day 1 to Day 57 for not previously vaccinated subjects. Related AEs = considered at least possibly related to study vaccination by the investigator; Severity = based on the greatest severity associated with a preferred term for a reported AE.
Time frame: Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Population: Unsolicited Safety Set, defined as all subjects in the FAS with any unsolicited AE data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QIVc | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE (Mild) | 308 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE (Severe) | 12 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE (Moderate) | 98 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Related AE | 70 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE | 418 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Related AE | 36 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE | 207 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE (Mild) | 164 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE (Moderate) | 41 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs | Any AE (Severe) | 2 Participants |
Secondary
Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs)
The percentage of subjects with at least one solicited AE Day 1 through Day 7 after any study vaccination.
Time frame: Day 1 to Day 7 after each vaccination (Day 1 to Day 7 for previously vaccinated subjects; Day 1 to Day 7 and Day 29 to Day 35 for not previously vaccinated subjects)
Population: Solicited Safety Set, defined as all subjects in the FAS with any solicited AE data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QIVc | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Solicited AEs | 940 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Solicited Local AEs | 656 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Solicited Systemic AEs | 681 Participants |
| QIVc | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Analgesic/Antipyretic Use | 240 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Analgesic/Antipyretic Use | 136 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Solicited AEs | 491 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Solicited Systemic AEs | 358 Participants |
| Comparator QIV | Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs) | Solicited Local AEs | 350 Participants |