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

NCT01662440 | Completed Phase 3 Results

• 2 other identifiers: V49_232011-005173-23
• Study Type: interventional
• Target: 661
• Locations: 3 countries
• Sites: 3

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.

Conditions

Rabies; Japanese Encephalitis

Keywords

Rabies; JE; accelerated schedule

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (13)

• RVNA Geometric Mean Concentrations (GMCs) At 28 Days After Last Active Vaccination

  Day 57 (28 days after last active vaccination)

• PRNT50 Geometric Mean Titers (GMTs) At 28 Days After Last Active Vaccination

  Day 57 (28 days after last active vaccination)

• Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 28 Days After Last Active Vaccination

  Day 36 and day 57 (28 days after last active vaccination)

• Percentage of Subjects With PRNT50 Titer ≥1:10 At 7 Days After Last Active Vaccination

  Day 15 and day 36 (28 after last active vaccination)

• Kinetics of Rabies Immune Response Measured as Percentage of Subjects With RVNA Concentration ≥0.5 IU/mL

  Day 1, 8, 15, 36, 57, 91, 181 and Day 366

Study Arms (4)

R/JE - Conv

ACTIVE COMPARATOR

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.

Biological: Rabies; Biological: Japanese Encephalitis; Other: Placebo

R/JE - Acc

EXPERIMENTAL

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.

Biological: Rabies; Biological: Japanese Encephalitis; Other: Placebo

R - Conv

ACTIVE COMPARATOR

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.

Biological: Rabies; Other: Placebo

JE - Conv

ACTIVE COMPARATOR

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.

Biological: Japanese Encephalitis; Other: Placebo

Interventions

Rabies BIOLOGICAL

Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).

R - Conv; R/JE - Acc; R/JE - Conv

Japanese Encephalitis BIOLOGICAL

Subjects received two doses of Japanese Encephalitis vaccine.

JE - Conv; R/JE - Acc; R/JE - Conv

Placebo OTHER

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

JE - Conv; R - Conv; R/JE - Acc; R/JE - Conv

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Vaccines: lead

Study Sites (3)

Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectious Diseases and Immunology Medical University of Vienna

Kinderspitalgasse 15, Vienna, A-1090, Austria

Location

Bernhard Nocht Institute for Tropical Medicine

Bernhard-Nocht-Strasse 74, Hamburg, D-20359, Germany

Location

The University of Zurich

Rämistrasse 71, Canton of Zurich, CH-8006, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 26994987 DERIVED

• 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.

  PMID: 26005163 DERIVED

MeSH Terms

Conditions

Rabies; Encephalitis, Japanese

Condition Hierarchy (Ancestors)

Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Mosquito-Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Results Point of Contact

• Title: Posting Director
• Organization: Novartis Vaccines

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines and Diagnostics

  Novartis Vaccines

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 10, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: October 1, 2013
• Last Updated: December 8, 2014
• Results First Posted: December 8, 2014

Record last verified: 2014-12

Locations

CH (1); DE (1); AU (1)