Clinical trial NCT04191148
Conditions: Urinary Tract Infections
Keywords: UTI Bacteriophage Phage
Sponsor: Locus Biosciences
Start date: 2019-12-30; Completion date: 2020-11-19
Enrollment: 36 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study LBx-1001 is a multi-center randomized, double-blind study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of LBP-EC01 in patients with indwelling urinary catheters, or requiring intermittent catheterization, and/or patients with asymptomatic bacteriuria caused by Escherichia coli (E. coli). This study population has been selected because LBP-EC01 is a phage cocktail where active bacterial host engagement is required to allow for amplification of the phage and evaluation of the safety and PK of the phage cocktail. Eligible patients will require confirmation of colonization with a urine sample taken within 10 days of randomization that cultures contain ≥10\^3 E. coli colony forming unit (CFU)/mL, without the patient having clinical signs or symptoms of an active urinary tract infection (UTI) requiring antibiotic treatment. Patients should have E. coli as the primary colonizing bacteria and must not have a secondary bacterial colonization at levels equal to or greater than that seen from E. coli.

Detailed description:
Approximately 30 patients 18 years of age or older with a history of urinary tract infection or colonization caused by E. coli who have indwelling urinary catheters, or who require intermittent catheterization, and/or patients with asymptomatic bacteriuria caused by E. coli colonization (≥10\^3 CFU/mL) on microbiological diagnosis, without clinical signs or symptoms of infection requiring antibiotic treatment will be enrolled. Patients will be screened for presence of E. coli colonization (≥10\^3 CFU/mL) prior to randomization and evaluated for potential bacterial susceptibility to LBP-EC01.

Secondary Objective: To evaluate the pharmacodynamics (PD) of LBP-EC01. Exploratory Objective: To explore the influence of LBP-EC01 on the urinary tract microbiota.

Arms: arm 1: crPhage cocktail arm 2: Lactated Ringer's solution, injection, USP
Interventions: intervention 1: LBP-EC01 intervention 2: Placebo
Intervention descriptions: intervention 1: crPhage cocktail: at approximately 1.5 x 10\^10 to 3.0 x 10\^10 PFU/vial dosed BID by intraurethral administration intervention 2: Lactated Ringers Solution for Injection dosed BID by intraurethral administration

Protocol documents:
Prot_000.pdf: 
Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
Version 1.4 
Protocol: LBx-1001 
01 Oct 2020 
Locus Biosciences, Inc  
Confidential 
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A MULTI-CENTER RANDOMIZED, DOUBLE-BLIND STUDY 
TO ASSESS THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS AND PHARMACODYNAMICS OF 
LBP-EC01 IN PATIENTS WITH LOWER URINARY TRACT 
COLONIZATION CAUSED BY E. COLI 
 
SHORT TITLE: “SAFETY, TOLERABILITY, AND 
PHARMACOKINETICS OF LBP-EC01 IN PATIENTS WITH 
LOWER URINARY TRACT COLONIZATION CAUSED BY E. 
COLI” 
 
Investigational Product: LBP-EC01 
Protocol Number: LBx-1001 
Development Phase: 1b 
National Clinical Trial (NCT) Identified Number:  N/A 
IND Sponsor: Locus Biosciences, Inc 
523 Davis Drive, Suite 350 
Morrisville, NC 27560 
 
Version Number:  1.4 
01 October 2020 
 


Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
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Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
2.1, 4.0, 
10.4.1. 
Updated to clarify that PD analysis will be 
conducted with urine samples across all 
timepoints collected: Baseline (Day 1), Day 
2, Day 3, Day 5, Day 7 (EOT), Day 14, and 
Day 28. 
Administrative clarification 
Confidentiality Statement:  The information in this document is confidential and is not to be disclosed without the 
written consent of Locus Biosciences, Inc. (Locus) except to the extent that disclosure would be required by law and 
for the purpose of evaluating and/or conducting a clinical study for Locus. Persons to whom the information is 
disclosed must be informed that the information is confidential and proprietary to Locus and that it may not be 
further disclosed to third parties. 


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Protocol Approval Page 
 
Study Title 
A Multi-Center Randomized, Double-Blind Study to Assess the Safety, 
Tolerability, Pharmacokinetics and Pharmacodynamics of LBP-EC01 in 
Patients With Lower Urinary Tract Colonization Caused by E. Coli 
Protocol Number: 
LBx-1001 
Protocol Version: 
Version 1.4 
Date: 
01 Oct 2020 
 
 
Approved for the Sponsor by:  
Name: Paul Kim, PhD 
Title:   Chief Development Officer 
            Locus Biosciences, Inc. 
 
 
 
 
Signature 
 
Date (ddmmmyyyy) 
 
01 Oct 2020


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Revision History 
Version 
Date 
Comment 
1.1 
28 FEB 2019 
For IRB/IND submission 
1.2 
22 MAR 2019 
Clarifications  
1.3 
04 OCT 2019 
Incorporation of FDA feedback 
1.4 
01 OCT 2020 
Clarifications/administrative change 
 


Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
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Study Contact Information 
 
Any serious adverse event (SAE) must be reported within 24 hours. See Section 9.3.6  for 
detailed adverse event reporting procedures. 
Study Contact Information 
Role in Study 
Name, Title, Address 
Telephone / fax / email 
Sponsor Medical Monitor 
Peter Potgieter, MD 
523 Davis Dr., Ste. 350 
Morrisville, NC 27560 
Phone: (949) 302-2930 
Email: peter.potgieter@locus-bio.com 
Contract Research 
Organization (CRO) 
Medical Monitor  
 
Brian Murphy, MD 
5375 Medpace Way 
Cincinnati, OH 45227 
 
Phone: (513) 579-9911 x12416 
Email: b.murphy1@medpace.com 
24-Hour SAE Reporting 
Medpace SAE Hotline – Clinical 
Safety 
 
Telephone number/SAE Hotline: +1-
800-730-5779 dial 3 or +1-513-579-9911 
dial 3 
Fax number: +1-866-336-5320 or +1-
513-579-0444 
Email: Medpace-
safetynotification@medpace.com 
 
 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
1. 
STATEMENT OF COMPLIANCE ...........................................................................10 
2. 
PROTOCOL SUMMARY ..........................................................................................11 
2.1. 
Synopsis ......................................................................................................................11 
3. 
INTRODUCTION ......................................................................................................17 
3.1. 
Study Rationale ...........................................................................................................17 
3.2. 
Background .................................................................................................................18 
3.2.1. 
Disease Background ...................................................................................................18 
3.2.2. 
Bacteriophage Therapy ...............................................................................................18 
3.2.3. 
Bacterial Host Range Analysis ...................................................................................20 
3.3. 
Risk/Benefit Assessment ............................................................................................20 
3.3.1. 
Known Potential Risks ...............................................................................................20 
3.3.1.1. 
Immediate Potential Risks ..........................................................................................20 
3.3.1.2. 
Long Term Potential Risks .........................................................................................20 
3.3.2. 
Known Potential Benefits ...........................................................................................21 
3.3.3. 
Assessment of Potential Risks and Benefits ...............................................................22 
4. 
OBJECTIVES AND ENDPOINTS ............................................................................23 
5. 
STUDY DESIGN .......................................................................................................24 
5.1. 
Overall Design ............................................................................................................24 
5.2. 
Scientific Rationale for Study Design ........................................................................25 
5.3. 
Justification for Dose ..................................................................................................25 
5.4. 
End of Study Definition ..............................................................................................25 
6. 
STUDY POPULATION .............................................................................................26 
6.1. 
Inclusion Criteria ........................................................................................................26 
6.2. 
Exclusion Criteria .......................................................................................................26 
6.3. 
Randomization Criteria ...............................................................................................27 
6.4. 
Lifestyle Considerations .............................................................................................27 
6.5. 
Screening and Screen Failures ....................................................................................27 
6.6. 
Strategies for Recruitment and Retention ...................................................................28 
7. 
STUDY TREATMENT ..............................................................................................29 
7.1. 
Treatment Administration ...........................................................................................29 
7.1.1. 
Investigational Medicinal Product Description ..........................................................29 


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7.1.2. 
Dosing and Administration .........................................................................................29 
7.2. 
Preparation/Handling/Storage/Accountability ............................................................30 
7.2.1. 
Acquisition and Accountability ..................................................................................30 
7.2.2. 
Formulation, Appearance, Packaging, and Labeling ..................................................31 
7.2.3. 
Product Storage and Stability .....................................................................................31 
7.2.4. 
Preparation ..................................................................................................................31 
7.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................31 
7.3.1. 
Randomization ............................................................................................................31 
7.3.2. 
Blinding ......................................................................................................................31 
7.3.3. 
Emergency Unblinding ...............................................................................................32 
7.4. 
Treatment Compliance ................................................................................................32 
7.5. 
Concomitant Therapy .................................................................................................32 
7.5.1. 
Rescue Medicine .........................................................................................................33 
8. 
TREATMENT DISCONTINUATION, STUDY DISCONTINUATION 
AND PATIENT DISCONTINUATION/ WITHDRAWAL ......................................34 
8.1. 
Discontinuation of Treatment .....................................................................................34 
8.2. 
Study Discontinuation ................................................................................................35 
8.3. 
Patient Discontinuation/Withdrawal from the Study ..................................................36 
8.4. 
Lost to Follow-Up.......................................................................................................36 
9. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................38 
9.1. 
Study Assessments......................................................................................................38 
9.1.1. 
Medical History and Demographic Data ....................................................................38 
9.1.2. 
Physical Examination .................................................................................................38 
9.1.3. 
Adverse Event Solicitation .........................................................................................38 
9.1.4. 
Pharmacokinetic Assessments ....................................................................................39 
9.1.4.1. 
Urine Pharmacokinetics ..............................................................................................39 
9.1.4.2. 
Blood Pharmacokinetics .............................................................................................39 
9.1.5. 
Pharmacodynamic Assessments .................................................................................40 
9.1.5.1. 
Urine Microbiology ....................................................................................................40 
9.1.6. 
Laboratory Assessments .............................................................................................40 
9.1.7. 
Screening Assessments ...............................................................................................41 
9.1.8. 
Biological Specimen Collection and Laboratory Evaluations ....................................41 
9.2. 
Safety and Other Assessments ....................................................................................42 


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9.3. 
Adverse Events and Serious Adverse Events .............................................................44 
9.3.1. 
Definition of Adverse Events .....................................................................................44 
9.3.1.1. 
Safety Parameters and Definitions ..............................................................................44 
9.3.1.2. 
Adverse Events ...........................................................................................................44 
9.3.2. 
Definition of Serious Adverse Events ........................................................................45 
9.3.3. 
Classification of an Adverse Event .............................................................................45 
9.3.3.1. 
Severity of an Adverse Event .....................................................................................45 
9.3.3.2. 
Expectedness ...............................................................................................................46 
9.3.4. 
Time Period and Frequency for Event Assessment and Follow-Up ...........................46 
9.3.5. 
Adverse Event Reporting ............................................................................................47 
9.3.6. 
Serious Adverse Event Reporting ...............................................................................48 
9.3.7. 
Reporting Events to Patients .......................................................................................48 
9.3.8. 
Events of Special Interest ...........................................................................................48 
9.3.9. 
Reporting of Pregnancy ..............................................................................................48 
9.3.9.1. 
Pregnancies in Female Patients ..................................................................................48 
9.3.9.2. 
Pregnancies in Female Partners of Male Patients .......................................................49 
9.3.9.3. 
Abortions ....................................................................................................................49 
9.3.9.4. 
Congenital Anomalies/Birth Defects ..........................................................................49 
9.4. 
Unanticipated Problems ..............................................................................................49 
9.4.1. 
Definition of Unanticipated Problems ........................................................................49 
9.4.2. 
Unanticipated Problem Reporting ..............................................................................50 
9.4.3. 
Reporting Unanticipated Problems to Patients ...........................................................50 
10. 
STATISTICAL CONSIDERATIONS .......................................................................51 
10.1. 
Statistical Hypotheses .................................................................................................51 
10.2. 
Sample Size Determination ........................................................................................51 
10.3. 
Populations for Analyses ............................................................................................51 
10.4. 
Statistical Analyses .....................................................................................................51 
10.4.1. 
General Approach .......................................................................................................51 
10.4.2. 
Safety Analyses ..........................................................................................................51 
10.4.3. 
Baseline Descriptive Statistics ....................................................................................52 
10.4.4. 
Planned Interim Analyses ...........................................................................................52 
No interim analysis is planned. ......................................................................................................52 
10.4.5. 
Exploratory Analyses ..................................................................................................52 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................53 
11.1. 
Regulatory, Ethical, and Study Oversight Considerations .........................................53 
11.1.1. 
Informed Consent Process ..........................................................................................53 
11.1.1.1. 
Consent/assent and Other Informational Documents Provided to Patients ................53 
11.1.1.2. 
Consent Procedures and Documentation ....................................................................53 
11.1.2. 
Study Discontinuation and Closure ............................................................................53 
11.1.3. 
Confidentiality and Privacy ........................................................................................54 
11.1.4. 
Future Use of Stored Specimens and Data .................................................................54 
11.1.5. 
Safety Oversight .........................................................................................................55 
11.1.6. 
Clinical Monitoring ....................................................................................................55 
11.1.7. 
Quality Assurance and Quality Control ......................................................................56 
11.1.8. 
Data Handling and Record Keeping ...........................................................................56 
11.1.8.1. 
Data Collection and Management Responsibilities ....................................................56 
11.1.8.2. 
Study Records Retention ............................................................................................58 
11.1.9. 
Protocol Deviations ....................................................................................................58 
11.1.10. 
Publication and Data Sharing Policy ..........................................................................58 
11.1.11. 
Conflict of Interest Policy ...........................................................................................59 
11.2. 
Additional Considerations ..........................................................................................59 
11.3. 
Abbreviations ..............................................................................................................60 
11.4. 
Protocol Amendment History .....................................................................................63 
12. 
REFERENCES ...........................................................................................................64 
 
LIST OF TABLES 
Table 1: 
Schedule of Assessments ............................................................................................14 
Table 2: 
Schedule of Blood and Urine Sampling .....................................................................16 
 
 


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1. 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Conference on Harmonisation (ICH) 
Good Clinical Practice (GCP), and applicable United States (US) Code of Federal Regulations 
(CFR). The PI will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the Investigational New Drug (IND) Sponsor, funding agency and 
documented approval from the Institutional Review Board (IRB), except where necessary to 
eliminate an immediate hazard(s) to the patients. All personnel involved in the conduct of this 
study have completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
form must be obtained before any patient is enrolled. Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented to the study. All 
changes to the consent form will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from patients who provided consent, using a 
previously approved consent form. 


Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
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2. 
PROTOCOL SUMMARY 
2.1. 
Synopsis  
Title: 
A MULTI-CENTER RANDOMIZED, DOUBLE-BLIND STUDY TO 
ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS 
AND PHARMACODYNAMICS OF LBP-EC01 IN PATIENTS WITH 
LOWER URINARY TRACT COLONIZATION CAUSED BY E. COLI 
Study Description: 
Study LBx-1001 is a multi-center randomized, double-blind study to assess 
the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) 
of LBP-EC01 in patients with indwelling urinary catheters, or requiring 
intermittent catheterization, and/or patients with asymptomatic bacteriuria 
caused by Escherichia coli (E. coli). This study population has been 
selected because LBP-EC01 is a phage cocktail where active bacterial host 
engagement is required to allow for amplification of the phage and 
evaluation of the safety and PK of the phage cocktail. Eligible patients will 
require confirmation of colonization with a urine sample taken within 10 
days of randomization that cultures contain ≥103 E. coli CFU/mL, without 
the patient having clinical signs or symptoms of an active urinary tract 
infection (UTI) requiring antibiotic treatment. Patients should have E. coli 
as the primary colonizing bacteria and must not have a secondary bacterial 
colonization at levels equal to or greater than that seen from E. coli. 
Patients may concomitantly receive standard of care treatment for a newly 
diagnosed symptomatic UTI caused by Gram-positive bacteria while on 
study with consultation of the medical monitor. Active or recent (within 14 
days prior to randomization) antimicrobial therapy will not be allowed. 
Analgesic use is permitted.  
A complete or abbreviated physical examination will be performed at the 
timepoints indicated in the Schedule of Assessments (SoA) table. An 
ultrasound assessment of the spleen and a spleen exam will be performed at 
the time points indicated in the SoA table. Adverse events (AEs) and 
concomitant medications will be monitored throughout the entire study 
(screening through follow-up). Vital signs: body temperature, blood 
pressure (BP), pulse rate and respiratory rate will be collected at the time 
points indicated in the SoA table. Electrocardiography (ECG) will also be 
performed as indicated on the SoA table. 
Special Safety Monitoring:  
General immunogenicity will be evaluated by assessing elevations in IgA, 
IgE, IgG and IgM levels across pre-treatment, Day 3, End of Treatment 
(EOT) and on follow-up visit on Day 14 and Day 28. 
Clinical Laboratory Tests:  
Hematology, coagulation, blood chemistry and urinalysis will be collected 
at the timepoints indicated in the SoA (Table 1). 
Objectives: 
Primary Objectives: 
To evaluate the safety, tolerability and PK of LBP-EC01 in patients ≥18yrs 
of age with lower urinary tract colonization caused by E. coli. 
Secondary Objective:  


Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
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To evaluate the pharmacodynamics (PD) of LBP-EC01. 
Exploratory Objective:  
To explore the influence of LBP-EC01 on the urinary tract microbiota.  
Endpoints: 
Primary Endpoints:  
• 
Safety and tolerability analysis of adverse events  
• 
Pharmacokinetic analysis 
Secondary Endpoints:  
• 
Reduction in urinary  E. coli burden at any of the following 
timepoints: Day 2, Day 3, Day 5, EOT, Day 14, and Day 28 
• 
Time to 1 log reduction in urinary E. coli count 
• 
Recurrence of E. coli colonization or incidence of infection based 
on clinical signs and symptoms 
• 
Evaluation of possible immunogenicity by measuring changes in 
IgA, IgE, IgG, IgM levels 
Study Population: 
Approximately 30 patients 18 years of age or older with a history of urinary 
tract infection or colonization caused by E. coli who have indwelling 
urinary catheters, or who require intermittent catheterization, and/or 
patients with asymptomatic bacteriuria caused by E. coli colonization (≥103 
CFU/mL) on microbiological diagnosis, without clinical signs or symptoms 
of infection requiring antibiotic treatment will be enrolled.  Patients will be 
screened for presence of E. coli colonization (≥103 CFU/mL) prior to 
randomization and evaluated for potential bacterial susceptibility to LBP-
EC01.   
Phase: 
1b 
Sites/ Facilities 
Enrolling Patients: 
Approximately 8 investigational sites in the US. 
Description of Study 
Intervention: 
Consenting adult male or female patients meeting entry criteria will be 
randomized 2:1 to receive either LBP-EC01 (approximately 1.5×107 – 
1.5×1013 PFU/vial - the maximum feasible dose based on the manufacturing 
process) or placebo (Lactated Ringer’s solution, injection, USP) twice-daily 
(BID) by urinary or indwelling catheter. LBP-EC01 is a mixture of 3 
distinct obligate lytic bacteriophages, each carrying a universal CRISPR 
RNA expression cassette embedded in the wild-type phage genome. 
Study Duration: 
Estimated duration of enrollment, treatment period and follow-up will be 
approximately 8 months. 
Patient Duration: 
Study duration for patients will be up to 56 days, which includes up to 21 
days for screening, 7 days of Investigational Medicinal Product (IMP) 
treatment, a Day 14 assessment, a Day 28 assessment (28 days after first 
dose), and at EOS (35 days after first dose). Patients will be in the clinic or 
hospital the evening prior to receiving the first dose of treatment and 
throughout the 7 days of treatment. 
Once the study is complete, patients should resume their regular 
medications and any catheters installed specifically for the conduct of the 


Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
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study should be replaced by new catheters at the discretion of their 
physician. 


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Table 1: 
Schedule of Assessments 
 
AE=adverse event; AM=morning administration; ECG=electrocardiogram; EOT=End of Treatment; EPT=early pregnancy test; IMP=investigational medicinal 
product; PK=pharmacokinetic; PM=evening administration; confirm=conduct assessment if not previously done or assessment is outside window (see footnote 
for assessment).  
Note: 
Urine Culture and Sensitivity at Screening should be collected and shipped to the central laboratories by Day -4 to allow time for results to be reported 
prior to patient randomization. 
a  A complete physical examination should include an evaluation of the head, eyes, ears, nose, throat, neck and lymph nodes, and the cardiovascular, 
dermatological, musculoskeletal, respiratory, gastrointestinal, genitourinary, and neurological systems. No invasive examinations (e.g., rectal examination) will 
Dose 13
Assessment
Day
(-21 to -7)
Day
(-6 to -1)
Day 7 (EOT)
Day 14
(± 3 days)
Day 28
(± 3 days)
Day 35m
AM
+6hr
PM
AM
PM
AM
PM
AM
PM
AM only
Clinic Visit
Clinic Visit
Telephone 
Contact
Written Informed Consent
X
Inclusion/ Exclusion Criteria
X
confirm
Demographics
X
confirm
Medical/ Medication History
X
confirm
Physical Examination a
X
confirm
X b
X b
X
X
Xn 
Spleen Evaluationc
X
X
X
X
Xn 
Vital Signs d, e
X
X
X
X
X
X
X
X
X
X
X
X
Xn 
12-lead ECG 
X
X
X
Xn 
Clinical Labs f
X
confirm 
X
X
X 
X (Day 
5)
 X 
X
X
Xn 
Urine Culture and Sensitivity 
X
confirm m
X
X
X
X (Day 
5)
X 
X
X
 
Urinalysis g
X
confirm
X
X
 
X
 
X (Day 
5)
 X 
X
X
Xn 
PK Sampling (Blood and Urine) h
X
X
X
X
X
X
X 
X
X
X 
X
X
 
Immunogenicity Assay
X
confirm
X
X
X
X
EPT Urine Pregnancy i
X
Xi
X
Randomization j
X
Drug IMP or Placebo 
Administration k
X
X
X
X
X
X
X
X
X
Unsolicted AE l
Solicited AE l 
X
X
X
X
X
X
X
X
X
X
X
X
X
Screening
Day 1
Day 2
Day 3
Doses 7 - 12
Day 4 - 6
Doses 1 - 6
In Hospital / Clinic ——— Treatment Period
X
X
X
X


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be performed. A symptom-directed physical examination will be performed at all other time points specified. A targeted physical examination may be 
performed as needed in response to adverse events or changes in medical history. 
b  Physical exam will be performed prior to AM dose. 
c Spleen evaluation will include ultrasound assessments for splenomegaly at Day -6 to -1, Day 3, and Day 7. Clinical examinations to assess for splenomegaly 
will be performed at all visits. Ultrasound assessment and clinical examinations may be performed at any time during the visit.  
d  Vital signs include single measurements of systolic and diastolic blood pressure, pulse rate, respiratory rate and oral body temperature. All measurements are to 
be taken after the patient has rested quietly for at least 5-10 minutes.  
e  During dosing, vital signs will be taken within 30 minutes prior to dosing and within 30 minutes after dosing (± 10 minutes) for the first 5 doses, and at 6 hours 
(± 30 minutes) after the first dose. Vital signs will be collected prior to the PM doses of Day 3 and Days 4-6, but do not need to be collected within 30 minutes 
of dosing. Vital signs can be taken at any time during the day for Day 7, Day 14, Day 28, and Day 35 (if a clinic visit). 
f  Clinical labs include assessment of hematology, clinical chemistry, lipids and coagulation. See Table 2 for timing of blood collection for these parameters.  If 
patient screening is done on Day -10 to Day -7 then this will not need to be repeated during Day -6 to -1. 
g  Urinalysis samples will be collected via catheter during the Treatment Period, at Day 14 and Day 28. If patient screening is done on Day -10 to Day -7 then no 
need to be repeated during Day -6 to Day -1. 
h  Blood and urine samples will be collected for PK analysis at the time points described in Table 2. 
i  Only women of childbearing potential. Day 1 will be obtained prior to the first dose. 
j  Randomization will take place on Day -1 or Day 1; patients will be randomized to receive active or placebo treatment. 
k AM dose is to be given at 8:00 AM ± 2 hr and PM dose is to be given 12 hr ± 3 hr after the AM dose.  Concomitant medications should be given during study 
conduct as required/prescribed.  Adverse Events will be monitored and reported from patient screening to end of study. 
l Patient diary cards will be provided to the patient to document AEs that occur between visits.  At Days 14, 28, and 35, the patient diary cards will be reviewed 
with the patient. AEs will be solicited at all visits and also once per day by telephone for the 7 days after the last dose. Unsolicited AEs will be collected at any 
time after the ICF is signed until the end of the study.  
m Urine culture sample should be obtained within 10 days of randomization and E. coli should be present at ≥103 CFU/mL.  If patient screening is done on Day -
10 to Day -7, then this collection will not need to be repeated during Day -6 to -1. Note: sample turnaround takes 48 -72 hours and therefore it is suggested to 
collect the sample no later than Day -4. 
n Day 35 will be a telephone contact to solicit and assess AEs. At the discretion of the investigator, the patient may be asked to return to the clinic/hospital for a 
Day 35 (± 3 days) Visit to follow-up on any abnormal/clinically significant findings from the Day 28 Visit (e.g. abnormal clinical laboratory results). 
Assessments as deemed necessary by the investigator may be performed to ensure patient safety.  
 
 


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Table 2: 
Schedule of Blood and Urine Sampling 
 
AE=adverse event; AM=morning administration; PK=pharmacokinetic; PM=evening administration; confirm=conduct assessment if not previously done or 
assessment is outside window (see footnote for assessment).  
Note: Sample turnaround takes 48 -72 hours and therefore it is suggested to collect the sample no later than Day -4 to allow time for results to be reported prior to 
patient randomization. 
a Pre-dosing PK samples for urine and blood will be collected after catheterization (if there is no existing catheter), up to 30 minutes prior to dosing. Post-dosing 
PK samples will be taken within 60 minutes after the catheter is released and re-clamped for 20 minutes to take additional urine and blood samples. The times 
of collection will be recorded.   
b Labs include hematology, clinical chemistry, lipids, and coagulation. If patient screening is done on Day -10 to Day -7 then this will not need to be repeated 
during Day -6 to -1. 
c Additional collection 6 hours (± 1 hr) after AM dose. 
d If patient screening is done on Day -10 to Day -7, then this collection will not need to be repeated during Day -6 to -1.  
e Urine culture sample should be obtained within 10 days of randomization and E. coli should be present at ≥103 CFU/mL. If patient screening is done on Day  
-10 to Day -7, then this collection will not need to be repeated during Day -6 to -1.  
f Day 35 will be a telephone contact to solicit and assess AEs. At the discretion of the investigator, the patient may be asked to return to the clinic/hospital for a 
Day 35 (± 3 days) Visit to follow-up on any abnormal/clinically significant findings from the Day 28 Visit (e.g. abnormal clinical laboratory results). 
Assessments as deemed necessary by the investigator may be performed to ensure patient safety. 


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3. 
INTRODUCTION 
3.1. 
Study Rationale  
Antimicrobial resistance (AMR) is one of the greatest risks to human health today and one of the 
greatest challenges to our civilization. It is estimated that by 2050 ten million people may be 
dying annually and the economic burden may hit $100 trillion (O’Neill, 2016). The Center for 
Disease Control and Prevent estimates that in the US, more than two million people are sickened 
every year with antibiotic-resistant infections, with at least 23,000 dying as a result (Centers for 
Disease Control and Prevention, 2013). 
Between 2010 and 2014, Extended Spectrum Beta-Lactamase (ESBL) rates among UTIs in the 
US increased from 7.8% to 18.3%, with the highest rates noted among hospital-associated 
infections (Lob et al, 2016). A recent epidemiological study showed that 14.9% of hospital-
acquired infections were caused by carbapenem resistant E. coli (Guh et al, 2015). Urinary tract 
infections caused by susceptible Enterobacteriaceae, compared with those caused by ESBL-
producing strains lead to greater median length of hospital stay, initial antibiotic failure and 
higher infection-related mortality (MacVane et al, 2015). The threat posed by these multi-drug 
and pan-resistant microorganisms are a dire warning to the world that we must increase our 
capacity to produce new modalities of antimicrobial therapy. There is particularly a great unmet 
need for novel compounds which are safe, effective and unaffected by existing resistance 
mechanisms (Payne et al, 2007; Talbot et al, 2006). The lack of antibiotic therapeutic options 
against multi- drug-resistant (MDR) bacteria has led to a revival in the investigative and rescue 
use of bacteriophage therapy in patients with difficult to treat life threatening infections where 
there are frequently no alternative antibiotic therapies (FDA-NIH Bacteriophage Workshop, 
2017). 
LBP-EC01 is a product containing a combination of 3 distinct obligate lytic bacteriophages 
(internally named as p0031-8, p004k-5, and p00ex-2) in equal amounts, each carrying a universal 
Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) ribonucleic acid (RNA) 
expression cassette (hereafter termed “crRNA cassette”) embedded in the wild-type phage 
genome. Each engineered CRISPR-enhanced bacteriophage (crPhage) is intended to retain wild-
type lytic activity. Both the individual crPhages and the crPhage cocktail will retain broad host 
range, if not an expanded host range, by their ability to transduce lethal crRNA constructs in the 
absence of productive lytic infection, and improved lethality for each crPhage to the cognate 
wild-type bacteriophage. LBP-EC01 is being developed for intravesicular administration for 
treatment of UTIs caused by E. coli including MDR and carbapenem-resistant (CR) strains.  
Phage-host PD are complex, and dependent on the replication rate of phages at the site of 
infection, as well as the density of susceptible bacterial hosts and the growth rate of that host in 
human tissues (Lavigne et al, 2013; Levin and Bull, 2004). Thus, for this first in human study 
(FIH) a population who has significant numbers of host bacteria has been chosen to evaluate the 
safety, tolerability and PK. 


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3.2. 
Background  
3.2.1. 
Disease Background 
Urinary tract infection is the most common infection in people with spinal cord injury (SCI), 
who need any form of bladder catheterization. Prolonged use of indwelling catheters increases 
the risk of UTI, the rate of hospital readmissions due to UTI, and long-term urological 
complications. Typical symptoms of UTI—dysuria, frequency, urgency, suprapubic discomfort 
and flank pain—are often absent in persons with SCI. Instead, non-specific symptoms of urinary 
leakage, change in voiding habits, worsening muscle spasm, increasing autonomic dysreflexia, 
sweating, malaise, and fever are often the presenting complaint for this population. Almost all 
persons with chronic indwelling catheters and about two-thirds of people using intermittent 
catheterization have bacteriuria. However, most cases of bacteriuria in this population represent 
bladder colonization, not UTI. In addition to the lack of specific symptoms, the presence of 
bacteriuria in this population results in the over-diagnosis of UTI in patients with SCI. Thus, the 
definition of UTI used in persons with SCI requires not only the presence of bacteriuria, but also 
evidence of significant pyuria, and subtle clinical manifestations that cannot be explained by 
another cause (Darouiche, 2010). The Infectious Disease Society of America defines catheter-
associated asymptomatic bacteriuria as the presence of ≥ 105 colony forming units (CFU)/mL of 
at least one bacterial species in the urine in catheterized or recently catheterized patients 
(preceding 48 hours) without symptoms suggestive of a UTI. A catheter-associated UTI is 
defined as the presence of ≥103 CFU/mL of at least one bacterial species in the urine of 
catheterized or recently catheterized patients with symptoms suggestive of a UTI (Hooten et al, 
2010). 
3.2.2. 
Bacteriophage Therapy 
Bacteriophages are viruses that infect and replicate within bacteria, and like other viruses, may 
have double-stranded or single-stranded deoxyribonucleic acid (DNA) or RNA genomes. Phages 
are generally specific to strains within a species due to their method of replication, which 
involves binding to a specific cell surface receptor on the host bacterial cell. The prototypical 
phage will attach to the relevant bacterial receptor, inject their genetic material, overtake the 
bacterial cellular machinery to instruct the cell to produce new phage virions, and then burst the 
host cell, releasing progeny. This mechanism of replication can be exploited to provide an 
advantageous antimicrobial effect in humans via phage therapy (Lavigne et al, 2013). 
Bacteriophage therapy has been used extensively since the 1930s, particularly in Poland and 
Eastern Europe, where it has been shown to be safe and well tolerated, with no obvious class 
related AEs in the clinic (Wittebole et al, 2014). Recently in 2 controlled studies, 1 in 40 patients 
with chronic leg ulcers, and the other in 24 patients with chronic otitis media, phage therapy was 
effective with no related AEs detected (Wright, et al, 2009; Rhoads et al, 2009). Another recent 
review suggested that bacteriophages could also be an efficacious and safe therapeutic modality 
in immunocompromised patients (Borysowski and Gorski, 2008). This lack of toxicity is a 
consequence of bacteriophage composition, which is almost entirely protein and DNA which 
results in minimal interaction with the body’s metabolism (Abedon and Thomas-Abedon, 2010). 
Several recent reports of phage therapy in individual patients have also confirmed the safety and 
efficacy of phage therapy used to treat MDR bacterial infections in critically ill patients 
(Schooley et al, 2017; LaVergne et al, 2018). 


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A 7-day non-Good Laboratory Practices (non-GLP) toxicology study was performed using a test 
article of the crPhage cocktail (crT37) containing crT7 and crT7M (derived from T7 and T3, 
respectively) phages.  These phages are similar to the phages in LBP-EC01 in that they are 
engineered to carry a CRISPR-Cas3 construct and that they target E. coli, however, the crT37 
phages contain a Type 1-E CRISPR-Cas system while LBP-EC01 contain Type 1-E and Type 1-
F CRISPR-Cas systems.  They also differ in that the crT37 cocktail was manufactured using a 
less stringent non-GMP manufacturing process while LBP-EC01 was manufactured according to 
GMP processes.  The crT37 cocktail was administered either intravenously (IV) (1.0x1011 
PFU/dose/phage) or intraurethrally (IU) (0.5x1011 PFU/dose/phage) once daily for seven 
consecutive days to female Crl:CD-1 mice. Groups 1 and 2 (9 female mice/group) were dosed IV 
with 0.1 mL of vehicle (1x Tris-buffered saline, pH 7.4) or test article.  Groups 3 and 4 (9 female 
mice/group) were dosed with 0.05 mL of vehicle or test article into the bladder by intracatheter 
instillation.   
The 7-day non-GLP toxicology study showed no crPhage-related mortality or moribundity, no 
effect on body weight, and no abnormal clinical observations for either route of administration. 
Possible test article-related effects in the Phage IV-treated group were limited to decreases in red 
blood cell mass-related parameters, increased reticulocyte counts, decreased eosinophils, and 
increased spleen, kidney, and decreased lung weights. Possible test article-related effects in the 
crPhage IU-treated group were limited to higher cholesterol and triglyceride levels. The clinical 
chemistry and organ weight results from this study should be viewed in the context of the small 
sample sizes used (3 for clinical chemistry and 6 for organ weights) and the possibility that 
alterations may be artifacts due to small sample size.   
Also, of note is that the crPhage preparations in these preclinical experiments used research-
grade non-GMP purification processes, which are not as robust as the GMP processes used to 
produce clinical trial material. Therefore, the test article production process did not effectively 
remove some of the residual impurities and endotoxin which has been known to cause tissue 
changes like splenomegaly (Seemann et al, 2017).   
The tissue samples obtained from the 7-day non-GLP toxicology study were preserved by flash 
freezing in liquid nitrogen and then stored at -80°C.  The tissues were sent to an independent 
outside pathology lab for processing and evaluation.  Due to the duration of time between tissue 
harvest and tissue processing and evaluation (approximately 27 months) the samples had 
undergone significant degradation and were unevaluable by the pathology lab. 
However, in conclusion, once daily IV or IU administration of crPhage was generally well 
tolerated (data on file). 
Antimicrobial proof-of-concept studies in standard murine models of antimicrobial efficacy, 
including representative peritonitis models showed 80% survival with a single-dose treatment 
compared to 0% with no treatment, and thigh infection models demonstrated ~1.5–5.5-log CFU 
reduction in 60 minutes compared to no treatment.  
A surrogate PK/PD and absorption, distribution, metabolism, and excretion study measured 
phages at high concentrations in the bladder (103 – 108 PFU/gram tissue up to 72 hours) and 
kidney (102 – 106 PFU/gram up to 12 hours) after a single intravesicular administration of 109 
PFU in healthy mice.  


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3.2.3. 
Bacterial Host Range Analysis 
Locus Biosciences has developed a product containing a combination of crPhages for the 
treatment of E. coli infection. The host range of each phage was measured via the change in area 
under the growth curve between untreated and phage-treated cultures across a diverse panel of 
clinical E. coli isolates. From a collection of over 150 phages, an optimized cocktail of 3 phages 
was selected that resulted in a cumulative host range of approximately 80% across a 153-strain 
panel of E. coli (phylogenetic distribution, A-10%; B1-15%; B2-48% D-27%; approximately 
20% of strains were MDR by MIC testing against 25 distinct antibiotics). Selected phages 
exhibited significant activity against these isolates at concentrations of 0.01 – 10 phage particles 
per bacterium. 
3.3. 
Risk/Benefit Assessment   
3.3.1. 
Known Potential Risks  
3.3.1.1. 
Immediate Potential Risks 
A potential concern for safety is the possibility of endotoxin release associated with active 
bacterial lysis. An in vitro endotoxin release study following exposure of 2 strains of E. coli to 
either bacteriophage or antibiotics has shown that endotoxin production is similar with 
bacteriophage lysis to that seen with amikacin therapy, and less than that seen with a beta lactam 
antibiotic (Dufour et al, 2017). Whilst the Locus phage-drug compound will contain small 
amounts of endotoxin, the manufacturing process will provide strict limits to the amount of 
endotoxin in the final drug product. The endotoxin exposure will be similar to that seen with 
rapidly effective bactericidal antibiotic therapy. 
A preclinical 7-day non-GLP toxicology study was performed where possible test article-related 
effects were observed including increased spleen weight in the Phage IV-treated group (see 
Section 3.2.2).  As such, splenomegaly may be a potential risk and will be monitored during the 
conduct of this study.    
Instrumentation or instillation of solutions into the bladder could induce autonomic dysreflexia in 
certain spinal injuries. Patients with severe autonomic dysreflexia will be excluded (see 
Section 6.2). Any instrumentation will be minimized and the intravesical dose volume will be 
approximately 60 mL and warmed to room temperature before instillation. All procedures related 
to drug preparation, instrumentation and catheter handling will be performed under sterile 
conditions to avoid introduction of infection. 
3.3.1.2. 
Long Term Potential Risks 
A potential safety concern with bacteriophage therapy (both wild type and CRISPR-enhanced 
bacteriophage), is the potential to transfer bacterial virulence factors or antibiotic resistance 
genes. The bacteriophages selected for LBP-EC01 drug cocktail production have been screened 
to exclude those with virulence genes or antibiotic resistance genes. There has been little 
information regarding any risk associated with phage cocktails, however, a recent bioinformatic 
analysis of a commercial Russian phage cocktail did not reveal undesired genes, and a small 
human volunteer trial did not associate adverse effects with oral bacteriophage exposure 
(McCallin et al, 2013).  


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In a Locus preclinical persistence and distribution study in mice treated with a cocktail of 2 
bacteriophages (crT7 and crT7M) administered by intra-urethral instillation, all phages showed 
persistence in the bladder for a limited period without any amplification. In another study by oral 
administration using a polymerase chain reaction (PCR)-based method of quantification, all 
phages had been cleared by 72 hours (Data on file). 
Bacteriophages as non-self antigens, may stimulate immunological responses resulting in 
detrimental effects for recipients, however, at present no evidence exists for this possibility. 
There is some concern that higher exposure to phages may result in the production of 
anti-bacteriophage antibodies that could potentially result in adverse reactions or neutralize 
therapeutic bacteriophage effects. A safety evaluation of bacteriophage therapy in 15 adult 
healthy volunteers using E. coli T4 phage administered orally indicated no increase in level of 
anti-bacteriophage immunoglobulin (Ig)G, IgM, and IgA in the serum after 1 month of dosing 
(Bruttin, 2005). In a cohort of patients treated with bacteriophage therapy for 15 to 60 days, by 
multiple routes of administration high anti-phage activity was found in 12.3% of patients within 
15 to 60 days of bacteriophage therapy. Preliminary observations performed in 15 patients with 
high anti-bacteriophage activity of sera suggest that the induction of anti-bacteriophage activity 
of patients’ sera during or after bacteriophage therapy does not exclude a good result for 
bacteriophage therapy (Łusiak-Szelachowska et al, 2014). The overall finding was of a generally 
low level of anti-bacteriophage antibodies in untreated subjects with only slight increase in 
anti-bacteriophage antibodies in bacteriophage treated patients which would be unlikely to result 
in major clinical concern. A further study by the same authors in 62 patients with various 
bacterial infections and 30 healthy volunteer controls was conducted to determine the association 
between the bacteriophage neutralization of patients' sera and the clinical outcome of 
bacteriophage therapy. The anti-bacteriophage activity of sera levels and clinical results 
indicated that the level of anti-bacteriophage activity was not correlated with outcome of 
bacteriophage therapy (Łusiak-Szelachowska et al, 2017). 
3.3.2. 
Known Potential Benefits  
Bacteriophage are bacteria-specific viruses that infect and replicate within bacteria. The 
prototypical phage will attach to the relevant bacterial receptor, inject their genetic material, 
overtake the bacterial cellular machinery to instruct the cell to produce new phage virions and 
then burst and destroy the host cell, releasing progeny. Phages are generally specific to strains 
within a bacterial species due to their method of replication, which involves binding to a specific 
cell surface receptor on the host bacterial cell. The antimicrobial effect of bacteriophages is 
therefore highly pathogen specific and given adequate exposure rapidly bactericidal. This 
bacteriophage activity is unrelated to any known mechanisms of antibiotic resistance and will 
therefore retain activity against MDR and extensive drug resistant (XDR) isolates. LBP-EC01 is 
a blend of 3distinct engineered bacteriophages (‘crPhages’) that each expresses an identical copy 
of a CRISPR-Cas3 construct targeting E. coli. The CRISPR construct is integrated into the phage 
genome without disrupting any genes necessary for the lytic lifestyle of the phage. This construct 
was optimized to leverage the Type I-E or Type I-F endogenous E. coli CRISPR-Cas3 system to 
simultaneously degrade 4 independent, highly conserved genes with functions related to cell 
division and maintenance (the ‘CRISPR array’). Each CRISPR target alone can efficiently kill E. 
coli with an average CFU reduction of 3.6 to >5.3log (below limit of detection) in plasmid-based 
transformation experiments (data on file). 


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This novel bacteriophage technology could make a major difference to the treatment of patients 
with severe infections caused by MDR and XDR pathogens. This could have a marked impact on 
managing individual infections as well as social benefits in helping to decrease the deleterious 
effect of AMR on future advances in surgery and cancer therapy. 
3.3.3. 
Assessment of Potential Risks and Benefits  
Instrumentation or instillation of solutions into the bladder could induce autonomic dysreflexia in 
certain spinal injuries. Patients with severe autonomic dysreflexia will be excluded. Any 
instrumentation will be minimized, and solution volume will be limited and warmed to room 
temperature before instillation. All procedures related to drug preparation, instrumentation and 
catheter handling will be performed under sterile conditions to avoid introduction of infection. 
Risks in this study are perceived to be low due to known lack of toxicity of phage therapy, 
whereas the benefits of establishing dosing and PK parameters as well as safety, are considered 
essential to progressing this type of therapy to the clinic. 
 


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4. 
OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
Pharmacokinetics,  
safety, tolerability 
• 
Levels of crPhage will be 
assessed by quantitative 
plaquing assay to determine 
levels in urine and blood 
• 
AEs, hematology, chemistry 
• 
Establish adequate 
dosing and exposure in 
urine and blood 
Secondary 
 
 
Pharmacodynamics of LBP-EC01 
• 
Reduction in urinary  E. coli 
burden at any of the following 
timepoints: Day 2, Day 3, Day 
5, EOT, Day 14, and Day 28 
• 
Time to 1 log reduction in 
urinary E. coli count 
• 
Recurrence of E. coli 
colonization or incidence of 
infection based on clinical 
signs and symptoms 
• 
Changes in IgA, IgE, IgG, 
IgM levels 
• 
Demonstrate reduction 
in level of E. coli 
colonization  
Exploratory 
 
 
To explore the influence of LBP-
EC01 on the urinary tract 
microbiota 
• 
Urine culture and sensitivity 
(persistent, recurrent E. coli, 
new colonizing new infections 
will be documented) 
• 
Evaluation of bacterial 
biomarkers (e.g. phage 
sensitivity/resistance, bacterial 
antibiotic resistance, bacterial 
metagenomic analysis) 
• 
Monitoring effect on 
microbiome 
• 
Evaluation of possible 
immunogenicity 
 
 


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5. 
STUDY DESIGN  
5.1. 
Overall Design 
This is a Phase 1b FIH study to assess safety, tolerability, and PK of LBP-EC01 in patients who 
have significant colonization of the urinary tract by E. coli.  It is a multi-center randomized, 
double-blind study in patients with indwelling urinary catheters, or who require intermittent 
urinary catheterization and/or patients with asymptomatic bacteriuria caused by E. coli.  
No formal hypothesis will be tested. Approximately 30 patients will be randomized 2:1 to 
receive either LBP-EC01 (at approximately 1.5×107 – 1.5×1013 PFU/vial - the maximum feasible 
dose based on manufacturing process) or inert placebo given twice daily for 7 days by 
intravesical catheter.  A new catheter will be installed at the beginning of the study and will be 
replaced at the discretion of the investigator. The study will be conducted in approximately 
8 sites in the US. Study duration for patients will be up to 56 days, which includes up to 21 days 
for screening, 7 days of Investigational Medicinal Product (IMP) treatment, a Day 14 assessment 
(14 days after first dose), a Day 28 assessment (28 days after first dose), and at EOS (35 days 
after first dose). Patients will be in the clinic or hospital the evening prior to receiving the first 
dose of treatment and throughout the 7 days of treatment.  Study enrollment will continue up to 
30 evaluable patients. 
The study will consist of a Screening Period of up to 21 days. On Day -1 patients will either be 
hospitalized or in a facility that can provide proper administration of study drug and then 
randomized to LBP-EC01 or placebo. The entire 7-day Treatment Period in which patients will 
receive 13 doses of IMP will be conducted with the patient in the clinic/hospital. In 
circumstances where the patient may not be able to be in clinic/hospital for the full 7 days of 
treatment, upon consultation between the treating physician and the study Medical Monitor, 
patients may be considered to be treated and monitored in clinic/hospital for Days 1-3 and then 
may be allowed to come back to the clinic/hospital for the PM dose on Day 3 and the remaining 
treatment from Days 4-7.  The EOT will be after the 13th dose on Day 7, after which the patient 
may be released from the clinic/hospital. The patient will return on Day 14 (±3 days) for the 
Day 14 Visit, and on Day 28 (±3 days) for the Day 28 Visit.  AE data will be collected 
throughout the study, including Day 28 through Day 35.  At Day 35, the patient will be contacted 
by telephone to assess any AEs or lab abnormalities since the Day 28 Visit. At the discretion of 
the investigator, the patient may be asked to return to the clinic/hospital for a Day 35 Visit 
(±3 days). Day 35 is the EOS. Assessments will be conducted as described in Table 1 and 
Table 2.  
Safety will be assessed throughout the study.  Spleen evaluations will include ultrasound 
assessments for splenomegaly at Day -6 to -1, Day 3, and Day 7 and clinical examinations to 
assess for splenomegaly will be performed at all visits.  In addition, attention will be focused on 
identifying any progression of a urinary colonization to an active infection, including the signs 
and symptoms of local vesicular reactions (e.g. bladder pain, hematuria).  Symptoms of active 
infection will be elicited during daily observations throughout the 7 days of treatment and to the 
end of study.  Symptoms of note in this population include dysuria, urinary frequency, urinary 
urgency, suprapubic discomfort and flank pain in addition to non-specific symptoms of urinary 
leakage, change in voiding habits, worsening muscle spasm, increasing autonomic dysreflexia, 


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sweating, malaise, and fever or hypothermia.  Urine microscopy and culture will be assessed 
frequently during the study (see Table 2).  
5.2. 
Scientific Rationale for Study Design 
Bacteriophages require host bacteria to engage and multiply thus healthy volunteer studies are 
unlikely to provide the environment to adequately explore dosing, PK, tolerability and 
multiplication of the active bacteriophage therapy in the infective disease setting. This planned 
population with significant urinary tract colonization with E. coli will provide an appropriate 
surrogate for evaluating these parameters in a relatively healthy population without the need for 
active antibiotic therapy. 
There have been no previous clinical PK studies with intravesical phage therapy or any well 
controlled studies in humans to help plan this dosing regimen. It is widely believed that adequate 
exposure is important to get early effective bacterial killing, thus a maximal feasible dose which 
is dependent on manufacturing limitations will be used.  
There is no formal hypothesis nor statistical analysis, however, 30 patients randomized 2:1 
should provide sufficient information for an initial safety, tolerability, and PK analysis. This will 
also provide early proof of concept data with careful microbiological analysis of host range 
response and effectiveness of the bactericidal activity. The placebo group will provide a 
sufficient control for evaluating safety in this FIH study. 
5.3. 
Justification for Dose 
Twice daily dosing with the maximal feasible dose, based on the manufacturing process 
(1x106 – 1x1012 PFU/mL which is approximately 1.5×107 – 1.5×1013 PFU/vial), of LBP-EC01 is 
planned. As bacteriophage therapy has been shown to be safe and effective and bactericidal 
activity is dependent on the number of bacteria infected by bacteriophages, early adequate 
exposure at the site of infection is important. Exposure of bacteria to sufficient numbers of 
bacteriophages without relying on multiplication within the host is considered to be the most 
efficient approach. Wild-type bacteriophage efficacy is dependent on host engagement, 
multiplication and lysis of the bacteria whereas with crPhage additional bactericidal activity is 
achieved by using the CRISPR-Cas3 system to simultaneously degrade independently, highly 
conserved genes with functions related to cell division and maintenance. As bacteriophage 
activity has been shown to be dependent on host exposure, we have selected the maximum 
feasible dose to be administered twice daily. 
5.4. 
End of Study Definition 
A patient is considered to have completed the study if he or she has completed all portions of the 
study including the last visit or the last scheduled procedure shown in the SoA (Table 1) 
The end of the study (EOS) is defined as the last date that patient safety data is collected (i.e., 
Day 35).   Once patients have completed Day 28, they may resume their regular medications and 
have any new intermittent catheters re-established as directed by their physician. 


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6. 
STUDY POPULATION 
6.1. 
Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
1. Provision of signed and dated informed consent form. 
2. Stated willingness to comply with all study procedures and availability for the duration of 
the study. 
3. Males or females 18 years of age or older. 
4. Patients with a lower urinary tract colonization caused by E. coli (≥103 CFU/mL) and 
who meet at least one of the following criteria: 
• Has an indwelling urinary catheter and medical documentation of a urinary tract 
infection by E. coli within the past 12 months 
• Requires intermittent catheterization and medical documentation of a urinary tract 
infection by E. coli within the past 12 months 
• Has medical documentation of a history of asymptomatic bacteriuria (i.e., lower 
urinary tract colonization) with E. coli at least once in the past 12 months 
5. Patients must have experience with urinary catheterization or have Medical Monitor 
approval if the patient does not have prior experience with catheterization.  
6. In good general health as evidenced by medical history and physical examination. 
7. Women of childbearing potential and men with female partners of childbearing potential 
must use two forms of effective contraception, at least 1 of which is a physical barrier 
method, during the study and which is recommended to continue for 2 weeks after 
completing the study. 
6.2. 
Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Patients with clinical signs of active UTI or other infection requiring antimicrobial 
treatment. These may include dysuria, urinary frequency, urinary urgency, suprapubic 
discomfort and flank pain in addition to non-specific symptoms of urinary leakage, 
change in voiding habits, worsening muscle spasm, increasing autonomic dysreflexia, 
sweating, malaise, and fever or hypothermia. Analgesic use is permitted. 
2. Patients who have received Gram-negative bacteria antimicrobials within 14 days of 
randomization.   
Note: Patients who are currently only receiving antibiotics with only Gram-positive 
activity (e.g., vancomycin, daptomycin, linezolid) to treat active infections against 
Gram-positive non-UTIs can be included in the trial.   
3. Presence of a surgically-modified bladder, except for a repaired ruptured bladder. 


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4. History of severe autonomic dysreflexia, which is defined as those patients who have a 
spinal cord injury and who have had a documented sudden increase in systolic blood 
pressure of greater than 40 mm Hg due to an irritation or stimulation (including bladder 
or bowel irritation) below the level of the spinal cord injury.  Autonomic dysreflexia can 
include findings of hypertensive crisis or emergency, clinically significant 
bradycardia/tachycardia, severe headache or other severe reaction requiring an acute 
intervention, so consultation with the Medical Monitor should take place if a history of 
severe autonomic dysreflexia is suspected but not clearly identified. 
5. Active severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, 
endocrine, pulmonary, cardiac, or neurologic disease per the investigator’s discretion. 
6. Any malignancies within the past 5 years (except those in remission). 
7. Unless deemed acceptable by the Investigator, prescription drugs, over-the-counter 
(OTC) medications and supplements that acidify the urine are excluded. 
8. Patients who have had allergic reactions to similar compounds, or any excipients. 
9. Participation in an investigational drug or device study within 1 month (or 7 half-lives of 
drug, whichever is longer) prior to randomization. 
10. Patients who are pregnant or expecting to conceive, are breast feeding or are planning to 
breast feed, within 1 month of completion of the study. 
6.3. 
Randomization Criteria 
Randomization criteria is expected to be met by Day -1. An individual who continues to meet all 
of the Inclusion and none of the Exclusion Criteria may proceed to randomization if the below 
criteria are met. There is no minimum time required between Screening and Randomization as 
long as patients meets all Inclusion criteria and none of the exclusion criteria for the study, 
including required lab testing. 
1. E. coli has been identified in a urinary sample obtained within 10 days of randomization 
and is present at ≥103 CFU/mL 
2. Patients with mixed colonization with additional Gram-negative or Gram-positive 
bacteria isolated will be eligible if the other bacteria are present with a CFU/mL that is 
less than the CFU/mL for E. coli within 10 days of randomization. 
6.4. 
Lifestyle Considerations 
During this study, patients will be admitted to a clinic or hospital for 7 days while investigational 
product or placebo is being administered. Outside of the days within clinic/hospital, patients will 
be asked to maintain normal activities. 
6.5. 
Screening and Screen Failures 
During the screening period, patients will complete the screening procedures outlined in Table 1.  
A urine sample will be taken within 10 days of randomization as part of the initial screening to 
test for colonization of E. coli at ≥103 CFU/mL. Patient urine samples will also be assessed for 
the presence of E. coli to be greater than any other bacteria.  Patients meeting the urine culture 


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criteria at the initial screening will then be asked to complete the remaining screening procedures 
per Table 1.  Patients continuing to meet all screening criteria can then be randomized into a 
treatment group.  Baseline urine samples will be tested to provide a baseline assessment of the 
response to LBP-EC01 by bacteriophage plaquing technique at the Central Lab, but these results 
are not necessary to randomize the subject.   
Screen failures are defined as patients who consent to participate in the clinical trial but are not 
subsequently randomized to the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure patients, to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demographic information, screen failure details, eligibility criteria, 
and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a 
recent antibiotic or insufficient urinary colonization may be re-screened. Re-screened patients 
will be assigned a new patient number from the initial screening. 
6.6. 
Strategies for Recruitment and Retention 
The following will be considered to recruit study patients: 
• There will be competitive enrollment across sites. 
• Source of patients will include but is not limited to inpatient or outpatient including 
patients with SCI or other patients that may require long-term or intermittent urinary 
catheterization; patients will be in hospital, or urology or special clinic settings. 
• Recruitment venues will be in-hospital or regular follow-up clinic visits. 
• Potential patients will be identified from medical records and previous history of 
urinary tract infection and cultures and will be approached either at clinic/hospital 
visits or by phone or mail contact. 
• Public media and other external types of recruitment strategies are anticipated. 
• No specific strategies that will be used to recruit and retain historically under-
represented populations. The majority of patients may have had SCI and will include 
all population groups. Women may be underrepresented because of their prevalence 
in SCI in in VA populations.  
• A patient stipend will be considered. Any travel and time required for the study may 
be compensated, according to approval from the site IRB. 


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7. 
STUDY TREATMENT 
7.1. 
Treatment Administration 
7.1.1. 
Investigational Medicinal Product Description 
LBP-EC01 is a clear to opalescent, colorless to slightly yellow, aqueous solution.  LBP-EC01 is 
a mixture of 3 crPhages internally named as p0031-8, p00ex-2, p004k-5, which are derived from 
wild-type myroviridae phages that target E. coli.  These phages have been engineered to contain 
an identical CRISPR-Cas3 construct and have been combined in equal amounts at 1×106 – 
1×1012 PFU/mL (equivalent to approximately 1.5×107 – 1.5×1013 PFU/vial). One vial of LBP-
EC01 containing approximately 15 mL of solution will be sterilely mixed with 45 mL of 
Lactated Ringer’s solution (injection, USP) by the site pharmacy prior to each dose administered 
(details will be included in the pharmacy manual). LBP-EC01 and placebo solutions will be 
indistinguishable.  
7.1.2. 
Dosing and Administration 
LBP-EC01 will be administered by bladder instillation via a newly placed urinary catheter BID 
at the maximum feasible dose, based on the manufacturing process (approximately 1.5×107 – 
1.5×1013 PFU/vial),  totaling approximately 60 mL of solution via sterile catheter tipped syringe 
(details will be included in the pharmacy manual). The urinary catheter will be clamped and the 
solution left in situ for a minimum of 30 minutes (to a maximum of 40 minutes) following 
instillation and then it will be placed on free drainage (duration of clamp should be documented).  
LBP-EC01 will be provided in a 20 mL vial containing approximately 15 mL of the crPhage 
cocktail.  This vial will be brought to room temperature prior to mixing with 45 mL of Lactated 
Ringer’s solution (injection, USP) under sterile conditions and placed into a sterile syringe with a 
catheter tip.  Handling and mixing of the vials making up LBP-EC01 will be done by the 
unblinded study pharmacist (details to be provided in the pharmacy manual). Placebo solution 
Lactated Ringer’s solution (injection, USP) will be brought to room temperature and will also be 
prepared by the pharmacist under aseptic technique and placed into a sterile catheter tipped 
syringe. The unblinded pharmacist will use the interactive voice/web-based response system 
(IVRS) system to determine the randomization allocation.  
The mixed blinded solutions will be provided to the investigator/nursing staff for administration.  
If not used immediately, the IMP combined with Lactated Ringer’s solution should be stored 
under refrigerated conditions and must be administered within 24 hours of preparation. Doses 
may be given at 8 AM within +/- a 2-hour window for the AM dose and 12 hours after the AM 
dose +/- a 3-hour window for the PM dose. The clinical site staff should consult with the 
Medical Monitor about any missed dose outside the allowable dosing window.  Typically, these 
missed doses should be given and documented following standard procedure. 


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All patients will receive a total of 13 doses of drug product or placebo across 7 days of treatment 
(a single morning dose will be given on Day 7) (see Table 1). All doses should be given using 
strict aseptic techniques and may be administered by clinic/hospital staff provided they have 
been given adequate training.  Upon completion of the study, patients requiring subsequent 
catheterization should have their study catheter replaced.  The catheter used in the study should 
be discarded per normal site policy. 
7.2. 
Preparation/Handling/Storage/Accountability 
7.2.1. 
Acquisition and Accountability 
All IMPs required for completion of this study (LBP-EC01 and placebo) will be provided by the 
Sponsor. The investigational site will acknowledge receipt of IMPs, to confirm the shipment 
condition and content. Any damaged shipments will be replaced by the Sponsor. 
The Investigator/study pharmacist is responsible for the control of biologics under investigation. 
Adequate records of the receipt (e.g., IMP Receipt Record) and disposition (e.g., IMP 
Dispensing Log) of the IMP must be maintained. The IMP Dispensing Log must be kept current 
and should contain the following information: 
• The identification of the patient to whom the IMP was dispensed (for example patient 
initials and date of birth). 
• The date(s), quantity of the IMP dispensed to the patient. 
• The date(s) and quantity of any IMP sent to the clinical site and replaced. 
• All records and drug supplies must be available for inspection by the Medpace 
Monitor at every monitoring visit. 
The IMP will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure (SOP) or returned to the Sponsor with the appropriate 
documentation. The site's method of IMP destruction must be agreed upon by the Sponsor. Local 
or institutional regulations may require immediate destruction of used IMP for safety reasons. In 
these cases, it may be acceptable for investigational study site staff to destroy dispensed IMP 
before a monitoring inspection provided that source document verification is performed on the 
remaining inventory and reconciled against the documentation of quantity shipped, dispensed, 
returned, destroyed and provided that adequate storage and integrity of drug has been confirmed. 
The site must obtain written authorization from the Sponsor/Medpace before any IMP is 
destroyed, and IMP destruction must be documented on the appropriate form. 
Written documentation of destruction must contain the following: 
• Identity medication number of IMP(s) destroyed. 
• Quantity of IMP(s) destroyed. 
• Date of destruction. 
• Method of destruction. 
• Name and signature of responsible person (or company) who destroyed IMP(s). 


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Accurate records of all IMPs received at, dispensed from, returned to, and disposed of by the 
study site should be recorded on the IMP Inventory Log. 
7.2.2. 
Formulation, Appearance, Packaging, and Labeling 
A full course of LBP-EC01 treatment will be contained in thirteen 20 mL vials filled with 
approximately 15 mL of drug product crPhage cocktail contained in a cardboard outer box. Each 
vial will contain approximately 15 mL of clear, to opalescent, colorless to slightly yellow, 
solution which will be individually labeled with the study identifier.  Each box will contain the 
vials for a single patient dose which should be stored refrigerated as described in Section 7.2.3.  
7.2.3. 
Product Storage and Stability 
Both LBP-EC01 and placebo (sterile Lactated Ringer’s solution, injection, USP) will be 
provided by the Sponsor via a Contract Manufacturing Organization.  A single patient’s full 
7-day treatment of LBP-EC01 (13 vials) will be packaged in a cardboard outer box.  Each vial of 
LBP-EC01 will contain approximately 15 mL of clear, to opalescent, colorless to slightly yellow, 
solution. The outer box secondary packaging will be labelled with the appropriate coding for the 
site pharmacy.   
Boxes of drug product vials should be stored at 4°C in the refrigerator at all times unless being 
prepared for use. Short exposures (less than 4 hrs) of the vials to room temperatures (25°C) are 
acceptable. The IMP drug cocktail mixed with Lactated Ringer’s solution (injection, USP) 
should be administered immediately but can be stored under refrigerated conditions for up to 
24 hours. If the IMP is exposed to conditions beyond these limits, the IMP should not be used 
and should be replaced by existing IMP at the site (using corresponding LBP-EC01 or placebo 
material dispensed by the site pharmacist) and the site should follow instructions contained in the 
Pharmacy Manual, to arrange for replacement of the material. 
7.2.4. 
Preparation 
Instruction for preparation of IMP will be included in a Pharmacy Manual supplied to the clinical 
sites.  
7.3. 
Measures to Minimize Bias: Randomization and Blinding 
7.3.1. 
Randomization 
Study patients will be randomly assigned to LBP-EC01 or placebo treatment groups in a 2:1 ratio 
using IVRS. 
7.3.2. 
Blinding 
This is a double-blind study. Blinding to study treatment allocation will be achieved through use 
of matching placebo solution and administration sets. Neither the patient, nor the Investigator, 
nor Medpace/Sponsor will be aware of the treatment allocation.  Key pharmacy staff involved in 
the preparation of the IMP or placebo will need to be unblinded.  


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7.3.3. 
Emergency Unblinding 
In the event of an emergency, the treatment code for an individual patient will be readily 
available to the Investigator and Sponsor/Medpace through the IVRS. If unblinding is necessary 
for patient management (in the case of an SAE), the Investigator will be able to break the 
treatment code by contacting the IVRS. Treatment codes should not be broken except in 
emergency situations. If the Investigator wishes to know the identity of the IMP for any other 
reason, he or she should contact the Medical Monitor directly. The Investigator should document 
and provide an explanation for any premature unblinding (e.g., accidental unblinding, unblinding 
due to an SAE). 
As per Health Authority reporting requirements, the Sponsor/Medpace will break the treatment 
code for all unexpected SAEs (see Section 9.3) that are considered by the Investigator to be 
related to IMP. 
Whenever disclosure of the identity of the IMP is necessary, adequate procedures will be in place 
to ensure integrity of the data. Any unblinding, at the investigating site end, will be documented 
in the study report with date, reason for identifying the drug and the name of all the person(s) 
who required unblinding. 
7.4. 
Treatment Compliance 
The Investigator/study pharmacist is responsible for the control of IMPs under investigation. 
Adequate records of the receipt (e.g., IMP Receipt Record) and disposition (e.g., IMP 
Dispensing Log) of the IMP must be maintained. The IMP Dispensing Log must be kept current 
and should contain the following information: 
• The identification of the patient to whom the IMP was dispensed (for example patient 
initials and date of birth). 
• The date(s), quantity of the IMP dispensed to the patient. 
• The date(s) and quantity of the IMP returned by the investigator/clinical site. 
• All records and drug supplies must be available for inspection by the Medpace 
Monitor at every monitoring visit. 
The pharmacy dispensing log will be monitored by study monitors at study visits and dosing 
compliance will be monitored on an ongoing process by the EDC system. 
7.5. 
Concomitant Therapy 
The following concomitant therapies will be allowed/excluded during the study: 
• Patients may receive standard of care for treatment of urinary symptoms. 
• Analgesics are permitted. 
• Antibiotics to treat newly active Gram positive non-urinary tract infections are 
permitted.  All other antibiotic use will not be permitted. Note: Antibiotics with 
Gram-positive coverage include, but are not limited to, vancomycin, daptomycin, and 
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• Urinary antiseptics will not be allowed. 
• Topical lidocaine and lubricants for catheter care are allowed. 
• Unless deemed acceptable by the Investigator, prescription drugs, over-the-counter 
(OTC) medications and supplements that acidify the urine are excluded. 
• Patients may continue to receive concomitant prescription medications (excluding 
Gram-negative antimicrobials), OTC medications and supplements for pre-existing 
conditions. 
• For this protocol, a prescription medication is defined as a medication that can be 
prescribed only by a properly authorized/licensed clinician. Medications to be 
reported in the electronic Case Report Form (eCRF) are concomitant prescription 
medications, OTC medications and supplements. Medications will be reported in the 
eCRF from Screening through to the EOS Visit.  
7.5.1. 
Rescue Medicine 
Any AE will be treated fully by appropriate medical and supportive treatment. There is no 
specific antidote or rescue medication. 


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8. 
TREATMENT DISCONTINUATION, STUDY 
PAUSING/SUSPENDING OF DOSING AND ENROLLMENT, 
AND PATIENT DISCONTINUATION/ WITHDRAWAL FROM 
STUDY 
Patients may withdraw voluntarily from the study or the PI may discontinue a patient from the 
study. There are no known AEs which have been specifically related to this product or this type 
of therapy which would result in discontinuation of study intervention or patient 
discontinuation/withdrawal. In addition, patients may discontinue the study intervention, but 
should, if at all possible, remain in the study for follow-up, especially for safety and 
pharmacodynamic study endpoints. Documentation for study intervention discontinuation and 
patient discontinuation/withdrawal from the study will be captured in the eCRF. This will 
capture the date and the specific underlying reason for discontinuation of study intervention or 
patient discontinuation/withdrawal. Study enrollment will continue up to the planned 
30 evaluable patients unless a decision is made by, or in conjunction with, the Sponsor to stop 
the study prior to meeting the target enrollment. 
Evaluation of safety signals will be conducted by a drug safety management committee (DSMC).  
The committee will review all potential safety signals including all adverse event (AE) and 
serious adverse event (SAE) reporting across the study to make a recommendation to the 
Sponsor on actions to take related to study-wide dosing, enrollment and stopping decisions.  The 
DSMC will include 3 suitably qualified individuals from the CRO and Sponsor (also see 
Section 11.1.5). 
8.1. 
Treatment Discontinuation  
There are no known or theoretical reasons or AEs that should require LBP-EC01 to be 
discontinued, however, if in the Investigators opinion it should be discontinued prior to planned 
EOT, it should be discussed with the Medical Monitor and study Sponsor. Discontinuation from 
LBP-EC01 or placebo does not mean discontinuation from the study, and remaining study 
procedures should be completed as indicated by the study protocol. If a clinically significant 
finding is identified (including, but not limited to changes from baseline) after enrollment, the 
Investigator or qualified designee will determine if any change in patient management is needed. 
Any new clinically relevant finding will be reported as an AE.  
A patient will be discontinued from therapy if they exhibit:  
• a Grade 3 or 4 IMP-related adverse event (AE) based on Division of AIDS (DAIDS) 
Table for Grading Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1, (https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf),  
• an IMP-related serious adverse event (SAE),  
• evidence of splenomegaly defined as a doubling of the largest dimension of the 
spleen from baseline (i.e. Day -6 to -1 assessment) or have hematologic evidence of 
splenic sequestration defined as a hematologic abnormality (i.e. anemia, leukopenia, 
thrombocytopenia) of Grade 3 or greater based on DAIDS criteria, or 
• any other conditions as deemed medically appropriate based on the Investigator's 
judgement. 


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If an antibiotic should become necessary for the treatment of a newly diagnosed UTI or a newly 
diagnosed Gram-negative non-urinary tract infection, the patient should be discontinued from 
treatment.  All remaining study assessments will be performed as planned. 
The data to be collected at the time of study discontinuation will include all activities required at 
the EOS visit per SoA (Table 1). 
8.2. 
Study Pausing/Suspending of Dosing and Enrollment 
Dosing for all patients and enrollment will be paused/suspended until a full cumulative data 
review is completed if any of the following occur: 
• Two or more subjects have the same or similar IMP-related Grade 3 or 4 AEs, based 
on DAIDS Table for Grading Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1, 
(https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf)  
• Any one subject has an IMP-related SAE, 
• Any observation of splenomegaly defined as a doubling of the largest dimension of 
the spleen from baseline (i.e. Day -6 to -1 assessment) or hematologic evidence of 
splenic sequestration defined as a hematologic abnormality (i.e. anemia, leukopenia, 
thrombocytopenia) of Grade 3 or greater based on DAIDS criteria, or 
• Any other conditions as deemed medically appropriate based on the Investigator's 
judgement. 
The Sponsor and/or DSMC may also pause/suspend dosing for any other reason based on 
emerging data from this or other ongoing studies. Should dosing be temporarily suspended, the 
IRB’s of the studies sites involved in the study and the FDA will be notified of the dosing 
suspension (See Section 9.4 – Unanticipated Problems) and the DSMC may review and discuss 
all available safety data from all patients participating in the study up until the time of the event. 
The DSMC will decide whether knowledge of the treatment assignment of any patient(s) is(are) 
necessary to make an appropriate decision about continuation of the study. If so, a request to 
unblind will be made and relevant data will be reviewed in an unblinded manner. All unblinding 
Standard Operating Procedures will be followed and documented as appropriate. 
Upon completion of the cumulative data review (whether fully blinded or partially unblinded), 
the DSMC may recommend to the Sponsor terminating the study or resuming study conduct. If 
study conduct is resumed, the DSMC may recommend, but is not limited to, one of the following 
actions to the Sponsor: 
• Continue dosing with the same number of patients originally planned 
• Change the frequency and/or duration of dosing at the current dose level (if there is 
thought to be a safety event after a certain number of doses) 
• De-escalate to a lower dose level 
Once an appropriate course of action has been determined the study IRBs and the FDA will be 
notified (see Section 9.4 - Unanticipated Problems). 
 


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8.3. 
Patient Discontinuation/Withdrawal from the Study 
Patients are free to withdraw from participation in the study at any time upon request, without 
prejudice to their continued care. 
An Investigator may discontinue or withdraw a patient from the study for the following reasons: 
• Pregnancy 
• Significant study intervention non-compliance  
• If a prohibited concomitant medication is required 
• If any clinical AE, laboratory abnormality, or other medical condition or situation 
occurs, including splenomegaly, such that continued participation in the study would 
not be in the best interest of the patient 
• Disease progression to active infection which requires discontinuation of the study 
intervention 
• If the patient meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• Termination of the study by the Sponsor or the regulatory authority. 
If a patient withdraws prematurely from the study due to the above criteria or any other reason, 
study staff should make every effort to complete the full panel of assessments scheduled for an 
Early Termination Visit. The reason for patient withdrawal must be documented in the electronic 
case report form (eCRF). 
The reason for patient discontinuation or withdrawal from the study will be recorded on source 
documentation and in the eCRF. Patients who sign the informed consent form and are 
randomized but do not receive the study intervention may be replaced.  
Note: patients may withdraw voluntarily from the study or discontinue the study intervention at 
any time. Investigators should, however, seek to minimize patient discontinuation/withdrawal 
from study except for safety reasons. 
8.4. 
Lost to Follow-Up 
Patients are considered lost to follow-up when they stop reporting to scheduled study visits and 
cannot be reached to complete all protocol-required study procedures.  
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
• The site will attempt to contact the patient and reschedule the missed visit or return 
for the next scheduled visit and counsel the patient on the importance of maintaining 
the assigned visit schedule and ascertain if the patient wishes to and/or should 
continue in the study. 
• Before a patient is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the patient (where possible, 3 telephone calls and, 
if necessary, a certified letter to the patient’s last known mailing address or local 


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equivalent methods). These contact attempts should be documented in the patient’s 
medical record or study file.  
• Should the patient continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 


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9. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Table 1). Blood and urine 
collection for assessment of PK, clinical laboratory values, urinalysis, urine cultures and 
sensitivity and immunogenicity are detailed in Table 2.  
9.1. 
Study Assessments  
9.1.1. 
Medical History and Demographic Data 
Medical history includes full urological history including urinary catheter management, previous 
UTIs with dates (Month/Year), any comorbid diseases, all surgeries, reproductive status, 
smoking history, use of alcohol and drugs of abuse and all concomitant medications (e.g., 
prescription drugs, OTCs, herbal or homeopathic remedies, nutritional supplements) used by the 
patient within 30 days prior to the Screening Visit. Demographic data will include date of birth 
(DOB), sex, and self-reported race/ethnicity. 
A full medical history will be taken at the Screening Visit, however, other medical history time 
points indicated in the SOA (Table 1) may be targeted to identify any changes and potential AEs. 
9.1.2. 
Physical Examination 
Any abnormality identified at baseline should be recorded on the General Medical History and 
Baseline Conditions eCRF. A complete or abbreviated physical examination will be performed at 
the time points indicated in the SOA (Table 1). 
A complete physical examination should include an evaluation of the head, eyes, ears, nose, 
throat, neck and lymph nodes, and the cardiovascular, dermatological, musculoskeletal, 
respiratory, gastrointestinal, genitourinary, and neurological systems. No invasive examinations 
(e.g., rectal examination) will be performed. 
At subsequent visits (or as clinically indicated), limited, symptom-directed physical 
examinations should be performed. Changes from baseline abnormalities should be recorded in 
study patient’s notes/source documents. New or worsened clinically significant abnormalities 
should be recorded as AEs on the Adverse Event eCRF. 
9.1.3. 
Spleen Evaluation  
Spleen evaluations will include ultrasound assessments for splenomegaly at Day -6 to -1 
(baseline), Day 3, and Day 7 and clinical examinations to assess for splenomegaly will be 
performed at all visits.  A clinical examination may also be performed at a clinic visit on Day 35 
at the discretion of the study investigator if there are abnormal or clinically significant findings at 
Day 28. 
9.1.4. 
 
Adverse Event Solicitation 
Adverse Events will be solicited before and after each dose on Days 1 – 7, once per day for the 
7 days after the last dose by telephone, at the follow-up visits on Days 14 and 28, and the 
telephone contact (or clinic visit at the discretion of the study investigator if there are abnormal 
or clinically significant findings at Day 28) on Day 35.  If the Day 14 visit occurs earlier or later 
than 14 days after initiating treatment the clinical staff will solicit AEs until Day 14 or the 


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Day 14 visit, whichever is the longer duration.  In addition to solicitation of general AEs, 
specific signs and symptoms of a UTI (e.g. dysuria, urinary frequency, urinary urgency, 
suprapubic discomfort and flank pain in addition to non-specific symptoms of urinary leakage, 
change in voiding habits, worsening muscle spasm, increasing autonomic dysreflexia, sweating, 
malaise, and fever or hypothermia) and local vesicular reaction (e.g., bladder pain, hematuria) to 
the study treatment will be solicited during Days 1-7 and for 7 days after the last dose of IMP or 
the Day 14 visit, whichever is longer. All AEs will be recorded on the Adverse Event eCRF.  
Patient diary cards will be provided to the patient to document AEs that occur between visits.  At 
Days 14, 28, and 35, the patient diary cards will be reviewed with the patient. All AEs will be 
recorded on the Adverse Event eCRF as described in Section 9.3 (Adverse Events and Serious 
Adverse Events).   
9.1.5. 
Pharmacokinetic Assessments 
Blood and urine samples for measurement of concentrations of LBP-EC01 will be collected at 
the timepoints in Table 1 and Table 2.  Blood for PK will be drawn immediately before urine 
sampling both pre- and post-dosing. The date and time of each urine and blood sample collection 
will be recorded in the eCRF 
Pre-dose PK urine and blood samples should be collected within 30 minutes prior to dosing; 
post-dose PK samples should be collected within 60 minutes after dosing. A post-dose urine and 
blood PK sample will be collected on Day 1, 6 hours after the first dose.  
9.1.5.1. 
Urine Pharmacokinetics 
At the start of the treatment period prior to the first dose a new catheter should be installed. 
Frequency of catheter changes during the treatment period will be at the discretion of the 
investigator. 
Urine will be collected as clean catheter specimens using the following procedure: 
Pre-dose: Bladder will be drained and then the catheter clamped for approximately 30 minutes; a 
clean catheter sample will be collected immediately before dosing (within 10 minutes) and the 
bladder will be fully evacuated prior to dosing. 
Post-dose: After administration of the IMP or placebo the catheter will be clamped for no less 
than 30 minutes (no longer than 40 minutes) post-dosing, then the catheter will be released, and 
the bladder contents drained. The catheter will be re-clamped and then sampled after 20 minutes. 
This same procedure will be used for each PK sampling time point.  
Urine concentrations of LBP-EC01 will be measured by a specific and validated quantitative 
bacterial plaquing assay. Samples collected for PK assessment will be separated from samples 
collected for microbiologic assessment and will be placed on ice immediately upon collection, 
stored refrigerated, and shipped immediately (overnight) at between 2°C and 8°C to the Central 
Lab for PK analysis as described in the laboratory manual. 
9.1.5.2. 
Blood Pharmacokinetics 
The PK samples at the EOT, Day 14 and Day 28 Visits will be obtained during the safety blood 
draws. 


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Blood concentrations of LBP-EC01 will be measured by a specific and validated quantitative 
bacterial plaquing assay. Samples collected for PK assessment will be separated from samples 
collected for microbiologic assessment and will be placed on ice immediately upon collection, 
stored refrigerated, and shipped immediately (overnight) at between 2°C and 8°C to the Central 
Lab for analysis as described in the laboratory manual. 
9.1.6. 
Pharmacodynamic Assessments  
9.1.6.1. 
Urine Microbiology 
Urine samples for culture and sensitivity will be collected at the timepoints specified in Table 2. 
Urine samples that are obtained outside of this schedule may be requested if available. 
Urine samples will be collected as clean catheter specimens (unless taken during screening from 
a non-catheterized patient then no catheter installation required) and will be sent to the Central 
Laboratory for quantitative culture and sensitivity of E. coli as outlined in Table 1 and Table 2. 
Quantitative culturing will be done for all E. coli isolates at the Central Lab. 
Pre-dose and post-dose samples of urine collected on Day 1, Day 2, Day 3, Day 5 and samples 
collected at EOT (Day 7) and the single samples taken at Day 14 and Day 28 Visits, will be 
aliquoted for microbiology from PK analysis. 
9.1.7. 
Laboratory Assessments 
Laboratory safety tests will be collected at timepoints specified in the SOA (Table 1) and the 
schedule of blood and urine sampling (Table 2). 
Samples for the following laboratory tests will be sent to the central laboratory for analysis: 
• Hematology: Hemoglobin, hematocrit, platelet count, red blood cell (RBC) count, 
mean corpuscular volume, absolute reticulocyte count, total and differential leucocyte 
(WBC) absolute count (neutrophils, eosinophils, lymphocytes, monocytes and 
basophils). 
• Serum chemistry: Albumin, alkaline phosphatase, alanine aminotransferase, 
aspartate aminotransferase, C-reactive protein, calcium, chloride, creatinine 
phosphokinase, gamma-glutamyl transferase, glucose, phosphate, potassium, 
creatinine, sodium, total bilirubin, total protein, troponin, urea, IL-6 and an 
immunoglobulin panel (IgA, IgE, IgG and IgM). 
• Coagulation: activated partial thromboplastin time, prothrombin time 
• Lipids: High density lipoprotein-cholesterol, low density lipoprotein cholesterol, 
triglycerides, total cholesterol. 
• Urinalysis and Microscopy A pre-dose catheter urine specimen will be collected for 
dipstick analysis of protein, blood, white blood cells, glucose, and pH and 
microscopy. 
• Pregnancy test: All women of childbearing potential (including those who have had 
a tubal ligation) will have an EPT urine pregnancy test at Screening, Day 1 prior to 
the first dose, and repeated at the Day 28 Visit (see Table 1). Results of the Day 1 


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pregnancy test will be reviewed to ensure that the patient is not pregnant prior to the 
first dose of study drug. The results will be documented in the eCRF. 
Additional blood or urine samples may be taken at the discretion of the Investigator if the results 
of any test fall outside the reference ranges, or clinical symptoms necessitate additional testing to 
monitor a patient’s safety. Where the clinical significance of abnormal lab results is considered 
uncertain, screening lab tests may be repeated before randomization to confirm eligibility. 
In the event of unexplained abnormal clinically significant laboratory test values, the tests should 
be repeated immediately and followed up until they have returned to the normal range and/or an 
adequate explanation of the abnormality is found. Results of central laboratory testing will be 
recorded on the eCRF or will be received as electronically-produced laboratory reports. 
Situations may arise when local laboratories are utilized such as stat safety labs. In these cases, 
reference ranges must be submitted where applicable. 
9.1.8. 
Screening Assessments 
Written informed consent for participation in the study must be obtained before performing any 
study-specific screening tests or evaluations. Informed Consent Forms for enrolled patients and 
for patients who are not subsequently enrolled will be maintained at the study site. All screening 
and pre-treatment assessments must be completed and reviewed to confirm that patients meet all 
eligibility criteria. The Investigator will maintain a screening log to record details of all patients 
screened and to confirm eligibility or record reasons for screening failure. An Eligibility 
Screening Form documenting the Investigator’s assessment of each screened patient with regard 
to the protocol’s inclusion and exclusion criteria is to be completed by the Investigator and kept 
at the investigational site. Screening assessments will be performed within 21 days prior to 
enrollment. For assessments, and timing of assessments at Screening, please see Table 1. 
9.1.9. 
Biological Specimen Collection and Laboratory Evaluations 
All laboratory evaluations will be performed at central laboratories, in compliance with Clinical 
Laboratory Improvement Amendments of 1988. 
• Clinical laboratory evaluations (hematology, clinical chemistry, coagulation, lipids, 
and urinalysis) will be performed by the Central Laboratory and affiliated labs using 
routine methodology (see Section 9.1.7). Approximately 40 mL of blood will be 
drawn at each of 7 timepoints (Screening, Day 1, Day 3, Day 5, Day 7 (EOT), Day 
14, and Day 28).  Repeat lab testing may be performed at Day 35 if there are 
abnormal or clinically significant findings at Day 28.   
• Screening microbiology evaluations:  Standard quantitative urine culture will be 
performed at Screening to identify E. coli colonization of ≥103 CFU/mL. Quantitation 
of non-E. coli bacteria will be done to confirm the predominance of E. coli as the 
primary bacteria colonizing the bladder.  This will be performed at the central 
microbiology laboratory (IHMA).  
• Pharmacodynamic microbiology: quantitative urine culture and sensitivity will be 
performed at the central microbiology laboratory for study visits between screening to 
Day 28 (see Table 2). The quantitative culture will include identification of genus and 
species and quantitation of E. coli.  Quantitation of non-E. coli bacteria will be done 


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at time of screening to confirm the predominance of E. coli as the primary bacteria 
colonizing the bladder and will be evaluated at Day 1, Day 2, Day 3, Day 5, Day 7 
(EOT), Day 14 and Day 28, to evaluate the presence and quantities of E. coli and 
non-E. coli bacteria before and after treatment with LBP-EC01. Antibiotic sensitivity 
of E. coli will be tested by the Central Lab and will include colistin and fosfomycin. 
• Urine culture: All E. coli isolates collected will be tested for phage sensitivity by the 
Central Lab using standard methodology developed at Locus.  
• Pharmacokinetic analysis will be performed by a quantitative bacterial plaquing assay 
to identify components of LBP-EC01. Methodology will be developed at the Central 
Lab. Instructions will be outlined in the laboratory procedures manual. 
• Immunogenicity assay to measure increases levels of antibodies (IgA, IgE, IgG, IgM) 
during treatment will be tested at specified visits (see Table 1 and Table 2). 
• Both blood and urine samples will be collected for general biomarker assessment.  
Biomarkers will include inflammatory biomarkers (e.g., interleukin [IL]-6), bacterial 
sensitivity to phage and bacterial metagenomic analysis which will be conducted on 
samples at the end of study. 
Special instructions for the preparation, handling, storage, and shipment of specimens will be 
detailed in the study’s Manual of Procedures (MOP). 
9.2. 
Safety and Other Assessments 
The following procedures/evaluations will be performed for safety evaluation: 
• Physical examination  
A targeted physical examination will be performed at the specified timepoints (or as 
clinically indicated). This will be a limited, symptom-directed physical examination 
only. Changes from baseline abnormalities should be recorded in patient’s notes. New 
or worsened clinically significant abnormalities should be recorded as AEs on the 
Adverse Event eCRF. 
• Spleen examination 
Spleen evaluations will include ultrasound assessments for splenomegaly at Day -6 to 
-1, Day 3, and Day 7 and clinical examinations to assess for splenomegaly will be 
performed at all visits.  A clinical examination may also be performed at a clinic visit 
on Day 35 at the discretion of the study investigator if there are abnormal or clinically 
significant findings at Day 28.  Splenomegaly defined as a doubling of the largest 
dimension of the spleen from baseline (i.e. Day -6 to -1 assessment) or hematologic 
evidence of splenic sequestration defined as a hematologic abnormality (i.e. anemia, 
leukopenia, thrombocytopenia) of Grade 3 or greater based on DAIDS criteria. 
• Adverse event solicitation 
Adverse events will be solicited before and after each dose on Days 1 - 7, once per 
day for the 7 days after the last dose by telephone, at the follow-up visits on Day 14 
(the clinical staff will solicit AEs until Day 14 or the Day 14 visit, whichever is the 


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longer duration, if the Day 14 visit does not occur on Day 14) and Day 28, and at the 
telephone contact (or clinic visit at the discretion of the study investigator if there are 
abnormal or clinically significant findings on Day 28) on Day 35.  In addition to 
solicitation of general AEs specific signs and symptoms of a UTI (e.g. dysuria, 
urinary frequency, urinary urgency, suprapubic discomfort and flank pain in addition 
to non-specific symptoms of urinary leakage, change in voiding habits, worsening 
muscle spasm, increasing autonomic dysreflexia, sweating, malaise, and fever or 
hypothermia) and local vesicular reaction (e.g., bladder pain, hematuria) to the study 
treatment will be solicited during Days 1-7 and for 7 days after the last dose of IMP 
or the Day 14 visit, whichever is longer.     
Patient diary cards will be provided to the patient to document AEs that occur 
between visits.  At Days 14, 28, and 35, the patient diary cards will be reviewed with 
the patient. All AEs will be recorded on the Adverse Event eCRF.   
• Vital signs  
Vital signs will include resting BP, heart rate, respiratory rate and oral body 
temperature and will be recorded at the timepoints specified in the SoA (Table 1). 
Additional vital signs pre- and post-dosing and 6 hours (on Day 1) post-dose will be 
recorded on the first day of treatment (see Table 1). 
• ECGs 
Triplicate 12-lead ECG recordings (i.e., 3 useful ECGs without artifacts) will be 
obtained within approximately 2-5 minutes at each specified timepoint for screening 
and safety. The average of the 3 readings will be used to determine ECG intervals 
(e.g., PR, QRS, QT). Additional unscheduled ECGs should be performed in case of 
abnormalities and if clinical symptoms occur. Whenever possible, the same 
brand/model of a standard high quality, high-fidelity electrocardiograph machine 
equipped with computer-based interval measurements should be used for each 
patient. The conditions should be as close as possible to pre-dose timepoints; this 
includes, but is not limited to, food intake, activity level, stressors and room 
temperature. To minimize variability, it is important that patients be in a resting 
position (semi-recumbent) for ≥10 minutes prior to each ECG evaluation. Body 
position should be consistently maintained for each ECG evaluation to prevent 
changes in heart rate.  
Environmental distractions (e.g., television, radio, conversation) should be avoided 
during the pre-ECG resting period and during ECG recording. In some cases, it may 
be appropriate to repeat abnormal ECGs to rule out improper lead placement as 
contributing to the ECG abnormality. For safety monitoring purposes, the Investigator 
or designee must review, sign, and date all ECG tracings. Paper or electronic copies 
will be kept as part of the patient’s permanent study file at the site. If considered 
appropriate by Sponsor, ECGs may be analyzed retrospectively at a central 
laboratory. 
The ECG characteristics, including heart rate, QRS duration, and PR, and QT 
intervals, will be recorded on the eCRF. QTcF (Fridericia’s correction) will be 
calculated and RR will be calculated and recorded on the eCRF. Changes in T-wave 


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and U-wave morphology and overall ECG interpretation will be documented on the 
eCRF. T-wave information will be captured as normal or abnormal, U-wave 
information will be captured in 2 categories: absent/normal or abnormal. 
• Biological specimen collection and laboratory evaluations. 
See Section 9.1.9 for all investigations. Any abnormal laboratory results will be 
flagged and followed up by the Medpace safety group on a real time basis. 
9.3. 
Adverse Events and Serious Adverse Events 
9.3.1. 
Definition of Adverse Events  
Adverse event means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug-related (21 CFR 312.32 [a]). 
9.3.1.1. 
Safety Parameters and Definitions 
Safety assessments will consist of monitoring and recording AEs, including SAEs and non-
serious AEs; measurement of protocol-specified safety laboratory assessments; measurement of 
protocol-specified vital signs, ECGs; and other protocol-specified tests that are deemed critical to 
the safety evaluation of the study. Certain types of events require immediate reporting to the 
Sponsor, as outlined in Section 9.3.6. 
9.3.1.2. 
Adverse Events 
According to the ICH guideline for GCP, an AE is any untoward medical occurrence in a clinical 
investigation subject administered a pharmaceutical product, regardless of causal attribution. An 
AE can therefore be any of the following: 
• Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product. 
• Any new disease or exacerbation of an existing disease (a worsening in the character, 
frequency, or severity of a known condition). 
• Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline. 
• Any deterioration in a laboratory value or other clinical test (e.g., ECG) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from IMP. 
• Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., screening invasive procedures 
such as biopsies). 
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9.3.2. 
Definition of Serious Adverse Events  
An AE or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or Medical Monitor/Sponsor, it results in any of the following outcomes:  
• Fatal (i.e., the AE actually causes or leads to death). 
• A life-threatening AE (i.e., the AE, in the view of the Investigator, places the patient 
at immediate risk of death). This does not include any AE that, had it occurred in a 
more severe form or was allowed to continue, might have caused death. 
• In-patient hospitalization or prolongation of existing hospitalization.  
• Results in persistent or significant disability/incapacity (i.e., the AE results in 
substantial disruption of the patient’s ability to conduct normal life functions). 
• Congenital anomaly/birth defect in a neonate/infant born to a mother exposed to IMP. 
• A significant medical event that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in the definition above. Examples 
of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization. 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
rated as mild, moderate, or severe, see Section 9.3.3.1. The event itself may be of relatively 
minor medical significance (such as severe headache without any further findings). Severity and 
seriousness need to be independently assessed for each AE recorded on the eCRF. 
Serious adverse events are required to be reported by the Investigator to Medpace/Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 9.3.6 for 
reporting instructions).  
9.3.3. 
Classification of an Adverse Event 
9.3.3.1. 
Severity of an Adverse Event 
All AEs will be assessed by the Investigator using the Division of AIDS (DAIDS) Table for 
Grading Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, 
(https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf).  In general, the 
following guidelines describe severity:  
• Grade 1 Mild: Mild symptoms causing no or minimal interference with usual social 
& functional activities with intervention not indicated 
• Grade 2 Moderate: Moderate symptoms causing greater than minimal interference 
with usual social & functional activities with intervention indicated 
• Grade 3 Severe: Severe symptoms causing inability to perform usual social & 
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• Grade 4 Potentially Life-Threatening: Potentially life-threatening symptoms 
causing inability to perform basic self-care functions with intervention indicated to 
prevent permanent impairment, persistent disability, or death 
• Grade 5 Death 
9.3.3.2. 
Relationship to Investigational Medicinal Product 
All AEs must have their relationship to study intervention assessed by the investigator who 
examines and evaluates the patient based on temporal relationship and his/her clinical judgment. 
The following guidance should be taken into consideration: 
• Temporal relationship of event onset to the initiation of IMP. 
• Course of the event, considering especially the effects of dose reduction, 
discontinuation of IMP, or reintroduction of IMP. 
• Known association of the event with the IMP or with similar treatments. 
• Known association of the event with the disease under study. 
• Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event. 
• Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event. 
The degree of certainty about causality will be graded using the categories below. In a clinical 
trial, the study product must always be suspect.  
• Related – The AE is known to occur with the IMP, there is a reasonable possibility 
that the IMP caused the AE, or there is a temporal relationship between the study 
intervention and event. Reasonable possibility means that there is evidence to suggest 
a causal relationship between the IMP and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the 
study intervention caused the event, there is no temporal relationship between the 
study intervention and event onset, or an alternate etiology has been established. 
9.3.3.3. 
Expectedness  
The Investigator will be responsible for determining whether an AE is expected or unexpected. 
An AE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the IMP. An AE or suspected 
adverse reaction is considered "unexpected" if it is not listed in the Investigator’s Brochure (IB) 
or is not listed at the specificity or severity that has been observed; or, if it is not consistent with 
the risk information described in the protocol. 
9.3.4. 
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a patient presenting for medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 


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on the appropriate eCRF. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All 
AEs occurring while in the study must be documented appropriately regardless of relationship. 
All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the patient is screened will be considered as 
baseline and not reported as an AE. However, if the patient’s condition deteriorates at any time 
during the study, it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. Adverse events characterized as intermittent 
require documentation of onset and duration of each episode. 
The Investigator or designee will record all AEs (non-serious and serious) with start dates 
occurring any time after informed consent is obtained until Day 35.  At each study visit, the 
Investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will be 
followed for outcome information until resolution or stabilization. 
9.3.5. 
Adverse Event Reporting  
Investigators will seek information on AEs at each patient contact. All AEs, whether reported by 
the patient or noted by study personnel, will be recorded in the patient’s medical record. Adverse 
events will then be reported on the Adverse Event eCRF as follows: 
• Investigators should use correct medical terminology/concepts when recording AEs 
on the Adverse Event eCRF. Avoid colloquialisms and abbreviations. 
• Only 1 AE term should be recorded in the event field on the Adverse Event eCRF.  
A consistent methodology of non-directive questioning should be adopted for eliciting AE 
information at all patient evaluation timepoints. Examples of non-directive questions include the 
following: 
“How have you felt since your last clinic visit?” 
“Have you had any new or changed health problems since you were last here?”  
In addition, solicited AEs will be recorded as per Section 9.2.   
The Investigator must record non-serious AEs and report them to the Sponsor according to the 
timetable for reporting as specified below: 
After informed consent has been obtained but prior to initiation of treatment, only SAEs 
caused by a protocol-mandated intervention should be reported (e.g., SAEs related to invasive 
procedures and urinary catheterization). Any other AE should not be reported. 
After initiation of treatment, all AEs and SAEs, regardless of relationship to IMP, will be 
reported until 28 days after the last dose of IMP (i.e. Day 35). 
After a period of 28 days from the last dose of IMP (i.e. Day 35), investigators should report 
any deaths, SAEs, or other AEs of concern that are believed to be related to prior treatment with 
IMP. 


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9.3.6. 
Serious Adverse Event Reporting  
All AEs considered serious by the PI, Sub-Investigator or which meets the definition of an SAE 
included in Section 9.3.2 must be submitted on an SAE form to the Medpace safety monitor. 
The Investigator will immediately report (within 24 hours) to the Medpace/Sponsor any SAE, 
whether or not considered IMP related, including those listed in the protocol or IB and must 
include an assessment of whether there is a reasonable possibility that the study intervention 
caused the event. 
All SAEs will be followed until satisfactory resolution or until the site Investigator deems the 
event to be chronic or the patient is stable. Other supporting documentation of the event may be 
requested by the Medpace Safety monitoring group/study Sponsor and should be provided as 
soon as possible. Medpace/Sponsor will be responsible for notifying the Food and Drug 
Administration (FDA) of any unexpected fatal or life-threatening suspected adverse reaction as 
soon as possible, but in no case later than 7 calendar days after the Sponsor’s initial receipt of the 
information. In addition, the Sponsor must notify FDA and all participating investigators in an 
IND safety report of potential serious risks, from clinical trials or any other source, as soon as 
possible, but in no case later than 15 calendar days after the Sponsor determines that the 
information qualifies for reporting. 
Study enrollment will be halted pending review of available clinical data for study drug-related 
SAEs that trigger a DSMC review (see Section 8.2). 
9.3.7. 
Reporting Events to Patients 
Study patients will be informed about AEs and SAEs on an individual or aggregate level 
depending on the potential seriousness of the risk to individuals. Any unexpected AEs and SAEs 
will be communicated to individuals at study visits or by telephone calls if deemed necessary 
depending on risk to the individuals. Study patients will be given written top line results when 
available after the study. 
9.3.8. 
Events of Special Interest  
Not applicable. 
9.3.9. 
Reporting of Pregnancy  
9.3.9.1. 
Pregnancies in Female Patients 
Female patients of childbearing potential will be instructed to immediately inform the 
Investigator if they become pregnant during the study (by the EOS visit). A Clinical Trial 
Pregnancy Reporting Form should be completed by the Investigator and submitted to 
Medpace/Sponsor within 24 hours after learning of the pregnancy. Pregnancy should not be 
recorded on the Adverse Event eCRF. The Investigator should discontinue IMP, if applicable, 
and counsel the patient, discussing the risks of the pregnancy and the possible effects on the 
fetus. Monitoring of the patient should continue until conclusion of the pregnancy. 


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9.3.9.2. 
Pregnancies in Female Partners of Male Patients 
Male patients will be instructed through the Informed Consent Form to immediately inform the 
Investigator if their partner becomes pregnant during the study (by the EOS visit). A Clinical 
Trial Pregnancy Reporting Form should be completed by the Investigator and submitted to 
Medpace/Sponsor within 24 hours after learning of the pregnancy. Attempts should be made to 
collect and report details of the course and outcome of any pregnancy in the partner of a male 
patient exposed to IMP. The pregnant partner will need to sign an Authorization for Use and 
Disclosure of Pregnancy Health Information to allow for follow-up on her pregnancy. Once the 
authorization has been signed, the Investigator will update the Clinical Trial Pregnancy 
Reporting Form with additional information on the course and outcome of the pregnancy. An 
Investigator who is contacted by the male patient or his pregnant partner may provide 
information on the risks of the pregnancy and the possible effects on the fetus, to support an 
informed decision in cooperation with the treating physician and/or obstetrician. 
9.3.9.3. 
Abortions 
Any spontaneous abortion should be classified as an SAE (as the Sponsor considers spontaneous 
abortions to be medically significant events), recorded on the Adverse Event eCRF, and reported 
to the Medpace/Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 9.3.6 ). Any induced abortion due to maternal toxicity and/or embryo-fetal toxicity 
should also be classified as and SAE , recorded on the Adverse Event eCRF, and reported to 
Medpace/Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 9.3.6 ). 
Elective abortion not associated with toxicity (e.g., induced abortion for personal reasons) does 
not require expedited reporting but should be reported as outcome of pregnancy on the Clinical 
Trial Pregnancy Reporting Form. 
9.3.9.4. 
Congenital Anomalies/Birth Defects 
Any congenital anomaly/birth defect in a child born to a female patient or female partner of a 
male patient exposed to IMP should be classified as an SAE, recorded on the Adverse Event 
eCRF, and reported to Medpace/Sponsor immediately (i.e., no more than 24 hours after learning 
of the event; see Section 9.3.6). 
9.4. 
Unanticipated Problems 
9.4.1. 
Definition of Unanticipated Problems  
The Office for Human Research Protections (OHRP) considers unanticipated problems (UPs) 
involving risks to participants or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the patient population being studied; 


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• Related or possibly related to participation in the research (“possibly related” means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and 
• Suggests that the research places study patients or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
9.4.2. 
Unanticipated Problem Reporting  
The Investigator will report UPs to the reviewing IRB and to Medpace/Sponsor lead PI. The UP 
report will include the following information: 
• Protocol identifying information: protocol title and number, PIs name, and the IRB 
project number; 
• A detailed description of the event, incident, experience, or outcome;  
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP;  
• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP. 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
• UPs that are SAEs will be reported to the IRB and to Medpace/Sponsor within 
24 hours of the Investigator becoming aware of the event.  
• Any other UP will be reported to the IRB and to Medpace/Sponsor as soon as 
possible, but in no event later than 10 working days after the Investigator first 
becoming aware of the problem.  
• All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or designee), 
and the OHRP within timeline in accordance with policy of the IRBs receipt of the 
report of the problem from the Investigator. 
A Sponsor/representative who conducts an evaluation of an UP shall report the results of such 
evaluation to the FDA and to all reviewing IRBs and participating investigators within 
10 working days after the Sponsor first receives notice of the UP. Thereafter the Sponsor shall 
submit such additional reports concerning the effect as FDA requests (21 CFR 812.150[b][1]).  
9.4.3. 
Reporting Unanticipated Problems to Patients 
Study patients will be informed about UPs on an individual or aggregate level depending on the 
potential seriousness of the risk to individuals. 


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10. 
STATISTICAL CONSIDERATIONS  
10.1. 
Statistical Hypotheses 
This is a Phase 1b study and primary outcomes are evaluation of safety, tolerability and PK. No 
formal hypothesis will be tested. 
10.2. 
Sample Size Determination 
A total of approximately 30 patients will be randomized in a 2:1 ratio to LBP-EC01 or placebo. 
This is a FIH study and the sample size should be sufficient to establish early safety and PK at a 
single dose level. 
10.3. 
Populations for Analyses 
The following data sets will be evaluated: 
• Safety Population: Patients who took at least 1 dose of IMP. 
• PK Population: Patients who took at least 1 dose of IMP with at least 1 analyzable PK 
sample. 
• PD Population: Patients who met enrollment criteria, who have a baseline PK 
assessment, and who took at least 1 dose of IMP. 
10.4. 
Statistical Analyses 
10.4.1. 
General Approach 
A separate Statistical Analysis Plan (SAP) will be developed prior to database lock. 
Pharmacokinetics 
• Individual and mean plasma concentrations and urine concentrations at each sampling 
time point for LBP-EC01 will be presented by listings and descriptive summary 
statistics. 
Pharmacodynamics 
• Change from baseline (Day 1) in E. coli quantitative culture concentration at Day 2, 
Day 3, Day 5, Day 7 (EOT), Day 14 and Day 28 in the urine will be summarized by 
treatment groups.  
• All other PD endpoints (time to 1 log reduction in urinary E. coli count, recurrence of 
E. coli colonization or incidence of infection) will be tabulated. 
10.4.2. 
Safety Analyses 
Safety and tolerability will be presented as: 
• Listings, summary tables, and graphs (individual plots and/or mean plots) by 
treatment group will be provided for safety and tolerability assessments. 
• Laboratory results will be presented as change results from baselines as shift tables. 


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Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA); 
each AE will be counted once only for a given patient unless severity increases. The severity, 
frequency, and relationship of AEs to IMP will be presented by System Organ Class (SOC) and 
preferred term groupings and will include start date, stop date, severity, relationship, 
expectedness, outcome, and duration. Adverse events leading to premature discontinuation from 
the IMP and SAEs will be presented in a listing. 
10.4.3. 
Baseline Descriptive Statistics 
Baseline characteristics, including demographics and laboratory measurements will be 
summarized using descriptive statistics. 
10.4.4. 
Planned Interim Analyses  
No interim analysis is planned. 
10.4.5. 
Exploratory Analyses 
Differences between indwelling and intermittent urinary catheterization populations will be 
compared.  
Any persisting microbiological isolates will be fully explored with bacteriophage host range, 
antibiotic resistance patterns and genetic sequencing of isolates. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Regulatory, Ethical, and Study Oversight Considerations 
11.1.1. 
Informed Consent Process 
11.1.1.1. Consent/assent and Other Informational Documents Provided to Patients 
Consent forms describing in detail the IMP, study procedures, and risks will be given to the 
patient and written documentation of informed consent is required prior to starting screening 
interventions. The following consent materials are submitted with this protocol.  
11.1.1.2. Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the patient’s agreeing to participate in the 
study and continues throughout the patient’s study participation. Consent forms will be IRB-
approved and the patient will be asked to read and review the document. The Investigator will 
explain the research study to the patient and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the patient’s comprehension of the purposes, 
procedures, and potential risks of the study and of their rights as research patients. Study patients 
will have the opportunity to carefully review the written consent form and ask questions prior to 
signing. The study patient s should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The patient will sign the informed 
consent form prior to any procedures being done specifically for the study. Patients must be 
informed that participation is voluntary and that they may withdraw from the study at any time, 
without prejudice. A copy of the informed consent form will be given to the patients for their 
records. The informed consent process will be conducted and documented in the source 
document (including the date), and the form signed, before the patient undergoes any study-
specific procedures. The rights and welfare of the patients will be protected by emphasizing to 
them that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. 
11.1.2. 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause as described in Section 8. Written notification, documenting the reason for 
study suspension or termination, will be provided by the suspending or terminating party to 
patients, Investigator, the IND, Sponsor and regulatory authorities. If the study is prematurely 
terminated or suspended, the PI will promptly inform patients, the IRB, and Sponsor and will 
provide the reason(s) for the termination or suspension. Patients will be contacted, as applicable, 
and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to patients 
• Demonstration of efficacy that would warrant stopping 
• Insufficient compliance to protocol requirements 


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• Data that are not sufficiently complete and/or evaluable 
• Poor protocol compliance 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB and/or FDA. 
11.1.3. 
Confidentiality and Privacy  
Patient confidentiality and privacy are strictly held in trust by the participating investigators, 
their staff, and the Sponsor(s) and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
patients. Therefore, the study protocol, documentation, data, and all other information generated 
will be held in strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of the Sponsor. All research 
activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the Sponsor, representatives of the IRB, 
regulatory agencies may inspect all documents and records required to be maintained by the 
Investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the patients in this study. The clinical study site will permit access to such 
records. 
The patient’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the reviewing IRB, Institutional policies, or Sponsor 
requirements. 
Patient’s research data, which are for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at the Medpace Data Coordinating Center. This will not include the 
patient’s contact or identifying information. Rather, individual patients and their research data 
will be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites and by Medpace Data Coordinating Center research 
staff will be secured and password protected. At the end of the study, all study databases will be 
de-identified and archived at the Sponsor or Medpace Data Coordinating Center. 
11.1.4. 
Future Use of Stored Specimens and Data  
Data collected for this study will be analyzed and stored at the Medpace Data Coordinating 
Center. After the study is completed, the de-identified, archived data will ultimately be 
transmitted to and stored by the Sponsor.  
With the patient’s approval and as approved by local IRBs, de-identified microbiological and 
biological samples will be stored at the Medpace and IHMA bio-sample repository. These 
samples could be used to further examine the causes of urinary tract and other infections to 
improve anti-microbial and bacteriophage therapy. The PK analysis data may be shared with 
future PK studies for population kinetics analyses. 
During the conduct of the study, an individual patient can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent with regard to 
bio-sample storage may not be possible after the study is completed.  


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11.1.5. 
Safety Oversight 
Safety oversight will be under the direction of the Medpace Safety Monitoring safety group, 
Medpace Medical Monitor and the Sponsor Medical Monitor.  A DSMC will review the 
available clinical data if the conditions outlined for suspending enrollment and treatment in 
Section 8 are met.  The DSMC will include 3 suitably qualified individuals.  The composition of 
the DSMC will be two medically trained representatives from the CRO (Medpace) and a 
delegate from the Sponsor.   
Periodic Review for Trends:  
Locus will be accountable for overall safety surveillance for the compound, including adverse 
event trend analysis and signal detection. Medpace will assist with the safety analyses and safety 
surveillance for this protocol by gathering and compiling all safety data for this study and 
facilitating regular safety reviews based on enrollment and occurrence of any AEs.  
This periodic review will occur monthly once 20% of subjects are randomized and may include 
the following data:  
• 
Laboratory and Clinical data   
• 
Serious Adverse Events and Adverse Events from the clinical database 
Data Management and Biostatistics from the CRO, if applicable, will compile the data to be 
reviewed. If a potentially unreported SAE is identified, the Medpace Medical Monitor (MM) or 
Lead Safety Physician will alert the Clinical Safety Manager to distribute the related safety 
information to the DSMC.  Medpace Clinical Safety will follow up with the site and Clinical 
Research Associate (CRA) adhering to the reporting guidelines outlined in Section 9.3. Monthly 
reviews of the compiled safety data will take place by the DSMC. 
Communication of Significant Findings:  
If deemed medically significant, the Medpace MM or Lead Safety Physician will alert Locus of 
overall study trends during review. Documentation of the reviews will be maintained in the Trial 
Master File.   
If a concerning trend in safety data or significant safety signal is identified by the DSMC, it will 
be submitted to participating regulatory agencies, Investigators, and IRBs as applicable.  This 
information will be submitted no later than calendar day (CD) 7 (death/life-threatening cases) or 
CD 15 (for all other cases), after the determination by Locus that the information qualifies for 
reporting. 
11.1.6. 
Clinical Monitoring 
Clinical site monitoring will be conducted to ensure that the rights and well-being of study 
patients are protected, that the reported study data are accurate, complete, and verifiable, and that 
the conduct of the study is in compliance with the currently approved protocol/amendment(s), 
with ICH GCP, and with applicable regulatory requirement(s).  
• Monitoring for this study will be performed by Medpace clinical monitors.  
• On-site and centralized monitoring will be performed. Frequency (e.g., early, for 
initial assessment and training, versus throughout the study. Monitoring will be 


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targeted verification of regulatory documentation, eligibility criteria endpoint, safety 
and other key data variables including PK assessments and microbiology. 
• The Sponsor will be provided electronic copies of monitoring reports within 15 days 
of visit. 
• Details of clinical site monitoring will be documented in a Clinical Monitoring Plan 
(CMP). The CMP describes in detail who will conduct the monitoring, at what 
frequency monitoring will be done, at what level of detail monitoring will be 
performed, and the distribution of monitoring reports. 
• Independent audits may be conducted by the Sponsor to ensure monitoring practices 
are performed consistently across all participating sites and that monitors are 
following the CMP. 
11.1.7. 
Quality Assurance and Quality Control 
The contract research organization (CRO; Medpace) will be responsible for data management of 
this study, including quality checking of the data. Sites will be responsible for data entry into the 
Electronic Data Capture (EDC) system. 
A comprehensive validation check program will verify the data. Discrepancies will be generated 
automatically in the system at the point of entry or added manually for resolution by the 
Investigator. 
Medpace will produce a Data Handling Manual that describes the quality checking to be 
performed on the data. Laboratory electronic data will be sent directly to Medpace, using 
Medpace’s standard procedures to handle and process the electronic transfer of these data. 
System backups for data stored by Medpace and records retention for the study data will be 
consistent with Medpace’s standard procedures. 
In the event of discrepant data, Medpace will request data clarification from the sites, which the 
sites will resolve electronically in the EDC system. 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are 
generated and biological specimens are collected, documented (recorded), and reported in 
compliance with the protocol, ICH GCP, and applicable regulatory requirements (e.g., GLP, 
Good Manufacturing Practices).  
The investigational site will provide direct access to all study-related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the Sponsor, and 
inspection by local and regulatory authorities. 
11.1.8. 
Data Handling and Record Keeping  
11.1.8.1. Data Collection and Management Responsibilities  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 


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Data for this study will be captured via an online EDC system. The data collected in the source 
documents is entered onto the study eCRF. An audit trail will maintain a record of initial entries 
and changes made; reasons for change; time and date of entry; and user name of person 
authorizing entry or change. For each patient enrolled, an eCRF must be completed and 
electronically signed by the PI or authorized delegate from the study staff. If a patient withdraws 
from the study, the reason must be noted on the eCRF. If a patient is withdrawn from the study 
because of a treatment-limiting AE, thorough efforts should be made to clearly document the 
outcome. 
The Investigator should ensure the accuracy, completeness and timeliness of the data reported to 
the Sponsor/CRO in the eCRFs and in all required reports. 
The eCRFs will be submitted electronically to the Sponsor/CRO and should be handled in 
accordance with instructions from the Sponsor/CRO. 
At the end of the study, the Sponsor will receive patient data for the study by site and will share 
this data with the study investigators for his or her site in a readable electronic format which 
must be kept with the study records. Acknowledgement of receipt of the data is required. 
Study monitors will perform ongoing source data verification to confirm that critical protocol 
data (i.e., source data) entered into the eCRFs by authorized site personnel are accurate, 
complete, and verifiable from source documents. 
Source documents (paper or electronic) are those in which patient data are recorded and 
documented for the first time. They include, but are not limited to, hospital records, clinical and 
office charts, laboratory notes, memoranda, patient-reported outcomes, evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies of transcriptions 
that are certified after verification as being accurate and complete, microfiche, photographic 
negatives, microfilm or magnetic media, X-rays, patient files, and records kept at pharmacies, 
laboratories, and medicotechnical departments involved in a clinical trial. 
Before study initiation, data to be entered directly into the eCRFs (i.e., no prior written or 
electronic record of the data) and considered source data must be defined in the Clinical 
Monitoring Plan. 
Source documents that are required to verify the validity and completeness of data entered into 
the eCRFs must not be obliterated or destroyed and must be retained per the policy for retention 
of records described in Section 11.1.8.3. 
To facilitate source data verification, the investigators and institutions must provide the Sponsor 
direct access to applicable source documents and reports for trial-related monitoring, Sponsor 
audits, and IRB/EC review. The investigational site must also allow inspection by applicable 
Health Authorities. 
11.1.8.2. Use of a Computerized System 
When clinical observations are entered directly into an investigational site’s computerized 
medical record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with Health Authority 
requirements pertaining to computerized systems used in clinical research. An acceptable 


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computerized data collection system allows preservation of the original entry of data. If original 
data are modified, the system should maintain a viewable audit trail that shows the original data 
as well as the reason for the change, name of the person making the change, and date of the 
change. 
11.1.8.3. Study Records Retention  
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IMP. These documents should be retained for a 
longer period, however, if required by local regulations. No records will be destroyed without the 
written consent of the Sponsor. It is the responsibility of the Sponsor to inform the Investigator 
when these documents no longer need to be retained. 
11.1.9. 
Protocol Deviations  
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or MOP 
requirements. The noncompliance may be either on the part of the patient, the Investigator, or the 
study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly.  
These practices are consistent with ICH GCP:  
• 4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3  
• 5.1 Quality Assurance and Quality Control, Section 5.1.1  
• 5.20 Noncompliance, Sections 5.20.1, and 5.20.2.  
It is the responsibility of the site Investigator to use continuous vigilance to identify and report 
deviations within 2 working days of identification of the protocol deviation, or within 2 working 
days of the scheduled protocol-required activity. All deviations must be verified in study source 
documents, and the CRAs will report them via the monitoring visit report (MVR) which will be 
entered into a ClinTrak SM listing. The sponsor will have access to this listing and the MVR. 
Protocol deviations must be sent to the reviewing IRB per their policies. The site Investigator is 
responsible for knowing and adhering to the reviewing IRB requirements. Further details about 
the handling of protocol deviations will be included in the Monitoring Plan and Protocol 
Deviation Plan.  
11.1.10. 
Publication and Data Sharing Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor prior to submission. 
This allows the Sponsor to protect proprietary information and to provide comments based on 
information from other studies that may not yet be available to the Investigator. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter trials only in their entirety and not as individual center data. In this case, a 
coordinating Investigator will be designated by mutual agreement.  


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Any formal publication of the study in which contribution of Sponsor personnel exceeded that of 
conventional monitoring will be considered as a joint publication by the Investigator and the 
appropriate Sponsor personnel. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
Any inventions and resulting patents, improvements, and/or know-how originating from the use 
of data from this study will become and remain the exclusive and unburdened property of the 
Sponsor, except where agreed otherwise. 
11.1.11. 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the design and 
conduct of this trial. The study leadership has established policies and procedures for all study 
group members to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
11.2. 
Additional Considerations 
Not applicable


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11.3. 
Abbreviations 
AE 
Adverse Event 
AMR 
Antimicrobial Resistance 
BP 
Blood Pressure 
BID 
Twice Daily 
CD 
Calendar Day 
CFR 
Code of Federal Regulations 
CFU 
Colony Forming Unit 
CMP 
Clinical Monitoring Plan 
CR 
Carbapenem-Resistant 
CRISPR 
Clustered Regularly Interspersed Short Palindromic Repeats 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CrPhage 
CRISPR-Enhanced Bacteriophage 
DNA 
Deoxyribonucleic Acid 
DSMC 
Drug Safety Management Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Forms 
EDC 
Electronic Data Capture 
EOS 
End of Study 
EOT 
End of Treatment 
ESBL 
Extended Spectrum Beta-Lactamase 


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FDA 
Food and Drug Administration 
FIH 
First In Human 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
Ig 
Immunoglobulin 
IL 
Interleukin 
IND 
Investigational New Drug  
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IV 
Intravenous 
IVRS 
Interactive Voice/Web-Based Response System 
IU 
Intraurethrally 
MBL 
Medpace Bioanalytical Laboratory 
MedDRA 
Medical Dictionary for Regulatory Activities 
MDR 
Multi-Drug Resistant 
MM 
Medical Monitor 
MOP 
Manual of Procedures 
NCT 
National Clinical Trial 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
OTC 
Over-The-Counter 


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PD 
Pharmacodynamic 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
(q)PCR 
(Quantitative) Polymerase Chain Reaction 
QTcF 
QT Interval With Fridericia’s Correction 
RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCI 
Spinal Cord Injury 
SoA 
Schedule of Assessments 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
UTI 
Urinary Tract Infection 
XDR 
Extensive Drug Resistant 
 
 


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11.4. 
Protocol Amendment History 
The table below is intended to capture changes of IRB-approved versions of the protocol, 
including a description of the change and rationale. A Summary of Changes table for the current 
amendment is located on the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
1.3 
04-Oct-2019 Updated to preclinical information, 
more detailed description of drug 
product, exclusion criteria and safety 
management sections 
Updates based on FDA 
feedback.  
1.4 
01-Oct-2020 Updated to clarify that PD analysis 
will be conducted with urine samples 
across all timepoints collected 
Administrative clarification 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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12. 
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Levin BR, Bull JJ. Population and evolutionary dynamics of phage therapy. Nat Rev Microbiol. 
2004;2(2):166-73. 
Lob SH, Nicolle LE, Hoban DJ, Kazmierczak KM, Badal RE, Sahm DF. Susceptibility patterns 
and ESBL rates of Escherichia coli from urinary tract infections in Canada and the United States, 
SMART 2010-2014. Diagn Microbiol Infect Dis. 2016;85(4):459- 65. 
Łusiak-Szelachowska M, Zaczek M, Weber-Dabrowska B, Miedzybrodzki R, Klak M, Fortuna 
W, et al. Phage neutralization by sera of patients receiving phage therapy. Viral Immunol. 
2014;27(6):295-304. 


Safety, tolerability and pharmacokinetics of LBP-EC01 in patients with lower urinary tract colonization caused by E. coli 
Version 1.4 
Protocol: LBx-1001 
01 Oct 2020 
Locus Biosciences, Inc  
Confidential 
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Rhoads DD, Wolcott RD, Kuskowski MA, Wolcott BM, Ward LS, Sulakvelidze A. 
Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial. J Wound 
Care. 2009;18(6):237-8, 240-3. 
Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, et. al. 
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with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 
2017; 61(10) doi: 10.1128/AAC.00954-17. 
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systemic inflammation. Journal of Biomedical Science. 2017; 24: 60.   
Talbot GH, Bradley J, Edwards JE Jr, Gilbert D, Scheld M, Bartlett JG, et al. Bad bugs need 
drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of 
the Infectious Diseases Society of America. Clin Infect Dis. 2006;42(5):657-68. 
Wittebole X, De Roock S, Opal SM. A historical overview of bacteriophage therapy as an 
alternative to antibiotics for the treatment of bacterial pathogens. Virulence. 2014;5:1, 226-35. 
Wright A, Hawkins CH, Anggård EE, Harper DR. A controlled clinical trial of a therapeutic 
bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a 
preliminary report of efficacy. Clin Otolaryngol. 2009;34(4):349-57. 

SAP_001.pdf: 

STATISTICAL ANALYSIS PLAN 
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Locus Biosciences, Inc 
LBx-1001 
CONFIDENTIAL 
Statistical Analysis Plan 
Version 1.0, 17Dec2020 
Page 3 of 23 
 
 
 
VERSION HISTORY 
 
Version 
Version Date 
Description 
1.0 
17Dec2020 
Initial approved version 


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LBx-1001 
CONFIDENTIAL 
Statistical Analysis Plan 
Version 1.0, 17Dec2020 
Page 4 of 23 
 
 
 
TABLE OF CONTENTS 
1 
Introduction ......................................................................................................................... 7 
2 
Study Overview ................................................................................................................... 7 
2.1 
Study Objectives .......................................................................................................... 7 
2.1.1 
Primary Objective ................................................................................................. 7 
2.1.2 
Secondary Objectives ........................................................................................... 7 
2.1.3 
Exploratory Objectives .......................................................................................... 7 
2.2 
Study Design ............................................................................................................... 7 
2.2.1 
Overview ............................................................................................................... 7 
2.2.2 
Randomization and Blinding ................................................................................. 8 
2.2.3 
Study Drug ............................................................................................................ 8 
2.2.4 
Sample Size Determination ................................................................................... 9 
2.3 
Study Endpoints ........................................................................................................... 9 
2.3.1 
Primary Endpoints ................................................................................................ 9 
2.3.2 
Secondary Endpoints ........................................................................................... 10 
2.3.3 
Exploratory Endpoints .......................................................................................... 10 
2.3.4 
Exploratory Analyses ........................................................................................... 10 
3 
Statistical Methodology ...................................................................................................... 10 
3.1 
General Considerations .............................................................................................. 10 
3.1.1 
Definition of Baseline ........................................................................................... 10 
3.1.2 
End of Treatment Definition ................................................................................. 11 
3.1.3 
End of Study Definition ........................................................................................ 11 
3.1.4 
Summary Statistics .............................................................................................. 11 
3.1.5 
Hypothesis Testing .............................................................................................. 11 
3.1.6 
Handling of Dropouts and Missing Data ............................................................... 11 
3.2 
Analysis Populations ................................................................................................... 11 
3.2.1 
Safety Population ................................................................................................. 11 
3.2.2 
Intent-to-Treat (ITT) Population ............................................................................ 11 
3.2.3 
Evaluable Population ........................................................................................... 11 
3.2.4 
PK Population ...................................................................................................... 12 
3.2.5 
PD Population ...................................................................................................... 12 
3.2.6 
Subgroup Analyses .............................................................................................. 12 
3.3 
Subject Data and Study Conduct ................................................................................ 12 
3.3.1 
Subject Disposition .............................................................................................. 12 
3.3.2 
Protocol Deviations .............................................................................................. 12 
3.3.3 
Analysis Populations ............................................................................................ 12 
3.3.4 
Demographic and Baseline Characteristics .......................................................... 13 
3.3.5 
Medical History .................................................................................................... 13 
3.3.6 
Prior and Concomitant Medications ..................................................................... 13 
3.3.7 
Catheterization ..................................................................................................... 13 
3.3.8 
Study Drug Administration and Exposure ............................................................. 14 


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3.4 
Pharmacokinetic Assessment ..................................................................................... 14 
3.4.1 
Sample Collections for Pharmacokinetic Analysis ................................................ 14 
3.4.2 
Handling Missing or Below the Lower Limit of Quantification Data........................ 14 
3.4.3 
Pharmacokinetic Concentration............................................................................ 15 
3.4.4 
Pharmacokinetic Parameters ............................................................................... 15 
3.5 
Pharmacodynamic Assessment .................................................................................. 16 
3.6 
Exploratory Assessment ............................................................................................. 17 
3.6.1 
Urine Culture and Sensitivity ................................................................................ 17 
3.6.2 
Bacterial Biomarkers ............................................................................................ 17 
3.6.3 
Microbiological Isolates ........................................................................................ 17 
3.7 
Safety Assessment ..................................................................................................... 17 
3.7.1 
Adverse Events (AEs) .......................................................................................... 18 
3.7.2 
Clinical Laboratory Tests...................................................................................... 18 
3.7.3 
Immunoglobulins .................................................................................................. 18 
3.7.4 
Vital Signs ............................................................................................................ 19 
3.7.5 
Body Weight, Height, and Body Mass Index ........................................................ 19 
3.7.6 
Electrocardiograms .............................................................................................. 19 
3.7.7 
Physical Examinations ......................................................................................... 19 
3.7.8 
Spleen Examinations ........................................................................................... 20 
4 
Data Safety Monitoring Committee .................................................................................... 20 
5 
Analysis Timing .................................................................................................................. 20 
5.1 
Interim Analysis .......................................................................................................... 20 
5.2 
Pre-Final Analysis ....................................................................................................... 20 
5.3 
Final Analysis .............................................................................................................. 20 
6 
Additional Analyses on The Impact of COVID-19 ............................................................... 21 
6.1 
General Consideration ................................................................................................ 21 
6.2 
Analysis Populations ................................................................................................... 21 
6.2.1 
COVID-19 Population .......................................................................................... 21 
6.3 
Subject Disposition ..................................................................................................... 21 
6.4 
Protocol Deviations ..................................................................................................... 21 
6.5 
Concomitant Medications ............................................................................................ 21 
6.6 
Safety Assessment ..................................................................................................... 21 
6.6.1 
Adverse Events (AEs) .......................................................................................... 21 
7 
Changes from Protocol-Specified Statistical Analyses ........................................................ 22 
8 
Programming Specifications ............................................................................................... 22 
Appendix A:  Laboratory Tests .................................................................................................. 23 


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Statistical Analysis Plan 
Version 1.0, 17Dec2020 
Page 6 of 23 
 
 
LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
ADaM 
Analysis Data Model 
AE 
Adverse event 
ATC 
Anatomical therapeutic chemical 
AUC 
Area under curve 
BID 
Twice daily 
BLQ 
Below limit of quantification 
BMI 
Body mass index 
CDISC 
Clinical Data Interchange Standards Consortium 
CFU 
Colony-Forming Unit 
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
CRISPR 
Clustered Regularly Interspersed Short Palindromic Repeats 
crPhages 
CRISPR-enhanced bacteriophage 
CSR 
Clinical Study Report 
DAIDS 
Division of AIDS (Acquired immunodeficiency syndrome) 
DSMC 
Data Safety Monitoring Committee 
E. coli 
Escherichia coli 
ECG 
Electrocardiogram 
EOS 
End of study 
EOT 
End of treatment 
FIH 
First in human 
GM 
Geometric mean 
IgA 
Immunoglobulin A 
IgE 
Immunoglobulin E 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMP 
Investigational Medicinal Product 
ITT 
Intent-to-Treat 
IVRS 
Interactive voice/web-based response system 
MedDRA 
Medical Dictionary for Regulatory Activities 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PFU 
Plaque-forming unit 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SDTM 
Study Data Tabulation Model 
SoA 
Schedule of Assessments 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
TFL 
Table, figure, listing 
USP 
United States Pharmacopeia 
UTI 
Uninary tract infection 
WBC 
White blood cell 
WHO 
World Health Organization 


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Statistical Analysis Plan 
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1 INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide a description of the statistical 
methods to be implemented for the analysis of data from the study with protocol number LBx- 
1001. The SAP will be finalized prior to database lock. Any deviations from the SAP after 
database lock will be documented in the final Clinical Study Report (CSR). 
 
2 STUDY OVERVIEW 
2.1 Study Objectives 
2.1.1 Primary Objective  
To evaluate the safety, tolerability, and pharmacokinetics (PK) of LBP-EC01 in patients ≥18yrs 
of age with lower urinary tract colonization caused by E. coli. 
2.1.2 Secondary Objectives  
To evaluate the pharmacodynamics (PD) of LBP-EC01. 
2.1.3 Exploratory Objectives  
To explore the influence of LBP-EC01 on the urinary tract microbiota. 
2.2 Study Design 
2.2.1 Overview  
This is a Phase 1b FIH study to assess safety, tolerability, PK, and PD of LBP-EC01 in patients 
who have significant colonization of the urinary tract by E. coli. It is a multi-center randomized, 
double-blind study in patients with indwelling urinary catheters, or who require intermittent 
urinary catheterization and/or patients with asymptomatic bacteriuria caused by E. coli. 
No formal hypothesis will be tested. Thirty-six patients will be randomized 2:1 to receive either 
LBP-EC01 (at approximately 1.5×107 - 1.5×1013 PFU/vial - the maximum feasible dose based on 
manufacturing process) or inert placebo given twice daily for 7 days by intravesical catheter. A 
new catheter will be installed at the beginning of the study and will be replaced at the discretion 
of the investigator. The study will be conducted in 7 sites in the US. Study duration for patients 
will be up to 56 days, which includes up to 21 days for screening, 7 days of Investigational 
Medicinal Product (IMP) treatment, a Day 14 assessment (14 days after first dose),                    
a Day 28 assessment (28 days after first dose), and an End of Study (EOS) assessment (35 
days after first dose). Patients will be in the clinic or hospital the evening prior to receiving the 
first dose of treatment and throughout the 7 days of treatment. 
The study will consist of a Screening Period of up to 21 days. On Day -1 patients will either be 
hospitalized or in a facility that can provide proper administration of study drug and then 
randomized to LBP-EC01 or placebo. The entire 7-day Treatment Period in which patients will 
receive 13 doses of IMP will be conducted with the patient in the clinic/hospital. In 
circumstances where the patient may not be able to be in clinic/hospital for the full 7 days of 
treatment, upon consultation between the treating physician and the study Medical Monitor, 
patients may be considered to be treated and monitored in clinic/hospital for Days 1-3 and then 
may be allowed to come back to the clinic/hospital for the PM dose on Day 3 and the remaining 
treatment from Days 4-7. The end of treatment (EOT) will be after the 13th dose on Day 7, after 
 
 


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Page 8 of 23 
 
 
 
which the patient may be released from the clinic/hospital. The patient will return on Day 14 (±3 
days) for the Day 14 Visit, and on Day 28 (±3 days) for the Day 28 Visit. AE data will be 
collected throughout the study, including Day 28 through Day 35. At Day 35, the patient will be 
contacted by telephone to assess any AEs or lab abnormalities since the Day 28 Visit. At the 
discretion of the investigator, the patient may be asked to return to the clinic/hospital for a Day 
35 Visit (±3 days). Day 35 is the end of study. Assessments will be conducted as described in 
Table 1 and Table 2 of the Protocol. 
Safety will be assessed throughout the study. Spleen evaluations will include ultrasound 
assessments for splenomegaly at Day -6 to -1, Day 3, and Day 7 and clinical examinations to 
assess for splenomegaly will be performed at all visits. In addition, attention will be focused on 
identifying any progression of a urinary colonization to an active infection, including the signs 
and symptoms of local vesicular reactions (e.g., bladder pain, hematuria). Symptoms of active 
infection will be solicited during daily observations throughout the 7 days of treatment and until 
the end of study. Symptoms of note in this population include dysuria, urinary frequency, urinary 
urgency, suprapubic discomfort and flank pain in addition to non-specific symptoms of urinary 
leakage, change in voiding habits, worsening muscle spasm, increasing autonomic dysreflexia, 
sweating, malaise, and fever or hypothermia. Urine microscopy and culture will be assessed 
frequently during the study (see Table 2 of the Protocol). 
2.2.2 Randomization and Blinding  
Study patients will be randomly assigned to LBP-EC01 or placebo treatment groups in a 2:1 
ratio using IVRS. 
This is a double-blind study. Blinding to study treatment allocation will be achieved through use 
of matching placebo solution and administration sets. Neither the patient, nor the Investigator, 
nor Medpace/Sponsor will be aware of the treatment allocation. Key pharmacy staff involved in 
the preparation of the IMP or placebo will need to be unblinded. 
In the event of an emergency, the treatment code for an individual patient will be readily 
available to the Investigator and Sponsor/Medpace through the IVRS. If unblinding is necessary 
for patient management (in the case of an SAE), the Investigator will be able to break the 
treatment code by contacting the IVRS. Treatment codes should not be broken except in 
emergency situations. If the Investigator wishes to know the identity of the IMP for any other 
reason, he or she should contact the Medical Monitor directly. The Investigator should document 
and provide an explanation for any premature unblinding (e.g., accidental unblinding, unblinding 
due to an SAE). 
As per Health Authority reporting requirements, the Sponsor/Medpace will break the treatment 
code for all unexpected SAEs (see Section 9.3 of the Protocol) that are considered by the 
Investigator to be related to IMP. 
Whenever disclosure of the identity of the IMP is necessary, adequate procedures will be in 
place to ensure integrity of the data. Any unblinding, at the investigating site end, will be 
documented in the study report with date, reason for identifying the drug and the name of all the 
person(s) who required unblinding. 
2.2.3 Study Drug  
LBP-EC01 is a clear to opalescent, colorless to slightly yellow, aqueous solution. LBP-EC01 is a 
mixture of 3 crPhages internally named as p0031-8, p00ex-2, p004k-5, which are derived from 
wild-type myroviridae phages that target E. coli. These phages have been engineered to contain 


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LBx-1001 
CONFIDENTIAL 
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an identical CRISPR-Cas3 construct and have been combined in equal amounts at 1×106 – 
1×1012 PFU/mL (equivalent to approximately 1.5×107 – 1.5×1013 PFU/vial). One vial of LBP- 
EC01 containing approximately 15 mL of solution will be sterilely mixed with 45 mL of Lactated 
Ringer’s solution (injection, USP) by the site pharmacy prior to each dose administered (details 
will be included in the pharmacy manual). LBP-EC01 and placebo solutions will be 
indistinguishable. 
LBP-EC01 will be administered by bladder instillation via a newly placed urinary catheter BID at 
the maximum feasible dose, based on the manufacturing process (approximately 1.5×107 – 
1.5×1013 PFU/vial), totaling approximately 60 mL of solution via sterile catheter tipped syringe 
(details will be included in the pharmacy manual). The urinary catheter will be clamped and the 
solution left in situ for a minimum of 30 minutes (to a maximum of 40 minutes) following 
instillation and then it will be placed on free drainage (duration of clamp should be documented). 
LBP-EC01 will be provided in a 20 mL vial containing approximately 15 mL of the crPhage 
cocktail. This vial will be brought to room temperature prior to mixing with 45 mL of Lactated 
Ringer’s solution (injection, USP) under sterile conditions and placed into a sterile syringe with a 
catheter tip. Handling and mixing of the vials making up LBP-EC01 will be done by the unblinded 
study pharmacist (details are provided in the pharmacy manual). Placebo solution           
Lactated Ringer’s solution (injection, USP) will be brought to room temperature and will also be 
prepared by the pharmacist under aseptic technique and placed into a sterile catheter tipped 
syringe. The unblinded pharmacist will use the IVRS system to determine the randomization 
allocation. 
The mixed blinded solutions will be provided to the investigator/nursing staff for administration. If 
not used immediately, the IMP combined with Lactated Ringer’s solution should be stored under 
refrigerated conditions and must be administered within 24 hours of preparation. Doses may be 
given at 8 AM within +/- a 2-hour window for the AM dose and 12 hours after the AM dose +/- a 
3-hour window for the PM dose. The clinical site staff should consult with the Medical Monitor 
about any missed dose outside the allowable dosing window. Typically, these missed doses 
should be given and documented following standard procedure. 
All patients will receive a total of 13 doses of drug product or placebo across 7 days of treatment 
(a single morning dose will be given on Day 7). All doses should be given using strict aseptic 
techniques and may be administered by clinic/hospital staff provided they have been given 
adequate training. Upon completion of the study, patients requiring subsequent catheterization 
should have their study catheter replaced. The catheter used in the study should be discarded 
per normal site policy. 
2.2.4 Sample Size Determination  
36 patients were randomized in a 2:1 ratio to LBP-EC01 or placebo. This is a FIH study and the 
sample size should be sufficient to establish early safety and PK at a single dose level. 
2.3 Study Endpoints 
2.3.1 
Primary Endpoints  
The primary endpoints involve summarizing the safety and tolerability of AEs and lab 
parameters, as well as the PK parameters of LBP-EC01. The PK parameters will be assessed 
as a combined set of all crPhages included in LBP-EC01 in both urine and blood. 


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Statistical Analysis Plan 
Version 1.0, 17Dec2020 
Page 10 of 23 
 
 
 
The blood PK parameters will include the following assessments of LBP-EC01: 
• 
Maximum concentration (Cmax) 
• 
Time to Cmax (Tmax) 
• 
Area under the concentration versus time curve (AUC) from time 0 to the last measurable 
concentration (AUC0-t) 
Other PK variables may be calculated as appropriate for the observed data. 
2.3.2 Secondary Endpoints  
The secondary endpoints involve summarizing PD parameters of LBP-EC01. These include: 
• 
Reduction in urinary E. coli burden at any of the following timepoints: Day 2, Day 3, Day 
5, Day 7 (EOT), Day 14, and Day 28 
• 
Time to 1 log reduction in urinary E. coli count 
• 
Recurrence of E. coli colonization or incidence of infection based on clinical signs and 
symptoms 
• 
Changes in IgA, IgE, IgG, and IgM levels 
2.3.3 Exploratory Endpoints  
The exploratory endpoints involve exploring the effects of LBP-EC01 on the urinary tract 
microbiota. These include: 
• 
Urine culture and sensitivity (persistent, recurrent E. coli, new colonizing new infections 
will be documented) 
• 
Evaluation of bacterial biomarkers (e.g., phage sensitivity/resistance, bacterial antibiotic 
resistance, bacterial metagenomic analysis) 
2.3.4 Exploratory Analyses  
Exploratory analyses will include: 
• 
Differences between indwelling and intermittent urinary catheterization populations will 
be compared 
• 
Any persisting microbiological isolates will be fully explored with bacteriophage host 
range, antibiotic resistance patterns and genetic sequencing of isolates 
 
3 STATISTICAL METHODOLOGY 
3.1 General Considerations 
3.1.1 Definition of Baseline   
Baseline is defined as the last measurement prior to the first dose of study drug unless 
otherwise specified. 


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Page 11 of 23 
 
 
 
3.1.2 End of Treatment Definition  
The EOT is defined as the last date the patient received study drug, which is scheduled at Day 
7. 
3.1.3 End of Study Definition  
A patient is considered to have completed the study if he or she has completed all portions of 
the study including the last visit or the last scheduled procedure shown in the SoA (Table 1 of 
the Protocol). 
The EOS is defined as the last date that patient safety data is collected (i.e., Day 35). Once 
patients have completed Day 28, they may resume their regular medications and have any new 
intermittent catheters re-established as directed by their physician. 
3.1.4 Summary Statistics  
Categorical data will generally be summarized with counts and percentages of patients. The 
denominator used for the percentage calculation will be clearly defined. Continuous data will 
generally be summarized with descriptive statistics including n (number of non-missing values), 
mean, median, standard deviation, minimum, and maximum. Geometric mean (GM), and GM 
CV% will also be provided for PK parameters. The value of zero will be excluded from the 
calculation of GM and GM CV%. 
3.1.5 Hypothesis Testing  
This is a Phase 1b study and primary outcomes are evaluation of safety, tolerability and PK. No 
formal hypothesis will be tested. 
3.1.6 Handling of Dropouts and Missing Data  
Generally, missing data will be noted but not be imputed unless otherwise specified. 
3.2 Analysis Populations 
3.2.1 Safety Population  
The Safety Population is defined as all randomized patients who receive at least one dose of 
study drug. All safety data will be analyzed using the Safety Population. 
3.2.2 Intent-to-Treat (ITT) Population  
The ITT Population is also defined as all randomized patients who receive at least one dose of 
study drug, thus the same as the Safety Population. The ITT Population will be the primary 
population for analysis of all secondary and exploratory endpoints except for those PD-related. 
3.2.3 Evaluable Population  
The Evaluable Population is defined as all patients in the ITT Population who completed the 
study and who have been dosed according to protocol for the first 4 days of treatment and who 
have not been subject to a suspension of treatment or who have not missed more than one 
dose of study drug during the remainder of treatment (i.e., Days 5-7). Patients who show 
disease progression to active infection will be discontinued from treatment and treated for their 
symptoms and will be followed for safety. These patients will be included in the Evaluable 
Population as long as they have been dosed according to protocol for the first 4 days of 


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treatment. The Evaluable Population will be a secondary population for analysis of the non-PD 
secondary and exploratory endpoints. 
A list of patients excluded from the Evaluable Population will be finalized prior to unblinding the 
randomized treatment assignments. 
3.2.4 PK Population  
The PK Population is defined as all patients who receive at least one dose of LBP-EC01 and 
have at least one measurable post-dose concentration of LBP-EC01. The PK Population will be 
the population for all PK analysis. 
3.2.5 PD Population  
The PD Population is defined as all randomized patients who met enrollment criteria, who 
receive at least one dose of study drug, have a baseline PK assessment, and have a baseline 
E. coli measurement at or above 1x103 Colony-Forming Unit (CFU)/mL. The PD Population will 
be the primary population for analysis of all PD-related secondary and exploratory endpoints. 
3.2.6 Subgroup Analyses  
Subgroup analyses of these Analysis populations may also be performed. Such subgroups 
include, but are not limited to: 
• 
Patients with indwelling catheterizations and patients with intermittent catheterizations 
• 
Patients with E. coli sensitive to LBP-EC01 and patients with E. coli insensitive to LBP- 
EC01 
3.3 Subject Data and Study Conduct 
3.3.1 Subject Disposition  
Counts and percentages of patients who were screened (signed informed consent), 
discontinued early during screening (screen failures), and randomized will be summarized in 
total based on all screened patients. 
Counts and percentages of patients who were randomized, discontinued early from the study, 
and completed the study will be summarized by treatment and in total based on all randomized 
patients. Reasons for early discontinuation will also be summarized. 
The disposition data, including screen failure reasons, will also be listed. 
3.3.2 Protocol Deviations  
Counts and percentages of patients with protocol deviations by deviation category will be 
summarized by treatment and in total based on all randomized patients and listed. 
3.3.2.1 
Eligibility Criteria  
Eligibility criteria (inclusion/exclusion) will be listed based on randomized patients. 
3.3.3 Analysis Populations  
Counts and percentages of patients in each analysis population will be summarized by 
treatment and in total based on all randomized patients. Reasons for exclusion from each 
analysis population may also be summarized. Data will be listed including randomization data. 


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3.3.4 Demographic and Baseline Characteristics  
The following demographic and baseline characteristics will be summarized: 
• 
Age (years) at enrollment 
• 
Sex 
• 
Childbearing potential 
• 
Race 
• 
Ethnicity 
• 
Height (cm) 
• 
Weight (kg) 
• 
Body mass index (BMI) (kg/m2) 
• 
Frequency and timing (within 1 month of Screening, within 1 year of Screening) of prior 
UTI 
• 
Prior antibiotic use (within 30 days of Screening) 
• 
Catheter use at Screening (none, indwelling, intermittent, other) 
Demographic and baseline characteristics will be summarized with descriptive statistics or 
counts and percentages of patients as appropriate by treatment and in total for all randomized 
patients and each defined analysis population. Data will also be listed. 
3.3.5 Medical History  
Medical history will be coded to system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA) version 22.0. Counts and percentages of patients 
with medical history by system organ class and preferred term will be summarized by treatment 
and in total based on all randomized patients. Data will also be listed. 
3.3.6 Prior and Concomitant Medications  
Medications will be coded to anatomical therapeutic chemical (ATC) class and preferred term 
using the WHO Drug Dictionary version March 2019G B3. For summary purposes, medications 
will be considered prior medications if they stopped prior to the first dose of study drug and 
concomitant medications if they were taken at any time after the first dose of study drug (i.e., 
started prior to the first dose of study drug and were ongoing or started after the first dose of 
study drug). 
If a medication has incomplete start or stop dates, dates will be imputed to determine whether a 
medication should be considered prior and/or concomitant. If a medication start date is 
incomplete, the first day of the month will be imputed for missing day and January will be 
imputed for missing month. If a medication stop date is incomplete, the last day of the month will 
be imputed for missing day and December will be imputed for missing month. Incomplete start 
and stop dates will be listed as collected without imputation. 
Counts and percentages of patients taking prior and concomitant medications by ATC class and 
preferred term will be summarized by treatment and in total based on the Safety Population. 
Data will also be listed. 
3.3.7 Catheterization  
Catheter use from screening through the End of Study will be logged. All catheter data will be 
listed for the Safey Population. 


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3.3.8 Study Drug Administration and Exposure   
Days of exposure to study drug will be calculated as date of last dose of study drug – date of 
first dose of study drug + 1. Days of exposure to study drug and number of doses received will 
be summarized by treatment based on the Safety Population with descriptive statistics and with 
counts and percentages of patients. Study administration data will be listed. 
3.4 Pharmacokinetic Assessment 
Of note, systemic absorption of LBP-EC01 may not occur due to the local route of administration 
and consequently, may result in little to no quantifiable LBP-EC01 concentrations in                
the blood for a subject’s PK profile. 
3.4.1 Sample Collections for Pharmacokinetic Analysis  
Blood and urine samples for PK will be collected at the times specified in Schedule of Blood and 
Urine Sampling of the Protocol (Table 2). 
Pre-dosing PK samples for urine and blood will be collected after catheterization (if there is no 
existing catheter), up to 30 minutes prior to dosing. Post-dosing PK samples will be taken within 
60 minutes after the catheter is released and re-clamped for 20 minutes to take additional urine 
and blood samples. 6 hour timepoint (±1 hour) will be collected after 6 hours following the AM 
dose 
Of note, urine PK data will not include volumes since a 20 mL aliquot is taken rather than the 
whole void urine volume. Patients are allowed to urinate freely outside of the specified 
collections. 
3.4.2 Handling Missing or Below the Lower Limit of Quantification Data  
Blood and urine PK data will follow the same rules for handling of missing or below limit of 
quantification (BLQ) data. 
For PK concentration data, if the actual sampling time is missing, but a valid concentration value 
has been measured, the concentration value will be flagged and the scheduled time point may 
be used for the calculation of PK parameters. 
In cases of missing pre-dose for the first dose of each treatment period, the missing 
components may be assumed as zero. For the other cases, the missing data will not be 
imputed. 
For semi-log plots, zero and BLQ values will be imputed as “0.1” for graphical purposes. 
For the individual concentration and PK parameter calculation of each treatment period, the 
following rules will be applied: 
• 
If one or more BLQ values occur before the first measurable concentration, they will be 
assigned a value of zero. 
• 
If BLQ values occur between measurable concentrations in a profile, the BLQ should be 
omitted (set to missing). 
• 
If BLQ values occur after the last measurable concentration in a profile, the BLQ should 
be omitted (set to missing). 


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For the concentration summary and mean concentration plot preparation of each treatment 
period, the following rules will be applied: 
• 
Mean concentration at any individual time point or defined time interval will only be 
calculated if at least half of the patients have valid values (i.e., quantifiable and not 
missing) at this time point or defined time interval for each treatment period 
• 
In cases where a mean value is not calculated due to the above criterion not being met, 
the value will be set to missing 
• 
BLQ values will be set to zero. 
3.4.3 Pharmacokinetic Concentration   
LBP-EC01 concentrations will be determined in both blood and urine by using a plaque forming 
assay and expressed in units of plaque forming units (PFU)/mL. 
Actual sampling times that are outside the sampling time windows may be excluded from 
concentration summary and mean concentration plotting but will still be used in the calculations 
of PK parameters and individual concentration plotting. 
Blood 
Individual blood concentrations of LBP-EC01 will be summarized by treatment at each nominal 
time point for the PK Population descriptively. Individual blood concentrations will also be listed 
for the PK Population. 
Individual blood concentration will be plotted by treatment against actual sampling time points 
relative to dosing time. Mean (±SD) concentration will be plotted on a linear and semi 
logarithmic scale against nominal time points by treatment, when available. 
Urine 
Individual urine concentrations of LBP-EC01 will be summarized by treatment at each nominal 
time point for the PK Population descriptively. Individual urine concentrations will also be listed 
for the PK Population. 
Individual urine concentration will be plotted by treatment against actual sampling time points 
relative to dosing time. Mean (±SD) concentration will be plotted against nominal time points by 
treatment, when available. 
3.4.4 Pharmacokinetic Parameters   
The following blood and urine PK parameters of LBP-EC01 will be determined using 
non-compartmental methods as appropriate: 


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Blood and Urine PK Parameters: 
 
Parameters 
Description 
Cmax,Dose 1 
Maximum concentration; determined directly from the concentration time 
profile; if the maximum concentration occurs at more than one time point, 
Cmax is defined as the first maximum value 
Tmax,Dose 1 
Time to Cmax of the first dose; determined directly from the concentration- 
time profile 
AUC0-t 
Area under the concentration vs time curve (AUC) from predose (time 0) 
to the last quantifiable concentration (Clast) for Dose 1 
Ctrough,max 
Minimum measured concentration from Day 1 (only including predose #2) 
through Day 7 
Cmax,all 
Max post-dose concentration determined from Day 1 through Day 7 
AICtrough 
Accumulation index using Ctrough (predose Day 7 / Ctrough,max) 
The actual collection times will be used for the calculation of PK parameters. The Linear-Log 
Trapezoidal method (equivalent to the Linear Up/Log Down option in WinNonlin) will be used in 
the computation of all AUC values. 
Additional PK parameters may be determined as appropriate. 
The blood and urine PK parameters will be listed and summarized by treatment using 
descriptive statistics for the PK Population. 
3.5 Pharmacodynamic Assessment 
The secondary endpoints concern the pharmacodynamics of LBP-EC01. These will be 
summarized by treatment based on the PD Population. 
E. coli assessments will be made at the timepoints specified in the SoA of the protocol. 
Incidence of the following endpoints will also be summarized with counts and percentages of 
patients at Day 1 (Baseline), Day 2, Day 3, Day 5, Day 7 (EOT), Day 14 and Day 28: 
• 
Reduction in urinary E. coli burden at timepoint from Baseline 
• 
Biological elimination of E. coli at timepoint after Baseline. Biological elimination is 
defined as measurement below 1x103 CFU/mL 
The following E. coli parameters will be derived based on all available post-Baseline data and 
summarized and listed: 
• 
Time to 1 log reduction in urinary E. coli from Baseline 
• 
Biological elimination at any timepoint. 
• 
Incidence and time to recurrence of E. coli colonization. Recurrence is defined as past 
biological elimination followed by increase above the patient’s baseline CFU/mL. 
• 
Incidence of infection based on clinical signs and symptoms defined as an adverse 
event marked as a UTI symptom and followed by antibiotic use. 


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E. coli parameters will be summarized first for the total CFU/mL in a patient (sum of CFU/mL for 
all E. coli strains) but may also be summarized by strain specific E. coli colonization (individual 
strain CFU/mL per patient). 
All E. coli assessment data will be listed. 
3.6 Exploratory Assessment 
The exploratory endpoints explore the influence of LBP-EC01 on the urinary tract microbiota. 
These will be summarized based by treatment on the ITT Population and Evaluable Population. 
3.6.1 Urine Culture and Sensitivity  
Urine culture and sensitivity assessments will be made at the timepoints specified in the SoA of 
the protocol. Incidence and summaries of CFU/mL levels of all non-E. coli bacteria isolated will 
be presented at each scheduled visit. Overall summaries of all bacteria (including E. coli) may 
also be presented. All data will be listed. 
3.6.2 Bacterial Biomarkers  
Bacterial biomarkers will be collected at the timepoints specified in the SoA of the protocol. 
3.6.2.1 
Phage Sensitivity/Resistance  
Phage sensitivity and resistance by E. coli isolates will be collected at the timepoints specified in 
the SoA of the protocol. Incidence of the following will be summarized by isolate for the cocktail 
and each individual phage: 
• 
Isolates that yield ennumerable plaques (PFU/mL) 
• 
Isolates that yield ennumerable plaques (PFU/mL) or that demonstrate “lysis from 
without” 
• 
Insensitive isolates (no ennumerable plaques or no “lysis from without”) 
All phage sensitivity and resistance will be listed by patient for each E. coli isolate, including E. 
coli sensitivity to the cocktail and to each individual phage. 
3.6.2.2 
Bacterial Antibiotic Resistance  
Patient incidence of antibiotic resistance will be summarized across all E. coli isolates. All 
patient antibiotic resistance data will be listed, including MIC values and interpretations. 
3.6.2.3 
Bacterial Metagenomics Analysis  
The metagenomics data will be available following the study’s completion, and this analysis will 
be described in a separate analysis plan. 
3.6.3 
Microbiological Isolates  
Any persisting microbiological isolates identified will have all related data listed, including 
bacteriophage host range and antibiotic resistance patterns. Genetic sequencing of isolates 
will be included in the separate metagenomics analysis. 
3.7 Safety Assessment 
Safety data will be summarized by actual treatment received (and in total for selected analyses) 
based on the Safety Population. 


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3.7.1 
Adverse Events (AEs)  
AEs will be captured from the date of informed consent through study completion. All AEs will 
be coded to system organ class and preferred term using MedDRA version 22.0. 
Treatment-emergent adverse events (TEAEs) are defined as AEs that start after the first dose of 
study drug. 
Adverse events of special interest include signs and symptoms of a urinary tract infection (UTI) 
and local vesicular reaction. 
An overview of AEs will be provided including counts and percentages of patients (and event 
counts) with the following: 
• 
Any TEAEs (overall and by maximum severity) 
• 
Any study drug related TEAEs (overall and by maximum severity) 
• 
Any TEAEs of special interest (overall and by maximum severity) 
• 
Any serious AEs (SAEs) 
• 
Any treatment-emergent serious AEs (TESEAEs) 
• 
Any TEAEs leading to discontinuation of study drug 
• 
Any TEAEs leading to discontinuation of study 
• 
Any AEs leading to death 
Counts and percentages of patients (and event counts) will also be presented by system organ 
class and preferred term for each of the categories in the overview. 
All AE data will be listed. Listings will be presented specifically for SAEs and TEAEs leading to 
discontinuation of study drug, as well as TEAEs of special interest. 
3.7.2 Clinical Laboratory Tests  
Blood and urine samples for clinical laboratory tests will be collected at timepoints specified in 
the SoA of the protocol and processed by a central laboratory. A list of laboratory tests to be 
performed is included in Appendix A. 
3.7.2.1 
Hematology, Chemistry, Coagulation, Lipids, and Urinalysis  
Values and changes from baseline will be presented at each scheduled visit and baseline by 
laboratory test. The incidence of abnormalities (as defined by normal ranges) prior to the first 
dose of study drug and after the first dose of study drug will be summarized with counts and 
percentages of patients. Data will be listed. 
3.7.2.2 
Pregnancy  
Pregnancy data will be listed. 
3.7.3 Immunoglobulins  
Total levels of each immunoglobulin (IgA, IgE, IgG, and IgM) from Baseline will be measured at 
the timepoints specified in the SoA and Schedule of Blood and Urine Sampling of the Protocol. 


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Values and changes from baseline will be summarized at each scheduled visit and baseline by 
immunoglobulin. The incidence of positive detection (defined as above normal range; see below) 
will also be summarized with counts and percentages of patients at the same timepoints. 
 
Immunoglobulin Normal Range 
Positive Detection 
IgA 
70 – 400 mg/dL (0.7 – 4.0 g/L) 
> 400 mg/dL (> 4.0 g/L) 
IgE 
<= 100 IU/mL 
> 100 IU/mL 
IgG 
700 – 1600 mg/dL (7.0 – 16.0 g/L) 
> 1600 mg/dL (> 16.0 g/L) 
IgM 
40 – 230 mg/dL (0.4 – 2.3 g/L) 
> 230 mg/dL (> 2.3 g/L) 
All immunoglobulin data will be listed. 
3.7.4 Vital Signs  
Vital signs will be measured at timepoints specified in the SoA of the protocol. Vital signs will 
consist of blood pressure, heart rate, respiratory rate, and oral body temperature. Values and 
changes from baseline will be presented at each scheduled visit and baseline by vital sign. Data 
will be listed. 
3.7.5 Body Weight, Height, and Body Mass Index  
Body weight, height, and BMI will be measured/calculated at the timepoints indicated in the SoA 
of the protocol and the values at Screening will be used to calculate BMI. Data will be listed. 
3.7.6 Electrocardiograms  
Triplicate 12-lead ECG recordings (i.e., 3 useful ECGs without artifacts) will be obtained within 
approximately 2-5 minutes at each specified timepoint indicated in the SoA of the protocol. The 
average of the 3 readings will be used to determine ECG intervals and inclusion in summaries. 
The following ECG parameters will be recorded: 
• 
Heart rate 
• 
PR interval 
• 
QRS interval 
• 
QT interval 
• 
QTc using Fridericia’s interval 
• 
RR interval 
Values and changes from baseline will be presented at each scheduled visit and baseline by 
ECG parameter. 
All ECGs will be evaluated by a qualified Investigator for the presence of abnormalities. All ECG 
data will be listed. 
3.7.7 Physical Examinations  
Targeted physical examinations will be performed at the specified timepoints in the SoA of the 
protocol (or as clinically indicated). These will be a limited, symptom-directed physical 
examination only. Conditions noted prior to study drug dosing will be recorded as medical 
history and those recorded after study drug dosing will be recorded as AEs. 


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3.7.8 Spleen Examinations  
Spleen evaluations will include ultrasound assessments for splenomegaly at the specified 
timepoints in the SoA of the protocol and clinical examinations to assess for splenomegaly will 
be performed at all visits. A clinical examination may also be performed at a clinic visit on Day 35 
at the discretion of the study investigator if there are abnormal or clinically significant findings at 
Day 28. 
Splenomegaly is defined as a doubling of the largest dimension of the spleen from baseline or 
hematologic evidence of splenic sequestration defined as a hematologic abnormality (i.e., 
anemia, leukopenia, thrombocytopenia) of Grade 3 or greater based on DAIDS criteria. 
Counts and percentages of patients with a doubling of the largest dimension of the spleen from 
baseline will be presented. The largest diameter of the spleen value and changes from baseline 
will be summarized at each scheduled visit and baseline. All spleen evaluation data will be 
listed. 
 
4 DATA SAFETY MONITORING COMMITTEE 
A Data Safety Monitoring Committee (DSMC) will monitor the safety of patients over the course 
of the study. The DSMC will meet once or more during the patient enrollment period to examine 
the unblinded accumulated safety data. Patients, investigators, site staff and in general all 
personnel directly involved in the conduct of the study will remain blinded to the patients’ 
treatment assignment until the completion of the study. 
Details related to the DSMC responsibilities, authorities, and procedures will be documented in 
a DSMC charter which will be finalized prior the first patient being enrolled in the study. 
 
5 ANALYSIS TIMING 
5.1 Interim Analysis 
No interim analysis is planned. 
5.2 Pre-Final Analysis 
After the database is locked and the Evaluable Population status has been determined for all 
patients, the randomized treatment assignments will be unblinded and the pre-final analysis will 
be generated. Pre-final TFLs will be provided for review. 
5.3 Final Analysis 
After all comments on the pre-final analysis have been resolved and the study database is 
declared final, the final analysis will be generated. Final TFLs will be provided, as well as SDTM 
data and ADaM data along with associated files, if requested. Associated files may include: 
annotated case report forms (CRFs), SDTM specifications, SDTM programs, ADaM 
specifications, ADaM programs, TFL programs, and CDISC Define packages for both SDTM 
and ADaM data. 


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6 ADDITIONAL ANALYSES ON THE IMPACT OF COVID-19 
6.1 General Consideration 
The COVID-19 pandemic may impact the conduct of the study from different aspects including 
quarantines, site closures, travel limitations, interruptions to the supply chain for the 
investigational product, or other considerations if site personnel or trial patients become infected 
with COVID-19. 
Start date and end date of COVID-19 impact will be determined to assess the impact of the 
COVID-19 pandemic to the study. COVID-19 impact date is defined as the date at which the site 
and/or overall study was impacted by COVID-19, resulting in changes to how assessments where 
conducted at the site and/or for the study overall. 
6.2 Analysis Populations 
6.2.1    COVID-19 Population  
The COVID-19 Population may be added and defined as all randomized patients who have 
been seriously impacted by COVID-19 and have missed critical endpoint assessments. 
Endpoint/safety analyses may be performed separately by including/excluding these patients. 
6.3 Subject Disposition 
Summaries of patients who discontinued early from the study due to COVID-19 impact will be 
added to the disposition summaries. 
In addition, subject disposition may be summarized and stratified by COVID-19 status (prior 
to/post to COVID-19 impact date). 
6.4 Protocol Deviations 
Protocol  deviations  related  to  COVID-19  will  be  categorized  and  summarized  and  listed 
separately. 
6.5 Concomitant Medications 
Counts and percentages of patients taking prior and concomitant medications that are used to 
treat COVID-19 by ATC class and preferred term may be summarized by treatment and in total 
based on the Safety Population. 
6.6 Safety Assessment 
6.6.1    Adverse Events (AEs)  
An overview of AEs may be provided including counts and percentages of patients (and event 
counts) and stratified by COVID-19 status (AEs start prior to/post to COVID-19 impact date). 
Counts and percentages of patients (and event counts) will be presented by system organ class 
and preferred term for COVID-19 related AEs. 


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7 CHANGES FROM PROTOCOL-SPECIFIED STATISTICAL ANALYSES 
No changes from the protocol-specified analyses have been made except for those detailed 
above to assess any impact of COVID-19. 
 
8 PROGRAMMING SPECIFICATIONS 
The creation of analysis datasets and all analyses will be performed using SAS® (version 9.4 or 
higher). PK parameters will be calculated via SAS® and confirmed with the results of Phoenix 
WinNonlin™ (version 8.1 or higher). 
All available data will be presented in patient data listings which will be sorted by patient and 
visit date as applicable. Detailed Programming Specifications will be provided in a separate 
document. 


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APPENDIX A: LABORATORY TESTS 
Samples for the following laboratory tests will be sent to the central laboratory for analysis: 
 
• Hematology: Hemoglobin, hematocrit, platelet count, red blood cell (RBC) count, mean 
corpuscular volume, absolute reticulocyte count, total and differential leucocyte (WBC) absolute 
count (neutrophils, eosinophils, lymphocytes, monocytes and basophils). 
• Serum chemistry: Albumin, alkaline phosphatase, alanine aminotransferase, aspartate 
aminotransferase, C-reactive protein, calcium, chloride, creatinine phosphokinase, gamma- 
glutamyl transferase, glucose, phosphate, potassium, creatinine, sodium, total bilirubin, total 
protein, troponin, urea, IL-6 and an immunoglobulin panel (IgA, IgE, IgG and IgM). 
• Coagulation: activated partial thromboplastin time, prothrombin time 
• Lipids: High density lipoprotein-cholesterol, low density lipoprotein cholesterol, triglycerides, 
total cholesterol. 
• Urinalysis and Microscopy A pre-dose catheter urine specimen will be collected for dipstick 
analysis of protein, blood, white blood cells, glucose, and pH and microscopy.