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

Phase 3

Completed

Conditions: Rabies

Interventions: Biological: Zagreb
Biological: Essen

Registration Number: NCT01680016

Lead Sponsor: Novartis Vaccines

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 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 644

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zagreb(≥6 to ≤17 Years)	Zagreb	-
Zagreb(≥51 Years)	Zagreb	-
Essen(≥6 to ≤17 Years)	Essen	-
Essen(≥51 Years)	Essen	-

Primary Outcome Measures

Name	Time	Method
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.	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	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	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 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	Days 1 to 7 postvaccination	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 Older Adults Who Reported Unsolicited Adverse Events (AEs)	from V1/day 1 (postvaccination) through V7/study termination day 43	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.
Number of Children Who Reported Unsolicited Adverse Events (AEs)	From V1/day 1 (postvaccination) through V7/study termination day 43	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.

Secondary Outcome Measures

Name	Time	Method
GMCs of RVNA Titer 42 Days After First Vaccination in Children.	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.	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.
Percentages of Children With RVNA Titers ≥0.5 IU/mL 14 Days After First Vaccination of Rabipur	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	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	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	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.