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

Purpose

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.

Condition	Intervention	Phase
Rabies Japanese Encephalitis	Biological: Rabies Biological: Japanese Encephalitis	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Prevention
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.

Resource links provided by NLM:

MedlinePlus related topics: Encephalitis Rabies

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Non-inferiority of the immune response to Rabies vaccine (administered concomitantly with JE vaccine) accelerated versus conventional schedule. [ Time Frame: 7 days after last active vaccine administration ] [ Designated as safety issue: No ]
Percentage of subjects with Rabies Virus Neutralizing Antibodies (RVNA) titer ≥ 0.5 IU/mL
Non-inferiority of the immune response to JE vaccine (administered concomitantly with Rabies vaccine) accelerated versus conventional schedule. [ Time Frame: 28 days after last active vaccine administration ] [ Designated as safety issue: No ]
Percentage of subjects with Plaque Reduction Neutralization Test (PRNT50) titer ≥ 1:10

Secondary Outcome Measures:

Rabies Virus Neutralizing Antibody Geometric Mean Titer [ Time Frame: 28 days after last active vaccination ] [ Designated as safety issue: No ]
Non-inferiority of the immune response of Rabies + JE versus Rabies vaccine as per conventional vaccination schedule.
Plaque Reduction Neutralization Test(PRNT50)Geometric Mean Titer [ Time Frame: 28 days after last active vaccination ] [ Designated as safety issue: No ]
Non-inferiority of the immune response to JE + Rabies versus JE vaccine as per conventional vaccination schedule.
Percentage of subjects with RVNA titer ≥0.5 IU/mL [ Time Frame: 28 days after last active vaccination ] [ Designated as safety issue: No ]
Non-inferiority of the immune response to Rabies + JE accelerated schedule versus Rabies vaccine as per conventional schedule
Percentage of subjects with PRNT50 ≥ 1:10 [ Time Frame: 7 days after last active vaccination ] [ Designated as safety issue: No ]
Non-inferiority of the immune response to JE +Rabies accelerated schedule versus JE vaccine as per conventional schedule
Percentage of subjects with RVNA titer ≥ 0.5 IU/mL and RVNA Geometric Mean Titer [ Time Frame: Days 1, 8, 15, 36, 57, 91, 181 and 366 ] [ Designated as safety issue: No ]
Kinetics of antibody response for Rabies on Days 1, 8, 15, 36, 57, 91, 181 and 366.
Percentage of subjects with PRNT50 ≥ 1:10 and PRNT50 Geometric Mean Titer [ Time Frame: Days1, 15, 22, 36, 57, 91, 181 and Day 366 ] [ Designated as safety issue: No ]
Kinetics of antibody response for JE on Days1, 15, 22, 36, 57, 91, 181 and Day 366
Proportion of subjects with solicited local reactions [ Time Frame: 7 days following each vaccination. ] [ Designated as safety issue: Yes ]
Proportion of subjects with solicited systemic and other reactions [ Time Frame: Day 1 (postvaccination) through Day 14 (inclusive) and Day 29 through Day 35 (inclusive). ] [ Designated as safety issue: Yes ]
Number of subjects with all AEs (including SAEs and AEs leading to subject withdrawal) [ Time Frame: Day 1 (postvaccination) through Day 57 (upon completion of clinic visit). ] [ Designated as safety issue: Yes ]
Number of subjects with all vaccine related SAEs [ Time Frame: Day 57 (post completion of clinic visit) through Day 366 (or study termination). ] [ Designated as safety issue: Yes ]
Number of subjects with all concomitant medications [ Time Frame: Day 1 through Day 57 ] [ Designated as safety issue: Yes ]

Enrollment:	660
Study Start Date:	August 2012
Estimated Study Completion Date:	October 2013
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group 1 Conventional (Rabies and JE Vaccines)	Biological: Rabies Biological: Japanese Encephalitis
Experimental: Group 2 Accelerated (Rabies and JE Vaccines)	Biological: Rabies Biological: Japanese Encephalitis
Active Comparator: Group 3 Conventional (Rabies Vaccine alone)	Biological: Rabies
Active Comparator: Group 4 Conventional (JE Vaccine alone)	Biological: Japanese Encephalitis

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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 female 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662440

Locations

Austria
Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectious Diseases and Immunology Medical University of Vienna
Kinderspitalgasse 15, Vienna, Austria, A-1090
Germany
Bernhard Nocht Institute for Tropical Medicine
Bernhard-Nocht-Strasse 74, Hamburg, Germany, D-20359
Switzerland
The University of Zurich
Rämistrasse 71, Zürich, Switzerland, CH-8006

Sponsors and Collaborators

Novartis Vaccines

Investigators

Study Chair:

Novartis Vaccines and Diagnostics

Novartis Vaccines

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:	NCT01662440 History of Changes
Other Study ID Numbers:	V49_23, 2011-005173-23
Study First Received:	August 2, 2012
Last Updated:	May 14, 2013
Health Authority:	Germany: Paul-Ehrlich-Institut Austria: Agency for Health and Food Safety Switzerland: Swissmedic

Keywords provided by Novartis:

Rabies
JE
accelerated schedule

Additional relevant MeSH terms:

Encephalitis
Encephalitis, Japanese
Rabies
Central Nervous System Viral Diseases
Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections

Encephalitis, Arbovirus
Arbovirus Infections
Encephalitis, Viral
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Rhabdoviridae Infections
Mononegavirales Infections

ClinicalTrials.gov processed this record on May 23, 2013