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

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 children.

Detailed Summary:
Sponsor: Novartis Vaccines

Current Primary Outcome:

  • The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]

    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 6 to <36 months, 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.

    As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years).

    CBER criterion 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 70%.

  • The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]

    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 3 to <9 years, 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 CBER criterion.

    As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years).

    CBER criterio

    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: Day 1 through Day 732 ]


    Current Secondary Outcome:

    • Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. [ Time Frame: Day 1, day 22, day 43 and day 387 ]

      Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 6 to <36 months is reported.

      The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.

      As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.

    • Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. [ Time Frame: Day 1, day 22, day 43 and day 387 ]

      Immunogenicity was measured as geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 3 to <9 years is reported.

      As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.

      The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.

    • Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. [ Time Frame: Day 1, day 22, day 43 and day 387 ]

      Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 9 to <18 years is reported.

      As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.

      The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.

    • Percentages Of Subjects Aged 6 to <36 Months, 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 aged 6 to <36 months, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

      European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

    • Percentages Of Subjects Aged 3 to <9 Years, 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 aged 3 to <9 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

      European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

    • Percentages Of Subjects Aged 9 to <18 Years, 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 aged 9 to <18 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.

      European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.

    • The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Day 22, day 43 and day 387 ]

      Immunogenicity was assessed in terms

      Original Secondary Outcome:

      Information By: Novartis

      Dates:
      Date Received: January 20, 2013
      Date Started: January 2013
      Date Completion:
      Last Updated: April 2, 2015
      Last Verified: April 2015