Influenza
Conditions
Brief summary
The purpose of this study is to determine the immunogenicity and safety profile of CSL Limited's Influenza Virus Vaccine compared to a US Licensed Comparator Influenza Virus Vaccine.
Interventions
BIOLOGICALCSL Limited Influenza Virus Vaccine (Afluria®)
A single 0.5 mL, intramuscular injection in the deltoid region of the arm on day 0.
BIOLOGICALUS Licensed Influenza Virus Vaccine (Fluzone®)
A single 0.5 mL, intramuscular injection in the deltoid region of the arm on day 0.
Sponsors
Seqirus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Males aged ≥ 65 years or females of non-childbearing potential aged ≥ 65 years ; 2. Written informed consent ; 3. Willingness to provide a blood sample.
Exclusion criteria
1. Known hypersensitivity to a previous dose of influenza vaccine or allergy to eggs, chicken protein, neomycin, polymyxin, or any components of the Study Vaccines; 2. Previous vaccination against influenza in 2008 or 2009 with seasonal trivalent inactivated influenza vaccine; 3. Known history of Guillain-Barré Syndrome; 4. Clinical signs of active infection and/or an oral temperature of greater than or equal to 100 degrees F (37.8 degrees C). 5. Have active or recent and clinically significant gastrointestinal/hepatic, renal, neurological, cardiovascular, respiratory, endocrine disorders or other medical disorders; 6. History of seizures; 7. Confirmed or suspected immunosuppressive condition, or a previously diagnosed immunodeficiency disorder; 8. Clinically significant history of malignancy 9. Current treatment, or treatment with radiotherapy or cytotoxic drugs at any time during the six months prior to administration of the Study Vaccine; 10. Current immunosuppressive or immunomodulative therapy; 11. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the Study Vaccine; 12. Participation in a clinical trial or use of an investigational compound within 30 days prior to receiving the Study Vaccine ; 13. Vaccination with a registered vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to receiving the Study Vaccine. 14. Current treatment with warfarin or other anticoagulants; 15. Major congenital defects; 16. Evidence, or history (within the previous 12 months) of drug or alcohol abuse; 17. Unwillingness or inability to comply with the study protocol including completion of adverse event diary cards; 18. History of psychiatric disorders; 19. Resident of long term care facility.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer 21 Days After the Study Vaccination | 21 days after vaccination | — |
| Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | 21 days after vaccination | Seroconversion rate was defined as the proportion of participants with a HI titer of less than 1:10 before vaccination achieving a HI antibody titer of 1:40 or more after vaccination, or with a HI titer of 1:10 or more before vaccination achieving a four-fold or greater increase in HI titer after vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Intensity of Unsolicited Adverse Events (UAEs) | 21 days after vaccination | Abbreviation UAE stands for Unsolicited Adverse Event. |
| Frequency and Intensity of Local and Systemic Solicited Symptoms | 5 days after vaccination | — |
| New Onsets of Chronic Illness | 180 days after vaccination | A NOCI was defined as the diagnosis of a chronic medical condition where the symptoms commenced or worsened following exposure to the study vaccine and may have included those potentially controllable by medication (e.g., glaucoma, hypertension). |
| Serious Adverse Events | 180 days after vaccination | — |
| Duration of Local and Systemic Solicited Symptoms | 5 days after vaccination | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Afluria® Group Participants received one dose of the 2008/2009 formulation of Afluria® by intramuscular injection. | 630 |
| Fluzone® Group Participants received one dose of the 2008/2009 formulation of Fluzone® by intramuscular injection. | 636 |
| Total | 1,266 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Fluzone® Group | Afluria® Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 636 Participants | 630 Participants | 1266 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 71.7 years STANDARD_DEVIATION 5.53 | 71.7 years STANDARD_DEVIATION 5.56 | 71.7 years STANDARD_DEVIATION 5.54 |
| Region of Enrollment United States | 636 participants | 630 participants | 1266 participants |
| Sex: Female, Male Female | 362 Participants | 364 Participants | 726 Participants |
| Sex: Female, Male Male | 274 Participants | 266 Participants | 540 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 142 / 630 | 119 / 636 |
| serious Total, serious adverse events | 22 / 630 | 26 / 636 |
Outcome results
Primary
Geometric Mean Titer 21 Days After the Study Vaccination
Time frame: 21 days after vaccination
Population: Evaluable Population: comprised participants who were vaccinated, provided blood samples before and after vaccination, did not experience a laboratory-confirmed influenza infection, and did not receive a contraindicated medication.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Afluria® Group | Geometric Mean Titer 21 Days After the Study Vaccination | H1N1 (A/Brisbane/59/2007) | 58.60 Titers |
| Afluria® Group | Geometric Mean Titer 21 Days After the Study Vaccination | H3N2 (A/Uruguay/716/2007) | 377.94 Titers |
| Afluria® Group | Geometric Mean Titer 21 Days After the Study Vaccination | B (B/Florida/4/2006) | 30.16 Titers |
| Fluzone® Group | Geometric Mean Titer 21 Days After the Study Vaccination | H1N1 (A/Brisbane/59/2007) | 58.45 Titers |
| Fluzone® Group | Geometric Mean Titer 21 Days After the Study Vaccination | H3N2 (A/Uruguay/716/2007) | 337.23 Titers |
| Fluzone® Group | Geometric Mean Titer 21 Days After the Study Vaccination | B (B/Florida/4/2006) | 33.31 Titers |
Primary
Percentage of Participants With Seroconversion 21 Days After the Study Vaccination
Seroconversion rate was defined as the proportion of participants with a HI titer of less than 1:10 before vaccination achieving a HI antibody titer of 1:40 or more after vaccination, or with a HI titer of 1:10 or more before vaccination achieving a four-fold or greater increase in HI titer after vaccination.
Time frame: 21 days after vaccination
Population: Evaluable Population: comprised participants who were vaccinated, provided blood samples before and after vaccination, did not experience a laboratory-confirmed influenza infection, and did not receive a contraindicated medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afluria® Group | Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | H1N1 (A/Brisbane/59/2007) | 38.6 Percentage of participants |
| Afluria® Group | Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | H3N2 (A/Uruguay/716/2007) | 69.0 Percentage of participants |
| Afluria® Group | Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | B (B/Florida/4/2006) | 28.9 Percentage of participants |
| Fluzone® Group | Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | H1N1 (A/Brisbane/59/2007) | 43.2 Percentage of participants |
| Fluzone® Group | Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | H3N2 (A/Uruguay/716/2007) | 68.7 Percentage of participants |
| Fluzone® Group | Percentage of Participants With Seroconversion 21 Days After the Study Vaccination | B (B/Florida/4/2006) | 33.8 Percentage of participants |
Secondary
Duration of Local and Systemic Solicited Symptoms
Time frame: 5 days after vaccination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any pain | 1.62 Days | Standard Deviation 2.094 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any tenderness | 2.04 Days | Standard Deviation 2.147 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any redness | 1.42 Days | Standard Deviation 0.692 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any swelling / induration | 2.58 Days | Standard Deviation 3.031 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any bruising | 6.50 Days | Standard Deviation 8.021 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any fever | 1 Days | Standard Deviation 0 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any headache | 2.08 Days | Standard Deviation 3.004 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any malaise | 1.86 Days | Standard Deviation 1.85 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any myalgia | 2.10 Days | Standard Deviation 3.193 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any chills | 1.40 Days | Standard Deviation 0.737 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any nausea | 1.62 Days | Standard Deviation 1.193 |
| Afluria® Group | Duration of Local and Systemic Solicited Symptoms | Any vomiting | 1 Days | Standard Deviation 0 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any nausea | 1.78 Days | Standard Deviation 0.972 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any pain | 1.70 Days | Standard Deviation 2.288 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any headache | 1.70 Days | Standard Deviation 1.782 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any tenderness | 1.90 Days | Standard Deviation 1.45 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any chills | 2.29 Days | Standard Deviation 4.341 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any redness | 2.67 Days | Standard Deviation 1.751 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any malaise | 2.08 Days | Standard Deviation 1.607 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any swelling / induration | 2.25 Days | Standard Deviation 2.028 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any vomiting | 1 Days | Standard Deviation 0 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any bruising | 10.50 Days | Standard Deviation 9.883 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any myalgia | 2.65 Days | Standard Deviation 3.961 |
| Fluzone® Group | Duration of Local and Systemic Solicited Symptoms | Any fever | 1 Days | Standard Deviation 0 |
Secondary
Frequency and Intensity of Local and Systemic Solicited Symptoms
Time frame: 5 days after vaccination
Population: Safety Population: comprised all participants who received study vaccine and provided safety follow-up safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any headache | 8.6 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any swelling / induration | 7.1 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any myalgia | 9.0 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any local solicited symptom | 40.2 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any malaise | 6.8 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any redness | 3.0 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any chills | 2.2 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any pain | 15.1 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any nausea | 1.7 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any bruising | 0.5 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any fever | 0.5 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any systemic solicited symptom | 17.6 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any vomiting | 0.3 Percentage of Participants |
| Afluria® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any tenderness | 36.2 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any vomiting | 0.3 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any local solicited symptom | 35.7 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any tenderness | 31.4 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any pain | 13.8 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any swelling / induration | 7.9 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any redness | 0.9 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any systemic solicited symptom | 17.5 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any headache | 10.5 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any myalgia | 7.7 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any malaise | 6.1 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any chills | 2.4 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any nausea | 1.4 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any fever | 0.6 Percentage of Participants |
| Fluzone® Group | Frequency and Intensity of Local and Systemic Solicited Symptoms | Any bruising | 0.6 Percentage of Participants |
Secondary
Frequency and Intensity of Unsolicited Adverse Events (UAEs)
Abbreviation UAE stands for Unsolicited Adverse Event.
Time frame: 21 days after vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afluria® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants with at least one UAE | 169 participants |
| Afluria® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants reported Grade 1 UAE | 77 participants |
| Afluria® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants reported Grade 2 UAE | 57 participants |
| Afluria® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants reported Grade 3 UAE | 35 participants |
| Fluzone® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants reported Grade 3 UAE | 35 participants |
| Fluzone® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants with at least one UAE | 171 participants |
| Fluzone® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants reported Grade 2 UAE | 68 participants |
| Fluzone® Group | Frequency and Intensity of Unsolicited Adverse Events (UAEs) | Number of participants reported Grade 1 UAE | 68 participants |
Secondary
New Onsets of Chronic Illness
A NOCI was defined as the diagnosis of a chronic medical condition where the symptoms commenced or worsened following exposure to the study vaccine and may have included those potentially controllable by medication (e.g., glaucoma, hypertension).
Time frame: 180 days after vaccination
Population: Safety Population: comprised all participants who received study vaccine and provided safety follow-up safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afluria® Group | New Onsets of Chronic Illness | Neoplasms benign, maligant and unspecified | 2 participants |
| Afluria® Group | New Onsets of Chronic Illness | Vascular disorders | 3 participants |
| Afluria® Group | New Onsets of Chronic Illness | Nervous system disorders | 0 participants |
| Afluria® Group | New Onsets of Chronic Illness | Gastrointestinal disorders | 1 participants |
| Afluria® Group | New Onsets of Chronic Illness | Number of participants with related NOCI | 0 participants |
| Afluria® Group | New Onsets of Chronic Illness | Hepatobiliary disorders | 1 participants |
| Afluria® Group | New Onsets of Chronic Illness | Eye disorders | 1 participants |
| Afluria® Group | New Onsets of Chronic Illness | Musculoskeletal and connective tissue disorders | 2 participants |
| Afluria® Group | New Onsets of Chronic Illness | Psychiatric disorders | 1 participants |
| Afluria® Group | New Onsets of Chronic Illness | Renal and urinary disorders | 1 participants |
| Afluria® Group | New Onsets of Chronic Illness | Cardiac disorders | 2 participants |
| Afluria® Group | New Onsets of Chronic Illness | Reproductive system and breast disorders | 2 participants |
| Afluria® Group | New Onsets of Chronic Illness | Number of participants with at least one NOCI | 14 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Reproductive system and breast disorders | 0 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Number of participants with at least one NOCI | 11 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Number of participants with related NOCI | 0 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Neoplasms benign, maligant and unspecified | 3 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Psychiatric disorders | 3 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Nervous system disorders | 1 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Eye disorders | 0 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Cardiac disorders | 0 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Vascular disorders | 1 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Gastrointestinal disorders | 1 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Hepatobiliary disorders | 0 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Musculoskeletal and connective tissue disorders | 2 participants |
| Fluzone® Group | New Onsets of Chronic Illness | Renal and urinary disorders | 0 participants |
Secondary
Serious Adverse Events
Time frame: 180 days after vaccination
Population: Safety Population: comprised all participants who received study vaccine and provided safety follow-up safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afluria® Group | Serious Adverse Events | Number of participants with at least one SAE | 22 participants |
| Afluria® Group | Serious Adverse Events | Number of participants with related SAE | 0 participants |
| Fluzone® Group | Serious Adverse Events | Number of participants with at least one SAE | 26 participants |
| Fluzone® Group | Serious Adverse Events | Number of participants with related SAE | 0 participants |