A Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of MVA-BN Yellow Fever Vaccine With and Without Montanide ISA-720 Adjuvant in 18-45 Year Old Healthy Volunteers
Condition: Yellow Fever; Yellow Fever Immunisation
MeSH terms: Yellow Fever; Fever; Hyperthermia
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the
      safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian
      Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female
      adult subjects. There are six dose groups in this study. Subjects who have never received a
      licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine
      administration and follow-up will be conducted in a double-blinded fashion. Subjects who have
      previously received two, 1 x 10^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic
      (MVA-BN) between 19 and 45 days apart by s ubcutaneous (SC) or intramuscular (IM) routes will
      be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I
      study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at
      each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or
      without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as
      to whether ISA 720 was administered. The primary objectives are the: 1) assessment of the
      safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without
      ISA 720; 2) comparison of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine
      administered with or without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN.
    

Detailed description: 
      This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the
      safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian
      Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female
      adult subjects. There are six dose groups in this study. Subjects who have never received a
      licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine
      administration and follow-up will be conducted in a double-blinded fashion. Subjects who have
      previously received two, 1 x 10^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic
      (MVA-BN) between 19 and 45 days apart by subcutaneous (SC) or intramuscular (IM) routes will
      be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I
      study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at
      each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or
      without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as
      to whether ISA 720 was administered. Subjects will be monitored for safety for one day, and
      if no pre-defined halting rule is met then two additional subjects (2nd sentinel group) one
      at each clinical site will be assigned to the group the previous subject was not assigned to.
      These subjects will be vaccinated and monitored as above. A total of 4 sentinel subjects will
      be vaccinated. The primary objectives are the: 1) assessment of the safety, tolerability, and
      reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720; 2) comparison of
      the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or
      without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN. The secondary objectives are
      the: 1) assessment of the immunogenicity against the MVA-BN backbone and Yellow Fever Virus
      (YF) antigen insert of MVA-BN-YF with and without ISA 720 as assessed by kinetics of the
      immune responses, seroconversion rates, and peak Geometric Mean Titer (GMT); 2) assessment of
      the impact of previous MVA-BN vaccination on peak immune responses to YF antigen in
      MVA-BN-YF; 3) comparison of the peak immunogenicity against YF antigen of 1 or 2 doses of
      MVA-BN-YF with or without ISA 720 with YF-VAX; 4) comparison of the peak immunogenicity
      against the MVA-BN backbone of 1 or 2 doses of MVA-BN-YF with or without ISA 720 with MVA-BN;
      5) assessment of durability of immune response to YF antigen and MVA-BN at 6 months after 2nd
      vaccination or placebo administration.
    

Intervention name(s): ISA-720; MVA Smallpox Vaccine; MVA-BN Yellow Fever Vaccine; Placebo; Placebo; YF Vax 17D Strain
Intervention type(s): Drug; Biological; Biological; Other; Other; Biological
Intervention description(s): The vaccine adjuvant ISA 720 will be used with Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) as vaccine adjuvant with a depot effect. This comprises slow release of antigen at the injection site, protection of antigen against degradation and strong stimulation of the immune response.; Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine (MVA BN(R)) is a purified live vaccine will be used as an active comparator.; Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.; 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.; 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.; Yellow Fever Vaccine (YF-VAX) is a vaccine prepared by culturing the 17D-204 strain of yellow fever virus in living avian leucosis virus-free (ALV-free) chicken embryos. Will be used as an active comparator.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Fever; Immunogenicity; MVA-BN; Reactogenicity; Vaccine; Yellow