Clinical trial NCT01662440: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rabies
Japanese Encephalitis
Keywords: Rabies
JE
accelerated schedule
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-08-10
Enrollment: 661
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 7 Days After Last Active Vaccination
timeFrame: Day 7 after last active vaccination (day 15 - group that received accelerated schedule, day 36 - group that received conventional schedule)
measure: Percentages of Subjects With PRNT50 Titer ≥1:10 At 28 Days After Last Active Vaccination
timeFrame: Day 28 after last active vaccination (day 36 - group that received accelerated schedule, day 57 - group that received conventional schedule)
Secondary outcomes:
measure: RVNA Geometric Mean Concentrations (GMCs) At 28 Days After Last Active Vaccination
timeFrame: Day 57 (28 days after last active vaccination)
measure: PRNT50 Geometric Mean Titers (GMTs) At 28 Days After Last Active Vaccination
timeFrame: Day 57 (28 days after last active vaccination)
measure: Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 28 Days After Last Active Vaccination
timeFrame: Day 36 and day 57 (28 days after last active vaccination)
measure: Percentage of Subjects With PRNT50 Titer ≥1:10 At 7 Days After Last Active Vaccination
timeFrame: Day 15 and day 36 (28 after last active vaccination)
measure: Kinetics of Rabies Immune Response Measured as Percentage of Subjects With RVNA Concentration ≥0.5 IU/mL
timeFrame: Day 1, 8, 15, 36, 57, 91, 181 and Day 366
measure: Kinetics of Rabies Immune Response Measured as the RVNA GMCs
timeFrame: Day 1, 8, 15, 36, 57, 91, 181, and 366
measure: Kinetics of JE Immune Response Measured as Percentage of Subjects With PRNT50 Titers ≥1:10
timeFrame: Days 1, 15, 22, 36, 57, 91, 181 and 366
measure: Kinetics of JE Immune Response Measured as PRNT50 GMTs
timeFrame: Day 1, 15, 22, 36, 57, 91, 181, and 366 (accelerated schedule) and day 1, 36, 57, 181, and 366 (conventional schedule)
measure: Number of Subjects Who Reported Solicited Local Adverse Events After Each Rabies Vaccination
timeFrame: Day 1 through day 7 after each vaccination (on day 1, 4, 8 and 29)
measure: Number of Subjects Who Reported Solicited Local AEs After Each JE Vaccination
timeFrame: Day 1 through day 7 after each vaccination (on day 1, 8 and 29)
measure: Number of Subjects Who Reported Solicited Local AEs After Each Placebo Injection
timeFrame: Day 1 through day 7 after each injection (day 1, 4, 8 and 29)
measure: Number of Subjects Who Reported Solicited Systemic AEs and Other Indicators of Reactogenicity After Each Vaccination
timeFrame: Day 1 through day 7 after each vaccination (day 1, 4, 8 and 29)
measure: Numbers of Subjects Reporting Unsolicited AEs After Any Vaccination From Day 1 Through Day 57
timeFrame: Day 1 through Day 57
Other outcomes:
Locations:
city: Kinderspitalgasse 15
country: Austria
facility: Institute of Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectious Diseases and Immunology Medical University of Vienna
state: Vienna
city: Bernhard-Nocht-Strasse 74
country: Germany
facility: Bernhard Nocht Institute for Tropical Medicine
state: Hamburg
city: Rämistrasse 71
country: Switzerland
facility: The University of Zurich
state: Zürich
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines and Diagnostics
role: STUDY_CHAIR
References:
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.
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.