Safety and Immunogenicity of 2 Different Vaccination Schedules of Rabies and Japanese Encephalitis Vaccines in Healthy Adult Subjects

Rabies Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01662440
• Other study ID #: V49_23
• Secondary ID: 2011-005173-23
• Status: Completed
• Phase: Phase 3
• First received: August 2, 2012
• Last updated: December 2, 2014
• Start date: August 2012
• Est. completion date: October 2013

Study information

• Verified date: December 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 661
• Est. completion date: October 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Males and females between 18 and 65 years of age (inclusive).

2. Subjects who have given written consent.

3. Individuals in good health as per investigator judgement.

Exclusion Criteria:

1. If female, pregnancy or unwillingness to practice acceptable contraception.

2. If female, pregnant or breast-feeding or any positive/indeterminate pregnancy test.

3. Contraindication or precaution against Rabies and Japanese Encephalitis vaccination.

4. Unable to comprehend and to follow all required study procedures for the whole period of the study.

5. Participating in any other clinical trial 30 days prior to first study visit.

6. History of previous rabies/rabies immunoglobulin and/or Japanese Encephalitis immunization.

7. Receiving or planning to receive anti-malarial medications (e.g. Mefloquine) 14 days prior to Day 1 vaccination through Day 43.

8. 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.

9. Ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks.

10. Individuals who are part of study personnel or close family members conducting this study.

11. Body temperature =38 degrees Celsius (= 100.4° F) within 3 days of intended study vaccination.

12. 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.

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Japanese
• Japanese Encephalitis
• Rabies

Intervention

Biological:
• Rabies
Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).
• Japanese Encephalitis
Subjects received two doses of Japanese Encephalitis vaccine.

Other:
• Placebo
Subjects received either two, three, four or five doses of normal saline, 0.9% w/v sodium chloride depending on the vaccine group.

Locations

Country	Name	City	State
Austria	Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectious Diseases and Immunology Medical University of Vienna	Kinderspitalgasse 15	Vienna
Germany	Bernhard Nocht Institute for Tropical Medicine	Bernhard-Nocht-Strasse 74	Hamburg
Switzerland	The University of Zurich	Rämistrasse 71	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 7 after last active vaccination (day 15 - group that received accelerated schedule, day 36 - group that received conventional schedule)
Primary	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.	Day 28 after last active vaccination (day 36 - group that received accelerated schedule, day 57 - group that received conventional schedule)
Secondary	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.	Day 57 (28 days after last active vaccination)
Secondary	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.	Day 57 (28 days after last active vaccination)
Secondary	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.	Day 36 and day 57 (28 days after last active vaccination)
Secondary	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.	Day 15 and day 36 (28 after last active vaccination)
Secondary	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.	Day 1, 8, 15, 36, 57, 91, 181 and Day 366
Secondary	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.	Day 1, 8, 15, 36, 57, 91, 181, and 366
Secondary	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).	Days 1, 15, 22, 36, 57, 91, 181 and 366
Secondary	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).	Day 1, 15, 22, 36, 57, 91, 181, and 366 (accelerated schedule) and day 1, 36, 57, 181, and 366 (conventional schedule)
Secondary	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).	Day 1 through day 7 after each vaccination (on day 1, 4, 8 and 29)
Secondary	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).	Day 1 through day 7 after each vaccination (on day 1, 8 and 29)
Secondary	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).	Day 1 through day 7 after each injection (day 1, 4, 8 and 29)
Secondary	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.	Day 1 through day 7 after each vaccination (day 1, 4, 8 and 29)
Secondary	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.	Day 1 through Day 57