Clinical Trial: Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Elderly Subjects

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II, Randomized, Observer-Blind, Multi-Center, Study to Evaluate Safety, Tolerability and Immunogenicity of an Adjuvanted Cell Culture-Derived H5N1 Subunit Influenz

Brief Summary: Evaluate Safety, Tolerability and Immune response of adjuvanted H5N1 cell culture derived influenza vaccine in elderly subjects

Detailed Summary:
Sponsor: Novartis Vaccines

Current Primary Outcome:

  • The Percentages Of Subjects Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. [ Time Frame: Baseline (day 1) and Three weeks after 2nd vaccination (day 43) ]

    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion.

    The CBER criterion for the elderly population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 60%.

  • The Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. [ Time Frame: Three weeks after 2nd vaccination (day 43) ]

    Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion.

    Seroconversion is defined as, a postvaccination titer ≥40 in subjects with a prevaccination HI titer <10; or in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.

    The CBER criterion for the elderly population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion

    Original Primary Outcome:

    • To select a vaccine dose based on the achievement of CBER criteria for further development [ Time Frame: Day 43 (3 weeks after second vaccination) ]
      Seroprotection and Seroconversion rate measured 3 weeks after second dose of vaccine administration
    • Percentage of subjects with solicited local and systemic adverse events [ Time Frame: 7 days post vaccination ]
    • Percentage of subjects with unsolicited adverse events [ Time Frame: 3 weeks post vaccination ]
    • Percentage of subjects with serious adverse events, medically attended adverse events, adverse events leading to withdrawal and adverse events of special interest [ Time Frame: Throughout the study ]


    Current Secondary Outcome:

    • Geometric Mean Ratios (GMR) Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. [ Time Frame: Day 1; day 22; day 43 and day 387 ]

      Immunogenicity was measured as the GMR. The ratio of postvaccination to prevaccination HI geometric mean titers (GMTs) is reported.

      The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.0 for subjects >60 years of age.

    • Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Day 1, day 22, day 43 and day 387. ]

      Immunogenicity was assessed in terms of percentage of subjects achieving HI titers >40, three weeks after second vaccination with aH5N1c according to the CHMP criterion.

      The European Licensure (CHMP) criterion is met if the percentage of subjects achieving HI titers ≥40 is >60%.

    • The Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Day 22, day 43 and day 387 ]

      Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, three weeks after receiving two injections of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.

      Seroconversion is defined as a postvaccination titer ≥40 in subjects with a prevaccination HI titer <10; or in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.

      The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion is >30%.



    Original Secondary Outcome:

    • Achievement of CHMP criteria 3 weeks after after second dose of vaccine administration [ Time Frame: Day 43 ]
      Seroprotection, Seroconversion rate and GMRs measured 3 weeks after second dose of vaccine administration
    • Achievement of CBER and CHMP criteria 3 weeks after first dose of vaccine administration [ Time Frame: Day 22 ]
      Seroprotection, Seroconversion rate and GMRs measured 3 weeks after first dose of vaccine administration
    • Achievement of CBER and CHMP criteria 3 weeks after booster dose of vaccine administration [ Time Frame: Day 387 ]
      Seroprotection, Seroconversion rate and GMRs measured 3 weeks after booster dose of vaccine administration


    Information By: Novartis

    Dates:
    Date Received: January 10, 2013
    Date Started: January 2013
    Date Completion:
    Last Updated: July 14, 2015
    Last Verified: July 2015