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

Rabies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01680016
• Other study ID #: V49_24
• Status: Completed
• Phase: Phase 3
• First received: September 3, 2012
• Last updated: April 22, 2014
• Start date: September 2012
• Est. completion date: January 2013

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 644
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Rabies

Intervention

Biological:
• Zagreb
Subjects received Zagreb schedule (2-1-1) i.e. 4 vaccinations of Rabipur at days 1 , 8 and 22
• Essen
Subjects received Essen schedule (1-1-1-1-1) i.e. 5 vaccinations of Rabipur at days 1, 4, 8, 15 and 29

Locations

Country	Name	City	State
China	Mengshan Center for Disease Prevention and Control (CDC)	Mengshan	Guangxi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	Before vaccination (day 1) and 14 days after first vaccination (day 15)	No
Primary	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	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.	Before vaccination (day 1) and 14 days after first vaccination (day 15).	No
Primary	Number of Children Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination of Rabipur	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.	Days 1 to 7 postvaccination	Yes
Primary	Number of Older Adults Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination of Rabipur	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.	Days 1 to 7 postvaccination	Yes
Primary	Number of Children Who Reported Unsolicited Adverse Events (AEs)	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.	From V1/day 1 (postvaccination) through V7/study termination day 43	Yes
Primary	Number of Older Adults Who Reported Unsolicited Adverse Events (AEs)	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.	from V1/day 1 (postvaccination) through V7/study termination day 43	Yes
Secondary	Percentages of Children With RVNA Titers =0.5 IU/mL 14 Days After First Vaccination of Rabipur	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.	Before vaccination (day 1) and 14 days after first vaccination (day 15).	No
Secondary	Percentages of Older Adults With RVNA Titers =0.5 IU/mL 14 Days After First Vaccination of Rabipur	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.	Before vaccination (day 1) and 14 days after first vaccination (day 15).	No
Secondary	Percentages of Children With RVNA Titers =0.5 IU/mL 42 Days After First Vaccination of Rabipur	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.	Before vaccination (day 1) and 42 days after first vaccination (day 43).	No
Secondary	Percentages of Older Adults With RVNA Titers =0.5 IU/mL 42 Days After First Vaccination of Rabipur	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.	Before vaccination (day 1) and 42 days after first vaccination (day 43).	No
Secondary	GMCs of RVNA Titer 42 Days After First Vaccination in Children.	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.	Before vaccination (day 1) and 42 days after first vaccination (day 43)	No
Secondary	GMCs of RVNA Titer 42 Days After the First Vaccination in Older Adults.	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.	Before vaccination (day 1) and 42 days after first vaccination (day 43)	No