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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00620815
First received: February 12, 2008
Last updated: September 17, 2012
Last verified: September 2012
  Purpose

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


Condition Intervention Phase
Influenza
Biological: MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine
Biological: Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1
Biological: Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine
Biological: Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1
Biological: Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine
Biological: MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
Official Title: A Phase II, Randomized, Placebo-controlled, Observer-blind, Multi Center Study on the Safety and Immunogenicity of Novartis Tetravalent Influenza Vaccine (Containing Both Interpandemic Strains and H5N1) in Adults Aged 18 Years and Above

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43. [ Time Frame: up to day 43 ] [ Designated as safety issue: No ]

    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:
  • Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination [ Time Frame: Upto 7 days after 1st vaccination ] [ Designated as safety issue: Yes ]
    Local reactions were collected upto 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.

  • Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination [ Time Frame: Upto 7 days after 2nd vaccination ] [ Designated as safety issue: Yes ]
    Local reactions were collected upto 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.

  • Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations. [ Time Frame: 7 days after first and second vaccinations each ] [ Designated as safety issue: Yes ]
    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 Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI)and at Least 4 Fold Rise in Titres by MN Assay-H5N1 Strain [ Time Frame: up to day 43 ] [ Designated as safety issue: No ]

    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)


  • Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2 [ Time Frame: Upto 43 days ] [ Designated as safety issue: No ]
    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.

  • Antibody Response Determined by HI and MN Assay. [ Time Frame: Upto 43 days ] [ Designated as safety issue: No ]
    Measurement of immunogenicity in terms of Geometric mean titres (GMTs) as determined by HI and MN assay.

  • Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination. [ Time Frame: Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43) ] [ Designated as safety issue: No ]

    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


  • Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit [ Time Frame: Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43) ] [ Designated as safety issue: No ]

    Frequency and functionality of vaccine antigen-specific CD4+ 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 CD3 mAb (aCD3)

    The change in frequency of T-cells was measured.



Enrollment: 601
Study Start Date: November 2007
Study Completion Date: December 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T/P-A
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
Biological: MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine
Tetravalent influenza vaccine (MF59-eTIV-H5N1)and placebo on day 1 followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1+V3
Experimental: A/P-T
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
Biological: Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1
Pandemic influenza vaccine plus placebo on day 1 followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1+V3
Active Comparator: A/S-A
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
Biological: Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine
Pandemic influenza vaccine plus seasonal influenza vaccine, 3-5 weeks later pandemic influenza vaccine , including serology blood draw at V1+V3
Experimental: T/P-A (V2 blood draw)
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
Biological: MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine
Tetravalent influenza vaccine (MF59-eTIV-H5N1)plus placebo followed 3-5 weeks later by pandemic influenza vaccine , including serology blood draw at V1, V2 and V3
Experimental: A/P-T (V2 blood draw)
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
Biological: Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1
Pandemic influenza vaccine plus placebo followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1, V2 and V3
Active Comparator: A/S-A (V2 blood draw)
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.
Biological: Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine
Pandemic influenza vaccine plus seasonal influenza vaccine followed 3-5 weeks later by pandemic influenza vaccine , including serology blood draw at V1, V2 and V3

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620815

Locations
Germany
ATRIUM Gesundheitszentrum;
Holzkirchen, Germany, 83607
International Medicine & Public Health Dept. of Infect. Diseases
Munich, Germany, 80799
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines and Diagnostics Novartis
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT00620815     History of Changes
Other Study ID Numbers: V101P1, 2007-002712-25
Study First Received: February 12, 2008
Results First Received: July 4, 2011
Last Updated: September 17, 2012
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
avian flu
seasonal influenza vaccine
influenza vaccine
prepandemic vaccine
virus strain with the potential to cause pandemic
tetravalent vaccine
Prophylaxis of influenza

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
Respiratory Tract Diseases
Respiratory Tract Infections
RNA Virus Infections
Virus Diseases
MF59 oil emulsion
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014