Please select the eligibility criteria that correspond to the clinical trial below.
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 Clostridium Difficile Toxin B (MDX-1388) in Patients Being Treated for Clostridium Difficile Associated Disease
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.


Options:
A: 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.
B: Inclusion Criteria:

* 18 years of age
* The presence of CDAD at the time of enrollment with no other likely etiology for the diarrhea
* Less than or equal to 48 hours of treatment with metronidazole, vancomycin or other antibacterial therapy specific for CDAD
* Baseline serum potassium \> 3.0 mmol (meq)/L
* Patient considered sufficiently stable clinically to likely complete a 6 week study period
C: Patient inclusion criteria

1. Age 18 years or older.
2. Able to provide informed consent.
3. Laboratory or pathology: confirmed diagnosis of recurrent CDI with symptoms (defined below) within the previous 180 days.
4. ≥ 2 episodes of CDI within 6 months and/or ongoing symptoms consistent with CDI despite treatment with oral vancomycin at a dose of at least 125 mg 4 times daily for at least 5 days.

Symptoms of CDI, diarrhea deﬁned as: 3 or more unformed bowel movements in 24 hours for a minimum of 2 days with no other causes for diarrhea. Subjects will be required to have laboratory or pathology-confirmed diagnosis of recurrent C. difficile infection where recurrence is deﬁned as return of diarrhea and positive stool test after a period of symptom resolution within 8 weeks of the first episode and has received at least a 10-day course of standard antibiotic therapy.

Patient exclusion criteria

1. Planned or actively participating in another clinical trial.
2. Patients with neutropenia with absolute neutrophil count \<0.5 x 109/L
3. Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray
4. Peripheral white blood cell count \> 30.0 x 10E9/L AND temperature \> 38.0 oC
5. Active gastroenteritis due to Salmonella, Shigella, E. coli 0157H7, Yersinia or Campylobacter.
6. Presence of colostomy
7. Unable to tolerate HBT or enema for any reason.
8. Requiring systemic antibiotic therapy for more than 7 days.
9. Actively taking Saccharomyces boulardii
10. Severe underlying disease such that the patient is not expected to survive for at least 30 days.
11. Any condition that, in the opinion of the investigator, that the treatment may pose a health risk to the subject.

Donor inclusion

1. Able to provide and sign informed consent.
2. Able to complete and sign the donor questionnaire
3. Able to adhere to fecal transplantation stool collection standard operating procedure.

Donor exclusion

1. Tested positive for any of the following: Human Immunodeficiency virus (HIV) 1/2, hepatitis IgM, hepatitis B (HBsAg), hepatitis C antibody, syphilis, human T- lymphotrophic virus (HTLV) 1/II and vancomycin resistant Enterococcus (VRE), methicillin resistant S. aureus (MRSA), Salmonella, Shigella, E.coli O157 H7, Yersinia and Campylobacter.
2. Detection of ova, parasites, C. difficile toxin, norovirus, adenovirus, rotavirus on stool examination
3. History of any type of active cancer or autoimmune disease
4. History of risk factors for acquisition of HIV, syphilis, Hepatitis B, Hepatitis C, prion or any neurological disease as determined by the donor questionnaire, appendix B.
5. History of gastrointestinal comorbidities, e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation or diarrhea
6. Receipt of blood transfusion from a country other than Canada in preceding 6 months
7. Antibiotic use or any systemic immunosuppressive agents in the 3 months prior to stool donation
8. Receipt of any type of live vaccine within 3 months prior to stool donation
9. Ingestion of nut or shell fish 3 days preceding donation if the recipient has known allergies to these food.
10. Any current or previous medical or psychosocial condition or behaviours which in the opinion of the investigator may pose risk to the recipients or the donor
D: To be eligible for enrollment, a participant must meet all of the following criteria prior to any study related procedures:

* Informed Consent obtained and signed
* Age ≥ 18 years
* If female, participant is non-lactating, and is either:

  * Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy
  * Of childbearing potential and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for 3 months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse
* Established non-severe or severe CDI (after Data Monitoring Committee \[DMC\] review) with a positive stool test for toxin A and/or B within 72 hours prior to first dose of study drug.

Exclusion Criteria:

A participant will not be enrolled if s/he meets any of the following criteria:

* Female and pregnant or lactating
* Toxic megacolon and/or known small bowel ileus
* Received treatment with intravenous (IV) immune globulin within 30 days prior to the first dose of study drug
* Antibacterial therapy specific for current CDI or that may be effective for CDI even if given for a different indication:

  * Received more than 24 hours of oral vancomycin for the current episode of CDI prior to first dose of study drug.
  * Received more than 24 hours of oral/intravenous metronidazole OR any other therapy specific for the current episode of CDI immediately prior to first dose of study drug unless the participant received at least 3 days of such therapy, and is considered a treatment failure for CDI.
  * Received more than 24 hours of oral/intravenous metronidazole for any other indication in the 3 days prior to first dose of study drug.
* Participants with more than 2 episodes of CDI within 90 days (that is, participants can be enrolled with their 1st recurrence/2nd episode)
* Major gastrointestinal (GI) surgery (that is, significant bowel resection including total colectomy with ileostomy) within 3 months of enrollment (this does not include appendectomy or cholecystectomy)
* History of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis
* Unable to stop loperamide, diphenoxylate, and cholestyramine during the duration of the study
* Unable to stop opiate treatment, unless on a stable dose as of onset of diarrhea and no change in dose planned for the duration of the study
* Known positive stool cultures for other enteropathogens, including but not limited to Salmonella, Shigella and Campylobacter
* Known stool studies positive for ova and/or parasites
* Known intolerance or hypersensitivity to daptomycin and/or vancomycin
* Poor concurrent medical risks with clinically significant co-morbid disease such that in the opinion of the Investigator the participant should not be enrolled
* Received an investigational drug or participated in any experimental procedure within 1 month prior to study entry
* Previously enrolled in this study
* Received an investigational vaccine against C. difficile
* Participants with known Hepatitis B or Hepatitis C who have alanine aminotransferase or aspartate aminotransferase \> 2.5 times the upper limit of normal (ULN) and/or bilirubin \> 1.5 times the ULN
* Human immunodeficiency virus positive, unless controlled (that is, on triple therapy) and with a CD4 \> 200 cells per millimeter cubed (cellsmm˄3)
* Anticipated that systemic antibacterial therapy for a non-CDI infections will be required for \>7 days after start of study therapy
* Concurrent therapy with daptomycin
* Unable to discontinue Saccharomyces or similar probiotic
* Known active IV drug or alcohol abuse
* Concurrent intensive chemotherapy, radiotherapy or biologic treatment for active malignancy (may only be enrolled after consultation with Medical Monitor)
* Unable to comply with the protocol requirements
* Any condition that, in the opinion of the Investigator, might interfere with study objectives
* Life expectancy is less than 6 weeks

Additional Exclusions for Participants with Severe CDI

In addition to the criteria listed above, a participant who meets the definition of severe CDI will not be enrolled if the participant meets any of the following criteria:

* Age \> 80
* Hypotension, defined by sustained systolic blood pressure \< 90 millimeters of mercury (mmHg), or need for vasopressors to maintain blood pressure
* Abdominal rebound tenderness on examination
* Acute kidney insufficiency defined by:

  * oliguria (\< 20 cubic centimeter \[cc\] urine output per hour over a 4 hour period not responsive to attempts to increase renal perfusion) or
  * non-perfusion (for example, pre-renal) related azotemia with initial creatinine (Baseline) \> 2.5 milligrams per deciliter (mg/dL) and blood urea nitrogen (BUN) \> 40 mg/dL with no prior history of chronic kidney disease
* Unable to tolerate oral medications due to persistent vomiting 2. White blood cell (WBC) count \> 30,000/mm˄3

Answer: A