Influenza, Human
Conditions
Brief summary
This is a study to assess the immune (antibody) response and safety of the 2012/2013 formulation of Enzira® (CSL Influenza vaccine) in healthy adult volunteers aged 18 years or older.
Interventions
BIOLOGICALCSL Influenza Vaccine
The study vaccine (CSL Influenza Vaccine) is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2012/2013 influenza season). The vaccine will be administered by intramuscular or subcutaneous injection.
Sponsors
Seqirus
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
* Males or females aged 18 years or older at the time of vaccination. * Females of child-bearing potential (i.e., ovulating, pre-menopausal, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen for the duration of the study. Females of child-bearing potential must return a negative urine pregnancy test result prior to vaccination with the vaccine.
Exclusion criteria
* Known hypersensitivity to a previous vaccination with influenza vaccine or allergy to eggs, ovalbumin, chicken protein, neomycin, polymyxin, or any components of the vaccine. * Clinical signs of an active infection. * A clinically significant medical condition. * Vaccination with a seasonal or experimental influenza virus vaccine in the 6 months preceding study entry. * Females who are pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | Approximately 21 days after vaccination | As per the criteria specified in the CPMP/BWP/214/96 Note for Guidance on Harmonisation of Requirements for Influenza Vaccines. For haemagglutination inhibition (HI), seroconversion (H1N1, H3N2, and B influenza virus strains) was defined as achieving a post-vaccination titre of ≥ 40 for those participants with a pre-vaccination HI titre of \< 10. A significant increase (H1N1, H3N2, and B influenza virus strains) was defined as a four-fold or greater increase in HI titre for those participants with a pre-vaccination HI titre of ≥ 10. |
| The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | Approximately 21 days after vaccination | GMFI (H1N1, H3N2, and B influenza virus strains) was defined as the geometric mean of the fold increases of post-vaccination antibody titre over the pre-vaccination antibody titre. |
| The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | Approximately 21 days after vaccination | For the H1N1, H3N2, and B influenza virus strains. Note: No SRH data were collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Intensity of Any Solicited Adverse Events (AEs). | During the 4 days after vaccination (Day 0 plus 3 days) | The percentage of participants reporting any solicited AEs and the percentage of participants reporting any solicited AEs with severe intensity. Note: Intensity of solicited AEs was collected for temperature only. Solicited local AEs collected included induration \>50 mm, erythema, ecchymosis, and pain at the vaccination site. Solicited systemic AEs collected included temperature above 38.0°C, chills, and malaise. Solicited AE intensity grading: Mild: symptoms were easily tolerated and there was no interference with daily activities; Moderate: enough discomfort to cause some interference with daily activities; Severe: symptoms that prevented normal, everyday activities. |
| Frequency of Any Unsolicited AEs. | After vaccination until the end of the study; approximately 21 days | The percentage of participants reporting any unsolicited AEs. Unsolicited AEs included AEs other than those specifically solicited. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adults Healthy volunteers aged 18 to 59 years received a single 0.5 mL dose of CSL Influenza Vaccine by intramuscular or subcutaneous injection. | 60 |
| Older Adults Healthy volunteers aged 60 years or older received a single 0.5 mL dose of CSL Influenza Vaccine by intramuscular or subcutaneous injection. | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | Adults | Older Adults | Total |
|---|---|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 12.5 | 69.2 years STANDARD_DEVIATION 6.69 | 52.2 years STANDARD_DEVIATION 19.78 |
| Sex: Female, Male Female | 38 Participants | 29 Participants | 67 Participants |
| Sex: Female, Male Male | 22 Participants | 31 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 60 | 18 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination.
GMFI (H1N1, H3N2, and B influenza virus strains) was defined as the geometric mean of the fold increases of post-vaccination antibody titre over the pre-vaccination antibody titre.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population included all participants who were vaccinated with CSL Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H1N1 strain | 17.51 geometric mean fold increase |
| Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H3N2 strain | 21.80 geometric mean fold increase |
| Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | B strain | 7.34 geometric mean fold increase |
| Older Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H1N1 strain | 7.78 geometric mean fold increase |
| Older Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | H3N2 strain | 9.88 geometric mean fold increase |
| Older Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | B strain | 2.44 geometric mean fold increase |
Primary
The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2.
For the H1N1, H3N2, and B influenza virus strains. Note: No SRH data were collected.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population included all participants who were vaccinated with CSL Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H1N1 strain | 94.9 percentage of participants |
| Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H3N2 strain | 100.0 percentage of participants |
| Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | B strain | 66.1 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H1N1 strain | 84.7 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | H3N2 strain | 100.0 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | B strain | 18.6 percentage of participants |
Primary
The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre.
As per the criteria specified in the CPMP/BWP/214/96 Note for Guidance on Harmonisation of Requirements for Influenza Vaccines. For haemagglutination inhibition (HI), seroconversion (H1N1, H3N2, and B influenza virus strains) was defined as achieving a post-vaccination titre of ≥ 40 for those participants with a pre-vaccination HI titre of \< 10. A significant increase (H1N1, H3N2, and B influenza virus strains) was defined as a four-fold or greater increase in HI titre for those participants with a pre-vaccination HI titre of ≥ 10.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population included all participants who were vaccinated with CSL Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H3N2 strain | 86.4 percentage of participants |
| Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H1N1 strain | 79.7 percentage of participants |
| Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | B strain | 59.3 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H1N1 strain | 55.9 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | H3N2 strain | 64.4 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | B strain | 18.6 percentage of participants |
Secondary
Frequency and Intensity of Any Solicited Adverse Events (AEs).
The percentage of participants reporting any solicited AEs and the percentage of participants reporting any solicited AEs with severe intensity. Note: Intensity of solicited AEs was collected for temperature only. Solicited local AEs collected included induration \>50 mm, erythema, ecchymosis, and pain at the vaccination site. Solicited systemic AEs collected included temperature above 38.0°C, chills, and malaise. Solicited AE intensity grading: Mild: symptoms were easily tolerated and there was no interference with daily activities; Moderate: enough discomfort to cause some interference with daily activities; Severe: symptoms that prevented normal, everyday activities.
Time frame: During the 4 days after vaccination (Day 0 plus 3 days)
Population: The Safety Population included all participants who received CSL Influenza Vaccine and provided follow-up safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Any solicited local AE | 46.7 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Induration > 50 mm | 0.0 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Erythema | 15.0 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Ecchymosis | 6.7 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Pain | 41.7 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Any solicited systemic AE | 15.0 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Temperature > 38°C for ≥ 24 hours | 0 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Severe temperature (> 40°C) | 0 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Chills | 10.0 percentage of participants |
| Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Malaise | 13.3 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Severe temperature (> 40°C) | 1.7 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Any solicited local AE | 18.3 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Any solicited systemic AE | 6.7 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Induration > 50 mm | 3.3 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Malaise | 6.7 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Erythema | 6.7 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Temperature > 38°C for ≥ 24 hours | 1.7 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Ecchymosis | 3.3 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Chills | 3.3 percentage of participants |
| Older Adults | Frequency and Intensity of Any Solicited Adverse Events (AEs). | Pain | 10.0 percentage of participants |
Secondary
Frequency of Any Unsolicited AEs.
The percentage of participants reporting any unsolicited AEs. Unsolicited AEs included AEs other than those specifically solicited.
Time frame: After vaccination until the end of the study; approximately 21 days
Population: The Safety Population included all participants who received CSL Influenza Vaccine and provided follow-up safety data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adults | Frequency of Any Unsolicited AEs. | 53.3 percentage of participants |
| Older Adults | Frequency of Any Unsolicited AEs. | 36.7 percentage of participants |