Lyophilized IMVAMUNE® (1x10^8 TCID50) Versus Liquid IMVAMUNE® (1x10^8 TCID50) Administered Subcutaneously and a Lower Dose Liquid IMVAMUNE® (2x10^7 TCID50) Administered Intradermally
Condition: Smallpox
MeSH terms: Smallpox
Study type: Interventional
Phase: Phase 2

Summary: 
      Due to recent concern of biowarfare and bioterrorism, the US government is making efforts to
      improve its ability to protect citizens against the smallpox virus. This study will evaluate
      safety of IMVAMUNE®, an investigational smallpox vaccine, and its ability to stimulate the
      immune system (the body's defense system). Two vaccine preparations have the same name but
      one is a liquid and one is a powder that has liquid added just before it is given. The
      vaccine that comes as a liquid will be injected (given as a shot) just under the skin
      (subcutaneously) or injected between the layers of the skin (intradermally). The powder
      formulation is only injected just under the skin. Approximately 495 adults, age 18 older born
      after 1971, which have not had smallpox vaccine before, may participate in the study for
      about 7 months.
    

Detailed description: 
      Smallpox was declared officially eradicated by the World Health Assembly in 1980. Despite the
      fact that the World Health Organization (WHO) officially declared smallpox to be eradicated,
      a new threat exists due to the potential use of variola virus as an agent for biological
      warfare and/or bio-terrorism. Following the events of September 11, 2001 the Division of
      Microbiology and Infectious Diseases/National Institute of Allergy and Infectious Diseases
      contracted for the advanced development of IMVAMUNE®. Initially, a lyophilized formulation
      was manufactured, which was reconstituted 'at the bedside' prior to administration in
      clinical and non-clinical settings. Due in part to the potential requirement for mass
      vaccinations coupled with the increased manufacturing time and other constrains associated
      with lyophilization, it was decided to transition to a liquid product formulation. Therefore,
      after 2005, clinical and non-clinical efforts have focused largely on the liquid formulation,
      though non-clinical studies with the lyophilized formulation continued. Presently, due to the
      potential need to be able to stockpile Modified Vaccinia Ankara (MVA) for an extended period
      of time, there is renewed interest in the lyophilized formulation. The purpose of this study
      is to compare the safety and immunogenicity of lyophilized IMVAMUNE® [1x10^8 tissue culture
      infectious dose 50 (TCID50)] versus liquid formulation IMVAMUNE® (1x10^8 TCID50) administered
      by the subcutaneous (SC) route and a lower dose liquid formulation IMVAMUNE® (2x10^7 TCID50)
      administered by the intradermal (ID) route in healthy vaccinia-naïve individuals. This study
      is designed as a randomized, non-placebo controlled, partially-blinded study (liquid versus
      lyophilized formulation by the SC route Group B versus A). The study staff is unblinded to
      Group C. The study will contain 3 arms: Group A [Number (N)=165] will receive a 2 dose
      regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) lyophilized formulation by the SC route
      on Day 0 and 28. Group B (N=165) will receive a 2 dose regimen of IMVAMUNE® (1x10^8
      TCID50/0.5 mL per dose) liquid formulation by the SC route on Day 0 and 28. Group C (N=165)
      will receive a 2 dose regimen of IMVAMUNE® (2x10^7 TCID50/0.1 mL per dose) liquid formulation
      by the ID route on Day 0 and 28. Safety will be measured by assessment of solicited local and
      systemic reactions within 15 days after each vaccination (Day 0-14), unsolicited adverse
      events for 28 days following the second vaccination (56 days following the initial
      vaccination for those subjects that fail to receive the second vaccination), and serious
      adverse events through six months post the final vaccination. Immunogenicity testing will
      include assessment of vaccinia-specific plaque reduction neutralizing antibody titers (PRNT)
      and enzyme linked immunosorbent assay (ELISA) mean geometric titers (GMT) based on individual
      peak titers. For each subject, the peak PRNT or ELISA will be defined as the largest titer
      among all available measurements post second vaccination.
    

Intervention name(s): MVA Smallpox Vaccine; MVA Smallpox Vaccine; MVA Smallpox Vaccine
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Vaccinia vaccine liquid formulation delivered by subcutaneous (SC) route at 1x10^8 TCID50 per 0.5 mL dose on Days 0 and 28.; Vaccinia vaccine liquid formulation delivered at lower dose [2x10^7 tissue culture infectious dose 50 (TCID50) per 0.1 mL dose] by intradermal (ID) route on Days 0 and 28.; Vaccinia vaccine lyophilized formulation delivered by subcutaneous (SC) route at 1x10^8 TCID50 per 0.5 mL dose on Days 0 and 28.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: IMVAMUNE®, smallpox, vaccine