Back to resultsSafety and Immunogenicity of 2 Different Vaccination Schedules of Rabies and Japanese Encephalitis Vaccines in Healthy Adult Subjects
Primary Purpose
Rabies, Japanese Encephalitis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rabies
Japanese Encephalitis
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Rabies focused on measuring Rabies, JE, accelerated schedule
Eligibility Criteria
Inclusion Criteria:
- Males and females between 18 and 65 years of age (inclusive).
- Subjects who have given written consent.
- Individuals in good health as per investigator judgement.
Exclusion Criteria:
- If female, pregnancy or unwillingness to practice acceptable contraception.
- If female, pregnant or breast-feeding or any positive/indeterminate pregnancy test.
- Contraindication or precaution against Rabies and Japanese Encephalitis vaccination.
- Unable to comprehend and to follow all required study procedures for the whole period of the study.
- Participating in any other clinical trial 30 days prior to first study visit.
- History of previous rabies/rabies immunoglobulin and/or Japanese Encephalitis immunization.
- Receiving or planning to receive anti-malarial medications (e.g. Mefloquine) 14 days prior to Day 1 vaccination through Day 43.
- Received any other vaccines within 2 weeks prior to enrollment in this study or plan to receive any vaccine within 4 weeks from the study vaccines.
- Ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks.
- Individuals who are part of study personnel or close family members conducting this study.
- Body temperature ≥38 degrees Celsius (≥ 100.4° F) within 3 days of intended study vaccination.
- Plans to travel within the next year to areas where Rabies and/or Japanese Encephalitis vaccine may be considered or offered. This includes but is not limited to India, Asia, Pacific-Rim, African countries.
Sites / Locations
- Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectious Diseases and Immunology Medical University of Vienna
- Bernhard Nocht Institute for Tropical Medicine
- The University of Zurich
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Active Comparator
Active Comparator
Arm Label
R/JE - Conv
R/JE - Acc
R - Conv
JE - Conv
Arm Description
Subjects received Rabies and Japanese Encephalitis (JE) vaccines following the conventional schedule, ie, Rabies vaccination on days 1, 8, and 29, and placebo on day 4 in the right arm or leg; and JE vaccination on day 1 and 29, and placebo on day 8 in the left arm.
Subjects received Rabies and JE vaccines following the accelerated schedule, ie, Rabies vaccination on days 1, 4, and 8, and placebo on day 29 in the right arm or leg; and JE vaccination on days 1 and 8, and placebo on day 29 in the left arm.
Subjects received Rabies vaccine following the conventional schedule, ie, Rabies vaccination on days 1, 8, and 29, and placebo on day 4 in the right arm or leg; and placebo on days 1, 8 and 29 in the left arm.
Subjects received JE vaccine following the conventional schedule, ie, placebo on days 1, 4, 8 and 29 in the right arm or leg; and JE vaccination on days 1 and 29 and placebo injection on day 8 in the left arm.
Outcomes
Primary Outcome Measures
Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 7 Days After Last Active Vaccination
Immune response was measured as the percentage of subjects with rabies virus neutralizing antibody (RVNA) concentrations ≥0.5 IU/mL, evaluated using the rapid fluorescent focus inhibition test at day 7 after last active vaccination, i.e. the third out of four vaccinations given in the accelerated Rabies vaccine schedule and the fourth out of four vaccinations given in the conventional Rabies vaccine schedule.
As per study design, this primary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs R - Conv.
Percentages of Subjects With PRNT50 Titer ≥1:10 At 28 Days After Last Active Vaccination
Immune response was measured as the percentages of subjects with a titer of ≥1:10 in a 50% plaque reduction neutralization test (PRNT50) 28 days after last active vaccination, ie, the second out of three vaccinations given in the accelerated JE vaccine schedule and the third out of three vaccinations given in the conventional JE vaccine schedule.
As per study design, this primary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs JE - Conv.
Secondary Outcome Measures
RVNA Geometric Mean Concentrations (GMCs) At 28 Days After Last Active Vaccination
Immune response was measured as the RVNA GMCs 28 days after last active vaccination, ie, day 57 for all groups that received the conventional schedule.
Data were adjusted using ANOVA model, as per protocol specification.
PRNT50 Geometric Mean Titers (GMTs) At 28 Days After Last Active Vaccination
Immune response was measured as the PRNT50 GMTs 28 days after last active vaccination, ie, day 57 for all groups that received the conventional schedule.
Data were adjusted using ANOVA model, as per protocol specifications.
Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 28 Days After Last Active Vaccination
Immune response was measured as the percentages of subjects with RVNA concentration ≥0.5 IU/mL 28 days after last active vaccination, ie, day 36 for the group that received the accelerated schedule and day 57 for the group that received the conventional schedule.
As per study design, this secondary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs R - Conv.
Percentage of Subjects With PRNT50 Titer ≥1:10 At 7 Days After Last Active Vaccination
Immune response was measured as the percentage of subjects with PRNT50 titer of ≥1:10 7 days after last active vaccination, ie, day 15 for the group that received the accelerated schedule and day 36 for the group that received the conventional schedule.
As per study design, this secondary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs JE - Conv.
Kinetics of Rabies Immune Response Measured as Percentage of Subjects With RVNA Concentration ≥0.5 IU/mL
To evaluate the kinetics of antibody response to Rabies vaccine, the immunogenicity was measured as the percentage of subjects with RVNA concentrations ≥0.5 IU/mL on days 1, 8, 15, 36, 57, 91, 181, and 366.
Kinetics of Rabies Immune Response Measured as the RVNA GMCs
To evaluate the kinetics of antibody response to Rabies vaccine, the immunogenicity was measured as the RVNA GMCs on days 1, 8, 15, 36, 57, 91, 181, and 366.
Kinetics of JE Immune Response Measured as Percentage of Subjects With PRNT50 Titers ≥1:10
To evaluate the kinetics of antibody response to JE vaccine, the immunogenicity was measured as the percentage of subjects with PRNT50 titer ≥1:10 on days 1, 15, 22, 36, 57, 91, 181, and 366 (group that received JE vaccine as an accelerated schedule) and days 1, 36, 57, 181, and 366 (group that received JE vaccine as a conventional schedule).
Kinetics of JE Immune Response Measured as PRNT50 GMTs
To evaluate the kinetics of antibody response to JE vaccine, the immunogenicity was measured as the PRNT50 GMTs on days 1, 15, 22, 36, 57, 91, 181, and 366 (group that received JE vaccine as an accelerated schedule) and days 1, 36, 57, 181, and 366 (group that received JE vaccine as a conventional schedule).
Number of Subjects Who Reported Solicited Local Adverse Events After Each Rabies Vaccination
Safety was assessed as the number of subjects who reported solicited local adverse events (AEs) after each rabies vaccination given according to accelerated or conventional schedule as follows: from day 1 through day 7 (vaccination on day 1; all Rabies groups), day 4 through day 10 (vaccination on day 4; in R/JE - Acc group only), day 8 through day 14 (vaccination on day 8; all Rabies groups), or day 29 through day 35 (vaccination on day 29; R/JE - Conv and R - Conv groups).
Number of Subjects Who Reported Solicited Local AEs After Each JE Vaccination
Safety was assessed as the number of subjects who reported solicited local AEs after each JE vaccination given according to accelerated or conventional schedule as follow: from day 1 through day 7 (vaccination on day 1; all JE groups), day 8 through day 14 (vaccination on day 8; R/JE - Acc group only), or day 29 through day 35 (vaccination on day 29; R/JE - Con and JE - Conv groups).
Number of Subjects Who Reported Solicited Local AEs After Each Placebo Injection
Safety was assessed as the number of subjects who reported solicited local AEs after each placebo injection given according to accelerated and conventional schedule as follow: from day 1 through day 7 (injection on day 1; R - Conv and JE - Conv groups), day 4 through day 10 (injection on day 4; in R/JE - Conv, R - Conv and JE - Conv groups), day 8 through day 14 (injection on day 8; in R/JE - Conv, R - Conv and JE - Conv groups), and day 29 through day 35 (injection on day 29; R/JE - Acc, R - Con and JE - Conv groups).
Number of Subjects Who Reported Solicited Systemic AEs and Other Indicators of Reactogenicity After Each Vaccination
Safety was assessed as the number of subjects who reported solicited systemic AEs and other indicators of reactogenicity after each vaccination given according to accelerated and conventional schedule.
Numbers of Subjects Reporting Unsolicited AEs After Any Vaccination From Day 1 Through Day 57
Safety was assessed as the number of subjects who reported unsolicited AEs after any vaccination given according to accelerated and conventional schedule.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01662440
Brief Title
Safety and Immunogenicity of 2 Different Vaccination Schedules of Rabies and Japanese Encephalitis Vaccines in Healthy Adult Subjects
Official Title
A Phase III, Multicenter, Observer-blind, Safety and Immunogenicity Study of Rabies Vaccine and Japanese Encephalitis Vaccine Administered Concomitantly and/or Separately According to 1 of 2 Different Preexposure Prophylaxis Schedules to Healthy Adult Subjects.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Vaccines
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Establish non-inferiority of the immune response and evaluate the safety and tolerability of Rabies and Japanese Encephalitis (JE) vaccines given concomitantly or alone and according to either of 2 schedules for preexposure prophylaxis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rabies, Japanese Encephalitis
Keywords
Rabies, JE, accelerated schedule
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
661 (Actual)
8. Arms, Groups, and Interventions
Arm Title
R/JE - Conv
Arm Type
Active Comparator
Arm Description
Subjects received Rabies and Japanese Encephalitis (JE) vaccines following the conventional schedule, ie, Rabies vaccination on days 1, 8, and 29, and placebo on day 4 in the right arm or leg; and JE vaccination on day 1 and 29, and placebo on day 8 in the left arm.
Arm Title
R/JE - Acc
Arm Type
Experimental
Arm Description
Subjects received Rabies and JE vaccines following the accelerated schedule, ie, Rabies vaccination on days 1, 4, and 8, and placebo on day 29 in the right arm or leg; and JE vaccination on days 1 and 8, and placebo on day 29 in the left arm.
Arm Title
R - Conv
Arm Type
Active Comparator
Arm Description
Subjects received Rabies vaccine following the conventional schedule, ie, Rabies vaccination on days 1, 8, and 29, and placebo on day 4 in the right arm or leg; and placebo on days 1, 8 and 29 in the left arm.
Arm Title
JE - Conv
Arm Type
Active Comparator
Arm Description
Subjects received JE vaccine following the conventional schedule, ie, placebo on days 1, 4, 8 and 29 in the right arm or leg; and JE vaccination on days 1 and 29 and placebo injection on day 8 in the left arm.
Intervention Type
Biological
Intervention Name(s)
Rabies
Intervention Description
Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).
Intervention Type
Biological
Intervention Name(s)
Japanese Encephalitis
Intervention Description
Subjects received two doses of Japanese Encephalitis vaccine.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Subjects received either two, three, four or five doses of normal saline, 0.9% w/v sodium chloride depending on the vaccine group.
Primary Outcome Measure Information:
Title
Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 7 Days After Last Active Vaccination
Description
Immune response was measured as the percentage of subjects with rabies virus neutralizing antibody (RVNA) concentrations ≥0.5 IU/mL, evaluated using the rapid fluorescent focus inhibition test at day 7 after last active vaccination, i.e. the third out of four vaccinations given in the accelerated Rabies vaccine schedule and the fourth out of four vaccinations given in the conventional Rabies vaccine schedule.
As per study design, this primary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs R - Conv.
Time Frame
Day 7 after last active vaccination (day 15 - group that received accelerated schedule, day 36 - group that received conventional schedule)
Title
Percentages of Subjects With PRNT50 Titer ≥1:10 At 28 Days After Last Active Vaccination
Description
Immune response was measured as the percentages of subjects with a titer of ≥1:10 in a 50% plaque reduction neutralization test (PRNT50) 28 days after last active vaccination, ie, the second out of three vaccinations given in the accelerated JE vaccine schedule and the third out of three vaccinations given in the conventional JE vaccine schedule.
As per study design, this primary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs JE - Conv.
Time Frame
Day 28 after last active vaccination (day 36 - group that received accelerated schedule, day 57 - group that received conventional schedule)
Secondary Outcome Measure Information:
Title
RVNA Geometric Mean Concentrations (GMCs) At 28 Days After Last Active Vaccination
Description
Immune response was measured as the RVNA GMCs 28 days after last active vaccination, ie, day 57 for all groups that received the conventional schedule.
Data were adjusted using ANOVA model, as per protocol specification.
Time Frame
Day 57 (28 days after last active vaccination)
Title
PRNT50 Geometric Mean Titers (GMTs) At 28 Days After Last Active Vaccination
Description
Immune response was measured as the PRNT50 GMTs 28 days after last active vaccination, ie, day 57 for all groups that received the conventional schedule.
Data were adjusted using ANOVA model, as per protocol specifications.
Time Frame
Day 57 (28 days after last active vaccination)
Title
Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 28 Days After Last Active Vaccination
Description
Immune response was measured as the percentages of subjects with RVNA concentration ≥0.5 IU/mL 28 days after last active vaccination, ie, day 36 for the group that received the accelerated schedule and day 57 for the group that received the conventional schedule.
As per study design, this secondary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs R - Conv.
Time Frame
Day 36 and day 57 (28 days after last active vaccination)
Title
Percentage of Subjects With PRNT50 Titer ≥1:10 At 7 Days After Last Active Vaccination
Description
Immune response was measured as the percentage of subjects with PRNT50 titer of ≥1:10 7 days after last active vaccination, ie, day 15 for the group that received the accelerated schedule and day 36 for the group that received the conventional schedule.
As per study design, this secondary immunogenicity outcome measure aimed to demonstrate non-inferiority of R/JE - Acc Vs JE - Conv.
Time Frame
Day 15 and day 36 (28 after last active vaccination)
Title
Kinetics of Rabies Immune Response Measured as Percentage of Subjects With RVNA Concentration ≥0.5 IU/mL
Description
To evaluate the kinetics of antibody response to Rabies vaccine, the immunogenicity was measured as the percentage of subjects with RVNA concentrations ≥0.5 IU/mL on days 1, 8, 15, 36, 57, 91, 181, and 366.
Time Frame
Day 1, 8, 15, 36, 57, 91, 181 and Day 366
Title
Kinetics of Rabies Immune Response Measured as the RVNA GMCs
Description
To evaluate the kinetics of antibody response to Rabies vaccine, the immunogenicity was measured as the RVNA GMCs on days 1, 8, 15, 36, 57, 91, 181, and 366.
Time Frame
Day 1, 8, 15, 36, 57, 91, 181, and 366
Title
Kinetics of JE Immune Response Measured as Percentage of Subjects With PRNT50 Titers ≥1:10
Description
To evaluate the kinetics of antibody response to JE vaccine, the immunogenicity was measured as the percentage of subjects with PRNT50 titer ≥1:10 on days 1, 15, 22, 36, 57, 91, 181, and 366 (group that received JE vaccine as an accelerated schedule) and days 1, 36, 57, 181, and 366 (group that received JE vaccine as a conventional schedule).
Time Frame
Days 1, 15, 22, 36, 57, 91, 181 and 366
Title
Kinetics of JE Immune Response Measured as PRNT50 GMTs
Description
To evaluate the kinetics of antibody response to JE vaccine, the immunogenicity was measured as the PRNT50 GMTs on days 1, 15, 22, 36, 57, 91, 181, and 366 (group that received JE vaccine as an accelerated schedule) and days 1, 36, 57, 181, and 366 (group that received JE vaccine as a conventional schedule).
Time Frame
Day 1, 15, 22, 36, 57, 91, 181, and 366 (accelerated schedule) and day 1, 36, 57, 181, and 366 (conventional schedule)
Title
Number of Subjects Who Reported Solicited Local Adverse Events After Each Rabies Vaccination
Description
Safety was assessed as the number of subjects who reported solicited local adverse events (AEs) after each rabies vaccination given according to accelerated or conventional schedule as follows: from day 1 through day 7 (vaccination on day 1; all Rabies groups), day 4 through day 10 (vaccination on day 4; in R/JE - Acc group only), day 8 through day 14 (vaccination on day 8; all Rabies groups), or day 29 through day 35 (vaccination on day 29; R/JE - Conv and R - Conv groups).
Time Frame
Day 1 through day 7 after each vaccination (on day 1, 4, 8 and 29)
Title
Number of Subjects Who Reported Solicited Local AEs After Each JE Vaccination
Description
Safety was assessed as the number of subjects who reported solicited local AEs after each JE vaccination given according to accelerated or conventional schedule as follow: from day 1 through day 7 (vaccination on day 1; all JE groups), day 8 through day 14 (vaccination on day 8; R/JE - Acc group only), or day 29 through day 35 (vaccination on day 29; R/JE - Con and JE - Conv groups).
Time Frame
Day 1 through day 7 after each vaccination (on day 1, 8 and 29)
Title
Number of Subjects Who Reported Solicited Local AEs After Each Placebo Injection
Description
Safety was assessed as the number of subjects who reported solicited local AEs after each placebo injection given according to accelerated and conventional schedule as follow: from day 1 through day 7 (injection on day 1; R - Conv and JE - Conv groups), day 4 through day 10 (injection on day 4; in R/JE - Conv, R - Conv and JE - Conv groups), day 8 through day 14 (injection on day 8; in R/JE - Conv, R - Conv and JE - Conv groups), and day 29 through day 35 (injection on day 29; R/JE - Acc, R - Con and JE - Conv groups).
Time Frame
Day 1 through day 7 after each injection (day 1, 4, 8 and 29)
Title
Number of Subjects Who Reported Solicited Systemic AEs and Other Indicators of Reactogenicity After Each Vaccination
Description
Safety was assessed as the number of subjects who reported solicited systemic AEs and other indicators of reactogenicity after each vaccination given according to accelerated and conventional schedule.
Time Frame
Day 1 through day 7 after each vaccination (day 1, 4, 8 and 29)
Title
Numbers of Subjects Reporting Unsolicited AEs After Any Vaccination From Day 1 Through Day 57
Description
Safety was assessed as the number of subjects who reported unsolicited AEs after any vaccination given according to accelerated and conventional schedule.
Time Frame
Day 1 through Day 57
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males and females between 18 and 65 years of age (inclusive).
Subjects who have given written consent.
Individuals in good health as per investigator judgement.
Exclusion Criteria:
If female, pregnancy or unwillingness to practice acceptable contraception.
If female, pregnant or breast-feeding or any positive/indeterminate pregnancy test.
Contraindication or precaution against Rabies and Japanese Encephalitis vaccination.
Unable to comprehend and to follow all required study procedures for the whole period of the study.
Participating in any other clinical trial 30 days prior to first study visit.
History of previous rabies/rabies immunoglobulin and/or Japanese Encephalitis immunization.
Receiving or planning to receive anti-malarial medications (e.g. Mefloquine) 14 days prior to Day 1 vaccination through Day 43.
Received any other vaccines within 2 weeks prior to enrollment in this study or plan to receive any vaccine within 4 weeks from the study vaccines.
Ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks.
Individuals who are part of study personnel or close family members conducting this study.
Body temperature ≥38 degrees Celsius (≥ 100.4° F) within 3 days of intended study vaccination.
Plans to travel within the next year to areas where Rabies and/or Japanese Encephalitis vaccine may be considered or offered. This includes but is not limited to India, Asia, Pacific-Rim, African countries.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines and Diagnostics
Organizational Affiliation
Novartis Vaccines
Official's Role
Study Chair
Facility Information:
Facility Name
Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectious Diseases and Immunology Medical University of Vienna
City
Kinderspitalgasse 15
State/Province
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Bernhard Nocht Institute for Tropical Medicine
City
Bernhard-Nocht-Strasse 74
State/Province
Hamburg
ZIP/Postal Code
D-20359
Country
Germany
Facility Name
The University of Zurich
City
Rämistrasse 71
State/Province
Zürich
ZIP/Postal Code
CH-8006
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
26994987
Citation
Cramer JP, Jelinek T, Paulke-Korinek M, Reisinger EC, Dieckmann S, Alberer M, Buhler S, Bosse D, Meyer S, Fragapane E, Costantini M, Pellegrini M, Lattanzi M, Dovali C. One-year immunogenicity kinetics and safety of a purified chick embryo cell rabies vaccine and an inactivated Vero cell-derived Japanese encephalitis vaccine administered concomitantly according to a new, 1-week, accelerated primary series. J Travel Med. 2016 Mar 19;23(3):taw011. doi: 10.1093/jtm/taw011. Print 2016 Mar.
Results Reference
derived
PubMed Identifier
26005163
Citation
Jelinek T, Cramer JP, Dieckmann S, Hatz C, Paulke-Korinek M, Alberer M, Reisinger EC, Costantini M, Gniel D, Bosse D, Lattanzi M. Evaluation of rabies immunogenicity and tolerability following a purified chick embryo cell rabies vaccine administered concomitantly with a Japanese encephalitis vaccine. Travel Med Infect Dis. 2015 May-Jun;13(3):241-50. doi: 10.1016/j.tmaid.2015.05.008. Epub 2015 May 18.
Results Reference
derived
Learn more about this trial
Safety and Immunogenicity of 2 Different Vaccination Schedules of Rabies and Japanese Encephalitis Vaccines in Healthy Adult Subjects
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