MVA Post-Event: Administration Timing and Boost Study
Condition: Smallpox
MeSH terms: Smallpox
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to evaluate an investigational smallpox vaccine, called
      IMVAMUNE®, with respect to safety and immune (body's defense system) response. Participants
      will include healthy adults, age 18 or older born after 1971, who have not had smallpox
      vaccine before. Volunteers were originally assigned to 1 of 5 groups. In July 2007, a hold
      was placed on the Dryvax® groups and the study was modified. Volunteers, numbering 197, will
      be assigned by chance to one of 3 groups to be vaccinated twice with IMVAMUNE® vaccine or
      placebo (inactive substance) in Groups A and B, or to receive a single vaccination with
      IMVAMUNE® or placebo in Group F. Volunteers will complete a memory aid (diary) for 15 days
      following vaccination. Blood samples will be collected. Volunteers may participate for up to
      425 days.
    

Detailed description: 
      The study will evaluate the IMVAMUNE® smallpox vaccine with respect to safety and
      optimization of immune responses by different vaccination regimens in vaccinia-naïve adults.
      Study subjects must be age 18 and older and born after 1971. Originally, 215 subjects were
      planned to be randomly assigned to 1 of 5 groups to be immunized twice with IMVAMUNE® vaccine
      or placebo subcutaneously in Groups A and B, or Dryvax® or placebo by scarification in Group
      C or both IMVAMUNE® and Dryvax® or 2 placebos in Groups D and Group E. In July, 2007,
      enrollment was halted at the request of Center for Biologics Evaluation and Research (CBER).
      At that time, enrollment included zero subjects in Group A, 2 subjects in Group B, 8 subjects
      in Group C, 6 subjects in Group D, and 4 subjects in Group E. CBER placed an official hold on
      the enrollment into the Groups that would administer Dryvax®, i.e., Groups C, D and E.
      Subjects previously enrolled into Groups C, D, and E will be followed according to the
      protocol. The protocol has been modified as follows. One hundred and ninety-five subjects
      will be randomly assigned to 1 of 3 groups to be immunized twice with IMVAMUNE® vaccine or
      placebo subcutaneously in Groups A and B, or to receive a single immunization with IMVAMUNE®
      or placebo subcutaneously in Group F. (NOTE: A total of 197 subjects will be randomly
      assigned to Groups A, B, and F as 2 subjects were previously enrolled in Group B.) Group A
      will receive IMVAMUNE® vaccine or placebo on Days 0 and 7. Group B will receive IMVAMUNE®
      vaccine or placebo on Days 0 and 28. Group F will receive a single dose of IMVAMUNE® at Day
      0. All subjects will complete a memory aid for 15 days following each vaccination. Groups C,
      D, and E will have the appropriate reactogenicity information collected until the vaccination
      lesion, if present is well dried. Adverse events will be collected for 28 days after each
      vaccination. Specimens will be collected for immunologic assays at the noted clinic visits,
      as well as 1 year post last vaccination. Serious adverse events will be collected throughout
      the study period. The primary safety objective is to evaluate the safety of IMVAMUNE® given
      as a single dose, IMVAMUNE® given in a 2 dose prime-boost regimen at Day 0 and 7 or Day 0 and
      28, IMVAMUNE® followed by a boost with Dryvax®, and IMVAMUNE® given simultaneously with
      Dryvax®. The primary immunogenicity objective is to determine if the Geometric Mean Titer
      (GMT) of neutralizing antibody [using Modified Vaccinia Ankara (MVA) as the target antigen]
      among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10^8, Days 0 and 7, Group A) is
      non-inferior to that among subjects receiving 2 doses of IMVAMUNE® (1×10^8, Days 0 and 28,
      Group B) at Day 14 following the 2nd dose. The secondary immunogenicity objective is to
      determine if the GMT, as assessed by enzyme linked immunosorbent assay (ELISA) (using MVA as
      the target antigen), among subjects receiving a regimen of 2 doses of IMVAMUNE® (1×10^8, Days
      0 and 7, Group A) is non-inferior to that among subjects receiving 2 doses of IMVAMUNE®
      (1×10^8, Days 0 and 28, Group B) at Day 14 following the 2nd dose. The tertiary
      immunogenicity objective is to characterize the kinetics, magnitude, and duration of cellular
      and humoral immune responses to IMVAMUNE® alone or IMVAMUNE® as a prime followed by a boost
      with IMVAMUNE® or Dryvax®, or Dryvax® alone.
    

Intervention name(s): Placebo (subcutaneous); Placebo (scarification); Dryvax®; IMVAMUNE®
Intervention type(s): Drug; Drug; Biological; Biological
Intervention description(s): 0.9 percent (weight/volume) sodium chloride injection, United States Pharmacopeia [Sterile Saline Placebo (SSP)].; Physiologic normal saline for injection.; Dryvax® Vaccinia Vaccine (~10^5 [plaque forming units (pfu)/dose] given via scarification, titer 10^8 pfu per mL after reconstitution).; IMVAMUNE® Vaccinia Vaccine delivered by subcutaneous (SC) route at titer 1X10^8 Tissue Culture Infections Dose50 per 0.5 mL dose.
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: smallpox, vaccine, IMVAMUNE®