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

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.