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

2 décembre 2014 mis à jour par: Novartis Vaccines

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.

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

661

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 65 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: 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.
Biologique: Rabies
Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).
Biologique: Japanese Encephalitis
Subjects received two doses of Japanese Encephalitis vaccine.
Autre: Placebo
Subjects received either two, three, four or five doses of normal saline, 0.9% w/v sodium chloride depending on the vaccine group.
Expérimental: 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.
Biologique: Rabies
Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).
Biologique: Japanese Encephalitis
Subjects received two doses of Japanese Encephalitis vaccine.
Autre: Placebo
Subjects received either two, three, four or five doses of normal saline, 0.9% w/v sodium chloride depending on the vaccine group.
Comparateur actif: 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.
Biologique: Rabies
Subjects received three doses of Rabies, whole virus vaccine (inactivated, Germany).
Autre: Placebo
Subjects received either two, three, four or five doses of normal saline, 0.9% w/v sodium chloride depending on the vaccine group.
Comparateur actif: 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.
Biologique: Japanese Encephalitis
Subjects received two doses of Japanese Encephalitis vaccine.
Autre: Placebo
Subjects received either two, three, four or five doses of normal saline, 0.9% w/v sodium chloride depending on the vaccine group.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentages of Subjects With RVNA Concentrations ≥0.5 IU/mL At 7 Days After Last Active Vaccination
Délai: 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.
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
Délai: 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.
Day 28 after last active vaccination (day 36 - group that received accelerated schedule, day 57 - group that received conventional schedule)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
RVNA Geometric Mean Concentrations (GMCs) At 28 Days After Last Active Vaccination
Délai: 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.
Day 57 (28 days after last active vaccination)
PRNT50 Geometric Mean Titers (GMTs) At 28 Days After Last Active Vaccination
Délai: 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.
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
Délai: 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.
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
Délai: 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.
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
Délai: 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.
Day 1, 8, 15, 36, 57, 91, 181 and Day 366
Kinetics of Rabies Immune Response Measured as the RVNA GMCs
Délai: 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.
Day 1, 8, 15, 36, 57, 91, 181, and 366
Kinetics of JE Immune Response Measured as Percentage of Subjects With PRNT50 Titers ≥1:10
Délai: 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).
Days 1, 15, 22, 36, 57, 91, 181 and 366
Kinetics of JE Immune Response Measured as PRNT50 GMTs
Délai: 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).
Day 1, 15, 22, 36, 57, 91, 181, and 366 (accelerated schedule) and day 1, 36, 57, 181, and 366 (conventional schedule)
Number of Subjects Who Reported Solicited Local Adverse Events After Each Rabies Vaccination
Délai: 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).
Day 1 through day 7 after each vaccination (on day 1, 4, 8 and 29)
Number of Subjects Who Reported Solicited Local AEs After Each JE Vaccination
Délai: 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).
Day 1 through day 7 after each vaccination (on day 1, 8 and 29)
Number of Subjects Who Reported Solicited Local AEs After Each Placebo Injection
Délai: 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).
Day 1 through day 7 after each injection (day 1, 4, 8 and 29)
Number of Subjects Who Reported Solicited Systemic AEs and Other Indicators of Reactogenicity After Each Vaccination
Délai: 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.
Day 1 through day 7 after each vaccination (day 1, 4, 8 and 29)
Numbers of Subjects Reporting Unsolicited AEs After Any Vaccination From Day 1 Through Day 57
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis Vaccines

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 août 2012

Achèvement primaire (Réel)

1 décembre 2012

Achèvement de l'étude (Réel)

1 octobre 2013

Dates d'inscription aux études

Première soumission

2 août 2012

Première soumission répondant aux critères de contrôle qualité

7 août 2012

Première publication (Estimation)

10 août 2012

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

8 décembre 2014

Dernière mise à jour soumise répondant aux critères de contrôle qualité

2 décembre 2014

Dernière vérification

1 décembre 2014

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • V49_23
  • 2011-005173-23 (Numéro EudraCT)

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