Influenza
Conditions
Keywords
Influenza, Virus, Vaccination, Immunisation
Brief summary
The purpose of this study is to assess the humoral immune response and safety of the parenteral formulation of the 2010/2011-season virosomal subunit influenza vaccine Inflexal V using two different HA antigen suppliers (AdImmune and CSL), in groups of young and elderly adults, using the EMA (European Medicines Agency) regulation as a guideline.
Detailed description
The objectives of this study are to evaluate the humoral immunogenicity and safety of the parenteral formulation of the 2010/2011-season influenza vaccine, Inflexal V, using HA antigen obtained from 2 different production facilities, and to compare the immunogenicity of both formulations to pre-defined EMA criteria for the annual relicensing of seasonal influenza vaccines. The evaluation will be done in young adults and elderly.
Interventions
BIOLOGICALInflexal V influenza vaccine (CSL HA Antigen) 2010
Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using CSL HA Antigen) 2010/2011, with intramuscular administration, containing per 0.5 mL dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus
BIOLOGICALInflexal V influenza vaccine (AdImmune HA antigen) 2010/2011
Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using AdImmune HA antigen) 2010/2011 with intramuscular administration, containing per 0.5 mL dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus
Sponsors
Crucell Holland BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy female and male adults * Aged ≥18 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 (including the H1N1 pandemic swine flu 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, 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 spouse and children of the investigator, or relative living in the same household as the investigator and/or are dependent on the investigator * Suspected non-compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | 3 weeks after vaccination (Day 22 ± 2 days) | The primary endpoints were 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 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT |
| Immunogenicity - Seroprotection Rate | 3 weeks after vaccination (Day 22 ± 2 days) | The primary endpoints were 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 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT |
| Immunogenicity - Seroconversion Rate | 3 weeks after vaccination (Day 22 ± 2 days) | The primary endpoints were 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 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Local and Systemic Adverse Events | Baseline (Day 1) and 3 weeks after vaccination (Day 22 ± 2 days) | Solicited local and systemic AEs, Unsolicited AEs, Tolerability and acceptability 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: 19 October 2010 to 09 November 2010; outpatient study
Participants by arm
| Arm | Count |
|---|---|
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | 109 |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | 111 |
| Subjects >60 Years - AdImmune HA Antigen | 110 |
| Subjects >60 Years - CSL HA Antigen | 110 |
| Total | 440 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Subjects ≥18 to ≤60 Years - CSL HA Antigen | Subjects >60 Years - AdImmune HA Antigen | Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Subjects >60 Years - CSL HA Antigen | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 63 Participants | 0 Participants | 57 Participants | 120 Participants |
| Age, Categorical Between 18 and 65 years | 111 Participants | 47 Participants | 109 Participants | 53 Participants | 320 Participants |
| Age Continuous | 39.9 years STANDARD_DEVIATION 12.1 | 66.5 years STANDARD_DEVIATION 5.5 | 39.5 years STANDARD_DEVIATION 11.18 | 66.4 years STANDARD_DEVIATION 5.06 | 53.1 years STANDARD_DEVIATION 16.14 |
| Region of Enrollment Switzerland | 111 participants | 110 participants | 109 participants | 110 participants | 440 participants |
| Sex: Female, Male Female | 50 Participants | 49 Participants | 54 Participants | 53 Participants | 206 Participants |
| Sex: Female, Male Male | 61 Participants | 61 Participants | 55 Participants | 57 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 57 / 109 | 58 / 111 | 25 / 110 | 30 / 110 |
| serious Total, serious adverse events | 0 / 109 | 0 / 111 | 0 / 110 | 0 / 110 |
Outcome results
Primary
Immunogenicity - Geometric Mean Titer Fold Increase From Baseline
The primary endpoints were 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 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT
Time frame: 3 weeks after vaccination (Day 22 ± 2 days)
Population: Intent-to-treat population, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H3N2 | 2.5 GMT fold increase |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H1N1 | 3.5 GMT fold increase |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: B-strain | 3.2 GMT fold increase |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H3N2 | 2.5 GMT fold increase |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H1N1 | 4.0 GMT fold increase |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: B-strain | 3.1 GMT fold increase |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: B-strain | 1.9 GMT fold increase |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H3N2 | 2.2 GMT fold increase |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H1N1 | 4.5 GMT fold increase |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H3N2 | 1.9 GMT fold increase |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: A/H1N1 | 3.4 GMT fold increase |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | GMT fold increase from baseline: B-strain | 2.1 GMT fold increase |
Primary
Immunogenicity - Seroconversion Rate
The primary endpoints were 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 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT
Time frame: 3 weeks after vaccination (Day 22 ± 2 days)
Population: Intent-to-treat population, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H1N1 | 45.0 percentage subjects |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: B-strain | 40.4 percentage subjects |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H3N2 | 27.5 percentage subjects |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H1N1 | 52.7 percentage subjects |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: B-strain | 44.5 percentage subjects |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H3N2 | 29.1 percentage subjects |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H3N2 | 25.5 percentage subjects |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H1N1 | 54.5 percentage subjects |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: B-strain | 20.9 percentage subjects |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H1N1 | 43.6 percentage subjects |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: B-strain | 20.0 percentage subjects |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Seroconversion Rate | Percentage of subjects seroprotected: A/H3N2 | 17.3 percentage subjects |
Primary
Immunogenicity - Seroprotection Rate
The primary endpoints were 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 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT
Time frame: 3 weeks after vaccination (Day 22 ± 2 days)
Population: Intent-to-treat population, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H1N1 | 99.1 percentage subjects |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: B-strain | 96.3 percentage subjects |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H3N2 | 99.1 percentage subjects |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H1N1 | 98.2 percentage subjects |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: B-strain | 97.3 percentage subjects |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H3N2 | 99.1 percentage subjects |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H3N2 | 100 percentage subjects |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H1N1 | 92.7 percentage subjects |
| Subjects >60 Years - AdImmune HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: B-strain | 85.5 percentage subjects |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H1N1 | 90.0 percentage subjects |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: B-strain | 86.4 percentage subjects |
| Subjects >60 Years - CSL HA Antigen | Immunogenicity - Seroprotection Rate | Percentage of subjects seroprotected: A/H3N2 | 99.1 percentage subjects |
Secondary
Number of Participants With Local and Systemic Adverse Events
Solicited local and systemic AEs, Unsolicited AEs, Tolerability and acceptability 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)
Population: Safety population, all vaccinated subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited systemic AEs | 14 participants |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | Unsolicited AEs | 14 participants |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | AEs (unsolicited and solicited) | 57 participants |
| Subjects ≥18 to ≤60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited local AEs | 45 participants |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | Unsolicited AEs | 21 participants |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited local AEs | 41 participants |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | AEs (unsolicited and solicited) | 58 participants |
| Subjects ≥18 to ≤60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited systemic AEs | 9 participants |
| Subjects >60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | AEs (unsolicited and solicited) | 25 participants |
| Subjects >60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | Unsolicited AEs | 8 participants |
| Subjects >60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited local AEs | 18 participants |
| Subjects >60 Years - AdImmune HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited systemic AEs | 6 participants |
| Subjects >60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | Unsolicited AEs | 11 participants |
| Subjects >60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | AEs (unsolicited and solicited) | 30 participants |
| Subjects >60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited systemic AEs | 4 participants |
| Subjects >60 Years - CSL HA Antigen | Number of Participants With Local and Systemic Adverse Events | Solicited local AEs | 21 participants |