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
  Purpose

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.


Condition Intervention Phase
Rabies
Biological: Zagreb
Biological: Essen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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 Children and Older Adults

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 644
Study Start Date: September 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zagreb(≥6 to ≤17 Years) Biological: Zagreb
Subjects received Zagreb schedule (2-1-1) i.e. 4 vaccinations of Rabipur at days 1 , 8 and 22
Experimental: Zagreb(≥51 Years) Biological: Zagreb
Subjects received Zagreb schedule (2-1-1) i.e. 4 vaccinations of Rabipur at days 1 , 8 and 22
Active Comparator: Essen(≥6 to ≤17 Years) 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
Active Comparator: Essen(≥51 Years) 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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT01680016

Locations
China, Guangxi
Mengshan Center for Disease Prevention and Control (CDC)
Mengshan, Guangxi, China, 530028
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01680016     History of Changes
Other Study ID Numbers: V49_24
Study First Received: September 3, 2012
Results First Received: January 7, 2014
Last Updated: April 22, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Novartis:
Rabies virus, postexposure, vaccine schedule, children, older adults

Additional relevant MeSH terms:
Rabies
Rhabdoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 27, 2014