Influenza
Conditions
Keywords
Influenza, Virus, Vaccination, Immunisation
Brief summary
This study is to assess whether the Northern Hemisphere 2009/2010 season influenza vaccine Inflexal V fulfills the EMEA requirements for re-registration of influenza vaccines.
Interventions
BIOLOGICALInflexal V
Inflexal V influenza vaccine, formulated for the WHO requirements of the 2009-2010 season, containing per 0.5 mL dose: * 15 µg hemagglutinin (HA) antigen of A/Brisbane/59/2007 (H1N1)-like virus * 15 µg HA antigen of A/Brisbane/10/2007 (H3N2)-like virus * 15 µg HA antigen of B/Brisbane/60/2008-like virus Dose: intramuscular administration (M. deltoides) of a single dose of 0.5 mL on Day 1
Sponsors
Crucell Holland BV
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy female and male adults * Aged ≥18 to ≤60 years or \>60 years on Day 1 * Written informed consent
Exclusion criteria
* Acute exacerbation of bronchopulmonary infection (cough, sputum, lung findings) or other acute disease * Acute febrile illness (≥38.0 °C) * Prior vaccination with an influenza vaccine in the past 330 days * Known hypersensitivity to any vaccine component * Previous history of a serious adverse reaction to influenza vaccine * History of egg protein allergy or severe atopy * Known blood coagulation disorder * Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of study vaccine, incl. oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent (inhaled or topical steroids are allowed) * Known immunodeficiency (incl. leukemia, cancer, HIV seropositivity) * Investigational medicinal product received in the past 3 months (90 days) * Treatment with immunoglobulins or blood transfusion(s) received in the past 3 months (90 days) * Pregnancy or lactation * Participation in another clinical trial * Employee at the investigational site, or relative or spouse of the investigator * Suspected non-compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion | Day 22 ± 2 days | Seroconversion rate was defined as the number of subjects with ≥4-fold increase in haemagglutination inhibition (HI) antibody titer and with a titer of ≥1:40 |
| Seroprotection | Day 22 ± 2 days | Seroprotection rate, defined as the number of subjects with HI antibody titer ≥1:40 |
| Fold Increase in Geometric Mean Titer (GMT) | Day 22/Day 1 | GMT-fold increase - calculated as the GMT on Day 22 divided by the baseline GMT value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Days 1 to 4 inclusive, and Day 22 | Safety assessments are made by the investigator at baseline and on Day 22 as well as by the subjects themselves (in a Subject Diary) for the 4-day period immediately following vaccination |
| Numbers of Subjects Reporting Solicited Systemic Adverse Events | Days 1 to 4 inclusive, and Day 22 | Safety assessments are made by the investigator at baseline and on Day 22 as well as by the subjects themselves (in a Subject Diary) for the 4-day period immediately following vaccination |
Countries
Switzerland
Participant flow
Recruitment details
Participants were recruited at one center in Switzerland First subject first visit (FSFV): 05-Jun-2009 Last subject last visit (LSLV): 30-Jun-2009
Participants by arm
| Arm | Count |
|---|---|
| Adults Adults from 18 to 60 years old inclusive | 57 |
| Elderly Elderly subjects aged over 60 years | 57 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Adults | Elderly | Total |
|---|---|---|---|
| Age Continuous | 42.3 years STANDARD_DEVIATION 12.3 | 68.5 years STANDARD_DEVIATION 5.8 | 55.4 years STANDARD_DEVIATION 16.3 |
| Sex: Female, Male Female | 31 Participants | 30 Participants | 61 Participants |
| Sex: Female, Male Male | 26 Participants | 27 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 | 29 / 57 | 16 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
Primary
Fold Increase in Geometric Mean Titer (GMT)
GMT-fold increase - calculated as the GMT on Day 22 divided by the baseline GMT value
Time frame: Day 22/Day 1
Population: ITT/ATP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | Fold Increase in Geometric Mean Titer (GMT) | A/Brisbane/59/2007 | 9.60 Fold (ratio) |
| Adults | Fold Increase in Geometric Mean Titer (GMT) | A/Brisbane/10/2007 | 9.25 Fold (ratio) |
| Adults | Fold Increase in Geometric Mean Titer (GMT) | B/Brisbane/60/2008 | 7.91 Fold (ratio) |
| Elderly | Fold Increase in Geometric Mean Titer (GMT) | A/Brisbane/10/2007 | 8.30 Fold (ratio) |
| Elderly | Fold Increase in Geometric Mean Titer (GMT) | B/Brisbane/60/2008 | 6.93 Fold (ratio) |
| Elderly | Fold Increase in Geometric Mean Titer (GMT) | A/Brisbane/59/2007 | 5.93 Fold (ratio) |
Primary
Seroconversion
Seroconversion rate was defined as the number of subjects with ≥4-fold increase in haemagglutination inhibition (HI) antibody titer and with a titer of ≥1:40
Time frame: Day 22 ± 2 days
Population: Intention-to-treat (ITT) and According-to-protocol (ATP) populations excludes one subject per group lost to follow up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | Seroconversion | A/Brisbane/59/2007 | 29 Number of subjects |
| Adults | Seroconversion | A/Brisbane/10/2007 | 37 Number of subjects |
| Adults | Seroconversion | B/Brisbane/60/2008 | 34 Number of subjects |
| Elderly | Seroconversion | A/Brisbane/59/2007 | 32 Number of subjects |
| Elderly | Seroconversion | A/Brisbane/10/2007 | 35 Number of subjects |
| Elderly | Seroconversion | B/Brisbane/60/2008 | 33 Number of subjects |
Primary
Seroprotection
Seroprotection rate, defined as the number of subjects with HI antibody titer ≥1:40
Time frame: Day 22 ± 2 days
Population: ITT/ATP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | Seroprotection | A/Brisbane/59/2007 | 47 Number of subjects |
| Adults | Seroprotection | A/Brisbane/10/2007 | 49 Number of subjects |
| Adults | Seroprotection | B/Brisbane/60/2008 | 51 Number of subjects |
| Elderly | Seroprotection | A/Brisbane/59/2007 | 47 Number of subjects |
| Elderly | Seroprotection | A/Brisbane/10/2007 | 51 Number of subjects |
| Elderly | Seroprotection | B/Brisbane/60/2008 | 46 Number of subjects |
Secondary
Numbers of Subjects Reporting Solicited Systemic Adverse Events
Safety assessments are made by the investigator at baseline and on Day 22 as well as by the subjects themselves (in a Subject Diary) for the 4-day period immediately following vaccination
Time frame: Days 1 to 4 inclusive, and Day 22
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | Numbers of Subjects Reporting Solicited Systemic Adverse Events | Malaise | 1 Subjects |
| Adults | Numbers of Subjects Reporting Solicited Systemic Adverse Events | Shivering | 0 Subjects |
| Adults | Numbers of Subjects Reporting Solicited Systemic Adverse Events | Fever | 0 Subjects |
| Elderly | Numbers of Subjects Reporting Solicited Systemic Adverse Events | Malaise | 0 Subjects |
| Elderly | Numbers of Subjects Reporting Solicited Systemic Adverse Events | Fever | 0 Subjects |
| Elderly | Numbers of Subjects Reporting Solicited Systemic Adverse Events | Shivering | 0 Subjects |
Secondary
Safety: Numbers of Subjects Reporting Solicited Local Adverse Events
Safety assessments are made by the investigator at baseline and on Day 22 as well as by the subjects themselves (in a Subject Diary) for the 4-day period immediately following vaccination
Time frame: Days 1 to 4 inclusive, and Day 22
Population: Safety population includes all subjects who received study vaccine
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adults | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Ecchymosis | 1 Subjects |
| Adults | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Erythema | 5 Subjects |
| Adults | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Induration | 1 Subjects |
| Adults | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Pain | 18 Subjects |
| Elderly | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Pain | 8 Subjects |
| Elderly | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Ecchymosis | 0 Subjects |
| Elderly | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Induration | 2 Subjects |
| Elderly | Safety: Numbers of Subjects Reporting Solicited Local Adverse Events | Erythema | 3 Subjects |