Clinical Trial: Phase II Study to Evaluate Safety and Immunogenicity of a Chikungunya Vaccine

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Double Blinded, Randomized, Priorix®- and Placebo-controlled, Trial to Evaluate the Optimal Dose of MV-CHIK Vaccine (Against Chikungunya Virus) in Regard to Immunogen

Brief Summary: The purpose of this study is to evaluate the immunogenicity and safety of a novel vaccine against Chikungunya virus after one or two vaccinations by comparison of two different dose levels.

Detailed Summary:

This is a double blinded, block-randomized, active- and placebo controlled, phase II trial, comparing two dose levels by assessing immunogenicity, safety and tolerability of MV-CHIK (a novel vaccine against Chikungunya virus).

Healthy male and female subjects aged 18-55 years will be randomized to one of six treatment groups (A, B, C. D, M1 or M2) differing in dosage and scheduling of vaccinations. Group A-D will be split in one arm receiving MV-CHIK and one control-arm receiving Priorix®.

All subjects of group A. B, C and D will receive three i.m. injections on study day 0, 28 and 196. Subjects of group A and B will receive MV-CHIK low dose or control-vaccine Priorix® (or equivalent measles vaccine) and subjects of group C and D will be treated with MV-CHIK high dose or control-vaccine (Priorix® or equivalent measles vaccine).

All subjects of group A, B, C and D additionally will be randomized to one of two treatment sequences: group A and C will receive MV-CHIK or control-vaccine Priorix® on study day 0 and 28, followed by placebo on day 196, and group B and D receive placebo on day 0 and MV-CHIK or Priorix® on day 28, followed by an additional vaccination of the same product on day196 (boosting vaccination).

All subjects of the measles booster group M1 and M2 will receive five i.m. injections on study day -28, 0, 28, 168 and 196. The first vaccination will be Priorix® (or equivalent measles vaccine) on study day -28. Group M1 will receive MV-CHIK low dose vaccinations on day 0 and day 28 and placebo on day 168 and 196. Group M2 will receive placebo on day 0 and 28 and MV-CHIK low dose on day 168 and on day 196.

All subjects will be followed fo
Sponsor: Themis Bioscience GmbH

Current Primary Outcome: Immunogenicity on day 56 confirmed by plaque reduction neutralization test (PRNT50) [ Time Frame: Study day 56 (e.g. 28 days after one or two vaccinations depending on treatment group). ]

Evaluation of immunogenicity 28 days after primary immunization regime, comprising one or two vaccinations, as confirmed by the presence of functional anti-chikungunya antibodies, determined by the plaque reduction neutralization test (PRNT50)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Immunogenicity confirmed by the presence of functional anti-chikungunya antibodies, determined by the plaque reduction neutralization test (PRNT50) [ Time Frame: Baseline until study day 224 ]
    Evaluation of immunogenicity on day 0, 28, 196 and 224; additionally for group M1 and M2 on day -28 and 168 as confirmed by the presence of functional anti-chikungunya antibodies, determined by the plaque reduction neutralization test (PRNT50).
  • Measurement of anti-measles antibodies [ Time Frame: Baseline until study day 56 ]
    Determination of anti-measles antibodies on day 0, 28, and 56; additionally for group M1 and M2 on day -28 by enzyme linked immunosorbent assay (ELISA).
  • Solicited local and systemic adverse events [ Time Frame: Randomization until study day 224 ]
    Evaluation of solicited local and systemic adverse events recorded in the subjects' diaries.
  • Serious adverse events [ Time Frame: Randomization until study day 224 ]
    Evaluation of all serious adverse events (SAEs) occurred throughout the clinical study
  • Rate of adverse events during the 28 day post-vaccination period [ Time Frame: 28 days after each vaccination ]
    Rate of adverse events occuring 28 day after each vaccination
  • Number of subjects with clinically relevant, abnormal laboratory values [ Time Frame: Screening until study day 224 ]
    Safety laboratory parameters (including hematology, serum chemistry, urinalysis) will be investigated three times throughout the study
  • Shedding of live recombinant virus until day 196 [ Time Frame: Baseline until study day 196 ]
    Shedding will be observed in a subset of subjects at one Austrian site by qualitative determination of live recombinant virus in blood, urine and saliva by polymerase chain reaction (PCR).
  • Chikungunya virus specific T cell responses [ Time Frame: Baseline until study day 224 ]
    Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood to determine the number of functional, Chikungunya virus specific T cells on day 0, 28, 56, 196 and 224 (treatment group A-D) and additionally on day 168 for treatment group M1 and M2
  • Pre-existing anti-vector immunity [ Time Frame: Baseline until study day 224 ]
    Interference of recently boosted measles immunity with immunogenicity of Chikungunya vaccine (M1 + M2) and relation of post-vaccination plaque reduction neutralization (PRNT50) titers and baseline anti-measles enzyme linked immunosorbent assay (ELISA) titers.
  • Immunogenicity confirmed by the presence of functional anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA) [ Time Frame: Baseline until study day 224 ]
    Evaluation of immunogenicity on day 0, 28, 196 and 224; additionally for group M1 and M2 on day -28 and 168, confirmed by the presence of anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA).


Original Secondary Outcome:

  • Immunogenicity confirmed by the presence of functional anti-chikungunya antibodies, determined by the plaque reduction neutralization test (PRNT50) [ Time Frame: Baseline until study day 224 ]
    Evaluation of immunogenicity on day 0, 28, 196 and 224; additionally for group M1 and M2 on day -28 and 168 as confirmed by the presence of functional anti-chikungunya antibodies, determined by the plaque reduction neutralization test (PRNT50).
  • Measurement of anti-measles antibodies [ Time Frame: Baseline until study day 56 ]
    Determination of anti-measles antibodies on day 0, 28, and 56; additionally for group M1 and M2 on day -28 by enzyme linked immunosorbent assay (ELISA).
  • Solicited local and systemic adverse events [ Time Frame: Randomization until study day 224 ]
    Evaluation of solicited local and systemic adverse events recorded in the subjects' diaries.
  • Serious adverse events [ Time Frame: Randomization until study day 224 ]
    Evaluation of all serious adverse events (SAEs) occurred throughout the clinical study
  • Rate of adverse events during the 28 day post-vaccination period [ Time Frame: 28 days after each vaccination ]
    Rate of adverse events occuring 28 day after each vaccination
  • Number of subjects with clinically relevant, abnormal laboratory values [ Time Frame: Screening until study day 224 ]
    Safety laboratory parameters (including hematology, serum chemistry, urinalysis) will be investigated three times throughout the study
  • Shedding of live recombinant virus until day 196 [ Time Frame: Baseline until study day 196 ]
    Shedding will be observed in a subset of subjects at one Austrian site by qualitative determination of live recombinant virus in blood, urine and saliva by polymerase chain reaction (PCR).
  • Chikungunya virus specific T cell responses [ Time Frame: Baseline until study day 224 ]
    Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood to determine the number of functional, Chikungunya virus specific T cells on day 0, 28, 56, 196 and 224 (treatment group A-D) and additionally on day -28 and 168 for treatment group M1 and M2
  • Pre-existing anti-vector immunity [ Time Frame: Baseline until study day 224 ]
    Interference of recently boosted measles immunity with immunogenicity of Chikungunya vaccine (M1 + M2) and relation of post-vaccination plaque reduction neutralization (PRNT50) titers and baseline anti-measles enzyme linked immunosorbent assay (ELISA) titers.
  • Immunogenicity confirmed by the presence of functional anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA) [ Time Frame: Baseline until study day 224 ]
    Evaluation of immunogenicity on day 0, 28, 196 and 224; additionally for group M1 and M2 on day -28 and 168, confirmed by the presence of anti-chikungunya antibodies, determined by enzyme linked immunosorbent assay (ELISA).


Information By: Themis Bioscience GmbH

Dates:
Date Received: July 28, 2016
Date Started: August 2016
Date Completion: August 2017
Last Updated: December 21, 2016
Last Verified: December 2016