Clinical Trial: Study of the Clinical Effectiveness of a Human Monoclonal Antibody to C. Difficile Toxin A and Toxin B in Patients With Clostridium Difficile Associated Disease

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

Official Title: A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Clinical Effectiveness of a Human Monoclonal Antibody to Clostridium Difficile Toxin A (GS-CDA1) and a Human Monoclonal Antibody to

Brief Summary: Patients with Clostridium difficile associated disease who fulfill the eligibility criteria will be approached to participate. All study patients must receive standard of care treatment for Clostridium difficile associated disease. Enrolled patients will be randomized to receive a single intravenous solution of a human monoclonal antibody (huMab) to C. difficile toxin A (GS-CDA1) combined with a human monoclonal antibody to C. difficile toxin B (MDX-1388) or 0.9% sodium chloride as placebo in a 1:1 treatment allocation.Patients will be evaluated for safety and clinical outcomes through day 84 +/- 10 days. Occurrence of adverse events, use of concomitant medications, and stool output will be assessed at scheduled phone contacts and study visits. Some patients enrolled will have a subsequent visit on day 168 ± 14 days.

Detailed Summary: This study is a phase II, randomized, double-blind, placebo-controlled study in patients diagnosed with Clostridium difficile associated disease. Patients with Clostridium difficile associated disease will be identified either from stool test results or by physician referral, and those who fulfill the eligibility criteria will be approached to participate. All study patients must receive standard of care treatment for Clostridium difficile associated disease. Enrolled patients will be randomized to receive a single intravenous solution of a human monoclonal antibody to C. difficile toxin A (GS-CDA1) combined with a human monoclonal antibody to C. difficile toxin B (MDX-1388) or 0.9% sodium chloride as placebo in a 1:1 treatment allocation. One hundred patients will be enrolled in the combination monoclonal antibody treated arm and 100 patients will be enrolled in the placebo arm. Patients will be evaluated through day 84 ± 10 days after receipt of study infusion for safety and clinical outcomes. Blood samples for safety analyses, anti-toxin A and anti-toxin B antibody measurements and human anti-human antibody (HAHA) titers will be collected at scheduled times. Study visits will occur on days 3 ± 1, 10 ± 2, 28 ± 3, 56 ± 7 and on day 84 ± 10 days. Occurrence of adverse events, use of concomitant medications, and record of stool output will be assessed at scheduled phone contacts and study visits. The first 20 patients enrolled will have a subsequent visit on day 168 ± 14 days for an additional blood collection for HAHA analysis.
Sponsor: University of Massachusetts, Worcester

Current Primary Outcome: Determine if the addition of C. difficile toxin A and toxin B human monoclonal anti-toxin antibodies to standard of care treatment reduces the proportion of subjects with recurrent CDAD compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]

Original Primary Outcome:

  • To describe the course of resolution of illness in the standard of care plus
  • placebo population and estimate by a number of exploratory analyses the presence
  • and magnitude of a favorable treatment effect provided by the addition of a
  • combination of human monoclonal antibodies to C. difficile toxin A and toxin B
  • with standard of care treatment.


Current Secondary Outcome:

  • Evaluate safety and tolerability of human monoclonal anti-toxin antibodies in patients receiving standard of care treatment for CDAD compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]
  • Determine if the addition of human monoclonal antibodies to C. difficile toxin A and toxin B and standard of care treatment; reduces the time to resolution of diarrhea in patients with CDAD compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]
  • Determine if the addition of human monoclonal antibodies to C. difficile toxin A and toxin B and standard of care treatment; reduces the proportion of patients who experience standard of care treatment failure compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]


Original Secondary Outcome:

  • To evaluate safety and tolerability of a human monoclonal antibody to C.
  • difficile toxin A (GS-CDA1) combined with a human monoclonal antibody to C.
  • difficile toxin B (MDX-1388) administered to patients receiving standard of care
  • treatment for C. difficile associated disease compared to patients receiving
  • standard of care and placebo.
  • To determine if the addition of a combination of human monoclonal antibodies to
  • C. difficile toxin A and C. difficile toxin B with standard of care treatment
  • reduces the proportion of patients with recurrent Clostridium difficile
  • associated disease after completion of standard of care treatment compared to
  • those patients receiving standard of care and placebo.


Information By: University of Massachusetts, Worcester

Dates:
Date Received: July 7, 2006
Date Started: July 2006
Date Completion:
Last Updated: October 26, 2010
Last Verified: October 2010