Phase II. Dose Ranging Study of the Safety and Efficacy of Orally Administered Lyophilized Fecal Microbiota Product (PRIM-DJ2727) for the Treatment of Recurrent Clostridium Difficile Infection (CDI)
Phase: PHASE2
Conditions: Recurrent C. Difficile Infection
Sponsor: The University of Texas Health Science Center, Houston

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IRB NUMBER: HSC-SPH-17-0614 
IRB APPROVAL DATE: 05/07/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase II. Dose Ranging Study of the Safety and Efficacy of Orally Administered Lyophilized Fecal Microbiota 
Product (PRIM-DJ2727) for the Treatment of Recurrent Clostridium difficile Infection (CDI) 
 
NCT03298048 
 
Version Date: 05/07/2018 

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IRB NUMBER: HSC-SPH-17-0614 
IRB APPROVAL DATE: 05/07/2018 
 
 
Clinical Study Protocol 
 
 
Phase II. Dose Ranging Study of the Safety and Efficacy of Orally Administered Lyophilized Fecal 
Microbiota Product (PRIM-DJ2727) for the Treatment of Recurrent Clostridium difficile Infection 
(CDI) 
 
IND Number: 17059 
Clinical Trial # NCT03298048 
Protocol Number: HSC-SPH-17-0614 
Version #: 4; 24 April 2018 
 
Investigational Product 
Lyophilized Healthy Donor Intestinal Bacteria 
 
Sponsor 
The University of Texas Health Science Center 
1200 Pressler Room 743 
Houston, TX 77030 
 
Principle Investigators: 
Dr. Herbert L. DuPont – Co-director responsible for review and evaluation of information relevant to the safety 
and efficacy of the study product 
Professor and Director, Center for Infectious Diseases, UT-SPH, |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
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Dr. Zhi-Dong Jiang – Co-director responsible for monitoring the conduct and progress of the clinical 
investigations and responsible for screening of donors and preparation of FMT for administration 
Associate Professor and Director, Enteric Pathogens Diagnostic Laboratory, Center for Infectious Diseases 
UT-SPH, |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
 
Dr. Andrew W. DuPont – serves on Advisory Committee, responsible for review and evaluation of information 
relevant to the safety of the study product 
Associate Professor, Internal Medicine, Gastroenterology, |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
 
Dr. Ned Snyder – responsible for monitoring the conduct and progress of the clinical investigations at Kelsey- 
Seybold Clinic study site 
Chief of Gastroenterology, Internal Medicine, Gastroenterology, |||||||||||||||||||||||||||||||||||||||||||||||||||||||| 
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Ashley Alexander, BS, MHSA - responsible for monitoring the conduct and progress of the clinical investigations at 
Kelsey-  Seybold Clinic study site 
Executive Director, Kelsey Research Foundation, |
| 
|
| 
 
 
Table of Contents 
SYNOPSIS .................................................................................................................................................................................... 5 
1. INTRODUCTION .................................................................................................................................................................... 8 
2. OBJECTIVE .......................................................................................................................................................................... 11 
3. STUDY DESIGN ................................................................................................................................................................... 11 
3.1 
Study Structure ................................................................................................................................................... 12 
3.2 
Definition of recurrent CDI for Study Entry ..................................................................................................... 12 
3.3 
Outcome Measure .............................................................................................................................................. 12 
3.4 
Data Safety and Monitoring Board................................................................................................................... 12 
4. SUBJECTS SELECTION AND WITHDRAWAL .............................................................................................................. 13 
4.1 
Inclusion Criteria ................................................................................................................................................. 13 
4.2 
Exclusion Criteria ................................................................................................................................................ 13 
4.3 
Vulnerable Population in Research: ................................................................................................................ 14 
4.4 
Subject Pre-screening, Screening and Re-screening:.................................................................................. 14 
4.5 
Subject Withdrawal or Termination .................................................................................................................. 15 
4.6 
Handling of Withdrawals and Discontinuation of Treatment ........................................................................ 16 
4.7 
Lost to Follow-up ................................................................................................................................................ 16 
4.8 
Receipt of Systemic Antibiotics, Non-Dietary Probiotics and Bile-acid Sequestrants during the Trial ..16 
4.9 
Termination of Study .......................................................................................................................................... 16 
5. INVESTIGATIONAL PRODUCT PRIM-DJ2727 (MICROBIOTA SUSPENSION) ....................................................... 16 
5.1 
Manufacture and Storage .................................................................................................................................. 16 
5.2 
Dose of FMT Product ......................................................................................................................................... 17 
5.3 
Method of Assigning Subjects to Study and Treatment ............................................................................... 17 
6. TREATMENT FAILURES AND RETREATMENT ........................................................................................................... 18 
7. STUDY PROCEDURES ...................................................................................................................................................... 19 
7.1 
Duration of Participation .................................................................................................................................... 19 
7.2 
Clinical Evaluations ............................................................................................................................................ 19 
7.3 
Clinical Response Evaluation ........................................................................................................................... 24 

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7.4 
Patient Laboratory Evaluations – Fecal Sample ........................................................................................... 25 
7.5 
Health Outcome Assessment ........................................................................................................................... 25 
7.6 
Subjective FMT Experience Assessment ....................................................................................................... 25 
8. STUDY SCHEDULE ............................................................................................................................................................ 25 
8.1 
Enrollment (Day -14 to -1) ................................................................................................................................. 25 
8.2 
Pretreatment Preparation (Day -4 to -1) Email or Phone Reminder ........................................................... 29 
8.3 
FMT Treatment (Day 1) ..................................................................................................................................... 29 
8.3.1 
Before Administering PRIM-DJ2727 
29 
8.3.2 
Administering PRIM-DJ2727 
30 
8.3.3 
After Administering PRIM-DJ2727 
30 
8.4 
FMT Treatment (Day 2 Phone Visit) ................................................................................................................ 31 
8.5 
Phone Visit Follow-up Days 1(+3), 7(+3), 14(+3), 30(+10), 60(+10), 90(+10) and 180 (+20) after 
treatment .............................................................................................................................................................. 31 
9. ASSESSMENT OF SAFETY AND EFFICACY ................................................................................................................ 32 
9.1 
Assessment of Safety (Definition) .................................................................................................................... 32 
9.1.1 
Adverse event: 
32 
9.1.2 
Suspected adverse reaction: 
32 
9.1.3 
Serious adverse event: ...................................................................................................................................... 33 
Any adverse event or suspected adverse reaction is considered serious if in 
33 
9.1.4 
Unexpected adverse event: 
33 
9.1.5 Adverse events of special interest (weight gain, new or worsening autoimmune conditions, and 
metabolic syndrome): 
33 
9.2 
Medical Conditions ............................................................................................................................................. 34 
9.3 
Monitoring for Safety .......................................................................................................................................... 34 
9.3.1 
Severity 
34 
9.3.2 
Relationship 
34 
9.4 
Pre-existing Signs and Symptoms and Medical Conditions ........................................................................ 35 
9.5 
Progression of Underlying Conditions and Anticipated events as an Adverse Event .............................. 35 
9.6 
Recording and Documenting Adverse Event ................................................................................................. 35 
9.7 
Investigator Reporting of Suspected Unexpected Serious Adverse event (SUSAR) ............................... 36 
9.8 
Notification of Post-Study Serious Adverse event ......................................................................................... 37 

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9.9 
Grading Adverse Event Severity ...................................................................................................................... 37 
9.10 
Halting Criteria .................................................................................................................................................... 38 
9.11 
Efficacy Endpoint ................................................................................................................................................ 38 
9.12 
Stool Analysis ...................................................................................................................................................... 38 
10. DATA COLLECTION AND ANALYSIS ............................................................................................................................. 39 
10.1 
Recording of Data .............................................................................................................................................. 39 
10.2 
Statistical Methods ............................................................................................................................................. 39 
10.2.1 
General Considerations 
39 
10.2.2 
Power Calculations 
39 
10.2.3 
Analysis Populations 
39 
10.2.4 
Randomization Procedures 
40 
10.2.5 
Analyses of Safety 
40 
10.2.6 
Efficacy Analyses 
40 
11. SUBJECT PAYMENT PROCESS ..................................................................................................................................... 40 
12. PROTECTING PRIVACY ................................................................................................................................................... 41 
13. CONTACTS ABOUT STUDY ............................................................................................................................................ 41 
TABLE 1: STUDY SCHEDULE: ............................................................................................................................................... 42 
TABLE 2: SEVERITY GRADING ............................................................................................................................................. 43 
14. REFERENCES ..................................................................................................................................................................... 48 

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Center For Infectious Diseases 
University of Texas School of Public Health 
HSC-SPH-17-0614 
 
 
SYNOPSIS 
TITLE 
Phase II. Dose Ranging Study of the Safety and Efficacy of Orally Administered 
Lyophilized Fecal Microbiota Product (PRIM-DJ2727) for the Treatment of 
Recurrent Clostridium difficile Infection (CDI) 
PROTOCOL 
HSC-SPH-17-0614 
SETTINGS 
Attending physicians will refer their patients with recurrent CDI (RCDI) for treatment 
with study drug (PRIM-DJ2727) and will continue to make clinical decisions related to 
overall health of their patients. Patients with RCDI can self-refer but must have 
attending physician who will provide non-transplant care. All subjects undergoing 
therapy will be handled as outpatients at the Kelsey-Seybold Clinic – Main Campus on 
W. Holcombe Blvd. or University of Texas School of Public Health, Center for 
Infectious Diseases. 
STUDY PURPOSE 
The purpose of the study is to determine the safety and efficacy of three different 
doses of lyophilized intestinal bacteria given orally in capsules for therapy in subjects 
with recurrent C. difficile Infection (RCDI). 
STUDY DESIGN 
Allocation: Randomized 
Endpoints: Safety, preliminary efficacy in preventing future bouts of CDI and 
improvement in intestinal flora diversity 
Intervention Model: Parallel 
assignment Masking: Double-blinded 
Primary Purpose: safe cure of CDI 
STUDY SCHEDULE 
Three hundred (360) eligible subjects (1:1:1:1 ratio) with recurrent CDI will be randomly 
assigned to receive PRIM-DJ2727 lyophilized intestinal bacteria capsules orally in one of 3 
dosage schedules: microbiota from 50g stool microbiota/day for 2 consecutive days; 100g 
stool microbiota for the 1st day and 50g for the 2nd day; 100g stool/day for 2 consecutive 
days with bowel preparation and Imodium; and a 4th control group will receive 100g 
stool/day for 2 consecutive days without bowel preparation and Imodium. An aliquot (2mL) 
of stool sample collected before dosing and at follow-up days 1,7,14,30,60 and 90 after 
FMT will be stored at -80C for future analysis (e.g. microbiome studies) 
INCLUSION 
CRITERIA 
All subjects 
1. Male and female subjects 18 years of age or older. 
2. Sexually active male and female subjects of childbearing potential agree to 
use an effective method of birth control during the study. 
3. Female subjects of childbearing potential must have a negative pregnancy test on 
the day of the procedure prior to administration of study drug. 
4. Subject/LAR willing and able to provide informed consent. 
5. Able to follow study procedures and follow-ups. 
6. Subject must have an attending physician who will provide non-transplant care. 
7. Medical history of ≥ 3 bouts of CDI in outpatient or ≥ 2 bouts of CDI in inpatient 
with either group having ≥ 2 positive fecal tests for C. difficile toxin and at least 
one bout of CDI within 6 months of  enrollment. 
8. Received at least two courses of standard-of-care antibiotic therapy for CDI. 
9. Have a refrigerator at home to store the second dose of FMT overnight. 

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HSC-SPH-17-0614 
 
 
EXCLUSION 
CRITERIA 
1. 
Unable to take capsules orally. 
2. 
Requiring systemic non-C. difficile antibiotic therapy within 14 days prior to FMT. 
3. 
Unwilling to stop taking non-dietary probiotics 24-96 hours prior to FMT. 
4. 
Unable to stop taking bile acid sequestrants (e.g. cholestyramine) 24-96 hours 
prior to FMT. 
5. 
Unable to stop use of drugs with CDI activity: oral vancomycin, oral or IV 
metronidazole, fidaxomicin, rifaximin or nitazoxanide 24-96 hours prior to FMT 
and after FMT. 
6. 
Receipt of CDI monoclonal antibodies as treatment for the most recent bout of 
CDI. 
7. 
Life expectancy of < 6 months. 
8. 
In the opinion of investigator, subject for any reason, should be excluded from the 
study. 
DURATION OF 
FOLLOWUP 
The duration of study participation for each subject is up to 216 days including 
screening (14 days), treatment (2 days) and follow-up (180-200 days). 
STUDY 
POPULATION 
The target population are adults (≥18 years old) with ≥3 bouts of CDI in outpatients or ≥2 
bouts of CDI in an inpatient with either group having ≥ 2 positive fecal tests for C. difficile 
toxin and at least one bout of CDI within 6 months of  enrollment. 
STUDY 
BLINDING 
This is a double-blinded study for the groups randomized to receive pre-treatment bowel 
prep and Imodium. 
DEFINITION OF 
TREATMENT 
FAILURE 
Treatment failure is defined as the presence of diarrhea (passage of ≥ 3 watery stools per 
24-hour period for two consecutive days) and C. difficile toxin A/B positive stool within 60 
days of FMT treatment plus receipt of anti-C. difficile antibiotics. 
STUDY AGENT, 
DOSE OF 
ADMINISTRATION 
Processed intestinal bacteria from a screened healthy donor will be administered 
lyophilized FMT to be given by the oral route. 
FMT will be given as follows: 
1. Group 1: With bowel prep and Imodium 
1st treatment day, lyophilized product generated from 50g of stool 
2nd treatment day, lyophilized product generated from 50g of stool 
2. Group 2: With bowel prep and Imodium 
1st treatment day, lyophilized product generated from 100g of stool 
2nd treatment day, lyophilized product generated from 50g of stool 
3. Group 3: With bowel prep and Imodium 
1st treatment day, lyophilized product generated from 100g of stool 
2nd treatment day, lyophilized product generated from 100g of stool 
4. Unblinded Group 4: (Without bowel prep and Imodium) 
1st treatment day, lyophilized product generated from 100g of stool 
2nd treatment day, lyophilized product generated from 100g of stool 
EFFICACY 
EVALUATION 
Primary Endpoint: 
 
Safety of FMT (lyophilized capsules with various doses) 
 
Prevention of subsequent bouts of CDI in 60 days post FMT. 
 
Safety of FMT (lyophilized capsules with same doses) without using pre-FMT 
bowel preparation and Imodium 
 
Prevention of subsequent bouts of CDI in 60 days post FMT without using pre- 
FMT bowel preparation and Imodium. 
Secondary Endpoint: 
 
To characterize improvement in microbiota diversity from baseline in subjects 
treated with various doses of lyophilized capsules. 

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University of Texas School of Public Health 
HSC-SPH-17-0614 
 
 
SAFETY 
EVALUATION 
To ensure safe study conduct during the study, an independent, non-blinded, external 
Data and Safety Monitoring Board (DSMB) will be established to perform safety 
evaluations on an ongoing basis. A DSMB charter will be developed and will detail the 
review of the safety data. The DSMB will have the power to stop the trial. 
STUDY STOPPING 
RULES 
Study may be halted or discontinued if the DSMB identifies a trend of more illnesses or 
side effects in one or more of the treatment groups. 

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Center For Infectious Diseases 
University of Texas School of Public Health 
HSC-SPH-17-0614 
 
 
 
1. INTRODUCTION 
1.1 Background 
During the past several years, C. difficile Infection (CDI) has become more frequent 
and severe, more refractory to standard therapy, with predictable recurrence rates of 25% 
after standard therapy1 , 2 . It is now accepted that the disruption of the normal balance of 
colonic microbiota secondary to antibiotics facilitates the development of CDI and 
improvements in the diversity and quantity of microbiota is associated with recovery of 
infection and prevention of disease recurrence. Studies have shown that subjects with 
recurrent CDI (RCDI) have decreased diversity of colonic flora with absolute reductions in 
counts of anaerobic species of Bacteroidetes and Firmicutes in their stool compared to 
subjects recovering from single episodes of CDI 
3. Numerous case reports and 
retrospective case series have demonstrated the benefit of intestinal microbiota 
transplantation (FMT) in subjects with severe or RCDI with cure rates over 80%-90% 4-8, 
making FMT standard therapy when multiple recurrences are seen 9. FMT involves 
administration of a suspension of intestinal bacteria obtained from a healthy individual into 
the GI tract of a patient with RCDI to promote normalization of flora 6. 
 
1.2 Our Previous Study (HSC-SPH-13-0119 and HSC-SPH-14-0020) 
 
Fecal Microbiota Transplantation Delivered by Colonoscopy 
 
A recently published study by our group found a single infusion of 50 g fresh,  
frozen or lyophilized fecal microbiota product obtained from a small number of healthy 
donors in the treatment of 72 patients with recurrent CDI given by colonoscopy led to cure 
in 87% 10. 
Our data from the recently published study suggested certain Firmicutes taxa might 
be negatively associated with CDI, which was consistent with the results of a previous 
study11. Noticeable changes in microbiota structures occurred by 7 days after FMT when 
the structures of the SUBJECTs closely resembled those of the donors. We observed 
multiple microbes at the family level consistently enriched in subjects with recurrent CDI 
after receipt of FMT: Lachnospiraceae, Ruminococcaceae and Bacteroidaceae. These 
bacteria are known to be dominant and are established early in life as key members of the 
human faecal microbiota. They are thought to play major ecologic roles in establishment 
and  maintenance  of  colonic  epithelial  health  12,13.  Lachnospiraceae  has  also      been 

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HSC-SPH-17-0614 
 
 
observed in an experimental animal model to suppress C. difficile 14. It will be important to 
determine the microbial composition at a finer species or strain level to better understand 
more fundamentally what is happening with FMT. 
The unique findings of our study were the comparative clinical efficacy and 
improvement of intestinal microbiome profiles resulting from the use of fresh, frozen and 
lyophilized donor microbiota products in the treatment of RCDI using a small number of 
non-related donors providing each product. Rates of cure were slightly less with the 
lyophilized product but well within the range of cures seen in the literature with fresh 
product 15. We demonstrated equivalent efficacy in a small number of donors supporting 
other studies showing non-related donors with a healthy microbiome are suitable sources 
of microbiota for FMT in patients with dysbiosis. 
Lyophilized microbiota are of particular interest for FMT because of their potential 
for prolonging storage time, and more importantly, oral administration in non-frozen 
capsules with lower volume resulting in the need to ingest fewer capsules 16. We 
hypothesize the slightly reduced efficacy of lyophilized material in this study related to loss 
of microbiota during the freezing process. We are currently exploring the use of lyophilized 
product given in capsules using a higher content of faecal microbiota and using a non- 
polyol cryoprotectant, which has been reported as possibly stabilizing culturable  
microbiota during the freezing process 17. The frozen product was effective in the present 
study without the use of cryoprotectants, and we do not know the effect of low 
temperatures on the anaerobes of most importance in FMT. Damage from long-term 
freezing of faecal bacteria has been shown to be lessened by adding 10% glycerol to the 
samples 18. We found that glycerol cannot be used in product to be lyophilized. 
Lyophilized microbiota are of particular interest for FMT because of their potential 
for prolonging storage time, and more importantly, oral administration in non-frozen 
capsules with lower volume resulting in the need to ingest fewer capsules 16. Lyophilized 
capsules were effective in the present study without the use of cryoprotectants, and we do 
not know the effect of low temperatures on the anaerobes of most importance in FMT. 
However, we are currently exploring the use of lyophilized product given in capsules using 
a higher content of fecal microbiota, using a cryoprotectant, to stabilize the microbiota 
during the freezing process 17. Lyophilized donor fecal microbiota have been used 
successfully in a small number of people suffering from recurrent CDI in a case report and 
one small series 19,20  and need further study. 

Center For Infectious Diseases 
University of Texas School of Public Health 
HSC-SPH-17-0614 
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FMT by Oral Capsules of Lyophilized FMT Product versus Enema using Frozen FMT Product 
 
In an ongoing study, 8 patients with RCDI were administered orally of 5g of 
lyophilized FMT product derived from 100g of fresh stool and 21 RCDI patients were given 
frozen product (via enema) obtained from 100g of fresh stool. Cure was seen in 5 of 8 
(63%) for the oral product and 20 of 21 (95%) for the frozen product given by enema. We 
then increased the dose of lyophilized product to 10g given over 2 consecutive days (5g 
each day, derived from a total of 200g of fresh stool per treatment). We saw cure in 10 of 
11 (91%) of treated subjects. This study demonstrated effectiveness of a single infusion  
via enema of frozen or lyophilized fecal microbiota capsules obtained from a small number 
of healthy donors in the treatment of recurrent CDI. Frozen FMT product has become 
widely used for microbial restoration in recurrent cases of CDI 21 and was shown to be 
equivalent to fresh donor product in a randomized double-blind comparison in 219 patients 
with recurrent CDI 22. 
 
In vivo Study to Determine Storage Time for Frozen and Lyophilized FMT Product 
 
Mice were divided into four groups for each storage time point assay, with each 
group containing 5 mice. The study design and time line are illustrated in Figure 1. All mice 
were treated with a mixture of antibiotics dissolved in drinking water. The mixture  
contained kanamycin (2 mg/day), gentamycin (0.175 mg/day), metronidazole (35 
mg/kg/day) and vancomycin (40 mg/kg/day) (Thermo Fisher Scientific, Waltham, MA). The 
antibiotic treatment started at day -4 and continued for three days. Mice were then fed 
regular water with clindamycin (10 mg/kg) (Chem-Impex International Inc., Wood Dale, IL) 
until day zero when C. difficile by gavage was administered via intraperitoneal injection of 
1.5x 105  colony-forming units (CFU) followed by FMT products. The time interval between 
C. difficile challenge and FMT administration was 30 to 60 minutes. The total volume for 
each gavage was less than 0.2 ml. The positive control of CDI disease group was fed with 
C. difficile alone in saline. The positive therapeutic control group was treated with fresh 
product. The test groups were treated with either frozen or lyophilized products stored for 
different time intervals (7, 9, 11 or 15 months). The mice were followed-up for clinical 
diarrhea occurrence (excretion of soft wet, unformed with moderate perianal a staining of 
the coat, or watery without solid pieces stool) 23. Fecal samples were collected at various 
time points and immediately stored at -80°C for further analysis. The FMT products’ 
efficacies were measured by time required to develop diarrhea after C. difficile    challenge 

Center For Infectious Diseases 
University of Texas School of Public Health 
HSC-SPH-17-0614 
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starting at day zero. 
We attempted to determine changes in major microbiota groups after freezing or 
lyophilization and storage for various lengths (7, 9, 11 or 15 months) by neutralization of 
CDI in mice experimentally infected. After antibiotic disruption of the intestinal microbiota, 
27/27 (100%) of the mice treated only with C. difficile developed diarrhea within 2 days of 
challenge. Diarrhea occurred in the following number of challenged mice given fresh, 
frozen or lyophilized FMT product stored for 7 months, respectively: 0/22 (0%); 0/5 (0%); 
and 0/5 (0%) (p=1.00). The number of mice developing diarrhea with 95% confidence 
interval and statistical results comparing frozen with the fresh FMT product stored 9 
months 3/5 (60%, 3, 95% CI: 1-6, p=0.0911), 11 months 5/5 (100%, 2, 95% CI: 2-3, 
p=0.0040), and 15 months 3/5 (60%, 2, 95% CI: 2-6, p=0.0566, frozen, 15 months). The 
values  for  lyophilized  products  stored  at  9  months  were  2/5  (40%,  6,  95%  CI:  1-6, 
p=0.1756), lyophilized, for 11 months 3/5 (60%, 2, 95% CI: 1-6, p=0.1095) and for 15 
months 2/5 (40%, 3, 95% CI: 2-3, p=0.0110). When comparing frozen and lyophilized 
products stored up to 7 months, there was no significant difference, with OR equal one 
(1.00) for both products. Both products showed a reduction in CDI neutralization after 7- 
month storage time. 
 
2. OBJECTIVE 
Primary endpoints of the study are to evaluate the safety of lyophilized product by 
capsules with various doses and the prevention of subsequent bouts of CDI in 60 days  
post FMT; and to evaluate the safety of lyophilized product by capsules with same doses 
without bowel preparation and Imodium, and the prevention of subsequent bouts of CDI     
in 60 days post FMT without bowel preparation and Imodium. The secondary endpoint is to 
characterize improvement in microbiota diversity from baseline in subjects treated with 
various doses of lyophilized capsules. 
Lyophilized FMT intestinal bacteria inoculate from well-screened healthy volunteer 
donors providing ≥100 grams of stool/FMT will be generated. Donor intestinal bacteria 
suspensions will be diluted (1:5 dilution) ≥ 500mL for  later  lyophilization  and 
encapsulation. Fecal samples from donors and recipients will be saved for future studies 
(e.g. microbiome analysis). 
 
3. STUDY DESIGN 
This is a single center, randomized, parallel assignment, double-blinded, safety and 

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Center For Infectious Diseases 
University of Texas School of Public Health 
HSC-SPH-17-0614 
efficacy study to be conducted in subjects  with recurrent CDI. Approximately 360 subjects 
will be enrolled in the study and randomized at 1:1:1:1 ratio to receive lyophilized donor 
intestinal bacteria with various doses (group 1 receiving healthy microbiota collected from 
50g stool for 2 consecutive days; group 2 receiving healthy microbiota collected from 100g 
stool on the 1st day of treatment and from 50g stool on the 2nd day of the treatment; group 
3 will receive healthy microbiota collected from 100g stool for 2 consecutive days using 
bowel prep and Imodium. An unblinded group 4 will receive healthy microbiota collected 
from 100g stool for 2 consecutive days without using bowel preparation and Imodium. All 
subjects will be followed for approximately 180-200 days following FMT treatment for 
safety. 
 
3.1 
Study Structure 
Recipient subjects must have a physician who agrees to accept care of the patient 
following FMT. Subjects consenting to treatment at Kelsey-Seybold Clinic (KSC) and the 
University of Texas School of Public Health must be willing to self-pay for the FMT with a 
money order or cashier’s check, or debit/credit card in the amount of $1,500 (see Section 
11). Insurance payment will not be accepted. All subjects will be treated at Kelsey-Seybold 
Clinic – Main Campus on Holcombe Blvd. Once the procedure is completed, the recipient’s 
care will be returned to their attending physician. Letters will be sent to physicians regarding 
the study and FMT completion. 
3.2 
Definition of recurrent CDI for Study Entry 
The definition of recurrent CDI for study entry is a medical history of ≥ 3 bouts of CDI in 
outpatients or ≥ 2 bouts of CDI in an inpatient with either group having ≥ 2 positive fecal 
tests for C. difficile toxin and at least one bout of CDI within 6 months of enrollment. Two of 
the three bouts must have a positive fecal C. difficile toxin test and one of the three bouts 
should be within 6 month of enrollment. 
3.3 
Outcome Measure 
Fecal microbiota diversity and phyla and family will be measured at the Alkek 
Microbiome Center at Baylor College of Medicine or other qualified laboratory (to  be 
clarified on form 1572). A number of clinical and safety endpoints will be examined during 
the trial related to worsening of underlying disease and events common in this population. 
Additionally we will look for symptoms of worsening diarrhea and test C. difficile toxins A/B. 
3.4 
Data Safety and Monitoring Board 
A committee of 3 faculty level people will serve as the DSMB reviewing primary and 

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secondary parameters and data from the study. Safety will be the greatest concern. The 
DSMB has the capacity to stop the study. The Board will meet at least three times during 
the study: At the study beginning; after 8-10 patients in each group have been studied and 
at the completion of the study (all subjects reached 180-200 days follow-up after FMT). 
 
 
 
 
 
 
 
SELECTION AND WITHDRAWAL 
4.1 
Inclusion Criteria 
4.1.1 Male and female subjects18 years of age or older. 
 
4. 
SUB 
JECTS 
4.1.2 Sexually active male and female subjects of childbearing potential agree to use an 
effective method of birth control during the study. 
4.1.3 Female subjects of childbearing potential must have a negative pregnancy test on the 
day of the procedure prior to administration of study drug. 
4.1.4 Subject/LAR willing and able to provide informed consent. 
4.1.5 Able to follow study procedures and follow-ups. 
4.1.6 Subject must have an attending physician who will provide non-transplant care. 
4.1.7 Medical history of ≥ 3 bouts of CDI in outpatient or ≥ 2 bouts of CDI in inpatient with 
either group having ≥ 2 positive fecal tests for C. difficile toxin and at least one bout of 
CDI within 6 months of enrollment. 
4.1.8 Received at least two courses of standard-of-care antibiotic therapy for CDI. 
4.1.9 Have a refrigerator at home to store the second dose of FMT overnight. 
4.2 
Exclusion Criteria 
4.2.1 Unable to take capsules orally. 
4.2.2 Requiring systemic non-C. difficile antibiotic therapy within 14 days prior to FMT. 
4.2.3 Unwilling to stop taking non-dietary probiotics 24-96 hours prior to FMT. 
4.2.4 Unable to stop taking bile acid sequestrants (e.g. cholestyramine) 24-96 hours prior 
to FMT. 
4.2.5 Unable to stop use of drugs with CDI activity: oral vancomycin, oral or IV 
metronidazole, fidaxomicin, rifaximin or nitazoxanide 24-96 hours prior to FMT and 
after FMT. 
Professional 
Name 
Pharmacist 
Dr. Kevin Garey 
Epidemiologist 
Dr. Lu-Yu Hwang 
Clinical Infectious Diseases Specialist 
Dr. Javier Adachi 

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4.2.7 Life expectancy of < 6 months. 
4.2.8 In the opinion of investigator, subject for any reason should be excluded from the study. 
 
4.3 
Vulnerable Population in Research: 
The elderly population particularly is susceptible to recurrent C. difficile infection (CDI) 
and some elderly patients may be cognitively impaired. Informed consent can be obtained from 
legally authorized representatives (LAR) if potential subjects have condition or circumstances 
that could impact their ability to make decision or consent. These subjects may include but are 
not limited to the cognitively impaired, demented, incapacitated, or otherwise mentally or 
physically incapable of communication. Before their enrollment, the study coordinators must be 
certain that a caretaker can properly record data called for in the study. 
The investigators or designee will assess subjects on their abilities to understand 
information and express a reasoned choice concerning the nature of the research, 
consequences of participations for the subject’s own situation, and consequences of the 
alternatives to participation. The investigators or designee will ask questions about the main 
elements of the study and judge whether the potential participant has a clear understanding. 
When an LAR agrees to the participation of the subject in the study, the consent would 
be obtained either from the patient’s legal guardian with the authority to make decisions 
regarding medical treatment (with proper paperwork to establish this) or a person designated as 
a surrogate decision-maker by the patient in a medical power of attorney or Advance Directive. 
The investigator or designee will ask for a copy of the legal document from the authorized 
representative. The LAR and the person obtaining consent would personally sign and date the 
consent form. A copy of the signed consent document will be given to the LAR. 
4.4 
Subject Pre-screening, Screening and Re-screening: 
Patients will be referred by a physician or self-referral to the study. Patient/LAR or 
physician will be provided a pre-screening form and requested to return the form with 
signed medical release and C. difficile related medical record (via email/fax/mail) for 
eligibility review. Pre-screening form and medical record received electronically will be kept 
securely in an access controlled network file service and will not be shared with anyone 
outside the study team. Any paper record will be kept securely in locked cabinet with 
access control. For potential subjects who are pre-screened but do not  enroll 
subsequently, the identifying information may be kept for 180 days of release, after which 
all identifying information will be destroyed and not retained with study records. A non- 
4.2.6 Receipt of CDI monoclonal antibodies as treatment for the most recent bout of CDI. 

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screened and the reasons for exclusion or not participating in the study. 
If a potential subject seems eligible on pre-screening, an appointment will be set up 
for in person enrollment and screening. Study personnel will advise potential subject as to 
this study’s purpose, requirements, and anticipated risks. Subject will be given the chance 
to review the informed consent form, will have the study explained in detail and any 
questions answered. Subjects who choose to enroll will sign the informed consent form, 
and the date of the consent form will serve as the first day of enrollment into the study. 
Subjects will be provided with a copy of the signed consent form. 
Consented subjects who meet all inclusion and none of the exclusion criteria will be 
assigned a Subject ID (FMT-R-03-XXX) and randomized. Subjects who do not meet the 
inclusion criteria and/or meet exclusion criteria will be considered screen failures. Screen 
failures or subjects who exit the study before receiving Treatment Day 1 dose will not 
count towards total randomization and their assigned Subject IDs will be retired. Screen 
failures or subjects who exit the study before receiving treatment Day 1 dose are allowed 
to be re-screened once for eligibility. Re-screens will be re-consented and re-randomized 
to a new Subject ID to ensure maintenance of blinding. 
Subject’s attending physician will continue to treat the subject’s primary disease(s) 
while the subject is a part of the study. The subject will continue all medications deemed 
as necessary and they will be recorded in the subject’s study record. Physicians caring for 
these subjects will have no limitations in how the subject’s primary disease(s) are 
managed. Antibiotics for C. difficile, non-dietary probiotics, and bile-acid sequestrants must 
be stopped 24-96 hours before the treatment. All other antibiotics must be stopped 14  
days prior to treatment. Subjects will be recommended not to use non-dietary probiotics 
and bile-acid sequestrants within 60 days after FMT treatment; however, subjects who 
take probiotics and bile-acid sequestrants within 60 days after treatment will not be 
excluded. 
4.5 
Subject Withdrawal or Termination 
Subject’s participation is considered complete approximately 180-200 days after 
FMT procedure; however, subjects may withdraw from the study at any time for any reason, 
without any consequence. In addition, a subject may be withdrawn from the study by the 
investigator for any reasons including the following: 
1. Lost to follow-up 
2. Adverse Event (AE) or Serious Adverse Event (SAE) 
identifiable  information  log  will  be  maintained  to  assess  the  number  of  patients pre- 

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3. Protocol violation/non-compliance 
4. Subject decision to withdraw consent 
5. Investigator decision to terminate the study 
4.6 
Handling of Withdrawals and Discontinuation of Treatment 
Subjects are free to withdraw at any time. The primary reason for withdrawals from 
the study will be recorded in the study exit form. Subjects who withdraw or are withdrawn 
will be encouraged to complete an Early Termination Phone Visit to assess for AEs. 
Subjects who withdraw will be discontinued from all study procedures. 
4.7 
Lost to Follow-up 
If subjects miss a treatment or follow-up, three attempts will be made by telephone 
or e-mail to contact and locate subjects. The contact attempts will be recorded on the study 
exit form. 
4.8 
Receipt of Systemic Antibiotics, Non-Dietary Probiotics and Bile-acid Sequestrants 
during the Trial 
If a subject takes a systemic (non-topical) antibiotic within 60 days after FMT treatment, 
they will be excluded from the efficacy part of the study and only followed for safety. Exclusion 
from efficacy means subjects will no longer provide stool specimens. However, subjects will 
continue to have phone visits and submit diaries till 180-200 days (the end of the study) for 
safety assessment (AEs). If they take systemic antibiotics more than 60 days after FMT 
treatment, they will be included in all aspects of the study. 
Subjects will be recommended not to use non-dietary probiotics and bile-acid 
sequestrants within 60 days after FMT treatment; however, subjects who take probiotics and 
bile-acid sequestrants within 60 days after treatment will not be excluded and continue to be 
followed for efficacy and safety. 
4.9 
Termination of Study 
Although the Principal Investigator has every intention of completing the study, he 
may terminate the study at any time for clinical, safety or administrative reasons. 
 
5. INVESTIGATIONAL PRODUCT PRIM-DJ2727 (MICROBIOTA SUSPENSION) 
5.1 
Manufacture and Storage 
PRIM-DJ2727 is manufactured by using current Good Laboratory Practices in The 
University of Texas Health Science Center at Houston School of Public Health’s Enteric 
Pathogen Diagnostic Laboratory (EPDL) which is a CLIA and CAP-certified laboratory. 
The FMT product for each treatment group contains bacteria from >100g filtered stool 

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from healthy donors. Product will be lyophilized at the University of Texas School of 
Public Health |  | , and compounded and packaged into capsule formulation at the 
|
 
 
| Because of 
individual diet variation in the donors and the FMT product being  lyophilized, the 
number of FMT capsules produced for each dose varies depending on the density of 
end product. Therefore, placebo capsules will be added to doses to maintain consistent 
number of capsules per treatment. Placebo capsules will be identical to the 
investigational product but will not contain intestinal bacteria. After packaging into 
capsules, the PRIM-DJ2727 will be stored in a sterilized refrigerator at 4C at the EPDL 
for up to 6 months in a test tube rack clearly labelled with the lot number and expiration 
date. 
5.2 
Dose of FMT Product 
Subjects will receive varying doses of PRIM-DJ2727 on two consecutive days of 
FMT. The clinical team will receive medications for each subject in labeled (see CMC 
protocol for label details) standard opaque pharmacy-type plastic containers for Day 1 or 
Day 2. Because of adding placebo capsules to maintain consistent number of capsules 
per treatment, the clinical trial personnel and subjects will be blinded as to the drug dose 
allocation. 
Subjects in group 1 will receive healthy microbiota collected from 50g stool for 2 
consecutive days with bowel prep and Imodium. Subjects in group 2 will receive healthy 
microbiota collected from 100g stool on the 1st day of treatment and from 50g stool on 
the 2nd day of the treatment with bowel prep and Imodium. Subjects in group 3 will 
receive healthy microbiota collected from 100g stool for two consecutive days with bowel 
prep and Imodium. Subjects in unblinded group 4 will receive healthy microbiota 
collected from 100g stool for two consecutive days without bowel prep and Imodium. 
5.3 
Method of Assigning Subjects to Study and Treatment 
The four groups will be assigned randomly on 1:1:1:1 ratio by computer table 
randomization method at the University of Texas School of Public Health. After enrollment of 
subject in the study, the study coordinator will send an email to the authorized person for 
randomization at the University of Texas School of Public Health including the schedule 
(date and time) of study procedure. The study coordinator will receive an email from the 
authorized person providing the subject identification number and confirmation of date and 
time for study drug delivery. For subjects randomized to unblinded treatment group 4, it will 
be noted in the email not to use bowel prep and Imodium. 

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5.4 
PRIM-DJ2727 Dispense and Handling 
After randomization, PRIM-DJ2727 capsules will be delivered to the clinic site in two 
single dose standard opaque plastic containers for Day 1 and Day 2 treatment. Two single 
dose containers will be labeled with the study drug, the name of the PI, number of capsules, 
lot number, date, and instructions (see CMC protocol for label details). Study personnel 
delegated by the investigator will open the day 1 dose container and administer capsules to 
subject with water. Delegated study personnel will dispense day 2 dose container to subject 
with an ice-pack to take home. Subject will be instructed to keep the day 2 dose container in 
refrigerator at home. 
 
6. TREATMENT FAILURES AND RETREATMENT 
Treatment failure is defined as the presence of diarrhea (passage of ≥ 3 watery 
stools per 24-hour period for two consecutive days) and C. difficile toxin A/B positive stool 
within 60 days of FMT treatment and receipt of anti-C. difficile antibiotics. 
If diarrhea (passage of ≥ 3 watery stools per 24-hour period for two consecutive 
days) occurs and CDI recurrence is suspected, subjects should inform study team and be 
recommended to contact their physician to perform a stool test for C. difficile. EPDL will test 
scheduled stool specimens and any unscheduled illness stool submitted up to days 60-70 
after treatment for C. difficile toxins A/B in weekly batches but this should not delay 
treatment. If the test is positive, they should be treated by their physician. The Principal 
Investigator will be available for consultation with the attending physician. Subjects who are 
determined treatment failures by the investigator will not be followed further for clinical 
parameters. They will be offered FMT retreatment with maximum dose (200g) from a 
different donor product if the subject and their physician wish to pursue this treatment. After 
at least 10-20 days of anti-CDI antibiotics (vancomycin or fidaxomicin) subjects will be 
eligible for second FMT after 24-96 hour washout. If there is a delay between completing 
treatment and second FMT, the subject will receive at least four days of vancomycin or 
fidaxomicin prior to FMT (PI can call in prescription if needed) to complete the treatment 24- 
96 hours before second FMT. Subjects will be recommended to follow a clear liquid diet the 
entire day before retreatment clinic visit. Bowel preparation and Imodium will not be required 
before retreatment. During retreatment clinic visit, vital signs and weight will not be assessed 
and subjects will be observed for 30 minutes after dosing. 
Retreatment Dosage: Day 1 (Clinic Visit) 
• Subjects are recommended to continue clear liquid diet until 1 hour after retreatment. 

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• Perform urine pregnancy test on all female subjects of childbearing potential prior to 
FMT administration. 
• Administer Day 1 dose and dispense Day 2 dose. 
• Observe the subject for 30 minutes after dosing. 
• Remind subject that Day 2 dose should be taken the next morning on empty 
stomach with water and release the subject. 
Retreatment Dosage: Day 2 (Phone Visit) 
• Ask that subject has taken the Day 2 dose. 
• Ask for any adverse events since Day 1 assessment. 
• A form letter may be faxed or emailed to subject’s physician about FMT completion. 
Subjects will be withdrawn from the study after retreatment Day 2 phone visit. After any 
second FMT, the subjects’ own physician will monitor and manage the patients’ illnesses. 
If a subject experiences diarrhea and C. difficile toxin A/B test is negative, then the 
subject is not considered a treatment failure as the presence of C. difficile was not 
established. The study investigator will evaluate the patient’s clinical picture and help decide 
whether the subject remains on the study. The PI will be available to discuss with subject’s 
physician about continuing illness to arrive at the best outcome for the subject. 
 
7. STUDY PROCEDURES 
7.1 
Duration of Participation 
The duration of study participation is up to 216 days. It includes the enrollment 
period up to 14 days, 2 days of treatment, and 180-200 days of follow up for treatment 
effect and safety. 
7.2 
Clinical Evaluations 
 
At the time of Enrollment, patients will be evaluated for inclusion and exclusion criteria. 
Demographics and current medications will be documented. Medical history will be obtained 
with particular attention to the recent CDI history (test result, treatment, hospitalization, 
weight and if any antibiotics used prior to first CDI episode). History will include obtaining 
information on solicited symptoms such as diarrhea, nausea, vomiting, gas/flatulence, 
abdominal distension, abdominal cramps/pain, constipation, rectal bleeding, fatigue/malaise, 
chills/shivering and fever (> 99.9 F) for two-week period prior to enrollment to establish 
baseline patterns should an adverse event occur in the future. 
 
Subjects will collect fresh stool samples at home and bring to the EPDL in transportation 
provided containers with an ice pack within 6 hours of collection if possible or as quickly as 

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possible before FMT and at follow up days 1(+3), 7(+3), 14(+3), 30(+10), 60(+10) and 
90(+10) and any unscheduled visit up to 60 days after FMT treatment (excluding weekends 
and holidays). Subject may collect pre-treatment stool on any day after enrollment and 
before bowel prep on day -1, and can bring stool sample on treatment Day 1 clinic visit. 
Stool samples collected from subjects until 60-70 days post FMT or at unscheduled visit up 
to 60-70 days will be tested for C. difficile toxins A/B at EPDL in weekly batches. All the stool 
samples will be stored at -80ºC for future microbiome analysis. If a subject is unable to bring 
stool sample for any reason (e.g. out of town), subject will be asked to ship the sample by 
Federal Express as expeditiously as possible. A FedEx shipping label, ice pack, Styrofoam 
container with shipping box and instructions will be provided to the subject to ship stool 
samples if they are not able to hand deliver the stools to the EPDL. The EPDL will be closed 
on weekends and holidays. If the follow-up day falls on Friday, Saturday or Sunday, subjects 
can ship the sample on Thursday or the following Monday. Stool samples that are received 
out of window are not a protocol deviation; however, missed stool samples are a protocol 
deviation. 
 
Subjects will be assessed for vital signs (blood pressure, heart rate, respiration rate, oral 
temperature, weight) at the day 1 of treatment clinic visit. 
 
Women of childbearing potential will undergo urine pregnancy testing (Qualitative HCG) to 
confirm absence of pregnancy at the day 1 of treatment clinic visit prior to administration of 
study drug. 
 
A diary completed by subject will be collected before FMT and on follow up days 7(+3), 
14(+3) 30(+10), 60(+10), 90(+10) and 180(+20) days after FMT treatment. Subjects  
may submit diaries with stool samples at the University of Texas School of Public 
Health, or may fax, email, or mail to the study site. For diary copies received in email or 
fax, an attempt will be made to obtain the originals from subjects to be taken to the  
study site subsequently. Diaries serve as tools for subjects to record daily bowel 
movements and weekly weight. Subjects will be recommended to measure weight at 
home each Sunday morning before eating and record on follow up diaries providing  
they have a scale or balance. If they do not have the means to measure their weight  
this is not a protocol deviation. Additionally, the pre-treatment diary will include daily 
record of solicited symptoms from day of enrollment until a day before treatment Day 1 
(prior to bowel prep) to establish baseline patterns should an adverse event occur in the 
future. Solicited symptoms include diarrhea, nausea, vomiting, gas/flatulence,  
abdominal    distension,    abdominal    cramps/pain,    constipation,    rectal    bleeding, 

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fatigue/malaise, chills/shivering and fever (>99.9 F). The diaries on follow up days 7 and 
180 will include a brief survey to assess subject-reported experience of FMT treatment. 
Diaries that are received out of the window or missed diaries are not a protocol 
deviation. 
Study assessments and procedures will include the following: 
 
Enrollment visit will occur on day -14 to -1 during which the informed consent will be 
obtained; inclusion and exclusion criteria will be reviewed; demographics, current 
medications, the medical history, and the CDI history (including information on 
solicited symptoms for two-week period prior to enrollment) will be reviewed and 
recorded. Subjects may already be taking or just have been prescribed antibiotics 
per standard of care to control recurrent CDI symptoms at the time of enrollment. 
Subjects who have completed antibiotic therapy will receive four days of oral 
vancomycin or fidaxomicin daily (PI can call in prescription if needed) prior to the 24- 
96 hours washout period. A stool collection kit along with IRB approved  
pretreatment prep instructions, pre-treatment diary, stool collection instructions and 
directions to drop specimen will be provided to subject. 
 
A stool sample will be collected by subject during enrollment period (prior to bowel 
prep) and a pre-treatment diary card will be completed by subject. Study personnel 
can obtain the stool and diary from subject on treatment Day 1 clinic visit. This stool 
will go to EPDL at the University of Texas School of Public Health. 
 
Day -4 to -1 before treatment: remind the subject by email or phone call about clinic 
appointment time, stopping antibiotic/probiotic/ bile-acid sequestrant, pre-treatment 
preparation and bringing pre-treatment diary and stool. Day -4 to -1(96 to 24 hours) 
before treatment: the last day of C. difficile antibiotics, non-dietary probiotics and 
bile-acid sequestrants. Subjects continue taking routine prescription medications. 
 
Day -1 before treatment: subjects follow a clear liquid diet the entire day. In the 
evening around 6:00pm, subjects (treatment groups 1-3) who were instructed by the 
study team during the enrollment will ingest bowel prep. 
Treatment Visit: Day 1 (Clinic Visit) 
 
Subjects are recommended to continue clear liquid diet until after treatment for 1 
hour. 
 
Ensure subject in treatment groups 1-3 has taken bowel prep the evening before 
and 4mg (2 capsules) of loperamide (Imodium) the morning of treatment (If Imodium 

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is missed, can be taken within 12 hours of FMT treatment). If bowel prep is  missed, 
subject can proceed with FMT and will be recorded as protocol deviation. 
 
Collect and review the pretreatment diary with subject to determine baseline pattern 
of solicited symptoms to assess for adverse events. 
 
Confirm that the C. difficile antibiotic was stopped 24-96 hours before the visit. 
 
Perform urine pregnancy test on all female subjects of childbearing potential prior to 
FMT administration. 
 
Weight and vital signs (blood pressure, heart rate, respiration rate, oral temperature) 
will be collected pre-treatment. 
 
Administer Day 1 dose and dispense Day 2 dose. 
 
Ask subject if experienced any objectionable taste or smell or difficulty swallowing 
the capsules and general reaction on taking PRIM-DJ2727 capsules. 
 
Observe the subject for 1 hour after dosing for any adverse events. 
 
Collect post-treatment vital signs (blood pressure, heart rate, respiration rate, oral 
temperature). 
 
Remind subject that Day 2 dose should be taken the next morning on empty 
stomach with water. 
 
Remind subject to continue taking routine prescription medications as needed, but 
antibiotics, non-dietary probiotics and bile-acid sequestrants may not be taken. 
 
Release subject with IRB approved aftercare instructions, follow-up paper diaries, 
visit scheduler, safe antibiotics list and specimen request form. 
Second Treatment Dosage: Day 2 (Phone Visit) 
 
Ask that subject has taken the Day 2 dose. 
 
Ask for any adverse events since Day 1 assessment. 
 
Remind subject to follow the aftercare instructions provided on Day 1. 
 
Remind subject to continue taking routine prescription medications as needed, but 
antibiotics, probiotics and bile-acid sequestrants may not be taken. 
 
Remind subject to completely fill the diaries, and submit diaries and stools at follow- 
up visits according to schedule and instructions provided by study personnel. 
 
A form letter to subject’s physician about FMT completion may be faxed or emailed. 
 
Follow Up and Safety Assessment Period (Phone Visits): Post Treatment Days 1(+3),  
7(+3), 14(+3), 30(+10), 60(+10), 90(+10) and 180(+20). 

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 
Assess subject for any adverse events, new illness symptoms, worsening of 
baseline illnesses including adverse events of special interest (new or worsening 
autoimmune conditions and metabolic syndrome) and change in medication.  
Review and assess subject-reported weight data from diaries for AE (>5% change 
from baseline weight) at days 60 and 180 phone visits. 
 
Assess subject for solicited symptoms such as diarrhea (passage of ≥ 3 watery 
stools per 24-hour period for two consecutive days), nausea, vomiting, 
gas/flatulence, abdominal distension, abdominal cramps/pain, constipation, rectal 
bleeding, fatigue/malaise, chills/shivering and fever (>99.9 F) for up to 60 days after 
treatment. 
 
If CDI recurrence is suspected, subjects should be recommended to contact their 
physician to perform a stool test for C. difficile. EPDL will test scheduled stool 
specimens and any unscheduled illness stool submitted up to days 60-70 after 
treatment for C. difficile toxins A/B in weekly batches but this should not delay 
treatment. If the test is positive, they should be treated by their physician. The 
Principal Investigator will be available for consultation with the attending physician.  
A form letter may be faxed or emailed to subject’s physician about CDI recurrence. 
 
Subject will be reminded to submit completed diary (except on follow up visit Day 1) 
and stool sample (except on follow up visit Day 180) and to put stool collection date 
on provided container (if already submitted, stool collection date should be 
confirmed). 
 
Stool samples will be collected at home by the subject and dropped off at the EPDL 
in the University of Texas School of Public Health in transportation provided 
containers with ice pack within 6 hours of collection if possible or as quickly as 
possible (excluding weekends and holidays). Stool sample will not be collected for 
follow up visit Day 180. If the subject is unable to bring stool sample for any reason 
(e.g. out of town), subject will be asked to ship the sample by Federal Express as 
expeditiously as possible. A FedEx shipping label, ice pack, Styrofoam container 
with shipping box and instructions will be provided to the subject to ship stool  
sample if they are not able to hand deliver to the EPDL. The EPDL will be closed on 
weekends and holidays. If the follow-up day falls on Friday, Saturday or Sunday, 
subjects can ship the sample on Thursday or the following Monday. Stool samples 
that are received out of window are not a protocol deviation; however, missed stool 
samples are a protocol deviation. 

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 
Diaries will be collected from subjects recording subject-reported daily bowel 
movements and weekly weight. The diaries on follow up days 7 and 180 will include 
a brief survey to assess subject-reported experience of FMT. Diary will not be 
collected on follow up day 1 after treatment. Subjects may submit diaries with stool 
samples to the University of Texas School of Public Health, or may fax, email, or 
mail to the study site. For diary copies received in email or fax, an attempt will be 
made to obtain the originals from subjects to be taken to the study site  
subsequently. Diaries that are received out of the window or missed diaries are not 
a protocol deviation. 
Unscheduled Visit (Phone): Subjects who have a suspected episode of CDI within 60-70 
days of FMT treatment may submit an unscheduled stool sample to EPDL. 
Early  Termination Visit (Phone): 
may  occur  any  time  before  180-200  days after FMT 
treatment. 
7.3 
Clinical Response Evaluation 
The clinical evaluation will include an evaluation of CDI recurrence to assess clinical 
response on each follow-up contact for 60 days after FMT. 
If subjects experience diarrhea (3 or more watery stools/day for two consecutive 
days) and suspect CDI recurrence, they should inform the study team and be  
recommended to contact their physician to perform a stool test for C. difficile. EPDL will test 
scheduled stool specimens and any unscheduled illness stool submitted up to days 60-70 
after treatment for C. difficile toxins A/B in weekly batches but this should not delay 
treatment. If the test is positive, they should be treated by their physician. The Principal 
Investigator will be available for consultation with the attending physician. A form letter may 
be faxed or emailed to subject’s physician about CDI recurrence. 
Subjects requiring a systemic Non- C. difficile antibiotic within 60 days following  
FMT treatment will be excluded from the study for efficacy analysis, but will be followed for 
safety. Exclusion from efficacy means subjects will no longer provide stool specimens. 
However, subjects will continue to have phone visits and submit diaries till 180-200 days 
(the end of the study) for safety assessment (AEs). Subjects requiring a systemic Non- C. 
difficile antibiotic 60 days after FMT treatment will continue to be followed for efficacy and 
safety. 
Subjects will be recommended not to use non-dietary probiotics and bile-acid 
sequestrants within 60 days after FMT treatment; however, subjects who take probiotics 
and bile-acid sequestrants within 60 days after treatment will not be excluded and continue 

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to be followed for efficacy and safety. 
7.4 
Patient Laboratory Evaluations – Fecal Sample 
Stool samples will be collected by the subject and brought to the EPDL within 6 
hours of collection if possible or as quickly as possible (if not feasible stool samples  
may be shipped via Federal Express) before FMT and at follow up days 1(+3), 7(+3), 
14(+3), 30(+10), 60(+10), 90(+10) and any unscheduled visit up to 60-70 days after 
FMT treatment (excluding weekends and holidays). Stool samples collected from 
subjects until 60-70 days post FMT or unscheduled visit will be tested for C. difficile 
toxins A/B at EPDL in weekly batches. All the stool samples will be stored at -80ºC for 
future metagenomics/microbiome analysis. 
The University of Texas Health Science Center at Houston Enteric Pathogens 
Diagnostic Laboratory may conduct future biochemical research on specimens routinely 
and specifically collected during this clinical study that may be used for future research 
and may be stored for up to 15 years. 
7.5 
Health Outcome Assessment 
Information such as mortality from any cause and hospitalizations will be collected 
through AE assessments. Subjects will report their solicited and unsolicited adverse 
events to study personnel on follow-up phone visits. 
7.6 
Subjective FMT Experience Assessment 
On Treatment Day 1 in clinic, study personnel will inquire from subject if  
experienced any objectionable taste or smell or difficulty swallowing the capsules and 
general reaction on taking PRIM-DJ2727 capsules. The diaries on follow up days 7 and 
180 will include a brief survey to assess subject-reported experience of FMT treatment. 
 
8. 
STUDY SCHEDULE 
8.1 
Enrollment (Day -14 to -1) 
The following study activities/data will be collected at the enrollment visit: 
 
After full explanation of the study protocol, have each subject sign an 
Informed Consent Form (ICF) before performance of any study-related 
procedures (including screening procedures). 
 
Assess each subject to ensure all inclusion criteria are met and no 
exclusion criteria met. 
 
Obtain standard demographics (date of birth, gender, ethnicity, race) 

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 
Obtain medical history to record baseline conditions, current medications 
and CDI history (test result, treatment, hospitalization, weight and if any 
antibiotics used prior to first CDI episode). History will include obtaining 
information on solicited symptoms such as diarrhea, nausea, vomiting, 
gas/flatulence, 
abdominal 
distension, 
abdominal 
cramps/pain, 
constipation, rectal bleeding, fatigue/malaise, chills/shivering, and fever 
(>99.9 F) for two-week prior to enrollment to determine baseline patterns 
should an adverse event occur in the future. 
 
Instruct patients that should they enroll in the study, they will need to 
meet the following requirements: 
o Sexually active male and female subjects of childbearing 
potential must use an effective contraceptive method of birth 
control throughout the study which may include any of the 
following; abstinence, barrier methods (such as a condom or 
diaphragm) used with a spermicide, approved hormonal 
contraceptives (such as birth control pills, patches, implants or 
injections), intrauterine device (IUD), or surgical sterilization (such 
as tubal ligation, hysterectomy, or vasectomy) at any time in the 
past. Post-menopausal women ≥45 years of age must be 
amenorrheic for at least six months to be considered to not have 
childbearing potential. 
o Probiotics and bile-acid sequestrants should be stopped 24-96 
hours before the FMT treatment. 
o On 24-96 hours before FMT, subjects take their last dose of 
antibiotic treatment for their CDI, non-dietary probiotics and bile- 
acid sequestrants. Any other antibiotics being taken must 
complete 14 days prior to FMT treatment. 
o On Day -1, all subjects must follow a clear liquid diet the entire 
day. In the evening around 6:00pm, subjects (treatment groups 1- 
3) must take bowel preparation i.e. 1 bottle (10 oz.) of  
magnesium citrate or patients with impaired kidney function take 
250mL of GoLytely. GoLytely will be prescribed by the  
investigator or nurse practitioner. If bowel prep is missed, subject 
can still proceed with FMT (noted as protocol deviation). 

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o On  Day  1,  subjects  (treatment  groups  1-3)  will  take  4mg   (2 
capsules) of loperamide (Imodium) the morning of treatment (if 
Imodium is missed, can be taken within 12 hours after FMT 
treatment). 
o On Day 1, subjects take first dose of oral capsules of PRIM- 
DJ2727 and recommended to continue their clear liquid diet for 1 
hour after dosing. 
o Stool samples will be collected by the subject before FMT and at 
follow up days 1, 7, 14, 30, 60, 90 and any unscheduled visit up 
to 60-70 days after FMT treatment and brought to the EPLD 
within 6 hours of collection if possible or as quickly as possible 
(excluding weekends and holidays). Subject can collect pre- 
treatment stool on any day after enrollment and before bowel  
prep on Day -1, and can bring stool sample on treatment day 1 
clinic visit. If a subject is unable to bring the sample to the EPDL 
(e.g. out of town), it may be shipped by Federal Express as 
expeditiously as possible. A FedEx shipping label, ice pack, 
Styrofoam container with shipping box and instructions will be 
provided to subjects to ship stool sample if they are not able to 
hand deliver to the EPDL. The EPDL will be closed on weekends 
and holidays. If the follow-up day falls on Friday, Saturday or 
Sunday, subjects can ship the sample on Thursday or the 
following Monday. 
o Subjects should inform the study team if they experience diarrhea 
(passage of ≥ 3 watery stools per 24-hour period for two 
consecutive days) suspecting CDI recurrence and contact their 
physician to perform a stool test for C. difficile. The EPDL will test 
scheduled stool specimens and any unscheduled illness stool 
submitted up to 60-70 days after treatment for C. difficile toxins 
A/B in weekly batches but this should not delay treatment. If the 
test is positive, they should be treated by their physician. The 
Principal Investigator will be available for consultation with the 
attending physician. A form letter may be faxed or emailed to 
subject’s physician about CDI recurrence. 

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o Subjects will need to complete and submit diaries before FMT 
and on follow up days 7, 14, 30, 60, 90 and 180 days after FMT 
treatment. Subject can deliver diaries with stool sample, or may 
be fax, email, or mail to the study site. For diary copies received 
in email or fax, an attempt will be made to obtain the originals 
from subjects to be taken to the study site subsequently. Diaries 
serve as a tool for the subject to record daily bowel movements 
and weekly weight. Subjects will be recommended to measure 
weight at home each Sunday morning before eating and record 
on follow up diaries, providing they have a scale or balance. If 
they do not have the means to measure their weight this is not a 
protocol deviation. Additionally, the pre-treatment diary will 
include daily record of solicited symptoms from enrollment until a 
day before treatment Day 1 to determine baseline patterns. 
Solicited symptoms include nausea, vomiting, gas/flatulence, 
abdominal distension, abdominal cramps/pain, constipation,  
rectal bleeding, fatigue/malaise, chills/shivering and fever  (>99.9 
F) The diaries on follow up days 7 and 180 after treatment will 
include a brief survey to assess subject-reported experience of 
FMT treatment. 
o Subjects will receive phone call from study personnel at follow up 
visit days 1, 7, 14, 30, 60, 90 and 180 days after FMT treatment 
(within windows specified in Table 1) Subjects will be assessed 
for any adverse events, new illness symptoms, worsening of 
baseline illnesses including adverse events of special interest 
(new or worsening autoimmune conditions, and metabolic 
syndrome) and change in medication. Subject-reported weight 
data from diaries will be assessed for AE at days 60 and 180 
phone visits. Subjects will be assessed for CDI recurrence and 
solicited symptoms (diarrhea, nausea, vomiting, gas/flatulence, 
abdominal distension, abdominal cramps/pain, constipation,  
rectal bleeding, fatigue/malaise, chills/shivering and fever (> 99.9 
F) for up to 60 days after treatment. Subjects will be reminded to 
submit completed diaries and stool samples. Diary will not be 

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collected  on  follow  up  visit  Day  1.  Stool  sample  will  not   be 
collected on follow up visit day 180. 
 
Provide subject with stool collection kits at enrollment for collecting stool 
samples before treatment and at follow up days along with IRB approved 
pretreatment prep instructions, pre-treatment diary, stool collection 
instructions and directions to drop specimen. 
8.2 
Pretreatment Preparation (Day -4 to -1) Email or Phone Reminder 
 
Remind the subject of the clinic appointment time. 
 
Remind the subject not to take antibiotics or probiotics 24-96 hours before FMT 
treatment day 1. 
 
Remind the subject to maintain a clear liquid diet on Day -1. 
 
Remind all subject to collect a stool sample (if not submitted), for subject groups 1-3, this 
should be before beginning the Magnesium Citrate or GoLytely bowel preparation. 
 
Remind the subject (treatment groups 1-3) to consume a 10 oz. bottle of Magnesium 
Citrate or 250ml of GoLytely bowel preparation for subjects with impaired kidney function 
(investigator or nurse practitioner will call in a prescription if needed) on evening (around 
6:00pm) before the FMT treatment Day 1 clinic visit. 
 
Remind the subject to take 4mg (2 capsules) of loperamide (Imodium) for study groups 
1-3 on the morning of the first day (Day 1) of the FMT treatment (can be taken within 12 
hour after FMT treatment if dose missed before). 
 
Remind the subject to continue taking routine prescription medications. 
 
Remind the subject to complete and bring the pretreatment diary card to the clinic visit. 
8.3 
FMT Treatment (Day 1) 
Subjects will arrive at the clinic on Treatment Day 1. 
8.3.1 Before Administering PRIM-DJ2727 
 
Medication containers (Day 1 and Day 2) of PRIM-DJ2727 will be taken 
from the EPDL to the clinic by study personnel. 
 
Obtain pretreatment stool sample from patient’s at-home collection and 
deliver to EPDL if stool sample has not been delivered to EPDL prior to 
Day 1 Treatment clinic visit. 
 
Obtain and review the pretreatment diary card with subject to determine 
baseline pattern of solicited symptoms. 

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 
Ensure subject (treatment groups 1-3) consumed a 10 oz. bottle of 
magnesium citrate or 250mL of GoLytely on Day -1. If bowel prep is 
missed, subject can still proceed with FMT and will be recorded as 
protocol deviation. 
 
Ensure subject (treatment groups 1-3) has taken 4mg (2 capsules) of 
loperamide (Imodium) that morning (can be taken within 12 hours after 
FMT if dose missed before). 
 
Confirm subject took their last doses of antibiotic treatment for the CDI 
24-96 hours before, non-dietary probiotics and bile-acid sequestrants are 
not being taken, and any antibiotic for non-CDI treatment has not been 
taken in the last 14 days. 
 
If applicable, perform urine pregnancy test. 
 
Collect pre-treatment weight and vital signs (blood pressure, heart rate, 
respiration rate, oral temperature). 
8.3.2 Administering PRIM-DJ2727 
 
Administer PRIM-DJ2727 capsules with water. Instruct subject that 
capsules are to be swallowed and not chewed. If subjects chew 
capsules, ask them to swallow and continue administering capsules. 
8.3.3 After Administering PRIM-DJ2727 
 
Observe subject in the clinic for > 60 minutes and assess for any 
adverse events. 
 
Ask subject if experienced any objectionable taste or smell or difficulty 
swallowing the capsules and general reaction on taking PRIM-DJ2727 
capsules. 
 
Collect post-treatment vital signs (blood pressure, heart rate, 
respiration rate, oral temperature). 
 
Provide subject with container of PRIM-DJ2727 for Day 2 treatment 
 
Remind the subject to take Day 2 PRIM—DJ2727 capsules empty 
stomach next morning with water. 
 
Remind subject to continue taking routine prescription medications as 
needed, but antibiotics, non-dietary probiotics and bile-acid sequestrants 
may not be taken. 
 
Release subject with IRB approved aftercare instructions, paper 
diaries, visit scheduler, safe antibiotics list and specimen request 
form. 

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8.4 
FMT Treatment (Day 2 Phone Visit) 
 
Ask subject to ensure PRIM-DJ2727 Day 2 capsules dose was taken. 
 
Ask for any adverse events since Day 1 assessment. 
 
Remind subject to follow the aftercare instructions provided on Day 1. 
 
Remind subject to take routine prescription medications as needed, but 
antibiotics, non-dietary probiotics and bile-acid sequestrants may not be taken. 
 
Remind subject to completely fill the diaries, and submit diaries and stools at 
follow-ups according to schedule and instructions provided by study team. 
 
A form letter may be sent to subject’s physician about FMT completion. 
8.5 
Phone Visit Follow-up Days 1(+3), 7(+3), 14(+3), 30(+10), 60(+10), 90(+10) and 180 
(+20) after treatment 
 
Contact the subject by phone and/or email at follow up days 1, 7, 14, 30, 60, and 90 
after treatment, within windows specified in Table 1 to: 
 
Remind subject to collect stool sample that will be placed in a transportation container 
with ice pack and delivered to the EPDL within 6 hours of collection if possible or as 
quickly as possible (excluding weekends and holidays) to be stored in the EPDL at -80o 
degrees for possible future testing. Remind subject to put stool collection date on 
provided container (if already submitted, stool collection date should be confirmed). 
Stool sample will not be collected for follow up visit Day 180. If hand delivery is not 
possible, stool sample may be shipped by Federal Express as expeditiously as possible. 
A FedEx shipping label, ice pack, Styrofoam container with shipping box and instructions 
will be provided to the subject to ship stool samples if they are not able to hand deliver to 
the EPDL. The EPDL will be closed on weekends and holidays. If follow-up day falls on 
Friday, Saturday or Sunday, subjects can collect and ship the sample on Thursday or 
the following Monday. 
 
Remind subject to bring completed diaries with the stool sample, or fax, or email, or mail 
to the study site. For diary copies received in email or fax, an attempt will be made to 
obtain the originals from subjects to be taken to the study site subsequently. Diary will 
not be collected on follow up visit day 1 after treatment. 
 
Assess subject for any adverse events, new illness symptoms, worsening of 
baseline illnesses including adverse events of special interest (new or worsening 
autoimmune conditions, and metabolic syndrome) and change in medication. 
Assess and review subject-reported weight data from diaries for AE (>5% change 
from baseline weight) at days 60 and 180 phone visits. 

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 
Assess subject for solicited symptoms such as diarrhea (passage of ≥ 3 watery stools 
per 24-hour period for two consecutive days), nausea, vomiting, gas/flatulence, 
abdominal distension, abdominal cramps/pain, constipation, rectal bleeding, 
fatigue/malaise, chills/shivering and fever (> 99.9 F) up to 60 days after treatment. 
 
If CDI recurrence is suspected, subjects should be recommended to contact their 
physician to perform a stool test for C. difficile. EPDL will test scheduled stool specimens 
and any unscheduled illness stool submitted up to 60-70 days after treatment for C. 
difficile toxins A/B in weekly batches but this should not delay treatment. If the test is 
positive, they should be treated by their physician. The Principal Investigator will be 
available for consultation with the attending physician. Subjects who are determined 
treatment failures by the investigator will not be followed further for clinical parameters. A 
form letter may be sent to subject’s physician about CDI recurrence. 
 
9. 
ASSESSMENT OF SAFETY AND EFFICACY 
9.1 
Assessment of Safety (Definition) 
9.1.1 Adverse event: 
Any untoward medical occurrence associated with the use of PRIM-DJ2727 whether or 
not considered drug related, and can therefore be 
 
Any symptom not previously reported by the subjects (medical history/pre- 
treatment diary). Wherever possible, a specific disease rather than individual 
associated signs and symptoms should be identified by the investigator. However, if 
an observed or reported sign or symptom is not considered a component of a 
specific disease by the investigator, it should be recorded as a separate adverse 
event. 
 
Clinical worsening of baseline parameters according to subject. 
 
A condition felt to be possibly related to treatment first detected or diagnosed 
after study drug administration 
All adverse events (AEs) that occur within 180-200 days after treatment will be 
recorded as indicated above. Recurrence of CDI is not to be recorded as  an 
adverse event unless hospitalization ≥ 24 hours is required for management, then 
recorded as serious adverse event. 
9.1.2 Suspected adverse reaction: 
Any adverse event for which there is a reasonable possibility that the study drug caused 
the adverse event. For the purposes of IND safety reporting, "reasonable possibility" means 

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there is evidence to suggest a causal relationship between the drug and the adverse event. 
9.1.3 Serious adverse event: 
Any adverse event or suspected adverse reaction is considered serious if in the view of the 
investigators it results in any of the following outcomes: 
 
Death 
 
Life-threatening adverse event 
 
Hospitalization ≥ 24 hours 
 
Prolongation of existing hospitalization 
 
Substantial disruption of the ability to conduct normal life 
functions 
 
Congenital abnormally/birth defect 
 
Important medical events that jeopardize the patient, such as 
allergic bronchospasm  requiring intensive treatment 
 
Persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions 
An emergency room visit without hospital admission will not be recorded as a 
serious adverse event (SAE) under this criterion, nor will hospitalization for a procedure 
scheduled or planned before signing of informed consent. 
Death and life-threatening AEs possibly related to the study are reported by study 
coordinator or investigator within 24 hours to the IRB. Other SAEs potentially related to the 
study will be reported to the IRB within 7 days. 
9.1.4 Unexpected adverse event: 
An adverse event or suspected adverse reaction is considered ‘unexpected’ if it is not 
described in the general investigational plan or is not listed at the specificity or severity that has 
been observed. 
9.1.5 Adverse events of special interest (weight gain, new or worsening autoimmune 
conditions, and metabolic syndrome): 
Adverse events of special interest such as new or worsening autoimmune conditions 
and metabolic syndrome will be asked from subjects during follow up phone visits. Subjects will 
be asked at the enrollment visit that how much they weighed before the first CDI episode to take 
into consideration any weight loss resulting from CDI bouts. To obtain baseline data, subjects 
will be weighed on treatment day 1 clinic visit prior to administration of FMT treatment. After 
FMT treatment, subjects will be recommended to measure weight at home each Sunday 
morning before eating and record on follow up diaries, providing they have a scale or balance. 

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To account for normal weight fluctuations, subject-reported weekly weight data from diaries will 
be assessed for AE (>5% change from baseline weight) at days 60 and 180 phone visits. 
9.2 
Medical Conditions 
1. During the follow up phone visits, the subject will be asked for any adverse 
event or medication change since the medical history/diary at baseline. 
2. Investigators will determine if any adverse event should be further studied. 
All actions will be recorded with medical condition and dates of adverse 
event and medication taken. The donor will be contacted and tested, if 
necessary. 
3. Subjects should be instructed on treatment days to contact the study 
personnel if they have any questions regarding an adverse event or the 
appropriateness of a medication after FMT. 
9.3 
Monitoring for Safety 
The following definitions of terms are guided by the International Conference of 
Harmonization and US Code of Federal Regulations (21 CFR 312.32). 
9.3.1 Severity 
The adverse event will be documented according to the following descriptors: 
 
Mild: associated with no limitation of usual activities or only slight 
discomfort 
 
Moderate: associated with limitation of usual activities or significant 
discomfort 
 
Severe: associated with inability to carry out usual activities or very 
marked discomfort 
9.3.2 Relationship 
The relationship of an adverse event to FMT will be assigned by the Investigator 
according to the following definitions: 
 
Probable: a reaction that follows a reasonable temporal sequence 
from the procedure that follows a known or expected response 
pattern to the suspected procedure and that could not be reasonably 
explained by the known characteristics of that subject’s clinical state 
 
Possible: a reaction that follows a reasonable temporal sequence 
from the procedure that follows a known or expected response 
pattern to the procedure but could readily have been produced by a 
number of other factors 

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 
Unlikely:  a  reaction  that  does  not  follow  a  reasonable   temporal 
sequence from the procedure but for which causality from FMT 
cannot be ruled out. 
 
Not related: a reaction for which sufficient data exist to indicate that 
the etiology is unrelated to the procedure 
9.4 
Pre-existing Signs and Symptoms and Medical Conditions 
Medical conditions that are present at or before the procedure that manifest 
with the same severity or frequency will not be recorded as an adverse event. Similarly, 
signs or symptoms related to a pre-existing disease will not be recorded as adverse 
event unless there is an increase in the severity or frequency of the signs or symptoms. 
The pre-existing conditions will be recorded in the Medical History. 
9.5 
Progression of Underlying Conditions and Anticipated events as an Adverse Event 
If the symptoms of the primary CDI continue on the study, this is not an AE. If new 
symptoms develop or worsen after treatment, this is considered an AE. 
Anticipated events include diarrhea, nausea, vomiting, gas/flatulence, abdominal 
distension, abdominal cramps/pain, constipation, rectal bleeding, fatigue/malaise, 
chills/shivering and fever (> 99.9 F), and may or may not be causally related to the FMT 
treatment or CDI. These anticipated events will be solicited from subjects at enrollment 
visit, via pre-treatment diary and at follow-up phone visits. For blinded treatment groups 
(1-3), mild to moderate diarrhea resulting from taking bowel prep starting a day before 
treatment and/or mild constipation from taking Imodium on treatment day up to one day 
after treatment are expected side effects, and should not be recorded as adverse 
events. 
9.6 
Recording and Documenting Adverse Event 
The study team must completely and promptly record each new adverse event and 
serious adverse event that occurs after the procedure, even if the relationship of 
adverse event to the procedure is assessed by the Investigator to be “unlikely” or “not 
related”. In addition, the investigator must document and follow serious adverse events 
and adverse events of special interest that occur from the procedure through 180-200 
days after the FMT. The Investigator should attempt, if possible, to establish a diagnosis 
based on the presenting signs and symptoms. If an adverse event meets the definition 
of a serious, unexpected and suspected (related to study drug/procedure) adverse 
reaction (SUSAR) then the Investigator must also complete the serious adverse event 
form/IND safety report, and send any supporting source documents to the University  of 

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Texas Health Science Center IRB and FDA as soon as the event is discovered within 
the defined timeline. 
At each visit, after the subject has had an opportunity to mention any problems 
spontaneously, the Investigator (or designee) will inquire about adverse event by asking 
the standard questions listed, such as: 
 
Have you had any new medical problems since your last visit? 
 
Have any medical problems present at your last visit changed, i.e., stopped, 
worsened, or improved? 
 
Have you taken any new medicines, other than study drug, since your last 
visit? 
Any spontaneous adverse event information provided by the subject will be 
recorded. If an adverse event has not resolved at the time of the final visit, the 
Investigator should evaluate the status of the adverse event at the follow-up phone 
contact and reflect the status of the adverse event (e.g. ongoing or resolved). 
The DSMB will issue a final report identifying adverse events related to study drug. 
9.7 
Investigator Reporting of Suspected Unexpected Serious Adverse event (SUSAR) 
Adverse events that meet all three definitions described above of a Suspected 
(related or possibly related to study drug or participation in the research), Unexpected 
and Serious Adverse Reaction (SUSAR) must be reported to the University of Texas 
Health Science IRB and FDA expeditiously. The investigator must report an adverse 
event as a suspected adverse reaction only if there is evidence to suggest a causal 
relationship between the drug and the adverse event. 
The investigator must report all suspected unexpected serious adverse reaction 
events to the University of Texas Health Science IRB/CPHS via iRIS within 7 calendar 
days after investigator recognizes or classifies the event as SUSAR unless the report 
involves the death of a participant, in which case the event needs to be reported to IRB 
within 24 hours after first knowledge by the investigator via facsimile or email or by 
telephone. 
The investigator must also report all suspected unexpected serious adverse 
reactions to the FDA as soon as possible but within a maximum of 15 calendar days of 
first knowledge by the investigator, unless the event is unexpected fatal or life- 
threatening suspected adverse reaction, in which case the event needs to be reported 
to the FDA as soon as possible but in no case later than 7 calendar days after the 
investigator's initial receipt of the information. 

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The reports should identify the subject by their unique subject number instead of 
names. The completed serious adverse event report forms will be used by the 
investigators in regulatory filings. The investigator is responsible for continuing to report 
to the University of Texas Health Science IRB and FDA within 15 calendar days of any 
new or relevant follow-up information obtained concerning the SUSAR event.  The 
results of any additional assessments conducted must also be reported to the University 
of Texas Health Science IRB and FDA. 
Serious and unexpected adverse events can be anticipated to occur during the 
course of the study regardless of drug exposure. Examples of such anticipated events 
may include but not limited to known consequences of any underlying disease or RCDI, 
events anticipated from any background regimen, events common in study population  
or recurrence or worsening of a condition relative to pretreatment baseline. Such events 
will not be reported individually as they are not informative as single cases to conclude 
that the event is a suspected adverse reaction. 
If an investigator is unsure about whether to report a finding as an adverse event, 
he will record the finding as an AE in study data. All adverse events will be reported in 
the annual and final clinical study reports as required by the applicable regulations. 
9.8 
Notification of Post-Study Serious Adverse event 
Investigators are not obligated to actively seek follow-up information for subjects 
with an adverse event after the conclusion of the study (i.e.>180-200 days after the  
FMT procedure). However, if the investigator becomes aware of an adverse event that 
occurs after the subject completes and the adverse event is recognized by the 
Investigator to be at least possibly related to study procedure, the investigator must 
notify the University of Texas Health Science Center IRB and FDA within 15 calendar 
days of making the determination about the event. 
9.9 
Grading Adverse Event Severity 
Adverse Events are to be graded by severity by the site investigator following FDA 
guidelines 
(http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulator 
yInformation/Guidances/Vaccines/ucm091977.pdf). For the classification of adverse 
events, severity is not the same as seriousness, which is defined in section  9.6. 
Severity is an indication of the intensity or a specific event (e.g., mild, moderate or 
severe). Classification of an event as serious relates to an event’s outcome or 
intervention  criteria  and  is  usually  associated  with  events  that  pose  a  threat  to a 

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HSC-SPH-17-0614 
subject’s life or functioning (Severity Grading Table). An event can be severe but not 
serious, such as a migraine. Using the definitions in Severity Grading Table at the end 
of the protocol, the site investigator will categorize the severity of an adverse event on 
the AE reports. 
9.10 
Halting Criteria 
Halting will take place if a serious adverse event is seen that is at least possibly 
related to FMT and if there is any suspected or confirmed transmission of a pathogen 
from the product to a study subject. The study will be halted temporarily until the DSMB 
makes a decision. Halting will also take place if the DSMB is concerned enough to stop 
the study to collect and analyze more clinical data. 
If a subject develops infection after FMT caused by a bacterial pathogen (e.g. 
urinary tract infection, sepsis, pneumonia), any potential pathogen isolated by a 
laboratory (e.g. E. coli from urinary tract) will be obtained if at all possible and compared 
with the same species identified from the donor using either culture or ribotyping 
techniques to determine if the FMT was responsible for transmission of a bacterium 
from the product to a subject. A form will be given to subjects to provide to their doctors 
if an infection is diagnosed after FMT, requesting to work with their laboratory to send 
the isolate to the University of Texas School of Public Health at 1200 Pressler Street, 
Room 740, Houston TX 77030 for further study. The research program will pay for any 
reasonable costs for obtaining and shipping of the bacteria. 
9.11 
Efficacy Endpoint 
The primary endpoints of the study are to evaluate the safety of lyophilized product by 
capsules with various doses and the prevention of subsequent bouts of CDI in 60 days 
post FMT; and to evaluate the safety of lyophilized product by capsules with same doses 
without bowel preparation and Imodium, and the prevention of subsequent bouts of CDI 
in 60 days post FMT without bowel preparation and Imodium. The secondary endpoint is 
to characterize improvement in microbiota diversity from baseline in subjects treated with 
various doses of lyophilized capsules. 
9.12 
Stool Analysis 
Stool samples for future metagenomics/microbiome analysis will be collected before 
FMT and at follow up days 1, 7, 14, 30, 60 and 90 and unscheduled visit (if any up to 60 
days) after FMT treatment. Stool samples collected up to 60 days after FMT treatment 
including unscheduled specimen (if any) will be tested for C. difficile toxins A/B at EPDL 
in weekly batches. All collected stool samples will be stored at -80C. Procedures for 

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stool sample collection and handling storage will be recorded. 
 
 
10. DATA COLLECTION AND ANALYSIS 
10.1 
Recording of Data 
The Investigator and/or designee must maintain adequate and accurate study 
related documents including source documents and regulatory documents. The study 
documents will be reviewed and signed by the investigators periodically. Study records 
will remain on file for a minimum of two years after the completion/termination of this 
study. 
10.2 
Statistical Methods 
10.2.1 
General Considerations 
All analyses will be performed, and all tables, figures, and data listings will be 
prepared using SAS (Cary, NC). Summary statistics for continuous variables will 
include the mean, standard deviation, median, minimum, and maximum value; 
categorical variables will be presented as counts and percentages. For all analyses, 
baseline is defined as the date of fecal transplantation. 
10.2.2 
Power Calculations 
Assuming recipients receiving 100g for both treatment days, 100g on the first treatment 
day and 50g on the second treatment, or 50g for both treatment days, or 100g for both 
treatment days without bowel prep and Imodium has 88%, 80%, 70% and 80% efficacy in 
preventing post RCDI respectively, it is determined that 348 recipients (1:1:1:1 ratio) would 
provide 85% power to detect a statistically significant difference in the distributions of efficacy 
between the 4 treatment groups at the two-sided α = 0.05 level of significance. Assuming 10% 
of patients would be lost to follow-up, 360 (90 in each group) recipients are planned. 
10.2.3 Analysis Populations 
Two primary analyses will be performed: 
1) 
Analysis for safety and efficacy between three groups (1-3) receiving varied 
doses of lyophilized product generated from stool (50g for both treatment days; 
100g on the first treatment day and 50g on the second treatment; 100g for both 
treatment days) 
2) 
Analysis for safety and efficacy between two groups (3 and 4) with and without 
bowel preparation and Imodium receiving same high doses of lyophilized 
product (100g for both treatment days). 

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University of Texas School of Public Health 
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 
All analyses will be conducted using the intent-to-treat population. Intent-to- 
treat is defined as all subjects who have started the procedure. 
 
Listings and summary tables with descriptive statistics will be prepared for 
demographic data (gender, date of birth, race/ethnicity), and medical history 
data. 
10.2.4 Randomization Procedures 
An independent statistician will develop a randomization list using SAS. 
Randomization in permuted blocks will be used to achieve balance across treatment 
groups. The randomization scheme consists of a sequence of blocks such that each 
block contains a pre-specified number of treatment assignments in random order. The 
purpose of this is to balance the randomization scheme at the completion of each 
block. The target sample size is 360 evaluable subjects. 
10.2.5 Analyses of Safety 
All adverse events and serious adverse events will be coded using the Medical 
Dictionary for Regulatory Activities Version 12.0, which is a registered trademark of the 
International Federation of Pharmaceutical Manufacturers and Associations. The 
number and percentage of subjects reporting at least one occurrence of an adverse 
event and/or serious adverse event for each system organ class and preferred term 
will be tabulated. Term will also be tabulated by severity and by the relationship to the 
procedure. For multiple occurrences of the same adverse event with different 
severities, the adverse event with the highest severity will be tabulated. For multiple 
occurrences of the same adverse event with different relationships to the procedure 
(related and not related); the adverse event will be tabulated as related. All adverse 
events and or serious adverse events for all subjects will be presented in data listings. 
Narratives will also be prepared for each serious adverse event. 
10.2.6 Efficacy Analyses 
While we will perform standard statistical analyses as outlined above, we do not 
expect to achieve statistical significance only trends. 
 
11. SUBJECT PAYMENT PROCESS 
Subjects will self-pay $1,500 by money order, cashier’s check or debit/credit card. 
Debit/credit card payments will be entered at the URL https://go.uth.edu/sph-cid by personnel 
at the University of Texas School of Public Health. A copy of transaction will be placed in the 
subject file. 

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12. PROTECTING PRIVACY 
This study protocol, documentation data, and all other information generated, will be held 
in strict confidence by the Investigators. The representatives of the Food and Drug 
Administration (FDA), the University of Texas Health Science Center at Houston, Kelsey 
Research Foundation, Kelsey-Seybold Clinics, and/or companies engaged with UTHealth 
for the commercialization of the results of the study may review research for the purposes 
of verifying research data. 
 
13. CONTACTS ABOUT STUDY 
For study details, the study coordinators at Kelsey Research Foundation |
| || 
For product related issues - Dr. Herbert L. DuPont |
| 
For subjects at Kelsey-Seybold Clinic - Dr. Ned Snyder |
| 
For University of Texas/Memorial Hermann Hospital - Dr. Andrew DuPont |
| The 
University of Texas Health Science Center Committee for the Protection of Human Subjects 
|
|. 
Kelsey Seybold Clinic Review Committee at |
| 

 
Center For Infectious Diseases 
University of Texas School of Public Health 
HSC-SPH-17-0614 
 
TABLE 1: STUDY SCHEDULE: 
 
Assessment and Procedures 
Enrollment 
(day -14 to -1) 
Treatment 
Days 
Follow Up and Safety Assessment Period via Telephone 
Un  
scheduled 
Visit 
Early 
Termination 
Visit 
Day 
1 
Day 
2 
Day 1 
(+3) 
Day 7 
(+3) 
Day 14 
(+3) 
Day 30 
(+10) 
Day 60 
(+10) 
Day 90 
(+10) 
Day 180 
(+20) 
Clinic 
Clinic 
Phone 
Phone 
Phone 
Phone 
Phone 
Phone 
Phone 
Phone 
Phone 
Phone 
Informed Consent 
X 
Inclusion/Exclusion Criteria 
X 
Demographics 
X 
Medical/CDI History 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization at University of 
Texas School of Public Health 
X 
Pre-treatment preparation 
reminder (day -4 to -1)1 
X 
Urine Pregnancy Test2 
X 
Confirmation of bowel prep 
and Imodium (groups 1-3)3 
X 
Vital signs4 and Weight5 
X 
Stool Collection 
X6 
X 
X 
X 
X 
X 
X 
X 
Study Drug Dose 
X 
X 
Diaries Distribution 
X 
X 
Diaries Receipt 7 
X 
X 
X 
X 
X 
X 
X 
X 
AE Assessment/Monitoring for 
Safety 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 Reminder can be via email or phone. 
2Perform urine pregnancy test only on female subjects’ of childbearing potential 
3 If bowel prep is missed, subject can still proceed with FMT (noted as protocol deviation). 
4Vital signs before treatment, observe, and repeat vitals after at least 60 minutes 
5 Weight measured before treatment only. Subjects will measure weight at home each Sunday morning before eating and record on diaries if they have a scale or 
balance. 
6Subject can collect stool any day after enrollment and before bowel prep on Day -1, and can bring stool sample on treatment day 1 clinic visit 
7 Diaries can be submitted with stool samples or emailed, faxed or mailed (original can be provided later) 
 
 
 
 
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TABLE 2: SEVERITY GRADING 
 
 
 
Parameter 
Grade 1: Mild 
Grade 2: 
Moderate 
Grade 
3: 
Severe 
Grade 4: 
Potentially Life- 
threatening 
Flatulence 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Symptoms 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
NA 
NA 
Belching 
(burping) 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Symptoms 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
NA 
NA 
Abdominal 
distension or 
bloating 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Symptoms 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
Symptoms 
causing inability 
to perform usual 
social and 
functional 
activities 
NA 

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Increased 
diarrhea 
Increase of ≤ 3 
stools over 
baseline per 
24- hour 
period 
Increase of 4 – 6 
stools over 
baseline per 24- 
hour period 
Bloody diarrhea 
if not present at 
baseline OR 
increase of ≥ 7 
stools over 
baseline per 
24- hour period 
OR IV fluid 
replacement 
indicated if not 
indicated at 
baseline 
Life-threatening 
consequences, e.g., 
hypotensive shock 
Abdominal 
cramping/pain 
Discomfort/pain 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Discomfort/pain 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
Discomfort/pain 
causing inability 
to perform 
usual social 
and functional 
activities 
Disabling pain causing inability 
to perform basic self-care OR 
inpatient hospitalization ≥ 24 
hours 
Constipation 
Occasional or 
intermittent 
symptoms, 
occasional use 
of stool 
softeners, 
laxatives, 
dietary 
modifications 
or enema 
Persistent 
symptoms with 
regular use of 
laxatives or 
enemas 
indicated 
Symptoms 
causing inability 
to perform 
usual social 
and/or 
functional 
activities 
Life-threatening consequences, 
e.g., obstruction, toxic 
megacolon 
Colitis 
No symptoms, 
Abdominal pain, 
Abdominal pain, 
Life-threatening 
regardless of 
mucus or blood 
fever, change in 
consequences, 
pathologic or 
in the stool 
bowel habits 
e.g., perforation, 
radiographic 
with ileus; 
bleeding, 
evidence of 
peritoneal signs 
ischemia, 
inflammation 
necrosis, toxic 
megacolon 

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Parameter 
Grade 1: Mild 
Grade 2: 
Moderate 
Grade 3: Severe Grade 4: Potentially Life- 
threatening 
Fever 
37.7 – 38.6°C 
38.7 – 39.3°C 
39.4 – 40.5°C 
> 40.5°C 
(99.9 – 101.5° 
(101.6 – 102.8° F) (102.9 – 104.9° 
(104.9° F) 
F) 
F) 
Fatigue/malaise 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Symptoms 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
Symptoms 
causing inability 
to perform 
usual social 
and functional 
activities 
Incapacitating fatigue/malaise 
symptoms causing inability to 
perform basic self-care 
functions 
Chills 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Symptoms 
Symptoms 
NA 
causing greater 
causing inability 
than minimal 
to perform usual 
interference with 
social and 
usual social and 
functional 
functional 
activities 
activities 
Rectal discomfort or No symptoms 
Symptomatic 
Symptoms 
NA 
irritation 
or symptoms 
with medical 
causing inability 
not requiring 
intervention 
to perform usual 
medical 
(topical 
social and 
intervention 
medications / 
functional 
treatments) 
activities or 
indicated 
requiring 
medical 
intervention 
other than 
topical 
medications / 
treatments 

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Parameter 
Grade 1: Mild 
Grade 2: 
Moderate 
Grade 3: 
Severe 
Grade 4: 
Potentially Life- threatening 
Rectal bleeding 
Mild or 
intermittent 
without 
transfusion 
Persistent without 
transfusion 
Requires 
transfusion 
Life-threatening consequences 
Nausea 
Transient (≤ 24 
hours) or 
intermittent 
nausea with 
nor or minimal 
interference 
with oral intake 
Persistent nausea 
resulting in 
decreased intake 
for 24-48 hours 
Persistent 
nausea 
resulting in 
decreased 
intake > 48 
hours OR 
aggressive 
rehydration 
indicated, e.g., 
IV fluids 
Life-threatening consequence, 
e.g., hypotensive shock 
Vomiting 
Transient (≤ 24 
hours) or 
intermittent 
vomiting with 
nor or minimal 
interference 
with oral intake 
Frequent 
episodes of 
vomiting with no 
or mild 
dehydration 
Persistent 
vomiting 
resulting in 
orthostatic 
hypotension OR 
aggressive 
rehydration 
indicated, e.g., 
IV fluids 
Life-threatening consequence, 
e.g., hypotensive shock 

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Parameter 
Grade 1: Mild 
Grade 2: 
Moderate 
Grade 3: 
Severe 
Grade 4: Potentially Life- 
threatening 
Hypotension 
NA 
Symptomatic, 
corrected with 
oral fluid 
replacement 
Symptomatic, 
IV fluids 
indicated 
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure 
Adverse event not 
identified elsewhere 
in this table 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
Symptoms 
causing greater 
than minimal 
interference with 
usual social and 
functional 
activities 
Symptoms 
causing inability 
to perform usual 
social and 
functional 
activities 
Symptoms causing inability to 
perform basic self-care 
functions OR medical or 
operative intervention indicated 
to prevent permanent 
impairment, persistent 
disability, or death 

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2. 
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3. 
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4. 
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