Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Study Assessing Safety, Tolerability, Immunogenicity of Three Dose Levels of ACAM3000 Modified Vaccinia Ankara Smallpox Vaccine in Adults With and Without Previous Smallpox Vaccination

This study will be a randomized, double-blind, placebo-controlled out-patient study conducted in multiple centers in the United States (US). Up to 700 healthy male and female adult subjects 18 to 55 years of age (inclusive), who have been previously vaccinated or subjects who are naïve to smallpox vaccine will be enrolled. Subjects will be randomized to 1 of 8 treatment groups with 100 (or 50 placebo) subjects per group in which they will receive either ACAM3000 MVA Smallpox Vaccine (1 of 3 dose levels) or placebo on Study Days 0 and 28. All personnel associated with the trial will be blinded as to treatment, with the exception of the study pharmacist who prepares the treatment for administration to each subject. There are 2 control groups in this study. A comparison of adverse events and other safety assessments between placebo and ACAM3000 MVA Smallpox Vaccine will be performed. In addition to serving as a control for safety, the previously vaccinated subjects receiving placebo will serve as a control for antibody and T-cell responses in persons with preexisting immunity who receive ACAM3000 MVA Smallpox Vaccine. Safety, tolerability, and immunogenicity data for 110 subjects undergoing primary immunization with graded doses of ACAM3000 MVA Smallpox Vaccine will be available following completion of Acambis protocol H-249-001, an ongoing phase I clinical trial. The doses levels in this study may be changed following the availability of results from protocol H-249-001. Statistical analysis will focus on comparisons among the dose levels of ACAM3000 MVA Smallpox Vaccine and comparisons of ACAM3000 MVA Smallpox Vaccine to placebo, as appropriate. A separate analysis will be performed for previously vaccinated and naïve subjects. Descriptive statistics will be used to compare demographic and baseline clinical data between stratum.