Influenza
Conditions
Keywords
cell culture, Safety, Influenza, Humans, Adults, Immunogenicity, Influenza vaccine, Vaccine
Brief summary
The purpose of the study is to compare the safety of & immune response to a single dose of GSK Biologicals' cell-culture based influenza vaccine 138842A with that of a US licensed, egg-based trivalent influenza vaccine \[Fluarix\] in healthy adults.
Interventions
BIOLOGICALTrivalent influenza vaccine GSK 138842A
IM injection on Day 0
BIOLOGICALFluarix
IM injection on Day 0
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes can and will comply with the requirements of the protocol * A male or non-pregnant, non-lactating female between 18 and 49 years of age at the time of vaccination * Access to a telephone for scheduled follow-up telephone contacts * Ability to provide written informed consent * Healthy subjects as established by medical history and physical 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 and continue such precautions for 2 months after receipt of the study vaccine. All women will have a pregnancy test on the day of vaccination.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period * Receipt of systemic glucocorticoids within 30 days of study enrollment * Administration of immunosuppressant, cytotoxic, or other immune-modifying drugs (other than glucocorticoids) or irradiation within 6 months prior to study enrollment or planned administration during the study period * Administration of immunoglobulins and/or blood products within 3 months prior to study enrollment or planned administration during the study period * Previous vaccination against influenza (2007-2008 influenza season) * History of anaphylactic or other allergic reaction to influenza vaccine, any other vaccine, or any vaccine component or excipient * History of Guillain-Barre Syndrome (GBS) * Acute disease, febrile illness, or upper respiratory infection at screening. * History of splenectomy * Any confirmed or suspected, acquired, congenital, or hereditary immunodeficiency or immunosuppressive condition (including human immunodeficiency virus \[HIV\]) based on medical history and physical examination * Acquired or congenital coagulation disorders or known thrombocytopenia * Current treatment with warfarin or heparin derivatives * Known use of an analgesic or antipyretic medication within 12 hours prior to treatment for the purposes of prophylaxis of adverse events * Any medical condition for which the US Advisory Committee on Immunization Practices recommends vaccination against influenza
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Solicited Local Symptoms. | During the 7-day (Days 0-6) post vaccination period | Solicited local symptoms were pain, redness and swelling at the injection site. Any = occurrence of a symptom regardless of intensity. |
| Number of Subjects With Solicited General Symptoms. | During the 7-day (Days 0-6) post vaccination period | Solicited general symptoms were arthralgia, fatigue, headache, muscle aches, shivering and temperature, assessed as oral temperature above or equal (≥) 38.0 degrees Celsius (°C). Any = occurrence of a symptom regardless of intensity or relationship to vaccination. |
| Number of Subjects With Medically Attended Adverse Events (MAEs). | During the entire study period (Days 0-182) | Medically-attended events (MAEs) refer to non-serious and serious events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits and hospitalization. Related MAE = MAE assessed by the investigator as related to the vaccination. |
| Number of Subjects With New Onset of Chronic Diseases (NOCDs). | During the entire study period (Days 0-182) | NOCDs include conditions such as autoimmune disorders, asthma, type I diabetes, or allergies. |
| Number of Subjects With Unsolicited Adverse Events (AEs). | During the 90-day (Days 0-89) post-vaccination period | Unsolicited AEs cover 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. Any unsolicited AE = any unsolicited AE regardless of intensity or relationship to vaccination. |
| Number of Subjects With Serious Adverse Events (SAEs). | During the entire study period (Days 0-182) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any SAE = any SAE regardless of intensity or relationship to vaccination. |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | At Day 21 | Titers are presented as geometric mean titers (GMTs). The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.) |
| Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | At Day 21 | A seroprotected subject was defined as a vaccinated subject with a serum HI antibody titer ≥ 1:40, a level of HI antibody that has been viewed as correlating with protection against influenza. The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.) |
| Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | At Day 21 | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer \<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.) |
| Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | At Day 0 and Day 21 | GMFR was defined as the geometric mean of the ratio of the post-vaccination inverse HI titer to the Day 0 inverse HI titer. The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GSK 1388442A Group Subjects aged 18 to 49 years of age at the time of vaccination received 1 dose of GSK 1388442A vaccine at Day 0. The GSK 1388442A vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | 101 |
| Fluarix Group Subjects aged 18 to 49 years of age at the time of vaccination received 1 dose of Fluarix® vaccine at Day 0. The Fluarix® vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | 99 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | GSK 1388442A Group | Fluarix Group | Total |
|---|---|---|---|
| Age, Continuous | 33.1 Years STANDARD_DEVIATION 10.24 | 31.6 Years STANDARD_DEVIATION 9.77 | 32.4 Years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 54 Participants | 52 Participants | 106 Participants |
| Sex: Female, Male Male | 47 Participants | 47 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 64 / 101 | 63 / 99 |
| serious Total, serious adverse events | 1 / 101 | 0 / 99 |
Outcome results
Primary
Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease.
GMFR was defined as the geometric mean of the ratio of the post-vaccination inverse HI titer to the Day 0 inverse HI titer. The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.)
Time frame: At Day 0 and Day 21
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom data concerning Immunogenicity outcomes variables were available and for whom assay results were available for antibodies against at least one study vaccine component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 1388442A Group | Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | H1N1 | 10.9 fold rise |
| GSK 1388442A Group | Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | H3N2 | 10.1 fold rise |
| GSK 1388442A Group | Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | MALAY. | 12.3 fold rise |
| Fluarix Group | Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | H1N1 | 17.8 fold rise |
| Fluarix Group | Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | H3N2 | 7.5 fold rise |
| Fluarix Group | Geometric Mean Fold-rise (GMFR) in 3 Strains of Influenza Disease. | MALAY. | 10.5 fold rise |
Primary
Number of Seroconverted Subjects Against 3 Strains of Influenza Disease.
A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer \<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.)
Time frame: At Day 21
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom data concerning Immunogenicity outcomes variables were available and for whom assay results were available for antibodies against at least one study vaccine component after vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK 1388442A Group | Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | H1N1 | 72 subjects |
| GSK 1388442A Group | Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | H3N2 | 68 subjects |
| GSK 1388442A Group | Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | MALAY. | 74 subjects |
| Fluarix Group | Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | H1N1 | 79 subjects |
| Fluarix Group | Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | H3N2 | 66 subjects |
| Fluarix Group | Number of Seroconverted Subjects Against 3 Strains of Influenza Disease. | MALAY. | 67 subjects |
Primary
Number of Seroprotected Subjects Against 3 Strains of Influenza Disease.
A seroprotected subject was defined as a vaccinated subject with a serum HI antibody titer ≥ 1:40, a level of HI antibody that has been viewed as correlating with protection against influenza. The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.)
Time frame: At Day 21
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom data concerning Immunogenicity outcomes variables were available and for whom assay results were available for antibodies against at least one study vaccine component after vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK 1388442A Group | Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | H1N1 | 90 subjects |
| GSK 1388442A Group | Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | H3N2 | 98 subjects |
| GSK 1388442A Group | Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | MALAY. | 99 subjects |
| Fluarix Group | Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | H1N1 | 97 subjects |
| Fluarix Group | Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | H3N2 | 98 subjects |
| Fluarix Group | Number of Seroprotected Subjects Against 3 Strains of Influenza Disease. | MALAY. | 96 subjects |
Primary
Number of Subjects With Medically Attended Adverse Events (MAEs).
Medically-attended events (MAEs) refer to non-serious and serious events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits and hospitalization. Related MAE = MAE assessed by the investigator as related to the vaccination.
Time frame: During the entire study period (Days 0-182)
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 1388442A Group | Number of Subjects With Medically Attended Adverse Events (MAEs). | 4 subjects |
| Fluarix Group | Number of Subjects With Medically Attended Adverse Events (MAEs). | 7 subjects |
Primary
Number of Subjects With New Onset of Chronic Diseases (NOCDs).
NOCDs include conditions such as autoimmune disorders, asthma, type I diabetes, or allergies.
Time frame: During the entire study period (Days 0-182)
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 1388442A Group | Number of Subjects With New Onset of Chronic Diseases (NOCDs). | 0 subjects |
| Fluarix Group | Number of Subjects With New Onset of Chronic Diseases (NOCDs). | 0 subjects |
Primary
Number of Subjects With Serious Adverse Events (SAEs).
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any SAE = any SAE regardless of intensity or relationship to vaccination.
Time frame: During the entire study period (Days 0-182)
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 1388442A Group | Number of Subjects With Serious Adverse Events (SAEs). | 1 subjects |
| Fluarix Group | Number of Subjects With Serious Adverse Events (SAEs). | 0 subjects |
Primary
Number of Subjects With Solicited General Symptoms.
Solicited general symptoms were arthralgia, fatigue, headache, muscle aches, shivering and temperature, assessed as oral temperature above or equal (≥) 38.0 degrees Celsius (°C). Any = occurrence of a symptom regardless of intensity or relationship to vaccination.
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 subjects with the documented dose. The analysis of solicited symptoms based on the Total Vaccinated cohort included only vaccinated subjects and doses with documented safety data (i.e., symptom screen /sheet completed).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK 1388442A Group | Number of Subjects With Solicited General Symptoms. | Arthralgia | 2 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited General Symptoms. | Fatigue | 19 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited General Symptoms. | Headache | 24 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited General Symptoms. | Muscle aches | 15 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited General Symptoms. | Shivering | 3 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited General Symptoms. | Temperature ≥ 38.0°C | 1 subjects |
| Fluarix Group | Number of Subjects With Solicited General Symptoms. | Shivering | 2 subjects |
| Fluarix Group | Number of Subjects With Solicited General Symptoms. | Arthralgia | 4 subjects |
| Fluarix Group | Number of Subjects With Solicited General Symptoms. | Muscle aches | 17 subjects |
| Fluarix Group | Number of Subjects With Solicited General Symptoms. | Fatigue | 15 subjects |
| Fluarix Group | Number of Subjects With Solicited General Symptoms. | Temperature ≥ 38.0°C | 0 subjects |
| Fluarix Group | Number of Subjects With Solicited General Symptoms. | Headache | 21 subjects |
Primary
Number of Subjects With Solicited Local Symptoms.
Solicited local symptoms were pain, redness and swelling at the injection site. Any = occurrence of a symptom regardless of intensity.
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 subjects with the documented dose. The analysis of solicited symptoms based on the Total Vaccinated cohort included only vaccinated subjects and doses with documented safety data (i.e., symptom screen /sheet completed).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK 1388442A Group | Number of Subjects With Solicited Local Symptoms. | Pain | 48 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited Local Symptoms. | Redness | 1 subjects |
| GSK 1388442A Group | Number of Subjects With Solicited Local Symptoms. | Swelling | 1 subjects |
| Fluarix Group | Number of Subjects With Solicited Local Symptoms. | Pain | 48 subjects |
| Fluarix Group | Number of Subjects With Solicited Local Symptoms. | Redness | 0 subjects |
| Fluarix Group | Number of Subjects With Solicited Local Symptoms. | Swelling | 0 subjects |
Primary
Number of Subjects With Unsolicited Adverse Events (AEs).
Unsolicited AEs cover 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. Any unsolicited AE = any unsolicited AE regardless of intensity or relationship to vaccination.
Time frame: During the 90-day (Days 0-89) post-vaccination period
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK 1388442A Group | Number of Subjects With Unsolicited Adverse Events (AEs). | 28 subjects |
| Fluarix Group | Number of Subjects With Unsolicited Adverse Events (AEs). | 21 subjects |
Primary
Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease.
Titers are presented as geometric mean titers (GMTs). The 3 influenza strains assessed were A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004 (MALAY.)
Time frame: At Day 21
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom data concerning Immunogenicity outcomes variables were available and for whom assay results were available for antibodies against at least one study vaccine component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK 1388442A Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | H1N1 | 183.7 titers |
| GSK 1388442A Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | H3N2 | 333.5 titers |
| GSK 1388442A Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | MALAY. | 316.6 titers |
| Fluarix Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | H1N1 | 501.4 titers |
| Fluarix Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | H3N2 | 315.5 titers |
| Fluarix Group | Titers for Serum Hemagglutination Inhibition (HI) Antibodies for 3 Strains of Influenza Disease. | MALAY. | 326.8 titers |