Safety and Immunogenicity of Two Doses of a Tetravalent Influenza Vaccine in Adults Aged 18 Years and Above

Phase 2

Completed

Conditions: Influenza

Interventions: Biological: MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine
Biological: Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1
Biological: MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine
Biological: Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine
Biological: Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine
Biological: Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1

Registration Number: NCT00620815

Lead Sponsor: Novartis Vaccines

Brief Summary: Evaluate the immune response and reactogenicity of H5N1 vaccination in adults aged 18 years and above (as part of a tetravalent vaccine)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 601

Inclusion Criteria

Healthy subjects (aged 18 years and above) who have signed an informed consent form

Exclusion Criteria

Any acute or chronic illness
Receipt of seasonal influenza vaccine for the current season 2007/2008
Known or suspected impairment/alteration of immune function
Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination
Any serious disease
Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein,neomycin or kanamycin or any other component of the study vaccine
Receipt of blood, blood products or immunoglobulins 3 months prior to vaccination

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
T/P-A	MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine	One dose of the tetravalent influenza vaccine (T) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by Aflunov (A) on day 22
A/P-T (V2 blood draw)	Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1	One dose of the Aflunov(A) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by additional blood draw at visit 2 (V2) prior to the Tetravalent influenza vaccination (T) on day 22.
T/P-A (V2 blood draw)	MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine	One dose of the tetravalent influenza vaccine (T) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by a blood draw at visit 2 (V2) prior to Aflunov (A) vaccination on day 22.
A/S-A (V2 blood draw)	Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine	One dose of Aflunov (A)and concomitantly, but in a different arm, one dose of licensed seasonal vaccine (S) on day 1, followed by an additional blood draw at visit 2 (V2) prior to Aflunov (A) vaccination on day 22.
A/S-A	Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine	One dose of Aflunov (A) and concomitantly, but in a different arm, one dose of licensed seasonal vaccine (S) on day 1, followed Aflunov (A) on day 22.
A/P-T	Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1	One dose of the Aflunov (A) and concomitantly, but in a different arm, one dose of placebo (P) on day 1, followed by Tetravalent influenza vaccine (T) on day 22.

Primary Outcome Measures

Name	Time	Method
To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43.	up to day 43	The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence. The statistical analysis was done based on the GMRs.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination	Up to 7 days after 2nd vaccination	Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.
Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2	Up to 43 days	Measurement of immunogenicity in terms of percentage of subjects achieving a titre ≥ 40/area ≥ 25mm\^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay.
Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit	Three weeks after 1st vaccination (day 22) and three weeks after 2nd vaccination (day 43)	Frequency and functionality of vaccine antigen-specific CD4+ (cluster of differentiation 4) T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb \[monoclonal antibody (aCD3)\]. The change in frequency of T-cells was measured.
Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination	Up to 7 days after 1st vaccination	Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently.
Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain	up to day 43	Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion. Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (≥ 10) for HI or a 50% increase in area for SRH. Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer ≥40 for HI (area ≥25 mm2 for SRH)
Antibody Response Determined by HI and MN Assay.	Up to 43 days	Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay.
Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations.	7 days after 1st and 2nd vaccinations each	Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.
Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination.	Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43)	The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects. Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC.

Trial Locations

Locations (2): ATRIUM Gesundheitszentrum;
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Holzkirchen, Germany
International Medicine & Public Health Dept. of Infect. Diseases
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Munich, Germany