Influenza
Conditions
Keywords
Immunogenicity, Children, Safety, Seasonal influenza, Fluarix
Brief summary
The purpose of this study is to investigate the immunogenicity, reactogenicity and safety of the new influenza vaccine GSK2282512A (FLU-Q-QIV) and compare its activity to the marketed vaccine Fluarix® (TIV) in young children 6 to 35 months of age.
Detailed description
The subjects will be randomized (1:1) in the 2 treatment groups to explore responses to vaccination in a sub-group analysis based on age (6 to 17 months, 18 to 35 months).
Interventions
BIOLOGICALQuadrivalent influenza GSK2282512A vaccine
1 or 2 doses administered intramuscularly (IM) in deltoid muscle or anterolateral thigh on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects) respectively.
BIOLOGICALFluarix
1 or 2 doses administered IM in deltoid muscle or anterolateral thigh, on Day 0 (primed subjects) and on Day 0 and Day 28 (unprimed subjects) respectively.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* Subject's parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * A male or female between, and including, 6 and 35 months of age at the time of the first vaccination. * Written informed consent obtained from the parent(s)/LAR(s) of the subject. * Subjects in stable health as determined by the investigator's clinical examination and assessment of subject's medical history. * Subjects are eligible regardless of history of administration of influenza vaccine in a previous season.
Exclusion criteria
* Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Routine registered childhood vaccinations are permitted. * Child in care. * Prior receipt of any seasonal or pandemic influenza vaccine within six months preceding the first dose of study vaccine, or planned use during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dosed. * Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. * History of Guillain-Barré syndrome within six weeks of receipt of prior influenza vaccine. * Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. * Acute disease and/or fever at the time of enrolment. * Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A Vaccine. | At Day 28 for primed subjects and at Day 56 for unprimed subjects | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria). This outcome concerns solely subjects in the GSK2282512A Group. |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | During the 7-day (Days 0-6) post-vaccination period | Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 swelling was greater than 100 millimeters (mm) i.e. \>100mm. |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | During the 7-day (Days 0-6) post-vaccination period | Solicited general symptoms assessed were drowsiness, irritability/fussiness and loss of appetite. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. |
| Number of Subjects Reporting Any, Grade 3 and Related Fever | During the 7-day (Days 0-6) post-vaccination period | Any fever was defined as any fever ≥38.0 degrees Celsius (°C) irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as fever ≥39.0 °C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any, Grade 3 and Related Fever | During the 4-day (Days 0-3) post-vaccination period | Any fever was defined as any fever ≥38.0 °C irrespective of intensity and relationship to vaccination. Related was defined as symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as fever ≥39.0 °C. |
| Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs) | During the entire study period (Day 0 to Day 180) | MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). |
| Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | At Day 0 (for all subjects) and 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects) | HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria) |
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | During the 28-day (Days 0-27) post-vaccination period. | An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. |
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | During the entire study period (Day 0 - Day 180) | A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. |
| Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | During the entire study period (Day 0 to Day 180) | Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. Any pIMD was defined as at least one pIMD experienced by the study subject. |
| Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix Vaccine | At Day 28 for primed subjects and at Day 56 for unprimed subjects | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria). This outcome concerns solely subjects in the Fluarix Group. |
| Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | At Day 0 (for all subjects) and Day 28 after last vaccine dose (Day 28 for primed subjects and Day 56 for unprimed subjects) | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria) |
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects) | MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria) |
Countries
Canada, Dominican Republic, Honduras
Participant flow
Recruitment details
Primed subjects: Received 2 doses of seasonal influenza vaccine separated by at least one month during the last season or had received at least 1 dose prior to last season. Unprimed subjects: Did not receive any seasonal influenza vaccine in the past or received only 1 dose for the first time in the last influenza season.
Pre-assignment details
5 subjects enrolled in the study were allocated subject numbers but the study vaccine dose was not administered.
Participants by arm
| Arm | Count |
|---|---|
| GSK2282512A Group Subjects aged between 6 to 35 months inclusive received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of quadrivalent influenza GSK2282512A vaccine.
Quadrivalent influenza GSK2282512A vaccine was administered intramuscularly in the left anterolateral thigh (subjects \< 12 months of age) or the deltoid muscle (subjects ≥ 12 months of age). | 299 |
| Fluarix Group Subjects aged between 6 to 35 months inclusive received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Fluarix vaccine.
Fluarix vaccine was administered intramuscularly in the left anterolateral thigh (subjects \< 12 months of age) or the deltoid muscle (subjects ≥ 12 months of age). | 302 |
| Total | 601 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Migrated/moved from study area | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | GSK2282512A Group | Fluarix Group | Total |
|---|---|---|---|
| Age, Continuous | 18.2 Months STANDARD_DEVIATION 8.17 | 18.1 Months STANDARD_DEVIATION 8.34 | 18.15 Months STANDARD_DEVIATION 8.25 |
| Sex: Female, Male Female | 155 Participants | 146 Participants | 301 Participants |
| Sex: Female, Male Male | 144 Participants | 156 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 200 / 299 | 211 / 302 |
| serious Total, serious adverse events | 9 / 299 | 8 / 302 |
Outcome results
Primary
Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A Vaccine.
A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria). This outcome concerns solely subjects in the GSK2282512A Group.
Time frame: At Day 28 for primed subjects and at Day 56 for unprimed subjects
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, in terms of antibody response measured by the Haemagglutination Inhibition assay, included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A Vaccine. | [H1N1, Day 28 = primed and Day 56 = unprimed] | 244 subjects |
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A Vaccine. | [H3N2, Day 28 = primed and Day 56 = unprimed] | 205 subjects |
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A Vaccine. | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 224 subjects |
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Quadrivalent Influenza GSK2282512A Vaccine. | [Victoria, Day 28 = primed and Day 56 = unprimed] | 210 subjects |
Primary
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 swelling was greater than 100 millimeters (mm) i.e. \>100mm.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Redness | 0 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Pain | 7 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Swelling | 5 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Redness | 6 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Swelling | 0 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Pain | 95 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Swelling | 0 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Pain | 91 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Redness | 6 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Redness | 0 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Any Swelling | 6 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Grade 3 Pain | 3 subjects |
Primary
Number of Subjects Reporting Any, Grade 3 and Related Fever
Any fever was defined as any fever ≥38.0 degrees Celsius (°C) irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as fever ≥39.0 °C.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Any Fever | 61 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Grade 3 Fever | 23 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Related Fever | 49 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Any Fever | 60 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Grade 3 Fever | 13 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Related Fever | 48 subjects |
Primary
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever).
Solicited general symptoms assessed were drowsiness, irritability/fussiness and loss of appetite. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Grade 3 Drowsiness | 9 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Related Irritability/fussiness | 104 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Any Irritability/fussiness | 118 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Any Loss of appetite | 99 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Related Drowsiness | 79 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Grade 3 Loss of appetite | 16 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Grade 3 Irritability/fussiness | 15 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Related Loss of appetite | 84 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Any Drowsiness | 93 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Related Loss of appetite | 83 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Any Drowsiness | 88 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Grade 3 Drowsiness | 9 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Related Drowsiness | 80 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Any Irritability/fussiness | 123 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Grade 3 Irritability/fussiness | 14 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Related Irritability/fussiness | 106 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Any Loss of appetite | 100 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms (Excluding Fever). | Grade 3 Loss of appetite | 14 subjects |
Secondary
Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains
HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria)
Time frame: At Day 0 (for all subjects) and 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, in terms of antibody response measured by the Haemagglutination Inhibition assay, included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H1N1, Day 0] | 9.6 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H1N1, Day 28 = primed and Day 56 = unprimed] | 157.1 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H3N2, Day 0] | 17.4 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H3N2, Day 28 = primed and Day 56 = unprimed] | 159.4 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Yamagata, Day 0] | 7.7 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 114.2 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Victoria, Day 0] | 10.6 Titers |
| GSK2282512A Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Victoria, Day 28 = primed and Day 56 = unprimed] | 111.4 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Victoria, Day 28 = primed and Day 56 = unprimed] | 15.6 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H1N1, Day 0] | 9.8 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Yamagata, Day 0] | 7.2 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H1N1, Day 28 = primed and Day 56 = unprimed] | 61.2 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Victoria, Day 0] | 9.3 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H3N2, Day 0] | 13.8 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 107.2 Titers |
| Fluarix Group | Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Influenza Strains | [H3N2, Day 28 = primed and Day 56 = unprimed] | 103.0 Titers |
Secondary
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains.
MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria)
Time frame: 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, in terms of antibody response measured by the Haemagglutination Inhibition assay, included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK2282512A Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [H1N1, Day 28 = primed and Day 56 = unprimed] | 16.4 Fold increase |
| GSK2282512A Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [H3N2, Day 28 = primed and Day 56 = unprimed] | 9.1 Fold increase |
| GSK2282512A Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 14.8 Fold increase |
| GSK2282512A Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [Victoria, Day 28 = primed and Day 56 = unprimed] | 10.5 Fold increase |
| Fluarix Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [Victoria, Day 28 = primed and Day 56 = unprimed] | 1.7 Fold increase |
| Fluarix Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [H1N1, Day 28 = primed and Day 56 = unprimed] | 6.2 Fold increase |
| Fluarix Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 14.8 Fold increase |
| Fluarix Group | Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains. | [H3N2, Day 28 = primed and Day 56 = unprimed] | 7.5 Fold increase |
Secondary
Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix Vaccine
A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria). This outcome concerns solely subjects in the Fluarix Group.
Time frame: At Day 28 for primed subjects and at Day 56 for unprimed subjects
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, in terms of antibody response measured by the Haemagglutination Inhibition assay, included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix Vaccine | [H1N1, Day 28 = primed and Day 56 = unprimed] | 154 subjects |
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix Vaccine | [H3N2, Day 28 = primed and Day 56 = unprimed] | 160 subjects |
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix Vaccine | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 222 subjects |
| GSK2282512A Group | Number of Seroconverted Subjects for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of Fluarix Vaccine | [Victoria, Day 28 = primed and Day 56 = unprimed] | 28 subjects |
Secondary
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)
A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Time frame: During the entire study period (Day 0 - Day 180)
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | Any SAEs | 9 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | Related SAEs | 1 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | Any SAEs | 8 subjects |
| Fluarix Group | Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | Related SAEs | 0 subjects |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Fever
Any fever was defined as any fever ≥38.0 °C irrespective of intensity and relationship to vaccination. Related was defined as symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 fever was defined as fever ≥39.0 °C.
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Any Fever | 46 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Grade 3 Fever | 16 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Related Fever | 39 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Any Fever | 42 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Grade 3 Fever | 8 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Fever | Related Fever | 38 subjects |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Time frame: During the 28-day (Days 0-27) post-vaccination period.
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Any Unsolicited AEs | 142 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Grade 3 Unsolicited AEs | 9 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Related Unsolicited AEs | 17 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Any Unsolicited AEs | 165 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Grade 3 Unsolicited AEs | 5 subjects |
| Fluarix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). | Related Unsolicited AEs | 13 subjects |
Secondary
Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs)
MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s).
Time frame: During the entire study period (Day 0 to Day 180)
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs) | 156 subjects |
| Fluarix Group | Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs) | 156 subjects |
Secondary
Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs)
Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. Any pIMD was defined as at least one pIMD experienced by the study subject.
Time frame: During the entire study period (Day 0 to Day 180)
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | Any pIMD(s) | 0 subjects |
| GSK2282512A Group | Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | Related pIMD(s) | 0 subjects |
| Fluarix Group | Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | Any pIMD(s) | 2 subjects |
| Fluarix Group | Number of Subjects Reporting Any Potential Immune-Mediated Diseases (pIMDs) | Related pIMD(s) | 0 subjects |
Secondary
Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2), Flu B/Hubei-Wujiagang/158/09 (Yamagata) and Flu B/Bri/60/08 (Victoria)
Time frame: At Day 0 (for all subjects) and Day 28 after last vaccine dose (Day 28 for primed subjects and Day 56 for unprimed subjects)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, in terms of antibody response measured by the Haemagglutination Inhibition assay, included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H1N1, Day 0] | 46 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H1N1, Day 28 = primed and Day 56 = unprimed] | 254 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H3N2, Day 0] | 93 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H3N2, Day 28 = primed and Day 56 = unprimed] | 231 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Yamagata, Day 0] | 26 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 242 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Victoria, Day 0] | 56 subjects |
| GSK2282512A Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Victoria, Day 28 = primed and Day 56 = unprimed] | 216 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Victoria, Day 28 = primed and Day 56 = unprimed] | 74 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H1N1, Day 0] | 47 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Yamagata, Day 0] | 24 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H1N1, Day 28 = primed and Day 56 = unprimed] | 169 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Victoria, Day 0] | 45 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H3N2, Day 0] | 74 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [Yamagata, Day 28 = primed and Day 56 = unprimed] | 229 subjects |
| Fluarix Group | Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains. | [H3N2, Day 28 = primed and Day 56 = unprimed] | 191 subjects |