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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT01680016
First received: September 3, 2012
Last updated: April 22, 2014
Last verified: April 2014

September 3, 2012
April 22, 2014
September 2012
January 2013   (final data collection date for primary outcome measure)
  • 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) ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 Essen (1-1-1-1-1) postexposure schedule.
  • Number of Older Adults Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination of Rabipur [ Time Frame: Days 1 to 7 postvaccination ] [ Designated as safety issue: Yes ]
    Safety was assessed as the number of subjects 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 Essen (1-1-1-1-1) postexposure schedule.
  • Number of Children Who Reported Unsolicited Adverse Events (AEs) [ Time Frame: From V1/day 1 (postvaccination) through V7/study termination day 43 ] [ Designated as safety issue: Yes ]
    The safety of Rabipur was assessed in terms of subjects(Children) exposed to study vaccine who reported all Unsolicited AEs (including serious adverse events [SAE]s and AEs leading to subject withdrawal) from V1/day 1 (postvaccination) through V7/study termination day 43.
  • Number of Older Adults Who Reported Unsolicited Adverse Events (AEs) [ Time Frame: from V1/day 1 (postvaccination) through V7/study termination day 43 ] [ Designated as safety issue: Yes ]
    The safety of Rabipur was assessed in terms of subjects(Older Adults) exposed to study vaccine who reported all Unsolicited AEs (including serious adverse events [SAE]s and AEs leading to subject withdrawal) from V1/day 1 (postvaccination) through V7/study termination day 43.
  • Local and systemic reactions [ Time Frame: 7 days after vaccination ] [ Designated as safety issue: Yes ]
  • AEs/SAEs [ Time Frame: 43 days ] [ Designated as safety issue: Yes ]
    Safety and tolerability of the two schedules as measured by AEs/SAEs and solicited event reporting
  • Geometric Mean Concentration of Rabies virus neutralizing antibody (RVNA)titers [ Time Frame: Day 14 after vaccination ] [ Designated as safety issue: No ]
    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.
Complete list of historical versions of study NCT01680016 on ClinicalTrials.gov Archive Site
  • 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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.
  • RVNA titers ≥ 0.5 IU/mL [ Time Frame: 14 days after first vaccination ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Randomized, Open-label Study Comparing Two Different Rabies Vaccine Schedules in Chinese Children and Older Adults
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 Children and Older Adults

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.

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Rabies
  • Biological: Zagreb
    Subjects received Zagreb schedule (2-1-1) i.e. 4 vaccinations of Rabipur at days 1 , 8 and 22
  • Biological: Essen
    Subjects received Essen schedule (1-1-1-1-1) i.e. 5 vaccinations of Rabipur at days 1, 4, 8, 15 and 29
  • Experimental: Zagreb(≥6 to ≤17 Years)
    Intervention: Biological: Zagreb
  • Experimental: Zagreb(≥51 Years)
    Intervention: Biological: Zagreb
  • Active Comparator: Essen(≥6 to ≤17 Years)
    Intervention: Biological: Essen
  • Active Comparator: Essen(≥51 Years)
    Intervention: Biological: Essen
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
644
January 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Individuals between 6-17 years of age and 51 years of age or older
  • Individuals who were in good health
  • Provided consent, complied with study procedures and duration of follow-up

Exclusion Criteria:

  • Contraindications to vaccination with rabies vaccine
  • Body temperature ≥37.5◦C (axillary) within 3 days of intended study vaccination
  • Known hypersensitivity to the components of the vaccine
  • Previously received any rabies vaccine or immune globulin
  • Previous or planned treatment with antimalarial medications
  • History of psychiatric disease, immune disorder, bleeding disorder, drug/alcohol abuse within the past 2 years, malignancy
  • Female subjects who were pregnant or unwilling to practice acceptable birth control methods
  • Individuals enrolled or plans to enroll in another investigational trial
Both
6 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
China
 
NCT01680016
V49_24
No
Novartis ( Novartis Vaccines )
Novartis Vaccines
Not Provided
Study Chair: Novartis Vaccines Novartis Vaccines
Novartis
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP