ACAM 3000 MVA at Harvard Medical School
Condition: Smallpox
MeSH terms: Smallpox
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to assess the safety of an experimental smallpox vaccine (MVA:
      Modified Vaccinia Ankara) and to compare the body's immune (system that fights disease)
      response to this vaccine. Participants will be assigned to 1 of 6 study groups. Each group
      will include 12 subjects, 10 will receive the modified smallpox vaccine and two will receive
      placebo, an inactive substance. The vaccine will be administered in 1 of 3 ways: under the
      skin; in the muscle; or between the muscle and the skin. Groups A and B will receive Dryvax®
      6-15 months after the initial MVA vaccine; groups C, D, E, and F will receive Dryvax® 6
      months after the initial MVA vaccine. Study procedures will include documenting side effects
      for 14 days after each vaccination, electrocardiogram (picture of the hearts activity) and
      blood samples. Participants will be involved in study related procedures for up to 18 months.
    

Detailed description: 
      The emergence of smallpox as a potential agent of bioterrorism has heightened concern about
      the vulnerability of the population to infection with this agent, and has led to proposals to
      undertake large scale smallpox immunization of military personnel and "first responders" in
      the United States, including certain health care workers. A particularly promising vaccine
      approach to the development of an effective, yet less reactogenic vaccine to smallpox is the
      use of Modified Vaccinia Ankara (MVA) as a vaccine. Despite the established efficacy of
      smallpox vaccination, the parameters of protective immunity against smallpox infection are
      incompletely understood. This is a phase I/II trial to be conducted under a placebo
      controlled double-blind, randomized allocation of study product. The purpose of this study is
      to assess the safety and immunogenicity of ACAM 3000 MVA in healthy vaccinia-naïve adult
      subjects. Participants will include 72 healthy, male or female, from the Boston metropolitan
      area. Six dose regimens will be studied initially: 10^6 or 10^7 tissue culture infectious
      dose 50 (TCID50) administered intradermally and 10^7 or 10^8 TCID50 administered
      intramuscularly or subcutaneously as 2 immunizations 1 month apart. Each arm will be
      comprised of 12 subjects, 10 of whom will receive ACAM3000 MVA and 2 of whom will receive
      placebo. A subsequent vaccinia vaccination will be offered to all patients. Consenting
      participants in Groups A and B will receive the vaccinia (Dryvax®) inoculation between 6 and
      15 months after the initial MVA / placebo vaccination. Consenting participants in groups C,
      D, E and F will receive the Dryvax® inoculation approximately 6 months after the initial MVA
      / placebo vaccination, coinciding with planned visit 13. Assessment of safety will be carried
      out by observation and measurement of acute clinical and laboratory evidence of reactions or
      toxicity; including clinical, electrocardiographic or laboratory evidence of myopericarditis.
      Assessment of immunogenicity will be carried out by the measurement of humoral and
      cell-mediated immune response to ACAM 3000 MVA and vaccinia, performed on blood samples
      obtained at various times prior to and after immunization over the one year period of the
      study. Response to vaccinia will be assessed clinically (effect on a "take") and the results
      will be correlated with immune responses to MVA. Subjects will be followed for
      reactogenicity. Clinical assessments and blood samples will be obtained sequentially for
      immunogenicity determinations.
    

Intervention name(s): MVA Smallpox Vaccine; MVA Smallpox Vaccine; Placebo; Placebo; MVA Smallpox Vaccine; Live vaccinia virus vaccine; Placebo
Intervention type(s): Biological; Biological; Other; Other; Biological; Biological; Other
Intervention description(s): MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10^7 or 10^8 TCID50 intramuscularly (IM).; MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10^7 or 10^8 TCID50 subcutaneously (SC).; Sterile saline (0.9%) volume of 0.5 ml intradermally in the deltoid.; Sterile saline (0.9%) volume of 0.5 ml subcutaneously in the deltoid.; MVA smallpox vaccine (ACAM3000 MVA) administered in two doses approximately 28 days apart in the following dose/route combination: 10^6 or 10^7 TCID50 intradermally (ID).; Dryvax® smallpox vaccine administered at approximately day 180, dosage 10^8 pfu/ml.; Sterile saline (0.9%) volume of 0.5 ml intramuscularly in the deltoid.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: MVA, smallpox, Acambis