Influenza Vaccines
Conditions
Keywords
Influenza
Brief summary
Vaccination is currently the most effective means of controlling influenza and preventing its complications and mortality in persons at risk. Once a year, a meeting of World Health Organization (WHO) experts takes place, leading to a recommendation on the influenza A and B strains that should be used for the production of vaccine for the coming influenza season. For the strains which do not change from the previous year, the vaccine can be formulated from the old mono bulk from the previous year. Bulks as old as 12 months may be blended to make trivalent inactivated vaccine (TIV) under the current Canadian and US licenses. This study is conducted to evaluate safety and immunogenicity of Fluviral vaccines made with the aged bulk material compared with the new bulk material. This protocol posting has been updated in order to comply with the FDA Amendment Act, Sept 2007.
Interventions
BIOLOGICALFluviral
One dose, Intramuscular injection
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study. * Male and female adults, 18 to 60 years. * Written informed consent obtained from the subject. * 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 the duration of the study.
Exclusion criteria
* Acute disease at the time of enrollment. * Any confirmed or suspected immunosuppressive condition * Presence of blood dyscrasias, including hemaglobinopathies and myelo- or lymphoproliferative disorder. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * A history of any demyelinating disease including Guillain-Barré syndrome. * Presence of an active neurological disorder. * Any significant disorder of coagulation that increases the risk of intramuscular injections or treatment with coumadin derivatives or heparin. * Receipt of an influenza vaccine within 6 months prior to study enrollment. * Administration of any vaccines within 30 days prior to study enrollment or during the study period. * 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. * Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned during the study. * Any known or suspected allergy to any constituent of Fluviral and/or a history of anaphylactic type reaction to consumption of eggs, and/or reactions to products containing mercury. * A history of severe adverse reaction to a previous influenza vaccination. * Lactating/nursing female. * Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Anti-H3 and B Strains | At Day 21 | GMTs for H1 strain is addressed as a secondary endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Seroconverted. | At Day 21. | The table shows the number of participants who have either a pre-vaccination titer \< 1:10 and a post-vaccination titer \>= 1:40 or a prevaccination titer \>= 1:10 and at least a 4-fold increase in post-vaccination titer, at Day 21. |
| Number of Seroprotected Participants. | At Days 0 and 21 | The table presents the number of participants with a serum haemagglutination inhibition (HI) titer \>= 1:40 that usually is accepted as indicating protection. |
| Seroconversion Factors Defined as the Fold Increase in Serum HI GMTs Post-vaccination for Influenza Antigen H1N1 | At Day 21 compared to Day 0 | Seroconversion factors are defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0, at Day 21. This table presents the SCF for the H1 strain. The SCF for the other strains are addressed in the next table. |
| The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B | At Day 21 compared to Day 0 | The fold increase in anti-HI GMTs for influenza antigen H1 is presented in the previous table. The fold increase corresponds to the Unit of Measure Factor. |
| Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | At Days 0 and 21 | The table contains GMTs of the H1 strains at Day 0 & 21 and of the H3 and B strains at Day 0 (values at Day 21 for H3 and B strains were primary outcome measures) |
| Number of Participants Reporting Solicited General Symptoms | During the 4-day period following each vaccination. | Solicited general symptoms assessed include bronchospasm, chills, cough, fatigue, fever, headache, joint pain at other location, muscle aches, red eyes, sore throat, and swelling of the face |
| Number of Participants Reporting Unsolicited Adverse Events (AE). | During the 21-day period following each 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. |
| Number of Participants Reporting Serious Adverse Events (SAE) | Within 21 days after vaccination | 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 Participants Reporting Solicited Local Symptoms | During the 4-day follow up period following vaccination. | Solicited local symptoms assessed include pain, redness and swelling. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Old Bulk This group received a full dose of Fluviral made from aged bulk material | 500 |
| New Bulk This group received a full dose of Fluviral made from new material | 500 |
| Total | 1,000 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Old Bulk | New Bulk | Total |
|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 12.08 | 40.1 years STANDARD_DEVIATION 12.01 | 40.1 years STANDARD_DEVIATION 12.04 |
| Sex: Female, Male Female | 296 Participants | 280 Participants | 576 Participants |
| Sex: Female, Male Male | 204 Participants | 220 Participants | 424 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 500 | 0 / 500 |
| other Total, other adverse events | 271 / 500 | 290 / 500 |
| serious Total, serious adverse events | 0 / 500 | 4 / 500 |
Outcome results
Primary
Geometric Mean Titers (GMTs) of Anti-H3 and B Strains
GMTs for H1 strain is addressed as a secondary endpoint
Time frame: At Day 21
Population: Analysis was performed on the According-To-Protocol cohort for immunogenicity, including subjects for whom results were available for that particular timepoint and who were not eliminated due to exclusion criteria.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Old Bulk | Geometric Mean Titers (GMTs) of Anti-H3 and B Strains | Anti-H3N2 antibody GMT | 369.6 Titer |
| Old Bulk | Geometric Mean Titers (GMTs) of Anti-H3 and B Strains | Anti-B antibody GMT | 269.6 Titer |
| New Bulk | Geometric Mean Titers (GMTs) of Anti-H3 and B Strains | Anti-H3N2 antibody GMT | 331.2 Titer |
| New Bulk | Geometric Mean Titers (GMTs) of Anti-H3 and B Strains | Anti-B antibody GMT | 245.0 Titer |
Secondary
Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains
The table contains GMTs of the H1 strains at Day 0 & 21 and of the H3 and B strains at Day 0 (values at Day 21 for H3 and B strains were primary outcome measures)
Time frame: At Days 0 and 21
Population: Analysis was performed on the According-To-Protocol cohort for immunogenicity, including subjects for whom results were available for that particular timepoint and who were not eliminated due to exclusion criteria.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Old Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-H1N1 antibody GMT at Day 0 (n=297, 292) | 15.1 Titer |
| Old Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-H1N1 antibody GMT at Day 21 (n=298, 291) | 188.1 Titer |
| Old Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-H3N2 antibody GMT at Day 0 (n=297, 292) | 30.4 Titer |
| Old Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-B antibody GMT at Day 0 (n=297, 292) | 29.3 Titer |
| New Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-B antibody GMT at Day 0 (n=297, 292) | 30.0 Titer |
| New Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-H1N1 antibody GMT at Day 0 (n=297, 292) | 15.7 Titer |
| New Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-H3N2 antibody GMT at Day 0 (n=297, 292) | 35.7 Titer |
| New Bulk | Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | Anti-H1N1 antibody GMT at Day 21 (n=298, 291) | 169.9 Titer |
Secondary
Number of Participants 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: Within 21 days after vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Bulk | Number of Participants Reporting Serious Adverse Events (SAE) | Any SAE | 0 participants |
| Old Bulk | Number of Participants Reporting Serious Adverse Events (SAE) | Fatal SAE | 0 participants |
| New Bulk | Number of Participants Reporting Serious Adverse Events (SAE) | Any SAE | 4 participants |
| New Bulk | Number of Participants Reporting Serious Adverse Events (SAE) | Fatal SAE | 0 participants |
Secondary
Number of Participants Reporting Solicited General Symptoms
Solicited general symptoms assessed include bronchospasm, chills, cough, fatigue, fever, headache, joint pain at other location, muscle aches, red eyes, sore throat, and swelling of the face
Time frame: During the 4-day period following each vaccination.
Population: Analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Chills | 60 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Joint pain at other location | 55 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Fatigue | 113 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Muscle aches | 141 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Bronchospasm | 26 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Red eyes | 32 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Axillary fever >= 37.5° Celsius (C) | 18 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Sore throat | 61 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Cough | 50 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Swelling of the face | 9 participants |
| Old Bulk | Number of Participants Reporting Solicited General Symptoms | Headache | 110 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Swelling of the face | 11 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Chills | 45 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Cough | 53 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Fatigue | 113 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Axillary fever >= 37.5° Celsius (C) | 9 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Headache | 101 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Joint pain at other location | 50 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Muscle aches | 138 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Red eyes | 31 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Sore throat | 62 participants |
| New Bulk | Number of Participants Reporting Solicited General Symptoms | Bronchospasm | 24 participants |
Secondary
Number of Participants Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, redness and swelling.
Time frame: During the 4-day follow up period following vaccination.
Population: Analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Bulk | Number of Participants Reporting Solicited Local Symptoms | Pain | 271 participants |
| Old Bulk | Number of Participants Reporting Solicited Local Symptoms | Redness | 88 participants |
| Old Bulk | Number of Participants Reporting Solicited Local Symptoms | Swelling | 59 participants |
| New Bulk | Number of Participants Reporting Solicited Local Symptoms | Pain | 290 participants |
| New Bulk | Number of Participants Reporting Solicited Local Symptoms | Redness | 97 participants |
| New Bulk | Number of Participants Reporting Solicited Local Symptoms | Swelling | 63 participants |
Secondary
Number of Participants 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 period following each vaccination.
Population: The analysis was performed on the Total Vaccinated Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Bulk | Number of Participants Reporting Unsolicited Adverse Events (AE). | 127 participants |
| New Bulk | Number of Participants Reporting Unsolicited Adverse Events (AE). | 129 participants |
Secondary
Number of Participants Who Seroconverted.
The table shows the number of participants who have either a pre-vaccination titer \< 1:10 and a post-vaccination titer \>= 1:40 or a prevaccination titer \>= 1:10 and at least a 4-fold increase in post-vaccination titer, at Day 21.
Time frame: At Day 21.
Population: Analysis was performed on the According-To-Protocol cohort for immunogenicity, including subjects for whom results were available for that particular timepoint and who were not eliminated due to exclusion criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Bulk | Number of Participants Who Seroconverted. | Anti-H1N1 | 218 participants |
| Old Bulk | Number of Participants Who Seroconverted. | Anti-H3N2 | 212 participants |
| Old Bulk | Number of Participants Who Seroconverted. | Anti-B | 205 participants |
| New Bulk | Number of Participants Who Seroconverted. | Anti-H1N1 | 197 participants |
| New Bulk | Number of Participants Who Seroconverted. | Anti-H3N2 | 187 participants |
| New Bulk | Number of Participants Who Seroconverted. | Anti-B | 185 participants |
Secondary
Number of Seroprotected Participants.
The table presents the number of participants with a serum haemagglutination inhibition (HI) titer \>= 1:40 that usually is accepted as indicating protection.
Time frame: At Days 0 and 21
Population: Analysis was performed on the According-To-Protocol cohort for immunogenicity, including subjects for whom results were available for that particular timepoint and who were not eliminated due to exclusion criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Bulk | Number of Seroprotected Participants. | Anti-H1N1 at Day 0 (n=297, 292) | 80 participants |
| Old Bulk | Number of Seroprotected Participants. | Anti-H1N1 at Day 21 (n=298, 291) | 276 participants |
| Old Bulk | Number of Seroprotected Participants. | Anti-H3N2 at Day 0 (n=297, 292) | 149 participants |
| Old Bulk | Number of Seroprotected Participants. | Anti-H3N2 at Day 21 (n=298, 291) | 293 participants |
| Old Bulk | Number of Seroprotected Participants. | Anti-B antibody GMT at Day 0 (n=297, 292) | 144 participants |
| Old Bulk | Number of Seroprotected Participants. | Anti-B antibody GMT at Day21 (n=298, 291) | 295 participants |
| New Bulk | Number of Seroprotected Participants. | Anti-B antibody GMT at Day 0 (n=297, 292) | 150 participants |
| New Bulk | Number of Seroprotected Participants. | Anti-H1N1 at Day 0 (n=297, 292) | 90 participants |
| New Bulk | Number of Seroprotected Participants. | Anti-H3N2 at Day 21 (n=298, 291) | 286 participants |
| New Bulk | Number of Seroprotected Participants. | Anti-H1N1 at Day 21 (n=298, 291) | 266 participants |
| New Bulk | Number of Seroprotected Participants. | Anti-B antibody GMT at Day21 (n=298, 291) | 285 participants |
| New Bulk | Number of Seroprotected Participants. | Anti-H3N2 at Day 0 (n=297, 292) | 154 participants |
Secondary
Seroconversion Factors Defined as the Fold Increase in Serum HI GMTs Post-vaccination for Influenza Antigen H1N1
Seroconversion factors are defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0, at Day 21. This table presents the SCF for the H1 strain. The SCF for the other strains are addressed in the next table.
Time frame: At Day 21 compared to Day 0
Population: Analysis was performed on the According-To-Protocol cohort for immunogenicity, including subjects for whom results were available for that particular timepoint and who were not eliminated due to exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Old Bulk | Seroconversion Factors Defined as the Fold Increase in Serum HI GMTs Post-vaccination for Influenza Antigen H1N1 | 12.5 Factor |
| New Bulk | Seroconversion Factors Defined as the Fold Increase in Serum HI GMTs Post-vaccination for Influenza Antigen H1N1 | 10.8 Factor |
Secondary
The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B
The fold increase in anti-HI GMTs for influenza antigen H1 is presented in the previous table. The fold increase corresponds to the Unit of Measure Factor.
Time frame: At Day 21 compared to Day 0
Population: Analysis was performed on the According-To-Protocol cohort for immunogenicity, including subjects for whom results were available for that particular timepoint and who were not eliminated due to exclusion criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Old Bulk | The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B | Anti-H3N2 | 12.1 Factor |
| Old Bulk | The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B | Anti-B | 9.2 Factor |
| New Bulk | The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B | Anti-H3N2 | 9.2 Factor |
| New Bulk | The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B | Anti-B | 8.1 Factor |