Clinical trial NCT01680016: A Randomized, Open-label Study Comparing Two Different Rabies Vaccine Schedules in Chinese Children and Older Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rabies
Keywords: Rabies virus, postexposure, vaccine schedule, children, older adults
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-09-06
Enrollment: 644
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility 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

Primary outcomes:
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.
timeFrame: Before vaccination (day 1) and 14 days after first vaccination (day 15)
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 the First Vaccination in Older Adults Aged ≥51 Years
timeFrame: Before vaccination (day 1) and 14 days after first vaccination (day 15).
measure: Number of Children Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination of Rabipur
timeFrame: Days 1 to 7 postvaccination
measure: Number of Older Adults Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination of Rabipur
timeFrame: Days 1 to 7 postvaccination
measure: Number of Children Who Reported Unsolicited Adverse Events (AEs)
timeFrame: From V1/day 1 (postvaccination) through V7/study termination day 43
measure: Number of Older Adults Who Reported Unsolicited Adverse Events (AEs)
timeFrame: from V1/day 1 (postvaccination) through V7/study termination day 43
Secondary outcomes:
measure: Percentages of Children With RVNA Titers ≥0.5 IU/mL 14 Days After First Vaccination of Rabipur
timeFrame: Before vaccination (day 1) and 14 days after first vaccination (day 15).
measure: Percentages of Older Adults With RVNA Titers ≥0.5 IU/mL 14 Days After First Vaccination of Rabipur
timeFrame: Before vaccination (day 1) and 14 days after first vaccination (day 15).
measure: Percentages of Children With RVNA Titers ≥0.5 IU/mL 42 Days After First Vaccination of Rabipur
timeFrame: Before vaccination (day 1) and 42 days after first vaccination (day 43).
measure: Percentages of Older Adults With RVNA Titers ≥0.5 IU/mL 42 Days After First Vaccination of Rabipur
timeFrame: Before vaccination (day 1) and 42 days after first vaccination (day 43).
measure: GMCs of RVNA Titer 42 Days After First Vaccination in Children.
timeFrame: Before vaccination (day 1) and 42 days after first vaccination (day 43)
measure: GMCs of RVNA Titer 42 Days After the First Vaccination in Older Adults.
timeFrame: Before vaccination (day 1) and 42 days after first vaccination (day 43)
Other outcomes:
Locations:
city: Mengshan
country: China
facility: Mengshan Center for Disease Prevention and Control (CDC)
state: Guangxi
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References:
citation: Li R, Li Y, Wen S, Wen H, Nong Y, Mo Z, Xie F, Pellegrini M. Immunogenicity and safety of purified chick-embryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: a randomized open-label study. Hum Vaccin Immunother. 2015;11(2):435-42. doi: 10.4161/21645515.2014.994460.