Monoclonal Antibody for Treatment of Inhalation Anthrax
Condition: Bacillus Anthracis (Anthrax)
MeSH terms: Anthrax
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the safety and pharmacokinetics (how long a drug
      stays in the bloodstream and how high the levels of the drug are at different times) of
      ETI-204 following intravenous (IV-into a vein) injections, and to evaluate the effects that
      ETI-204 may have on the pharmacokinetics of oral (by mouth) ciprofloxacin, an antibiotic
      approved by the U.S. Food and Drug Administration (FDA). ETI-204 is an experimental drug (not
      approved by the FDA) intended to protect against anthrax (a bacterial infection).
      Approximately 36 male and female healthy volunteers ages 18 to 50 will be in this study.
      Participation in this study may last up to eight weeks. Volunteers will have a single IV dose
      of the ETI-204 study drug or placebo (inactive substance, and some participants will also
      receive ciprofloxacin. They will stay in the Clinical Pharmacology Unit at least 36 hours
      after the dose.
    

Detailed description: 
      This initial study with ETI-204 will examine the safety and pharmacokinetics of ETI-204
      following IV administration both in the absence and presence of ciprofloxacin. The
      pharmacokinetics of ciprofloxacin in the presence of ETI-204 will also be determined. This
      study is a placebo-controlled, double-blind, randomized study which will be conducted at a
      single site. Healthy male and female volunteers will be recruited from the Columbus, OH area,
      and will have a maximum participation period of 7 months for each subject (from enrollment to
      end of follow-up period). The study population will roughly parallel the ethnicity of this
      geographic area. Because this is the first time that ETI-204 is studied in man, individuals
      under the age of 18 will not be permitted to participate in the study. Part 1 is a
      randomized, placebo-controlled, double-blind study being conducted at a single study site.
      Part 2 will be double-blind with respect to ETI-204 but not blinded for oral ciprofloxacin.
      Part 1 of the study is the dose escalation portion, in which the safety, tolerability, and
      pharmacokinetics of single IV doses of ETI-204 will be evaluated. Three dose levels are
      proposed for study: 18 mg, 54 mg, and 108 mg. At each dose level, 3 males and 3 females will
      be randomly assigned to active drug and 1 male and 1 female will be randomly assigned to
      placebo. Thus, at least 24 subjects will be studied in Part 1. Part 2 of the study will
      determine the safety, tolerability and pharmacokinetics of a single IV dose (108 mg dose from
      part 1, presuming no safety or tolerability issues), and whether or not there is an effect of
      ETI-204 on ciprofloxacin pharmacokinetics. There will be 2 groups of 6 subjects each. The
      first cohort will receive ETI-204 plus ciprofloxacin and the second will receive ETI-204
      placebo plus ciprofloxacin. Together with the comparable group from part 1, this will allow
      the determination of the effects of ciprofloxacin on ETI-204 pharmacokinetics and of ETI-204
      on ciprofloxacin pharmacokinetics. Subjects will receive ciprofloxacin 500 mg or placebo
      every 12 hours for a total of 14 days beginning at the time of ETI-204/placebo
      administration. It is anticipated that the number of subjects in part 1 of the study (18
      receiving active ETI-204 and 6 receiving placebo) will be sufficient to allow a preliminary
      assessment of safety and efficacy (ETI-204 concentration). In part 2, 12 subjects will
      receive active ETI-204 (108 mg dose from part 1, presuming no safety or tolerability issues).
      Of these, 6 will also receive oral ciprofloxacin and 6 will serve as the controls (i.e.,
      ETI-204 alone). An additional cohort of 6 subjects will receive ETI-204 placebo and oral
      ciprofloxacin. This number of subjects should be sufficient to provide an indication of the
      presence of a drug-drug interaction between ETI-204 and ciprofloxacin, but not necessarily
      the magnitude. All statistical comparisons will be performed using two sided tests at an
      alpha level of 0.05 unless specifically stated otherwise. All statistical null hypotheses
      assert that there are no differences between treatments. Because this is the first study in
      man with ETI-204, the full risks can not be determined. ETI-204 is being tested for its
      utility in preventing the life-threatening sequelae that may occur following exposure to
      anthrax. The results of this study could demonstrate that ETI-204 has an acceptable safety
      profile and that it has a pharmacokinetic profile that will provide for serum concentrations
      of the drug (antibody) over time that will be effective in preventing the toxicity of one of
      the exotoxins produced by B. anthracis.
    

Intervention name(s): Ciprofloxacin 500 mg; ETI-204 (Anthim)
Intervention type(s): Drug; Drug
Intervention MeSH terms: Ciprofloxacin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Treatment
Keywords: anthrax, Bacillus anthracis, monoclonal antibody, ETI-204