Influenza
Conditions
Keywords
Influenza, Virus, Vaccination, Immunisation
Brief summary
A study to assess whether the Northern Hemisphere 2008/2009 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 ofr the 2008-2009 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/Florida/4/2006-like virus Dose: intramuscular administration (M. deltoideus) of a single dose of 0.5 mL on Day 1
Sponsors
Crucell Holland BV
Study design
Allocation
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; oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent are excluded; 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 proportion 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 proportion 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: Incidence of 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 |
| Incidence of 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 FSFV: 09-Jul-2008 LSLV: 30-Jul-2008
Participants by arm
| Arm | Count |
|---|---|
| Group A Adults from 18 to 60 years old inclusive | 55 |
| Group B Elderly subjects aged over 60 years | 56 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age Continuous | 39.2 years STANDARD_DEVIATION 13 | 69.3 years STANDARD_DEVIATION 5.2 | 54.4 years STANDARD_DEVIATION 18 |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 51 Participants |
| Sex: Female, Male Male | 29 Participants | 31 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 55 | 20 / 56 |
| serious Total, serious adverse events | 0 / 55 | 0 / 56 |
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) |
|---|---|---|---|
| Group A | Fold Increase in Geometric Mean Titer (GMT) | A/Brisbane/59/2007 | 9.97 Fold (ratio) |
| Group A | Fold Increase in Geometric Mean Titer (GMT) | A/Uruguay/716/2007 | 11.54 Fold (ratio) |
| Group A | Fold Increase in Geometric Mean Titer (GMT) | B/Florida/4/2006 | 9.90 Fold (ratio) |
| Group B | Fold Increase in Geometric Mean Titer (GMT) | A/Brisbane/59/2007 | 4.36 Fold (ratio) |
| Group B | Fold Increase in Geometric Mean Titer (GMT) | A/Uruguay/716/2007 | 17.40 Fold (ratio) |
| Group B | Fold Increase in Geometric Mean Titer (GMT) | B/Florida/4/2006 | 2.36 Fold (ratio) |
Primary
Seroconversion
Seroconversion rate was defined as the proportion 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 exclude one subject lost to follow up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Seroconversion | B/Florida/4/2006 | 34 Subjects |
| Group A | Seroconversion | A/Brisbane/59/2007 | 27 Subjects |
| Group A | Seroconversion | A/Uruguay/716/2007 | 32 Subjects |
| Group B | Seroconversion | A/Uruguay/716/2007 | 43 Subjects |
| Group B | Seroconversion | B/Florida/4/2006 | 20 Subjects |
| Group B | Seroconversion | A/Brisbane/59/2007 | 17 Subjects |
Primary
Seroprotection
Seroprotection rate, defined as the proportion of subjects with HI antibody titer ≥1:40
Time frame: Day 22 ± 2 days
Population: ITT/ATP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Seroprotection | A/Brisbane/59/2007 | 52 Subjects |
| Group A | Seroprotection | A/Uruguay/716/2007 | 39 Subjects |
| Group A | Seroprotection | B/Florida/4/2006 | 53 Subjects |
| Group B | Seroprotection | A/Brisbane/59/2007 | 39 Subjects |
| Group B | Seroprotection | A/Uruguay/716/2007 | 49 Subjects |
| Group B | Seroprotection | B/Florida/4/2006 | 54 Subjects |
Secondary
Incidence of 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) |
|---|---|---|---|
| Group A | Incidence of Solicited Systemic Adverse Events | Malaise | 8 Subjects |
| Group A | Incidence of Solicited Systemic Adverse Events | Shivering | 0 Subjects |
| Group B | Incidence of Solicited Systemic Adverse Events | Malaise | 3 Subjects |
| Group B | Incidence of Solicited Systemic Adverse Events | Shivering | 0 Subjects |
Secondary
Safety: Incidence of 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) |
|---|---|---|---|
| Group A | Safety: Incidence of Solicited Local Adverse Events | Ecchymosis | 1 Subjects |
| Group A | Safety: Incidence of Solicited Local Adverse Events | Erythema | 6 Subjects |
| Group A | Safety: Incidence of Solicited Local Adverse Events | Induration | 7 Subjects |
| Group A | Safety: Incidence of Solicited Local Adverse Events | Pain | 30 Subjects |
| Group B | Safety: Incidence of Solicited Local Adverse Events | Pain | 12 Subjects |
| Group B | Safety: Incidence of Solicited Local Adverse Events | Ecchymosis | 1 Subjects |
| Group B | Safety: Incidence of Solicited Local Adverse Events | Induration | 3 Subjects |
| Group B | Safety: Incidence of Solicited Local Adverse Events | Erythema | 6 Subjects |