Exploratory Study to Assess Delivery of LMN-201 Components Via Enteric Capsules in the Gut of Individuals With Ostomies
Phase: PHASE1
Conditions: C. Diff. Infections
Sponsor: Lumen Bioscience, Inc.

CLINICAL STUDY PROTOCOL 
Document Date: Version 1.2, November 18, 2021 
NCT #: NCT04893239 
 

 
 
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Lumen Bioscience, Inc.  
 
Exploratory study to assess delivery of LMN-201 components via enteric 
capsules in the gut of individuals with ileostomies  
 
Protocol Study Number CDI01 
 
 
 
 
Investigational Product: LMN-201 
 
LMN-201 is a cocktail consisting of a bacteriophage lysin specific for C. difficile organism and three VHH-
derived proteins that bind and inhibit C. difficile toxin B, delivered in whole, spray-dried spirulina biomass 
 
 
Version 1.2 
 
November 18, 2021 
 
Statement of Confidentiality 
Information contained within the Clinical Protocol, including unpublished data, is the property of Lumen 
Bioscience, Inc. and is provided in strict confidence to Investigators, potential Investigators, or consultants 
for review. This information shall not be disclosed to third parties without prior written authorization from 
Lumen Bioscience, Inc. except as necessary to obtain informed consent from study participants who may 
receive this product. 
 
 
 
Principal Investigator: 
Carl Mason, MD 
Senior Medical Director 
Lumen Bioscience, Inc. 
1441 N. 34th Street, Suite 300 
Seattle, WA 98103, USA 
cmason@lumen.bio 
 
Lead Site Principal Investigator: 
James Daveson, MD 
Director 
Coral Sea Clinical Research Institute 
Suite 7, 76 Willetts Road 
North Mackay QLD 4740 
james@coralseaclinical.com 
 
Company Sponsor: 
Lumen Bioscience, Inc. 
1441 N. 34th Street, Suite 300 
Seattle, WA 98103, USA 
(206) 899-1904 
www.lumen.bio 
 
 
Local Sponsor: 
Avance Clinical 
Level 1, 2 Ann Nelson Drive, Thebarton 
South Australia 5031 
Phone: +61 8 8249 4788 
www.avancecro.com 
 

 
 
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PRINCIPAL INVESTIGATOR’S AGREEMENT 
 
 
An exploratory study to assess delivery of LMN-201 components via enteric capsules in the 
gut of individuals with ileostomies 
 
I have received and read the Investigators’ Brochure for LMN-201. I have read this clinical protocol 
and agree to conduct the study as outlined in this protocol and according to the International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
guidelines, The Nuremberg Code, The Belmont Report, The Declaration of Helsinki 2000, US 21 
CFR Part 50--Protection of Human Subjects, 32 CFR 219 (The Common Rule), and all regulations 
pertinent to the Department of Defense, and relevant regional and/or national laws. 
Confidentiality of all information received or developed in connection with this protocol will be 
maintained by me, as well as all other personnel involved in the clinical trial who are employed or 
contracted by me or my organization. 
 
 
 
 
 
 
 
 
Date 
Site Principal Investigator 
 
 
 

 
 
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SPONSOR SIGNATURE 
 
 
 
 
 
 
 
Carl Mason, MD 
 
Date 
Senior Medical Director 
 
 
 
 

 
 
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CONTACT INFORMATION 
 
Table 1: Contact Information 
Role in Study 
Name 
Address and Telephone  
Site Principal Investigator (PI) 
Dr. James Daveson 
Coral Sea Clinical Research Institute 
Suite 7, 76 Willetts Road 
North Mackay QLD 4740 
Phone: +61 7 4910 9532 
Email: james@coralseaclinical.com 
Data Management/ 
Safety Reporting 
Contract Research Organization 
Florin Bercu 
Avance Clinical 
Level 1, 2 Ann Nelson Drive, Thebarton 
South Australia 5031 
www.avancecro.com 
Phone: +61 8 8249 4788 
Email: Florin.Bercu@avancecro.com 
Sponsor Medical Monitor/ 24-Hour 
Emergency Contact 
Dr. Carl Mason 
Lumen Bioscience, Inc. 
1441 N. 34th Street, Suite 300 
Seattle, WA 98103, USA 
Phone: +1(206) 899-1904 
Mobile: +1(805) 455-8593 
Email: cmason@lumen.bio 
 
 
 

 
 
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Table of changes, version 1.1 
Location  
Reason 
Date 
Edited to use the term ‘ileostomy’ rather than ‘ostomy’ 
All 
HREC request 
27MAY21 
Clarified enrollment criteria for second cohort 
Synopsis 
HREC request 
27MAY21 
Clarified that first cohort participants will receive only one of 
the VHH proteins, administered in 3 capsules 
Synopsis 
HREC request 
27MAY21 
Modified exploratory objectives and endpoints  
Synopsis, 
Section 4  
Sponsor-
initiated 
change  
27MAY21 
Removed statements that “no AEs were observed” in 
preclinical studies 
Sections 3.1 
and 3.2 
HREC request 
27MAY21 
Clarified that no GLP or toxicology studies have been 
conducted with LMN-201  
Section 3.2 
HREC request 
27MAY21 
Clarified that immediate release capsules may be used in the 
second cohort 
Section 5.1 
HREC request 
27MAY21 
Added descriptions of Vcaps Enteric and Vcaps Plus capsules  
Section 9.4 
HREC request 
27MAY21 
Removed label design as not needed in the protocol 
Section 9.7 
Sponsor-
initiated 
change 
27MAY21 
Edited to use the term ‘ileostomy’ rather than ‘ostomy’ 
throughout the PICF 
PICF 
HREC request 
27MAY21 
The following statements were added to p. 4, point 6: “The 
size of each capsule is about 20 mm. If you would like to see 
what the capsule looks like, the study staff can show you an 
empty capsule at the screening visit.”   
PICF, p. 4 
HREC request 
27MAY21 
“Therapeutic Goods of Australia [TGA]” was changed to 
“Australian Therapeutic Goods Administration [TGA].” 
PICF, p. 2 
HREC request 
27MAY21 
An explanation of LMN-201 was added to the section What is 
the purpose of this research? (p. 2): “To be effective, the 
capsules must deliver LMN-201, undamaged, to the end of 
the small intestine. This is where the LMN-201 components 
will be effective in treating C. difficile bacterial infection by 
specifically destroying the C. difficile bacteria and binding to 
the toxins produced by the C. difficile bacteria. This study will 
give the researchers information about if the LMN-201 
components are still present at the end of the small 
intestine.” 
PICF, p. 2 
HREC request 
27MAY21 
The following statement was added to point 4 on p. 3 and p. 
4: “Women who are pregnant, planning to become pregnant, 
or are breastfeeding, cannot participate in this study” 
PICF, p. 3 and 4 
HREC request 
27MAY21 
The following statement was added to the Study Visit section: 
“You may start eating again 2 hours after administration of 
the study drug. You will be provided snacks and up to two 
meals during the study visit.” 
PICF, p. 3 
HREC request 
27MAY21 
The following statement has been added above the text in 
bold in the “Pregnancies, Breastfeeding, and Birth Control 
Information” section: “It is highly recommended that you 
inform your partner of your participation in this study and 
PICF, p. 7 
HREC request 
27MAY21 

 
 
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that highly effective methods of contraception (as detailed 
above) are strongly recommended.” 
Opioid test was mistakenly included in the procedures done 
at the study visit. This was removed Study Visit Section. 
Opioid test will only be done at the screening visit 
PICF, p. 4 and 5 
Sponsor-
initiated 
change 
27MAY21 
 
 
 
 
 
 

 
 
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Table of Contents 
PRINCIPAL INVESTIGATOR’S AGREEMENT ...........................................................................................2 
SPONSOR SIGNATURE ........................................................................................................................3 
CONTACT INFORMATION ...................................................................................................................4 
TABLE OF CONTENTS ..........................................................................................................................7 
1. PROTOCOL SUMMARY....................................................................................................................9 
1.1 Synopsis ............................................................................................................................................... 9 
2. LIST OF ABBREVIATONS AND TERMS ............................................................................................. 13 
3. INTRODUCTION ............................................................................................................................ 14 
3.1 Background and Rationale ................................................................................................................ 14 
3.2 Risk/Benefit Assessment ................................................................................................................... 15 
4. OBJECTIVES AND ENDPOINTS ....................................................................................................... 15 
5. STUDY DESIGN ............................................................................................................................. 16 
5.1 General Study Design ........................................................................................................................ 16 
5.2 Study Duration and Enrollment ......................................................................................................... 17 
5.3 Justification of Dose .......................................................................................................................... 17 
5.4 End of Study Definition ...................................................................................................................... 17 
6. STUDY POPULATION ..................................................................................................................... 17 
6.1 Inclusion Criteria ............................................................................................................................... 17 
6.2 Exclusion Criteria ............................................................................................................................... 17 
6.3 Recruitment, Screening, and Enrollment .......................................................................................... 18 
7. STUDY SCHEDULE ......................................................................................................................... 18 
7.1 Screening (within 15 days prior to study visit) .................................................................................. 18 
7.2 Study Visit .......................................................................................................................................... 18 
7.3. Concomitant Medications ................................................................................................................ 19 
7.4 Early Termination .............................................................................................................................. 19 
8. STUDY EVALUATIONS ................................................................................................................... 19 
8.1 Specimen Preparation, Handling, and Shipping ................................................................................ 19 
9. INVESTIGATIONAL PRODUCT ........................................................................................................ 19 
9.1 Investigational Product (IP) ............................................................................................................... 19 
9.2 Dosing Regimen ................................................................................................................................ 20 
9.3 Dispensing of IP ................................................................................................................................. 20 
9.4 Dosage Form ..................................................................................................................................... 20 
9.5 Route of Administration .................................................................................................................... 20 

 
 
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9.6 Timing of Dose .................................................................................................................................. 20 
9.7 Packaging and Labelling ................................................................................................................... 20 
9.8 Storage and Handling ....................................................................................................................... 21 
9.9 Study Intervention Compliance ......................................................................................................... 21 
10. SAFETY MANAGEMENT ............................................................................................................... 21 
10.1 Adverse Events (AEs) ....................................................................................................................... 21 
10.2 Documenting and Reporting AEs .................................................................................................... 21 
10.3 Expedited Recording of Serious Adverse Events (SAEs) ................................................................... 21 
11. STATISTICAL CONSIDERATIONS ................................................................................................... 22 
11.1 Introduction ..................................................................................................................................... 22 
11.2 Sample Size Considerations ............................................................................................................. 22 
11.3 Safety .............................................................................................................................................. 22 
12. DATA HANDLING AND RECORD KEEPING ..................................................................................... 23 
13. CLINICAL TRIAL MATERIAL ACCOUNTABILITY ............................................................................... 23 
14. QUALITY CONTROL (QC)/QUALITY ASSURANCE (QA) ................................................................... 23 
14.1 QC/QA Monitoring .......................................................................................................................... 23 
14.2 Audits and Inspections .................................................................................................................... 23 
14.3 Protocol Deviation Management .................................................................................................... 24 
14.4 Clinical Research Monitoring .......................................................................................................... 24 
14.5 Medical Monitor.............................................................................................................................. 24 
15. REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ............................................. 25 
15.1 IRB/IEC ............................................................................................................................................. 25 
15.2 Written Informed Consent .............................................................................................................. 25 
15.3 Subject Compensation ..................................................................................................................... 26 
15.4 Privacy and Confidentiality ............................................................................................................. 26 
15.5 Regulatory Documentation ............................................................................................................. 26 
15.6 Protection of Human Subjects ......................................................................................................... 26 
16. REFERENCES ............................................................................................................................... 26 
 
 

 
 
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1. PROTOCOL SUMMARY  
1.1 Synopsis 
Study Title: Exploratory study to assess delivery of LMN-201 components via enteric capsules in the 
gut of individuals with ileostomies  
Study Number: CDI01 
Phase of development: Phase 1 
Investigational Product: Components of LMN-201 (a cocktail consisting of a bacteriophage lysin 
specific for C. difficile organism and three VHH-derived proteins that bind and inhibit C. difficile 
toxin B, delivered in whole, spray-dried spirulina (Arthrospira platensis) biomass 
Sponsor: Lumen Bioscience, Inc. 
Principal Investigator (PI): James Daveson, MD  
Study Center: Coral Sea Clinical Research Institute 
Study Objectives 
(Primary): 
• 
To determine if enteric capsules are sufficient to deliver LMN-201 
therapeutic proteins (VHH proteins and lysin) to the terminal ileum. 
Study Objectives 
(Exploratory): 
• 
To document the presence of LMN-201 therapeutic proteins at the 
terminal ileum 
• 
To determine variability between individuals in the quantity of LMN-201 
therapeutic proteins at the terminal ileum 
Subject Population 
Adults aged 19 and above with mature ileostomy  
Study Design 
This is a Phase 1, multi-site, open label, exploratory study of LMN-201 to 
evaluate the function of enteric capsules on drug release.  
Eligible volunteers with mature ileostomies will be enrolled and sequentially 
assigned to treatment. After documentation of informed consent, subjects will 
be asked to swallow 4 enteric capsules of LMN-201 components, 1 enteric 
capsule containing ring-shaped transit markers, and 1 immediate release 
capsule containing tube-shaped transit markers. Every hour following 
ingestion, ileostomy fluid will be collected, weighed, filtered, and analyzed. 
The procedure will be repeated for 4 hours after capsules and/or transit 
markers are observed in the collected ileostomy fluid, or 12 hours after 
ingestion, whichever time is shorter. 
In the first cohort, participants will receive only one of the LMN-201 VHH 
proteins administered in 3 enteric capsules as well as 1 enteric capsule 
containing lysin, 1 enteric capsule containing ring-shaped transit markers, and 
1 immediate release capsule containing tube-shaped transit markers. In the 
second cohort, participants will receive 1 enteric capsule of each of the LMN-
201 VHH proteins as well as 1 enteric capsule containing lysin, 1 enteric 

 
 
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capsule containing ring-shaped transit markers, and 1 immediate release 
capsule containing tube-shaped transit markers. 
The trial will be adapted between the first and the second cohort in the 
following manner: 
• 
If intact enteric capsules are observed in the ileostomy fluid of more than 
one participant 
o And the transit time is less than 4 hours, then a fluid restriction to less 
than 150 ml per hour will be implemented for the second cohort. 
o And the transit time is greater than 4 hours, then immediate release 
capsules will be utilized for the second cohort. 
• 
If the number of enteric capsules that remain encapsulated in the 
ileostomy fluid is less than 20% 
o Then the number of subjects in the second cohort will decrease from 
six to three.  
Number of Subjects 
Enrollment is planned for 2 cohorts of up to 6 subjects per cohort  
Study Duration 
Estimated time from when study opens to enrollment until completion of data 
analysis is 1-2 months.  
Participant 
Duration 
Each participant will complete the study in a single calendar day. The screening 
visit, to be completed up to 15 days prior to study visit, will take 1-2 hours.  
Inclusion Criteria 
• 
Adult (19 years of age or older) 
• 
Stable ileostomy (no revisions in the last 6 months) 
• 
Medically stable, but may be on medications for chronic conditions 
• 
Willing to participate in the clinical trial 
Exclusion Criteria 
• 
Individuals unable or unwilling to provide adequate informed consent 
• 
Non-English-speaking individuals 
• 
Clinically significant disease 
• 
Pregnancy, anticipated pregnancy, or breastfeeding  
• 
Use of anti-diarrheal medicine 
• 
Gastroparesis 
• 
Opioid use 
Study Endpoints 
(Primary) 
• 
Presence or absence of capsules and/or transit markers in ileostomy fluid 
by visual observation 
Study Endpoints 
(Exploratory) 
• 
Detect presence of LMN-201 therapeutic proteins (VHHs and lysin) in 
collected ileostomy fluid by EIA 
• 
Quantitate LMN-201 therapeutic proteins (VHHs and lysin) in collected 
ileostomy fluid by EIA 

 
 
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Safety and 
Tolerability 
Parameters 
All dosed subjects will be evaluated for any safety and/or tolerability concerns 
 

 
 
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1.2 Schedule of Activities (SoA) 
 
 
Screening 
Visit 
Study Visit 
End of Study 
Day -15 to 0 
Dose 
Follow up 
 
Hour 0 
Hourly for 4 hours following 
observation of any transit markers 
or capsules, or for 12 hours, 
whichever time is shorter  
Study Procedures 
 
 
 
 
Consent 
X 
 
 
 
Inclusion/exclusion criteria  
X 
X 
 
 
Medical History 
X 
 
 
 
Physical Exam 
X 
X 
 
 
Vitals signs 
X 
X 
X 
 
Urine Sample 
X 
X 
 
 
Study investigational 
product (IP) administered 
 
X 
 
 
Collect ileostomy fluid for 
analysis1  
 
X 
X 
 
Record AEs 
 
 
X 
 
Ship ileostomy fluid 1 
 
 
 
X 
1 See Manual of Procedures (MOP) for complete descriptions. 
 
 

 
 
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2. LIST OF ABBREVIATONS AND TERMS 
ADME 
Absorption, Distribution, Metabolism, and Elimination 
AE 
Adverse event 
CDI 
C. difficile infection 
CRF 
Case report form 
eCRF 
Electronic case report form 
EIA 
Enzyme Immunoassay 
GI 
Gastrointestinal tract 
 
 
cGMP 
Current Good Manufacturing Practices 
GRAS 
Generally Regarded as Safe 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IP 
Investigational product 
IRB 
Institutional Review Board 
MOP 
Manual of Procedures 
PI 
Principal Investigator 
SAE 
Serious adverse event 
US FDA 
United States Food and Drug Administration 
VHH 
Binding domain fragment of a single-domain camelid antibody 
 
 
 

 
 
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3. INTRODUCTION  
3.1 Background and Rationale  
Targeted delivery of any therapeutic agent is the key consideration of efficacy. Typically, therapeutic 
agents are delivered by oral or injection pathways and are then subjected to Absorption, Distribution, 
Metabolism, and Elimination (ADME) effects. Each of these effects reduces the amount of active product 
able to be delivered to the site of action, thus reducing efficacy.  
Lumen’s solution to treat and prevent enteric diseases is to provide the drug directly to the site of 
action, bypassing ADME effects. Delivering the therapeutic biomolecule within a safe food product, for 
example, spirulina (Arthrospira platensis) biomass, that is not absorbed by the intestinal tract removes 
any loss of the active agent by gastric digestion.  
Distribution concerns are thus fully eliminated as the product is delivered directly to the site of disease. 
With protein-based biomolecules, digestion of the therapeutic is the functional equivalent to 
metabolism within the gastrointestinal (GI) tract and remains the most significant challenge. Elimination, 
through the function of the GI tract, is linear and predictable. Most importantly, it does not reduce the 
amount of active agent at the site of action. Transit time, however, can affect the duration of action.  
Severe C. difficile colitis is associated with significant morbidity and mortality worldwide (Balsells et al., 
2019). It causes an inflammatory colitis that can lead to diarrhea, abdominal pain, fever, and malaise. 
The biomolecules Lumen Bioscience has developed to treat and prevent C. difficile infection (CDI) need 
to be delivered, undigested, and in a fully functional form to the distal small bowel and large intestine to 
be effective. LMN-201 in its final form will be a ‘cocktail’ of several prophylactic proteins of two distinct 
classes: a bacteriophage lysin, and several engineered binding domain fragments of a single-domain 
camelid antibody (VHHs) delivered orally within whole, spray-dried spirulina biomass. The spirulina-
bioencapsulated therapeutic proteins are delivered in vegetable-based, enteric delivery capsules of 500 
mg total spirulina biomass. Such capsules are designed to release the drug product at or before the 
terminal ileum, the earliest point in the GI tract where conditions, including CDI, become established in 
most patients. These capsules are commonly used and procured from an industry provider (Vcaps 
Enteric, Capsugel, a Lonza company) and are covered by an active Drug Master File with the United 
States Food and Drug Administration (US FDA).  
The first class of LMN-201 contains a single representative: a bacteriophage-derived lytic enzyme that is 
highly specific for degrading the C.  difficile cell wall resulting in rapid hypotonic death (Wang, et al., 
2015). These lytic enzymes, also called ‘endolysins’ or simply ‘lysins’, are a class of cell wall hydrolases 
with a narrow spectrum of activity. Research by the Fischetti Lab at Rockefeller University has shown 
that these enzymes efficiently kill all clinical isolate C.  difficile strains tested to date, while leaving 
commensal bacteria undisturbed.  
The second class consists of several VHHs that neutralize C. difficile exotoxins. Prior research has shown 
toxin B to be the primary driver of the disease pathology (Carter et al., 2015). Lumen Bioscience has 
developed three distinct VHHs that target different epitopes of toxin B.  
As discussed further in the Investigator’s Brochure, the safety and efficacy of LMN-201’s therapeutic 
proteins were evaluated in a series of in vitro and in vivo studies. In silico assessments of target epitope 
homology to human and commensal bacterial proteomes showed a low risk of cross-reactivity. The 

 
 
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efficacy of LMN-201 was successfully demonstrated in both mouse and hamster challenge models of 
CDI. These data strongly support the evaluation of LMN-201 in human subjects. 
This is a preliminary study to determine if enteric capsules containing constituents of LMN-201 are 
sufficient to deliver therapeutic proteins to the terminal ileum. 
3.2 Risk/Benefit Assessment  
Spirulina has a well-established and documented safety profile, leading the US FDA to conclude that 
spirulina is Generally Regarded as Safe (GRAS) and requires no further toxicity studies. Possible non-
serious adverse events (SAEs) have been reported with spirulina intended as a nutritional supplement. 
The US FDA MedWatch from January 2001 to July 2009 identified the most common non-SAEs from 
spirulina as: nausea; diarrhea; vomiting; fatigue; headache; dizziness; itching; rash, and abdominal 
cramps. These reports lacked information on the quantity, duration, individual history, or quality of 
spirulina used and were based on non-GMP spirulina (Marles et al., 2011).  
VHH antibodies are too large for systemic absorption through the gut lining and are directed with high 
specificity at pathogen target epitopes, unlike anything in the human body. As a result, the risk of off-
target toxicity in humans is close to zero. Lumen Bioscience completed a successful Phase 1 clinical trial 
in Australia in March 2020 with its initial VHH candidate, LMN-101. Systemic absorption of the 
engineered prophylactic protein was not detected, and there were no significant AEs. 
Lytic enzymes have an excellent profile for an orally dosed anti-microbial targeted to organisms in the GI 
tract. Similar to VHHs, they are too large to be systemically absorbed, greatly reducing concerns of 
immunogenicity. Bacteriophages produce lytic enzymes that are ubiquitous in the human GI tract. At 
any given time, as many as 1012 bacteriophage are present in the human gut (Shkoporov et al., 2019). 
Humans are continuously exposed to lytic enzymes during normal microbiome activity with no known ill 
effects. An intravenous (IV)-infused Staphylococcus aureus specific lytic enzyme, CF-301, has been 
shown to be safe and effective in Phase 2 clinical trials (Fowler et al., 2020), further demonstrating the 
safety of this class of enzymes. Lysozyme, the canonical member of this enzyme family, is a broad 
spectrum bacteriolytic enzyme. It is approved for use in several countries, including Japan (Hashida, et 
al., 2002), and possesses various applications for oral administration as contemplated by Lumen 
Bioscience. The US FDA has concluded that lysins are also GRAS and has required no further toxicity 
studies from other companies producing oral lysin-containing products. 
These safety records are consistent with the results generated by Lumen in a non-GLP safety study 
involving administration of LMN-201 to mice. No GLP studies or formal toxicology studies have been 
conducted with this product. 
While participation may not offer direct medical benefit to subjects, an effective CDI preventative would 
offer a societal benefit. Considering the overall burden of the disease, the Sponsor considers the 
potential benefits of participation to exceed the risks. 
4. OBJECTIVES AND ENDPOINTS  
OBJECTIVES 
ENDPOINTS 
Primary 
 
To determine if enteric coating on components of 
LMN-201 is sufficient to deliver therapeutic proteins 
to the terminal ileum.  
Presence or absence of capsules and/or transit 
markers in ileostomy fluid by visual observation  

 
 
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OBJECTIVES 
ENDPOINTS 
Exploratory 
 
To document the presence of LMN-201 
therapeutic proteins at the terminal ileum 
 
Detect presence of LMN-201 therapeutic proteins 
(VHHs and lysin) in collected ileostomy fluid by EIA 
 
Exploratory  
 
To determine variability between individuals in 
the quantity of LMN-201 therapeutic proteins at 
the terminal ileum 
Quantitate LMN-201 therapeutic proteins (VHHs 
and lysin) in collected ileostomy fluid by EIA 
 
5. STUDY DESIGN  
5.1 General Study Design  
This is a Phase 1, multi-site, open label, nonrandomized, exploratory study to assess delivery of LMN-201 
components via enteric capsules.  
The trial will be evaluated through 2 cohorts of up to 6 subjects each. The first cohort will utilize specific 
components to allow analysis of individual component digestion. Eligible subjects with mature 
ileostomies will be consented, enrolled, assigned to treatment sequentially, and asked to swallow the 
following:  
 
Number of capsules administered to subject—First cohort 
Subject 
Anti-toxin B 
VHH-1 
Anti-toxin B 
VHH-2 
Anti-toxin B 
VHH-3 
Lysin 
capsules 
Capsule with 
tube-shaped  
transit markers 
Capsule  
with ring-shaped  
transit markers 
1 
3 
— 
— 
1 
1 
1 
2 
3 
— 
— 
1 
1 
1 
3 
— 
3 
— 
1 
1 
1 
4 
— 
3 
— 
1 
1 
1 
5 
— 
— 
3 
1 
1 
1 
6 
— 
— 
3 
1 
1 
1 
Every hour after ingestion, ileostomy fluid will be collected, weighed, filtered, and analyzed for the 
presence of capsules and/or transit markers. This procedure will be repeated for four hours after the 
capsules and/or transit marker are observed in the ileostomy collection, or 12 hours after ingestion, 
whichever time is shorter. 
The trial will be adapted between the first and the second cohort in the following manner: 
• 
If intact enteric capsules are observed in the ileostomy fluid of more than one participant 
o And the transit time is less than 4 hours, then a fluid restriction to less than 150 ml per hour will 
be implemented for the second cohort. 
o And the transit time is greater than 4 hours, then immediate release capsules will be utilized for 
the second cohort. 
• 
If the number of enteric capsules that remain encapsulated in the ileostomy fluid is less than 20% 
o Then the number of subjects in the second cohort will decrease to three.  

 
 
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The second cohort, allowing for the above changes, will utilize a ‘cocktail’ formulation of VHHs. Subjects 
will be asked to swallow the following: 
 
Number of capsules administered to subject—Second cohort 
Subject 
Anti-toxin B 
VHH-1 
Anti-toxin B 
VHH-2 
Anti-toxin B 
VHH-3 
Lysin 
capsules 
Capsule with 
tube-shaped  
transit markers 
Capsule  
with ring-shaped  
transit markers 
1 
1 
1 
1 
1 
1 
1 
2 
1 
1 
1 
1 
1 
1 
3 
1 
1 
1 
1 
1 
1 
Any changes not described above will only be implemented once a protocol amendment has been 
submitted to the appropriate Institutional Review Board (IRB) or Independent Ethics Committee (IEC), 
and has been reviewed and approved.  
5.2 Study Duration and Enrollment  
Estimated duration for the main protocol (i.e., start of screening through to data analysis) is anticipated 
to be approximately 1-2 months. Subjects will be screened for eligibility within 15 days before the start 
of the study. The estimated time it will take for each individual participant to complete all study visits is 
less than or equal to 12 hours.  
5.3 Justification of Dose  
The dose chosen for this preliminary evaluation is primarily convenience-based for each component and 
is the amount that can adequately fit into one capsule. 
 
5.4 End of Study Definition  
Each subject will complete the study in a single calendar day. Each cohort will be considered completed 
when the total number of participants have completed their participation. The study will be considered 
completed when both cohorts have completed their participation and the data has been delivered and 
approved. 
6. STUDY POPULATION  
6.1 Inclusion Criteria  
Individuals must meet all of the following criteria to be eligible to participate in this study:   
• 
Willing to participate in the clinical trial 
• 
Able and willing to provide informed consent 
• 
Stable ileostomy (no revisions in the last 6 months) 
• 
At least 19 years old  
• 
Medically stable, but may be on medications for chronic conditions 
6.2 Exclusion Criteria  
Individuals will be excluded from this study if they meet any of the following criteria:  
• 
Unable or unwilling to provide adequate informed consent  
• 
Non-English speakers  
• 
Clinically significant disease 

 
 
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• 
Women who are pregnant, intending to become pregnant, or breastfeeding 
• 
Use of anti-diarrheal medicine 
• 
Suffer gastroparesis 
• 
Opioid use 
6.3 Recruitment, Screening, and Enrollment   
Healthy volunteers with mature ileostomies will be recruited by the site PI using advertising approved by 
the appropriate IRB/IEC. Volunteers who express interest in participating in the study will be asked to 
complete a pre-screen to assess general health status and basic eligibility. Potential volunteers 
determined to have an ileostomy and otherwise be generally healthy and meeting basic eligibility 
requirements will be scheduled for an in-person screening. Volunteers will be carefully screened on the 
details of the protocol and their time commitment.  
7. STUDY SCHEDULE 
7.1 Screening (within 15 days prior to study visit) 
Volunteers will be screened for eligibility within 15 days before the study visit. Volunteers will be screened 
according to predefined inclusion criteria as described in section 6.1. See section 6.2 for a list of exclusion 
criteria. The following procedures will be performed at screening: 
 
• 
Informed Consent 
• 
Medical history, including existing medical conditions 
• 
Record concomitant medications 
• 
Physical exam 
• 
Vital signs including heart rate, respiratory rate, seated blood pressure, and temperature 
• 
Urine sample 
 
7.2 Study Visit  
Subjects will be asked to refrain from eating after 11 p.m. the night before arrival at study facility. The 
following procedures will be performed upon arrival: 
• 
Assessment of inclusion/exclusion criteria 
• 
Record concomitant medications 
• 
Vital signs including heart rate, respiratory rate, seated blood pressure, and temperature 
• 
Physical exam 
• 
Urine sample 
• 
Collect ileostomy fluid 
• 
Administer study product 
After IP is administered, the following procedures will be conducted every hour until study staff observe 
capsules or transit markers in ileostomy fluid collection: 
• 
Collect ileostomy fluid for analysis as described in MOP  
• 
Monitor for AEs and measure vital signs 

 
 
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After any transit markers is observed in the ileostomy fluid, study staff will repeat ileostomy fluid 
collection procedures hourly for a minimum of 4 additional hours or 12 hours total study participation, 
whichever comes first.   
Participants can start eating 2 hours after dosing. 
7.3. Concomitant Medications 
Concomitant medication use will be documented. 
7.4 Early Termination  
Subjects have the right to withdraw from the study at any time and for any reason. Subjects who 
withdraw their consent will not receive any further study drug but will be offered all follow-up safety 
assessments. 
Subjects who withdraw from the study prior to treatment will be replaced per recruitment and 
enrollment processes outlined above in 6.3.  
8. STUDY EVALUATIONS  
8.1 Specimen Preparation, Handling, and Shipping 
Ileostomy fluid is collected prior to the administration of study capsules, filtered, and aliquoted (either 
unadulterated or supplemented with purified proteins and protease inhibitor to use as a positive 
control). Once study capsules are administered, ileostomy content is collected hourly for the duration of 
the protocol (up to 12 hours). Upon collection, they are filtered, and the retained material is examined 
for the presence of intact capsules, capsule remnants, and transit markers. If these are observed, a 
photograph is taken to record the findings. The pH and volume of the filtrate are measured and 
recorded. Five 10 mL aliquots are prepared, supplemented with a protease inhibitor, and immediately 
flash frozen and stored at -80 ˚C until shipment. For shipment, one positive control, half of the pre-
treatment samples, and 1 tube from each timepoint are assembled and transported on dry ice to Lumen 
Bioscience at the end of the study.  
9. INVESTIGATIONAL PRODUCT  
9.1 Investigational Product (IP) 
The investigational product (IP), individually encapsulated components of LMN-201, will be supplied by 
Lumen Bioscience. LMN-201 is being developed to be a cocktail consisting of a bacteriophage lysin 
specific for degrading the C. difficile organism and three VHH-derived proteins designed to bind and 
inhibit C. difficile toxin B, delivered in whole, spray-dried spirulina biomass. 
The LMN-201 drug substance is manufactured using four stable cell lines engineered to express the 
respective lysin and VHHs. The substance is manufactured under Current Good Manufacturing Practices 
(cGMP) using recombinant DNA processes and controls. The cells are cultured using chemically defined, 
animal-product-free basal medium under photoautotrophic growth conditions, using bicarbonate and 
CO2 as the carbon source. After harvesting and rinsing with a dilute solution of trehalose, cells are spray 
dried to produce drug substance. The drug substance is fully tested against established specifications 
prior to release for further processing and use in clinical studies. Each strain contains a single 

 
 
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prophylactic protein, and the prophylactic protein ‘cocktails’ are generated by growing these strains 
separately, spray drying them separately, and finally dry-mixing the resulting powders together. 
The LMN-201 drug product is manufactured at Lumen Bioscience’s cGMP manufacturing facility in 
Seattle, Washington, US. The individually encapsulated components of drug substance are provided in 
pre-formulated capsules. The individually encapsulated components of LMN-201 drug product are 
tested for potency and purity defined by established specifications. Lumen Bioscience’s cell banking 
protocols are designed to comply with ICH guideline Q5D for microbial cells. LMN-201 drug products and 
the tube-shaped transit markers will be filled into Vcaps Enteric intrinsically enteric vegetarian capsules 
size 00 (Capsugel). Ring-shaped transit markers will be provided in manufacturers non-enteric capsules 
(Medifactia AB). 
Transit markers (Transit-Pellets™ Radiopaque Markers, manufactured by Medifactia AB) will also be 
provided by Lumen Bioscience.  
9.2 Dosing Regimen  
Subjects will receive individually encapsulated components of LMN-201, taken as four (4) capsules (500 
mg biomass in each capsule), orally. In addition, they will receive an immediate release capsule 
containing ring-shaped transit markers and an enteric capsule containing tube-shaped transit markers to 
allow calculation of transit time and encapsulation dissolution visually.  
9.3 Dispensing of IP 
The investigational team will dispense individually encapsulated components of LMN-201 and transit 
markers-containing capsules according to the study protocol. 
9.4 Dosage Form  
LMN-201 ingredients are spray-dried spirulina biomass and trehalose. Individually encapsulated 
components of LMN-201 doses (500 mg) are packaged in size 00, white, opaque capsules (Capsugel, 
Morristown, NJ, US), Vcaps Enteric (first cohort) and Vcaps Plus (second cohort, if adapted). Vcaps 
Enteric capsules incorporate pH-controlled release technology designed to release encapsulated 
components at or before the terminal ileum. Vcaps Plus capsules are immediate release capsules 
designed to release encapsulated components in the stomach. No capsules contain any materials of 
human or animal origin.  
9.5 Route of Administration  
Individually encapsulated components of LMN-201 and transit markers must be administered orally and 
will be taken with water only.   
9.6 Timing of Dose 
Capsules are to be self-administered by subjects upon confirmation of subject desire for participation.  
9.7 Packaging and Labelling  
The IP will be provided in a single dose packet with the appropriate labels. 
 
 

 
 
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9.8 Storage and Handling  
All IPs will be kept in a locked area with limited access. Capsules containing IP should be stored at room 
temperature, 59-77°F (15-25°C) and protected from moisture, light, and extreme heat during storage. 
Only subjects enrolled in the study may receive the IP in accordance with all applicable regulatory 
requirements. Upon the completion of the study, this material will be subjected to final inspection and 
reconciliation. At that time, all unused, partially used, and fully used (empty) container(s) along with a 
packing slip must be destroyed as per Pharmacy Manual. Documentation of destruction will be retained 
by the investigational pharmacy with the study files. 
9.9 Study Intervention Compliance 
A member of the study team will witness the ingestion of the IP. 
10. SAFETY MANAGEMENT 
10.1 Adverse Events (AEs)  
The Principal Investigator (PI) is responsible documenting AEs according to the guidelines below.  
An AE is any untoward medical occurrence or change in a clinical trial subject having received a biologic 
or medicinal product, whether or not considered treatment related. This may occur in any phase of the 
clinical study. 
Events meeting the AE definition include:  
• 
Any noxious, pathological, or unintended change in anatomical, physiologic, or metabolic 
functions as indicated by physical signs, symptoms, and/or clinically significant laboratory 
abnormalities 
• 
Exacerbation or worsening of pre-existing conditions or events  
• 
Intercurrent illnesses, injuries, or vaccine or drug interaction 
• 
Worsening of abnormal clinical laboratory values  
Stable, pre-existing conditions and/or elective procedures are not AEs. 
10.2 Documenting and Reporting AEs 
All observed or volunteered AEs regardless of suspected causal relationship to the IP will be recorded on 
the AE page(s) of the case report form (CRF). The investigator must assess all AEs for seriousness, 
severity, and relation to IP.  
The PI will follow all AEs, regardless of seriousness or severity, until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator.  
The investigator is responsible for ensuring appropriate clinical management of all AEs until they are 
resolved or stabilized at a level acceptable to the investigator. Appropriate clinical management of AEs is 
at the discretion of the investigator.  
10.3 Expedited Recording of Serious Adverse Events (SAEs) 
Any SAE must be reported to the Sponsor within 24 hours.  

 
 
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Instructions: 
The following information should be sent via email (preferred) or telephone: 
• 
Protocol IND number, IP, PI name, and contact number 
• 
Subject identification number 
• 
Serious adverse event (SAE), onset date, date of IP administration, severity, relationship, and 
subject’s status 
AND email the following documents to Medical Monitor, Lumen Bioscience: 
• 
Cover sheet 
• 
Adverse Event (AE) CRF 
• 
Supplemental SAE Report Form 
• 
Concomitant Medication CRF or a list of concomitant medications 
• 
Medical record progress notes including pertinent laboratory/diagnostic test results 
The PI will assess all SAEs as being either related or unrelated to the administered product. 
Investigators are required to forward safety information provided by the Sponsor’s representative to the 
IRB/IEC. All SAEs will be reported to the IRB/IEC within 24 hours of the PI becoming aware of the event: 
Bellberry Limited HREC 
123 Glen Osmond Road Eastwood Adelaide 
South Australia 5063 
Phone: (08) 8361 3222 
Email: bellberry@bellberry.com.au 
11. STATISTICAL CONSIDERATIONS  
11.1 Introduction  
Safety, clinical outcomes, and outcome data will be entered into the data system. Data will be edited 
with standard strategies for range and consistency checks. AEs for all subjects will be included in the 
safety analysis. 
11.2 Sample Size Considerations  
No statistical hypothesis is required to be tested. Therefore, no formal sample size calculations have 
been made. The sample size has been determined to be up to six (6) per cohort to provide preliminary 
information.  
Overall, up to 12 human subjects will be exposed to the IP.  
11.3 Safety  
Preliminary analysis of safety and tolerability will include all subjects who received study drug. Safety 
will be evaluated from reported AEs, physical examination findings, and vital signs. 

 
 
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12. DATA HANDLING AND RECORD KEEPING 
The PI will maintain complete and accurate documentation for the study. All required study data will be 
clearly and accurately recorded by authorized study personnel in the electronic CRFs (eCRFs). Only 
designated study site personnel shall record or change data in an eCRF. The PI will be responsible for the 
procurement of data and for quality of data recorded in the eCRFs. Original observations entered 
directly into the eCRFs are considered source data. Study-specific procedures detail how each form will 
be completed. The study coordinator will ensure accuracy of the CRFs. All source documents will be 
retained at the site. 
A detailed data management plan will be written and approved by the study team and the PI. The plan 
will be drafted prior to study initiation but will be finalized before study close-out and database lock. 
13. CLINICAL TRIAL MATERIAL ACCOUNTABILITY  
The site PI is responsible for maintaining accurate records of the processing and use of all clinical trial 
materials. All used, unused, or undispensed study medication must be accounted for by the site PI. 
Drug accountability will be conducted during monitoring visits to ensure appropriate receipt, storage, 
dispensing, and documentation of returned Clinical Trial Materials. 
14. QUALITY CONTROL (QC)/QUALITY ASSURANCE (QA) 
14.1 QC/QA Monitoring 
During the study and at the close-out, a monitor from Lumen Bioscience or its representative will have 
regular contacts with the investigational site for the following:  
• 
Provide information and support to the Investigator(s) 
• 
Confirm that facilities remain acceptable 
• 
Confirm that the investigational team is adhering to the protocol, data is being accurately 
recorded in the CRFs, and IP accountability checks are being performed 
• 
Perform source data verification. This includes a comparison of the data in the CRFs with the 
subject’s medical records at the hospital or practice, and other records relevant to the study. 
This will require direct access to all original records for each subject (e.g., clinic charts) 
• 
Record and report any protocol deviations not previously sent to Lumen Bioscience 
• 
Confirm AEs and SAEs have been properly documented on CRFs and confirm any SAEs have been 
forwarded to Lumen Bioscience or its representative and those SAEs that met criteria for 
reporting have been forwarded to the IRB/IEC and/or FDA 
The monitor will be available between visits if the Investigator(s) or other staff needs information or 
advice. The PI assumes ultimate responsibility for the conduct of the study and remains readily 
accessible throughout the duration of the study.  
14.2 Audits and Inspections  
Authorized representatives of Lumen Bioscience or a regulatory authority may visit the site to perform 
audits or inspections, including source data verification. The purpose of a Lumen Bioscience audit or 
inspection is to systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analyzed, and accurately 

 
 
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reported according to the protocol, Good Clinical Practice (GCP) guidelines of the International 
Conference on Harmonization, and any applicable regulatory requirements. The Investigator should 
contact Lumen Bioscience immediately if contacted by a regulatory agency about an inspection.  
The Investigator agrees to allow the monitor to inspect the drug storage area, study drug stocks, drug 
accountability records, subject charts and study source documents, and other records relative to study 
conduct.  
To ensure compliance with GCP and all applicable regulatory requirements, Lumen Bioscience may 
conduct one or more quality assurance audits.  
14.3 Protocol Deviation Management  
Other than minimal-risk changes, all unanticipated major problems involving human subjects or others 
will be reported promptly to the IRB/IEC. No such changes will be made to the research without IRB/IEC 
approval unless necessary to eliminate apparent immediate hazards to human subjects. Minor minimal-
risk deviations necessitated during the trial will be made on site as needed and documented for 
subsequent review within a reasonable time period. 
Deviations from the protocol that potentially impact on subject safety will be promptly reported to the 
Medical Monitor, IRB/IEC, and the Sponsor. Other deviations will be reported at the time of continuing 
review. 
14.4 Clinical Research Monitoring  
Lumen Bioscience monitoring responsibilities will be provided by an independent Clinical Research 
Associate (CRA). Monitoring will be conducted according to an approved monitoring plan and applicable 
SOPs. The CRA or other authorized representatives of the Sponsor may inspect all documents and 
records maintained by the PI. The clinical study site will permit access to such records. The PI will obtain, 
as part of informed consent, permission for authorized representatives of the Sponsor, or regulatory 
authorities, to review, in confidence, any records identifying individuals in this clinical study. 
The PI will notify the Sponsor within 24 hours following contact by a regulatory agency. The PI and study 
coordinator will be available to respond to reasonable requests and audit queries made by authorized 
representatives of regulatory agencies. The PI will provide the Sponsor with copies of all correspondence 
that may affect the review of the current study or his/her qualification as a PI in clinical studies 
conducted by the Sponsor. The Sponsor will provide any needed assistance in responding to regulatory 
audits or correspondence. The PI will permit independent auditors (employees of the Sponsor or an 
external company designated by the Sponsor) to verify source data validation of the regularly monitored 
clinical trial. The auditors will compare the entries in the CRFs with the source data and evaluate the 
study site for its adherence to the clinical study protocol and GCP guidelines and applicable regulatory 
requirements. The Sponsor will arrange local monitoring prior to beginning, at initiation, during the 
study, and at closeout by the study monitor or designee. 
14.5 Medical Monitor  
The Medical Monitor shall be available for consultation with the PI and serves as liaison between the 
clinical study site and the Sponsor. The study investigators will consult with the Medical Monitor on 
issues related to subject enrollment and continued participation as needed. The Medical Monitor is 
required to review all unanticipated problems involving risk to subjects, SAEs, and all subject deaths 

 
 
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associated with the protocol, and provide an unbiased written report of the event. At a minimum, the 
Medical Monitor should comment on the event outcomes, and in the case of a SAE or death, comment 
on the relationship to participation in the study. The Medical Monitor should indicate concurrence or 
non-concurrence with the details of the report provided by the PI. Reports for events determined by 
either the PI or Medical Monitor to be related or unrelated to participation and reports of events 
resulting in death should be promptly forwarded to the ethics board.  
15. REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS  
15.1 IRB/IEC  
The PI must verify that the ethics board has approved the clinical protocol, Informed Consent Form (ICF), 
and recruitment materials for the investigation prior to conducting study evaluations. Initial ethics board 
approval, and all materials approved by the ethics board for this study including the ICF and recruitment 
materials, must be maintained by the Investigator and made available for inspection. 
All amendments to the protocol, ICF, and/or questionnaires, including a change of PI, will be submitted to 
the ethics board for review and approval prior to implementation. The PI is responsible for informing the 
ethics board of any amendment to the protocol. 
The PI is also responsible for providing the ethics board with reports of any reportable serious adverse 
reactions from any other study conducted with the IP. Lumen Bioscience will provide this information to 
the PI. 
15.2 Written Informed Consent  
The ICF will be prepared by the Sponsor. The ICF will clearly describe the nature, scope, and potential 
risks and benefits of the study, in a language that the subject understands. The ICF will conform to all 
the requirements for informed consent according to ICH GCP and US FDA guidelines (21 CFR 50) and will 
include any additional elements required by the Investigator’s institution or local regulatory authorities. 
The ICF will adhere to the ethical principles that have their origin in the Declaration of Helsinki.  
Prior to the beginning of the study, the Sponsor will obtain the IRB/IEC’s written approval/favorable 
opinion of the written ICF. The IRB/IEC approved ICF will be given to each volunteer. The volunteers will 
be given adequate time to discuss the study with the PI or site staff and to decide whether or not to 
participate. Each volunteer who agrees to participate in the trial and who signs the ICF will be given a 
copy of the signed, dated, and witnessed document. The original signed ICF will be retained by the 
Investigator in the study files. 
The ICF and any other information provided to subjects will be revised whenever important new 
information becomes available that is relevant to the subject's consent. The PI will obtain the IRB/IEC’s 
written approval/favorable opinion prior to the use of the revised documents. The PI, or person 
designated by the PI, will fully inform the subject of all pertinent aspects of the study and of any new 
information relevant to the subject's willingness to continue participation in the study.  Subjects will 
read and sign any and all revised ICFs.  
The PI or research staff designee will ensure that the volunteer or legally authorized representative is 
given full and adequate oral and written information about the nature, purpose, possible risks, and 

 
 
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potential benefits of the study. The subject or legally authorized representative must also be notified that 
the subject is free to discontinue from the study at any time. The subject or legally authorized 
representative should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent, or the signed and dated informed consent of a legally 
authorized representative, must be obtained before conducting any study procedures. The PI must 
maintain the original, signed ICF. A copy of the signed ICF must be given to the subject or legally authorized 
representative. 
15.3 Subject Compensation  
Compensation for participation will be provided only for completed study procedures designated for 
compensatory payment. If a volunteer is eligible to participate in the investigational protocol after 
screening, the subject will be compensated for study participation-associated time and travel.  
15.4 Privacy and Confidentiality  
The PI will exercise all reasonable precautions within the constraints of the applicable regulatory 
requirements to maintain the confidentiality of subjects’ identities. On exported electronic source data or 
any other documents submitted to the Sponsor, subjects will only be identified by subject number. 
Documents not for submission to the Sponsor, e.g., subject identification log and original ICF, will be 
maintained by the PI in strict confidence. 
15.5 Regulatory Documentation 
Before the trial starts, Essential Documents as defined in ICH E6 will be generated and placed in both the 
Investigator’s and Sponsor’s files. Additional Essential Documents will be added to both files as new 
information becomes available and at the completion or termination of the trial as defined in ICH E6. 
15.6 Protection of Human Subjects 
 
Declaration of Helsinki  
The Investigator will conduct this study in accordance with the Declaration of Helsinki (1964) including all 
amendments up to and including the October 2013 revision. 
 
Good Clinical Practice and Regulatory Compliance 
The Investigator will conduct this study in accordance with the principles of GCP (current ICH guidelines) 
and the requirements of all local regulatory authorities regarding the conduct of clinical trials and the 
protection of human subjects. 
 
The study will be conducted as described in the approved protocol in accordance with the obligations of 
clinical Investigators set forth in the Form FDA 1572. 
16. REFERENCES 
Balsells, E., Shi, T., Leese, C., Lyell, I., Burrows, J., Wiuff, C., Campbell, H., Kyaw, M. H., & Nair, H. (2019). 
Global burden of Clostridium difficile infections: A systematic review and meta-analysis. Journal of 
Global Health, 9(1). https://doi.org/10.7189/jogh.09.010407 
Carter, G. P., Chakravorty, A., Pham Nguyen, T. A., Mileto, S., Schreiber, F., Li, L., Howarth, P., Clare, S., 
Cunningham, B., Sambol, S. P., Cheknis, A., Figueroa, I., Johnson, S., Gerding, D., Rood, J. I., Dougan, G., 

 
 
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Lawley, T. D., & Lyras, D. (2015). Defining the Roles of TcdA and TcdB in Localized Gastrointestinal 
Disease, Systemic Organ Damage, and the Host Response during Clostridium difficile Infections.  mBio,  
6(3), e00551. https://doi.org/10.1128/mBio.00551-15 
Hashida, S., Ishikawa, E., Nakamichi, N., & Sekino, H. (2002). Concentration of egg white lysozyme in the 
serum of healthy subjects after oral administration. Clinical and experimental pharmacology & 
physiology, 29(1-2), 79–83. https://doi.org/10.1046/j.1440-1681.2002.03605.x 
Marles, R. J., Barrett, M. L., Barnes, J., Chavez, M. L., Gardiner, P., Ko, R., Mahady, G. B., Low Dog, T., 
Sarma, N. D., Giancaspro, G. I., Sharaf, M., & Griffiths, J. (2011). United States pharmacopeia safety 
evaluation of spirulina.Critical reviews in food science and nutrition,  51(7), 593–604. 
https://doi.org/10.1080/10408391003721719  
Shkoporov, A. N., Clooney, A. G., Sutton, T., Ryan, F. J., Daly, K. M., Nolan, J. A., McDonnell, S. A., 
Khokhlova, E. V., Draper, L. A., Forde, A., Guerin, E., Velayudhan, V., Ross, R. P., & Hill, C. (2019). The 
Human Gut Virome Is Highly Diverse, Stable, and Individual Specific.  Cell host & microbe,  26(4), 527–
541.e5. https://doi.org/10.1016/j.chom.2019.09.009 
Wang, Q., Euler, C. W., Delaune, A., & Fischetti, V. A. (2015). Using a Novel Lysin To Help Control 
Clostridium difficile Infections.  Antimicrobial agents and chemotherapy, 59(12), 7447–7457. 
https://doi.org/10.1128/AAC.01357-15