Seasonal Influenza Vaccine
Conditions
Keywords
Influenza vaccine
Brief summary
Annual trial for registration of sub-unit influenza vaccine produced in mammalian cell culture, using the strain composition 2007/2008, when administered to adult and elderly subjects
Interventions
BIOLOGICALcTIV
One dose (0.5 mL) of cell culture-derived influenza vaccine, administered in the deltoid muscle
Sponsors
Novartis Vaccines
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Subjects eligible for enrollment into this study are male and female adults who were: 1. ≥ 18 years of age, mentally competent, willing and able to give informed consent prior to study entry 2. available for all the visits scheduled in the study and able to comply with all study requirements 3. in good health as determined by: * medical history * physical examination * clinical judgment of the investigator Written informed consent had to be obtained from all the subjects before enrollment in the study after the nature of the study had been explained.
Exclusion criteria
Subjects were not to be enrolled into the study if at least one of the following criteria was fulfilled: 1. Any serious chronic or acute disease such as: 1. Cancer (leukemia, lymphomas, neoplasm), except for benign or localized skin cancer and non-metastatic prostate cancer not presently treated with chemotherapy 2. Congestive heart failure 3. Advanced arteriosclerotic disease 4. Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy and/or acute exacerbation of a COPD within the last 14 days. 5. Autoimmune disease (including rheumatoid arthritis), if under immunosuppressive therapy (see below) 6. Insulin dependent diabetes mellitus 7. Acute or progressive hepatic disease 8. Acute or progressive renal disease 9. Severe neurological or psychiatric disorder 2. History of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study vaccine or chemically related substances 3. Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age) resulting for example from: 1. Receipt of immunosuppressive therapy (chronic therapy with immunosuppressive drugs, any parenteral or oral corticosteroid (substitution dose in case of absence of suprarenal function allowed) or cancer chemotherapy/radiotherapy) within the last 2 months and for the full length of the study, 2. Receipt of immunostimulants, 3. Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months and for the full length of the study, 4. Suspected or known HIV infection or HIV-related disease. 4. Known or suspected history of drug or alcohol abuse 5. Bleeding diathesis or receive anticoagulants of the coumarin type 6. Women who are pregnant or woman of childbearing potential unwilling to practice acceptable contraception for the duration of the study (21 days) 7. Influenza immunization or laboratory confirmed influenza within the last 6 months and more than one influenza immunization within the past 12 months 8. Immunization with any other vaccine and/or any investigational vaccine four weeks prior to study start 9. Any significant acute or chronic infections requiring systemic antibiotic treatment or antiviral therapy within the last 7 days 10. Fever (i.e. body temperature ≥ 38.0°C) within the past 3 days prior to study entry 11. Simultaneous participation in another clinical study 12. Any condition, which, in the opinion of the investigator, might prevent the subject from participation or interfere with the evaluation of the study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | 3 weeks postvaccination (Day 22) | Pre and postvaccination geometric mean titers against all 3 strains were assessed by hemagglutination inhibition (HI) assay using egg derived antigen in adults and elderly subjects. |
| Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | 3 weeks postvaccination (Day 22) | Geometric mean ratio (GMR) of Day 22 / Day 1 geometric mean antibody titers was assessed by hemagglutination inhibition (HI)assay using egg derived antigen in adults and elderly subjects. The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (Day22 / Day1) in HI antibody titer is \>2.5 for adults and \>2.0 for elderly subjects. |
| Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | 3 weeks postvaccination (Day 22) | HI titer as assessed by hemagglutination inhibition (HI) assay using egg derived antigen in adults and elderly subjects. This criterion is met according to European (CHMP) guideline if the percentages of subjects achieving HI titers ≥40 is \>70% for adults and \>60% for elderly subjects. |
| Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | 3 weeks postvaccination (Day 22) | Proportion of subjects with either seroconversion (antibody increase from \< 10 pre vaccination to ≥40 post vaccination) or significant increase (antibody titer of ≥10 pre vaccination and 4-fold antibody increase post vaccination). According to the CHMP criteria, the percentages of subjects achieving seroconversion or significant increase should be \>40% for adults and \>30% for elderly subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Local and Systemic Reactions | 3 days postvaccination | To evaluate the safety and tolerability of cell culture derived vaccine (cTIV) in adults and elderly subjects in terms of number of subjects reporting local and systemic reactions after 1 vaccine dose. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| cTIV (Adults) Adults 18-60 years of age received one dose of cell culture derived trivalent influenza vaccine (cTIV). | 68 |
| cTIV (Elderly) Elderly subjects \>= 61 years of age received one dose of cell culture derived trivalent influenza vaccine (cTIV). | 67 |
| Total | 135 |
Baseline characteristics
| Characteristic | cTIV (Adults) | cTIV (Elderly) | Total |
|---|---|---|---|
| Age Continuous | 37.4 years STANDARD_DEVIATION 12.3 | 67.4 years STANDARD_DEVIATION 4.7 | 52.3 years STANDARD_DEVIATION 17.7 |
| Sex: Female, Male Female | 39 Participants | 25 Participants | 64 Participants |
| Sex: Female, Male Male | 29 Participants | 42 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 68 | 21 / 67 |
| serious Total, serious adverse events | 0 / 68 | 0 / 67 |
Outcome results
Primary
Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV)
Geometric mean ratio (GMR) of Day 22 / Day 1 geometric mean antibody titers was assessed by hemagglutination inhibition (HI)assay using egg derived antigen in adults and elderly subjects. The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (Day22 / Day1) in HI antibody titer is \>2.5 for adults and \>2.0 for elderly subjects.
Time frame: 3 weeks postvaccination (Day 22)
Population: Analysis was done on per protocol set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| cTIV (Adults) | Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | A/H1N1 (Day 22 / Day1) | 29 Ratio |
| cTIV (Adults) | Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | A/H3N2 (Day 22 / Day1) | 11 Ratio |
| cTIV (Adults) | Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | B (Day 22 / Day1) | 12 Ratio |
| cTIV (Elderly) | Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | A/H1N1 (Day 22 / Day1) | 8.74 Ratio |
| cTIV (Elderly) | Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | A/H3N2 (Day 22 / Day1) | 3.53 Ratio |
| cTIV (Elderly) | Geometric Mean Ratio After 1 Dose of the Cell Culture Derived Vaccine (cTIV) | B (Day 22 / Day1) | 2.51 Ratio |
Primary
Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV).
Pre and postvaccination geometric mean titers against all 3 strains were assessed by hemagglutination inhibition (HI) assay using egg derived antigen in adults and elderly subjects.
Time frame: 3 weeks postvaccination (Day 22)
Population: Analysis was done on per protocol set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| cTIV (Adults) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Prevaccination (Day 1) | 22 Titer |
| cTIV (Adults) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Postvaccination (Day 22) | 624 Titer |
| cTIV (Adults) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Prevaccination (Day 1) | 36 Titer |
| cTIV (Adults) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Postvaccination (Day 22) | 405 Titer |
| cTIV (Adults) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Prevaccination (Day 1) | 8.16 Titer |
| cTIV (Adults) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Postvaccination (Day 22) | 96 Titer |
| cTIV (Elderly) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Prevaccination (Day 1) | 16 Titer |
| cTIV (Elderly) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Prevaccination (Day 1) | 23 Titer |
| cTIV (Elderly) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Postvaccination (Day 22) | 283 Titer |
| cTIV (Elderly) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Postvaccination (Day 22) | 199 Titer |
| cTIV (Elderly) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Postvaccination (Day 22) | 40 Titer |
| cTIV (Elderly) | Geometric Mean Titers (GMT) After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Prevaccination (Day 1) | 80 Titer |
Primary
Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV).
HI titer as assessed by hemagglutination inhibition (HI) assay using egg derived antigen in adults and elderly subjects. This criterion is met according to European (CHMP) guideline if the percentages of subjects achieving HI titers ≥40 is \>70% for adults and \>60% for elderly subjects.
Time frame: 3 weeks postvaccination (Day 22)
Population: Analysis was done on per protocol set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| cTIV (Adults) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Prevaccination (Day 1) | 35 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Postvaccination (Day 22) | 96 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Prevaccination (Day 1) | 51 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Postvaccination (Day 22) | 97 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Prevaccination (Day 1) | 13 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Postvaccination (Day 22) | 79 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Prevaccination (Day 1) | 28 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Prevaccination (Day 1) | 37 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Postvaccination (Day 22) | 96 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 Postvaccination (Day 22) | 96 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B Postvaccination (Day 22) | 66 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With HI Titer ≥40 After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 Prevaccination (Day 1) | 72 Percentages of Subjects |
Primary
Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV).
Proportion of subjects with either seroconversion (antibody increase from \< 10 pre vaccination to ≥40 post vaccination) or significant increase (antibody titer of ≥10 pre vaccination and 4-fold antibody increase post vaccination). According to the CHMP criteria, the percentages of subjects achieving seroconversion or significant increase should be \>40% for adults and \>30% for elderly subjects.
Time frame: 3 weeks postvaccination (Day 22)
Population: Analysis was done on per protocol set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| cTIV (Adults) | Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 | 79 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 | 72 Percentages of Subjects |
| cTIV (Adults) | Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B | 65 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H1N1 | 67 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | A/H3N2 | 40 Percentages of Subjects |
| cTIV (Elderly) | Percentages of Subjects With Seroconversion or Significant Increase After 1 Dose of Cell Culture Derived Vaccine (cTIV). | B | 25 Percentages of Subjects |
Secondary
Number of Subjects Reporting Local and Systemic Reactions
To evaluate the safety and tolerability of cell culture derived vaccine (cTIV) in adults and elderly subjects in terms of number of subjects reporting local and systemic reactions after 1 vaccine dose.
Time frame: 3 days postvaccination
Population: Analysis was done on safety set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Pain | 31 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Fatigue | 10 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Induration | 4 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Headache | 12 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Swelling | 2 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Sweating | 2 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Fever ( ≥ 38°C) | 0 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Myalgia | 3 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Ecchymosis | 1 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Arthralgia | 4 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Malaise | 5 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Chills | 0 Subjects |
| cTIV (Adults) | Number of Subjects Reporting Local and Systemic Reactions | Redness/Erythema | 0 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Chills | 0 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Redness/Erythema | 2 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Swelling | 2 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Pain | 16 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Ecchymosis | 2 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Induration | 4 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Fever ( ≥ 38°C) | 0 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Malaise | 3 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Fatigue | 8 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Headache | 9 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Sweating | 3 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Myalgia | 2 Subjects |
| cTIV (Elderly) | Number of Subjects Reporting Local and Systemic Reactions | Arthralgia | 3 Subjects |