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

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

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.

Study Overview

• Status: Completed
• Conditions: Pandemic; Avian Influenza
• Intervention / Treatment: Biological: MF59-eH5N1; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a

• Study Type: Interventional
• Enrollment (Actual): 405
• Phase: Phase 2

Contacts and Locations

Study Locations

• Colombia
  • Bogotà, Colombia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concomitant alone; 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; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: Concomitant +Mixed; 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; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: Concomitant +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	Biological: MF59-eH5N1; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: Mixed; 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; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: Mixed and mixed; 1 dose of MF59-eH5N1 mixed extemporaneously with eTIV_a on day 1, day 22, and day 382	Biological: MF59-eH5N1; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: Mixed+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	Biological: MF59-eH5N1; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: 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	Biological: MF59-eH5N1; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a
Experimental: eTIV_a+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	Biological: MF59-eH5N1; Biological: eTIV_a; Biological: MF59-eH5N1 + eTIV_a

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis
• Collaborators: Novartis Vaccines
• Investigators: Study Chair: Novartis Drug Information Services +1 800 244 7668, Novartis

Publications and helpful links

General Publications

• Lopez P, Caicedo Y, Sierra A, Tilman S, Banzhoff A, Clemens R. Combined, concurrent, and sequential administration of seasonal influenza and MF59-adjuvanted A/H5N1 vaccines: a phase II randomized, controlled trial of immunogenicity and safety in healthy adults. J Infect Dis. 2011 Jun 15;203(12):1719-28. doi: 10.1093/infdis/jir191.
• Lopez P, Caicedo Y, Sierra A, Tilman S, Clemens R, Banzhoff A. Combined administration of MF59-adjuvanted A/H5N1 prepandemic and seasonal influenza vaccines: long-term antibody persistence and robust booster responses 1 year after a one-dose priming schedule. Clin Vaccine Immunol. 2013 May;20(5):753-8. doi: 10.1128/CVI.00626-12. Epub 2013 Mar 27.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: May 31, 2007
• First Submitted That Met QC Criteria: May 31, 2007
• First Posted (Estimate): June 1, 2007

Study Record Updates

• Last Update Posted (Estimate): February 3, 2014
• Last Update Submitted That Met QC Criteria: December 31, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: influenza vaccine; Seasonal influenza vaccine; Bird flu; Prepandemic vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; MF59 oil emulsion
• Other Study ID Numbers: V87P5