Immunogenicity, Safety and Tolerability of Prepandemic Influenza and Seasonal Influenza Vaccine in Adult Subjects
- Conditions
- PandemicAvian Influenza
- Interventions
- Biological: MF59-eH5N1Biological: eTIV_aBiological: MF59-eH5N1 + eTIV_a
- Registration Number
- NCT00481065
- Lead Sponsor
- Novartis
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 405
- Healthy subjects
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mixed MF59-eH5N1 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 Mixed eTIV_a 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 MF59-eH5N1+eTIV_a eTIV_a 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 Mixed MF59-eH5N1 + eTIV_a 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 Mixed and mixed MF59-eH5N1 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1, day 22, and day 382 Mixed and mixed eTIV_a 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1, day 22, and day 382 Mixed and mixed MF59-eH5N1 + eTIV_a 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1, day 22, and day 382 Mixed+MF59-eH5N1 MF59-eH5N1 + eTIV_a 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 MF59-eH5N1+eTIV_a MF59-eH5N1 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 Concomitant +MF59-eH5N1 MF59-eH5N1 + eTIV_a 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 Mixed+MF59-eH5N1 eTIV_a 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 Concomitant +Mixed eTIV_a 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 Concomitant alone MF59-eH5N1 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. Concomitant alone eTIV_a 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. Concomitant alone MF59-eH5N1 + eTIV_a 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. Concomitant +Mixed MF59-eH5N1 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 Concomitant +Mixed MF59-eH5N1 + eTIV_a 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 Concomitant +MF59-eH5N1 MF59-eH5N1 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 Concomitant +MF59-eH5N1 eTIV_a 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 Mixed+MF59-eH5N1 MF59-eH5N1 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 MF59-eH5N1+eTIV_a MF59-eH5N1 + eTIV_a 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 eTIV_a+MF59-eH5N1 MF59-eH5N1 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 eTIV_a+MF59-eH5N1 eTIV_a 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 eTIV_a+MF59-eH5N1 MF59-eH5N1 + eTIV_a 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
- Primary Outcome Measures
Name Time Method Geometric Mean Ratio After Two or Three Vaccinations of the MF59-eH5N1 Influenza Vaccine 21 days after second and third vaccinations (day 22 and day 43) 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.
Number of Subjects Who Responded to Two Vaccinations of the Seasonal eTIV_a Influenza Vaccines (Strain H1N1) 21 days after second vaccination (day 43) 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.Number of Subjects Who Responded to Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccines (Strain H3N2) 21 days after second and third vaccinations (day 43 and day 403) 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.Number Subjects Who Responded to Two or Three Vaccinations of the MF59-H5N1 Influenza Vaccine 21 days after second and third vaccinations (day 43 and day 403) 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.Number of Subjects Who Responded to Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccines (Strain B) 21 days after second and third vaccinations (day 43 and day 403) 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.Geometric Mean Ratio After Two Doses of the Seasonal eTIV_a Influenza Vaccine (Strain H1N1) 21 days after second vaccination (day 43) 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.
Geometric Mean Ratio After Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccine (Strain H3N1) 21 days after second and third vaccinations (day 43 and day 403) 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.
Geometric Mean Ratio After Two or Three Vaccinations of the Seasonal eTIV_a Influenza Vaccine (Strain B) 21 days after second and third vaccinations (day 43 and day 403) 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects Reporting Local and Systemic Reactions by Vaccination 21 days after second and third vaccinations (day 43 and day 403) 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.
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 21 days after booster vaccination (day 403) 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.Geometric Mean Ratio After the Booster Vaccination Against the MF59-eH5N1 Influenza Vaccine Mixed Extemporaneously With the Seasonal eTIV_a Influenza Vaccine 21 days after booster vaccination (day 403) 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.