Influenza
Conditions
Keywords
Influenza, Virus, Vaccination, Virosomal influenza vaccine
Brief summary
The study is to assess whether the virosomal influenza vaccine for season 2012/2013 fulfills the EMA requirements for re-registration of influenza vaccines.
Interventions
BIOLOGICALVirosomal influenza vaccine
Intramuscular administration (M. deltoideus) of a single dose of 0.5 mL virosomal influenza vaccine
Sponsors
Crucell Holland BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy female and male adults aged ≥18 on Day 1 * Written informed consent * Female subjects of childbearing potential using and willing to continue using an acceptable method of contraception unless surgically sterilized/hysterectomized or post-menopausal for more than 2 years
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 the study vaccine, including oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent (inhaled or topical steroids are allowed) * Known immunodeficiency (incl. leukemia, HIV seropositivity), cancer * Investigational medicinal product received in the past 3 months (90 days) starting from the first day of the month following the last visit in a previous study * 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 of the investigator * Subjects who in the view of the investigator will not comply with study procedures and/or visit requirements as per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection | Day 22 +/- 2 days | Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40 (The primary endpoints are the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997) |
| Seroconversion | Day 22 +/- 2 days | Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40 (The primary endpoints are the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997) |
| Geometric Mean Titer | Day 22 +/- 2 days | GMT of HI antibodies and fold-increase in GMT (The primary endpoints are the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Baseline (Day 1) and 3 weeks after vaccination (Day 22 ± 2 days) | Solicited local and systemic AEs, Unsolicited AEs Unsolicited AEs were collected from baseline (Day 1) to 3 weeks after vaccination (Day 22 ± 2 days). Solicited local and systemic AEs were collected by subjects diary from Day 1 (day of vaccination) to Day 4 |
Countries
Switzerland
Participant flow
Recruitment details
Recruitment period: 03 August 2012 to 27 August 2012; outpatient study
Participants by arm
| Arm | Count |
|---|---|
| Elderly Subjects Aged Over 60 Years | 55 |
| Adults From 18 to 60 Years Old Inclusive | 55 |
| Total | 110 |
Baseline characteristics
| Characteristic | Adults From 18 to 60 Years Old Inclusive | Elderly Subjects Aged Over 60 Years | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 32 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 23 Participants | 78 Participants |
| Age, Continuous | 41.0 years STANDARD_DEVIATION 11.52 | 66.2 years STANDARD_DEVIATION 4.42 | 53.6 years STANDARD_DEVIATION 15.37 |
| Region of Enrollment Switzerland | 55 participants | 55 participants | 110 participants |
| Sex: Female, Male Female | 30 Participants | 34 Participants | 64 Participants |
| Sex: Female, Male Male | 25 Participants | 21 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 55 | 32 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 |
Outcome results
Primary
Geometric Mean Titer
GMT of HI antibodies and fold-increase in GMT (The primary endpoints are the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997)
Time frame: Day 22 +/- 2 days
Population: Intent-to-treat, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elderly Subjects Aged Over 60 Years | Geometric Mean Titer | GMT fold increase: A/H1N1 | 4.25 GMT fold increase from baseline |
| Elderly Subjects Aged Over 60 Years | Geometric Mean Titer | GMT fold increase: B strain | 2.78 GMT fold increase from baseline |
| Elderly Subjects Aged Over 60 Years | Geometric Mean Titer | GMT fold increase: A/H3N2 | 2.70 GMT fold increase from baseline |
| Adults From 18 to 60 Years Old Inclusive | Geometric Mean Titer | GMT fold increase: A/H1N1 | 4.62 GMT fold increase from baseline |
| Adults From 18 to 60 Years Old Inclusive | Geometric Mean Titer | GMT fold increase: B strain | 3.27 GMT fold increase from baseline |
| Adults From 18 to 60 Years Old Inclusive | Geometric Mean Titer | GMT fold increase: A/H3N2 | 2.78 GMT fold increase from baseline |
Primary
Seroconversion
Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40 (The primary endpoints are the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997)
Time frame: Day 22 +/- 2 days
Population: Intent-to-treat, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elderly Subjects Aged Over 60 Years | Seroconversion | Percentage seroconverted subjects: A/H1N1 | 43.6 percentage of subjects |
| Elderly Subjects Aged Over 60 Years | Seroconversion | Percentage seroconverted subjects: A/H3N2 | 27.3 percentage of subjects |
| Elderly Subjects Aged Over 60 Years | Seroconversion | Percentage seroconverted subjects: B strain | 34.5 percentage of subjects |
| Adults From 18 to 60 Years Old Inclusive | Seroconversion | Percentage seroconverted subjects: A/H1N1 | 58.2 percentage of subjects |
| Adults From 18 to 60 Years Old Inclusive | Seroconversion | Percentage seroconverted subjects: A/H3N2 | 36.4 percentage of subjects |
| Adults From 18 to 60 Years Old Inclusive | Seroconversion | Percentage seroconverted subjects: B strain | 43.6 percentage of subjects |
Primary
Seroprotection
Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40 (The primary endpoints are the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997)
Time frame: Day 22 +/- 2 days
Population: Intent-to-treat, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elderly Subjects Aged Over 60 Years | Seroprotection | Percentage seroprotected subjects: A/H1N1 | 94.5 percentage of subjects |
| Elderly Subjects Aged Over 60 Years | Seroprotection | Percentage seroprotected subjects: A/H3N2 | 100 percentage of subjects |
| Elderly Subjects Aged Over 60 Years | Seroprotection | Percentage seroprotected subjects: B strain | 100 percentage of subjects |
| Adults From 18 to 60 Years Old Inclusive | Seroprotection | Percentage seroprotected subjects: A/H1N1 | 100 percentage of subjects |
| Adults From 18 to 60 Years Old Inclusive | Seroprotection | Percentage seroprotected subjects: A/H3N2 | 100 percentage of subjects |
| Adults From 18 to 60 Years Old Inclusive | Seroprotection | Percentage seroprotected subjects: B strain | 100 percentage of subjects |
Secondary
Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability
Solicited local and systemic AEs, Unsolicited AEs Unsolicited AEs were collected from baseline (Day 1) to 3 weeks after vaccination (Day 22 ± 2 days). Solicited local and systemic AEs were collected by subjects diary from Day 1 (day of vaccination) to Day 4
Time frame: Baseline (Day 1) and 3 weeks after vaccination (Day 22 ± 2 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elderly Subjects Aged Over 60 Years | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | AEs (unsolicited and unsolicited) | 23 participants |
| Elderly Subjects Aged Over 60 Years | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Solicited local AEs | 20 participants |
| Elderly Subjects Aged Over 60 Years | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Solicited systemic AEs | 1 participants |
| Elderly Subjects Aged Over 60 Years | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Unsolicited AEs | 4 participants |
| Adults From 18 to 60 Years Old Inclusive | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Solicited local AEs | 30 participants |
| Adults From 18 to 60 Years Old Inclusive | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | AEs (unsolicited and unsolicited) | 32 participants |
| Adults From 18 to 60 Years Old Inclusive | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Unsolicited AEs | 5 participants |
| Adults From 18 to 60 Years Old Inclusive | Number of Participants With Local and Systemic Adverse Events, as a Measure of Safety and Tolerability | Solicited systemic AEs | 7 participants |