Influenza
Conditions
Brief summary
The purpose of the study is to assess the efficacy and safety of CSL's 2009/2010 formulation of the Enzira vaccine.
Interventions
BIOLOGICALInactivated Influenza Vaccine (2009 / 2010 formulation)
A single 0.5mL intramuscular injection into the deltoid region of the arm on Day 0.
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 at the time of providing informed consent * Participants are capable of understanding the purposes and risks of the study and are able to provide written informed consent * Willing and able to adhere to all protocol requirements * Able to provide a sample of approximately 17 mL of venous blood on two separate occasions without undue distress/discomfort * 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
Exclusion criteria
* Known hypersensitivity to a previous dose of influenza vaccine or allergy to eggs, chicken protein, neomycin, polymyxin, or any components of the Enzira® vaccine * Clinical signs of an active infection and/or an elevated oral temperature (≥ 38.0°C) at study entry * A clinically significant medical or psychiatric condition * A confirmed or suspected immunosuppressive condition * History of seizures * History of Guillain-Barré Syndrome * Vaccination with a seasonal influenza virus vaccine or with an experimental influenza virus vaccine in the 6 months preceding study entry * Currently receiving treatment with radiotherapy or cytotoxic drugs, or have received such treatment within the 6 months preceding administration of Enzira® vaccine * Currently receiving systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within the 3 months preceding study entry * Currently receiving immunoglobulins and/or any blood products or have received such treatment within the 3 months preceding the administration of Enzira® vaccine * Currently participating in another investigational study or recent study participation ending 3 months preceding administration of Enzira® vaccine * Currently receiving treatment with warfarin or other anticoagulants * Evidence or history of substance or alcohol abuse within the 12 months before study entry * Females of child bearing potential who are planning to become pregnant or planning to discontinue contraceptive precautions during the study period * Females who are pregnant or lactating * Any issues that, in the opinion of the investigator, would render the subject unsuitable for study participation
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 is defined as achieving a post-vaccination titre of ≥ 40 for those participants with a pre-vaccination HI titre of \< 10; significant increase is 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 is 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency of Any Solicited Local Reactions. | During the 4 days after vaccination (Day 0 plus 3 days) | The number of participants reporting any solicited local reactions. |
| The Frequency of Any Solicited Systemic Symptoms. | During the 4 days after vaccination (Day 0 plus 3 days) | The number of participants reporting any solicited systemic symptoms. |
| The Incidence of Any Unsolicited Adverse Events (AEs). | After vaccination until the end of the study; approximately 21 days | The number of participants reporting any unsolicited adverse events. Unsolicited adverse event (UAE) grading: Mild: Symptoms were easily tolerated and did not interfere with normal, everyday activities. Moderate: Enough discomfort to have caused some interference with normal, everyday activities. Severe: Symptoms that prevented normal, everyday activities. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adults Healthy volunteers aged 18 to 59 years | 60 |
| Older Adults Healthy volunteers aged 60 years or older | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Adults | Older Adults | Total |
|---|---|---|---|
| Age, Continuous | 35.3 years STANDARD_DEVIATION 12.31 | 66.2 years STANDARD_DEVIATION 5.92 | 50.7 years STANDARD_DEVIATION 18.24 |
| Sex: Female, Male Female | 27 Participants | 29 Participants | 56 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 60 | 11 / 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 is 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 comprised all participants who were vaccinated with the study vaccine, provided both pre- and post-vaccination antibody titre results, and were not excluded from the analyses (eg, for the use of a prohibited medication or a laboratory-confirmed influenza virus infection between Visits 1 and 2).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | A/Brisbane/59/2007 (H1N1) - like strain | 27.86 percentage of participants |
| Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | A/Brisbane/10/2007( H3N2) - like strain | 30.32 percentage of participants |
| Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | B/Brisbane/60/2008 - like strain | 12.85 percentage of participants |
| Older Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | A/Brisbane/59/2007 (H1N1) - like strain | 5.02 percentage of participants |
| Older Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | A/Brisbane/10/2007( H3N2) - like strain | 9.80 percentage of participants |
| Older Adults | The Geometric Mean Fold Increase (GMFI) in Antibody Titre After Vaccination. | B/Brisbane/60/2008 - like strain | 6.13 percentage of participants |
Primary
The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2.
Time frame: Approximately 21 days after vaccination
Population: The Evaluable Population comprised all participants who were vaccinated with the study vaccine, provided both pre- and post-vaccination antibody titre results, and were not excluded from the analyses (eg, for the use of a prohibited medication or a laboratory-confirmed influenza virus infection between Visits 1 and 2).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | A/Brisbane/59/2007 (H1N1) - like 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. | A/Brisbane/10/2007( H3N2) - like 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/Brisbane/60/2008 - like strain | 85.0 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | A/Brisbane/59/2007 (H1N1) - like strain | 91.4 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | A/Brisbane/10/2007( H3N2) - like strain | 94.8 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving a HI Titre ≥ 40 or Single Radial Haemolysis (SRH) Area ≥ 25 mm2. | B/Brisbane/60/2008 - like strain | 60.3 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 is defined as achieving a post-vaccination titre of ≥ 40 for those participants with a pre-vaccination HI titre of \< 10; significant increase is 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 comprised all participants who were vaccinated with the study vaccine, provided both pre- and post-vaccination antibody titre results, and were not excluded from the analyses (eg, for the use of a prohibited medication or a laboratory-confirmed influenza virus infection between Visits 1 and 2).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | A/Brisbane/10/2007 (H3N2) - like strain | 93.3 percentage of participants |
| Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | A/Brisbane/59/2007 (H1N1) - like strain | 91.7 percentage of participants |
| Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | B/Brisbane/60/2008 - like strain | 76.7 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | A/Brisbane/10/2007 (H3N2) - like strain | 63.8 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | A/Brisbane/59/2007 (H1N1) - like strain | 53.4 percentage of participants |
| Older Adults | The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre. | B/Brisbane/60/2008 - like strain | 46.6 percentage of participants |
Secondary
The Frequency of Any Solicited Local Reactions.
The number of participants reporting any solicited local reactions.
Time frame: During the 4 days after vaccination (Day 0 plus 3 days)
Population: The Safety Population comprised all participants who received study vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Frequency of Any Solicited Local Reactions. | Any erythema | 22 participants |
| Adults | The Frequency of Any Solicited Local Reactions. | Any pain | 26 participants |
| Adults | The Frequency of Any Solicited Local Reactions. | Any ecchymosis | 5 participants |
| Adults | The Frequency of Any Solicited Local Reactions. | Any solicited local reaction | 32 participants |
| Adults | The Frequency of Any Solicited Local Reactions. | Any induration larger than 50 mm | 1 participants |
| Older Adults | The Frequency of Any Solicited Local Reactions. | Any induration larger than 50 mm | 2 participants |
| Older Adults | The Frequency of Any Solicited Local Reactions. | Any erythema | 12 participants |
| Older Adults | The Frequency of Any Solicited Local Reactions. | Any solicited local reaction | 22 participants |
| Older Adults | The Frequency of Any Solicited Local Reactions. | Any pain | 14 participants |
| Older Adults | The Frequency of Any Solicited Local Reactions. | Any ecchymosis | 4 participants |
Secondary
The Frequency of Any Solicited Systemic Symptoms.
The number of participants reporting any solicited systemic symptoms.
Time frame: During the 4 days after vaccination (Day 0 plus 3 days)
Population: The Safety Population comprised all participants who received study vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Frequency of Any Solicited Systemic Symptoms. | Any solicited systemic symptom | 7 participants |
| Adults | The Frequency of Any Solicited Systemic Symptoms. | Any temperature above 38°C for 24 hours or longer | 1 participants |
| Adults | The Frequency of Any Solicited Systemic Symptoms. | Any chills | 6 participants |
| Adults | The Frequency of Any Solicited Systemic Symptoms. | Any malaise | 5 participants |
| Older Adults | The Frequency of Any Solicited Systemic Symptoms. | Any malaise | 5 participants |
| Older Adults | The Frequency of Any Solicited Systemic Symptoms. | Any solicited systemic symptom | 5 participants |
| Older Adults | The Frequency of Any Solicited Systemic Symptoms. | Any chills | 2 participants |
| Older Adults | The Frequency of Any Solicited Systemic Symptoms. | Any temperature above 38°C for 24 hours or longer | 0 participants |
Secondary
The Incidence of Any Unsolicited Adverse Events (AEs).
The number of participants reporting any unsolicited adverse events. Unsolicited adverse event (UAE) grading: Mild: Symptoms were easily tolerated and did not interfere with normal, everyday activities. Moderate: Enough discomfort to have caused some interference with normal, everyday activities. Severe: Symptoms that prevented normal, everyday activities.
Time frame: After vaccination until the end of the study; approximately 21 days
Population: The Safety Population comprised all participants who received study vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants with at least one UAE | 25 participants |
| Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants reporting mild UAE | 20 participants |
| Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants reporting moderate UAE | 12 participants |
| Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants reporting severe UAE | 0 participants |
| Older Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants reporting severe UAE | 0 participants |
| Older Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants with at least one UAE | 21 participants |
| Older Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants reporting moderate UAE | 3 participants |
| Older Adults | The Incidence of Any Unsolicited Adverse Events (AEs). | Number of participants reporting mild UAE | 21 participants |