High Dose IMVAMUNE® in Vaccinia-Naive Individuals
Condition: Variola Major (Smallpox)
MeSH terms: Vaccinia; Smallpox
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this research is to compare the ability of a new investigational smallpox
      vaccine called IMVAMUNE® to produce a strong immune response against smallpox disease if
      given as one single, higher dose compared with two lower doses given one month apart. Another
      purpose of the study is to see how quickly someone might be protected against smallpox.
      Volunteers will be vaccinia-naïve adults age 18 and older (born after 1971) divided into 2
      groups. Volunteers in Group A will receive a high dose of vaccine given in 2 shots on day 0
      followed by a placebo (inactive substance) shot on day 28. Group B will receive the standard
      dose of vaccine and placebo given in 2 shots on day 0 followed by a standard dose shot on Day
      28. Study participation will include 10 planned study visits over approximately 7 months.
    

Detailed description: 
      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. As a consequence, there is an urgent need for a safe
      and efficacious vaccine to protect the public against smallpox. To date, the majority of
      clinical studies with Modified Vaccinia Ankara (MVA) have studied a prime-boost vaccination
      regimen, with a dose of up to 1×10^8 tissue culture infectious dose 50 (TCID50) of MVA
      administered on Days 0 and 28. While this vaccination regimen induces a robust immune
      response that is protective in a variety of animal models and is appropriate for a
      pre-smallpox release scenario, in the event of a confirmed release of smallpox, a more rapid
      vaccination regimen that provides a protective immune response would be desirable. Ideally,
      at least short-term protection could be obtained with a single dose of vaccine. While a
      single dose of MVA at 1×10^8 TCID50, does induce an immune response in the majority of
      recipients, it is possible that a higher dose of MVA could provide a more rapid and/or
      stronger immune response relative to a single, standard 1×10^8 TCID50 dose of MVA. The goal
      of this study is to examine the kinetics and magnitude of the immune response of a single
      high dose of MVA (5×10^8 TCID50) relative to both a single and prime/boost regimen using the
      standard doses (1×10^8 TCID50) of MVA. This study will complement a current, ongoing study,
      DMID Protocol 06-0012, which is examining the immune response to compressed prime/boost
      dosing regimens of MVA administered at (1×10^8 TCID50). Upon the completion of these studies,
      clinical data will be generated which will inform policy makers about different options for
      post-event utilization of available smallpox vaccines. The study is designed as a randomized,
      non-placebo controlled, double blinded study containing two arms: Group A (N=45) will receive
      a single high dose of IMVAMUNE® (5x10^8 TCID50, consisting of two 0.5 mL injections) vaccine
      on Day 0 and a single saline placebo dose (single 0.5 mL injection) on Day 28 to match the
      two dose regimen of Group B. Group B (N=45) will receive a standard two dose regimen of
      IMVAMUNE® (1x10^8 TCID50) vaccine on Day 0 (consisting of 0.5 mL injection of vaccine and 0.5
      mL injection of saline placebo) and Day 28 (single 0.5 mL injection of vaccine). Safety will
      be measured by assessment of adverse events for 28 days following the last vaccination (56
      days following the initial vaccination for those subjects that fail to receive the second
      dose) and for serious adverse events at six months post the final vaccination, and
      reactogenicity to the vaccines for 15 days following each vaccination. Immunogenicity testing
      will include antibody testing [enzyme linked immunosorbent assay (ELISA) and plaque reduction
      neutralizing antibody titers (PRNT)] and cellular immune responses [(INF-gamma enzyme linked
      immunospot (ELISPOT)] following each vaccination and at six months post the final
      vaccination. In addition, ELISA responses, using MVA VR-1508 as the target antigen and PRNT
      using vaccinia WR (Western Reserve) as the target antigen will be explored. Participants will
      include 90 healthy, vaccinia-naïve adults, aged 18 and older (born after 1971). Study
      duration will be approximately 13 months (7 months/subject).
    

Intervention name(s): IMVAMUNE® High Dose; Placebo; IMVAMUNE® Standard Dose
Intervention type(s): Biological; Drug; Biological
Intervention description(s): IMVAMUNE® Vaccinia Vaccine, undiluted, delivered by subcutaneous route on Day 0 at high dose 5×10^8 TCID50 (5×10^8 TCID50 per 1.0 mL dose - administered as 2 x 0.5 mL.; 0.5 mL injection of saline placebo administered with vaccine on Day 0 (Group B) or single saline placebo dose (single 0.5 mL injection) on Day 28 (Group A).; IMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route on Day 0 and 28 at standard dose (diluted with saline by study pharmacist to (1×10^8 tissue culture infectious dose 50 [TCID50] per 0.5 mL dose)
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: smallpox, vaccine, IMVAMUNE®