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

 1. Patient > 18 years of age with diarrhea associated with a positive stool test for C.
 difficile toxin(s). Patients may be diagnosed with C. difficile by
 hospital/clinic/reference microbiology laboratory test or by a rapid diagnostic test
 performed by the study staff and positive test result must be within 14 days of
 enrollment.

 2. Patient must receive standard of care treatment for C. difficile associated disease.
 Standard of care treatment should include either metronidazole by mouth or
 intravenously or vancomycin by mouth.

 3. Patient or legal representative must have read, understood, and provided written
 informed consent and Health Insurance Portability and Accountability Act (HIPAA)
 authorization after the nature of the study has been fully explained.

 Exclusion Criteria:

 1. History of chronic diarrheal illness such as ulcerative colitis or Crohn's disease.

 2. Score of 4 on modified Horn's index

 3. Severe C. difficile colitis with planned surgery in less than 24 hours.

 4. Positive pregnancy test within 24 hours of study infusion or an unwillingness to
 undergo pregnancy testing in females of child-bearing potential. Females capable of
 child-bearing must agree not to become pregnant from the time of study enrollment
 until at least 3 months after completion of study infusion. If a woman is sexually
 active and has no history of hysterectomy or tubal ligation, she must agree to use
 hormonal or barrier birth control with spermicidal gel.

 5. Breastfeeding.

 6. Receipt of other investigational study agent within previous 30 days.

 7. Any other condition that in the opinion of the investigator would jeopardize the
 safety or rights of the patient participating in the study or make it unlikely the
 patient could complete the study.