Microbial Restoration for Individuals With One or More Recurrences of Clostridium Difficile Associated Disease (CDAD)

This is a multi-center, randomized, placebo controlled, partially blinded trial comparing the
safety and efficacy of fecal microbiota transplantation versus placebo both delivered by
rectal enema in subjects 18 years of age or older with recurrent Clostridium difficile
Associated Disease (CDAD). 162 (108 in the FMT group, 54 in the placebo group) male or female
subjects will be enrolled in the study. Subjects must have had treatment for most recent CDAD
with at least 10 days of either metronidazole po/IV (500 mg tid), oral vancomycin (at least
125 mg qid), or oral fidaxomicin (200 mg bid) and have no diarrheal symptoms (<3 unformed
stools per 24 hour period) off antibiotics during the washout period. Enrolled subjects will
be randomized at each site to receive either FMT by enema or placebo by enema in a 2:1 ratio.
The study is described as partially blinded because by design subjects are to be blinded only
to a certain point. Subjects will be followed for clinical response (efficacy) and safety.
Study duration is 4 years, subject participation duration is approximately 3 years. Primary
study objectives are to: 1) evaluate the safety of FMT(s) delivered by enema vs. placebo
delivered by enema, 2) determine efficacy of FMT delivered by enema vs. placebo delivered by
enema. Secondary objectives are to: 1) evaluate the sustained clinical response rate of FMTs
delivered by enema vs. placebo delivered by enema, 2) evaluate the rate of recurrent CDAD, 3)
evaluate the time to recurrent CDAD.

Inclusion Criteria:

1. Providing permission to access the medical record.

2. Male or non-pregnant female 18 years or older at the time of enrollment.

3. Able to provide signed and dated informed consent.

4. = / > 2 episodes of CDAD in the past 6 months, including the last episode if present
at screening*.

*Defined by = / > 1 confirmed positive CDAD by diagnostic methods and another
occurrence substantiated by medical history.

5. Completed treatment course of at least 10 days of oral vancomycin, oral/IV
metronidazole, or oral fidaxomicin for the most recent episode prior to enrollment.

6. Controlled diarrheal symptoms (<3 unformed stools per 24 consecutive hour period).

7. Deemed likely to survive for 1 year after enrollment.

8. Women of childbearing potential** (includes females who are postmenopausal <1 year) in
sexual relationships with men must use an acceptable method of contraception*** from
30 days prior to enrollment until 4 weeks after completing study treatment.

**Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy,
hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal
sterilization) with documented radiological confirmation test at least 90 days after
the procedure, and still menstruating or < 1 year of the last menses if menopausal.
Also includes females who are postmenopausal < 1 year.

***Includes, but is not limited to, barrier with additional spermicidal foam or jelly,
intrauterine device, hormonal contraception (started at least 30 days prior to study
enrollment), intercourse with men who underwent vasectomy.

9. Males must agree to avoid impregnation of women between Day 1 and 28 days following
each administration of the study product.

10. Negative urine or serum pregnancy test within 24 hours of enrollment and
randomization.

11. Is able to provide blood and fecal specimens.

12. Is able to complete a test of comprehension.

Exclusion Criteria:

1. Previous FMT within the previous 12 months prior to study enrollment.

2. Use of the following drugs in last 3 months: such as monoclonal antibodies to B and T
cells, anti-TNF agents, glucocorticoids*, antimetabolites*, calcineurin inhibitors***,
mycophenolate mofetil.

*For example, > 20 mg of prednisone (or equivalent) given daily or on alternative days
for 2 weeks or more.

- azathioprine, 6-mercaptopurine

- ,tacrolimus, cyclosporine

3. Requiring antibiotics in the past 2 weeks prior to receiving the enema for a condition
other than CDAD or scheduled to be used in the upcoming 2 weeks.

4. Unable to tolerate enema for any reason.

5. Any GI cancer in the past year or any actively treated malignancy.

6. Patients with a history of severe anaphylactic food allergy.

7. Any history of cirrhosis.

8. Untreated HIV disease.****

****If no HIV screening results are available in the medical record from within the
last six months, a HIV screening test will be performed during screening.

9. Other severe immunosuppression or immunodeficiency.

10. Severe OR acute disease at the time of enrollment.*****

*****Temperature >100.4 degrees Fahrenheit (38 degrees Celsius) or heart rate less
than 45 bpm or greater than 130 bpm, or systolic blood pressure less than 80 mm Hg or
greater than 155 mm Hg, or diastolic blood pressure greater than 100 mm Hg, or at the
discretion of the investigator

11. Major surgery of the GI tract in the past 6 months.

12. Having a non tolerance****** to or any component of vancomycin, loperamide or
GoLYTELY.

******tolerance is defined as the absence of immunoglobulin E-mediated allergy (e.g.,
urticaria, angioedema, bronchospasm, or anaphylaxis) and the absence of severe allergy
(e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis)

13. Any history of inflammatory bowel disease (IBD) including ulcerative colitis, Crohn's
disease, indeterminate colitis or celiac disease.

14. Irritable bowel syndrome (IBS) within the past 12 months or any active uncontrolled
gastrointestinal disorders or diseases.

*******GI obstruction, ileus, gastric retention, bowel perforation, toxic colitis or
toxic megacolon, persistent infectious gastroenteritis, persistent or chronic diarrhea
of unknown etiology, or refractory/severe Clostridium difficile infection (severe CDAD
identified as leukocytosis with a white blood cell count greater than 15,000 cells/mL
or an increase in the serum creatinine level to 1.5 times the premorbid level),
chronic diarrhea of unknown cause for 6 weeks or more.

15. Unable to comply with protocol requirements.

16. Participation in any other clinical drug research trial within 30 days prior to
enrollment or for 1 year after enrollment that might interfere with the safety and
efficacy assessment.

17. A condition that would jeopardize the safety or rights of the subject, would make it
unlikely for the subject to complete the study, or would confound the results of the
study.