CDC Anthrax Vaccine Clinical Trial
Condition: Healthy
MeSH terms: Anthrax
Study type: Interventional
Phase: Phase 4

Summary: 
      Anthrax Clinical Trial Objectives:

      To assess whether:

        -  Anthrax vaccine (AVA or BioThrax, BioPort Corp. Lansing MI) administered by the
           intramuscular (IM) route elicits antibody responses that are not inferior (i.e.,
           "non-inferior") to that achieved by the currently licensed schedule.

        -  BioThrax administered by the IM route and containing fewer numbers of doses elicits
           antibody responses that are not inferior (i.e., "non-inferior") to that achieved by the
           currently licensed schedule.

        -  Differences in reactogenicity exist between the IM and subcutaneous (SQ) administration
           of BioThrax.

      Additionally for the final report we will assess whether:

        -  Occurrence of adverse events following AVA administration is influenced by selected risk
           factors.
    

Detailed description: 
      This study is a 43-month prospective, randomized, double-blind, placebo-controlled comparison
      of immunogenicity and reactogenicity elicited by BioThrax given by different routes of
      administration (SQ versus IM) and dosing regimens (as many as 8 doses versus as few as 4
      doses). Sterile saline is used as the placebo where doses are dropped in regimens using AVA,
      and in the all-placebo study group.

      This study is conducted among a total of 1564 healthy adult men and women (18 to 61 years of
      age) at five sites in the United States. Participants were randomized into one of 6 study
      groups with 260 participants per group. One group receives BioThrax given as currently
      licensed (SQ with 6 doses followed by annual boosters); another group is given placebo IM
      (130 participants) or SQ (130 participants) in the currently licensed dosing regimen. The
      four other groups receive BioThrax IM in modified dosing regimens; placebo is given when a
      dose of BioThrax is omitted from the licensed dosing regimen. There are a total of 25
      required visits for this study, during which all participants receive an injection of vaccine
      or placebo (8 injections total), have a blood sample drawn (16 or 17 total), and have an
      in-clinic examination for adverse events (22 total).

      Immunogenicity is assessed by assaying 16 serial blood samples obtained from all participants
      and a 17th sample from a subset of participants before vaccination and at other specified
      times. Total anti-protective antigen IgG antibody (anti-PA IgG) is quantified using a
      standardized and validated enzyme-linked immunosorbent assay (ELISA); the primary study
      endpoints are 4-fold rise in antibody titer and antibody concentration relative to the
      pre-vaccination titers or assay reactivity threshold. A subset of serum samples is also
      assayed in an in vitro toxin neutralization assay (TNA) to measure the functional activity of
      anti-BioThrax antibodies. The kinetics of the immune response to BioThrax are examined at 3
      time points in the study and blood samples from a subset of participants will be further
      tested in correlates of protection and immunogenetics substudies. All adverse events (AEs),
      including vaccine reactogenicity, are actively monitored. While all AEs will be ascertained
      among study participants, several endpoints will be defined based on the likelihood of their
      occurrence and/or their clinical importance. Of primary interest is the occurrence of local
      AEs such as warmth, tenderness, itching, pain, arm motion limitation, erythema, induration,
      nodule, and bruise. Systemic AEs such as fever, fatigue, muscle ache, headache, temperature,
      and painful axillary adenopathy are also evaluated.

      This study is expected to provide the basis for consideration of change in route of BioThrax
      administration from SQ to IM and reduction in number of vaccine doses required for primary
      and booster immunization.

      There is an interim analysis of data collected through each participant's first 7 months of
      this study for consideration in changing the route of BioThrax administration from SQ to IM,
      and elimination of the 2 week vaccine priming dose.

      At the end of the study, the Sponsor will present the entire results of the trial to FDA for
      consideration in elimination of additional doses from the licensed BioThrax schedule. At that
      time, the Sponsor will also supplement these data with results from parallel non-human
      primate challenge studies and additional research on immunologic correlates of protection.
    

Intervention name(s): BioThrax or Anthrax Vaccine Adsorbed
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Anthrax; Vaccine; Immunogenicity; Reactogenicity