E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevent the attack rates of influenza during both pandemic and interpandemic periods.
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1.To demonstrate the noninferior immunogenicity of 2 intramuscular (IM) doses of Fluad to Agriflu and Fluzone (coprimary) in terms of both seroconversion1 and geometric mean titers (GMTs), as measured by hemagglutination inhibition (HI) assay in all 3 homologous strains in subjects aged 6 through <72 months.
2.To demonstrate the noninferiority of 2 IM doses of Agriflu to Fluzone in terms of both seroconversion rates and GMTs, as measured by HI assay in all 3 homologous strains in subjects aged 6 through <36 months. |
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E.2.2 | Secondary objectives of the trial |
1.To demonstrate the superior immunogenicity of 2 IM doses of Fluad to Fluzone and Agriflu in terms of seroconversion rates and GMTs, as measured by HI assay
2.To evaluate the above Fluad objective(s) in the age subgroups 24 through <72 months, 6 through <36 months, and 36 through <72 months as well as in subgroups by underlying conditions (subjects at risk/not at risk) and baseline serostatus (naive/nonnaive subjects).
3. To evaluate the superior immunogenicity of 2 IM doses of Fluad to Fluzone and Agriflu in terms of seroconversion and GMTs, as measured by HI assay in heterologous strains.
4. To evaluate the immunogenicity of Fluad, Fluzone and Agriflu in terms of seroprotection rates, seroconversion rates and GMTs as well as GMT ratios, as measured by HI assay at day 29, day 50, and day 209.
5. To demonstrate a statistically significantly higher response in GMT at day 29 for at least 1 homologous strain for Fluad as compared to Agriflu and Fluzone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Children 6 months to 72 months of age |
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E.4 | Principal exclusion criteria |
1.Who had been hospitalized at the time of enrollment
2.Who had any serious reaction or hypersensitivity to any vaccine component, eggs, or chicken protein
3.Who had known impairment of the immune function
4.Who had fever interfering with normal daily activities at the time of enrollment
5.Who had received licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in the study
6.Concomitant participation in another clinical study
7.Who had surgery planned during the study period that in the investigator's opinion would have interfered with the study visits schedule. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains
2.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titers Against Homologous Strains
3.Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains (6 to <36 Months)
4.Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects 6 to <36 Months of Age |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <24 Months)
2.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains (6 to <24 Months)
3.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <72 Months)-FAS
4.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers Against Homologous Strains (6 to <72 Months)-FAS
5.The HI GMTs Against Homologous Strains, by Vaccine Group
6.Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains
7.Percentage of Subjects With HI Titers ≥40 Against Homologous Strains, by Vaccine Group
8.Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Homologous Strains
9.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, Subjects at Risk/Not at Risk, by Age Subgroup
10.Comparison of Antibody Responses of aTIV Versus Comparator TIV and TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Subgroup
11.Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Sub Group-FAS
12.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, at Risk/Not at Risk, by Age Sub Group-FAS
13.The HI GMTs Against Heterologous Strains, by Vaccine Group (6 to <72 Months Age Group)
14.Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Heterologous Strains
15.Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, After One Vaccination
16.Number of Subjects Reporting Solicited Adverse Events After Vaccination
17.Number of Subjects Reporting Unsolicited Adverse Events After Vaccination |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Comparision of Antibodies Responses of aTIV With TIV and Comparator TIV : Day 1, Day 50
GMTs: Day 1, Day 29, Day 50, Day 209
GMR and Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase: Day 29, Day 50, Day 209
Solicited Adverse Events: Day 1 to Day 7
Unsolicited Adverse Events: Day 1 to Day 394 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Australia |
Chile |
Philippines |
South Africa |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 18 |