Influenza
Conditions
Brief summary
The purpose of this study is to evaluate the immunogenicity and the safety of GlaxoSmithKline Biologicals' seasonal influenza vaccine, Fluarix, compared to Fluzone (a US-licensed vaccine) in children, 6 to 35 months of age.
Interventions
BIOLOGICALFluarix
One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection. Two different doses are tested.
BIOLOGICALFluzone
One (Day 0) or two (Day 0 and Day 28) doses by intramuscular injection.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* A male or female child aged 6 to 35 months at the time of the first vaccination; children who may or may not have had previous administration of influenza vaccine in a previous season are acceptable. * Subjects having a parent/guardian who the investigator believes can and will comply with the requirements of the protocol. * Written informed consent obtained from the subject's parent/guardian.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the administration of the study vaccine, or planned use during the study period. Routine, registered childhood vaccinations are not an exclusion criterion. * History of hypersensitivity to any vaccine. * History of allergy or reactions likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. * Receipt of an influenza vaccine outside of this study, during current (2008-09) flu season. * Administration of immunoglobulins and/or blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | Day 0 (PRE), Day 28 or Day 56 (POST) | GMTs and their 95% confidence interval are presented for all 3 viral strains comprised in the vaccine. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects |
| Number of Subjects Who Seroconverted | Day 28 or Day 56 | Seroconversion is defined as the number of subjects with either a pre-vaccination anti-HA titer \< 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a minimum 4-fold increase at post-vaccination titer. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Solicited Local Symptoms | During a 4-day follow-up period after vaccination | Solicited local symptoms assessed include pain, redness and swelling. |
| Number of Subjects Reporting Solicited General Symptoms | During a 4-day follow-up period after vaccination | Solicited general symptoms assessed include drowsiness, irritability, loss of appetitie, and temperature. |
| Number of Seroprotected Subjects | Day 0 (PRE), Day 28 or Day 56 (POST) | A seroprotected subject is a subject with a serum anti-HA titer ≥ 1:40 Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects |
| Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | During the entire study (Day 0 until Month 6) | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. NOCDs assessed include for example: diabetes, asthma, allergies, autoimmune disease, cancer, neuropathic disorders |
| Number of Subjects Reporting Rare Serious Events | During the entire study (Day 0 until Month 6) | Rare serious events have an occurrence rate of 1/300 (0.3%). |
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | During a 28-day follow-up period after vaccination | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product |
| Seroconversion Factor | Day 28 or Day 56 | Seroconversion factor is defined as the fold increase in serum anti-HA GMTs post-vaccination (Day 28 or 56) compared to pre-vaccination (Day 0). Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects |
Countries
Hong Kong, Mexico, Taiwan, Thailand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluarix Dose A Group Subjects were administered 1 or 2 doses\* of Fluarix vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children \>12 months of age) or in the anterolateral thigh (children \<12 months of age).
\* Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses. | 1,107 |
| Fluarix Dose B Group Subjects were administered 1 or 2 doses\*, half the volume of dose A, of Fluarix vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children \>12 months of age) or in the anterolateral thigh (children \<12 months of age).
\* Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses. | 1,106 |
| Fluzone Group Subjects were administered 1 or 2 doses\* of Fluzone vaccine (at Day 0 or at Days 0 and 28) intramuscularly, in the non-dominant upper arm (children \>12 months of age) or in the anterolateral thigh (children \<12 months of age).
\* Only those subjects who had no history of prior influenza vaccination (i.e. unprimed subjects) received 2 doses. | 1,104 |
| Total | 3,317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 28 | 29 | 23 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 12 | 6 |
Baseline characteristics
| Characteristic | Fluarix Dose A Group | Fluarix Dose B Group | Fluzone Group | Total |
|---|---|---|---|---|
| Age, Continuous | 20.9 months STANDARD_DEVIATION 8.07 | 20.9 months STANDARD_DEVIATION 8.42 | 21.0 months STANDARD_DEVIATION 8.23 | 20.9 months STANDARD_DEVIATION 8.24 |
| Sex: Female, Male Female | 539 Participants | 517 Participants | 560 Participants | 1616 Participants |
| Sex: Female, Male Male | 568 Participants | 589 Participants | 544 Participants | 1701 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 805 / 1,107 | 791 / 1,106 | 808 / 1,104 |
| serious Total, serious adverse events | 35 / 1,107 | 29 / 1,106 | 31 / 1,104 |
Outcome results
Primary
Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains
GMTs and their 95% confidence interval are presented for all 3 viral strains comprised in the vaccine. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects
Time frame: Day 0 (PRE), Day 28 or Day 56 (POST)
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluarix Dose A Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Brisbane (PRE) | 10.4 titre |
| Fluarix Dose A Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Brisbane (POST) | 106.1 titre |
| Fluarix Dose A Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Uruguay (PRE) | 12.1 titre |
| Fluarix Dose A Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Uruguay (POST) | 125.6 titre |
| Fluarix Dose A Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | B/Florida (PRE) | 8.4 titre |
| Fluarix Dose A Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | B/Florida (POST) | 113.0 titre |
| Fluarix Dose B Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | B/Florida (POST) | 164.4 titre |
| Fluarix Dose B Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Brisbane (PRE) | 10.6 titre |
| Fluarix Dose B Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Uruguay (POST) | 158.7 titre |
| Fluarix Dose B Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | B/Florida (PRE) | 8.9 titre |
| Fluarix Dose B Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Brisbane (POST) | 131.6 titre |
| Fluarix Dose B Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Uruguay (PRE) | 11.2 titre |
| Fluzone Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Brisbane (POST) | 232.4 titre |
| Fluzone Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Uruguay (PRE) | 11.6 titre |
| Fluzone Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | B/Florida (POST) | 176.4 titre |
| Fluzone Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Uruguay (POST) | 280.3 titre |
| Fluzone Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | A/Brisbane (PRE) | 10.9 titre |
| Fluzone Group | Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains | B/Florida (PRE) | 8.3 titre |
Primary
Number of Subjects Who Seroconverted
Seroconversion is defined as the number of subjects with either a pre-vaccination anti-HA titer \< 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a minimum 4-fold increase at post-vaccination titer. Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects
Time frame: Day 28 or Day 56
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluarix Dose A Group | Number of Subjects Who Seroconverted | A/Uruguay | 747 Participants |
| Fluarix Dose A Group | Number of Subjects Who Seroconverted | A/Brisbane | 636 Participants |
| Fluarix Dose A Group | Number of Subjects Who Seroconverted | B/Florida | 812 Participants |
| Fluarix Dose B Group | Number of Subjects Who Seroconverted | A/Uruguay | 808 Participants |
| Fluarix Dose B Group | Number of Subjects Who Seroconverted | A/Brisbane | 699 Participants |
| Fluarix Dose B Group | Number of Subjects Who Seroconverted | B/Florida | 864 Participants |
| Fluzone Group | Number of Subjects Who Seroconverted | A/Brisbane | 929 Participants |
| Fluzone Group | Number of Subjects Who Seroconverted | B/Florida | 904 Participants |
| Fluzone Group | Number of Subjects Who Seroconverted | A/Uruguay | 988 Participants |
Secondary
Number of Seroprotected Subjects
A seroprotected subject is a subject with a serum anti-HA titer ≥ 1:40 Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects
Time frame: Day 0 (PRE), Day 28 or Day 56 (POST)
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluarix Dose A Group | Number of Seroprotected Subjects | A/Brisbane (POST) | 699 Participants |
| Fluarix Dose A Group | Number of Seroprotected Subjects | A/Uruguay (PRE) | 222 Participants |
| Fluarix Dose A Group | Number of Seroprotected Subjects | B/Florida (POST) | 872 Participants |
| Fluarix Dose A Group | Number of Seroprotected Subjects | A/Brisbane (PRE) | 185 Participants |
| Fluarix Dose A Group | Number of Seroprotected Subjects | A/Uruguay (POST) | 788 Participants |
| Fluarix Dose A Group | Number of Seroprotected Subjects | B/Florida (PRE) | 171 Participants |
| Fluarix Dose B Group | Number of Seroprotected Subjects | A/Uruguay (POST) | 846 Participants |
| Fluarix Dose B Group | Number of Seroprotected Subjects | B/Florida (PRE) | 181 Participants |
| Fluarix Dose B Group | Number of Seroprotected Subjects | B/Florida (POST) | 902 Participants |
| Fluarix Dose B Group | Number of Seroprotected Subjects | A/Brisbane (POST) | 754 Participants |
| Fluarix Dose B Group | Number of Seroprotected Subjects | A/Brisbane (PRE) | 186 Participants |
| Fluarix Dose B Group | Number of Seroprotected Subjects | A/Uruguay (PRE) | 193 Participants |
| Fluzone Group | Number of Seroprotected Subjects | B/Florida (POST) | 935 Participants |
| Fluzone Group | Number of Seroprotected Subjects | A/Brisbane (PRE) | 206 Participants |
| Fluzone Group | Number of Seroprotected Subjects | A/Brisbane (POST) | 986 Participants |
| Fluzone Group | Number of Seroprotected Subjects | A/Uruguay (PRE) | 214 Participants |
| Fluzone Group | Number of Seroprotected Subjects | B/Florida (PRE) | 166 Participants |
| Fluzone Group | Number of Seroprotected Subjects | A/Uruguay (POST) | 1012 Participants |
Secondary
Number of Subjects Reporting Rare Serious Events
Rare serious events have an occurrence rate of 1/300 (0.3%).
Time frame: During the entire study (Day 0 until Month 6)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluarix Dose A Group | Number of Subjects Reporting Rare Serious Events | Pneumonia | 0 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Rare Serious Events | Bronchiolitis | 0 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Rare Serious Events | Pneumonia | 0 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Rare Serious Events | Bronchiolitis | 3 Participants |
| Fluzone Group | Number of Subjects Reporting Rare Serious Events | Pneumonia | 3 Participants |
| Fluzone Group | Number of Subjects Reporting Rare Serious Events | Bronchiolitis | 3 Participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD)
An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. NOCDs assessed include for example: diabetes, asthma, allergies, autoimmune disease, cancer, neuropathic disorders
Time frame: During the entire study (Day 0 until Month 6)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluarix Dose A Group | Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | SAE | 35 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | NOCD | 10 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | SAE | 29 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | NOCD | 8 Participants |
| Fluzone Group | Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | SAE | 31 Participants |
| Fluzone Group | Number of Subjects Reporting Serious Adverse Events (SAE) and New Onset of Chronic Diseases (NOCD) | NOCD | 9 Participants |
Secondary
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed include drowsiness, irritability, loss of appetitie, and temperature.
Time frame: During a 4-day follow-up period after vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, including all vaccinated subjects for whom data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluarix Dose A Group | Number of Subjects Reporting Solicited General Symptoms | Loss of appetite | 281 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Solicited General Symptoms | Temperature | 67 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Solicited General Symptoms | Irritability | 386 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Solicited General Symptoms | Drowsiness | 293 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited General Symptoms | Drowsiness | 317 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited General Symptoms | Irritability | 387 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited General Symptoms | Temperature | 69 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited General Symptoms | Loss of appetite | 273 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited General Symptoms | Temperature | 72 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited General Symptoms | Drowsiness | 298 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited General Symptoms | Irritability | 375 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited General Symptoms | Loss of appetite | 270 Participants |
Secondary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, redness and swelling.
Time frame: During a 4-day follow-up period after vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, including all vaccinated subjects for whom data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fluarix Dose A Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 259 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 403 Participants |
| Fluarix Dose A Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 152 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 249 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 406 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 170 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 363 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 129 Participants |
| Fluzone Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 253 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AE)
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: During a 28-day follow-up period after vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluarix Dose A Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 565 Participants |
| Fluarix Dose B Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 541 Participants |
| Fluzone Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 562 Participants |
Secondary
Seroconversion Factor
Seroconversion factor is defined as the fold increase in serum anti-HA GMTs post-vaccination (Day 28 or 56) compared to pre-vaccination (Day 0). Post-vaccination timepoints: Day 28 for primed or Day 56 for unprimed subjects
Time frame: Day 28 or Day 56
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Fluarix Dose A Group | Seroconversion Factor | A/Uruguay | 10.4 fold increase |
| Fluarix Dose A Group | Seroconversion Factor | A/Brisbane | 10.2 fold increase |
| Fluarix Dose A Group | Seroconversion Factor | B/Florida | 13.4 fold increase |
| Fluarix Dose B Group | Seroconversion Factor | A/Uruguay | 14.2 fold increase |
| Fluarix Dose B Group | Seroconversion Factor | A/Brisbane | 12.4 fold increase |
| Fluarix Dose B Group | Seroconversion Factor | B/Florida | 18.4 fold increase |
| Fluzone Group | Seroconversion Factor | A/Brisbane | 21.4 fold increase |
| Fluzone Group | Seroconversion Factor | B/Florida | 21.4 fold increase |
| Fluzone Group | Seroconversion Factor | A/Uruguay | 24.1 fold increase |