Influenza
Conditions
Brief summary
This study is designed to test the immunogenicity and reactogenicity of the Fluarix™/Influsplit SSW® influenza vaccine containing the influenza strains recommended for the 2008-2009 season.
Interventions
BIOLOGICALFluarix™
Single intramuscular dose on Day 0
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female aged 18 years or above at the time of the vaccination. * Written informed consent obtained from the subject. * Healthy subjects or with well-controlled chronic diseases as established by medical history and clinical examination before entering into the study. * If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the vaccination or planned use during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. * Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned during the study. * Administration of an influenza vaccine within 1 year preceding the study start. * Administration of an influenza vaccine other than the study vaccine during the entire study * Clinically or virologically confirmed influenza infection within 1 year preceding the study start * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. * Not stabilized or clinically serious chronic underlying disease. * Lactating female. * History of chronic alcohol consumption and/or drug abuse. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Any condition which, in the opinion of the investigator, prevents the subject from participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection Power | At Day 21 | Seroprotection power is defined as the number of subject who had a pre-vaccination titer \< 1:40 and a post-vaccination titer ≥ 1:40 |
| Number of Seroprotected Subjects | At Day 0 and 21 | A seroprotected subject is a subject with a serum HI antibody titer ≥ 1:40 |
| Number of Serconverted Subjects | At Day 21 | A seroconverted subject is a subject with a pre-vaccination serum HI titer \< 1:10 and a post-vaccination serum HI titer ≥ 1:40, or a pre-vaccination serum HI titer ≥ 1:10 and a fold increase (Day 21/Day 0) ≥ 4 |
| Serconversion Factor | At Day 21 | Seroconversion factor, defined as the fold increase in serum HI GMT post-vaccination compared to pre-vaccination (Day 0), is presented for all three vaccine influenza virus strains |
| Hemagglutination Inhibition (HI) Antibody Titer | At Day 0 and 21 | Titers given as geometric mean titer (GMT) were presented for all three vaccine influenza virus strains |
| Number of Subjects With HI Antibody Titer Above the Cut-off Value | At Day 0 and 21 | The cut-off value assessed was ≥ 1:10 and was presented for all three vaccine influenza virus strains |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | During the 21-day (Day 0-20) post-vaccination period | 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. |
| Number of Subjects Reporting Serious Adverse Events (SAE) | During the 21-day (Day 0-20) post-vaccination period | 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. |
| Number of Subjects Reporting Solicited Symptoms | During the 4-day (Day 0-3) post-vaccination period | Solicited local symptoms assessed include ecchymosis, induration, pain, redness, and swelling. Solicited general symptoms assessed include arthralgia, fatigue, headache, myalgia, shivering, sweating, and fever |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluarix Adult Group Subjects who are 18-40 years of age received one dose of Fluarix™ | 61 |
| Fluarix Elderly Group Subjects who are ≥ 60 years of age received one dose of Fluarix™ | 59 |
| Total | 120 |
Baseline characteristics
| Characteristic | Fluarix Adult Group | Fluarix Elderly Group | Total |
|---|---|---|---|
| Age, Continuous | 39.1 years STANDARD_DEVIATION 13.26 | 68.8 years STANDARD_DEVIATION 5.25 | 53.7 years STANDARD_DEVIATION 18.01 |
| Sex: Female, Male Female | 36 Participants | 34 Participants | 70 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 61 | 30 / 59 |
| serious Total, serious adverse events | 1 / 61 | 0 / 59 |
Outcome results
Primary
Hemagglutination Inhibition (HI) Antibody Titer
Titers given as geometric mean titer (GMT) were presented for all three vaccine influenza virus strains
Time frame: At Day 0 and 21
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluarix Adult Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Brisbane (Day 0) | 13.6 titer |
| Fluarix Adult Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Brisbane (Day 21) | 165.5 titer |
| Fluarix Adult Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Uruguay (Day 0) | 7.6 titer |
| Fluarix Adult Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Uruguay (Day 21) | 90.7 titer |
| Fluarix Adult Group | Hemagglutination Inhibition (HI) Antibody Titer | B/Brisbane (Day 0) | 102.1 titer |
| Fluarix Adult Group | Hemagglutination Inhibition (HI) Antibody Titer | B/Brisbane (Day 21) | 785.3 titer |
| Fluarix Elderly Group | Hemagglutination Inhibition (HI) Antibody Titer | B/Brisbane (Day 0) | 108.0 titer |
| Fluarix Elderly Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Brisbane (Day 0) | 11.6 titer |
| Fluarix Elderly Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Uruguay (Day 21) | 120.6 titer |
| Fluarix Elderly Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Brisbane (Day 21) | 68.2 titer |
| Fluarix Elderly Group | Hemagglutination Inhibition (HI) Antibody Titer | B/Brisbane (Day 21) | 524.0 titer |
| Fluarix Elderly Group | Hemagglutination Inhibition (HI) Antibody Titer | A/Uruguay (Day 0) | 9.7 titer |
Primary
Number of Serconverted Subjects
A seroconverted subject is a subject with a pre-vaccination serum HI titer \< 1:10 and a post-vaccination serum HI titer ≥ 1:40, or a pre-vaccination serum HI titer ≥ 1:10 and a fold increase (Day 21/Day 0) ≥ 4
Time frame: At Day 21
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluarix Adult Group | Number of Serconverted Subjects | A/Brisbane | 44 subjects |
| Fluarix Adult Group | Number of Serconverted Subjects | A/Uruguay | 44 subjects |
| Fluarix Adult Group | Number of Serconverted Subjects | B/Brisbane | 39 subjects |
| Fluarix Elderly Group | Number of Serconverted Subjects | B/Brisbane | 30 subjects |
| Fluarix Elderly Group | Number of Serconverted Subjects | A/Brisbane | 30 subjects |
| Fluarix Elderly Group | Number of Serconverted Subjects | A/Uruguay | 39 subjects |
Primary
Number of Seroprotected Subjects
A seroprotected subject is a subject with a serum HI antibody titer ≥ 1:40
Time frame: At Day 0 and 21
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluarix Adult Group | Number of Seroprotected Subjects | A/Brisbane (Day 0) | 15 subjects |
| Fluarix Adult Group | Number of Seroprotected Subjects | A/Brisbane (Day 21) | 55 subjects |
| Fluarix Adult Group | Number of Seroprotected Subjects | A/Uruguay (Day 0) | 5 subjects |
| Fluarix Adult Group | Number of Seroprotected Subjects | A/Uruguay (Day 21) | 47 subjects |
| Fluarix Adult Group | Number of Seroprotected Subjects | B/Brisbane (Day 0) | 48 subjects |
| Fluarix Adult Group | Number of Seroprotected Subjects | B/Brisbane (Day 21) | 61 subjects |
| Fluarix Elderly Group | Number of Seroprotected Subjects | B/Brisbane (Day 0) | 50 subjects |
| Fluarix Elderly Group | Number of Seroprotected Subjects | A/Brisbane (Day 0) | 9 subjects |
| Fluarix Elderly Group | Number of Seroprotected Subjects | A/Uruguay (Day 21) | 43 subjects |
| Fluarix Elderly Group | Number of Seroprotected Subjects | A/Brisbane (Day 21) | 40 subjects |
| Fluarix Elderly Group | Number of Seroprotected Subjects | B/Brisbane (Day 21) | 59 subjects |
| Fluarix Elderly Group | Number of Seroprotected Subjects | A/Uruguay (Day 0) | 8 subjects |
Primary
Number of Subjects With HI Antibody Titer Above the Cut-off Value
The cut-off value assessed was ≥ 1:10 and was presented for all three vaccine influenza virus strains
Time frame: At Day 0 and 21
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluarix Adult Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Brisbane (Day 0) | 36 subjects |
| Fluarix Adult Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Brisbane (Day 21) | 61 subjects |
| Fluarix Adult Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Uruguay (Day 0) | 19 subjects |
| Fluarix Adult Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Uruguay (Day 21) | 57 subjects |
| Fluarix Adult Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | B/Brisbane (Day 0) | 60 subjects |
| Fluarix Adult Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | B/Brisbane (Day 21) | 61 subjects |
| Fluarix Elderly Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | B/Brisbane (Day 0) | 58 subjects |
| Fluarix Elderly Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Brisbane (Day 0) | 35 subjects |
| Fluarix Elderly Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Uruguay (Day 21) | 58 subjects |
| Fluarix Elderly Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Brisbane (Day 21) | 58 subjects |
| Fluarix Elderly Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | B/Brisbane (Day 21) | 59 subjects |
| Fluarix Elderly Group | Number of Subjects With HI Antibody Titer Above the Cut-off Value | A/Uruguay (Day 0) | 23 subjects |
Primary
Serconversion Factor
Seroconversion factor, defined as the fold increase in serum HI GMT post-vaccination compared to pre-vaccination (Day 0), is presented for all three vaccine influenza virus strains
Time frame: At Day 21
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluarix Adult Group | Serconversion Factor | A/Brisbane | 12.2 factor |
| Fluarix Adult Group | Serconversion Factor | A/Uruguay | 12.0 factor |
| Fluarix Adult Group | Serconversion Factor | B/Brisbane | 7.7 factor |
| Fluarix Elderly Group | Serconversion Factor | A/Brisbane | 5.9 factor |
| Fluarix Elderly Group | Serconversion Factor | A/Uruguay | 12.4 factor |
| Fluarix Elderly Group | Serconversion Factor | B/Brisbane | 4.9 factor |
Primary
Seroprotection Power
Seroprotection power is defined as the number of subject who had a pre-vaccination titer \< 1:40 and a post-vaccination titer ≥ 1:40
Time frame: At Day 21
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects unprotected at pre-vaccination and with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluarix Adult Group | Seroprotection Power | B/Brisbane (N=13; 9) | 13 subjects |
| Fluarix Adult Group | Seroprotection Power | A/Brisbane (N=46; 50) | 40 subjects |
| Fluarix Adult Group | Seroprotection Power | A/Uruguay (N=56; 51) | 42 subjects |
| Fluarix Elderly Group | Seroprotection Power | A/Brisbane (N=46; 50) | 32 subjects |
| Fluarix Elderly Group | Seroprotection Power | A/Uruguay (N=56; 51) | 35 subjects |
| Fluarix Elderly Group | Seroprotection Power | B/Brisbane (N=13; 9) | 9 subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAE)
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.
Time frame: During the 21-day (Day 0-20) post-vaccination period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluarix Adult Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 1 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 0 subjects |
Secondary
Number of Subjects Reporting Solicited Symptoms
Solicited local symptoms assessed include ecchymosis, induration, pain, redness, and swelling. Solicited general symptoms assessed include arthralgia, fatigue, headache, myalgia, shivering, sweating, and fever
Time frame: During the 4-day (Day 0-3) post-vaccination period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Induration | 19 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 10 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Redness | 24 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Headache | 8 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Ecchymosis | 3 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Myalgia | 15 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 16 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Shivering | 4 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Pain | 36 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Sweating | 5 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Arthralgia | 6 subjects |
| Fluarix Adult Group | Number of Subjects Reporting Solicited Symptoms | Fever | 0 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Fever | 0 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Ecchymosis | 0 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Induration | 7 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Pain | 22 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Redness | 11 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 6 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Arthralgia | 2 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 8 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Headache | 8 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Myalgia | 7 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Shivering | 5 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Solicited Symptoms | Sweating | 4 subjects |
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 the 21-day (Day 0-20) post-vaccination period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluarix Adult Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 7 subjects |
| Fluarix Elderly Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 6 subjects |