Influenza
Conditions
Keywords
Influenza, Virus, Vaccination, Immunisation
Brief summary
A study to assess whether the Northern Hemisphere 2009/2010 season influenza vaccine Inflexal V is as immunogenic as a locally sourced competitor vaccine in young children.
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. deltoideus) of a single dose of 0.5 mL on Days 0 and 28
BIOLOGICALAgrippal
Agrippal influenza vaccine Dose: intramuscular administration (M. deltoideus) of a single dose of 0.25 mL on Days 0 and 28
Sponsors
Crucell Holland BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* ≥6months to ≤35 months-old healthy children (male or female) born at term after normal pregnancy * Recording of medical history and physical examination reveal no abnormality * The parent/legal guardian of the participating child must sign the written informed consent and agree to provide a blood sample taken from the child pre- and post-immunization
Exclusion criteria
* Hypersensitivity to eggs, chicken proteins, polymyxin B, neomycin or any component of the vaccine * Previous vaccination against influenza * At time of enrollment, presentation of clinical symptoms of active infection and/or body temperature ≥38°C * Confirmation or suspicion of immunosuppressed status (including cancer), or confirmation of immunodeficiency disease (congenital or acquired including HIV) * Medical treatment (\>2 weeks) with immune suppressant or immune modulating drugs including systemic steroids during the last 3 months before immunization or at present, as follows: long-term oral prednisone or other equivalent steroid: ≥0.5mg/kg/day (note: administration of local or inhaled steroids before or during the study is allowed) * Treatment with immunoglobulins or blood products during the last 3 months before immunization or such treatment scheduled during the study * Participation in other clinical trials during the last 3 months before immunization or intention to participate during this study period * At present or during the last 6 months before immunization: radiotherapy or treatment with cytotoxic drugs * Other vaccination with a killed vaccine within 14 days before immunization or with an attenuated vaccine within 28 days before immunization (note: after subject inclusion vaccines of the immunization program for children are allowed upon the physician's discretion. However, immunization on the same day must be avoided) * Family history of Guillain-Barré Syndrome * Severe congenital deficiency or disease * Antecedent of neurological disease or epileptic attack * Severe cardiopulmonary disease with possibility to influence the study result * Disturbance of coagulation or under anticoagulant treatment, likely to be contraindicated to i.m. injection * Suspected non-compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity, Assessed by the Haemagglutination (HI) Test | 3 weeks after the 2nd vaccination | Seroconversion rate post-immunization. Seroconversion is defined as a post-vaccination titer of ≥1:40 for those with a pre-vaccination HI titer of \<1:10 and as ≥ four-fold increase in HI titer for those with a pre-vaccination HI titer of ≥1:10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fold Increase in Geometric Mean Titer (GMT) | 3 weeks after the 2nd vaccination | GMT-fold increase - calculated as the GMT on Day 49 divided by the baseline GMT value |
| Seroprotection | 3 weeks after the 2nd vaccination | Seroprotection rate, defined as a post-vaccination HI titer of 1:40. |
| Safety: Incidence of Solicited and Unsolicited Adverse Events | Solicited AEs: Days 1-4 and 28-31, and Days 28 and 49; unsolicited AEs: until study end | Safety assessements were made by the investigator at baseline and on Days 28 and 49, as well as by the subjects themselves (in Subjects Diaries) for the 4-day period following each vaccination. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inflexal V 0.5 mL The safety data are shown for the safety population (N = 452 for this group). | 452 |
| Inflexal V 0.25 mL The safety data are shown for the safety population (N = 451 for this group). | 451 |
| Agrippal 0.25 mL The safety data are shown for the safety population (N = 451 for this group). | 451 |
| Total | 1,354 |
Baseline characteristics
| Characteristic | Inflexal V 0.25 mL | Agrippal 0.25 mL | Inflexal V 0.5 mL | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 451 Participants | 451 Participants | 452 Participants | 1354 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 1.8 years STANDARD_DEVIATION 0.7 | 1.8 years STANDARD_DEVIATION 0.7 | 1.8 years STANDARD_DEVIATION 0.7 | 1.8 years STANDARD_DEVIATION 0.7 |
| Region of Enrollment China | 451 participants | 451 participants | 452 participants | 1354 participants |
| Sex: Female, Male Female | 215 Participants | 206 Participants | 227 Participants | 648 Participants |
| Sex: Female, Male Male | 236 Participants | 245 Participants | 225 Participants | 706 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 | 57 / 452 | 37 / 451 | 55 / 451 |
| serious Total, serious adverse events | 0 / 452 | 1 / 451 | 1 / 451 |
Outcome results
Primary
Immunogenicity, Assessed by the Haemagglutination (HI) Test
Seroconversion rate post-immunization. Seroconversion is defined as a post-vaccination titer of ≥1:40 for those with a pre-vaccination HI titer of \<1:10 and as ≥ four-fold increase in HI titer for those with a pre-vaccination HI titer of ≥1:10.
Time frame: 3 weeks after the 2nd vaccination
Population: According-to-protocol population: subjects who received both doses of influenza vaccine, with available pre- and post-vaccination titers and without major protocol violations
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.5 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: A/H3N2 | 90.5 percentage of participants |
| Inflexal V 0.5 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: A/H1N1 | 97.2 percentage of participants |
| Inflexal V 0.5 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: B-strain | 57.5 percentage of participants |
| Inflexal V 0.25 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: A/H3N2 | 83.4 percentage of participants |
| Inflexal V 0.25 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: A/H1N1 | 89.7 percentage of participants |
| Inflexal V 0.25 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: B-strain | 47.9 percentage of participants |
| Agrippal 0.25 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: A/H1N1 | 92.7 percentage of participants |
| Agrippal 0.25 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: B-strain | 37.2 percentage of participants |
| Agrippal 0.25 mL | Immunogenicity, Assessed by the Haemagglutination (HI) Test | Percentage of subjects seroconverted: A/H3N2 | 82.6 percentage of participants |
Comparison: This statistical anaylsis evaluated the non-inferiority of 0.5 mL Inflexal V vs. 0.25 mL Agrippal for the A/H1N1 strain.p-value: 0.003695% CI: [1.4, 7.5]Chi-squared
Comparison: This statistical anaylsis evaluated the non-inferiority of 0.25 mL Inflexal V vs. 0.25 mL Agrippal for the A/H1N1 strain.p-value: 0.146595% CI: [-7, 1]Chi-squared
Comparison: This statistical anaylsis evaluated the non-inferiority of 0.5 mL Inflexal V vs. 0.25 mL Agrippal for the A/H3N2 strain.p-value: <0.00195% CI: [3.3, 12.7]Chi-squared
Comparison: This statistical anaylsis evaluated the non-inferiority of 0.25 mL Inflexal V vs. 0.25 mL Agrippal for the A/H3N2 strain.p-value: 0.749395% CI: [-4.5, 6.2]Chi-squared
Comparison: This statistical anaylsis evaluated the non-inferiority of 0.5 mL Inflexal V vs. 0.25 mL Agrippal for the B-strain.p-value: 095% CI: [13.5, 27]Chi-squared
Comparison: This statistical anaylsis evaluated the non-inferiority of 0.25 mL Inflexal V vs. 0.25 mL Agrippal for the B-strain.p-value: 0.002995% CI: [3.7, 17.6]Chi-squared
Secondary
Fold Increase in Geometric Mean Titer (GMT)
GMT-fold increase - calculated as the GMT on Day 49 divided by the baseline GMT value
Time frame: 3 weeks after the 2nd vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.5 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: A/H3N2 | 72.5 Fold (ratio) |
| Inflexal V 0.5 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: A/H1N1 | 36.6 Fold (ratio) |
| Inflexal V 0.5 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: B-strain | 9.2 Fold (ratio) |
| Inflexal V 0.25 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: A/H3N2 | 48.8 Fold (ratio) |
| Inflexal V 0.25 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: A/H1N1 | 25.9 Fold (ratio) |
| Inflexal V 0.25 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: B-strain | 7.0 Fold (ratio) |
| Agrippal 0.25 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: A/H1N1 | 25.4 Fold (ratio) |
| Agrippal 0.25 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: B-strain | 5.3 Fold (ratio) |
| Agrippal 0.25 mL | Fold Increase in Geometric Mean Titer (GMT) | GMT fold increase from baseline: A/H3N2 | 54.2 Fold (ratio) |
Secondary
Safety: Incidence of Solicited and Unsolicited Adverse Events
Safety assessements were made by the investigator at baseline and on Days 28 and 49, as well as by the subjects themselves (in Subjects Diaries) for the 4-day period following each vaccination.
Time frame: Solicited AEs: Days 1-4 and 28-31, and Days 28 and 49; unsolicited AEs: until study end
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.5 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one solicited AE | 32.3 percentage of subjects with AEs |
| Inflexal V 0.5 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one AE | 38.5 percentage of subjects with AEs |
| Inflexal V 0.5 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one unsolicited AE | 12.6 percentage of subjects with AEs |
| Inflexal V 0.25 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one solicited AE | 29.1 percentage of subjects with AEs |
| Inflexal V 0.25 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one AE | 33.0 percentage of subjects with AEs |
| Inflexal V 0.25 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one unsolicited AE | 8.2 percentage of subjects with AEs |
| Agrippal 0.25 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one AE | 35.7 percentage of subjects with AEs |
| Agrippal 0.25 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one unsolicited AE | 12.2 percentage of subjects with AEs |
| Agrippal 0.25 mL | Safety: Incidence of Solicited and Unsolicited Adverse Events | Subjects with at least one solicited AE | 29.5 percentage of subjects with AEs |
Secondary
Seroprotection
Seroprotection rate, defined as a post-vaccination HI titer of 1:40.
Time frame: 3 weeks after the 2nd vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inflexal V 0.5 mL | Seroprotection | Percentage of subjects seroprotected: A/H3N2 | 91.3 percentage seroprotected subjects |
| Inflexal V 0.5 mL | Seroprotection | Percentage of subjects seroprotected: A/H1N1 | 97.6 percentage seroprotected subjects |
| Inflexal V 0.5 mL | Seroprotection | Percentage of subjects seroprotected: B-strain | 60.3 percentage seroprotected subjects |
| Inflexal V 0.25 mL | Seroprotection | Percentage of subjects seroprotected: A/H3N2 | 84.5 percentage seroprotected subjects |
| Inflexal V 0.25 mL | Seroprotection | Percentage of subjects seroprotected: A/H1N1 | 92.1 percentage seroprotected subjects |
| Inflexal V 0.25 mL | Seroprotection | Percentage of subjects seroprotected: B-strain | 51.3 percentage seroprotected subjects |
| Agrippal 0.25 mL | Seroprotection | Percentage of subjects seroprotected: A/H1N1 | 93.2 percentage seroprotected subjects |
| Agrippal 0.25 mL | Seroprotection | Percentage of subjects seroprotected: B-strain | 39.6 percentage seroprotected subjects |
| Agrippal 0.25 mL | Seroprotection | Percentage of subjects seroprotected: A/H3N2 | 82.8 percentage seroprotected subjects |