FMT for MDRO Colonization After Infection in Renal Transplant Recipients

Potential participants who meet key eligibility criteria [adults who have undergone renal
transplantation and have a history of infection with the Target Multidrug Resistant Organisms
(MDRO)] will be approached for consideration of study participation. For this study, Target
MDRO colonization is defined as a positive bacterial culture of either carbapenem-resistant
Enterobacteriaceae (CRE), vancomycin-resistant Enterococcus (VRE), Extended Spectrum
Beta-Lactamases (ESBL), and/or multidrug resistant (MDR) Pseudomonas from stool or perirectal
swab sampling.

The 20 trial participants will be randomized in a 1:1 ratio to one of two arms: the control
arm [not receiving Allogeneic Human Stool in Glycerol (10%; AHSG) via Fecal Microbiota
Transplant (FMT)] and the experimental arm (receiving AHSG via FMT). Participants in the
control arm participants can crossover to receive the treatment after completing a study
cycle without FMT. Each cycle lasts 6 weeks and participants will complete a maximum of 2
treatment cycles; participants randomized to the experimental arm will complete a maximum of
two cycles and those randomized to the control arm will complete up to three cycles. Upon
completion of the final cycle, all trial participants will be followed for just over 6
months.

In addition to the trial participants, there will also be one stool donor participant. The
consented, screened, and eligible stool donor will be identified from an established group of
stool donors and will undergo screening procedures that are specific to this study. This
individual will donate human stool for the preparation of the AHSG (known as the
investigational new drug (IND) product for this study). Upon processing of AHSG, the stool
donor will enter the Follow-Up Period and remain available for communication to the study
team (if necessary) until the Study Completion Date. However, no scheduled study assessments
are required of the stool donor.

Inclusion Criteria:

- Ability to understand and willingness to sign a written informed consent document.

- Ability and willingness to comply with study protocol requirements and receive the IND
product via rectal retention enema, which was manufactured from a pre-selected stool
donor participant.

- History of MDRO infection with at least one of the following Target MDROs: CRE, VRE,
ESBL, or MDR Pseudomonas.

- Not on systemic antibiotics for any reason other than if MDRO infection was recent and
potential participant is still taking antibiotics for target MDRO at time of
screening. If the latter, then participant must complete antibiotic course by Study
Day -2

- Stool or Perirectal swab sampling with a positive Target MDRO (e.g CRE, VRE, ESBL,
and/or MDR Pseudomonas) result within two weeks prior to enrollment, confirmed by a
Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.

- Prior receipt of a living or deceased donor renal transplant.

- Performance status of either: American Society of Anesthesiology (ASA) Classification
Score of I-III, Eastern Cooperative Oncology Group (ECOG) performance status score of
0-2, or Karnofsky Performance Score (KPS) of 50-100%.

- At least one prior course of systemic antibiotics since renal transplant.

- If applicable, willingness to discontinue probiotics or other microbiota restoration
therapies during screening at least seven days prior to the first intervention.

- The effects of FMT on the developing human fetus are unknown. For this reason, women
of child-bearing potential (WOCBP) and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation.

- Negative blood or urine human chorionic gonadotropin (hCG) testing on the day of FMT
for WOCBP with documentation of negative test result

- Negative baseline Human Immunodeficiency Virus (HIV) test

- Known screening drug monitoring level (e.g., tacrolimus); not subjected to screening
window

- Known serology CMV status confirmed either by Medical History (if positive). If no
mention of positivity in medical records, serology is tested within 30 days of
enrollment for:

1. Cytomegalovirus (CMV) by polymerase chain reaction (PCR)

2. Cytomegalovirus (CMV), serology Immunoglobulin G (IgG)

Exclusion Criteria:

- Female participants who are pregnant, breastfeeding, lactating, or planning a
pregnancy during study duration (through 4 weeks after the last dose of IND product).

- Prior gastrointestinal surgery or intervention:

1. Ileostomy (in the last 3 months)

2. Colostomy (in the last 3 months)

3. Gastric or colon resection (in the last 3 months)

4. Bariatric surgery (any prior history)

5. Total colectomy (any prior history)

- Any of the following gastrointestinal conditions:

1. Irritable Bowel Syndrome (IBS) with diarrhea in the last 12 months

2. Crohn's disease

3. Ulcerative Colitis

4. Celiac disease

5. Untreated in-situ colorectal cancer

6. Microscopic or ulcerative colitis

7. Toxic megacolon or ileus

8. Tube feeding (current or planned)

- Known positive stool studies or cultures in the last 30 days for:

1. Ova

2. Parasites

3. Salmonella

4. Shigella

5. Campylobacter

6. Clostridium difficile (an enteropathogen) as tested by the Xpert C. difficile
platform

7. Other enteropathogens - defined as any positive result on the Biofire FilmArray
Gastrointestinal Panel, (Campylobacter, Plesiomonas, Salmonella, Vibrio,
Yersinia, Enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia
coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), Shigella, Cryptosporidium,
Cyclospora, Entamoeba, Giardia, Adenovirus, Astrovirus, Norovirus, Rotavirus,
Sapovirus).

- Known uncontrolled intercurrent illness(es) such as, but not limited to:

1. Ongoing or active infection

2. Symptomatic congestive heart failure

3. Unstable angina pectoris

4. Cardiac arrhythmia

5. Any other intercurrent acute illness that in the opinion of the investigator will
preclude subject from entering the study

- Compromised immune system other than transplant immunosuppression:

1. HIV-positive as identified by one of the following:

1. Positive HIV 1/2 antibody test result

2. Positive HIV p24 antigen test result

3. Prior diagnosis of HIV

4. Active or history of administration of combination antiretroviral therapy
(cART)

2. Known Absolute Neutrophil (ANC) <1000 neutrophils per cubic millimeter (mm^3) in
the last 3 months

3. Active malignancy requiring intensive induction chemotherapy, radiotherapy, or
biologic treatment either concurrently or in the last 2 months

4. Acute leukemia

5. History of bone marrow transplantation (allogeneic or autologous) in the last 3
years

- History of organ transplant rejection in the last 6 months

- Significant food allergy to foods that are part of the stool donor participant's diet.

- Life expectancy is 24 weeks or less.

- Any condition that, in the opinion of the investigator, might interfere with study
objectives or limit compliance with study requirements, including but not limited to:

1. Known active intravenous drug or alcohol abuse

2. Psychiatric illness

3. Social situation

- Participated in an investigational study that also meets one of the following
criteria:

1. Received an interventional agent (drug, device, or procedure) in the last 28 days

2. Enrollment on this study or any other interventional study for MDROs