Clinical Trial: Phase 1 PK Study of XOMA 3AB

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I, Blinded, Placebo-controlled, Dose-escalation Study of the Safety and Pharmacokinetics of XOMA 3AB Administered Intravenously in Healthy Adults

Brief Summary: This is a phase I, single-center, placebo-controlled, double-blinded, dose escalation study of anti-botulinum toxin monoclonal antibodies in healthy adult volunteers. Volunteers will be hospitalized in the Johns Hopkins Phase 1 unit during the infusion and until after the 24-hour blood draw. Three escalating dose cohorts of a combination of three anti-botulinum monoclonal antibodies will be evaluated. Each cohort will consist of eight volunteers in which they will receive a single intravenous infusion of active drug or placebo. Placebo will be normal saline. Volunteers will be followed for safety for up to 120 days after infusion depending on dose cohort.

Detailed Summary: This is a phase I, single-center, placebo-controlled, double-blinded, dose escalation study of anti-botulinum toxin monoclonal antibodies in healthy adult volunteers. Volunteers will be hospitalized in the Johns Hopkins Phase 1 unit during the infusion and until after the 24-hour blood draw. Three escalating dose cohorts of a combination of three anti-botulinum monoclonal antibodies will be evaluated. Each cohort will consist of eight volunteers in which they will receive a single intravenous infusion of active drug or placebo. Placebo will be normal saline. Volunteers will be followed for safety for up to 120 days after infusion depending on dose cohort.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Safety and tolerability of XOMA 3AB: occurrence of adverse events and serious adverse events. [ Time Frame: Day 0 to Day 90 and to Day 120 (depending on dose cohort). ]
  • Safety and tolerability of XOMA 3AB: Changes from baseline in vital signs, physical examinations, chemistry and complete blood count with differential laboratory studies, dipstick urinalysis, and electrocardiograms. [ Time Frame: Day 0, 1, 2, 3, 7, 14, 28, 42, 56, Day 90 and to 120 days (depending on dose cohort). ]


Original Primary Outcome:

  • Safety and tolerability of XOMA 3AB: occurrence of adverse events and serious adverse events. [ Time Frame: Day 0 to Day 90 and to Day 120 (depending on dose cohort). ]
  • Safety and tolerability of XOMA 3AB: Changes from baseline in vital signs, physical examinations, chemistry and hematology laboratory studies, urinalysis, and electrocardiograms. [ Time Frame: Day 0, 1, 2, 3, 7, 14, 28, 42, 56, Day 90 and to 120 days (depending on dose cohort). ]


Current Secondary Outcome:

  • Immunogenicity: measuring Human anti-human antibodies (HAHA) to XOMA 3AB [ Time Frame: Day 0, 28, 56, 90 and 120 days (depending on dose cohort). ]
  • Pharmacokinetics of XOMA 3AB:Area under the curve to the last time with a measurable value (AUC(0-t)) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Volume of distribution (Vz) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Total clearance (CL) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Elimination half-life (t½) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Elimination rate constant (gimel z) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Area under the curve to infinity (AUC(inf)) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Time to Cmax (Tmax) measured from end of infusion [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Maximum plasma titer/concentration (Cmax) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Mean residence time (MRT) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]


Original Secondary Outcome:

  • Immunogenicity: measuring Human anti-human antibodies (HAHA) to XOMA 3AB [ Time Frame: Day 0, 28, 56, 90 and 120 days (depending on dose cohort). ]
  • Pharmacokinetics of XOMA 3AB: Area under the curve to infinity (AUC(inf)) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Elimination half-life (t½) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB:Area under the curve to the last time with a measurable value (AUC(0-t)) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Volume of distribution (Vz) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Total clearance (CL) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Mean residence time (MRT) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Elimination rate constant (gimel z) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Time to Cmax (Tmax) measured from end of infusion [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]
  • Pharmacokinetics of XOMA 3AB: Maximum plasma titer/concentration (Cmax) [ Time Frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort) ]


Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: May 5, 2011
Date Started: May 2011
Date Completion:
Last Updated: December 4, 2014
Last Verified: May 2013