PRISM-EXT: An Open-Label Extension of CP101 Trials Evaluating Oral Full-Spectrum Microbiota™ (CP101) in Subjects With Recurrence of Clostridium Difficile Infection
Phase: PHASE2
Conditions: Clostridium Difficile Infection, Recurrent Clostridium Difficile Infection, C. Diff, CDI, Recurrent C. Diff, rCDI, C. Difficile, Recurrent CDI, FMT, Fecal Microbiota, Fecal Transplant
Sponsor: Finch Research and Development LLC.



 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CP101-CDI-E02 
Recurrent C. difficile Infection 
 
20 December 2019 
 
Finch Research and Development LLC – Confidential 
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PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CP101-CDI-E02 
Version: 
4.0 (Amendment 03) 
Protocol Title: 
PRISM-EXT: An Open-Label Extension of CP101 Trials 
Evaluating Oral Full-Spectrum Microbiota® (CP101) in Subjects 
with Recurrence of Clostridium difficile Infection 
Protocol (Version) Date: 
20 December 2019 
 
I acknowledge that I have read and understand the protocol named above and agree to conduct 
the study according to the protocol named above. I also agree and will adhere to terms and 
procedures in accordance with United States Food and Drug Administration (FDA)/Health 
Canada regulations, including all federal and locally applicable regulations and laws, and in 
compliance with the International Council for Harmonisation (ICH) GCP E6 (R2) guidelines. 
I assure that the study drug supplied by the Sponsor will be used only as described in the 
protocol named above. 
 
  
 
Signature of Principal Investigator  
 
 
 
 Date 
 
Printed Name of Principal Investigator 
 
 
  
 
 
  
 

 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CP101-CDI-E02 
Recurrent C. difficile Infection 
 
20 December 2019 
 
Finch Research and Development LLC – Confidential 
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1.0 
DOCUMENT HISTORY 
The summary of changes was moved to a separate document. 

 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CP101-CDI-E02 
Recurrent C. difficile Infection 
 
20 December 2019 
 
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2.0 
SYNOPSIS 
Title of Study:  
PRISM-EXT: An Open-Label Extension of CP101 Trial Evaluating Oral Full-Spectrum Microbiota® (CP101) in 
Subjects with Recurrence of Clostridium difficile Infection 
Protocol Number: CP101-CDI-E02 
Phase of Development: 2 (Open-Label Safety Study) 
Test Drug: Oral Full-Spectrum Microbiota® (CP101) 
Indication: Recurrent Clostridium difficile infection 
(CDI) 
Study Centers: Approximately 65 study sites in the United States and Canada 
Objectives: 
The objectives are: 
• 
To evaluate the safety of CP101 treatment in 1) Subjects in PRISM3 who had a CDI recurrence within 8 
weeks of receiving CP101 or placebo; OR 2) adults with recurrent CDI who are eligible for direct study 
entry into PRISM-EXT 
 
• 
To evaluate the efficacy of CP101 treatment in 1) Subjects in PRISM3 who had a CDI recurrence within 8 
weeks of receiving CP101 or placebo; OR 2) adults with recurrent CDI who are eligible for direct study 
entry into PRISM-EXT 
Methodology:  
This is an open-label study including: 
1. Eligible subjects from CDI-001 (subsequently referred to as PRISM3; NCT03110133).  
OR 
2. Adults with recurrent CDI who are eligible for direct study entry into PRISM-EXT 
 
Qualifying subjects from PRISM3, OR adults with recurrent CDI who are eligible for direct study entry may enroll 
into PRISM-EXT.  This study will evaluate the safety and efficacy in reducing recurrence of CDI in subjects 
enrolled in PRISM3 who had a CDI recurrence within 8 weeks of receiving CP101 or placebo and adults with 
recurrent CDI (direct entry). Subjects who experienced recurrent CDI will undergo screening procedures. Subjects 
who meet eligibility criteria will be eligible to be enrolled in the extension study and administered CP101.  
  
 Subjects 
will be monitored for recurrence of CDI, safety, and tolerability for 24 weeks following receipt of CP101. The 
primary efficacy and safety endpoints will be evaluated at 8 weeks post-treatment, and all subjects will continue to 
be followed for an additional 16 weeks for safety and recurrence of CDI.  
 
To qualify for the study, subjects must either have: 
1. Previously enrolled in PRISM3, had a CDI recurrence within 8 weeks of receiving CP101 or placebo, and 
have completed the PRISM3 end of study visit. The definition of recurrent CDI for subjects previously 
enrolled in PRISM3 is: a) diarrhea (> 3 unformed stools [Bristol Stool Scale score of 6 or 7] per day) for 2 
or more consecutive days; b) a stool specimen testing positive for Clostridium difficile (C. difficile) by the 
testing algorithm; and c) requiring a course of standard-of-care CDI antibiotics. Additionally, to qualify, 
recurrent CDI subjects must have received standard-of-care CDI antibiotics for the most recent CDI 
recurrence (for 10-42 days, with exact duration, antibiotic type, and dose at the discretion of the 
Investigator) and have an adequate clinical response, defined as ≤ 3 unformed stools in 24 hours for 2 or 
more consecutive days during standard-of-care CDI antibiotics prior to Treatment. 
OR 
2. Recurrent CDI eligible for direct study entry. Recurrent CDI for direct entry is defined as: a) ≥ 2 episodes 
of CDI occurring within the previous 6 months (inclusive of the current episode); b) received standard-of-

 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CP101-CDI-E02 
Recurrent C. difficile Infection 
 
20 December 2019 
 
Finch Research and Development LLC – Confidential 
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9. 
Initiation of any systemic cancer treatment (e.g. chemotherapy, radiotherapy, biologic, other) for 
active malignancy that is planned 8 weeks prior to Treatment or during the 8 weeks following 
Treatment. Subjects on maintenance treatment for malignancy may be treated after consultation with 
the Medical Monitor; 
10. 
Initiation or escalation of immunosuppressive agents, at the discretion of the Investigator, for any 
condition during the 8 weeks prior to Treatment or planned during the 8 weeks following Treatment. 
Subjects on stable immunosuppressive agents or short-courses may be treated after consultation with 
the Medical Monitor. NOTE: Solid organ transplant recipients are excluded. 
11. 
Compromised immune system, including, but not limited to, a known history of human 
immunodeficiency virus infection and a cluster of differentiation 4 count that is unknown or 
documented to be < 200 cells/mm3 within the last year, or an acquired immunodeficiency 
syndrome-defining illness; or at the discretion of the Investigator; 
12. 
Fecal transplant for any condition, regardless of route of administration in the last year or plans to 
undergo during the study; NOTE: CP101 use in PRISM3 is not exclusionary.  
13. 
Major intra-abdominal surgery (e.g., bowel resection) within the past 60 days prior to Screening 
(excluding appendectomy or cholecystectomy), history of total colectomy/ileostomy and/or planned 
invasive surgery/hospitalization during the study; 
a) NOTE: Subjects with history of bariatric surgery may be treated after consultation with the 
Medical Monitor; 
14. 
Use of a systemic antibiotic for any condition (other than CDI therapy for the current recurrence) 
during the Screening period, or any anticipated use of a systemic antibiotic for any condition other 
than CDI during the study for 8 weeks after Treatment. This includes subjects who have a known 
medical procedure that requires antibiotic prophylaxis (e.g., elective surgical procedure or dental 
procedure requiring prophylactic antibiotics) scheduled during the study; 
15. 
Unable to discontinue drugs that are specifically used as antiperistaltic agents (e.g., intended to control 
diarrhea, including but not limited to loperamide, diphenoxylate-atropine, or opioids); 
a) NOTE: Opioids prescribed for chronic pain or other indications are allowed if stable dose or 
decreasing dose during the course of the study. Changes in regimen should be discussed with the 
Medical Monitor; 
16. 
Active drug, chemical, or alcohol dependency as determined by the Investigator through history or 
optional toxicology screen; 
17. 
Enrollment in any other investigational drug or device study within 30 days prior to Treatment (Day 
1) or within 5 half-lives of the last dose of the previous investigational compound, whichever is 
longer; NOTE: CP101 use in PRISM3 is not exclusionary. 
18. 
Pregnant, breast-feeding, or considering becoming pregnant during the study;  
19. 
Clinically significant abnormal laboratory values including, but not limited to, white blood cell count 
≥ 15 × 109, laboratory evidence of acute kidney injury, or absolute neutrophil count of 
< 1× 109 neutrophils at Screening; or 
20. 
Any acute or chronic medical comorbidity, psychiatric, social, or other circumstances that, in the 
opinion of the Investigator, may interfere with study compliance, completion, or accurate assessment 
of study outcomes/safety. 
NOTE: To be eligible for Treatment, the above listed Inclusion/Exclusion Criteria as well as the following 
additional Inclusion Criteria must be satisfied: 
Treatment (Day 1) Inclusion Criteria: 
1. 
An outpatient prior to Treatment; 
a) NOTE: Subject may be enrolled while an inpatient in an acute care facility but must be 
discharged prior to Treatment on Day 1. Subjects residing in an assisted living center, long term 
care facility, or rehabilitation center may be treated; 

 
 
 
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Recurrent C. difficile Infection 
 
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3.0 
TABLE OF CONTENTS 
1.0 
DOCUMENT HISTORY.................................................................................................... 4 
2.0 
SYNOPSIS .......................................................................................................................... 5 
3.0 
TABLE OF CONTENTS .................................................................................................. 15 
4.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................... 19 
5.0 
INTRODUCTION ............................................................................................................ 21 
5.1 
Background Information on Clostridium difficile Colitis ............................................. 21 
5.2 
Fecal Microbiota Transplantation for Clostridium difficile Colitis .............................. 21 
5.3 
Product Summary and Rationale .................................................................................. 22 
5.4 
Experience with Full-Spectrum Microbiota®................................................................ 22 
5.4.1 
FSM®, Lyophilized Formulation ............................................................................ 23 
5.4.1.1 
 .................................................................................. 23 
5.4.1.1.1 
 ........................................................................ 25 
5.4.2 
Clinical Safety of FSM®, Frozen and Lyophilized ................................................. 27 
5.4.3 
Potential Risks and Benefits ................................................................................... 28 
5.4.4 
Dose Selection ........................................................................................................ 29 
5.5 
PRISM3 Study (CDI-001) ............................................................................................ 29 
6.0 
STUDY OBJECTIVES ..................................................................................................... 30 
7.0 
INVESTIGATIONAL PLAN ........................................................................................... 31 
7.1 
Overall Study Design .................................................................................................... 31 
7.2 
Study Sites .................................................................................................................... 33 
7.3 
Duration of Study .......................................................................................................... 33 
7.4 
Criteria for Study Termination...................................................................................... 33 
8.0 
SELECTION AND WITHDRAWAL OF SUBJECTS .................................................... 34 
8.1 
Inclusion Criteria .......................................................................................................... 34 
8.2 
Exclusion Criteria ......................................................................................................... 35 
8.3 
Treatment (Day 1) Inclusion Criteria ............................................................................ 37 
8.4 
Reasons for Study Discontinuation ............................................................................... 37 
8.5 
Subject Identification and Number Assignment ........................................................... 38 
9.0 
TREATMENT .................................................................................................................. 39 
9.1.1 
Description of Study Drug ...................................................................................... 39 
9.1.2 
Dose and Regimen of Study Drug .......................................................................... 39 
9.1.3 
Dosage Form, Manufacturing, Packaging, and Labeling of Study Drug................ 39 

 
 
 
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9.1.4 
Storage of Study Drug ............................................................................................ 40 
9.1.5 
Study Drug Accountability Procedures .................................................................. 40 
9.1.6 
Antibiotic Therapy .................................................................................................. 40 
9.1.7 
Concomitant Therapy and Restricted Medications ................................................. 40 
9.1.8 
Diet .......................................................................................................................... 41 
10.0 
ASSESSMENT OF EFFICACY ...................................................................................... 42 
10.1 
Stool Sample Analyses ................................................................................................. 42 
10.1.1 Bristol Stool Scale................................................................................................... 42 
10.1.2 
 ........................... 43 
10.1.3 Assessment for Antibiotic-Resistant Bacteria ........................................................ 43 
10.1.4 Clostridium difficile Toxin by Testing Algorithm and NAP1/BI/027 Subtyping... 44 
10.2 
Subject Memory Aid ..................................................................................................... 44 
10.2.1 Gastrointestinal Symptoms and Medications .......................................................... 47 
10.2.2 Unformed Stools and Diarrhea Assessments .......................................................... 47 
11.0 
ASSESSMENT OF SAFETY ........................................................................................... 48 
11.1 
Adverse Events ............................................................................................................. 48 
11.1.1 Serious Adverse Events .......................................................................................... 50 
11.1.1.1 
Serious Adverse Event Reporting .................................................................... 51 
11.1.1.2 
 ................................................................................................. 52 
11.2 
Contraception Requirements and Pregnancy ................................................................ 52 
11.2.1 Contraception Requirements ................................................................................... 52 
11.2.2 Pregnancy ................................................................................................................ 53 
11.3 
Vital Signs, Height, and Weight ................................................................................... 54 
11.4 
Physical Examinations .................................................................................................. 54 
11.5 
Clinical Safety Laboratory Evaluations ........................................................................ 54 
12.0 
STUDY PROCEDURES BY VISIT ................................................................................ 56 
12.1 
Study Visits Description ............................................................................................... 56 
12.1.1 Screening (On-site Visit) ........................................................................................ 56 
12.1.2 Treatment (Day 1; On-site Visit) ............................................................................ 57 
12.1.3 Week 1 (Telephone Contact) .................................................................................. 58 
12.1.4 Week 7 (Telephone Contact) .................................................................................. 58 
12.1.5 Week 8 (On-site Visit) ............................................................................................ 59 
12.1.6 Week 23 (Telephone Contact) ................................................................................ 59 
12.1.7 Week 24/Early Termination Visit (On-site Visit) ................................................... 59 

 
 
 
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Recurrent C. difficile Infection 
 
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12.1.8 Routine Telephone Follow-Up ............................................................................... 60 
12.1.9 Unscheduled Visit for Suspected Recurrence of CDI............................................. 60 
13.0 
STATISTICAL METHODS ............................................................................................. 62 
13.1 
Study Endpoints ............................................................................................................ 62 
13.1.1 Primary Endpoints .................................................................................................. 62 
13.1.2 Secondary Endpoints .............................................................................................. 62 
13.1.3 Other Safety Endpoint............................................................................................. 62 
13.1.4 
 .............................................................................................. 62 
13.2 
Statistical Analysis Overview ....................................................................................... 62 
13.3 
Analysis Populations ..................................................................................................... 63 
13.4 
Subject Disposition ....................................................................................................... 63 
13.5 
Efficacy Analysis .......................................................................................................... 64 
13.5.1 Primary Endpoint .................................................................................................... 64 
13.5.2 Secondary 
 Endpoints.................................................................... 64 
13.6 
Safety Analysis ............................................................................................................. 64 
13.7 
 ............................................................................................. 65 
13.8 
Determination of Sample Size ...................................................................................... 65 
13.9 
Quality control and quality assurance ........................................................................... 66 
13.10 Monitoring Procedures.................................................................................................. 66 
13.11 Study Site Training ....................................................................................................... 67 
14.0 
ETHICS............................................................................................................................. 68 
14.1 
Ethics and Good Clinical Practice ................................................................................ 68 
14.2 
Confidentiality Regarding Study Subjects .................................................................... 68 
14.3 
Future Use of Stored Specimens ................................................................................... 68 
14.4 
Institutional Review Board/Independent Ethics Committee......................................... 69 
14.5 
Informed Consent.......................................................................................................... 69 
14.6 
 .................................................. 71 
15.0 
DATA HANDLING AND RECORD KEEPING ............................................................ 72 
15.1 
Recording of Data and Retention of Documents .......................................................... 72 
15.2 
Case Report Forms ........................................................................................................ 72 
15.3 
Data Management ......................................................................................................... 73 
15.3.1 
......................................................................... 73 
15.3.2 Data Errors .............................................................................................................. 73 
15.3.3 
 ................................................................................. 73 

 
 
 
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Recurrent C. difficile Infection 
 
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4.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ARB 
Antibiotic-resistant bacteria  
BMI 
Body mass index 
BSS 
Bristol Stool Scale 
C. difficile 
Clostridium difficile 
CDI 
Clostridium difficile infection 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CRA 
Clinical Research Associate 
CRE 
Carbapenem-resistant Enterobacteriaceae 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSMC 
Data and Safety Monitoring Committee 
eCRF 
Electronic case report form 
EDC 
Electronic Data Capture 
ESBL 
Extended-spectrum ß-lactamase  
FDA 
Food and Drug Administration 
FMT 
Fecal microbiota transplantation 
FSM® 
Full-Spectrum Microbiota® 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
hCG 
Human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
IBD 
Inflammatory bowel disease 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
ITT 
Intent-to-Treat 
MDSEC 
Multidrug-sensitive Escherichia coli 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
NAP1 
North American Pulse-field type 1 
NCI 
National Cancer Institute 
PP 
Per-Protocol 

 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
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Recurrent C. difficile Infection 
 
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PPI 
Proton pump inhibitors 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
UTI 
Urinary tract infection 
VRE 
Vancomycin-resistant enterococci 
WHO 
World Health Organization 
 

 
 
 
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Recurrent C. difficile Infection 
 
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5.0 
INTRODUCTION 
5.1 
Background Information on Clostridium difficile Colitis 
Clostridium difficile (C. difficile) colitis or pseudomembranous colitis is a colitis (inflammation 
of the large intestine) resulting from infection with C. difficile, a spore-forming bacterium. It 
causes an infectious diarrhea called C. difficile-associated diarrhea. Latent symptoms of 
C. difficile infection (CDI) often mimic some flu-like symptoms and may mimic disease 
flare-ups in people with inflammatory bowel disease (IBD)-associated colitis. C. difficile releases 
toxins that may cause bloating and diarrhea with abdominal pain, which may become severe. 
CDI is a disease that is increasing in incidence and severity in the United States. [1] In a review 
from the National Hospital Discharge Survey, CDI incidence increased from 4.5 per 1,000 total 
adult discharges in 2001 to 8.2 per 1,000 total adult discharges in 2010. [2] The infections 
remain primarily healthcare-related but are seen more and more in the community setting. In 
2011, C. difficile was estimated to be responsible for approximately 500,000 infections and 
29,000 deaths. [3] The rate of severe CDI disease is also increasing, including CDI caused by 
strains such as ribotype 027 that produces a third toxin, or binary toxin, and shows resistance to 
fluoroquinolone antibiotics. There is evidence that infection with 027 is a significant risk factor 
for relapse. [4] This strain is more prevalent in healthcare institutions than in community-based 
infection cases (30.7% versus 18.8% in healthcare institutions and in community-based cases, 
respectively, p < 0.001).  
Patients with recurrent CDI may initially respond to treatment with oral vancomycin or 
metronidazole. The recurrence of CDI symptoms can be caused by germination of residual 
C. difficile spores or acquisition of a new CDI. Diarrhea often recurs within days to weeks after 
antibiotics are stopped, in part because the antibiotics themselves destabilize the microbial 
community structure of the distal gut. Fidaxomicin, introduced in 2011, [5] offers an alternative 
antibiotic treatment and is included in the American College of Gastroenterology guidelines for 
mild-to-moderate disease. 
5.2 
Fecal Microbiota Transplantation for Clostridium difficile Colitis 
Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy, has been used 
since the late 1950’s to treat patients with recurrent CDI who are unresponsive to antibiotic 
therapy. FMT has been used even longer in the veterinary field. A randomized trial comparing 
duodenal infusion administration of FMT showed superiority to vancomycin therapy in treating 
recurrent CDI. [6] Published clinical case studies and series [7,8] have expanded these data and 
show that FMT has high efficacy (85-100%) by a variety of gastrointestinal (GI) routes for 
treating patients with recurrent CDI. Routes of administration include retention enema, 
colonoscopic delivery, and nasogastric or nasojejunal tube. These findings have been detailed in 
updated reviews. [9,10] Use of FMT achieved similar results in a cohort of 
immunocompromised patients, [11] with few serious adverse events (SAEs), or procedure- or 
microbiota-related adverse events, including no related infectious complications. A study 
comparing a 10-day course of vancomycin followed by a pulse regimen with the same antibiotic, 
versus a 3-day course of vancomycin followed by FMT with stool by colonoscopy resulted in 
18 of 20 patients treated resolving C. difficile-related diarrhea. This was in contrast to 5 of 19 

 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
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Recurrent C. difficile Infection 
 
20 December 2019 
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Protocol CP101-CDI-E02 
Recurrent C. difficile Infection 
 
20 December 2019 
 
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6.0 
STUDY OBJECTIVES 
The objectives of this open-label extension study are: 
• To evaluate the safety of CP101 treatment in 1) subjects in PRISM3 who had a CDI 
recurrence within 8 weeks of receiving CP101 or placebo; OR 2) adults with recurrent 
CDI who are eligible for direct entry into PRISM-EXT. 
• To evaluate the efficacy of CP101 treatment in 1) subjects in PRISM3 who had a CDI 
recurrence within 8 weeks of receiving CP101 or placebo; OR 2) adults with recurrent 
CDI who are eligible for direct entry into PRISM-EXT. 

 
 
 
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Recurrent C. difficile Infection 
 
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c) Has received a course of standard-of-care CDI antibiotics for the most recent CDI 
episode (for 10-42 days, with exact duration, antibiotic type, and dose at the 
discretion of the Investigator); AND  
d) Has an adequate clinical response, defined as ≤3 unformed stools in 24 hours for 
2 or more consecutive days during standard-of-care CDI antibiotics prior to 
Treatment.  
4. 
Willingness to abstain from consuming non-dietary probiotics through Week 8 after 
Treatment; 
5. 
Women must fulfill at least 1 of the following criteria:  
a) Post-menopausal, defined as amenorrhea ≥ 1 year; 
b) Surgically sterile: hysterectomy, bilateral oophorectomy, or tubal ligation; or 
c) Abstinent or willing to use adequate contraception from Screening through the 
Week 24 visit, per Section 11.2; and 
6. 
Deemed to have life expectancy of 8 weeks or greater. 
8.2 
Exclusion Criteria 
1. 
Admitted to, or expected to be admitted to, an intensive care unit for any medical 
reason; 
a) NOTE: Residents of long term care facilities, such as nursing homes and 
rehabilitation centers, are eligible for study entry; 
b) NOTE: Patient visits to clinics, urgent care centers, acute care hospitals, or 
emergency departments are allowed; however, subject must be an outpatient prior 
to Treatment; 
2. 
Stools known to be positive for ova and/or parasite(s), or other enteric pathogens 
(e.g., Salmonella, Shigella, and/or Campylobacter) within 28 days prior to Screening; 
3. 
Inability to ingest capsules (e.g., severe nausea, vomiting, and/or dysphagia); 
4. 
Known or suspected toxic megacolon and/or known small bowel ileus; 
5. 
Prior history, evidence, or diagnosis of inflammatory bowel disease (e.g., Crohn’s 
disease, ulcerative colitis, indeterminate colitis, or microscopic colitis); 
6. 
Recent diagnosis (< 6 months prior to Screening) of diarrhea-predominant irritable 
bowel syndrome (post-infection or not related to an enteric infection). Subjects with 
diarrhea-predominant irritable bowel syndrome ≥ 6 months prior to Screening may be 
treated after consultation with the Medical Monitor;  
7. 
Current diagnosis of chronic diarrheal illness with pre-CDI baseline diarrhea 
(≥ 3 loose stools in a 24-hour period). This includes but is not limited to celiac 
disease, bile salt diarrhea, chronic pancreatitis, and short gut syndrome; 
8. 
Past administration of bezlotoxumab (Zinplava™), or past enrollment in a C. difficile 
vaccine study within 12 months of Treatment; 
9. 
Initiation of any systemic cancer treatment (e.g. chemotherapy, radiotherapy, 
biologic, other) for active malignancy that is planned 8 weeks prior to Treatment or 
during the 8 weeks following Treatment. Subjects on maintenance treatment for 
malignancy may be treated after consultation with the Medical Monitor; 

 
 
 
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10. 
Initiation or escalation of immunosuppressive agents, at the discretion of the 
Investigator, for any condition during the 8 weeks days prior to Treatment or planned 
during the 8 weeks following Treatment. Subjects on stable immunosuppressive 
agents or short-courses may be treated after consultation with the Medical Monitor. 
NOTE: Solid organ transplant recipients are excluded. 
11. 
Compromised immune system, including, but not limited to, a known history of 
human immunodeficiency virus infection and a cluster of differentiation 4 count that 
is unknown or documented to be < 200 cells/mm3 within the last year, or an acquired 
immunodeficiency syndrome -defining illness; or at the discretion of the Investigator;  
12. 
Fecal transplant for any condition, regardless of route of administration in the last 
year or plans to undergo during the study; NOTE: CP101 use is not exclusionary. 
13. 
Major intra-abdominal surgery (e.g., bowel resection) within the past 60 days prior to 
Screening (excluding appendectomy or cholecystectomy), history of total 
colectomy/ileostomy, and/or planned invasive surgery/hospitalization during the 
study; 
a) NOTE: Subjects with history of bariatric surgery may be treated after consultation 
with the Medical Monitor; 
14. 
Use of a systemic antibiotic for any condition (other than CDI therapy for the current 
recurrence) during the Screening period, or any anticipated use of a systemic 
antibiotic for any condition other than CDI during the study for 8 weeks after 
Treatment. This includes subjects who have a known medical procedure that requires 
antibiotic prophylaxis (e.g., elective surgical procedure or dental procedure requiring 
prophylactic antibiotics) scheduled during the study; 
15. 
Unable to discontinue drugs that are specifically used as antiperistaltic agents 
(e.g., intended to control diarrhea, including but not limited to loperamide, 
diphenoxylate-atropine, or opioids); 
a) NOTE: Opioids prescribed for chronic pain or other indications are allowed if 
stable dose or decreasing dose during the course of the study. Changes in regimen 
should be discussed with the Medical Monitor; 
16. 
Active drug, chemical, or alcohol dependency as determined by the Investigator 
through history or optional toxicology screen; 
17. 
Enrollment in any other investigational drug or device study within 30 days prior to 
Treatment (Day 1) or within 5 half-lives of the last dose of the previous 
investigational compound, whichever is longer; NOTE: CP101 use is not 
exclusionary. 
18. 
Pregnant, breast-feeding, or considering becoming pregnant during the study; 
19. 
Clinically significant abnormal laboratory values including, but not limited to, white 
blood cell count ≥ 15 × 109, laboratory evidence of acute kidney injury, or absolute 
neutrophil count of < 1× 109 neutrophils at Screening; or 
20. 
Any acute or chronic medical comorbidity, psychiatric, social, or other circumstances 
that, in the opinion of the Investigator, may interfere with study compliance, 
completion, or accurate assessment of study outcomes/safety. 

 
 
 
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Discontinued or withdrawn subjects will not be replaced. 
8.5 
Subject Identification and Number Assignment 
At Screening, site personnel will use interactive response technology (IRT) to register the 
subject. If the subject was previously enrolled in PRISM3, the subject’s identification number 
given from the PRISM3 trial will remain the same. If the subject is a direct entry into PRISM-
EXT at Screening, site personnel will use IRT to register the subject and a subject identification 
number in the format of XXX-XXXX will be generated. The same number will be used to 
identify the subject throughout the study, including subject transfer to another site, if applicable. 
This number will be entered on all documentation. A subject identification number will not be 
assigned to more than one subject. If a subject is not eligible to receive treatment, or if a subject 
discontinues from the study, the subject identification number cannot be assigned to another 
subject.  
 

 
 
 
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the reported GI symptoms, in order to make informed data-reporting decisions. If the Memory 
Aid is not returned to the clinic, the subject can contact study site staff during the Follow-up 
Period to report the above information. Study staff will add a source note to document the 
collected data, as needed. If a solicited adverse event is Grade 2 or greater on telephone contact 
at Week 1, an unscheduled visit will be arranged as soon as possible for evaluation and 
confirmation of the event. For all subsequent telephone contacts, including Week 7 and Week 
23, adverse events will be managed according to good clinical practice at the discretion of the 
treating physician.  
The solicited signs and symptoms will be entered in the eCRF. All solicited adverse events will 
not only be entered in the eCRF but also analyzed in the final study report, along with other 
safety analyses, and reported in an expedited manner if they meet the regulatory definition of a 
serious and unexpected suspected adverse reaction.  

 
 
 
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Table 10.b 
Solicited Adverse Event Severity Grading Table 
Event 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Life-Threatening) 
Abdominal 
cramping/pain/ 
tenderness 
Transient discomfort 
over baseline causing no 
or minimal interference 
with ADL  
Marked discomfort over 
baseline causing greater than 
minimal interference with 
ADL, but still acceptable  
Incapacitating discomfort 
over baseline causing 
considerable interference 
with ADL; unacceptable  
Disabling pain 
causing inability to 
perform basic 
activities  
Nausea 
Transient symptoms over 
baseline causing loss of 
appetite without 
alternation in eating 
habits  
Marked symptoms over 
baseline; oral intake 
decreased without significant 
weight loss, dehydration or 
malnutrition  
Incapacitating symptoms 
over baseline; inadequate 
oral caloric or fluid intake, 
tube feeding, TPN. or 
hospitalization indicated  
NA 
Dehydration  
Increased oral fluid 
indicated; dry mucous 
membranes; diminished 
skin turgor 
IV fluids indicated 
< 24 hours 
IV fluids or hospitalization 
indicated  
Life-threatening 
consequences; 
urgent intervention 
indicated  
Bloating 
Transient symptoms over 
baseline causing no or 
minimal interference 
with ADL  
Marked symptoms over 
baseline causing greater than 
minimal interference with 
ADL, but still acceptable  
Incapacitating symptoms 
over baseline causing 
considerable interference 
with ADL; unacceptable 
NA 
Poor appetite 
(e.g., anorexia) 
Loss of appetite without 
alteration of eating habits 
compared to baseline 
Oral intake altered without 
significant weight loss or 
malnutrition; oral nutrition 
supplements indicated  
Associated with significant 
weight loss or malnutrition 
(e.g., inadequate oral 
caloric and/or fluid intake); 
tube feeding or TPN 
indicated  
Life-threatening 
consequences; 
urgent intervention 
indicated  
Unformed stool 
(BSS score of 
6 or 7) 
Increase of ≤ 3 stools 
over baseline in 24 hours 
Increase of 4-6 stools over 
baseline in 24 hours 
Bloody diarrhea, if not 
present at baseline; increase 
of ≥ 7 stools over baseline 
in 24 hours; OR IV fluid 
replacement indicated  
Life-threatening 
symptoms and/or 
consequences 
(e.g., hypotensive 
shock) 
Vomiting 
1-2 episodes (separated 
by 5 minutes) in 24 hours 
3-5 episodes (separated by 
5 minutes) in 24 hours 
³ 6 episodes (separated by 5 
minutes) in 24 hours; tube 
feeding, TPN, or 
hospitalization indicated  
Life-threatening 
consequences; 
urgent intervention 
indicated  
Blood or pus in 
stool 
Asymptomatic or mild 
symptoms compared to 
baseline; clinical or 
diagnostic observations 
only; intervention not 
indicated 
Moderate symptoms 
compared to baseline; 
minimal, local, or 
non-invasive interventions 
indicated; limiting 
age-appropriate instrumental 
ADL 
Severe or medically 
significant symptoms 
compared to baseline but 
not immediately 
life-threatening; 
hospitalization or 
prolongation of existing 
hospitalization indicated; 
disabling; limiting self-care 
ADL  
Life-threatening 
consequences; 
urgent intervention 
indicated 
Stool incontinence  
Transient symptoms over 
baseline; occasional use 
of pads required 
Marked symptoms over 
baseline; daily use of pads 
required 
Severe symptoms over 
baseline; elective operative 
intervention indicated 
NA 
Fecal urgency 
Transient symptoms over 
baseline causing no or 
minimal interference 
with ADL 
Marked symptoms over 
baseline causing greater than 
minimal interference with 
ADL, but still acceptable 
Incapacitating symptoms 
over baseline causing 
considerable interference 
with ADL; unacceptable 
NA 
Fever 
38.0-39.0°C 
(100.4-102.2°F) 
> 39.0-40.0°C 
(102.3-104.0°F) 
> 40.0°C (> 104.0°F) for 
≤ 24 hours 
> 40.0°C 
(> 104.0°F) for 
> 24 hours 
ADL = activities of daily living; BSS = Bristol Stool Scale; IV = intravenous; NA = not applicable; 
TPN = total parenteral nutrition. 
Source: Adapted from the National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) 

 
 
 
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10.2.1 Gastrointestinal Symptoms and Medications 
The presence of any GI symptoms should be captured with the assistance of the Memory Aid. 
Any new medications will be recorded (name/type, dose, frequency, and reason for taking). 
10.2.2 Unformed Stools and Diarrhea Assessments 
The primary clinical efficacy outcome is prevention of CDI recurrence. Recurrent CDI is defined 
as a) diarrhea (> 3 unformed stools [BSS score of 6 or 7] per day) for 2 or more consecutive 
days; b) a stool specimen testing positive for C. difficile by a testing algorithm (see Figure 10.a); 
and c) requiring a course of standard-of--care CDI antibiotics. Testing for CDI will be as 
described in Section 10.1.4. 
If a subject has CDI recurrence in the study, then CDI will not be recorded as an adverse event; 
instead, it will be considered an on-study recurrent CDI episode and will be included in the 
determination of efficacy (Section 13.5). If the on-study recurrent CDI episode results in 
hospitalization of the subject for more than 24 hours, this will be recorded as an SAE and 
reported per the criteria for safety reporting. The occurrence and frequency of stools and 
occurrence of urgency and stool incontinence will be assessed at Screening and through 
completion of the Week 1 telephone contact. 
In addition, subjects are to report diarrhea (as defined above) promptly to the study coordinator 
at any time during the study. The study coordinator will then instruct the subject on when he/she 
should return to the clinic and whether a stool sample should be collected based on the signs and 
symptoms.  

 
 
 
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11.0 
ASSESSMENT OF SAFETY 
11.1 
Adverse Events 
The adverse event reporting period will begin from the signing of the informed consent form and 
will continue through study completion or, in the case of withdrawal, until the outcome is 
determined. Adverse events will be assessed at each visit and through telephone contact with the 
subject. A neutral question, such as “How have you been feeling since your last visit?” may be 
asked. The term “adverse event” could include any of the following events that develop or 
increase in severity during the course of the study: 
1. 
Any signs or symptoms, regardless of severity, and whether or not ascribed to the 
study drug; 
2. 
Any clinically significant laboratory abnormality; or 
3. 
Any abnormality detected during physical examination. 
Any laboratory abnormalities deemed clinically significant by the Investigator must be reported 
as an adverse event. A clinically significant abnormality is a confirmed abnormality (by repeat 
test) that is changed sufficiently from baseline so that, in the judgment of the Investigator, a 
change in management is warranted. This alteration may include: monitoring the laboratory test 
further, initiating other diagnostic tests or procedures, changing ongoing treatment, or 
administering new treatment. If the abnormal laboratory test is part of a known syndrome or 
disease, the syndrome/disease, and not the individual laboratory test, should be recorded as the 
adverse event.  
The primary clinical efficacy outcome is prevention of CDI recurrence. Recurrent CDI is defined 
as a) diarrhea (> 3 unformed stools [BSS score of 6 or 7] per day) for 2 or more consecutive 
days; b) a stool specimen testing positive for C. difficile by a testing algorithm (see Figure 10.a); 
and c) requiring a course of standard-of-care CDI antibiotics. If a subject has CDI recurrence in 
the study, then CDI will not be recorded as an adverse event; instead, it will be considered an 
on-study recurrent CDI episode and will be included in the determination of efficacy (Section 
13.5). If the on-study recurrent CDI episode results in hospitalization of the subject for more than 
24 hours, this will be recorded as an SAE and reported per the criteria for safety reporting. 
Surgical procedures themselves are not adverse events; they are therapeutic measures for 
conditions that require surgery. The condition for which the surgery is required may be an 
adverse event, if it occurs or is detected during the study period. Planned surgical measures 
permitted by the clinical study protocol and the condition(s) leading to these measures are not 
adverse events, if the condition(s) is (are) known before the start of the study drug dosing. In the 
latter case, the condition should be reported as medical history. 
The Clinical Investigator will follow all subjects withdrawn from the study due to any adverse 
event until the outcome is determined and where appropriate, additional written reports will be 
provided. 
The intensity of an adverse event will be graded according to the scale below in addition to the 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 
for Grading the Severity of Adult Adverse Events. The clinical significance of the adverse event 
is determined by the Investigator. The Investigator is encouraged to consult with the 
Medical Monitor, as needed, to discuss the case. 

 
 
 
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• Concomitant drug- 
o The other drugs the subject is taking or the treatment the subject receives should be 
examined to determine whether any of them might be recognized to cause the event in 
question. 
• Known response pattern for this class of study drug- 
o Clinical and/or preclinical data may indicate whether a particular response is likely to 
be a class effect. 
• Exposure to physical and/or mental stresses- 
o The exposure to stress might induce adverse changes in the recipient and provide a 
logical and better explanation for the event. 
• The pharmacology and pharmacokinetics of the study drug- 
o The known pharmacologic properties (absorption, distribution, metabolism, and 
excretion) of the study drug should be considered. 
11.1.1 Serious Adverse Events 
SAEs are defined as any untoward medical occurrence that at any dose:  
• Results in death;  
• Is life-threatening (the term "life-threatening" in the definition of "serious" refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to 
an event which hypothetically might have caused death if it were more severe); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability and/or incapacity;  
• Results in a congenital anomaly and/or birth defect; or 
• Is any important medical event, based on medical and scientific judgment, which may not 
be immediately life-threatening or result in death or hospitalization, but may pose 
substantial risks to the subject or may require medical intervention to prevent 1 of the 
other outcomes listed in the definition above. 
Another definition of SAE that should be classified and reported as such for this protocol 
includes: 
• Suspected transmission of an infectious agent (e.g., any pathogenic organism, virus, or 
infectious particle) via the study drug. 
The following hospitalizations or situations will not be reported as SAEs in this study unless an 
unpredicted complication results in prolonged hospitalization: 
• Visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered "important medical event" or the event is 
life -threatening); 
• Elective surgery, planned prior to signing consent (recorded on Medical History); 
• Admission for a planned medical/surgical procedure prior to signing consent (recorded 
on Medical History); 

 
 
 
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Week 24 visit. For the purposes of the study, highly effective contraception is defined as: 
• Combination of an established form of hormonal contraception (oral, injected, or 
implanted) or an intrauterine device or intrauterine system;  
And at least 1 of the following: 
• A physical barrier method of contraception with use of a spermicide such as condom or 
occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream 
suppository. The use of barrier contraceptives should always be supplemented with the 
use of a spermicide, unless not available in a country; 
• Male vasectomy with negative semen analysis documentation. The use of contraception 
does not apply if the male partner has been vasectomized at least 6 months before dosing; 
and/or 
• Complete abstinence may be considered an acceptable method of contraception at the 
discretion of the Investigator. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, or post-ovulation methods) and withdrawal are not considered acceptable 
methods of contraception. 
The combination of 2 barrier methods, periodic abstinence (e.g., calendar, ovulation, 
symptothermal, or post-ovulation methods), and withdrawal are not considered acceptable 
methods of contraception.  
11.2.2 Pregnancy 
Although pregnancy is not always considered an adverse event or SAE by regulatory definition, 
for this study, pregnancies must be handled as SAEs for data transmission purposes. In the event 
that a pregnancy complication occurs or elective termination of a pregnancy is required for 
medical reasons, then the complication will be recorded as an adverse event or SAE as 
appropriate. 
While elective and uncomplicated induced abortion not required for medical reasons does not 
constitute an adverse event or SAE (even if the subject is hospitalized to undergo abortion), 
spontaneous abortion is considered a fatal event and must be reported as an adverse event and 
SAE as appropriate.  
Any pregnancy complication or elective termination of a pregnancy for medical reasons will be 
recorded as an adverse event or, if appropriate, as an SAE. A spontaneous abortion is always 
considered an SAE and should be reported as described in the SAE Reporting section 
(Section 11.1.1.1). 
Women of childbearing potential enrolled in this study will have serum human chorionic 
gonadotropin (hCG) pregnancy testing administered during Screening and urine pregnancy 
testing thereafter. Women who are post-menopausal for ≥ 1 year or surgically sterile will not 
undergo pregnancy testing. 
Any pregnancy and/or suspected pregnancy that occurs during the study in a female subject 
should be reported. Any pregnancy and/or suspected pregnancy will be followed for outcome.  
The Investigator must notify the Sponsor immediately after the pregnancy is confirmed. If the 
subject has received the study drug prior to becoming pregnant, the subject will continue the 
efficacy assessment and follow-up periods, and measures of safety and efficacy will be obtained.  

 
 
 
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The subject will be followed until the outcome of the pregnancy is determined. It is the 
responsibility of the Investigator to obtain and document pregnancy information on the most 
recent Pregnancy Report Form. Furthermore, any SAE occurring as outcome of the pregnancy 
must be reported to the Medical Monitor.  
11.3 
Vital Signs, Height, and Weight 
Vital signs (blood pressure, heart rate, and temperature) will be assessed per standard-of-care as 
listed in the Schedule of Observations (Table 1.a). Vital signs will be measured before and after 
(within 60 minutes) study drug administration. Body temperature should be taken at all visits 
where vital signs are measured. Vital signs and body temperature should also be measured at 
time of recurrence, if any. 
Body weight and height (Screening only) will be measured per standard-of-care (the height will 
not be re-measured if it has been collected in the PRISM3 trial). Height and weight will be used 
to calculate body mass index (BMI). A pre-CDI medically documented weight or BMI will be 
obtained. BMI will be calculated from weight collected at Week 8 and Week 24 as well. 
11.4 
Physical Examinations 
A complete physical examination (including evaluation of general appearance/mental status; 
head, eyes, ears, nose, throat; and the following body systems: skin, heart, lungs, abdomen, and 
extremities) will be performed at the time points listed in the Schedule of Observations 
(Table 1.a).  
The Investigator will perform the symptom-directed physical examinations based on subjects’ 
signs and symptoms at the time points listed in the Schedule of Observations (Table 1.a). 
11.5 
Clinical Safety Laboratory Evaluations 
Samples of blood and urine are scheduled for collection at Screening, at Treatment (Day 1) prior 
to study drug administration, and at Week 8; specific tests performed at each visit are shown in 
Table 11.a. In the event that the Screening period is planned for > 30 days, additional clinical 
safety laboratory evaluations may be conducted at the discretion of the Investigator.  
The total volume of blood collected at scheduled study visits will be up to 123 mL. Additional 
follow-up samples for clinical laboratory testing should be obtained as clinically indicated. A 3-
mL serum aliquot will be collected at each time point and archived for safety testing as may be 
required by emergence of adverse conditions. 
Subjects with a white blood cell count ≥ 15 × 109, laboratory evidence of acute kidney injury, or 
an absolute neutrophil count of < 1× 109 neutrophils at Screening are to be excluded from the 
study.  
All clinical laboratory testing, with the exception of optional drug testing or on-site urine 
pregnancy testing during the treatment period for females of childbearing potential, will be 
performed by the central clinical laboratory. 

 
 
 
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BMI). Reasons for the categories will be described in the Clinical Study Report. Graphical 
displays may be presented for selected results.  
A Statistical Analysis Plan (SAP) will be written to describe in detail all statistical analyses 
planned for the study. It will be accompanied by mock Tables, Figures, and Listings. The SAP 
will be finalized and approved by signatures and dates prior to database lock. The SAP will take 
precedence over the protocol for details about the statistical analyses for the study. In addition to 
the SAP, other graphical representations of the results may be produced after review of the data 
(post-hoc).  
Verbatim terms recorded for medical history conditions, surgical history procedures, and adverse 
events will be mapped to a SOC and preferred term using the Medical Dictionary for Regulatory 
Activities (MedDRA), and all prior and concomitant medications will be coded using the World 
Health Organization (WHO) Drug Dictionary. 
13.3 
Analysis Populations  
All analyses will be performed separately for subjects previously enrolled in PRISM3 and direct 
entry subjects as well as for both groups combined. 
In each group four analysis populations are defined as follows: 
Intent-to-Treat population  
(ITT or All enrolled) 
All subjects enrolled.  
The modified ITT population  
(mITT or Full Analysis population)  
 
All subjects in the ITT population who receive at least 
1 capsule of study drug at Treatment (Day 1). The 
mITT population will be the primary analysis 
population for all efficacy analyses.  
Per-Protocol population  
(PP population) 
 
All subjects in the mITT population who have not 
violated key Inclusion/Exclusion Criteria, Treatment 
Criteria, and/or have not had a major protocol 
deviation in a way that could influence the efficacy 
assessment.  
Safety population 
All enrolled subjects who received at least 1 capsule of 
study drug. Unless otherwise stated, the Safety 
population will be the default analysis population for 
all safety analyses.  
13.4 
Subject Disposition 
Subject disposition will be presented for all subjects. The number of subjects who are treated, 
complete the study, and discontinue from the study will be provided. The reasons for early 
discontinuation will also be presented. These tables and listings will be presented for data 
through Week 8 and then cumulative through Week 24. Differences in study disposition between 
Week 8 and Week 24 will be explored by characterizing the subject demographics and 
subsequent outcomes. 

 
 
 
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13.9 
Quality control and quality assurance 
In addition to the routine monitoring procedures, the Sponsor or its designees, may conduct 
audits of clinical research activities in accordance with internal standard operating procedures to 
evaluate compliance with the study protocol, GCP regulations, and ICH GCP E6 Guideline. The 
Sponsor, its designee, or a regulatory authority may wish to conduct an audit or inspection 
(during the study or after its completion). If an inspection is requested by a regulatory authority, 
the Investigator will inform the Sponsor immediately that this request has been made. 
13.10 Monitoring Procedures 
Qualified representatives of the Sponsor or its designees (e.g., CRAs) will monitor the study 
according to a predetermined written monitoring plan. Monitoring visits provide the Sponsor 
with the opportunities to do the following: 
• Evaluate the progress of the study; 
• Verify the accuracy and completeness of eCRFs; 
• Assure that all protocol requirements, applicable laws and/or regulations, and 
Investigator’s obligations are being fulfilled; and 
• Resolve any inconsistencies in the study records. 
The Investigator must allow the CRAs to periodically review, at mutually convenient times 
during the study and after the study has been completed, all eCRFs and office, hospital, study 
drug, and laboratory records supporting the participation of each subject in the study. The eCRFs 
and other documentation supporting the study must be kept up-to-date by the Investigator and the 
research staff at the study site. These study materials must be available for review by the CRA, 
and/or other qualified representatives of the Sponsor, at each monitoring visit. 
Before study initiation, at an initiation visit conducted on site, by video conference, or at an 
Investigator’s meeting, a Sponsor representative will review the protocol, eCRFs, and other 
study documents with the Investigators and their staff. During the study, the Sponsor CRA or 
designee will visit the study site regularly to check the completeness of subject records, accuracy 
of entries on the eCRFs, adherence to the protocol and to ICH GCP, progress of enrollment, and 
also to ensure that study drug is being stored, dispensed, and accounted for according to 
specifications. 
The Investigator must give the CRA access to relevant hospital or clinical records to confirm 
their consistency with the eCRF entries. No information in these records about the identity of the 
subjects will leave the study center. The Sponsor monitoring standards require full verification 
for the presence of informed consent, HIPAA authorization, adherence to the 
Inclusion/Exclusion Criteria, documentation of SAEs, and recording of efficacy and safety 
variables. Additional checks of the consistency of source data with the eCRFs will be performed 
according to the study -specific monitoring plan. Representatives of the Sponsor must be allowed 
to visit all study site locations periodically to assess the data quality and study integrity. On site, 
they will review study records and directly compare them with source documents, discuss the 
conduct of the study with the Investigator, and verify that the facilities remain acceptable, 
amongst other duties.  

 
 
 
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In addition, the study may be evaluated by the Sponsor’s internal auditors and government 
inspectors who must be allowed access to eCRFs, source documents, other study files, and study 
facilities. Sponsor audit reports will be kept confidential. The Investigator must notify the 
Sponsor promptly of any inspections scheduled by regulatory authorities, and promptly forward 
copies of inspection reports to the Sponsor. 
The CRA will follow an “Issue Escalation” process in order to ensure that each issue identified 
during a monitoring visit is appropriately documented, reported, and resolved in a timely manner 
in accordance with the plan’s requirements. 
13.11 Study Site Training 
The Sponsor or their designated representative will provide investigational staff training prior to 
study initiation. Training topics will include but are not limited to: study background and 
rationale, clinical data summary, protocol review, ICH GCP, study specific procedures, study 
drug review, adverse event reporting, eCRFs, study documentation, informed consent process, 
study monitoring, and enrollment of women of childbearing potential, as applicable. 

 
 
 
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14.0 
ETHICS 
14.1 
Ethics and Good Clinical Practice 
This study will be conducted in compliance with the appropriate protocol, ICH GCP guidelines, 
the principles of the Declaration of Helsinki, and all other applicable regulatory requirements. 
Participating study sites must obtain written approval of the study protocol, informed consent 
documents, other supporting documents, and any advertising for subject recruitment from an 
appropriate IEC or IRB prior to study initiation. Any amendments to the protocol or consent 
materials must be approved in writing before they are implemented. 
Study personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks. This study will not use the services of study 
personnel where sanctions have been invoked or where there has been scientific misconduct or 
fraud (e.g., loss of medical license, debarment). All potential serious breaches must be reported 
to the Sponsor immediately. A serious breach is a breach of the conditions and principles of ICH 
GCP in connection with the study or the protocol, which is likely to affect, to a significant 
degree, the safety or physical or mental integrity of the subjects of the study or the scientific 
value of the study. 
The regulatory files at the study site should contain all required regulatory documents, 
study -specific documents, and important communications. Regulatory files will be checked at 
each participating study site for regulatory compliance prior to study initiation, throughout the 
study, as well as at the study closure. 
14.2 
Confidentiality Regarding Study Subjects 
Applicable data privacy laws and regulations must be adhered to. Investigators must assure that 
the privacy of subjects, including their personal identity and all personal medical information, 
will be protected at all times, as required by law. Study sites may be required by their institutions 
to obtain authorization from subjects for use of Protected Health Information. Study sites will be 
responsible for communicating with their IRBs/IECs and obtaining the appropriate approvals or 
waivers to be in regulatory compliance with HIPAA. In eCRFs and other study documents 
submitted to the Sponsor or its designee, subjects will be identified by their initials, subject 
number, date of birth, and gender. Personal medical information may be reviewed and/or copied 
for research, quality assurance, and/or data analysis. This review may be conducted by the CRA, 
properly authorized persons on behalf of the Sponsor, an independent auditor, IRBs/IECs or 
regulatory authorities. Personal medical information will always be treated as confidential. 
14.3 
Future Use of Stored Specimens 
Subject stool samples will be collected, stored, and tested as indicated in the protocol. In 
addition, subjects will be asked to give informed consent to store samples for future testing 
within the study, as may be required by emergence of adverse conditions. 
 
 

 
 
 
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14.4 
Institutional Review Board/Independent Ethics Committee 
Before implementing this study, the protocol, the proposed ICF, and other information provided 
to subjects must be reviewed by an IRB/IEC. A signed and dated statement that the protocol, 
ICF, subject recruitment materials/process (e.g., advertisements), and any other written 
information to be provided to subjects have been approved by the IRB/IEC must be given to the 
Sponsor or designee prior to study initiation. The name and occupation of the chairperson and 
the members of the IRB/IEC (preferred) or the IRB’s Health and Human Safety Assurance 
number must be supplied to the Sponsor or its designee. This committee, as required by local law 
or procedure, will approve any amendments to the protocol that need formal approval. The 
IRB/IEC will also be notified of all other administrative amendments (i.e., administrative 
changes). The Investigator or Sponsor should also provide the IRB/IEC with a copy of the 
Investigator’s Brochure or product labeling, information to be provided to subjects and any 
updates. The Investigator or Sponsor should provide the IRB/IEC with reports, updates, and 
other information (e.g., expedited safety reports, amendments, and administrative letters) 
according to regulatory requirements or institution procedures.  
Study sites will be responsible for maintaining signed ICFs as source documents for quality 
assurance review and regulatory compliance. 
14.5 
Informed Consent 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout study participation. Extensive discussion of risks and possible 
benefits of study participation will be provided to subjects and their families, if applicable. 
Investigators must ensure that subjects, or, in those situations where consent cannot be given by 
subjects, their legally acceptable representatives, are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they 
volunteer to participate. The Investigator or Sub-Investigator will explain to each subject (or 
legally authorized representative) the nature of the research study, its purpose, the procedures 
involved, the expected duration of subject participation, alternative treatment, potential risks and 
benefits involved, and any discomfort that may occur during the subject’s participation in the 
study. Each subject will be informed that participation in the study is voluntary and that he/she 
may withdraw from the study at any time and that withdrawal of consent will not affect his/her 
subsequent medical treatment or relationship with the treating physician. Each subject will be 
provided the opportunity to ask questions and have them answered by the Investigator or Sub-
Investigator. The ICF should be given by means of a standard written statement, written in non-
technical language. The subject should read and consider the statement before signing and dating 
it and should be given a copy of the signed ICF. No subject can enter the study and no study-
related procedures can be done before his/her informed consent has been obtained. The 
Investigator must submit the ICF with the protocol for IRB/IEC approval.  
The Sponsor will supply a proposed ICF template that complies with regulatory requirements, 
includes all elements required by ICH GCP and applicable regulatory requirements, and is 
considered appropriate for the study. The sample ICF will adhere to the ethical principles that 
have their origin in the Declaration of Helsinki. Any changes to the proposed ICF suggested by 
the Investigator must be agreed to by the Sponsor or its designee before submission to the 

 
 
 
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IRB/IEC, and a copy of the approved version must be provided to the Sponsor or designee after 
IRB/IEC approval. 
Investigators must: 
1. 
Provide a copy of the ICF and written information about the study in the language in 
which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood. 
2. 
Allow time necessary for the subject or the subject’s legally acceptable representative 
to enquire about the details of the study. 
3. 
Obtain an ICF signed and personally dated by the subject or the subject’s legally 
acceptable representative and by the person who conducted the informed consent 
discussion. 
4. 
Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF and any 
other information to be provided to the subjects, prior to the beginning of the study, 
and after any revisions are completed for new information.  
5. 
If informed consent is initially given by a subject’s legally acceptable representative 
or legal guardian, and the subject subsequently becomes capable of making and 
communicating their informed consent during the study, then consent must 
additionally be obtained from the subject. 
6. 
Revise the ICF whenever important new information becomes available that is 
relevant to the subject’s consent. The Investigator, or a person designated by the 
Investigator, should fully inform the subject or the subject’s legally acceptable 
representative or legal guardian, of all pertinent aspects of the study and of any new 
information relevant to the subject’s willingness to continue participation in the study. 
This communication should be documented. 
7. 
The ICF must also include a statement that the Sponsor and regulatory authorities 
have direct access to subject records. Subjects unable to give their written consent 
(e.g., stroke subjects or subjects with severe dementia) may only be enrolled in the 
study with the consent of a legally acceptable representative. The subject must also be 
informed about the nature of the study to the extent compatible with the subject’s 
understanding, and should he/she become capable, personally sign and date the ICF 
as soon as possible. The explicit wish of a subject unable to give his or her written 
consent, who is capable of forming an opinion and assessing this information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should 
be considered by the Investigator. The rights, safety, and well-being of the study 
subjects are the most important considerations and should prevail over interests of 
science and society. 
A copy of the signed ICF will be given to the subject for his/her records. The rights and welfare 
of the subjects will be protected by emphasizing to them that the quality of their clinical care will 
not be adversely affected if they decline to participate in this study. 
The consent process will be documented in the clinical or research record.  

 
 
 
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Recurrent C. difficile Infection 
 
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18.0 
REFERENCES
1. 
Gerding DN, Lessa FC. The epidemiology of Clostridium difficile infection inside and 
outside health care institutions. Infect Dis Clin North Am. 2015 Mar;29(1):37-50. 
PubMed PMID: 25582647. 
2. 
Reveles KR, Lee GC, Boyd NK, Frei CR. The rise in Clostridium difficile infection 
incidence among hospitalized adults in the United States: 2001-2010. Am J Infect 
Control. 2014 Oct;42(10):1028-32. PubMed PMID: 25278388. 
3. 
Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the 
United States. N Engl J Med. 2015 Feb;372(9):825-34. PubMed PMID: 25714160. 
4. 
Marsh JW, Arora R, Schlackman JL, Shutt KA, Curry SR, Harrison LH. Association of 
relapse of Clostridium difficile disease with BI/NAP1/027. J Clin Microbiol. 
2012 Dec;50(12):4078-82. PubMed PMID: 23052318. Pubmed Central 
PMCID: PMC3502988. 
5. 
Marra F, Ng K. Controversies around epidemiology, diagnosis and treatment of 
Clostridium difficile infection. Drugs. 2015 Jul;75(10):1095-118. 
PubMed PMID: 26113167. 
6. 
van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for 
recurrent Clostridium difficile. N Engl J Med. 2013 Jan;368(5):407-15. 
PubMed PMID: 23323867. 
7. 
Patel NC, Griesbach CL, DiBaise JK, Orenstein R. Fecal microbiota transplant for 
recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience. Mayo Clin 
Proc. 2013 Aug;88(8):799-805. PubMed PMID: 23910407. 
8. 
Dutta SK, Girotra M, Garg S, et al. Efficacy of combined jejunal and colonic fecal 
microbiota transplantation for recurrent Clostridium difficile Infection. Clin 
Gastroenterol Hepatol. 2014 Sep;12(9):1572-6. PubMed PMID: 24440222. 
9. 
Drekonja D, Reich J, Gezahegn S, et al. Fecal Microbiota Transplantation for Clostridium 
difficile infection: A systematic review. Ann Intern Med. 2015 May;162(9):630-8. 
PubMed PMID: 25938992. 
10. 
Khoruts A, Weingarden AR. Emergence of fecal microbiota transplantation as an 
approach to repair disrupted microbial gut ecology. Immunol Lett. 
2014 Dec;162(2 Pt A):77-81. PubMed PMID: 25106113. 
11. 
Kelly CR, Ihunnah C, Fischer M, et al. Fecal microbiota transplant for treatment of 
Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 
2014 Jul;109(7):1065-71. PubMed PMID: 24890442. 
12. 
Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal microbiota 
transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium 
difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43. 
PubMed PMID: 25728808. 
13. 
Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and 
prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 
Apr;108(4):478-98; quiz 99. PubMed PMID: 23439232. 
 
 

 
 
 
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Recurrent C. difficile Infection 
 
20 December 2019 
 
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14. 
Debast S, Bauer M, Kuijper E. European Society of Clinical Microbiology and Infectious 
Diseases: Update of the treatment guidance document for Clostridium difficile infection. 
Clin Microbiol and Infect. 2014 Mar:20(suppl 2):1-26. PubMed PMID: 24118601. 
15. 
Staley C, Hamilton MJ, Vaughn BP, et. al. Successful resolution of recurrent Clostridium 
difficile infection using freeze-dried, encapsulated fecal microbiota; pragmatic cohort 
study. Am J Gastroenterol. 2017 Jun;112(6):940-7. PubMed PMID: 28195180. 
16.  
IND 17336, CP101, Section 9, Prior Human Use, Original IND submitted January 2017. 
17. 
Osman M, O’Brien K, Stoltzner Z, et. al. Safety and efficacy of fecal microbiota 
transplantation for recurrent Clostridium difficile infection from an international public 
stool bank: Results from a 2,050 patient multi-center cohort. Poster session presented at: 
Infectious Diseases Week 2016 October 26-30 New Orleans, LA. 
18. 
Moayyedi P, Yuan Y, Baharith H, Ford A. Faecal microbiota transplantation for 
Clostridium difficile associated diarrhoea: A systematic review of randomised controlled 
trials. Med J Aust. 2017 Aug;207(4):166-72. PubMed PMID: 28814204. 
19. 
Lee C, Steiner T, Petrof E, et. al. Frozen vs fresh fecal microbiota transplantation and 
clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: A 
randomized clinical trial. JAMA. 2016 Jan;315(2):142-9. PubMed PMID: 26757463. 
20. 
Kelly C, Khoruts A, Staley C, et. al. Effect of fecal microbiota transplantation on 
recurrence in multiply recurrent Clostridium difficile infection: A randomized trial. Ann 
Intern Medicine. 2016 Nov;165(9), 609-16. PubMed PMID: 27547925. 
21. 
De Leon L, Watson J, Kelly C. Transient flare of ulcerative colitis after fecal microbiota 
transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol. 
2013 Aug;11(8):1036-8. PubMed PMID: 23669309. 
22. 
Qazi T, Amaratunga T, Barnes E, Fischer M, Kassam Z, Allegretti J. The risk of 
inflammatory bowel disease flares after fecal microbiota transplantation: systematic 
review and meta-analysis. Gut Microbes. 2017 Nov:8(6):574-588. 
PubMed PMID: 28723262. 
23. 
Brandt L, Aroniadis O, Mellow M, et. al. Long-term follow-up of colonoscopic fecal 
microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 
2012 Jul:107(7), 1079-87. PubMed PMID: 22450732. 
24. 
Quera R, Espinoza R, Estay C, Rivera D. Bacteremia as an adverse event of fecal 
microbiota transplantation in a patient with Crohn's disease and recurrent Clostridium 
difficile infection. J Crohns Colitis. 2014 Mar;8(3):252-3. PubMed PMID: 24184170. 
25. 
Leffler D, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015 Apr;372(16): 
1539-48. PubMed PMID: 25875259. 

 
 
 
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Protocol CP101-CDI-E02 
Recurrent C. difficile Infection 
 
20 December 2019 
 
Finch Research and Development LLC – Confidential 
Page 79 of 79 
19.0 
APPENDICES  
19.1 
Electronic Product Labels for Standard CDI Antibiotics 
19.1.1 Oral Vancomycin 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/50606slr020_vancocin_lbl.pdf 
19.1.2 Fidaxomicin 
https://www.merck.com/product/usa/pi_circulars/d/dificid/dificid_pi.pdf 
19.1.3 Metronidazole 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/12623slr059_flagyl_lbl.pdf