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

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ClinicalTrials.gov Identifier: NCT01662440
Recruitment Status : Completed
First Posted : August 10, 2012
Results First Posted : December 8, 2014
Last Update Posted : December 8, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Tracking Information
First Submitted Date  ICMJE August 2, 2012
First Posted Date  ICMJE August 10, 2012
Results First Submitted Date  ICMJE October 6, 2014
Results First Posted Date  ICMJE December 8, 2014
Last Update Posted Date December 8, 2014
Study Start Date  ICMJE August 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2014)
  • Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 7 Days After Last Active Vaccination [ Time Frame: Day 7 after last active vaccination (day 15 - group that received accelerated schedule, day 36 - group that received conventional schedule) ]
    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 [ Time Frame: Day 28 after last active vaccination (day 36 - group that received accelerated schedule, day 57 - group that received conventional schedule) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2012)
  • 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 ]
    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 ]
    Percentage of subjects with Plaque Reduction Neutralization Test (PRNT50) titer ≥ 1:10
Change History Complete list of historical versions of study NCT01662440 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2014)
  • RVNA Geometric Mean Concentrations (GMCs) At 28 Days After Last Active Vaccination [ Time Frame: Day 57 (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 [ Time Frame: Day 57 (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 [ Time Frame: Day 36 and day 57 (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 [ Time Frame: Day 15 and day 36 (28 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 [ Time Frame: Day 1, 8, 15, 36, 57, 91, 181 and Day 366 ]
    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 [ Time Frame: Day 1, 8, 15, 36, 57, 91, 181, and 366 ]
    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 [ Time Frame: Days 1, 15, 22, 36, 57, 91, 181 and 366 ]
    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 [ Time Frame: Day 1, 15, 22, 36, 57, 91, 181, and 366 (accelerated schedule) and day 1, 36, 57, 181, and 366 (conventional schedule) ]
    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 [ Time Frame: Day 1 through day 7 after each vaccination (on day 1, 4, 8 and 29) ]
    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 [ Time Frame: Day 1 through day 7 after each vaccination (on day 1, 8 and 29) ]
    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 [ Time Frame: Day 1 through day 7 after each injection (day 1, 4, 8 and 29) ]
    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 [ Time Frame: Day 1 through day 7 after each vaccination (day 1, 4, 8 and 29) ]
    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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2012)
  • Rabies Virus Neutralizing Antibody Geometric Mean Titer [ Time Frame: 28 days after last active vaccination ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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. ]
  • 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). ]
  • 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). ]
  • Number of subjects with all vaccine related SAEs [ Time Frame: Day 57 (post completion of clinic visit) through Day 366 (or study termination). ]
  • Number of subjects with all concomitant medications [ Time Frame: Day 1 through Day 57 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of 2 Different Vaccination Schedules of Rabies and Japanese Encephalitis Vaccines in Healthy Adult Subjects
Official Title  ICMJE 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.
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Rabies
  • Japanese Encephalitis
Intervention  ICMJE
  • Biological: Rabies
    Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).
  • Biological: 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.
Study Arms  ICMJE
  • Active Comparator: R/JE - Conv
    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.
    Interventions:
    • Biological: Rabies
    • Biological: Japanese Encephalitis
    • Other: Placebo
  • Experimental: R/JE - Acc
    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.
    Interventions:
    • Biological: Rabies
    • Biological: Japanese Encephalitis
    • Other: Placebo
  • Active Comparator: R - Conv
    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.
    Interventions:
    • Biological: Rabies
    • Other: Placebo
  • Active Comparator: JE - Conv
    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.
    Interventions:
    • Biological: Japanese Encephalitis
    • Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 2, 2014)
661
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2012)
660
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Germany,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01662440
Other Study ID Numbers  ICMJE V49_23
2011-005173-23 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Vaccines )
Study Sponsor  ICMJE Novartis Vaccines
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Novartis Vaccines and Diagnostics Novartis Vaccines
PRS Account Novartis
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP