Influenza
Conditions
Keywords
Influenza, Adults, Elderly, Immunology, Safety
Brief summary
The purpose of this study is to evaluate the safety of a single intramuscular (IM) injection of the cell derived subunit trivalent nonadjuvanted influenza vaccine in adult and elderly subjects and the antibody response to each influenza vaccine antigen, as measured by hemagglutination inhibition (HI) at approximately 21 days postimmunization in adult and elderly subjects in compliance with the requirements of the current EU recommendations for clinical trials related to yearly licensing of influenza vaccines.
Interventions
BIOLOGICALCell derived subunit trivalent nonadjuvanted vaccine
A single 0.5 mL dose of the cell derived subunit trivalent nonadjuvated influenza vaccine (TIVc) supplied in prefilled syringes and administered intramuscularly in the deltoid muscle (preferably) of the non dominant arm.
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
1. Male and female volunteers of 18 years of age or older; 2. Individuals able to comply with all the study requirements; 3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.
Exclusion criteria
1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study. 2. Individuals with any serious chronic or acute disease (in the judgment of the investigator), including but not limited to: * Medically significant cancer (except for benign or localized skin cancer, cancer in remission for ≥10 years or localized prostate cancer that has been clinically stable for more than 2 years without treatment); * Medically significant advanced congestive heart failure (ie. NYHA class III and IV); * Chronic obstructive pulmonary disease (COPD; i.e., GOLD Stage III and IV); * Autoimmune disease (including rheumatoid arthritis, except for Hashimoto's thyroiditis that has been clinically stable for ≥5 years); * Diabetes mellitus type I; * Poorly controlled diabetes mellitus type II; * Advanced arteriosclerotic disease; * History of underlying medical condition such as major congenital abnormalities requiring surgery, chronic treatment, or associated with developmental delay (e.g., Down's syndrome); * Acute or progressive hepatic disease; * Acute or progressive renal disease; * Severe neurological (es. Guillain-Barré syndrome) or psychiatric disorder; * Severe asthma. 3. Individuals with history of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study vaccine (e.g.Influenza viral protein). 4. Individuals with 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: * receipt of immunosuppressive therapy (any parenteral or oral corticosteroid or cancer chemotherapy/radiotherapy) within the past 60 days and for the full length of the study; * receipt of immunostimulants; * receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivatives within the past 3 months and for the full length of the study; * suspected or known HIV infection or HIV-related disease. 5. Individuals with known or suspected history of drug or alcohol abuse. 6. Individuals with a bleeding diathesis or conditions associated with prolonged bleeding time that in the investigator's opinion would interfere with the safety of the subject. 7. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study. 8. Individuals with history or any illness that, in the opinion of the investigator, pose additional risk to the subjects due to participation in the study. 9. Individuals who within the past 6 months have: * had any laboratory confirmed seasonal or pandemic influenza disease; * received any seasonal or pandemic influenza vaccine. 10. Individuals who received any other vaccine within 4 weeks prior to enrollment in this study or who are planning to receive any vaccine during the study. 11. Individuals with any acute or chronic infections requiring systemic antibiotic treatment or antiviral therapy within the last 7 days. 12. Individuals that have experienced fever (i.e., axillary temperature ≥38°C) within the last 3 days of intended study vaccination. 13. Individuals participating in any clinical trial with another investigational product 4 weeks prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. 14. Individuals who are part of study personnel or close family members conducting this study. 15. BMI \>35 kg/m2. 16. Females who are pregnant (confirmed by positive urine pregnancy test) or nursing (breastfeeding). Females of childbearing potential who refuse to use an acceptable method of birth control for the whole duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | Day 22 | Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in hemagglutination inhibition (HI) titer, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using HI cell-derived antigen assay. As per the European (CHMP) criteria, seroconversion or significant increase in titer is defined as the percentage of subjects with a prevaccination HI titer \<10 to a postvaccination HI titer ≥40; or in subjects with a prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. This criterion is met according to CHMP guideline if percentage of subjects achieving seroconversion or significant increase in HI titer is \>40% (≥18 years to ≤60 years) or 30% (≥61 years). |
| Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | Day 22 | Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI geometric mean titers (GMTs), directed against each of three vaccine strains, three weeks after vaccination (day 22). The CHMP criterion was met if the geometric mean increase (GMR, day 22/day 1) in HI antibody titer is \>2.5 (≥18 years to ≤60 years) or \>2.0 (≥61 years). |
| Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | Day 1 and 22 | Immunogenicity was measured as the percentage of subjects achieving HI titer ≥40 against each of three vaccine strains at baseline (day 1) and three weeks after TIVc vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving HI titer ≥40 is \>70% (≥18 years to ≤60) or 60% (≥61 years). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | From day 1 through day 4 postvaccination | Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 up to and including day 4 after TIVc vaccination. |
| Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | Day 1 to Day 22 | The number of subjects in both age groups reporting any unsolicited AEs between Day 1 to Day 22 after receiving one dose of TIVc. |
Countries
Germany
Participant flow
Recruitment details
Subjects were enrolled at one study centre in Germany.
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| 18-60 Y Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination | 63 |
| ≥ 61 Y Subjects ≥61 years of age who received one TIVc vaccination | 63 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | 18-60 Y | ≥ 61 Y | Total |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 11.4 | 68.0 years STANDARD_DEVIATION 4.7 | 52.7 years STANDARD_DEVIATION 17.7 |
| Sex: Female, Male Female | 33 Participants | 31 Participants | 64 Participants |
| Sex: Female, Male Male | 30 Participants | 32 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 63 | 30 / 63 |
| serious Total, serious adverse events | 0 / 63 | 0 / 63 |
Outcome results
Primary
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc
Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI geometric mean titers (GMTs), directed against each of three vaccine strains, three weeks after vaccination (day 22). The CHMP criterion was met if the geometric mean increase (GMR, day 22/day 1) in HI antibody titer is \>2.5 (≥18 years to ≤60 years) or \>2.0 (≥61 years).
Time frame: Day 22
Population: Analysis was done on the PP set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18-60 Y | Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 | 13 Ratio |
| 18-60 Y | Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 | 6.38 Ratio |
| 18-60 Y | Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | B | 5.63 Ratio |
| ≥ 61 Y | Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 | 5.79 Ratio |
| ≥ 61 Y | Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 | 4.21 Ratio |
| ≥ 61 Y | Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc | B | 3.54 Ratio |
Primary
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc
Immunogenicity was measured as the percentage of subjects achieving HI titer ≥40 against each of three vaccine strains at baseline (day 1) and three weeks after TIVc vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving HI titer ≥40 is \>70% (≥18 years to ≤60) or 60% (≥61 years).
Time frame: Day 1 and 22
Population: Analysis was done on the PP set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18-60 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 (Day 1) | 56 Percentages |
| 18-60 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 (Day 22) | 98 Percentages |
| 18-60 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 (Day 1) | 86 Percentages |
| 18-60 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 (Day 22) | 100 Percentages |
| 18-60 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | B (Day 1) | 54 Percentages |
| 18-60 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | B (Day 22) | 98 Percentages |
| ≥ 61 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | B (Day 1) | 40 Percentages |
| ≥ 61 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 (Day 1) | 61 Percentages |
| ≥ 61 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 (Day 22) | 100 Percentages |
| ≥ 61 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 (Day 22) | 100 Percentages |
| ≥ 61 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | B (Day 22) | 85 Percentages |
| ≥ 61 Y | Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 (Day 1) | 85 Percentages |
Primary
Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc
Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in hemagglutination inhibition (HI) titer, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using HI cell-derived antigen assay. As per the European (CHMP) criteria, seroconversion or significant increase in titer is defined as the percentage of subjects with a prevaccination HI titer \<10 to a postvaccination HI titer ≥40; or in subjects with a prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. This criterion is met according to CHMP guideline if percentage of subjects achieving seroconversion or significant increase in HI titer is \>40% (≥18 years to ≤60 years) or 30% (≥61 years).
Time frame: Day 22
Population: Analysis was done on the per-protocol (PP) set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18-60 Y | Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 | 73 Percentages |
| 18-60 Y | Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 | 67 Percentages |
| 18-60 Y | Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | B | 63 Percentages |
| ≥ 61 Y | Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H1N1 | 58 Percentages |
| ≥ 61 Y | Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | A/H3N2 | 45 Percentages |
| ≥ 61 Y | Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc | B | 42 Percentages |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc.
The number of subjects in both age groups reporting any unsolicited AEs between Day 1 to Day 22 after receiving one dose of TIVc.
Time frame: Day 1 to Day 22
Population: Analysis was done on the safety set population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18-60 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | At least possibly related AEs | 5 Number of Subjects |
| 18-60 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | At least possibly related SAEs | 0 Number of Subjects |
| 18-60 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | Serious AEs | 0 Number of Subjects |
| 18-60 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | AEs leading to withdrawal | 0 Number of Subjects |
| 18-60 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | Any AEs | 9 Number of Subjects |
| ≥ 61 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | AEs leading to withdrawal | 0 Number of Subjects |
| ≥ 61 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | Any AEs | 12 Number of Subjects |
| ≥ 61 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | At least possibly related AEs | 7 Number of Subjects |
| ≥ 61 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | Serious AEs | 0 Number of Subjects |
| ≥ 61 Y | Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. | At least possibly related SAEs | 0 Number of Subjects |
Secondary
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination)
Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 up to and including day 4 after TIVc vaccination.
Time frame: From day 1 through day 4 postvaccination
Population: Analysis was done on the safety dataset i.e. the subjects in the exposed population who provided postvaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site swelling | 1 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Myalgia | 27 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site pain | 29 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Arthralgia | 2 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site erythema | 1 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Headache | 13 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Chills/shivering | 1 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Sweating | 10 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site induration | 0 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Fatigue | 15 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Malaise | 5 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Fever (≥38°C) | 0 Number of subjects |
| 18-60 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site ecchymosis | 1 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Fever (≥38°C) | 0 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site ecchymosis | 4 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site erythema | 0 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site swelling | 2 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site induration | 2 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Injection site pain | 17 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Chills/shivering | 1 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Malaise | 2 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Myalgia | 12 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Arthralgia | 0 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Headache | 4 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Sweating | 7 Number of subjects |
| ≥ 61 Y | Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) | Fatigue | 7 Number of subjects |