Immunogenicity, Safety and Tolerability of Prepandemic Influenza and Seasonal Influenza Vaccine in Adult Subjects

Study Overview
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Brief Summary
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This study evaluates the immunogenicity, safety and tolerability of an H5N1 vaccine with a seasonal trivalent influenza vaccine, containing the strains recommended by WHO for the 2007 influenza season in the Southern Hemisphere.

Official Title
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A Phase II, Randomized, Controlled, Open Label, Single-Center Study to Evaluate the Immunogenicity, Safety and Tolerability of an H5N1-vaccine and a Seasonal Influenza Vaccine in Adult Subjects

Conditions
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Pandemic, Avian Influenza

Intervention / Treatment
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* Biological: MF59-eH5N1
* Biological: eTIV_a
* Biological: MF59-eH5N1 + eTIV_a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concomitant alone<br>1 dose of MF59-eH5N1 into one arm and 1 dose of eTIV_a into the other arm on day 1 then 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382. | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: Concomitant +Mixed<br>1 dose of MF59-eH5N1 into one arm and 1 dose of eTIV_a into the other arm on day 1, 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 22, and 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: Concomitant +MF59-eH5N1<br>1 dose of MF59-eH5N1 into one arm and 1 dose of eTIV_a into the other arm on day 1, 1 dose of MF59-eH5N1 on day 22, and 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: Mixed<br>1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1 and 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: Mixed and mixed<br>1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1, day 22, and day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: Mixed+MF59-eH5N1<br>1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1, 1 dose of MF59-eH5N1 on day 22, and 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: MF59-eH5N1+eTIV_a<br>1 dose of MF59-eH5N1 on day 1, 1 dose of eTIV_a on day 22, and 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |
| Experimental: eTIV_a+MF59-eH5N1<br>1 dose of eTIV_a on day 1, 1 dose of MF59-eH5N1 on day 22, and 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 382 | Biological: MF59-eH5N1<br> <br> Biological: eTIV_a<br> <br> Biological: MF59-eH5N1 + eTIV_a<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Subjects Who Responded to Two or Three Vaccinations of the MF59-H5N1 Influenza Vaccine | Seroconversion (serocon.) is defined as negative pre-vaccination serum (titer <10 for HI [Haemagglutination Inhibition], area ≤4 mm^2 for SRH [Single Radial Haemolysis]) / positive post-vaccination titer (titer ≥ 40 for HI, area ≥ 25 mm^2 for SRH). Significant increase in antibody titer is defined as at least a fourfold increase from non-negative pre-vaccination serum (HI ≥ 10) or at least 50% increase in the SRH area. Seroprotection is defined as a HI titer ≥40 and a SRH area ≥25 mm^2. | 21 days after second and third vaccinations (day 43 and day 403) | 
| Geometric Mean Ratio After Two or Three Vaccinations of the MF59-eH5N1 Influenza Vaccine | Geometric mean Ratio (GMR) was calculated for the haemagglutination inhibition (HI), microneutralization (MN) and single-radial haemolysis (SRH) result as well as the associated 95% confidence intervals. GMR was calculated as 21 days after second and third vaccinations over day 1. | 21 days after second and third vaccinations (day 22 and day 43) | 
| Number of Subjects Who Responded to Two Vaccinations of the Seasonal eTIV_a Influenza Vaccines (Strain H1N1) | seroconversion: negative pre-vaccination serum (HI titer <10, SRH area =<4 mm^2)/positive post-vaccination titer (HI titer =>10) or at least 50% increase in the SRH area. Seroprotection is defined as a HI titer ≥40 and a SRH area ≥25 mm^2. | 21 days after second vaccination (day 43) | 
| Number of Subjects Who Responded to Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccines (Strain H3N2) | seroconversion (serocon.): negative pre-vaccination serum (HI titer <10, SRH area =<4 mm^2)/positive post-vaccination titer (HI titer =>10) or at least 50% increase in the SRH area. Seroprotection is defined as a HI titer ≥40 and a SRH area ≥25 mm^2. | 21 days after second and third vaccinations (day 43 and day 403) | 
| Number of Subjects Who Responded to Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccines (Strain B) | seroconversion (serocon.): negative pre-vaccination serum (HI titer <10, SRH area =<4 mm^2)/positive post-vaccination titer (HI titer =>10) or at least 50% increase in the SRH area. Seroprotection is defined as a HI titer ≥40 and a SRH area ≥25 mm^2. | 21 days after second and third vaccinations (day 43 and day 403) | 
| Geometric Mean Ratio After Two Doses of the Seasonal eTIV_a Influenza Vaccine (Strain H1N1) | For each vaccine group, the least squares GMRs were calculated for the haemagglutination inhibition (HI) results as well as the associated 95% confidence intervals. GMR was calculated over day 1. | 21 days after second vaccination (day 43) | 
| Geometric Mean Ratio After Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccine (Strain H3N1) | For each vaccine group, the least squares GMRs were calculated for the haemagglutination inhibition (HI) results for each time point of the study, as well as the associated 95% confidence intervals. GMR was calculated over day 1. | 21 days after second and third vaccinations (day 43 and day 403) | 
| Geometric Mean Ratio After Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccine (Strain B) | For each vaccine group, the least squares GMRs were calculated for the haemagglutination inhibition (HI) results for each time point of the study, as well as the associated 95% confidence intervals. GMR was calculated over day 1. | 21 days after second and third vaccinations (day 43 and day 403) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Local and Systemic Reactions by Vaccination | The evaluate the safety of the administration of two or three vaccinations of MF59-eH5N1 influenza vaccine, either given sequentially, concomitantly or mixed extemporaneously with seasonal eTIV_a influenza vaccine. | 21 days after second and third vaccinations (day 43 and day 403) | 
| Number of Subjects With Immunogenicity Results After the Booster Vaccination Against the MF59-eH5N1 Influenza Vaccine Mixed Extemporaneously With the Seasonal eTIV_a Influenza Vaccine | Booster was given on day 382; seroconversion: negative pre-vaccination serum (HI titer <10, SRH area ≤ 4 mm^2)/positive post-vaccination titer (HI titer ≥10) or at least 50% increase in SRH area; Seroprotection is defined as a HI titer ≥40 and a SRH area ≥25 mm^2. The number of subjects achieving seroconversion or significant increase and seroprotection were calculated at day 382. | 21 days after booster vaccination (day 403) | 
| Geometric Mean Ratio After the Booster Vaccination Against the MF59-eH5N1 Influenza Vaccine Mixed Extemporaneously With the Seasonal eTIV_a Influenza Vaccine | For each vaccine group, the least squares GMRs were calculated for the HI and SRH results for each time point of the study, as well as the associated 95% confidence intervals. GMR was calculated over day 382 for all time points for the booster dose. | 21 days after booster vaccination (day 403) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bird flu, influenza vaccine, Seasonal influenza vaccine, Prepandemic vaccine