Influenza
Conditions
Keywords
Influenza, Virus, Vaccination, Immunisation
Brief summary
The study aims to evaluate the immunogenicity of a single full (0.5 mL) dose and a 0.25 mL 2-dose regime of Inflexal V in unprimed children aged 6 - \<36 months, using the EMA guideline for the re-registration of the seasonal influenza vaccine in adults (aged ≥18 ≤60 years) as reference.
Interventions
BIOLOGICALInflexal V
vaccination with Inflexal V 0.25 mL administered twice, 4 weeks apart
Sponsors
Crucell Holland BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female children * Aged ≥6 to \<36 months on Day 1 * Born at a gestational age ≥37 weeks * Written informed consent * No previous influenza vaccination
Exclusion criteria
* Acute respiratory infection or other acute disease * Acute febrile illness (≥38.0 °C) * Past vaccination with an influenza vaccine, including vaccination against the influenza strain A/California/7/2009 (H1N1)-like virus * Laboratory-confirmed infection with any influenza strain, including the pandemic influenza strain H1N1 (A/California/7/2009 (H1N1)-like virus) * Known hypersensitivity to any vaccine component * Known 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 for ≥14 days (inhaled or topical steroids are allowed) * Known immunodeficiency (including 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) * Vaccination with the MMR vaccine in the past 4 weeks, or planned within the study period * Participation in another clinical trial * Child or legal charge of the investigator or an employee at the study site, or living in the same household as the investigator/employee and/or dependent on the investigator/employee * Suspected non-compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen | Seroprotection rate |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited local and systemic AEs were collected from Day 1 (day of vaccination) to Day 4 inclusive using a subject diary |
Countries
Italy
Participant flow
Recruitment details
Recruitment period: 05 October - 17 January 2011; Location: University of Milan
Participants by arm
| Arm | Count |
|---|---|
| Inflexal V 0.25 mL x 2 Two 0.25 mL doses (on Day 1 and 29) | 103 |
| Inflexal V 0.5 mL x 1 One 0.5 mL dose (on Day 1) | 102 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 6 |
| Overall Study | Migrated/moved from study area | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Inflexal V 0.5 mL x 1 | Inflexal V 0.25 mL x 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 102 Participants | 103 Participants | 205 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 1.8 years STANDARD_DEVIATION 0.61 | 1.8 years STANDARD_DEVIATION 0.52 | 1.8 years STANDARD_DEVIATION 0.57 |
| Region of Enrollment Italy | 102 participants | 103 participants | 205 participants |
| Sex: Female, Male Female | 37 Participants | 37 Participants | 74 Participants |
| Sex: Female, Male Male | 65 Participants | 66 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 51 / 102 | 48 / 101 | 49 / 100 |
| serious Total, serious adverse events | 1 / 102 | 0 / 101 | 5 / 100 |
Outcome results
Primary
Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference
Seroprotection rate
Time frame: This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen
Population: Intention to treat population, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroprotected: A/H1N1 | 99.0 percentage subjects |
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroprotected: A/H3N2 | 99.0 percentage subjects |
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroprotected: B-strain | 92.2 percentage subjects |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroprotected: A/H1N1 | 98.0 percentage subjects |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroprotected: A/H3N2 | 97.0 percentage subjects |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroprotected: B-strain | 86.9 percentage subjects |
Primary
Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference
Seroconversion rate
Time frame: This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen
Population: Intention to treat population, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroconverted: A/H1N1 | 92.9 percentage subjects |
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroconverted: A/H3N2 | 99.0 percentage subjects |
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroconverted: B-strain | 92.9 percentage subjects |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroconverted: A/H1N1 | 95.5 percentage subjects |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroconverted: A/H3N2 | 97.0 percentage subjects |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | Percentage of subjects seroconverted: B-strain | 86.9 percentage subjects |
Primary
Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference
GMT-fold increase - calculated as the GMT on Day 22 divided by the baseline GMT value
Time frame: This assesment was done for immunogenicity data collected at Day 29 after completion of designated vaccination regimen
Population: Intention to treat population, vaccinated subjects with available pre- and post-vaccination titers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | GMT fold increase from baseline: A/H1N1 | 25.5 Fold (ratio) |
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | GMT fold increase from baseline: A/H3N2 | 31.6 Fold (ratio) |
| Inflexal V 0.25 mL x 2 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | GMT fold increase from baseline: B-strain | 12.8 Fold (ratio) |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | GMT fold increase from baseline: A/H1N1 | 19.6 Fold (ratio) |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | GMT fold increase from baseline: A/H3N2 | 24.6 Fold (ratio) |
| Inflexal V 0.5 mL x 1 | Immunogenicity of a Single Full (0.5 mL) Dose and a 0.25 mL 2-dose Regimen of Inflexal V, Using the EMA Guideline for the Re-registration of the Seasonal Influenza Vaccine in Adults (Aged ≥18 to ≤60 Years) as Reference | GMT fold increase from baseline: B-strain | 14.7 Fold (ratio) |
Secondary
Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability
Time frame: Solicited local and systemic AEs were collected from Day 1 (day of vaccination) to Day 4 inclusive using a subject diary
Population: Safety population, all vaccinated subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.25 mL x 2 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | AEs (unsolicited and solicited) | 51 participants |
| Inflexal V 0.25 mL x 2 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Unsolicited AEs | 29 participants |
| Inflexal V 0.25 mL x 2 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited local AEs | 22 participants |
| Inflexal V 0.25 mL x 2 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited systemic AEs | 16 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited systemic AEs | 16 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Unsolicited AEs | 32 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | AEs (unsolicited and solicited) | 48 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited local AEs | 16 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | AEs (unsolicited and solicited) | 49 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Unsolicited AEs | 30 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited local AEs | 17 participants |
| Inflexal V 0.5 mL x 1 | Number of Participants With Local and Systemic Adverse Events as a Measure of Safety and Tolerability | Solicited systemic AEs | 20 participants |