Clinical Trial: A Randomized, Open-label Study Comparing Two Different Rabies Vaccine Schedules in Chinese Children and Older Adults

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

Official Title: A Phase IIIb, Randomized, Open-label Study Comparing Two Different Rabies Vaccine Post-exposure Schedules (Zagreb 2-1-1 and Rabipur® Essen 1-1-1-1-1) in Chinese Child

Brief Summary: This study was designed to evaluate the safety and immunogenicity of two simulated postexposure rabies vaccination schedules (Zagreb 2-1-1 and Essen 1-1-1-1-1) in Chinese children and older adults.

Detailed Summary:

This study was designed to evaluate the safety and immunogenicity of Rabipur Zagreb (2-1-1) and Rabipur Essen (1-1-1-1-1) simulated post exposure vaccination schedules in Chinese children and older adults. Subjects randomized to Group 1 (Zagreb) will receive 4 doses of rabies vaccine Day 1 (2 doses), and on Day 8 and Day 22. Subjects randomized to Group 2 (Essen) will receive 5 doses of rabies vaccine on Days 1, 4, 8, 15, and 29. First vaccine will be administered on study Day 1.

240 children and 400 older adults, a total of 640, is planned to be enrolled into the study. Subjects will be divided further into age subsets of equal numbers within each age cohort (children: 6 to 11 years of age and 12 to 17 years of age; older adults: 51 to 60 years of age and 61 years of age and older. Within each age subset, subjects will be assigned randomly in a 1:1 ratio.

The primary objective is to establish the non-inferiority of the Rabipur Zagreb (2-1-1) schedule relative to the conventional Rabipur Essen (1-1-1-1-1) schedule based on geometric mean titers (GMC), and the secondary objective is to assess the percent of subjects with rabies virus neutralizing titer ≥ 0.5 IU/mL 14 days after the first vaccinations (study Day 15) for each schedule and age cohort


Sponsor: Novartis Vaccines

Current Primary Outcome:

  • Non-inferiority in Immune Response of the Zagreb Postexposure Schedule of Rabipur to That of the Conventional Essen Postexposure Schedule of Rabipur as Measured by GMC of RVNA Titer 14 Days After First Vaccination in Children Aged ≥6 to ≤17 Years. [ Time Frame: Before vaccination (day 1) and 14 days after first vaccination (day 15) ]
    Immunogenicity was measured as the geometric mean concentrations (GMCs) of rabies virus neutralizing antibody (RVNA) titer , evaluated using the rapid fluorescent focus inhibition test, before vaccination and 14 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
  • Non-inferiority in Immune Response of the Zagreb Postexposure Schedule of Rabipur to That of the Conventional Essen Postexposure Schedule of Rabipur as Measured by GMC of RVNA Titer 14 Days After the First Vaccination in Older Adults Aged ≥51 Years [ Time Frame: Before vaccination (day 1) and 14 days after first vaccination (day 15). ]
    Immunogenicity was measured as the GMCs of Rabies Virus Neutralizing Antibody (RVNA) titer , evaluated using the rapid fluorescent focus inhibition test, before vaccination and 14 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
  • Number of Children Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination of Rabipur [ Time Frame: Days 1 to 7 postvaccination ]
    Safety was assessed as the number of children who reported solicited local and systemic adverse events from day 1 up to and including day 7 after any vaccination of Rabipur as per Zagreb (2-1-1) and Esse

    Original Primary Outcome:

    • Geometric Mean Concentration of Rabies virus neutralizing antibody (RVNA)titers [ Time Frame: Day 14 after vaccination ]
      Non inferiority of the (2-1-1) postexposure schedule to that of the conventional (1-1-1-1-1) postexposure schedule, as measured by GMC of RVNA titers 14 days after vaccination in children and older adults.
    • Local and systemic reactions [ Time Frame: 7 days after vaccination ]
    • AEs/SAEs [ Time Frame: 43 days ]
      Safety and tolerability of the two schedules as measured by AEs/SAEs and solicited event reporting


    Current Secondary Outcome:

    • Percentages of Children With RVNA Titers ≥0.5 IU/mL 14 Days After First Vaccination of Rabipur [ Time Frame: Before vaccination (day 1) and 14 days after first vaccination (day 15). ]
      Immunogenicity was measured as the percentages of subjects who achieved RVNA titers ≥0.5 IU/mL, 14 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
    • Percentages of Older Adults With RVNA Titers ≥0.5 IU/mL 14 Days After First Vaccination of Rabipur [ Time Frame: Before vaccination (day 1) and 14 days after first vaccination (day 15). ]
      Immunogenicity was measured as the percentages of subjects who achieved RVNA titers ≥0.5 IU/mL, 14 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
    • Percentages of Children With RVNA Titers ≥0.5 IU/mL 42 Days After First Vaccination of Rabipur [ Time Frame: Before vaccination (day 1) and 42 days after first vaccination (day 43). ]
      Immunogenicity was measured as the percentages of subjects who achieved RVNA titers ≥0.5 IU/mL, 42 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
    • Percentages of Older Adults With RVNA Titers ≥0.5 IU/mL 42 Days After First Vaccination of Rabipur [ Time Frame: Before vaccination (day 1) and 42 days after first vaccination (day 43). ]
      Immunogenicity was measured as the percentages of subjects who achieved RVNA titers ≥0.5 IU/mL, 42 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
    • GMCs of RVNA Titer 42 Days After First Vaccination in Children. [ Time Frame: Before vaccination (day 1) and 42 days after first vaccination (day 43) ]
      Immunogenicity was measured as the GMCs of RVNA titers, evaluated using the rapid fluorescent focus inhibition test, before vaccination and 42 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.
    • GMCs of RVNA Titer 42 Days After the First Vaccination in Older Adults. [ Time Frame: Before vaccination (day 1) and 42 days after first vaccination (day 43) ]
      Immunogenicity was measured as the GMCs of RVNA titers, evaluated using the rapid fluorescent focus inhibition test, before vaccination and 42 days after first vaccination of Rabipur as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.


    Original Secondary Outcome:

    • RVNA titers ≥ 0.5 IU/mL [ Time Frame: 14 days after first vaccination ]
      Percentages of subjects with RVNA titer ≥ 0.5 IU/mL 14 days after the first vaccination.
    • GMC and percentage of subjects with RVNA titer ≥ 0.5 IU/mL [ Time Frame: 42 days after first vaccination ]


    Information By: Novartis

    Dates:
    Date Received: September 3, 2012
    Date Started: September 2012
    Date Completion:
    Last Updated: April 22, 2014
    Last Verified: April 2014