Conditions: Clostridium Difficile Infection Recurrence
Keywords: Clostridium Difficile Infection CP101 Crestovo FMT CDI C. difficile C. diff Recurrent Clostridium Difficile Infection Recurrent C. diff Recurrent CDI Finch Fecal transplant Fecal microbiota transplant rCDI Finch Therapeutics
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 206
Healthy volunteers: no

Brief summary:
Subjects with recurrent C. difficile infection will receive an oral dose of CP101 capsules one time in Treatment Group I or matching placebo one time in Treatment Group II. The purpose of this study is to demonstrate the safety and effectiveness of CP101 to prevent recurrence of C. difficile.

Subjects with confirmed C. difficile recurrence within 8 weeks after administration of study drug (CP101 or placebo) may be eligible to enroll in the open-label extension study (CP101-CDI-E02) and will receive CP101.

Detailed description:
This is a Multicenter, Double-Blind, Parallel-Arm, Placebo-Controlled, Phase 2 Study of the Efficacy, Safety, and Tolerability of Oral Full-Spectrum MicrobiotaTM (CP101) in Subjects with Recurrence of Clostridium difficile Infection (CDI).

Arms:
arm 1: Full Spectrum Microbiota Capsule arm 2: Matching Placebo Capsule

Interventions: intervention 1: Full Spectrum Microbiota intervention 2: Placebo
Intervention descriptions: intervention 1: Orally administered donor derived microbiota intervention 2: Placebo for CP101

Protocol document:
Prot_000.pdf: 
 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
01 March 2019 
 
Finch Research and Development LLC – Confidential 
Page 1 of 79 
 
 
 
CLINICAL STUDY PROTOCOL  
 
A Multicenter, Double-Blind, Parallel-Arm, Placebo-Controlled, Phase 2 
Study of the Efficacy, Safety, and Tolerability of Oral Full-Spectrum 
Microbiota® (CP101) in Subjects with Recurrence of Clostridium difficile 
Infection (PRISM3) 
 
Sponsor: 
Finch Research and Development LLC 
200 Inner Belt Road, Suite 400 
Somerville, MA 02143  
Protocol Number: 
CDI-001 
IND Number: 
17336 
Investigational Product: 
Full-Spectrum Microbiota® (CP101) 
Indication: 
Recurrent Clostridium difficile infection (CDI) 
Development Phase: 
2 
Sponsor’s Responsible  
 
Medical Officer: 
 
 
 
 
 
 
Version: 
Version 3.0 (22 December 2016) 
Version 4.0 (13 March 2017) Amendment 01  
Version 5.0 (31 August 2017) Amendment 02 
 
Version 6.0 (22 February 2018) Amendment 03 
Version 7.0 (01 March 2019) Amendment 04 
 
 
 
CONFIDENTIALITY STATEMENT 
This document contains confidential information of Finch Research and Development LLC (the Sponsor) which 
must not be reproduced, published, or otherwise disclosed to anyone other than the recipient(s), members of the 
ethics committee(s) or regulatory authorities. The document and the information contained herein cannot be used 
for any purpose other than the evaluation or conduct of the clinical investigation described in this document 
without prior written approval from Finch Research and Development LLC. The foregoing shall not apply to 
disclosure required by applicable laws or governmental regulations. Notice must be provided to Finch Research 
and Development LLC of any such disclosure as soon as practicable. 
 
 




 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
Finch Research and Development LLC – Confidential 
Page 3 of 79 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CDI-001 
Version: 
7.0 (Amendment 04) 
Protocol Title:  
A Multicenter, Double-Blind, Parallel-Arm, Placebo-Controlled, 
Phase 2 Study of the Efficacy, Safety, and Tolerability of Oral 
Full-Spectrum Microbiota® (CP101) in Subjects with Recurrence 
of Clostridium difficile Infection (PRISM3) 
Protocol (Version) Date:  
01 March 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)/International 
Council for Harmonisation (ICH) guidelines, including all federal and locally applicable 
regulations and laws. 
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 CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
Finch Research and Development LLC – Confidential 
Page 4 of 79 
1.0 
DOCUMENT HISTORY 
The summary of changes was moved to a separate document. 




 
 
 
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Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
Finch Research and Development LLC – Confidential 
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The primary clinical outcome is recurrence of CDI and is defined as 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 a testing algorithm (see figure below); and c) requiring a course of 
standard-of-care CDI antibiotics. Secondary outcomes include assessment of decolonization of antibiotic-resistant 
bacteria (ARB) and 
 
 
  
 
 
Subject Population: 
Approximately 200 subjects 18 years of age or older, who experience recurrent CDI, and who respond to a 
standard-of-care CDI antibiotic regimen for the most recent CDI episode will be randomized to study drug. 
Inclusion/Exclusion Criteria: 
Study eligibility will be evaluated during the Screening visit, which will take place prior to the Randomization visit 
(Day 1).  
Inclusion Criteria: 
1. 
Ability to provide written informed consent; 
2. 
Men or women 18 years of age or older; 
3. 
Recurrent CDI* as defined by: 
a)  3 episodes of CDI, with 2 episodes occurring within the previous 12 months (inclusive of the 
current episode); OR  
b) 2 episodes of CDI occurring within the previous 6 months (inclusive of the current episode) AND 
65 years of age or older; 
*NOTE: CDI is defined by: 
a) History of diarrhea ( 3 unformed stools per day) for 2 or more consecutive days; AND 
b) A stool specimen documented as testing positive for C. difficile within 60 days prior to 
Randomization. Testing for CDI may include: 
 
 
 
 
 
 
 
 
 


 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
Finch Research and Development LLC – Confidential 
Page 7 of 79 
 
 
 
 
AND 
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 Randomization. 
4. 
Willingness to abstain from consuming non-dietary probiotics through Week 8 after Randomization; 
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. 
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 Randomization; 
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 randomized 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 Randomization;  
9. 
Initiation of any systemic cancer treatment (e.g. chemotherapy, radiotherapy, biologic, others) for 
active malignancy that is planned 8 weeks prior to Randomization or during the 8 weeks following 
Randomization. Subjects on maintenance treatment for malignancy may be randomized 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 Randomization or planned during the 8 weeks following 
Randomization. Subjects on stable immunosuppressive agents or short-courses may be randomized 
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 cluster of differentiation 4 count that is unknown or 


 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
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Page 8 of 79 
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; 
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 randomized 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 Randomization. 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 Randomization 
(Day 1) or within 5 half-lives of the last dose of the previous investigational compound, whichever is 
longer; 
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 Randomization, the above listed Inclusion/Exclusion Criteria as well as the following 
additional Inclusion Criteria must be satisfied: 
Randomization (Day 1) Inclusion Criteria: 
1. 
An outpatient prior to Randomization; 
a) NOTE: Subject may be enrolled while an inpatient in an acute care facility, but must be 
discharged prior to Randomization on Day 1. Subjects residing in an assisted living center, 
long-term care facility, or rehabilitation center may be randomized; 
2. 
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); 
3. 
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 Randomization; and 
4. 
 
 
 


Full-Spectrum Microbiota® – Oral CP101 
Protocol CDI-001 
Recurrent C. difficile Infection 
 01 March 2019 
Finch Research and Development LLC – Confidential 
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Test Product, Dose, and Mode of Administration: 
The active ingredient of CP101, 
, is derived from the stools of normal healthy donors 
who are highly screened, tested, and monitored in a clinically structured donation program. 
 
 
  
 
 
 Eligible subjects will be allocated to 1 of 2 treatment 
groups in a 1:1 ratio: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Not applicable. 
Duration of Treatment: 
, including active drug (CP101) and placebo; subjects will be monitored through 
Week 24 following Randomization. 
Criteria for Evaluation: 
Efficacy: Clinical signs and symptoms of recurrent CDI, including frequency and consistency of stools, will be 
confirmed by a C. difficile stool testing algorithm, as described above. North American Pulse-field type 1 
(NAP1)/BI/027 subtyping will be performed if symptoms are consistent with recurrent CDI. 
 
, stool will be assessed for ARB, 
 
 An overview of evaluations to be performed is outlined in 
the Schedule of Observations (Table 1.a). 
Safety: Safety will be assessed via adverse event monitoring, concomitant medication use, physical examinations, 
vital signs, electrocardiograms, clinical laboratory safety analyses, and pregnancy testing (if female is of 
childbearing potential). 
Statistical Methods: 
For the primary efficacy endpoint, the proportion of subjects with sustained clinical cure, defined as absence of 
recurrent CDI through Week 8, will be tested using a Chi-Square test for treatment group differences. The primary 
efficacy analysis will be conducted for the Intent-to-Treat (ITT), modified ITT (mITT), and Per-Protocol (PP) 
populations. 
 
 
 
 
 
 
 
 
 
  
Endpoints: 
Primary Endpoints: 
•
Proportion of subjects experiencing sustained clinical cure, defined as absence of recurrent CDI, through
Week 8, and
•
Incidence of adverse events through Week 8


 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
Finch Research and Development LLC – Confidential 
Page 10 of 79 
Secondary Endpoints: 
The secondary endpoints are: 
• 
Proportion of subjects experiencing recurrent CDI with ribosomal NAP1/BI/027 C. difficile subtype 
through Week 8; 
• 
Time-to-first recurrent CDI episode during the study (Day 1 through Week 8); 
• 
Proportion of subjects experiencing sustained clinical cure at Week 24; 
• 
Time-to-first recurrent CDI episode during the study (Day 1 through Week 24); 
• 
Incidence of hospitalization due to recurrent CDI through Week 8 and through Week 24; 
• 
Incidence of decolonization of ARB, defined as vancomycin-resistant enterococci, extended-spectrum 
ß-lactamase organisms, or carbapenem-resistant Enterobacteriaceae at Week 8 and Week 24 among 
co-colonized subjects; 
• 
 
 
• 
Change in body mass index (BMI) by Week 8 and Week 24 relative to medically documented pre-CDI 
BMI; and 
• 
 
Other Safety Endpoint: 
The other safety endpoint is: 
• 
Incidence of adverse events through Week 24. 
 
 
 
 
 
 
 
 
 
 




 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
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Page 12 of 79 
1 The Screening visit includes the entire Screening period up to the time of Randomization. The Screening period is limited to 60 days 
between the signing of informed consent and Randomization. Where referenced as the Screening visit, study-required tests and 
procedures may be performed on 1 day or across multiple days, but preferably closest to the time of Randomization. During the 
Screening visit, potential study subjects will be fully informed regarding the nature of the study and possible adverse events, and will 
receive a copy of the informed consent form for review. All subjects must have a stool specimen documented as testing positive for 
C. difficile performed at the site or local laboratory within the previous 60 days from Randomization. After the Screening visit, 1 phone 
call will be made to the subject as a reminder for the upcoming Randomization visit. 
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.  
2 
 
 
 
 
If the subject experiences diarrhea for 2 or more consecutive days during the washout period, the Investigator should 
contact the Medical Monitor. 
3 If a subject discontinues from the study early, the subject will be asked to return to the clinic within 14 days after discontinuation to 
undergo the Week 24 assessments prior to study discharge. All other subjects will have their final visit at Week 24  14 days. 
4 The signing of the informed consent form initiates the screening process. Obtain signed, written informed consent and permission to use 
Protected Health Information (in accordance with the Health Insurance Portability and Accountability Act). Informed consent must be in 
place prior to performing any study procedures. 
5 To be performed prior to study drug administration. NOTE: Missing stool sample does not preclude the subject from Randomization.  
6 Includes CDI history (e.g., number of prior episodes) and a pre-CDI medically documented weight or BMI will be obtained.  
7 Subjects will be issued a paper Memory Aid at the time of informed consent and given training on its use. The Memory Aid data will be 
discussed at the Screening visit and Randomization visit (Day 1) after drug administration. At Week 1 telephone call, the Memory Aid 
data will be discussed and subjects will be reminded to bring it to the Week 4 visit.  
8 To be performed in the event of a suspected CDI recurrence at the timepoints marked as (X). For stool sample, instructions for at-home 
stool sample collection, handling, storage, and transportation/shipping are included in the Laboratory Manual and an instruction sheet 
will be distributed to subjects. 
9. Subjects will be contacted by telephone. Subjects will be asked about any adverse events, including occurrence of diarrhea. If a subject 
reports diarrhea, the study staff will review the timing of those episodes and the subject may be asked to submit a stool sample for 
C. difficile testing. Subjects will be asked about their general well-being, changes in their health status, medications, and over-the-
counter remedies, and will be reminded about their next study visit. From Screening through study completion, subjects will be reminded 
to record all relevant information on their Memory Aid, as applicable. If a solicitated 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 adverse events will be managed according to good clinical practice at the discretion of the treating 
physician.  
      At Week 4, 8, 24 visits every effort will be made to conduct an on-site assessment. However, under extenuating subject circumstances 
that make an on-site visit not feasible and after all reasonable measures to enable the subject’s on-site visit have been exhausted, a 
telephone assessment will be conducted.   
 10 Randomization will occur 
 
. Eligible subjects will be allocated to 1 of 2 treatment groups in a 1:1 ratio.  
11 For the most recent CDI episode, the subject will have received standard-of-care CDI antibiotics (10-42 days; with exact duration, 
antibiotic type, and dose at the discretion of the Investigator). 
12 
 
13 Subjects will have completed a mandatory washout 
 
 
 
 Study drug will be administered under direct supervision of 
clinic staff as an oral dose (
. Subjects will 
remain in the clinic for observation for at least 1 hour post-dose.  
14 A complete physical examination will be performed (including evaluation of general appearance/mental status; head, eyes, ears, nose, 
throat; and the following body systems: skin, heart, lungs, abdomen, and extremities). 
15 The Investigator will perform symptom-directed physical examinations based on subjects’ signs and symptoms. 
16 Vital signs (blood pressure, heart rate, and temperature) will be measured per standard-of-care. 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. 
17 Height will be measured at the Screening visit only per standard-of-care.  
18 Subjects should be weighed per standard-of-care. Height and weight will be used to calculate BMI. BMI will be calculated from weight 
collected at Week 8 and Week 24 as well. 
19  Vital signs will be measured before and after (within 60 minutes) study drug administration. 
20 Single 12-lead ECG will be performed per standard-of-care at Screening and at Week 8. Evidence of clinically significant abnormalities 
during the Screening visit may result in exclusion from the study. At Week 24, the 12-lead ECG will be performed only if there are 
findings at the Week 8 ECG, or if the subject has symptoms requiring an ECG.  


 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
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21 
 
 
 
 
 
 
 
 
 
 
       
22 Optional (at the discretion of the Investigator) drug screen includes cotinine (not exclusionary), amphetamines, barbiturates, 
benzodiazepines, cannabinoids (not exclusionary), cocaine, opiates (not exclusionary), and alcohol. 
23 Women of childbearing potential enrolled in this study will have serum hCG pregnancy testing administered during Screening and urine 
pregnancy testing thereafter, at the discretion of the Investigator. Women who are post-menopausal for  1 year or surgically sterile will 
not undergo pregnancy testing. 
24 The adverse event reporting period will begin with informed consent and will continue through study completion or, in the case of 
withdrawal, until the outcome is determined. Adverse events will be collected after study drug administration on Day 1. Subjects will be 
asked about any adverse events, including occurrence of diarrhea. If a subject reports diarrhea, the study staff will review the timing of 
those episodes and the subject may be asked to submit a stool sample for C. difficile testing. Subjects will be asked about their general 
well-being, changes in their health status, medications, and over-the-counter remedies. 
25 
 
 
 
 
26 Stool sample collection for the assessment for ARB, defined as vancomycin-resistant enterococci, extended-spectrum ß-lactamase 
organisms, or carbapenem-resistant Enterobacteriaceae, will be performed on samples obtained at Screening, Randomization (Day 1) 
prior to study drug administration, Week 8, and Week 24. Assessment for ARB may also be performed at any other visit or time point 
(e.g., time of recurrence, if any). 
 
 


 
 
 
Full-Spectrum Microbiota® – Oral CP101 
 
Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
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3.0 
TABLE OF CONTENTS 
1.0 
DOCUMENT HISTORY.................................................................................................... 4 
2.0 
SYNOPSIS .......................................................................................................................... 5 
3.0 
TABLE OF CONTENTS .................................................................................................. 14 
4.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................... 18 
5.0 
INTRODUCTION ............................................................................................................ 20 
5.1 
Background Information on Clostridium difficile Colitis ............................................. 20 
5.2 
Fecal Microbiota Transplantation for Clostridium difficile Colitis .............................. 20 
5.3 
Product Summary and Rationale .................................................................................. 21 
5.4 
Experience with Full-Spectrum Microbiota®................................................................ 21 
5.4.1 
FSM®, Lyophilized Formulation ............................................................................ 22 
5.4.1.1 
 .................................................................................. 22 
5.4.1.1.1 
 ........................................................................ 24 
5.4.2 
Clinical Safety of FSM®, Frozen and Lyophilized ................................................. 26 
5.4.3 
Potential Risks and Benefits ................................................................................... 27 
5.4.4 
Dose Selection ........................................................................................................ 28 
6.0 
STUDY OBJECTIVES ..................................................................................................... 29 
7.0 
INVESTIGATIONAL PLAN ........................................................................................... 30 
7.1 
Overall Study Design .................................................................................................... 30 
7.2 
Study Sites .................................................................................................................... 31 
7.3 
Duration of Study .......................................................................................................... 31 
7.4 
Criteria for Study Termination...................................................................................... 32 
8.0 
SELECTION AND WITHDRAWAL OF SUBJECTS .................................................... 33 
8.1 
Inclusion Criteria .......................................................................................................... 33 
8.2 
Exclusion Criteria ......................................................................................................... 34 
8.3 
Randomization (Day 1) Inclusion Criteria .................................................................... 35 
8.4 
Reasons for Study Discontinuation ............................................................................... 36 
8.5 
Subject Identification and Number Assignment ........................................................... 36 
9.0 
TREATMENTS ................................................................................................................ 38 
9.1.1 
Description of Study Drug ...................................................................................... 38 
9.1.1.1 
CP101 .............................................................................................................. 38 
9.1.1.2 
Placebo............................................................................................................. 38 
9.1.2 
Dose and Regimen of Study Drug .......................................................................... 38 


 
 
 
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9.1.3 
Dosage Form, Manufacturing, Packaging, and Labeling of Study Drug................ 39 
9.1.4 
Storage of Study Drug ............................................................................................ 39 
9.1.5 
Method of Randomizing Subjects to Study Drug ................................................... 39 
9.1.6 
Study Drug Blinding ............................................................................................... 39 
9.1.7 
Study Drug Unblinding ........................................................................................... 39 
9.1.8 
Study Drug Accountability Procedures .................................................................. 40 
9.1.9 
Antibiotic Therapy .................................................................................................. 41 
9.1.10 Concomitant Therapy and Restricted Medications ................................................. 41 
9.1.11 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... 43 
10.2 
Subject Memory Aid ..................................................................................................... 44 
10.2.1 Gastrointestinal Symptoms and Medications .......................................................... 46 
10.2.2 Unformed Stools and Diarrhea Assessments .......................................................... 46 
11.0 
ASSESSMENT OF SAFETY ........................................................................................... 47 
11.1 
Adverse Events ............................................................................................................. 47 
11.1.1 Serious Adverse Events .......................................................................................... 49 
11.1.1.1 
Serious Adverse Event Reporting .................................................................... 50 
11.1.1.2 
 ................................................................................................. 51 
11.2 
Contraception Requirements and Pregnancy ................................................................ 51 
11.2.1 Contraception Requirements ................................................................................... 51 
11.2.2 Pregnancy ................................................................................................................ 52 
11.3 
Vital Signs, Height, and Weight ................................................................................... 53 
11.4 
Physical Examinations .................................................................................................. 53 
11.5 
Electrocardiograms ....................................................................................................... 53 
11.6 
Clinical Safety Laboratory Evaluations ........................................................................ 53 
12.0 
STUDY PROCEDURES BY VISIT ................................................................................ 55 
12.1 
Study Visits Description ............................................................................................... 55 
12.1.1 Screening (On-site Visit) ........................................................................................ 55 
12.1.2 Randomization (Day 1; On-site Visit) .................................................................... 56 


 
 
 
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Recurrent C. difficile Infection 
 
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12.1.3 Week 1 (Telephone Contact) .................................................................................. 57 
12.1.4 Week 2 and Week 3 (Telephone Contact) .............................................................. 57 
12.1.5 Week 4 (On-site Visit) ............................................................................................ 58 
12.1.6 Week 7 (Telephone Contact) .................................................................................. 58 
12.1.7 Week 8 (On-site Visit) ............................................................................................ 58 
12.1.8 Week 11 (Telephone Contact) ................................................................................ 59 
12.1.9 Week 12 (Telephone Contact) ................................................................................ 59 
12.1.10 Week 23 (Telephone Contact) ................................................................................ 59 
12.1.11 Week 24/Early Termination Visit (On-site Visit) ................................................... 59 
12.1.12 Routine Telephone Follow-Up ............................................................................... 60 
12.1.13 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 
Overview ....................................................................................................................... 62 
13.3 
Analysis Populations ..................................................................................................... 63 
13.4 
Subject Disposition ....................................................................................................... 63 
13.5 
Efficacy Analysis .......................................................................................................... 64 
13.5.1 Primary Endpoints .................................................................................................. 64 
13.5.2 Secondary 
 Endpoints.................................................................... 64 
13.6 
Safety Analysis ............................................................................................................. 65 
13.7 
 ............................................................................................. 66 
13.8 
Determination of Sample Size ...................................................................................... 66 
14.0 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................ 67 
14.1 
Monitoring Procedures.................................................................................................. 67 
14.2 
Study Site Training ....................................................................................................... 68 
15.0 
ETHICS............................................................................................................................. 69 
15.1 
Ethics and Good Clinical Practice ................................................................................ 69 
15.2 
Confidentiality Regarding Study Subjects .................................................................... 69 
15.3 
Future Use of Stored Specimens ................................................................................... 69 
15.4 
Institutional Review Board/Independent Ethics Committee......................................... 70 




 
 
 
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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 
ECG 
Electrocardiogram 
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 


 
 
 
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PP 
Per-Protocol 
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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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 patients on the 








 
 
 
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5.4.1.1.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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5.4.3 
Potential Risks and Benefits 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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5.4.4 
Dose Selection 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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6.0 
STUDY OBJECTIVES 
The objectives of this Phase 2 study are: 
• To evaluate the safety and tolerability of CP101 treatment compared to placebo in adults 
with previously treated recurrent CDI. 
• To evaluate the efficacy of CP101 treatment relative to placebo in adults with previously 
treated recurrent CDI. 




 
 
 
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Subjects will be issued a paper Memory Aid at the time of informed consent (Section 10.2) and 
given training on its use in order to aid in capturing the following information: occurrence of GI 
symptoms, frequency of stools, fecal urgency, stool incontinence, BSS, and any new medications 
taken (including antibiotics for treatment of CDI). Subjects will return the Memory Aid to the 
clinic and will review it with the coordinator at the Screening visit and Randomization (Day 1) 
after drug administration. At Week 1 telephone call, the Memory Aid data will be discussed, and 
subjects will be reminded to bring it to the Week 4 visit. In the event of suspected CDI 
recurrence, the Memory Aid recorded after Week 1 will be discussed at unscheduled visit(s). 
Clinical signs and symptoms of recurrent CDI, including frequency and consistency of stools, 
will be confirmed by a C. difficile stool testing algorithm (see Figure 10.a). North American 
Pulse-field type 1 (NAP1)/BI/027 subtyping will be performed if symptoms are consistent with 
recurrent CDI. 
, stool will be assessed for ARB, and 
 
. An overview of evaluations to be performed is outlined in the Schedule of Observations 
(Table 1.a).  
Safety will be assessed via adverse event monitoring, concomitant medication use, physical 
examinations, vital signs, electrocardiograms (ECGs), clinical safety laboratory evaluations, and 
pregnancy testing (if female is of childbearing potential). 
 
 
  
If a subject discontinues from the study early, the subject will be asked to return to the clinic 
within 14 days after discontinuation to undergo the scheduled Week 24 assessments prior to 
study discharge. All other subjects will have their final visit at Week 24  14 days. 
7.2 
Study Sites 
 
 
7.3 
Duration of Study 
The study duration will be approximately 24 weeks following Randomization visit, including an 
8-week Efficacy and Safety Assessment Period and an additional 16-week safety and CDI 
Recurrence Follow-up Period.  
 
 


 
 
 
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7.4 
Criteria for Study Termination 
The study will be completed as planned unless any of the following criteria are satisfied that 
require temporary suspension or early termination of the study: 
• New information regarding the safety or efficacy of the study drug that indicates a change 
in the known risk/benefit profile for the compound, such that the risk/benefit is no longer 
acceptable for subjects participating in the study; 
• 
 
 
 
 
 
 
• Significant violation of International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP) that compromises the ability to achieve the study objectives or 
compromises subject safety; and 
• Sponsor decision. 
Should the study be terminated, all relevant study documentation and study drug must be 
returned to the Sponsor. 


 
 
 
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8.0 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Study eligibility will be evaluated during the Screening visit, which will take place prior to the 
Randomization visit (Day 1).  
8.1 
Inclusion Criteria 
1. 
Ability to provide written informed consent; 
2. 
Men or women 18 years of age or older; 
3. 
Recurrent CDI* as defined by: 
a)  3 episodes of CDI, with 2 episodes occurring within the previous 12 months 
(inclusive of the current episode); OR  
b) 2 episodes of CDI occurring within the previous 6 months (inclusive of the 
current episode) AND 65 years of age or older; 
*NOTE: CDI is defined by: 
a) History of diarrhea ( 3 unformed stools per day) for 2 or more consecutive 
days; AND 
b) A stool specimen documented as testing positive for C. difficile within 60 
days prior to Randomization. Testing for CDI may include: 
i. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
AND 
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 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 Randomization; 
4. 
Willingness to abstain from consuming non-dietary probiotics through Week 8 after 
Randomization; 
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 


 
 
 
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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 Randomization; 
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 
randomized 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 Randomization; 
9. 
Initiation of any systemic cancer treatment (e.g. chemotherapy, radiotherapy, 
biologic, others) for active malignancy that is planned 8 weeks prior to 
Randomization or during the 8 weeks following Randomization. Subjects on 
maintenance treatment for malignancy may be randomized 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 Randomization or planned 
during the 8 weeks following Randomization. Subjects on stable immunosuppressive 
agents or short-courses may be randomized 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;  


 
 
 
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12. 
Fecal transplant for any condition, regardless of route of administration in the last 
year or plans to undergo during the study; 
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 randomized 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 
Randomization. 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 
Randomization (Day 1) or within 5 half-lives of the last dose of the previous 
investigational compound, whichever is longer; 
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 Randomization, the above listed Inclusion/Exclusion Criteria as well as 
the following additional Inclusion Criteria must be satisfied: 
8.3 
Randomization (Day 1) Inclusion Criteria 
1. 
An outpatient prior to Randomization; 
a) NOTE: Subject may be enrolled while an inpatient in an acute care facility, but 
must be discharged prior to Randomization on Day 1. Subjects residing in an 
assisted living center, long-term care facility, or rehabilitation center may be 
randomized; 


 
 
 
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2. 
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); 
3. 
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 
Randomization; and 
4. 
Subject has completed a washout 
 
 
 
 
8.4 
Reasons for Study Discontinuation 
All subjects will be free to discontinue study participation at any point during the study, for any 
reason, and without prejudice to their further medical care. In addition, the Investigator can 
discontinue a subject from the study at any time. Subjects will be encouraged to remain in the 
study through Week 24, regardless of the occurrence of adverse events, study outcome, or 
Week 8 results. 
The primary reason for a subject’s withdrawal should be recorded in the subject’s source record 
and on the electronic case report form (eCRF) using 1 of the following categories: 
• Adverse event: The subject experiences an adverse event that impacts the safety of 
continued participation in this study or the subject is unwilling to continue because of an 
adverse event. 
• Subject voluntary withdrawal. 
• Investigator withdrawal of subject. 
• Lost to follow-up: In the case of subjects lost to follow-up, attempts to contact the subject 
must be made and documented in the subject’s medical records.  
• Study termination: The Sponsor, DSMC, IRB/IEC, or regulatory agency terminates the 
study. 
• Other: Any other reasons, based upon the medical judgment of the Investigator and 
discussion with the Medical Monitor. 
If a subject discontinues from the study early, the subject will be asked to return to the clinic 
within 14 days after discontinuation to undergo the scheduled Week 24 assessments prior to 
study discharge. 
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. A subject identification number in the format of XXX-XXXX will be generated in IRT, 
and will be used to identify the subject throughout the study, including subject transfer to another 
site. This number will be entered on all documentation. A subject identification number will not 
be assigned to more than 1 subject. If a subject is not eligible to receive treatment, or if a subject 


 
 
 
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discontinues from the study, the subject identification number cannot be assigned to another 
subject.  
 




 
 
 
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9.1.3 
Dosage Form, Manufacturing, Packaging, and Labeling of Study Drug 
CP101 and placebo will be formulated as capsules for oral administration. The study sites will be 
supplied with study drug in a double-blind manner (i.e., placebo capsules will be identical in 
size, smell, texture, and appearance to CP101 capsules).  
 
 
. 
 
 
 
 
Refer to the Pharmacy Manual for additional information. 
9.1.4 
Storage of Study Drug 
 
 
  
Refer to the Pharmacy Manual for additional information. 
9.1.5 
Method of Randomizing Subjects to Study Drug 
The unblinded study biostatistician will create the randomization schedule which will be 
uploaded in the IRT for implementation. Subjects who satisfy the randomization eligibility 
criteria will be randomized in a 1:1 ratio to receive CP101 or placebo via the IRT. There is no 
stratification to be used in the randomization. The Investigator or the Investigator’s designee will 
enter all screening information, including demographics, and will confirm Inclusion/Exclusion 
Criteria in order to obtain the subject randomization number and a corresponding bottle number 
for treatment assignment. 
9.1.6 
Study Drug Blinding 
The study drug blind will be maintained through Week 8. Subjects, the Sponsor, Investigators, 
and all study site personnel involved with the study, carrying out study procedures, evaluating 
subjects, entering study data, and/or evaluating study data will remain blinded to treatment 
allocations until all subjects have completed the Week 8 assessments and the database has been 
locked for the analysis at Week 8. The Investigators, study site personnel, and subjects will 
remain blinded until Week 24.  
Active and placebo product will be identical with the exception of a unique identification number 
on the bottle label.  
9.1.7 
Study Drug Unblinding 
Investigators shall not break the study blind during the study, and Investigators should treat all 
subjects as if they had received CP101. However, in situations in which knowledge of the 
subject's study drug is necessary for clinical management, the Investigator must first attempt to 


 
 
 
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contact the Medical Monitor or designee (contact information is on the Signature Page of this 
document), to discuss and agree to the need for unblinding to occur. The Medical Monitor or 
designee will answer calls 24 hours a day, 7 days a week, and 365 days of the year. In situations 
in which the Investigator has tried, but is unable to reach the Medical Monitor or designee, 
he/she should use best judgment, based on the nature and urgency of the clinical situation, and 
may proceed with unblinding without having successfully reached and discussed the situation 
with the Medical Monitor or designee. 
Once a subject’s treatment assignment has been unblinded, the Medical Monitor and study 
coordinator should be notified within 24 hours of unblinding of the treatment. Information 
relating to unblinding (e.g., date and time of the call to the Medical Monitor by the Investigator, 
reason for unblinding, and date and time of unblinding) shall be clearly recorded in the subject’s 
study file and in the electronic data capture (EDC) system, as part of relevant standard operating 
procedures. In addition, the Investigator should consider whether the clinical event prompting 
unblinding should be considered an adverse event or SAE, according to the regulatory definitions 
or criteria for adverse events or SAEs, and if so, submit an adverse event/SAE report to Sponsor 
or designee (see Section 11.0). 
Sponsor or designee will also unblind any SAE reports that are unexpected, and considered to be 
related to the study drug, in accordance with safety reporting guidance and regulations. 
9.1.8 
Study Drug Accountability Procedures 
Responsibility for study drug accountability at the study site rests with the Investigator; however, 
the Investigator may delegate applicable study drug accountability duties to an appropriately 
trained pharmacist or designee. Inventory and accountability records must be maintained and 
must be readily available for inspection by the CRA and are open to inspection at any time by 
any applicable regulatory authorities. 
The Investigator or designee will be expected to collect and retain all used, unused, and partially 
used study drug bottles. The Investigator or designee must maintain records that document the 
following: 
• Study drug delivery to the study site, 
• Shipping conditions upon arrival, 
• Inventory at the study site, 
• Storage conditions at the study site, 
• Bottle number assigned to each subject, and 
• 
 
These records should include dates, quantities, and batch/serial numbers (if available). 
The study drug must be used only in accordance with the protocol.  
Prior to study site closure or at appropriate monitoring intervals, a representative from the 
Sponsor or its designee will perform clinical study material accountability and reconciliation 
before clinical study materials are returned to the Sponsor or its designee. The Investigator will 
retain the original documentation regarding clinical study material accountability as well as 
clinical study material return and/or destruction, and copies will be sent to the Sponsor. 


 
 
 
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9.1.9 
Antibiotic Therapy 
Subjects who present with a current recurrent CDI episode during Screening, defined as: 
a)  3 episodes of CDI, with 2 episodes occurring within the previous 12 months (inclusive of 
the current episode); OR b) 2 episodes of CDI occurring within the previous 6 months (inclusive 
of the current episode) AND 65 years of age or older will be evaluated for inclusion in the study. 
To qualify, recurrent CDI subjects must have received 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 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 
Randomization. 
9.1.10 
Concomitant Therapy and Restricted Medications 
 
 
 
 
 
 
9.1.11 
Diet 
 
 
 
 
 


 
 
 
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10.0 
ASSESSMENT OF EFFICACY 
The primary clinical outcome of 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. NAP1/BI/027 subtyping will be performed if symptoms are 
consistent with recurrent CDI. 
will be evaluated and stool will be 
assessed for ARB and 
 at multiple 
time points. 
10.1 
Stool Sample Analyses 
Stool samples will be collected and analyzed as shown in the Schedule of Observations 
(Table 1.a).  
A stool specimen documented as testing positive for C. difficile by local testing performed at the 
site or local laboratory is required within the 60 days prior to Randomization for inclusion in the 
study. Subjects will be excluded if there is known testing on stool specimens 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. 
Further stool samples will be collected at Screening while the subject is completing a course of 
standard-of-care CDI antibiotics for the most recent CDI episode or during a washout period 
 prior to 
Randomization and at Randomization prior to study drug administration. 
 
 
, assessment for ARB 
(Section 10.1.3), and safety testing.  
 
 
 
  
In the event that CDI recurrence is suspected, stool samples will also be used for NAP1/BI/027 
subtyping, as well as testing for CDI using a C. difficile testing algorithm (see Figure 10.a and 
Section 10.1.4).  
Complete instructions for collection, handling, storage, and transportation/shipping of stool 
samples will be provided in a separate Laboratory Manual. 
10.1.1 
Bristol Stool Scale 
Stool samples will be collected at Screening while the subject is completing a course of 
standard-of-care CDI antibiotics for the most recent CDI episode or during the washout period, 
at Randomization (Day 1) prior to study drug administration, Week 8 visit, Week 24 visit, and at 
any time there is a suspected CDI recurrence up to Week 24, as described in Section 10.1. All 
samples will be described using the 7-point BSS (Table 10.a). The BSS score will be recorded 
and reviewed by the Investigator. 
 
  


 
 
 
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Table 10.a 
Bristol Stool Scale 
 
10.1.2 
 
 
 
 
 
 
10.1.3 
Assessment for Antibiotic-Resistant Bacteria 
Stool sample collection for the assessment for ARB, defined as vancomycin-resistant enterococci 
(VRE), extended-spectrum ß-lactamase organisms (ESBL), or carbapenem-resistant 
Enterobacteriaceae (CRE), will be performed on samples obtained at Screening, Randomization 
(Day 1) prior to study drug administration, Week 8, and Week 24. Assessment for ARB may also 
be performed at any other visit or time point (e.g., time of recurrence, if any). 
10.1.4 
 
 
 


 
 
 
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Figure 10.a 
  
10.2 
Subject Memory Aid 
Subjects will be issued a Memory Aid at the time of informed consent and given training on its 
use. The Memory Aid will be discussed at the Screening Visit, Randomization (Day 1) after drug 
administration. At the Week 1 telephone call, the Memory Aid data will be discussed, and 
subjects will be reminded to bring it to the Week 4 visit. In the event of suspected CDI 
recurrence, the Memory Aid recorded after Week 1 will be discussed at unscheduled visit(s). 
Subjects will use the Memory Aid to assist in obtaining the following information as detailed in 
Table 10.b: 
• Occurrence (see Table 10.b) of GI symptoms, including: abdominal cramping, abdominal 
pain, abdominal tenderness, nausea, dehydration, bloating, poor appetite, unformed 
stools, vomiting, blood or pus in stool, stool incontinence, and fecal urgency; 
• Frequency of stools; 
• Recording of temperature, if the subject detects a fever; 
• BSS for each stool recorded; and 
• Any new medications taken (over-the-counter and prescription; including antibiotics for 
treatment of CDI).  
The study site staff will review the Memory Aid with the subject and obtain clarification if 
needed. The study staff will enter the data in the eCRF, as applicable. The Investigator may be 
required to review and document their interpretation of the BSS responses, in combination with 
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 solicitated adverse event is Grade 2 or greater during the 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, adverse events will be managed 
according to good clinical practice at the discretion of the treating physician.  


 
 
 
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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.  
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 
 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 


 
 
 
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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) 
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 outcome of 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 diarrhea ( 3 unformed stools [BSS score of 6 or 7] per day) for 2 or more 
consecutive days) accompanied by confirmation of CDI by a C. difficile testing algorithm, and 
received additional CDI standard-of-care therapy, then diarrhea 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). 
The occurrence and frequency of stools and occurrence of urgency and stool incontinence will be 
assessed from Screening through completion of the Week 1 telephone visit. 
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 with informed consent 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 outcome of 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 diarrhea for 2 or more consecutive days 
accompanied by confirmation of C. difficile as described above, and received additional CDI 
standard-of-care therapy, then diarrhea 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).  
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 considered or 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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• Routine health assessment requiring admission for baseline/trending of health status 
(e.g., routine colonoscopy); 
• Medical/surgical admission for purpose other than remedying ill health state and was 
planned prior to entry into the study. Appropriate documentation is required in these 
cases;  
• Admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (e.g., lack of housing, economic 
inadequacy, care-giver respite, family circumstances, administrative); and 
• A suspected clinical endpoint event, regardless of when the event occurs, should not be 
reported as an adverse event. A suspected clinical endpoint event includes recurrent CDI. 
11.1.1.1 Serious Adverse Event Reporting 
All SAEs and pregnancies occurring while the subject is in the study or within 30 days after the 
subject received their study dose must be reported within 24 hours of the knowledge of the event, 
whether or not considered to be related to study drug.  
All SAEs should be reported after the subject signs the informed consent and followed until 
resolution, stabilization, or until the Investigator provides sufficient evidence that no further 
information can be obtained.  
 
 
 
 
 
 
  
  
  
  
  
  
Although not all information required for a complete SAE form may be readily available at the 
time of the event, the Investigator must include sufficient information on the SAE form to allow 
for a complete medical assessment. This should include at a minimum the subject number, study 
site number, detailed description of the event, seriousness criteria, intensity, and 
causality/relationship to study drug.  
After submission of the initial report, the Investigator will provide follow-up information to 
 as requested (e.g., concomitant medications and hospital discharge 
summary) to further evaluate the event and assure that all appropriate information is received. 
Once all information is received and the SAE has been deemed appropriate for closure, the SAE 
form must be signed and dated by the Investigator within the adverse event eCRF.  


 
 
 
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The Investigator will be responsible for informing the IRB/IEC of the SAE in accordance with 
institutional policies and procedures including relevant initial and follow-up information about 
the SAE. 
11.1.1.2 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
11.2 
Contraception Requirements and Pregnancy 
11.2.1 
Contraception Requirements 
All women of childbearing potential must practice effective contraception from Screening 
through the Week 24 visit. For the purposes of this study, women who do not meet 1 of the 
criteria listed below for non-childbearing potential are considered to be physiologically capable 
of becoming pregnant and are, therefore, defined as women of childbearing potential: 
• Criteria for non-childbearing potential: 
o Post-menopausal: defined as amenorrhea  1 year, or 
o 6 weeks after surgical bilateral oophorectomy with or without hysterectomy, or  
o Hysterectomy, or 
o Bilateral tubal ligation. 
If a female subject does not fulfill post-menopausal or surgically sterile criteria, the subject 
must be abstinent or willing to practice effective contraception from Screening through the 
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;  


 
 
 
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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.  
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 


 
 
 
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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. 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 
Electrocardiograms 
Single 12-lead ECGs will be performed per standard-of-care at the time points listed in the 
Schedule of Observations (Table 1.a). Evidence of clinically significant abnormalities during the 
Screening visit may result in exclusion from the study. A 12-lead ECG will only be performed at 
Week 24 if there are findings at the Week 8 ECG or if the subject has symptoms requiring an 
ECG.  
11.6 
Clinical Safety Laboratory Evaluations 
Samples of blood and urine are scheduled for collection at Screening, at Randomization (Day 1) 
prior to study drug administration, and at Weeks 4, 8, and 24; 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 approximately 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.  




 
 
 
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12.0 
STUDY PROCEDURES BY VISIT 
Subjects who provide informed consent and meet all the eligibility criteria for participation in 
this study will be enrolled. To qualify for this study, subjects must be experiencing recurrent CDI 
as defined in Section 7.1. 
The study consists of a Screening Period, an 8-week Efficacy and Safety Assessment Period, 
followed by an additional 16-week Safety and CDI Recurrence Follow-Up Period. Overall, 
subjects will be monitored for 24 weeks after the Randomization visit. 
Stool samples will be collected before or after each scheduled clinic visit. Subjects may also be 
asked to bring a stool sample for unscheduled visits. Instructions for collection, handling, 
storage, and transportation/shipping are included in the Laboratory Manual. 
12.1 
Study Visits Description 
12.1.1 
Screening (On-site Visit) 
The Screening period is limited to 
 
. Where referenced as the Screening visit, study-required tests and procedures 
may be performed on 
, but preferably 
 
. In the event that the Screening period is planned for 
, additional 
clinical safety laboratory evaluations may be conducted at the discretion of the Investigator. 
 During the Screening visit, potential study subjects will be fully informed regarding the nature 
of the study and possible adverse events, and will receive a copy of the informed consent form 
(ICF) for review. Potential study subjects must read the ICF and sign the document after the 
Investigator or designee has answered all questions to the study candidate’s satisfaction, with 
further procedures only proceeding after the ICF has been signed. The original signed ICF will 
be retained by the Investigator and a copy will be given to the subject. 
Study candidates will be evaluated for study entry according to the Inclusion/Exclusion Criteria 
(Sections 8.1 and 8.2). The Investigator will evaluate the results of all examinations, including 
clinical laboratory tests and stool sample analyses, and will determine each candidate’s 
suitability for the study. 
 
. The 
following procedures will be performed at Screening: 
• Obtain signed, written informed consent and permission to use Protected Health 
Information (in accordance with the Health Insurance Portability and Accountability Act 
[HIPAA]) (see Section 15.5 for consent requirements). Refusal to provide this permission 
excludes an individual from eligibility for study participation. Record the date informed 
consent was given and who conducted the process on the appropriate source 
documentation. Informed consent must be in place prior to performing any study 
procedures.  
• Determine study eligibility through review of the Inclusion/Exclusion Criteria 
(see Sections 8.1 and 8.2). 
• A stool specimen documented as testing positive for C. difficile performed at the site or 
local laboratory is required within the 60 days prior to Randomization for inclusion in the 
study. Subjects will be excluded if there is known testing on stool specimens known to be 


 
 
 
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positive for ova and/or parasite(s), or other enteric pathogens (e.g., Salmonella, Shigella, 
and/or Campylobacter) within 28 days prior to Screening. 
• Obtain demographics and medical history, including: 
o Number of prior episodes of CDI; and 
o A pre-CDI medically documented weight or BMI. 
• Distribute paper Memory Aid and provide training on proper use. Record patient status at 
the time of informed consent and collect.  
• Start/continue treatment of standard-of-care CDI antibiotics for the most recent CDI 
episode (10-42 days; with exact duration, antibiotic type, and dose at the discretion of the 
Investigator). 
• 
  
• Perform a symptom-directed physical examination based on subjects’ signs and 
symptoms. 
• Collect vital signs, height, and weight per standard-of-care.  
• Perform 12-lead ECG per standard-of-care. 
• Obtain blood and urine samples for clinical laboratory safety testing and optional drug 
screen. 
• Obtain a blood sample from all women of childbearing potential for pregnancy testing, at 
the discretion of the Investigator. 
• Inquire about concomitant medications and adverse events. 
• Collect stool sample while the subject is completing a course of standard-of-care CDI 
antibiotics for the most recent CDI episode. Samples will undergo BSS stool assessment 
(Section 10.1.1) and will be used for fecal microbiome analysis, including, but not 
limited to, 
 assessment for ARB 
(Section 10.1.3), and safety testing.  
• After the Screening visit, perform a follow-up phone call 1 time as a reminder for the 
upcoming Randomization visit. 
12.1.2 
Randomization (Day 1; On-site Visit) 
Prior to study drug administration: 
• 
 
 
 
 
 
• 
 
• Perform a complete physical examination. 
• Per standard-of-care, collect weight and vital signs within 60 minutes prior to study drug 
administration. 
• Obtain blood and urine samples for clinical laboratory safety testing. 




 
 
 
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• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13. 
• Remind subject to bring Week 1 Memory Aid to Week 4 visit. 
12.1.5 
 Week 4 (On-site Visit) 
Note: Every effort will be made to conduct an on-site assessment at Week 4. However, under 
extenuating subject circumstances that make an on-site visit not feasible and after all reasonable 
measures to enable the subject’s on-site visit have been exhausted, a telephone assessment will 
be conducted.   
• Perform a symptom-directed physical examination based on subjects’ signs and 
symptoms. 
• Collect vital signs and weight per standard-of-care. 
• Obtain blood and urine samples for clinical laboratory safety testing. 
• Inquire about concomitant medications and adverse events since the last visit. 
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13.  
• Collect Week 1 Memory Aid. 
12.1.6 
Week 7 (Telephone Contact) 
• Perform follow-up phone call including a reminder for the next visit. 
• Review Memory Aid data with the subject, as applicable.  
• Inquire about concomitant medications and adverse events since the last visit. 
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13.  
12.1.7 
Week 8 (On-site Visit) 
Note: Every effort will be made to conduct an on-site assessment at Week 8. However, under 
extenuating subject circumstances that make an on-site visit not feasible and after all reasonable 
measures to enable the subject’s on-site visit have been exhausted, a telephone assessment will 
be conducted.   
• 
 
• Review Memory Aid data with the subject, as applicable.  
• Perform a symptom-directed physical examination based on subjects’ signs and 
symptoms. 
• Collect vital signs and weight per standard-of-care. 
• Perform 12-lead ECG per standard-of-care. 
• Obtain blood and urine samples for clinical laboratory safety testing. 
• Obtain urine sample from all women of childbearing potential for pregnancy testing. 


 
 
 
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• Inquire about concomitant medications and adverse events since the last visit.  
• 
 
 
 
 
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13.  
12.1.8 
 Week 11 (Telephone Contact) 
• Perform follow-up phone call including a reminder for the next visit. 
• Review Memory Aid data with the subject, as applicable.  
• Inquire about concomitant medications and adverse events since the last visit.  
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13. 
12.1.9 
Week 12 (Telephone Contact) 
• Perform follow-up phone call including a reminder for the next visit. 
• Review Memory Aid data with the subject, as applicable.  
• Inquire about concomitant medications and adverse events since the last visit.  
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13. 
12.1.10 
Week 23 (Telephone Contact) 
• Perform follow-up phone call including a reminder for the next visit. 
• Review Memory Aid data with the subject, as applicable.  
• Inquire about concomitant medications and adverse events since the last visit.  
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13. 
12.1.11 
Week 24/Early Termination Visit (On-site Visit) 
Note: Every effort will be made to conduct an on-site assessment at Week 24/Early Termination. 
However, under extenuating subject circumstances that make an on-site visit not feasible and 
after all reasonable measures to enable the subject’s on-site visit have been exhausted, a 
telephone assessment will be conducted.   
• 
 
 
  
• Perform a symptom-directed physical examination based on subjects’ signs and 
symptoms. 
• Collect vital signs and weight per standard-of-care. 


 
 
 
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• Perform a symptom-driven 12-lead ECG per standard-of-care. If there are findings at the 
Week 8 ECG or if the subject is experiencing symptoms requiring an ECG, the Week 24 
ECG is mandatory as a follow-up. 
• Obtain blood and urine samples for clinical laboratory safety testing. 
• Obtain urine sample from all women of childbearing potential for pregnancy testing, at 
the discretion of the Investigator. 
• Inquire about concomitant medications and adverse events since the last visit.  
• Collect stool sample. Samples will undergo 
 
 
 assessment for ARB (Section 10.1.3), and safety testing. 
 
• In the event that CDI recurrence is suspected, conduct the unscheduled visit procedures 
as detailed in Section 12.1.13.  
12.1.12 
Routine Telephone Follow-Up  
Subjects will be contacted by telephone as described above and in the Schedule of Observations 
(Table 1.a). Subjects will be asked about any adverse events, including occurrence of diarrhea. If 
a subject reports diarrhea, the study staff will review the timing of those episodes and the subject 
may be asked to submit a stool sample for C. difficile testing (Figure 10.a). Subjects will be 
asked about their general well-being, changes in their health status, medications, and 
over-the-counter remedies and will be reminded about their next study visit. From Screening 
through study completion, subjects will be reminded to record all relevant information on their 
Memory Aid, as applicable. Note: At Week 4, 8, 24 visits every effort will be made to conduct 
an on-site assessment. However, under extenuating subject circumstances that make an on-site 
visit not feasible and after all reasonable measures to enable the subject’s on-site visit have been 
exhausted, a telephone assessment will be conducted.   
12.1.13 
Unscheduled Visit for Suspected Recurrence of CDI 
Subjects are to report diarrhea promptly to the study coordinator at any time during the study. 
Any subject with diarrhea ( 3 unformed stools [BSS score of 6 or 7] per day) for 2 or more 
consecutive days must collect a stool sample and return with this sample to the clinic for an 
unscheduled visit. 
• Collect stool sample. Samples will undergo 
 
 
 assessment for ARB (Section 10.1.3), and safety testing. 
Perform NAP1/BI/027 subtyping if symptoms are consistent with recurrent CDI.  
• 
 
• Collect Memory Aid, resupply subject with a new Memory Aid, and review. 
• Inquire about concomitant medications and adverse events since the last visit.  
• Perform a symptom-directed physical examination based on subjects’ signs and 
symptoms. 
• Collect vital signs and weight per standard-of-care. 


 
 
 
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• Assess subject for signs and symptoms of CDI recurrence. 
• Perform laboratory testing, as clinically indicated, including testing stool for CDI using a 
C. difficile testing algorithm (see Figure 10.a). 
• 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 


 
 
 
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13.0 
STATISTICAL METHODS 
13.1 
Study Endpoints 
13.1.1 
Primary Endpoints 
The primary endpoints are: 
• Proportion of subjects experiencing sustained clinical cure, defined as absence of 
recurrent CDI, through Week 8, and 
• Incidence of adverse events through Week 8. 
13.1.2 
Secondary Endpoints 
The secondary endpoints are: 
• Proportion of subjects experiencing recurrent CDI with ribosomal NAP1/BI/027 
C. difficile subtype through Week 8; 
• Time-to-first recurrent CDI episode during the study (Day 1 through Week 8); 
• Proportion of subjects experiencing sustained clinical cure at Week 24; 
• Time-to-first recurrent CDI episode during the study (Day 1 through Week 24); 
• Incidence of hospitalization due to recurrent CDI through Week 8 and through Week 24; 
• Incidence of decolonization of ARB, defined as VRE, ESBL organisms, or CRE at 
Week 8 and Week 24 among co-colonized subjects; 
• 
 
 
• Change in BMI by Week 8 and Week 24 relative to medically documented pre-CDI BMI; 
and 
• Incidence of newly diagnosed autoimmune disease through Week 8 and Week 24. 
13.1.3 
Other Safety Endpoint 
The other safety endpoint is: 
• Incidence of adverse events through Week 24. 
13.1.4 
 
 
• 
  
13.2 
Overview 
Descriptive statistical methods will be used to summarize study data, with hypothesis testing 
performed for the primary efficacy endpoints at Week 8. Unless stated otherwise, the term 
“descriptive statistics” refers to number of subjects (n), mean, median, standard deviation, 
minimum, and maximum for continuous data, and refers to frequencies and percentages for 
categorical data. For some data that may be presented as continuous variables, there may be 
scientific reasons to present those data in constructed categories as well (e.g., BMI). Reasons for 


 
 
 
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the categories will be described in the Clinical Study Report. Graphical displays may be 
presented for selected results.  
A stand-alone 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 for 
Week 8. 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 an 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  
Four analysis populations are planned for the study: 
Intent-to-Treat population  
(ITT or All Randomized) 
All subjects randomized into the study. The ITT 
population will be analyzed according to the treatment 
group to which subjects were randomized.  
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 Randomization (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, 
Randomization 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. Analyses of safety will be 
performed based on treatment received, even if 
different from the treatment group to which subjects 
were randomized. 
13.4 
Subject Disposition 
Subject disposition will be presented for all subjects. The number of subjects who are 
randomized, 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, treatment group, and subsequent outcomes. 


 
 
 
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13.5 
Efficacy Analysis 
13.5.1 
Primary Endpoints 
For the primary efficacy endpoint, the proportion of subjects with sustained clinical cure, defined 
as absence of recurrent CDI through Week 8, will be tested using a Chi-Square test for treatment 
group differences. The primary efficacy analysis will be conducted for the ITT, mITT, and PP 
populations, as defined in Section 13.3. The mITT population will be the primary analysis 
population for all efficacy analyses.  
For the primary efficacy analysis, the active treatment group will be compared to the placebo 
group. The null hypothesis will be tested at a p-value  0.05.  
Null Hypothesis: There is no difference between the proportion of subjects with sustained 
clinical cure, defined as absence of recurrent CDI through Week 8, in the CP101 group 
compared to the placebo group. 
Sensitivity analyses of the primary efficacy outcome in the mITT population and PP population 
will also be conducted in the active treatment group versus placebo group using Chi-Square tests. 
Further details regarding sensitivity analyses will be discussed in the SAP. 
13.5.2 
Secondary 
 Endpoints 
All comparisons of the secondary endpoints will be performed at a 2-sided 0.05 significance 
level, and no corrections for multiple testing will be made.  
• The proportion of subjects experiencing recurrent CDI through Week 8 in each treatment 
group will be stratified by ribosomal NAP1/BI/027 C. difficile subtype and compared 
using Fisher’s exact test for group and subtype differences.  
• The time-to-first on-study CDI recurrence and associated 95% confidence interval (CI) 
will be estimated using the Kaplan-Meier method by treatment group through Week 8. 
• Proportion of subjects experiencing sustained clinical cure at Week 24. 
• The time-to-first on-study CDI recurrence and associated 95% CI will be estimated using 
the Kaplan-Meier method by treatment group through Week 24.  
• Incidence rate and 95% CIs will be used to test for treatment differences for incidence of 
hospitalization due to recurrent CDI through Week 8 and then through Week 24. 
• Incidence rate and 95% CIs will be used to test for treatment differences for incidence of 
decolonization of ARB, defined as VRE, ESBL organisms, or CRE at Week 8 and 
Week 24 among co-colonized subjects. 
• 
 
• Change in BMI by Week 8 and Week 24 relative to medically documented pre-CDI BMI. 
• Incidence rate and 95% CIs will be constructed for any newly diagnosed autoimmune 
disease for the study population, presented by treatment group through Week 8 and Week 
24. 
 
 


 
 
 
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13.6 
Safety Analysis  
All safety data will be presented in subject listings. 
For the primary safety endpoint, the incidence rate will be presented by treatment group for 
adverse events reported through Week 8.  
For the other safety endpoint, the incidence rate will be presented by treatment group for adverse 
events reported through Week 24. 
Adverse events will be tabulated by MedDRA SOC and preferred term. The occurrence of 
TEAEs will be summarized by treatment group using MedDRA SOCs, preferred terms, and 
severity.  
All adverse events will be listed for individual subjects showing both verbatim and preferred 
terms. Separate summaries of treatment-emergent SAEs and TEAEs related to study drug will be 
generated. 
Any event reported on the eCRF that occurs on or after the initiation of study drug is defined as 
treatment-emergent. Additionally, it will be assumed that an adverse event that was reported to 
have started at Randomization (Day 1) without an associated onset time may have occurred after 
the initiation of study drug. Hence, adverse events occurring at Randomization (Day 1) with no 
associated onset time are assumed to be treatment-emergent. 
Descriptive summaries of clinical laboratory results will be presented by study visit. Laboratory 
abnormalities will be graded according to NCI CTCAE. The number and percentage of subjects 
experiencing treatment-emergent graded toxicities will be summarized by treatment group and 
severity grade. Laboratory toxicity shifts from baseline to post-baseline assessments will be 
summarized by treatment group. Changes from baseline in laboratory tests will be summarized 
for each treatment group. 
Physical examination findings and vital signs will be summarized for any abnormal findings that 
are considered clinically significant in the opinion of the Investigator. These will be recorded as 
adverse events or be captured on the medical history if they are already present during Screening. 
Descriptive summaries of vital signs will be presented by study visit. Descriptive summaries of 
quantitative changes in vital signs will be presented by treatment group and study visit. Vital sign 
results will be reviewed for clinically notable abnormalities, according to predefined criteria, and 
adverse changes will be summarized. 
ECG results will be reviewed for clinically notable abnormalities according to predefined 
criteria. Subjects exhibiting Grade 3 or Grade 4 PR or QTc intervals will be summarized. 
Prior and concomitant medications will be mapped to a WHO Drug Dictionary preferred term 
and study drug classification. The number and percent of subjects taking concomitant 
medications will be summarized using preferred terms and study drug classifications. 
In this study, diarrhea is considered an adverse event and is defined as  3 unformed stools 
(BSS score of 6 or 7) per day. If a subject has diarrhea for 2 or more consecutive days and is 
accompanied by a positive test for C. difficile by a testing algorithm (see Figure 10.a.), and 
received additional standard-of-care CDI therapy, then diarrhea 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). 


 
 
 
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13.7 
 
 
 
  
 
 
 
 
 
 
 
 
 
13.8 
Determination of Sample Size 
 
 
 
 
 
 
 
 
 
 
  
 


 
 
 
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14.0 
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 principles of ICH GCP. The Sponsor, its designee, or a regulatory 
authority may wish to conduct an 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. 
14.1 
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, 
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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. 
14.2 
Study Site Training 
The Sponsor will provide quality 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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15.0 
ETHICS 
15.1 
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 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. 
15.2 
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. 
15.3 
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 consent to store samples for future testing within the 
study, as may be required by emergence of adverse conditions. 
 
 


 
 
 
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15.4 
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 before 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. 
15.5 
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 designee 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. 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 
IRB/IEC, and a copy of the approved version must be provided to the Sponsor after IRB/IEC 
approval. 


 
 
 
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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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15.6 
 
 
 
 
 
 
  


 
 
 
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16.0 
DATA HANDLING AND RECORD KEEPING 
16.1 
Recording of Data and Retention of Documents 
All information required by the protocol should be provided; any omissions or corrections should 
be explained. All eCRFs should be completed within a timely manner, preferably no more than 
3 days after the subject’s visit, so that the data manager and CRA may check the entries for 
completeness, accuracy, and legibility. An EDC system will be deployed for this study. The 
eCRFs will be completed by the authorized study site personnel. Electronic queries will be used 
to communicate eligible discrepant data with the study sites. An electronic version of the final 
eCRF book for each subject will be forwarded to the study sites for record keeping at the study 
site closure. 
The Investigator must maintain source documents for each subject in the study. All information 
on eCRFs will be traceable to these source documents, which are generally maintained in the 
subject’s file. The source documents will contain all demographic and medical information, 
including laboratory data, ECGs, etc., and also a copy of the signed ICF/HIPAA authorization, 
which should indicate the study number and title of the study. Essential documents, as listed 
below, will be retained by the Investigator for the maximum period required to comply with 
national and international regulations, or institutional procedures, or for the period specified by 
the Sponsor, whichever is longer. The Sponsor will notify the Investigator(s)/institution(s) when 
study-related records are no longer required to be retained. The Investigator agrees to adhere to 
the document retention procedures by signing the protocol. The Investigator must contact the 
Sponsor prior to destroying any records associated with the study.  
If the Investigator withdraws from the study (e.g., relocation or retirement), the records shall be 
transferred to a mutually agreed-upon designee (e.g., another Investigator or IRB). Notice of 
such transfer will be given in writing to the Sponsor. Essential documents include: 
1. 
Signed protocol and all amendments, 
2. 
IRB/IEC approvals for the study protocol and all amendments, 
3. 
All source documents and laboratory records, 
4. 
eCRF copies, 
5. 
Subjects’ ICF/HIPAA authorizations, and 
6. 
Any other pertinent study documents.  
16.2 
Case Report Forms 
 
 
 
 
 
 
 
 
 


 
 
 
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16.3 
Data Management 
16.3.1 
 
 
 
 
 
 
 
 
16.3.2 
Data Errors 
Errors, omissions, or requests for clarification at the study site will be queried; queries will be 
entered into the EDC system for resolution by study sites.  
16.3.3 
 
 
 
 
 
 
 
 
 
  
16.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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17.0 
 
 
 
 
 


 
 
 
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Recurrent C. difficile Infection 
 
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18.0 
 
 
 
 
 
 


 
 
 
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Recurrent C. difficile Infection 
 
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19.0 
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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Protocol CDI-001 
Recurrent C. difficile Infection 
 
 01 March 2019 
 
Finch Research and Development LLC – Confidential 
Page 78 of 79 
 
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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Recurrent C. difficile Infection 
 
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20.0 
APPENDICES  
20.1 
Electronic Product Labels for Standard CDI Antibiotics 
20.1.1 
Oral Vancomycin 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/50606slr020_vancocin_lbl.pdf 
20.1.2 
Fidaxomicin 
https://www.merck.com/product/usa/pi_circulars/d/dificid/dificid_pi.pdf 
20.1.3 
Metronidazole 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/12623slr059_flagyl_lbl.pdf 

SAP_001.pdf: 
 
 
 
 
Statistical Analysis Plan 
(SAP) 
 
A Multicenter, Double-Blind, Parallel-Arm, Placebo-
Controlled, Phase 2 Study of the Efficacy, Safety, and 
Tolerability of Oral Full-Spectrum Microbiota™ (CP101) in 
Subjects with Recurrence of Clostridium difficile Infection 
 
 
 
Protocol Number: CDI-001 
 
 
Version: 2.0, 12 April 2021 
 
 
Finch Research and Development LLC 
200 Inner Belt Road, Suite 400 
Somerville, MA 02143 
 
 
 
Confidentiality Statement: 
This document contains confidential information of Finch Research and Development LLC (the Sponsor) which must 
not be reproduced, published, or otherwise disclosed to anyone other than the recipient(s), members of the ethics 
committee(s) or regulatory authorities. The document and the information contained herein cannot be used for any 
purpose other than the evaluation or conduct of the clinical investigation described in this document without prior 
written approval from Finch Research and Development LLC. The foregoing shall not apply to disclosure required by 
applicable laws or governmental regulations. Notice must be provided to Finch Research and Development LLC of 
any such disclosure as soon as practicable. 




CDI-001 
Version 2.0, 12 April 2021 
 
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VERSION HISTORY 


CDI-001 
Version 2.0, 12 April 2021 
 
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CDI-001 
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CDI-001 
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TABLE OF CONTENTS 
 
SAP APPROVAL FORM..................................................................................................2 
TABLE OF CONTENTS ..................................................................................................6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................8 
1. 
INTRODUCTION ........................................................................................10 
2. 
STUDY OBJECTIVES ................................................................................10 
3. 
STUDY DESIGN ..........................................................................................10 
3.1. 
General Study Design and Plan ......................................................................10 
3.2. 
Study Population .............................................................................................13 
3.3. 
Randomization ................................................................................................13 
3.4. 
Blinding ..........................................................................................................13 
3.5. 
Study Assessments..........................................................................................15 
4. 
SAMPLE SIZE JUSTIFICATION .............................................................18 
5. 
EFFICACY ENDPOINTS ...........................................................................18 
5.1. 
Primary Endpoints ..........................................................................................18 
5.2. 
Secondary Endpoints ......................................................................................18 
5.3. 
Other Safety Endpoint ....................................................................................19 
5.4. 
 ....................................................................................19 
6. 
SAFETY ASSESSMENT .............................................................................19 
6.1. 
Adverse Events ...............................................................................................19 
6.2. 
Clinical Safety Laboratory Evaluations ..........................................................20 
6.3. 
Physical Examinations ....................................................................................20 
6.4. 
Vital Signs, Height, and Weight .....................................................................21 
6.5. 
Electrocardiograms .........................................................................................21 
6.6. 
 ................................................................................................21 
6.7. 
 .....................22 
7. 
ANALYSIS POPULATIONS ......................................................................22 
7.1. 
Intent-to-Treat Population (ITT) or All Randomized .....................................22 
7.2. 
Modified ITT Population (mITT or Full Analysis population) ......................22 
7.3. 
Per-Protocol (PP) Population ..........................................................................22 
7.4. 
Week 24 Per-Protocol (PP) Population ..........................................................22 


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7.5. 
Safety Population ............................................................................................22 
8. 
STATISTICAL ANALYSIS ........................................................................22 
8.1. 
General Statistical Considerations ..................................................................23 
8.1.1. 
General Analysis Approach ............................................................................23 
8.1.2. 
 ...............................................................23 
8.1.3. 
Baseline Definition .........................................................................................24 
8.1.4. 
Multiplicity .....................................................................................................24 
8.1.5. 
Derived Data ...................................................................................................24 
8.2. 
Study Subjects ................................................................................................25 
8.2.1. 
Subject Disposition .........................................................................................25 
8.2.2. 
Protocol Deviations ........................................................................................25 
8.2.3. 
Demographic and Baseline CDI Characteristics ............................................26 
8.2.4. 
Medical and Surgical History .........................................................................27 
8.2.5. 
Prior and Concomitant Medications ...............................................................27 
8.2.6. 
Study Drug Compliance .................................................................................27 
8.3. 
Efficacy Analyses ...........................................................................................28 
8.3.1. 
Primary Efficacy Analyses .............................................................................28 
8.3.2. 
Secondary Efficacy Analyses .........................................................................29 
8.3.3. 
 .......................................................................32 
8.3.4. 
Subgroup Analyses .........................................................................................32 
8.4. 
Safety Analyses ..............................................................................................33 
8.4.1. 
Adverse Events ...............................................................................................34 
8.4.2. 
Clinical Laboratory Evaluations .....................................................................35 
8.4.3. 
Vital Signs ......................................................................................................35 
8.4.4. 
Electrocardiograms (ECG) .............................................................................35 
8.4.5. 
Physical Examination .....................................................................................35 
9. 
TIMING OF PRIMARY ENDPOINT ANALYSIS...................................35 
10. 
REFERENCES .............................................................................................36 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
 
AE 
Adverse event 
ARB 
Antibiotic-resistant bacteria  
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body mass index 
BSS 
Bristol Stool Scale 
C. difficile 
Clostridium difficile 
CDI 
Clostridium difficile infection 
CI 
Confidence interval 
CRE 
Carbapenem-resistant Enterobacteriaceae 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSMC 
Data and Safety Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic Data Capture 
EIA 
Enzyme immunoassay 
ESBL 
Extended-spectrum ß-lactamase  
FMT 
Fecal microbiota transplantation 
GI 
Gastrointestinal 
hCG 
Human chorionic gonadotropin 
IRT 
Interactive response technology 
ITT 
Intent-to-Treat 
MAR 
Missing at random 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
NAP1 
North American Pulse-field type 1 
NCI 
National Cancer Institute 
PCR 
Polymerase chain reaction 
PCS 
Potentially clinically significant 
PP 
Per-Protocol 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 


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SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
VRE 
Vancomycin-resistant enterococci 
WHO 
World Health Organization 
 
 
 


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1. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) is created based on Protocol CDI-001 (Version 7.0 
[Amendment 04], March 01, 2019) and describes in detail the statistical methodology and the 
statistical analyses to be conducted for the above-mentioned protocol. Any deviations from this 
analysis plan will be substantiated by sound statistical rationale and will be documented in the 
final clinical study report. Changes to the primary efficacy hypothesis or analysis prior to database 
lock would require an amendment to the protocol and SAP. 
2. 
STUDY OBJECTIVES 
The objectives of this Phase 2 study are: 
 To evaluate the safety and tolerability of CP101 treatment compared to placebo in adults with 
previously treated recurrent Clostridium difficile infection (CDI). 
 To evaluate the efficacy of CP101 treatment relative to placebo in adults with previously 
treated recurrent CDI. 
3. 
STUDY DESIGN 
3.1. 
General Study Design and Plan 
This is a double-blind, placebo-controlled, parallel-arm, multicenter study comparing the safety, 
tolerability, and efficacy of CP101 treatment relative to placebo in adults with previously treated 
recurrent CDI. Subjects who are experiencing recurrent CDI will undergo screening procedures. 
Subjects who meet eligibility criteria will be randomized to study drug.  
 
  
 
 
 Subjects will be monitored for recurrence of CDI, safety, and 
tolerability for 24 weeks following Randomization. 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 be experiencing recurrent CDI defined as: a)  3 episodes 
of CDI, with 2 episodes occurring within the previous 12 months (inclusive of the current episode); 
OR b) 2 episodes of CDI occurring within the previous 6 months (inclusive of the current episode) 
AND 65 years of age or older. Additionally, to qualify, recurrent CDI subjects must have received 
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 have an adequate 






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If a subject discontinues from the study early, the subject will be asked to return to the clinic within 
14 days after discontinuation to undergo the scheduled Week 24 assessments prior to study 
discharge. All other subjects will have their final visit at Week 24  14 days. 
3.2. 
Study Population 
Approximately 200 subjects 18 years of age or older, who experience recurrent CDI, and who 
respond to a standard-of-care CDI antibiotic regimen for the most recent CDI episode will be 
randomized to the study drug.  
3.3. 
Randomization  
 
 
 
 
 
 
 
3.4. 
Blinding  
The study drug blind will be maintained through Week 8. Subjects, the Sponsor, Investigators, and 
all study site personnel involved with the study, carrying out study procedures, evaluating subjects, 
entering study data, and/or evaluating study data will remain blinded to treatment allocations until 
all subjects have completed the Week 8 assessments and the database has been locked for the 
analysis at Week 8. The Investigators, study site personnel, and subjects will remain blinded until 
Week 24.  
Active study drug and placebo will be identical with the exception of a unique identification 
number on the bottle label. 
Investigators shall not break the study blind during the study, and Investigators should treat all 
subjects as if they had received CP101. However, in situations in which knowledge of the subject's 
study drug is necessary for clinical management, the Investigator must first attempt to contact the 
Medical Monitor or designee, to discuss and agree to the need for unblinding to occur. The Medical 
Monitor or designee will answer calls 24 hours a day, 7 days a week, and 365 days of the year. In 
situations in which the Investigator has tried, but is unable to reach the Medical Monitor or 
designee, he/she should use best judgment, based on the nature and urgency of the clinical 
situation, and may proceed with unblinding without having successfully reached and discussed the 
situation with the Medical Monitor or designee. 
Once a subject’s treatment assignment has been unblinded, the Medical Monitor and study 
coordinator should be notified within 24 hours of unblinding of the treatment. Information relating 
to unblinding (e.g., date and time of the call to the Medical Monitor by the Investigator, reason for 
unblinding, and date and time of unblinding) shall be clearly recorded in the subject’s study file 
and in the electronic data capture (EDC) system, as part of relevant standard operating procedures. 
In addition, the Investigator should consider whether the clinical event prompting unblinding 


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should be considered an adverse event or serious adverse event (SAE), according to the regulatory 
definitions or criteria for adverse events or SAEs, and if so, submit an adverse event/SAE report 
to Sponsor or designee.  
Sponsor or designee will also unblind any SAE reports that are unexpected, and considered to be 
related to the study drug, in accordance with safety reporting guidance and regulations. 






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 10 Randomization will occur 
 
 Eligible subjects will be allocated to 1 of 2 treatment groups in a 1:1 ratio.  
11 For the most recent CDI episode, the subject will have received standard-of-care CDI antibiotics (10-42 days; with exact 
duration, antibiotic type, and dose at the discretion of the Investigator). 
12 
 
13 Subjects will have completed a mandatory washout 
 
 
 Study drug will be 
administered under direct supervision of clinic staff as an oral dose 
 
 Subjects will remain in the clinic for observation for at least 1 hour post-dose.  
14 A complete physical examination will be performed (including evaluation of general appearance/mental status; head, eyes, 
ears, nose, throat; and the following body systems: skin, heart, lungs, abdomen, and extremities). 
15 The Investigator will perform symptom-directed physical examinations based on subjects’ signs and symptoms. 
16 Vital signs (blood pressure, heart rate, and temperature) will be measured per standard-of-care. 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. 
17 Height will be measured at the Screening visit only per standard-of-care.  
18 Subjects should be weighed per standard-of-care. Height and weight will be used to calculate BMI. BMI will be calculated 
from weight collected at Week 8 and Week 24 as well. 
19  Vital signs will be measured before and after (within 60 minutes) study drug administration. 
20 Single 12-lead ECG will be performed per standard-of-care at Screening and at Week 8. Evidence of clinically significant 
abnormalities during the Screening visit may result in exclusion from the study. At Week 24, the 12-lead ECG will be 
performed only if there are findings at the Week 8 ECG, or if the subject has symptoms requiring an ECG.  
21 
 
 
 
 
 
 
 
 
 
 
 
       
22 Optional (at the discretion of the Investigator) drug screen includes cotinine (not exclusionary), amphetamines, barbiturates, 
benzodiazepines, cannabinoids (not exclusionary), cocaine, opiates (not exclusionary), and alcohol. 
23 Women of childbearing potential enrolled in this study will have serum hCG pregnancy testing administered during 
Screening and urine pregnancy testing thereafter, at the discretion of the Investigator. Women who are post-menopausal for  
1 year or surgically sterile will not undergo pregnancy testing. 
24 The adverse event reporting period will begin with informed consent and will continue through study completion or, in the 
case of withdrawal, until the outcome is determined. Adverse events will be collected after study drug administration on Day 
1. Subjects will be asked about any adverse events, including occurrence of diarrhea. If a subject reports diarrhea, the study 
staff will review the timing of those episodes and the subject may be asked to submit a stool sample for C. difficile testing. 
Subjects will be asked about their general well-being, changes in their health status, medications, and over-the-counter 
remedies. 
25 
 
 
 
 
26 Stool sample collection for the assessment for ARB, defined as vancomycin-resistant enterococci, extended-spectrum 
ß-lactamase organisms, or carbapenem-resistant Enterobacteriaceae, will be performed on samples obtained at Screening, 
Randomization (Day 1) prior to study drug administration, Week 8, and Week 24. Assessment for ARB may also be 
performed at any other visit or time point (e.g., time of recurrence, if any). 
 
 


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4. 
SAMPLE SIZE JUSTIFICATION 
 
 
 
 
 
 
 
 
 
 
  
5. 
EFFICACY ENDPOINTS  
5.1. 
Primary Endpoints 
The primary endpoints are: 
 Proportion of subjects experiencing sustained clinical cure, defined as absence of 
recurrent CDI, through Week 8, and 
 Incidence of adverse events through Week 8. 
5.2. 
Secondary Endpoints 
The secondary endpoints are: 
 Proportion of subjects experiencing recurrent CDI with ribosomal NAP1/BI/027 
C. difficile subtype through Week 8; 
 Time-to-first recurrent CDI episode during the study (Day 1 through Week 8); 
 Proportion of subjects experiencing sustained clinical cure at Week 24; 
 Proportion of subjects experiencing CDI Recurrence through Week 24; 
 Time-to-first recurrent CDI episode during the study (Day 1 through Week 24);  
 Incidence of hospitalization due to recurrent CDI through Week 8 and through Week 
24; 
 Incidence of decolonization of antibiotic resistant bacteria (ARB), defined as 
Vancomycin-resistant enterococci (VRE), Extended spectrum ß-lactamase (ESBL) 
organisms, or Carbapenem-resistant Enterobacteriaceae (CRE) at Week 8 and Week 
24 among co-colonized subjects; 
 
 
 
 Change in BMI by Week 8 and Week 24 relative to medically documented pre-CDI 
BMI; and 






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6.4. 
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). 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. Height and 
weight will be used to calculate 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. 
6.5. 
Electrocardiograms 
Single 12-lead ECGs will be performed per standard-of-care at the time points listed in the 
Schedule of Observations (Table 1). Evidence of clinically significant abnormalities during the 
Screening visit may result in exclusion from the study. A 12-lead ECG will only be performed 
at Week 24 if there are findings at the Week 8 ECG or if the subject has symptoms requiring 
an ECG. 
6.6. 
  
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 


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6.7. 
 
 
 
 
 
 
 
7. 
ANALYSIS POPULATIONS 
7.1. 
Intent-to-Treat Population (ITT) or All Randomized 
All subjects randomized into the study. The ITT population will be analyzed according to the 
treatment group to which subjects were randomized. 
7.2. 
Modified ITT Population (mITT or Full Analysis population) 
All subjects in the ITT population who receive at least 1 capsule of study drug at 
Randomization (Day 1). The mITT population will be the primary analysis population for all 
efficacy analyses. 
7.3. 
Per-Protocol (PP) Population  
All subjects in the mITT population who have received at least 80% of study medication, 
completed 8 weeks of follow up or had documented CDI recurrence prior to the 8-week follow-
up and did not have any major protocol deviation that affect the efficacy or safety of the study 
drug. 
7.4. 
Week 24 Per-Protocol (PP) Population  
All subjects in the mITT population who have received at least 80% of study medication, 
completed 24 weeks of follow up or had documented CDI recurrence prior to the 24-week 
follow-up and did not have any major protocol deviation that affect the efficacy or safety of 
the study drug.  The Week 24 PP Population will be used for all analyses of the Week 24 
endpoints where the PP Population is specified. 
7.5. 
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. Analyses 
of safety will be performed based on treatment received, even if different from the treatment 
group to which subjects were randomized.  
8. 
STATISTICAL ANALYSIS 


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8.1. 
General Statistical Considerations 
8.1.1. 
General Analysis Approach 
 All table summaries and listings will present the results by study drug (CP101 and placebo). 
 For purposes of all analysis and reporting, days will be numbered relative to the first day 
of dosing. Day 1 will be defined as the date on which a subject receives the first dose of 
study drug, as recorded on the electronic case report form (eCRF). The day prior to the first 
dose of study drug is Day -1;  
 Descriptive statistical methods will be used to summarize study data, with hypothesis 
testing performed for the primary efficacy endpoints at Week 8. Unless stated otherwise, 
the term “descriptive statistics” refers to number of subjects (n), mean, median, standard 
deviation, minimum, and maximum for continuous data, and refers to frequencies and 
percentages for categorical data, along with 95% confidence interval (CI) as appropriate. 
For categorical data summary, number of subjects with missing data will be included and 
percentages will be calculated based on the total number of subjects in the specified 
analysis population. For some data that may be presented as continuous variables, there 
may be scientific reasons to present those data in constructed categories as well (e.g., BMI). 
Reasons for the categories will be described in the Clinical Study Report.  
 Individual data listings of all data represented on the eCRF will be presented. Sort order 
for data listings will be subject identification number, visit, and time point where 
appropriate.  
 The SAP will be finalized and approved by signatures and dates prior to database lock for 
Week 8 and Week 24. The SAP will take precedence over the protocol for details about 
the statistical analyses for the study except the primary efficacy analyses which would 
require a protocol amendment. In addition to the analyses specified in the SAP, other 
exploratory analyses and 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 MedDRA, and all prior 
and concomitant medications will be coded using the World Health Organization (WHO) 
Drug Dictionary (B3 September 2018). 
8.1.2. 
 
 
 
 
 
 
 
 
 
 


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8.1.3. 
Baseline Definition 
For all efficacy and safety endpoints, baseline is defined as the last measurement or assessment 
prior to the administration of study drug. 
8.1.4. 
Multiplicity  
All comparisons of the secondary endpoints will be performed at a 2-sided 0.05 significance 
level, and no corrections for multiple testing will be made. 
8.1.5. 
Derived Data 
 Age will be calculated using the subject’s date of birth and the date the subject signed 
informed consent [integer part of (informed consent date - birth date)/365.25]. 
 Change from baseline values will be calculated as the value at a post-baseline time point 
minus the baseline value.   
 The Day on which an AE occurrence is noted will be calculated relative to the date of the 
first dose of study drug; Day = (date of AE – date of first dose) if date of AE is before 
date of first dose, Day = (date of AE – date of first dose + 1) if date of AE is on or after 
date of first dose.    
 Other derived variables summarized in  tables (with individual values provided in listings) 
will be described in footnotes of the tables where appropriate. 
The detailed derivation for the efficacy and safety data will be documented in a separate 
derived datasets specification. 


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8.2. 
Study Subjects 
8.2.1. 
Subject Disposition 
The number of subjects who are randomized, treated, complete the study, and discontinue from 
the study will be summarized by treatment group and in total for the ITT population. Subject 
disposition will also be summarized by study site. 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For screen failures, a summary will be provided by reason of screen failure. 
 
 
 
  
In addition, the total number of subjects for each defined population will be tabulated. Reasons 
for exclusions from analyses populations will be tabulated.  
8.2.2. 
Protocol Deviations 
The number of subjects with at least one reportable protocol deviation, and the number of 
subjects with at least one reportable deviation in each deviation category defined in the study 
protocol deviation plan will be presented based on the ITT and mITT populations. In addition, 
the protocol deviations related to COVID-19 pandemic will be categorized and summarized 
separately.  
Protocol deviations will also be listed by subject. 


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8.2.3. 
Demographic and Baseline CDI Characteristics  
The following demographics will be summarized: 
 Age (years) and age categorized as <65 vs. ≥65 years, and <70, 70-79, or ≥80 years; 
 Sex;  
 Race; 
 Ethnicity; 
 Pre-CDI weight (kg); 
 Height (cm);  
 Pre-CDI BMI (kg/m2); 
 Charlson comorbidity index (CCI)1 and CCI categories (<3 and ≥3). 
The following baseline CDI characteristics will be summarized:  
 CARDS score2 and score categories (<5, 5-9, 10-14, and ≥15); 
 GEIH-CDI score3 and score categories (≤3 and >3); 
 Previous CDI-associated hospitalization; 
 Previous CDI episodes  
o Total number of CDI episode in previous 12 months  
 Recurrent CDI category  
o ≥ 3 episodes with 2 episodes occurring in the previous 12 months 
o 2 episodes of CDI occurring in the previous 6 months AND 65 years or older 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
  
 
  
 
 
 
 
 
   


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 Recurrent CDI history – Standard-of-care CDI antibiotics for most recent study entry-
qualifying episode 
o Vancomycin and length categories (≤10, 10-14, 15-42, and ≥43 days) 
o Fidaxomicin and length categories (≤10, 10-14, 15-42, and ≥43 days) 
o Metronidazole and length categories (≤10, 10-14, 15-42, and ≥43 days) 
o CDI antibiotic combination and length categories (≤10, 10-14, 15-42, and ≥43 
days) 
o Other and length categories (≤10, 10-14, 15-42, and ≥43 days) 
 Medications (at Randomization)  
o Proton pump inhibitor vs no proton pump inhibitor  
o Immunosuppressive agents vs no immunosuppressive agents 
Demographic and baseline characteristics will be summarized with descriptive statistics or 
counts and percentages of subjects as appropriate by treatment group in all analysis 
populations. 
8.2.4. 
Medical and Surgical History  
Medical and surgical history terms will be coded using MedDRA (Version 20.1). Medical and 
surgical history will be summarized by treatment group and MedDRA SOC and preferred term 
in all analysis populations.  
All Medical and surgical history will be listed by subject.  
8.2.5. 
Prior and Concomitant Medications  
Prior and concomitant medications will be coded using the WHO Drug Dictionary (B3 
September 2018). Prior medications will include medications used before the administration 
of study drug. Any medications used on or after the administration of study drug will be 
included as concomitant medications.  
The number and percentage of subjects taking prior medications will be summarized in all 
analysis populations by Anatomical Therapeutic Chemical (ATC) class and preferred term for 
each treatment group. 
The number and percentage of subjects taking concomitant medications will be summarized 
in the same manner. 
All prior and concomitant medications and procedures will be listed by subject.  
8.2.6. 
Study Drug Compliance    
 
 
 
 In addition, summary tables will be provided to show the number and percentage 




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Where: 
p1 = the primary efficacy outcome in the CP101 group 
p2 = the primary efficacy outcome in the placebo group  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
8.3.2. 
Secondary Efficacy Analyses 
All comparisons of the secondary endpoints will be performed at a 2-sided 0.05 significance 
level, and no corrections for multiple testing will be made.  
Proportion of subjects with sustained clinical cure through Week 8 in the PP Population 
Analysis of proportion of subjects with sustained clinical cure through Week 8 will be 
performed for the PP Population. 
Proportion of subjects experiencing recurrent CDI through Week 8 by ribosomal 
NAP1/BI/027 subtype at CDI recurrence  
The proportion of subjects experiencing recurrent CDI at Week 8 will be summarized by 
ribosomal NAP1/BI/027 C. difficile subtype at CDI recurrence for the mITT and PP 
populations and compared using Chi-Square or Fisher’s exact test, as appropriate, within each 
subtype (NAP1/BI/027 vs. not NAP1/BI/027). 
 
 
 
 
 




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Incidence of hospitalization due to recurrent CDI through Week 8 and Week 24 
Incidence of hospitalization (including emergency room visits) due to recurrent CDI is defined 
as the number of subjects who were hospitalized due to recurrent CDI divided by the total 
number of subjects in the analysis population. Incidence of hospitalization due to recurrent 
CDI at Week 8 and Week 24 will be summarized by treatment group for the mITT and PP 
populations and tested using Chi-Square or Fisher’s exact test as appropriate. In addition, 
duration of hospitalization will be summarized by treatment group. Duration of hospitalization 
will be summarized by treatment group for the mITT and PP populations and tested using a T-
test for treatment group difference. Duration of hospitalization is calculated as the total number 
of days of hospitalization. 
Incidence of decolonization of ARB at Week 8 and Week 24 
Incidence of decolonization of ARB is defined as the number of subjects who experienced 
decolonization of ARB (VRE, ESBL organisms, or CRE) divided by the total number of 
subjects with ARB at baseline in the analysis populations. Incidence of decolonization of ARB 
at Week 8 and Week 24 will be summarized by treatment group for the mITT and PP 
populations and tested using a Chi-Square or Fisher’s exact test as appropriate.   
 
 
 
 
 
 
 
 
Change in BMI at Week 8 and Week 24 
Change from pre-CDI BMI will be calculated at the specified study visit as the value at the 
specified study visit minus the pre-CDI value. Change in BMI at Week 8 and Week 24 relative 


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to medically documented pre-CDI BMI will be summarized by treatment group in the mITT 
and PP populations.   
8.3.3. 
 
 
 
 
 
 
 
   
 
 
 
 
  
 
 
 
 
  
 
  
 
  
 
 
 
 
 
 
8.3.4. 
Subgroup Analyses 
The following subgroups based on baseline characteristics will be used for subgroup analyses 
for the primary efficacy endpoint in the mITT and PP populations.  
 Age group (<65 years vs.  ≥65 years) 
 Age group (<70, 70-79, and ≥80 years) 
 Gender group (male vs. female) 
 Race group (Caucasian vs. others) 
 Charlson Comorbidity Index (<3 vs. ≥3) 


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 CARDS score (<5, 5-9, 10-14, and ≥15) 
 GEIH-CDI score (≤3 vs. >3) 
 Previous CDI episodes - total number of CDI episode in previous 12 months 
 Recurrent CDI category  
o ≥3 episodes of CDI with 2 occurring in within the previous 12 months  
o 2 episodes of CDI occurring within the previous 6 months and 65 years old or 
greater  
 Previous CDI-associated hospitalization  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Ad-hoc Analyses 
Additional analyses may be performed and will be considered as ad-hoc analyses and 
exploratory in nature.    
8.4. 
Safety Analyses 
All safety summaries and analyses will be performed on the Safety population. All subjects 
will be summarized according to the treatment actually received. 


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Safety will be evaluated by presenting summaries of AEs, vital signs, laboratory evaluations   
and ECG parameters. For each safety parameter, unless otherwise stated, the last assessment 
made prior to the administration of study drug will be used as the baseline value for all 
analyses. 
8.4.1. 
Adverse Events 
Any event reported on the eCRF that occurs during or after the administration of study drug is 
defined as treatment-emergent adverse event (TEAE). Additionally, it will be assumed that an 
adverse event that was reported to have started at Randomization (Day 1) without an associated 
onset time may have occurred after the administration of study drug. Hence, adverse events 
occurring at Randomization (Day 1) with no associated onset time are assumed to be treatment-
emergent. 
For the primary safety endpoint, the incidence rate of TEAEs will be presented by treatment 
group through Week 8. 
For the other safety endpoints, the incidence rate of TEAE will be presented by treatment group 
through Week 24. 
In addition, an overview of TEAEs will be provided which summarizes the incidence of the 
following information: 
 All TEAEs 
 Drug-related TEAEs 
 Maximum severity of TEAEs  
 Deaths 
 Serious adverse events (SAEs) 
The number and percentage of subjects who experienced at least one TEAE will be presented 
by system organ class and preferred term. Drug-related TEAEs, withdrawals due to TEAEs, 
and all SAEs will be summarized in the same manner.  
Although a subject may have two or more TEAEs, the subject is counted only once within a 
System Organ Class and Preferred Term category. The same subject may contribute to two or 
more preferred terms in the same System Organ Class category. 
A list of subjects who have SAEs, and a list of subjects who discontinue from study drug will 
be provided. All adverse events will be listed.  
Newly diagnosed autoimmune disease will be reported as an AE. Newly diagnosed 
autoimmune disease is defined autoimmune disease occurs on or after the administration of 
study drug. Incidence of newly diagnosed autoimmune disease at Week 8 and Week 24 will 
be summarized by treatment group for the Safety population. The number and percentage of 
subjects who experienced treatment-emergent autoimmune disease will be presented by system 
organ class and preferred term.  
The solicited signs and symptoms collected will be entered in the eCRF and will be graded for 
severity. The number and percentage of subjects who experienced solicited signs and 
symptoms will be presented by treatment group and severity. 


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8.4.2. 
Clinical Laboratory Evaluations 
Descriptive statistics for clinical laboratory tests for hematology, chemistry, and coagulation 
listed in Table 2 will be presented by study visit as well as the change from baseline.  
Laboratory abnormalities will be graded according to NCI CTCAE Version 4.03 (for analytes 
where CTCAE grading applies). The number and percentage of subjects experiencing 
treatment-emergent graded toxicities will be summarized by treatment group and severity 
grade. A shift table, presenting the 2-way frequency tabulation for baseline and the worst post-
treatment value according to the NCI-CTCAE grade, will be provided by treatment group. For 
laboratory parameters with no CTCAE grading, shift tables (with categories of low, normal, 
high) from baseline to worst post-treatment value will be provided by treatment group. Both 
scheduled and unscheduled post-treatment values during the treatment period will be 
considered. 
All clinical laboratory data will be listed. Values outside the normal ranges will be identified 
in the data listings with flags for low (L) and high (H). 
8.4.3. 
Vital Signs 
Descriptive statistics for vital signs (temperature, heart rate, blood pressure and respiratory 
rate) will be presented by study visit and for the change from baseline. Descriptive statistics 
for weight will be presented by study visit and for the change from pre-CDI weight.  
A listing of all vital signs will be provided by subject. 
8.4.4. 
Electrocardiograms (ECG) 
Descriptive statistics will be provided for 12-lead ECG findings (heart rate, QRS, PR, RR, and 
QT, and QTcF) and changes from baseline for each scheduled visit in the Safety Population.  
QTcF will be calculated as follows: 
 
 
All ECG measurements and the overall interpretation will be listed by subject. 
8.4.5. 
Physical Examination 
Physical examination findings will be summarized for any abnormal findings that are 
considered clinically significant in the opinion of the Investigator. These will be recorded as 
adverse events or be captured on the medical history if they are already present during 
Screening. 
Physical examination findings will be listed by subject.  
9. 
TIMING OF PRIMARY ENDPOINT ANALYSIS 
Selected analysis will be performed after database lock for Week 8. After week 8 database is 
locked, the database will be unblinded by the independent unblinded personnel at Medpace 


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only. The unblinded analysis results will be delivered to the Sponsor and blinding procedures  
will continue to be adhered to as described in the protocol.  
10. 
REFERENCES 
1. Suidan RS, Leitao MM Jr, Zivanovic O, Gardner GJ, Long Roche KC, Sonoda Y, Levine 
DA, Jewell EL, Brown CL, Abu-Rustum NR, Charlson ME, Chi DS. Predictive value of the 
Age-Adjusted Charlson Comorbidity Index on perioperative complications and survival in 
patients undergoing primary debulking surgery for advanced epithelial ovarian cancer. 
Gynecol Oncol. 2015; 138(2):236-251.  
2. Kassam Z, Cribb Fabersunne C, Smith MB, Alm EJ, Kaplan GG, Nguyen GC, 
Ananthakrishnan AN. Clostridium difficile associated risk of death score (CARDS): a novel 
severity score to predict mortality among hospitalised patients with C. difficile infection 
Aliment Pharmacol Ther. 2016; 43(6):725-733.  
3. Cobo J, Merino E, Martinez C, Cozar-Listo A, Shaw E, Marrodan T, Calbo E, Bereciartua 
E, Sanchez-Munoz LA, Salavert M, Perez-Rodriguez MT, Garcia-Rosado D, Bravo-Ferrer JM, 
Galvez-Acebal J, Henriquez-Camacho C, Cuquet J, Pino-Calm B, Torres L, Sanchez-Porto A, 
Fernandez-Felix BM, Nosocomial Infection Study Group. Prediction of recurrent Clostridium 
difficile infection at the bedside: the GEIH-CDI score. Int J Antimicrob Agents. 2018; 
51(3):393-398.