Influenza
Conditions
Keywords
Influenza, adults, different lots, trivalent subunit influenza virus vaccine (IVV), trivalent subunit influenza vaccine
Brief summary
The purpose of this research is to demonstrate immunologic equivalence of three consecutive production lots of the subunit influenza vaccine compared to egg-derived inactivated influenza vaccine in healthy subjects 18 to 49 years of ages. In addition, this study is to show how safe and well tolerated a conventional inactivated subunit influenza vaccine, licensed in many countries outside the United States, is compared to an inactivated influenza vaccine, licensed in the United States.
Interventions
BIOLOGICALLot A of Influenza virus vaccine
1 injection of the trivalent subunit influenza virus vaccine (lot A) administered intramuscularly
BIOLOGICALLot B of Influenza virus vaccine
1 injection of the trivalent subunit influenza virus vaccine (lot B) administered intramuscularly
BIOLOGICALLot C of Influenza virus vaccine
1 injection of the trivalent subunit influenza virus vaccine (lot C) administered intramuscularly
BIOLOGICALComparator influenza virus vaccine
1 injection of the trivalent subunit influenza virus vaccine administered intramuscularly
BIOLOGICALAll 3 consecutive lots of influenza virus vaccine pooled
1 injection of the pooled trivalent subunit influenza virus vaccine administered intramuscularly
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 49 years of age; * In good health as determined by medical history and physical examination; * Able and willing to provide written informed consent prior to any study procedure; * Able to comply with all study procedures and available for all clinic visits scheduled in the study.
Exclusion criteria
* Any serious disease, such as: cancer, autoimmune disease (including rheumatoid arthritis), advanced arteriosclerotic disease or complicated diabetes mellitus * History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, polymyxin, or any other vaccine component, chemically related substance, or component of the potential packaging materials (latex); * Known or suspected impairment/alteration of immune function * Receipt of an influenza vaccine within 6 months prior to Visit 1; * Current drug or alcohol abuse or a history of drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of the study objectives; * Laboratory-confirmed influenza disease within 6 months prior to Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs), by Vaccine Lots | 21 days after vaccination | The immunologic equivalence of three consecutive production lots of the influenza virus vaccine was measured in terms of GMTs for all vaccine influenza strains. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Solicited Local and Systemic Symptoms | 7 days after vaccination | Solicited local and systemic reactions were assessed after vaccination for the two vaccines (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each of the three consecutive production lots of the investigational influenza virus vaccine. |
| Number of Subjects With at Least One Unsolicited Adverse Event | 3 weeks after vaccination | Number of subjects reporting at least one unsolicited adverse event, regardless of the assessement of relatedness to the study vaccines (each of the three consecutive production lots of the investigational influenza virus vaccine, the pooled influenza virus vaccine, and the comparator influenza vaccine). |
| Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 21 days after vaccination | The GMTs and 95% CIs were calculated for each of the vaccine group (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each strain. |
| Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | 21 days after vaccination | The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%. |
| Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | 21 days after vaccination | The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%. |
| Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | 21 days after vaccination | The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%. |
Countries
Dominican Republic
Participant flow
Recruitment details
Participants were recruited at 1 Center along with a satellite center in the Dominican Republic.
Participants by arm
| Arm | Count |
|---|---|
| Influenza Virus Vaccine (Lot A) One injection of lot A of the investigational influenza virus vaccine | 430 |
| Influenza Virus Vaccine (Lot B) One injection of lot B of the investigational influenza virus vaccine | 431 |
| Influenza Virus Vaccine (Lot C) One injection of lot C of the investigational influenza virus vaccine | 429 |
| Comparator Influenza Vaccine One injection of the comparator influenza virus vaccine | 217 |
| Total | 1,507 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Inappropriate Enrollment | 5 | 4 | 1 | 1 |
| Overall Study | Lost to Follow-up | 27 | 29 | 31 | 19 |
| Overall Study | Unable to classify | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 7 | 12 | 4 |
Baseline characteristics
| Characteristic | Influenza Virus Vaccine (Lot A) | Influenza Virus Vaccine (Lot B) | Influenza Virus Vaccine (Lot C) | Comparator Influenza Vaccine | Total |
|---|---|---|---|---|---|
| Age Continuous | 31.1 years STANDARD_DEVIATION 8.8 | 31.2 years STANDARD_DEVIATION 8.6 | 31.3 years STANDARD_DEVIATION 8.9 | 31.3 years STANDARD_DEVIATION 8.7 | 31.2 years STANDARD_DEVIATION 8.7 |
| Race/Ethnicity, Customized Arabic | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 7 participants | 11 participants | 9 participants | 3 participants | 30 participants |
| Race/Ethnicity, Customized Caucasian | 1 participants | 2 participants | 1 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 421 participants | 418 participants | 418 participants | 214 participants | 1471 participants |
| Race/Ethnicity, Customized Native Amer/Alaskan | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 309 Participants | 306 Participants | 291 Participants | 154 Participants | 1060 Participants |
| Sex: Female, Male Male | 121 Participants | 125 Participants | 138 Participants | 63 Participants | 447 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1,209 | 0 / 202 |
| serious Total, serious adverse events | 11 / 1,209 | 4 / 202 |
Outcome results
Primary
Geometric Mean Titers (GMTs), by Vaccine Lots
The immunologic equivalence of three consecutive production lots of the influenza virus vaccine was measured in terms of GMTs for all vaccine influenza strains.
Time frame: 21 days after vaccination
Population: The analysis was performed on the per-protocol population, defined as all subjects enrolled who:~* received all the relevant doses of vaccine correctly, and~* provided evaluable serum samples at the relevant time points, and~* had no major protocol deviation
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Influenza Virus Vaccine (Lot A) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain A/H3N2 | 352 Titers |
| Influenza Virus Vaccine (Lot A) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain A/H1N1 | 566 Titers |
| Influenza Virus Vaccine (Lot A) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain B | 99 Titers |
| Influenza Virus Vaccine (Lot B) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain A/H3N2 | 313 Titers |
| Influenza Virus Vaccine (Lot B) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain A/H1N1 | 518 Titers |
| Influenza Virus Vaccine (Lot B) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain B | 93 Titers |
| Influenza Virus Vaccine (Lot C) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain A/H1N1 | 513 Titers |
| Influenza Virus Vaccine (Lot C) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain B | 86 Titers |
| Influenza Virus Vaccine (Lot C) | Geometric Mean Titers (GMTs), by Vaccine Lots | Strain A/H3N2 | 359 Titers |
Comparison: H01 LotA ≠ LotB versus H1 LotA = LotB H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% confidence interval (CI) on the geometric mean titer (GMT) ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.92, 1.29]ANOVA
Comparison: H02 LotA ≠ LotC versus H12 LotA = Lotc H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.93, 1.31]ANOVA
Comparison: H03 LotB ≠ LotC versus H13 LotB = LotC H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.85, 1.2]ANOVA
Comparison: H03 LotA ≠ LotB versus H13 LotA = LotB H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.97, 1.3]ANOVA
Comparison: H03 LotA ≠ LotC versus H13 LotA = LotC H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.85, 1.13]ANOVA
Comparison: H03 LotB ≠ LotC versus H13 LotB = LotC H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.76, 1.01]ANOVA
Comparison: H03 LotA ≠ LotB versus H13 LotA = LotB H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.91, 1.23]ANOVA
Comparison: H03 LotA ≠ LotC versus H13 LotA = LotC H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.99, 1.33]ANOVA
Comparison: H03 LotB ≠ LotC versus H13 LotB = LotC H0 refers to the null hypothesis of non-equivalence (inconsistency) in that the two-sided 95% CI on the GMT ratio is outside the equivalence range (0.67 to 1.5). H1 refers to the alternative hypothesis of equivalence (consistency) in that the two-sided 95% CI on the GMT ratio is within the equivalence range (0.67 to 1.5).95% CI: [0.94, 1.26]ANOVA
Secondary
Geometric Mean Titers (GMTs), by Vaccine Group and Strain
The GMTs and 95% CIs were calculated for each of the vaccine group (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each strain.
Time frame: 21 days after vaccination
Population: The analysis was performed on the per-protocol population, defined as all subjects enrolled who:~* received all the relevant doses of vaccine correctly, and~* provided evaluable serum samples at the relevant time points, and~* had no major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Influenza Virus Vaccine (Lot A) | Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 532 titers |
| Influenza Virus Vaccine (Lot B) | Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 341 titers |
| Influenza Virus Vaccine (Lot C) | Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 93 titers |
| Comparator Influenza Vaccine (Strain A/H1N1) | Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 799 titers |
| Comparator Influenza Vaccine (Strain A/H3N2) | Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 683 titers |
| Comparator Influenza Vaccine (Strain B) | Geometric Mean Titers (GMTs), by Vaccine Group and Strain | 99 titers |
Secondary
Number of Subjects Reporting Solicited Local and Systemic Symptoms
Solicited local and systemic reactions were assessed after vaccination for the two vaccines (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each of the three consecutive production lots of the investigational influenza virus vaccine.
Time frame: 7 days after vaccination
Population: The analysis was performed on the safety population, defined as all subjects who provided post-baseline safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Local Reaction | 114 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Induration (mm) | 19 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Chills | 30 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fever (≥38C) | 17 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Headache | 100 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Pain | 96 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Swelling (mm) | 15 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Erythema (mm) | 15 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fatigue | 29 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Myalgia | 73 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Systemic Reaction | 148 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Ecchymosis (mm) | 14 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Arthralgia | 19 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Sweating | 14 Participants |
| Influenza Virus Vaccine (Lot A) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Malaise | 45 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Headache | 94 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Pain | 87 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Systemic Reaction | 148 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Local Reaction | 96 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fever (≥38C) | 24 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Sweating | 14 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Erythema (mm) | 12 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Chills | 28 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Induration (mm) | 19 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Arthralgia | 25 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Myalgia | 75 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Swelling (mm) | 24 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Malaise | 52 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Ecchymosis (mm) | 13 Participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fatigue | 41 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Chills | 29 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Local Reaction | 100 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Erythema (mm) | 17 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Induration (mm) | 24 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Swelling (mm) | 14 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Ecchymosis (mm) | 14 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Pain | 85 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Systemic Reaction | 147 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Malaise | 47 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Myalgia | 65 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Arthralgia | 25 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Headache | 98 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Sweating | 20 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fatigue | 41 Participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fever (≥38C) | 13 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Ecchymosis (mm) | 41 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fatigue | 111 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Malaise | 144 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Swelling (mm) | 53 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Myalgia | 213 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Local Reaction | 310 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Arthralgia | 69 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Induration (mm) | 62 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Chills | 87 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Headache | 292 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Erythema (mm) | 44 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Sweating | 48 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fever (≥38C) | 54 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Systemic Reaction | 443 Participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Pain | 268 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Chills | 17 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Headache | 48 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Systemic Reaction | 76 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Malaise | 25 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Any Local Reaction | 54 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Induration (mm) | 12 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fatigue | 16 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Fever (≥38C) | 7 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Myalgia | 40 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Swelling (mm) | 14 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Sweating | 9 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Arthralgia | 14 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Pain | 44 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Erythema (mm) | 9 Participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects Reporting Solicited Local and Systemic Symptoms | Ecchymosis (mm) | 9 Participants |
Secondary
Number of Subjects With at Least One Unsolicited Adverse Event
Number of subjects reporting at least one unsolicited adverse event, regardless of the assessement of relatedness to the study vaccines (each of the three consecutive production lots of the investigational influenza virus vaccine, the pooled influenza virus vaccine, and the comparator influenza vaccine).
Time frame: 3 weeks after vaccination
Population: The analysis was performed on the safety population, defined as all subjects who provided post-baseline safety data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Influenza Virus Vaccine (Lot A) | Number of Subjects With at Least One Unsolicited Adverse Event | 189 participants |
| Influenza Virus Vaccine (Lot B) | Number of Subjects With at Least One Unsolicited Adverse Event | 33 participants |
| Influenza Virus Vaccine (Lot C) | Number of Subjects With at Least One Unsolicited Adverse Event | 56 participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Number of Subjects With at Least One Unsolicited Adverse Event | 68 participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Number of Subjects With at Least One Unsolicited Adverse Event | 65 participants |
Secondary
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1)
The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%.
Time frame: 21 days after vaccination
Population: The analysis was performed on the per-protocol population, defined as all subjects enrolled who:~* received all the relevant doses of vaccine correctly, and~* provided evaluable serum samples at the relevant time points, and~* had no major protocol deviation
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Influenza Virus Vaccine (Lot A) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroprotection (HI titer => 40) | 98 percentages of participants |
| Influenza Virus Vaccine (Lot A) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroconversion | 95 percentages of participants |
| Influenza Virus Vaccine (Lot B) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroprotection (HI titer => 40) | 99 percentages of participants |
| Influenza Virus Vaccine (Lot B) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroconversion | 94 percentages of participants |
| Influenza Virus Vaccine (Lot C) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroprotection (HI titer => 40) | 98 percentages of participants |
| Influenza Virus Vaccine (Lot C) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroconversion | 93 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroconversion | 94 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroprotection (HI titer => 40) | 98 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroprotection (HI titer => 40) | 98 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1) | Seroconversion | 96 percentages of participants |
Secondary
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2)
The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%.
Time frame: 21 days after vaccination
Population: The analysis was performed on the per-protocol population, defined as all subjects enrolled who:~* received all the relevant doses of vaccine correctly, and~* provided evaluable serum samples at the relevant time points, and~* had no major protocol deviation
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Influenza Virus Vaccine (Lot A) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroprotection (HI titer ≥40) | 99 percentages of participants |
| Influenza Virus Vaccine (Lot A) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroconversion | 70 percentages of participants |
| Influenza Virus Vaccine (Lot B) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroprotection (HI titer ≥40) | 98 percentages of participants |
| Influenza Virus Vaccine (Lot B) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroconversion | 64 percentages of participants |
| Influenza Virus Vaccine (Lot C) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroprotection (HI titer ≥40) | 99 percentages of participants |
| Influenza Virus Vaccine (Lot C) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroconversion | 68 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroconversion | 67 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroprotection (HI titer ≥40) | 99 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroprotection (HI titer ≥40) | 99 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2) | Seroconversion | 84 percentages of participants |
Secondary
Percentage of Subjects With Seroprotection and Seroconversion (Strain B)
The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: * the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%. * the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI\<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum \[HI≥10\]), for HI antibody met or exceeded 40%.
Time frame: 21 days after vaccination
Population: The analysis was performed on the per-protocol population, defined as all subjects enrolled who:~* received all the relevant doses of vaccine correctly, and~* provided evaluable serum samples at the relevant time points, and~* had no major protocol deviation
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Influenza Virus Vaccine (Lot A) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroconversion | 85 percentages of participants |
| Influenza Virus Vaccine (Lot A) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroprotection (HI titer ≥40) | 88 percentages of participants |
| Influenza Virus Vaccine (Lot B) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroconversion | 86 percentages of participants |
| Influenza Virus Vaccine (Lot B) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroprotection (HI titer ≥40) | 88 percentages of participants |
| Influenza Virus Vaccine (Lot C) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroconversion | 81 percentages of participants |
| Influenza Virus Vaccine (Lot C) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroprotection (HI titer ≥40) | 84 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroprotection (HI titer ≥40) | 87 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H1N1) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroconversion | 84 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroconversion | 86 percentages of participants |
| Comparator Influenza Vaccine (Strain A/H3N2) | Percentage of Subjects With Seroprotection and Seroconversion (Strain B) | Seroprotection (HI titer ≥40) | 90 percentages of participants |