Conditions: COVID-19
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 295
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, placebo-controlled study of camostat mesilate in ambulatory patients with confirmed COVID-19 with at least one risk factor for severe illness.

Detailed description:
Participants will be randomized in a 2:1 ratio of camostat:placebo. Approximately 300 participants are planned to be enrolled (200 participants to camostat mesilate and 100 participants to placebo). Participants will be treated with camostat mesilate 200 mg or placebo drug orally 4 times a day for 14 days, and receive local standard of care (SOC) in addition to study drug. Participants will be followed until Day 28. Participants will be seen in the clinic for assessments, blood draws, and mid-turbinate nasal samples on Screening/Day 1, Day 7, Day 15 and early termination.

Arms:
arm 1: Participants will receive camostat mesilate for 14 days in addition to standard of care treatment. arm 2: Participants will receive placebo for 14 days in addition to standard of care treatment.

Interventions: intervention 1: Camostat Mesilate intervention 2: Placebo
Intervention descriptions: intervention 1: Camostat mesilate administered as oral 100 mg round tablets. Study dose: Two 100 mg tablets (200 mg total) taken orally 4 times daily for 14 days. intervention 2: Placebo administered as oral round tablets. Study dose: Two placebo tablets taken orally 4 times daily for 14 days.

Protocol document:
Prot_000.pdf: 
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1 
CLINICAL STUDY PROTOCOL 
 
 
 
Sagent Pharmaceuticals, Inc. 
Protocol Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the 
Efficacy of Camostat Mesilate for the Treatment of Confirmed COVID-19 in Outpatients 
(CAMostat Efficacy vs. pLacebo for Outpatient Treatment of COVID-19 [CAMELOT]) 
Protocol Number: NI03-CV19-001 
 
IND Number: 
149504 
Name of Investigational Product: 
Camostat mesilate 
Phase of Development: 
2 
Indication: 
COVID-19 
Sponsor: 
Sagent Pharmaceuticals 
1901 N. Roselle Road, Suite 450 
Schaumburg, IL 60195 
 
Protocol Version:  
4.0 
 
Protocol Date: 
07-October-2020 
 
-CONFIDENTIAL AND PROPRIETARY- 
This document and its contents are the property of and confidential to Sagent Pharmaceuticals. It is intended 
solely for the recipient and must not be disclosed to any other party with prior written permission from Sagent 
Pharmaceuticals. Any unauthorized copying or use of this document is prohibited. 
 
 
 




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INVESTIGATOR SIGNATURE PAGE 
Protocol Title: 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of 
the Efficacy of Camostat Mesilate for the Treatment of Confirmed 
COVID-19 in Outpatients 
Protocol Number: 
NI03-CV19-001 
Confidentiality and Current Good Clinical Practice (GCP)/E6(R2)/Compliance 
Statement 
• 
I, the undersigned, have reviewed this protocol, including appendices, and I will conduct the 
study as described in compliance with this protocol (and any amendments), GCP, and relevant 
International Council for Harmonisation (ICH) guidelines. 
• 
I am thoroughly familiar with the appropriate use of the study drug, as described in this protocol 
and any other information provided by Sagent Pharmaceuticals including, but not limited to, the 
current investigator’s brochure. 
• 
Once the protocol has been approved by the institutional review board (IRB), I will not modify 
this protocol without obtaining prior approval of Sagent Pharmaceuticals and of the IRB. I will 
submit the protocol amendments and/or any informed consent form modifications to Sagent 
Pharmaceuticals and the IRB, and approval will be obtained before any amendments are 
implemented. 
• 
I ensure that all persons or party assisting me with the study are adequately qualified and 
informed about the Sagent Pharmaceuticals study drug and of their delegated study-related duties 
and functions as described in the protocol. 
• 
I ensure that source documents and trial records that include all pertinent observations on each of 
the site’s trial subjects will be attributable, legible, contemporaneous, original, accurate, and 
complete.  
• 
I understand that all information obtained during the conduct of the study with regard to the 
subjects’ state of health will be regarded as confidential. No subjects’ names will be disclosed. 
All subjects will be identified by assigned numbers on all case report forms, laboratory samples, 
or source documents forwarded to the Sponsor. Clinical information may be reviewed by the 
Sponsor or its agents or regulatory agencies. Agreement must be obtained from the subject before 
disclosure of subject information to a third party. 
• 
Information developed in this clinical study may be disclosed by Sagent Pharmaceuticals to other 
clinical investigators, regulatory agencies, or other health authority or government agencies as 
required. 
<Name> 
<Title> 
Investigator Signature 
Date (DD-MM-YYYY) 
Institution 


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2 
SYNOPSIS 
Title of Study: 
CAMostat Efficacy vs. pLacebo for Outpatient Treatment of COVID-
19 (CAMELOT Trial)  
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the 
Efficacy of Camostat Mesilate for Treatment of COVID-19 in Outpatients  
Protocol Number: 
NI03-CV19-001 
Investigators/Study Sites: 
Up to ~25 sites planned in United States 
Subjects 
Approximately 300 outpatients (200 in the camostat mesilate group and 100 
in the placebo group) 
Indication 
Treatment of non-hospitalized adult subjects diagnosed with coronavirus 
disease 2019 (COVID-19) infection 
Phase of Development: 
Phase 2 
Objectives: 
The primary objective of this study is: 
• 
To evaluate the clinical efficacy of camostat mesilate in 
ambulatory subjects with confirmed COVID-19 
The secondary objective of this study is: 
• 
Evaluate the safety profile of camostat mesilate in ambulatory 
subjects with confirmed COVID-19 
Study Endpoints: 
Primary endpoint:  
• 
Proportion of subjects requiring COVID-19 related hospitalization 
(including emergency room visit) or who die due to any cause within 
28 days of randomization 
Secondary Endpoints: 
Survival/Mortality 
• 
The overall survival rate (the proportion of randomized subjects who 
survive up to Day 15 and Day 28) 
Clinical Improvement 
• 
Time to resolution of fever from randomization up to Day 28 
• 
Time to hospitalization or death following randomization up to Day 28 
• 
Proportion of subjects with no viral shedding (yes/no) using reverse 
transcriptase-polymerase chain reaction (RT-PCR) at Day 7, Day 15, 
and at Early Termination. 
Safety/Tolerability 
• 
Incidence of adverse events (AEs) and serious adverse events (SAEs) 
of any grade from randomization up to Day 28 
• 
Cumulative incidence of grade 3 and 4 AEs from randomization up to 
Day 28 
• 
Incidence of discontinuation from study due to an AE/SAE 
(discontinued subjects will be followed up to Day 28) 


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• 
Change from baseline in clinical laboratory parameters 
• 
Change from baseline in vital signs (heart rate, blood pressure, 
peripheral capillary oxygen saturation [SpO2]) 
Study Design: 
This is a randomized, double-blind, placebo-controlled study of camostat 
mesilate in ambulatory outpatients with confirmed COVID-19 with at least 
one risk factor for severe illness. Subjects will be randomized in a 2:1 ratio 
of camostat mesilate:placebo. Approximately 300 subjects are planned to be 
enrolled (200 subjects to camostat mesilate and 100 subjects to placebo). 
Subjects will be treated with camostat mesilate 200 mg orally 4 times a day 
for 14 days, and receive local standard of care (SOC) in addition to study 
drug. Subjects in the control arm will receive 2 placebo tablets 4 times a 
day for 14 days, as well as local SOC. Subjects will be followed until Day 
28. Subjects will complete a symptom eDiary daily from Day 1 (first dose 
of study drug) through Day 15. Subjects will be seen in the clinic for 
assessments on Day 1, Day 7 and Day 15. Mid-turbinate nasal samples will 
be obtained at Screening, Day 7 and Day 15. Instructions for obtaining 
proper nasal samples will be provided. Subjects who withdraw from the 
study prior to completion of the 14-day treatment period will be asked to 
return for an Early Termination visit for blood draws and a mid-turbinate 
swab collection. 
Selection of Subjects: 
Inclusion Criteria:  
1. 
Adults willing and able to provide informed consent before 
performing study procedures  
2. Adults aged ≥ 18 years at time of informed consent  
3. Subjects must have written notification of laboratory confirmed 
COVID-19 infection performed prior to screening, at a local 
laboratory by RT-PCR or other commercial or public health assay 
in any specimen. Subjects should be randomized within 72 hours 
of receiving this notification (note that all subjects will also 
undergo RT-PCR testing of mid-turbinate samples at a central 
laboratory on a specimen collected during the baseline visit (Day 
1), but entry to the study is based on previously completed local 
testing for clinical purposes). 
4. Have a mild or moderate form of COVID-19 defined as a SpO2 
> 94% at screening 
5. Subjects must have at least 1 of the following risk factors for 
severe illness: 
a. 
Aged 65 years or older 
b. Hypertension 
c. 
Diabetes mellitus  
d. Chronic lung disease including asthma, chronic 
obstructive pulmonary disease (COPD), and interstitial 
lung disease (e.g., idiopathic pulmonary fibrosis) 
e. 
Chronic cardiac conditions, including coronary artery 
disease (CAD), heart failure, congenital heart disease, 
cardiomyopathy 
f. 
Severe obesity (body mass index [BMI] ≥ 40 kg/m2) 


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g. Chronic liver disease, including cirrhosis 
6. Must agree not to enroll in another study of an investigational 
agent or take any other drug that has been granted Emergency Use 
Authorization prior to completion of Day 28 
7. If women of childbearing potential (WOCBP) or men whose 
sexual partners are WOCBP, must be able and willing to use at 
least 1 highly effective method of contraception during the study 
and for 90 days after receiving the last dose of study drug. A 
female subject is considered to be a WOCBP following menarche 
and until she is in a postmenopausal state for 12 months or 
otherwise permanently sterile (for which acceptable methods 
include hysterectomy, bilateral salpingectomy, and bilateral 
oophorectomy). Contraceptive use by men or women should be 
consistent with local regulations regarding the methods of 
contraception for those participating in clinical studies. 
Exclusion Criteria:  
1. Physician makes a decision that trial involvement is not in subjects' 
best interest, or any condition that does not allow the protocol to be 
followed safely 
2. Known severe liver disease (e.g., Child Pugh score > 12, AST > 5 
times upper limit) 
3. SaO2/SpO2 ≤ 94% in room air condition, or the arterial oxygen 
partial pressure (PaO2)/fractional inspired oxygen (FiO2) ratio 
< 300 mmHg 
4. Known allergic reaction to camostat mesilate or one of its 
excipients 
5. Known severe renal impairment  or receiving dialysis 
6. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose 
examination 
7. Receipt of any experimental treatment for COVID-19, including 
agents with actual or possible direct acting antiviral activity, 
including, but not limited to, hydroxychloroquine, 
lopinavir/ritonavir, tocilizumab, ivermectin, or remdesivir within 
the 30 days prior to the time of the screening evaluation. No 
off-label use of a drug for COVID-19 is allowed. 
8. History of human immunodeficiency virus infection on highly 
active antiretroviral therapy (HAART) 
Planned Sample Size: 
Assuming that the proportions of outpatients who are hospitalized for 
COVID-19 related disease or die due to any reason within 28 days of 
randomization are 30% and 15% for placebo and camostat mesilate groups, 
respectively, based on the two-sided Fisher's Exact Test, at the target 
significance level of 5%, 275 outpatients (183 in camostat mesilate group 
and 92 in placebo group) are needed to achieve 80% power. Thus, 
approximately 300 outpatients (200 in the camostat mesilate group and 100 
in the placebo group) will be randomized to account for subject drop-out. 
Investigational Therapy: 
Camostat mesilate as 100 mg tablets, taken orally. Study dose: two 100 mg 
tablets (200 mg total) taken 4 times a day for 14 days.  


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Reference Therapy: 
Placebo tablet identical in appearance to camostat mesilate. Study dose: two 
placebo tablets taken 4 times a day for 14 days. 
Treatment Duration: 
Subjects will be treated for 14 days and followed until Day 28  
Efficacy Assessments: 
Hospitalization (Primary Efficacy Endpoint) is defined as status changing 
from ambulatory care to COVID-19 related hospitalization or death due to 
any cause on or prior to Day 28. Presenting to the emergency room is 
considered hospitalization. 
Resolution of fever is defined as the time (in hours) from initiation of study 
treatment (active or placebo) until normalization of fever (≤ 37.2 °C oral) 
and sustained for at least 72 hours; this will only be assessed in subjects 
who experienced a fever within 24 hours of enrollment. 
Overall survival rate defined as the proportion of randomized subjects who 
survive up to Day 15 and Day 28. 
Proportion of subjects with no viral shedding (yes/no) using RT-PCR at 
Day 7 and Day 15. 
Safety Assessments: 
• Incidence of AEs: overall, treatment-related, grade 3 or higher in 
severity, serious, fatal, and those resulting in treatment discontinuation 
• Changes from baseline in clinical laboratory values judged as clinically 
significant will be listed as AEs. Laboratory values of interest will be 
monitored, including platelet counts, liver function tests (aspartate 
aminotransferase [AST], alanine aminotransferase [ALT], alkaline 
phosphatase [ALP], gamma-glutamyl transferase [GGT]), and 
potassium levels.  
• Changes from baseline of vital signs (i.e., blood pressure, SpO2, and 
heart rate) 
Statistical Methods and 
Planned Analyses: 
The detailed methodology for summary and statistical analysis of the data 
collected in this trial will be documented in a Statistical Analysis Plan 
(SAP).  
In general, all efficacy endpoints and major safety endpoints will be 
summarized using descriptive statistics (e.g., proportions for categorical 
data, means and standard deviations for continuous data, median for time-
to-event data). The primary and key secondary efficacy endpoints will be 
analyzed using appropriate statistical models.  
Analysis Populations: 
The Intent-to-Treat (ITT) population will include all subjects who are 
randomized. Subjects will be analyzed according to their study treatment 
assignment, not according to the treatment actually received. The ITT 
population will be used for evaluating primary and secondary efficacy 
endpoints and subject characteristics. 
The Per-Protocol (PP) population will include all subjects in the ITT 
population who complete the 28-day study and have no major protocol 
deviations. The PP population will be used for primary and secondary 
efficacy endpoints. 


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The Safety population will consist of subjects who receive at least 1 dose of 
study medication (camostat mesilate or placebo). The Safety population 
will be used for all summaries of safety and tolerability data. 
Efficacy Analyses 
The primary endpoint (the proportion of subjects requiring COVID-19 
related hospitalization or who died due to any cause within 28 days of 
randomization) will be analyzed using the Fisher exact test in ITT and PP 
populations. The primary endpoint will also be analyzed using the Mantel-
Haenszel (MH) test, and the 95% Clopper-Pearson confidence interval (CI) 
will be reported. In addition, the continuity-corrected Newcombe CI for the 
proportional difference between treatment groups will be reported. The 
logistic regression model with treatment group, sex, race, duration of 
symptoms prior to enrollment, age groups (<65 versus ≥ 65 years) and other 
risk factors as covariates may be used to investigate the potential influences 
of demographic and baseline characteristics. The odds ratios and their 95% 
CIs will be estimated. 
The overall survival rate up to Day 28 will be analyzed in ITT and PP 
populations similar to the primary analysis.  
Similar methods, as per the primary endpoint, will be used to analyze the 
proportion of subjects with no viral shedding at Day 7 and Day 15. Time to 
resolution of fever from randomization up to Day 28 and time to 
hospitalization or death following randomization up to Day 28 will be 
summarized with Kaplan-Meier curves. A log-rank test will be used to 
analyze these time-to-event endpoints. The median event time and their 
corresponding 2-sided 95% CIs will be provided for each treatment arm. 
The Cox proportional hazard model with treatment group, sex, race, 
duration of symptoms, age groups (< 65 versus ≥ 65 years) and other risk 
factors as covariates may be used to investigate the potential influences of 
demographic and baseline characteristics. The hazard ratios and their 95% 
CIs will be estimated. Additionally, the change from baseline in clinical 
symptoms and viral shedding will be summarized using shift tables.  
A sensitivity analysis for efficacy endpoints will be performed for central 
laboratory confirmed COVID-19 subjects in the ITT population. 
Safety Analyses 
All AEs will be coded using the current MedDRA dictionary. Treatment-
emergent AEs (TEAEs), SAEs, grade 3 or 4 TEAEs, and TEAEs leading to 
study discontinuations will be summarized using discrete summaries by 
system organ class and preferred term for each treatment group. TEAEs 
will be summarized by severity and relationship separately.  
Laboratory data and vital signs will be summarized descriptively. 
Missing Data Handling  
Missing data handling methods will be described in the SAP. 


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3 
TABLE OF CONTENTS 
1 
CLINICAL STUDY PROTOCOL ....................................................................................1 
2 
SYNOPSIS ........................................................................................................................4 
3 
TABLE OF CONTENTS ..................................................................................................9 
3.1 
List of In-text Tables ..................................................................................................12 
3.2 
List of In-text Figures .................................................................................................13 
4 
LIST OF ABBREVIATIONS .........................................................................................14 
5 
INTRODUCTION ...........................................................................................................16 
5.1 
Background on COVID-19.........................................................................................16 
5.1.1 
Overview of COVID-19 Disease .......................................................................16 
5.2 
Background on Camostat Mesilate .............................................................................17 
5.2.1 
Nonclinical Studies ............................................................................................18 
5.2.2 
Clinical Studies ..................................................................................................19 
5.3 
Clinical Risks/Benefits of Camostat Mesilate ............................................................20 
5.4 
Study Rationale ..........................................................................................................22 
6 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................22 
6.1 
Study Objectives .........................................................................................................22 
6.1.1 
Primary Objective ..............................................................................................22 
6.1.2 
Secondary Objectives .........................................................................................22 
6.2 
Study Endpoints..........................................................................................................23 
6.2.1 
Primary Endpoint ...............................................................................................23 
6.2.2 
Secondary Endpoints ..........................................................................................23 
7 
INVESTIGATIONAL PLAN .........................................................................................23 
7.1 
Description of Overall Study Design and Plan...........................................................23 
7.2 
Discussion of Study Design and Dosing ....................................................................24 
7.3 
End of Study ...............................................................................................................24 
8 
SELECTION OF STUDY POPULATION .....................................................................25 
8.1 
Inclusion Criteria ........................................................................................................25 
8.2 
Exclusion Criteria .......................................................................................................26 
8.3 
COVID-19 RT-PCR Test at Central Laboratory ........................................................26 
8.4 
Rescreening ................................................................................................................26 
8.5 
Study Withdrawal, Removal, and Discontinuation of Subjects .................................26 
9 
TREATMENTS ...............................................................................................................28 
9.1 
Details of Study Treatments .......................................................................................28 


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9.2 
Dosage Schedule ........................................................................................................28 
9.3 
Measures to Minimize Bias: Study Treatment Assignment and Blinding .................28 
9.3.1 
Method of Study Treatment Assignment ...........................................................28 
9.3.2 
Blinding 29 
9.4 
Dosage Modification ..................................................................................................29 
9.5 
Treatment Accountability and Compliance ................................................................29 
9.6 
Prior and Concomitant Therapies/Interventions .........................................................30 
9.6.1 
Prior and Concomitant Medications ..................................................................30 
10 
STUDY PROCEDURES .................................................................................................30 
10.1 Study Visits ................................................................................................................33 
10.1.1 
Screening/Baseline and Day 1 Visit ...................................................................33 
10.1.2 
Onsite Visits on Day 7, Day 15, Unscheduled Visit, Early Termination Visits / 
Telephone Visits on Day 21, Day 28 .................................................................33 
10.1.3 
Daily Assessments and Procedures by Subject ..................................................34 
10.2 Informed Consent .......................................................................................................34 
10.3 Study Procedures ........................................................................................................34 
11 
EFFICACY ASSESSMENTS .........................................................................................34 
11.1 Subject eDiary ............................................................................................................35 
11.2 Hospitalization (Primary Efficacy Endpoint) .............................................................35 
11.3 Resolution of Fever (Secondary Efficacy Endpoint) ..................................................35 
11.4 Viral Shedding ............................................................................................................35 
12 
SAFETY ASSESSMENTS .............................................................................................36 
12.1 Medical History ..........................................................................................................36 
12.2 Vital Signs and Body Temperature – On-Site Visits..................................................36 
12.3 Laboratory Assessments .............................................................................................36 
12.4 Adverse Events ...........................................................................................................37 
12.4.1 
Adverse Events ..................................................................................................37 
12.4.2 
Serious Adverse Events .....................................................................................39 
12.4.3 
Serious Adverse Event Reporting ......................................................................40 
12.4.4 
Suspected Unexpected Serious Adverse Reactions ...........................................41 
12.4.5 
Pregnancy ...........................................................................................................41 
13 
STATISTICAL ANALYSIS ...........................................................................................42 
13.1 Determination of Sample Size ....................................................................................42 
13.2 Analysis Populations ..................................................................................................43 
13.3 Efficacy Analysis........................................................................................................43 


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13.3.1 
Analysis of Primary Efficacy Endpoint .............................................................43 
13.3.2 
Analysis of Secondary Efficacy Endpoints ........................................................43 
13.4 Safety Analysis ...........................................................................................................44 
13.5 Interim Analysis .........................................................................................................44 
14 
STUDY MANAGEMENT ..............................................................................................45 
14.1 Approval and Consent ................................................................................................45 
14.1.1 
Regulatory Guidelines ........................................................................................45 
14.1.2 
Institutional Review Board ................................................................................45 
14.1.3 
Informed Consent ...............................................................................................45 
14.2 Data Handling .............................................................................................................45 
14.3 Source Documents ......................................................................................................46 
14.4 Record Retention ........................................................................................................46 
14.5 Monitoring ..................................................................................................................46 
14.6 Quality Control and Quality Assurance .....................................................................47 
14.7 Protocol Amendment and Protocol Deviation ............................................................47 
14.7.1 
Protocol Amendment .........................................................................................47 
14.7.2 
Protocol Deviations ............................................................................................47 
14.8 Ethical Considerations ................................................................................................47 
14.9 Financing and Insurance .............................................................................................48 
14.10 Publication Policy/Disclosure of Data........................................................................48 
15 
REFERENCES ................................................................................................................49 
16 
APPENDICES .................................................................................................................51 
16.1 APPENDIX 1 - CONTRACEPTION GUIDELINES ................................................52 
16.2 APPENDIX 2 – GUIDELINES FOR NASAL TURBINATE SWAB COLLECTION 
PROCEDURE ............................................................................................................53 
 


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3.1 
List of In-text Tables 
Table 1. Schedule of Assessments ........................................................................................31 
Table 2. Laboratory Assessments..........................................................................................37 
Table 3. Classification of Adverse Events by Intensity ........................................................38 
Table 4. Classification of Adverse Events by Relationship to Study Drug ..........................39 
 
 
 


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3.2 
List of In-text Figures 
Figure 1. Study Schematic ......................................................................................................24 


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4 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACE2 
angiotensin converting enzyme II 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ARDS 
acute respiratory distress syndrome 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CAD 
coronary artery disease 
CBC 
complete blood count 
CDC 
Centers for Disease Control 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cmax 
maximum serum concentration 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FiO2 
fractional inspired oxygen 
FSH 
follicle stimulating hormone 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
HAART 
highly active antiretroviral therapy 
HIPAA 
Health Insurance Portability Accountability Act 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IRB 
institutional review board 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOA 
mechanism of action 
NSAID 
nonsteroidal anti-inflammatory drug 
PaO2 
arterial oxygen partial pressure 
PCR 
polymerase chain reaction 
PI 
principal investigator 
PK 
pharmacokinetic 
PP 
per protocol 
QID 
4 times daily 


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Abbreviation 
Definition 
RT-PCR 
reverse transcriptase-polymerase chain reaction 
SAE 
serious adverse event 
SaO2 
oxygen saturation 
SAP 
statistical analysis plan 
SARS 
severe acute respiratory syndrome 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SpO2 
peripheral capillary oxygen saturation 
SOC 
standard of care 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TID 
3 times daily 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
US 
United States 
 
 


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5 
INTRODUCTION 
On 31 December 2019, the World Health Organization (WHO) was informed of a cluster of 
cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province of China. The 
severe acute respiratory syndrome – coronavirus-2 (SARS-CoV-2) was identified as the 
causative virus of the disease currently referred to as coronavirus disease 2019 (COVID-19) by 
Chinese authorities on 07 January 2020 (WHO, 2020). 
The rapid spread of COVID-19 presents an increasing threat to human health globally. The virus 
has subsequently spread throughout the world and was declared a pandemic by the WHO on 
11 March 2020. Among patients infected with SARS CoV-2 are cases progressing to severe 
disease symptoms including acute respiratory distress syndrome (ARDS), pneumonia, 
pulmonary edema, and organ failure. These pathologies are driven by local and systemic 
inflammatory events (Cascella et al, 2020). As of the writing of this protocol, the number of 
cases of COVID-19 exceeds 7 million and the resulting number of deaths worldwide continue to 
climb. 
5.1 
Background on COVID-19 
5.1.1 Overview of COVID-19 Disease 
Gandhi et al, 2020 discusses the presentation, management, prevention, and control of patients 
with mild or moderate COVID-19. SARS-CoV-2 is a novel betacoronavirus related to bat 
coronaviruses that was thought to originate from a seafood market in Wuhan, China, where live 
animals were sold. There is much still unknown about COVID-19, but data from China indicated 
that 81% of people who become infected have a mild or moderate form of the disease (with no or 
mild pneumonia), 14% have a severe disease, and 5% have a critical form of the disease.   
COVID-19 is spread from person to person through an infected person’s respiratory droplets 
from coughs, sneezes, or even just speaking. It may also be contracted from a contaminated 
surface when a person touches the surface and then touches their face, transferring the virus to a 
mucosal membrane. Droplets are able to travel for approximately 2 meters from the infected 
person and then fall. Standing at least 1.8 meters (6 feet) apart from others will reduce the 
likelihood of transmission. The virus may live on certain surfaces (cardboard, plastic, and 
stainless steel) for days; therefore, sterilizing surfaces with antibacterial cleaners will also reduce 
transmission. Personal protective equipment for health care workers is essential to prevent the 
spread of COVID-19. Testing and diagnosis of patients is important so that those who are 
infected can self-isolate to prevent the spread to others (Gandhi et al, 2020).  
An infected person may or may not display symptoms. Presymptomatic people may infect others 
for 1 to 3 days before displaying symptoms, and the virus is detectable during this time. The time 
from exposure to the time of displaying symptoms can be from 2 to 14 days, with 97.5% of 
people displaying symptoms within 11.5 days after infection. Patients usually have high viral 
levels in nasopharyngeal samples just before or soon after symptoms start. Viral levels will 


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continue to be detectable but will fall over the next week. Patients with severe COVID-19 illness 
may continue viral shedding longer, but how long viral shedding continues is not known at this 
time (Gandhi et al, 2020).  
COVID-19 is diagnosed by using reverse transcriptase-polymerase chain reaction (RT-PCR) 
from a nasopharyngeal swab sample. The sensitivity of this assay is high but not 100%; therefore 
repeat testing is important if the person continues to exhibit symptoms, has knowingly been 
exposed, or lives in an area where there are a high number of COVID-19 cases (Gandhi et al, 
2020).  
The most common symptoms of a mild to moderate COVID-19 infection are fever, cough, sore 
throat, malaise, and myalgia. Anorexia, nausea, diarrhea, anosmia, and ageusia are often 
reported. Dyspnea may occur (usually 5 to 8 days after symptom onset) and is suggestive of 
more severe disease, often a precursor to hospitalization. Dyspnea can occur in patients with 
moderate disease but the oxygen saturation is usually at least 94% on room air (Gandhi et al, 
2020). Importantly, clinical deterioration typically does not occur until more than 5 to 7 days 
following symptom onset, suggesting there is a window of opportunity for antiviral therapy early 
in the infection prior to the subsequent onset of severe systemic inflammation. 
Certain comorbid conditions render a person more susceptible to contracting COVID-19 and 
contribute to worsening of the disease to a more severe version. These conditions include: age 
≥ 65 years, cardiovascular disease, chronic lung disease, hypertension, diabetes, obesity, and 
diseases that weaken the immune system (Gandhi et al, 2020).  
Patients with mild or moderate COVID-19 are usually instructed to recover at home, where they 
can be isolated, observed, monitored, and receive supportive care. However, some patient’s 
conditions may deteriorate, especially those with comorbid conditions, which most often 
happens a week after onset of symptoms. These patients should be monitored closely. Patients 
with mild to moderate disease are able to monitor their own oxygen saturation levels if they are 
given a pulse oximeter (Gandhi et al, 2020).  
Other than supportive care, remdesivir is the only treatment at this time that has proven efficacy 
from a Phase 3 randomized, placebo-controlled clinical trial, but, importantly, this was only 
administered to hospitalized patients with severe COVID-19. A preliminary report of early 
unblinding of the results showed a statistically significant, shortened time to recovery in the 
group that received remdesivir (11 days) compared with those who received placebo (15 days). 
Kaplan-Meier estimates of mortality by 14 days were 7.1% for remdesivir and 11.9% for 
placebo, which was not a statistically significant difference (Beigel JH et al, 2020). There 
currently is no vaccine that provides immunity against COVID-19. 
5.2 
Background on Camostat Mesilate 
Camostat mesilate was approved for human use in Japan with the indication of “remission of 
acute symptoms of chronic pancreatitis” on 31 January 1985. Subsequent post-marketing 
surveillance revealed no significant problems with the efficacy or safety.  


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A paper by Hoffman et al published 16 April 2020 provided key insights into the first step of 
SARS-CoV-2 infection; namely, how the virus is able to get into human cells. Scientists found 
that the cellular protein protease TMPRSS2 is necessary for SARS-CoV-2 to enter lung cells, 
which is similar to SARS-CoV-1 (Hoffmann et al, 2020). Entry of SARS-CoV-2 into the cell 
depends on the cell entry receptor protein angiotensin converting enzyme II (ACE2) and the 
serine protease TMPRSS2. A protein on the viral surface called a spike attaches to the ACE2 
receptor on the human cell and then TMPRSS2 cleaves the spike protein, allowing the virus to 
enter the cell and replicate inside of it. In this study, viral entry was inhibited by camostat 
mesilate, which is a known TMPRSS2 inhibitor. Therefore, camostat mesilate is a biologically 
plausible candidate to prevent the infection of SARS-CoV-2 or stop the progression of 
COVID-19 once a person is infected.  
Camostat mesilate is already licensed in Japan and South Korea to treat chronic pancreatitis and 
reflux esophagitis. A clinical trial using camostat mesilate for chronic pancreatitis is currently 
ongoing in the United States (US) and is sponsored by Nichi-Iko Pharmaceutical Co., Ltd, 
Sagent’s parent company. Because camostat mesilate is a known inhibitor of TMPRSS2 and has 
already been approved in Japan and South Korea and is currently under study for approval to 
treat pancreatitis in the United States, it is a potential candidate for the treatment of COVID-19, 
one that could be available much sooner than a drug that would still have to go through all 
development phases.  
A Danish clinical trial using camostat mesilate is currently ongoing in subjects diagnosed with 
COVID-19. Subjects in this trial will receive two 100 mg pills of camostat mesilate or placebo 
3 times daily (TID) for 5 days; however, justification for this dosing is not publicly available. 
This study is designed to treat subjects in the United States with mild to moderate confirmed 
COVID-19 with a dosing regimen of 200 mg 4 times daily (QID) for 14 days. Dosing is based on 
the antiviral indication, as well as current data related to pharmacokinetics (PK) and safety. 
5.2.1 Nonclinical Studies 
Because camostat mesilate has been approved since 1985 in Japan, numerous nonclinical studies 
have been performed to evaluate its safety. Camostat mesilate has been studied in rats, mice, 
dogs, rabbits, hamster cells (hERG gene), various bacteria (Ames mutation test), and healthy 
humans. Nonclinical studies, including in-vitro and in-vivo pharmacology; PK including 
administration, distribution, metabolism, and excretion; safety pharmacology; toxicology and 
toxicokinetic evaluations; genotoxicity; tolerance studies; and reproduction and development 
studies have all been completed. Camostat mesilate’s effect on general symptoms, central 
nervous system, autonomic nervous system, cardiorespiratory system, reproduction, and urinary 
system as well as local irritation and antigenicity have all been evaluated. The test methods and 
results of these studies can be found in the current version of the Investigator’s Brochure (Sagent 
Pharmaceuticals, 2020). 


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5.2.2 Clinical Studies 
Camostat mesilate or Foipan®, has been approved in Japan since 1985 for the remission of acute 
symptoms of chronic pancreatitis and postoperative reflux esophagitis. Much of the results and 
data in this section are from clinical studies presented as part of the Japanese drug approval 
process. 
FOY-251 and GBA were found to be the primary metabolites of camostat mesilate when 
administered to normal, healthy subjects. FOY-251, the active metabolite, has a half-life in blood 
of approximately 75 minutes. Plasma kallikrein was suppressed for 2 to 4 hours following 
administration of camostat mesilate. 
Nine studies using camostat mesilate enrolling a total population of 216 subjects with acute, 
chronic, or postoperative pancreatitis were conducted, with the majority of subjects dosed at 
200 mg TID. The duration of dosing ranged from 2 weeks to more than 13 weeks. Few adverse 
events (AEs) were reported and no serious adverse events (SAEs) were documented from these 
studies. These studies did not have formal statistical tests, but did show a decrease in serum and 
urinary amylase levels throughout the treatment period (Kinami et al, 1980; Hirayama et al, 
1980a; Abe et al, 1980; Fujiwara et al, 1980; Hayawaka et al, 1980; Hirono, 1980; Horiguchi et 
al, 1980; Kubota and Meada, 1980; Tanaka and Tsuchiya, 1980). 
Two studies by Hirayama et al were conducted on subjects with pancreatitis (Hirayama et al, 
1980a, Hirayama et al, 1980b). In both of these studies, camostat mesilate was dosed at 200 mg 
TID. Both studies showed that camostat mesilate significantly reduced serum and urine amylase 
levels. Only 1 AE was reported in the camostat mesilate group compared with none in the 
placebo group.  
A PK and safety Phase 1/2 study (NI03-001) is currently being conducted in the United States 
with 2 phases (Ramsey et al, 2019). In the first phase, a single-dose of camostat mesilate at doses 
of 100 mg, 200 mg, and 300 mg were administered to 18 subjects with chronic pancreatitis. At 
all doses, camostat mesilate displayed markedly lower exposure (maximum serum concentration 
[Cmax] and area under the curve [AUC]) than the 2 metabolites. 4-GBA exposure appeared to be 2 
to 3 times higher than that of FOY-251. Camostat mesilate exposure did not increase as the doses of 
camostat mesilate increased, which may be explained by the markedly low exposure of camostat 
mesilate at all doses. FOY-251 exposure increased as the doses of camostat mesilate increased from 
100 mg to the 200 mg, but not from the 200 mg to the 300 mg. 4-GBA exposure (both Cmax and 
AUC) increased as the doses of camostat mesilate increased from 100 mg to the 200 mg, but only the 
AUC slightly increased from the 200 mg to the 300 mg. There were no deaths or SAEs, and 3 out of 
18 subjects reported 4 treatment-emergent adverse events (TEAEs). Two TEAEs were mild and 2 
were moderate in severity, with both of the mild TEAEs considered by the investigator to be possibly 
related to camostat mesilate. They occurred in the same subject and were an episode of dizziness and 
one episode of hot flashes after a single dose of 100 mg dose. Three of the TEAEs were reported 
following a dose of 100 mg camostat mesilate and the fourth TEAE was reported following a dose of 
300 mg camostat mesilate. Laboratory hematology and clinical chemistry data showed no trends 


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following camostat mesilate administration and there were no individual clinically significant 
abnormalities. Camostat mesilate had no significant effect on heart rate or blood pressure at any dose 
tested. The data from the first phase of this study suggested that the camostat mesilate is safe to 
administer to subjects with chronic pancreatitis as a single dose up to and including 300 mg. 
The second phase of Study NI03-001 is a randomized, double-blind, placebo-controlled study of 
3 doses of camostat mesilate (100 mg, 200 mg, and 300 mg) administered TID for 28 days for 
the treatment of chronic pancreatitis associated pain. This study is still ongoing and data remain 
blinded. Six SAEs (nephrolithiasis, diabetic ketoacidosis, abdominal pain [2 events], pancreatitis, 
pancreatitis acute) have been reported from 3 subjects. All events required hospitalization and 
each event resolved. All events were considered by the investigator as not related to study drug. 
All but 1 event occurred in the 28-day follow-up period after the last treatment.  
There are no expected concerns of safety for camostat mesilate. The safety profile of this class of 
drugs is favorable. Two studies done as far back as 1980 in subjects with pancreatitis reported 
that adverse effects were rare (< 3%), mostly mild, such as pruritus, increased thirst and appetite, 
and lightheadedness (Abe et al, 1980; Ishii et al, 1980). 
5.3 
Clinical Risks/Benefits of Camostat Mesilate 
Camostat mesilate has been available in Japan for 30 years where it is used for the treatment for 
relief of the acute symptoms of chronic pancreatitis and postoperative reflux esophagitis. The 
following is taken directly from the package insert for Foipan® (camostat mesilate) and is 
considered an important precaution:  
Foipan Tablet® 100 mg should not be administered to patients with severe chronic 
pancreatitis requiring dietary restrictions such as gastric aspiration, or abstaining 
from food or drink.  
In terms of the AEs seen in humans with chronic pancreatitis, in 3806 subjects 
subject to reporting of adverse reactions in the clinical trial at the approval stage 
and in the post-marketing surveillance study, 83 adverse reactions (including 
abnormal clinical laboratory test values) were observed in 69 of 3806 subjects 
(1.8%). The main adverse reactions were 15 cases of rash (0.4%), 9 cases of 
itching (pruritus; 0.2%), 10 cases of nausea (0.3%), 7 cases of abdominal 
discomfort (0.2%), and 6 cases of abdominal bloating (0.2%).  
From a postoperative reflux esophagitis investigation for FOIPAN performed up 
to the time of approval and in the Drug Use Investigation, 75 AEs were reported 
in 57 (1.3%) out of 4224 subjects. The major AEs were 12 (0.3%) cases of hepatic 
function abnormalities such as increased AST and ALT, 8 (0.2%) cases of 
diarrhea, and 5 (0.1%) cases of nausea.  
The Foipan® package insert also details the following significant adverse reactions:  
Symptoms of Shock and Anaphylaxis 


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Shock or anaphylactoid symptoms were reported from post-marketing 
surveillance. No specific antibody production has been reported with the drug in 
antigenicity studies in animals. However, in view of time course of symptom 
development (symptoms developed within 30 minutes after dosing in most cases), 
initial symptoms (dermatitis such as welts, itching sensation, and erythema, 
vertigo, feeling poorly, dull headache, sweaty, cold sweat, edema/swelling, 
dyspnea, and decrease in blood pressure), and subjects who had a past history of 
administration of this drug had experienced symptoms of hypersensitivity (e.g., 
urticaria, itching sensation and edema), these may have occurred due to 
anaphylactic reactions. 
Thrombocytopenia 
Serious decreased platelets have been reported from post-marketing surveillance. 
Symptoms included subcutaneous hemorrhage, oral hemorrhage, and epistaxis. The 
number of days until the onset was within 1 month after administration in most cases. 
Possible idiopathic thrombocytopenic purpura was suspected in some reported cases. 
In subacute and chronic toxicity studies of the drug, the decrease in platelets was not 
observed, and the mechanism of pathogenesis remains unknown. 
Hepatic Function Disorder, Jaundice 
Hepatic function disorder and jaundice (both with unknown frequency), accompanied 
by extreme elevation of aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), and gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) 
have been reported from post-marketing surveillance. Initial symptoms included 
general fatigue, nausea and vomiting, and jaundice. Most of disorders occurred 
without subjective symptoms and identified by medical examinations. The duration 
from the beginning of dosage to onset was 12 months in many cases. Some disorders 
occurred (identified) after the end of administration of the drug. In subacute and 
chronic toxicity studies of the drug, hepatic function abnormal was not observed, and 
the mechanism of pathogenesis remains unknown. 
Hyperkalemia 
Serious hyperkalemia has been reported from post-marketing surveillance, 
although the frequency is unknown due to spontaneous reporting. Most of the 
disorders occurred without subjective symptoms and were identified by medical 
examinations. Abnormal electrocardiograms or electrocardiogram abnormalities 
with clinical symptoms (general fatigue and sensation of heaviness in chest) were 
observed in some cases. The duration from the beginning of dosage to the onset 
was within 2 months in most cases. In subacute and chronic toxicity studies of the 
drug, abnormal changes in potassium levels were not observed, and the 
mechanism of pathogenesis remains unknown.  


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Overall, the evidence of clinical activity and the AE profile observed support a positive benefit-
to-risk ratio for subjects with COVID-19 who are treated with camostat mesilate. 
Details regarding known or anticipated benefits and risks, as well as reasonably anticipated AEs 
for camostat mesilate may be found in the IB (Sagent Pharmaceuticals, 2020). 
5.4 
Study Rationale 
The primary objective is to evaluate the efficacy of camostat mesilate in ambulatory subjects 
with confirmed COVID-19 infection. Based on the mechanism of action (MOA) of camostat in 
vitro to inhibit viral entry, subjects with nonsevere disease will be enrolled. Secondary objectives 
and endpoints include an assessment of efficacy of camostat mesilate evaluating the proportion 
of subjects requiring COVID-19 related hospitalization or death due to any cause, the overall 
survival rate, time to hospitalization, resolution of fever, and viral shedding. Safety objectives 
include assessments of AEs, vital signs, and laboratory parameters. 
This study will be executed during a worldwide outbreak of COVID-19, resulting in capacity 
issues at many medical facilities and concerns about the safety of healthcare providers caring for 
these sick patients. Consequently, this study is designed to minimize the burden on clinical sites, 
including minimizing the number of required assessments and interventions, while protecting the 
safety of participants and retaining scientific rigor. 
The investigational product and reference product (placebo) will be identical and 
indistinguishable to masked study personnel to limit bias in study assessments. Most 
interventions and assessments may be accomplished in conjunction with the schedule dictated by 
standard of care (SOC). 
6 
STUDY OBJECTIVES AND ENDPOINTS 
6.1 
Study Objectives 
6.1.1 Primary Objective 
The primary objective of this study is: 
• To evaluate the clinical efficacy of camostat mesilate in ambulatory subjects with 
confirmed COVID-19 
6.1.2 Secondary Objectives 
The secondary objective of this study is: 
• Evaluate the safety profile of camostat mesilate in ambulatory subjects with confirmed 
COVID-19 


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6.2 
Study Endpoints 
6.2.1 Primary Endpoint 
• Proportion of subjects requiring COVID-19 related hospitalization (including emergency 
room visit) or who die due to any cause within 28 days of randomization  
6.2.2 Secondary Endpoints 
Survival/Mortality 
• The overall survival rate (the proportion of randomized subjects who survive up to Day 15 
and Day 28) 
Clinical Improvement 
• Time to resolution of fever from randomization up to Day 28 
• Time to hospitalization or death following randomization up to Day 28 
• Proportion of subjects with no viral shedding (yes/no) using RT-PCR at Day 7, Day 15, and 
at Early Termination (for subjects withdrawn prior to completing the 14-day treatment 
period) 
 
Safety/Tolerability 
• Incidence of AEs and SAEs of any grade from randomization up to Day 28 
• Cumulative incidence of grade 3 and 4 AEs from randomization up to Day 28 
• Incidence of discontinuation from study due to an AE/SAE (discontinued subjects will be 
followed up until Day 28) 
• Change from baseline in clinical laboratory parameters 
• Change from baseline in vital signs (heart rate, blood pressure, peripheral capillary oxygen 
saturation [SpO2]) 
7 
INVESTIGATIONAL PLAN 
7.1 
Description of Overall Study Design and Plan 
This is a randomized, double-blind, placebo-controlled study of camostat mesilate in ambulatory 
outpatients with confirmed COVID-19 with at least one risk factor for severe illness. Subjects 
will be randomized in a 2:1 ratio of camostat mesilate:placebo. Approximately 300 subjects are 
planned to be enrolled (200 subjects to camostat mesilate and 100 subjects to placebo). Subjects 
will be treated with camostat mesilate 200 mg orally QID for 14 days and receive local SOC in 
addition to study drug. Subjects in the control arm will receive 2 placebo tablets orally QID for 
14 days, as well as local SOC. All subjects will be followed until Day 28. Subjects will complete 
a symptom eDiary daily from Day 1 (first dose of study drug) through Day 15. Subjects will be 
coming into the clinic for assessments on Day 1, Day 7 and Day 15. Mid-turbinate nasal samples 
will be obtained at Screening, Day 7 and Day 15. Instructions for obtaining proper nasal samples 
will be provided. Subjects who withdraw from the study prior to completion of the 14-day 


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treatment period will be asked to return for an Early Termination visit for blood draws and a 
mid-turbinate swab collection. On Day 28 (end of study), a study team member will record 
subject disposition.  
Figure 1 presents the study design. 
Figure 1. 
Study Schematic 
 
Abbreviations: COVID-19 = coronavirus disease 2019; SOC=standard of care. 
a 
The Screening/Baseline and Day 1 visit assessments can be done on the same day.  
 
7.2 
Discussion of Study Design and Dosing 
Camostat mesilate will be dosed at 200 mg (two 100 mg tablets) taken orally QID (800 mg/day 
total) for 14 days. This dosing was selected based on the requirement to have a constant presence 
of camostat mesilate in the circulation. It is well accepted that after 5 half-lives there is no, or 
negligible amounts, of drug left in the blood stream. The measurable half-life of camostat is in 
the region of 75 minutes and therefore 5 half-lives would be 6.25 hours. The approved dose of 
camostat in Japan is 200 mg TID but taking that dose in the treatment of COVID-19 would only 
provide coverage for approximately 18 to 19 hours and not the 24 hours coverage that is 
required. Therefore, a dose of 200 mg QID would theoretically offer 24 hours coverage at some 
level. In order to have 24 hours coverage of serine protease inhibition, a dose of 200 mg QID is 
appropriate and would not be expected to cause SAEs, especially if given for a limited period of 
14 days. More detailed information can be found in the camostat mesilate IB. 
The target population in this study is ambulatory subjects who have confirmed, mild to moderate 
COVID-19 who have at least 1 risk factor to develop complications. Subjects with mild to 
moderate disease were chosen because of the known method of action of camostat mesilate to 
block entry of the SARS-CoV-2 virus into the human cell. Camostat mesilate blocks TMPRSS2, 
a cellular protein protease that is necessary for SARS-CoV-2 to enter lung cells. It is 
hypothesized that a drug with this MOA will prevent the worsening and progression of COVID-
19 and prevent hospitalization.  
7.3 
End of Study  
A subject will have fulfilled the requirements for study completion if/when the subject has 
completed all study periods, including the end of study visit on Day 28, which is the last 


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scheduled visit as indicated in the Schedule of Assessments (Table 1). Subjects who terminate 
prior to completing the 14-day treatment period are asked to complete the Early Termination 
visit. 
8 
SELECTION OF STUDY POPULATION 
Section 7.1 provides information regarding number of subjects planned to be enrolled. 
8.1 
Inclusion Criteria 
Individuals must meet all of the following criteria to be included in the study: 
1. Adults willing and able to provide informed consent before performing study procedures 
2. Adults aged ≥ 18 years at time of informed consent 
3. Subjects must have written notification of laboratory confirmed COVID-19 infection 
performed prior to screening, at a local laboratory by RT-PCR or other commercial or 
public health assay in any specimen. Subjects should be randomized within 72 hours of 
receiving this notification. 
(NOTE: all subjects will also undergo RT-PCR testing of mid-turbinate samples at a 
central laboratory on a specimen collected during the Screening/Baseline and Day 1 visit, 
but entry to the study is based on previously completed local testing for clinical 
purposes). 
4. Have a mild or moderate form of COVID-19 defined as a SpO2 > 94% at screening 
5. Subjects must have at least 1 of the following risk factors for severe illness: 
a. Aged 65 years or older 
b. Hypertension 
c. Diabetes mellitus 
d. Chronic lung disease including asthma, chronic obstructive pulmonary disease 
(COPD), and interstitial lung disease (e.g., idiopathic pulmonary fibrosis) 
e. Chronic cardiac conditions, including coronary artery disease (CAD), heart 
failure, congenital heart disease, cardiomyopathy 
f. Severe obesity (body mass index [BMI] ≥ 40 kg/m2) 
g. Chronic liver disease, including cirrhosis 
6. Must agree not to enroll in another study of an investigational agent or take any other 
drug that has been granted Emergency Use Authorization prior to completion of Day 28 
7. If women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP, 
must be able and willing to use at least 1 highly effective method of contraception during 
the study and for 90 days after receiving the last dose of study drug. A female subject is 
considered to be a WOCBP following menarche and until she is in a postmenopausal state 
for 12 months or otherwise permanently sterile (for which acceptable methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). Contraceptive use by 
men or women should be consistent with local regulations regarding the methods of 


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contraception for those participating in clinical studies. Information on contraceptive use 
during the study is presented in Appendix 1. 
 
8.2 
Exclusion Criteria 
Individuals meeting any of the following criteria at screening or baseline are ineligible to 
participate in this study: 
1. Physician makes a decision that trial involvement is not in subjects' best interest, or any 
condition that does not allow the protocol to be followed safely 
2. Known severe liver disease (e.g., Child Pugh score > 12, AST > 5 times upper limit) 
3. Oxygen saturation (SaO2)/SpO2 ≤ 94% in room air condition, or the arterial oxygen partial 
pressure (PaO2)/fractional inspired oxygen (FiO2) ratio < 300 mmHg 
4. Known allergic reaction to camostat mesilate or one of its excipients 
5. Known severe renal impairment  or receiving dialysis 
6. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination 
7. Receipt of any experimental treatment for COVID-19, including agents with actual or 
possible direct acting antiviral activity, including, but not limited to, hydroxychloroquine, 
lopinavir/ritonavir, tocilizumab, ivermectin, or remdesivir within the 30 days prior to the 
time of the screening evaluation. No off-label use of a drug for COVID-19 is allowed. 
8. History of human immunodeficiency virus infection on highly active antiretroviral therapy 
(HAART). 
8.3 
COVID-19 RT-PCR Test at Central Laboratory 
Subjects who test positive for COVID-19 at the local laboratory will be enrolled if the subject 
meets all other entry criteria requirements. Nasal mid-turbinate swab samples are also to be 
obtained at the Screening/Baseline and Day 1 visit for central laboratory viral testing for 
COVID-19 as a baseline assessment and to test for viral shedding. If a subjects’ test performed at 
the local laboratory is positive for COVID-19 but the test performed at the central laboratory is 
negative, the subject will stay in the study and complete all study visits. The reason for this is 
that RT-PCR testing is not sensitive enough to be accurate 100% of the time. These subjects will 
provide safety data for camostat mesilate. Statistical analysis for efficacy endpoints may be 
adjusted for subjects who fall into this category. 
8.4 
Rescreening 
Individuals who sign the informed consent form (ICF) to participate in the study but who do not 
subsequently meet all the requirements as outlined in the inclusion and exclusion criteria and 
therefore do not enroll (screen failures) may not be rescreened. 
8.5 
Study Withdrawal, Removal, and Discontinuation of Subjects 
Subjects who discontinue study treatment or who are withdrawn from the study for any reason 
must have the date and the reason for study discontinuation recorded on the electronic case 


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report form (eCRF). Subjects who discontinue early from the study will be asked to return to the 
study site within 3 to 7 days of the last administration of study drug to complete assessments as 
indicated in the Schedule of Assessments (Table 1) (Early Termination Visit). 
In the event that a subject discontinues prematurely from the study because of a TEAE or SAE, 
the TEAE or SAE will be followed up until it resolves (returns to normal or baseline values) or 
stabilizes, or until it is judged by the investigator to no longer be clinically significant and 
thereafter until Day 28. 
Upon discontinuation every effort will be made to follow the subjects until Day 28 for all study 
outcomes unless there is death of the subject, hospitalization, withdrawal of consent by the 
subject or the subject is lost to follow up. 
Once a subject is withdrawn from the study, the subject may not reenter the study. 
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons 
including, but not limited to, the following: 
• AE and/or SAE 
• subject withdrawal of consent: at any time, a subject's participation in the study may be 
terminated at his/her request or on the basis of the investigator’s clinical judgment. The 
reason for subject withdrawal will be noted on the eCRF. 
• intercurrent illness: a condition, injury, or disease unrelated to the primary diagnosis that 
became apparent during treatment and necessitated the subject’s termination from the 
study 
• general or specific changes in the subject's condition that renders him/her ineligible for 
further treatment according to the inclusion/exclusion criteria 
• subject fails to adhere to the protocol requirements (e.g., drug noncompliance, failure to 
return for defined number of visits)  
• lost to follow-up: the subject stopped coming for visits, and study personnel were unable 
to contact the subject 
• pregnancy, as indicated in Section 12.4.5. 
Additionally, the Sponsor may stop the study at any time for safety, regulatory, legal, or other 
reasons aligned with good clinical practice (GCP). This study may be terminated at the discretion 
of the Sponsor or any regulatory agency. An investigator may elect to discontinue or stop the 
study at his or her study site for any reason, including safety or low enrollment. 


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9 
TREATMENTS 
9.1 
Details of Study Treatments 
Camostat mesilate, N, N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate 
methanesulfonate, a guanidinobenzoic acid derivative is an orally active protease inhibitor with 
potent inhibitory effects on trypsin, plasma kallikrein, plasmin, thrombin, C1r and C1 esterase but 
does not attenuate α-chymotrypsin, pepsin, or pancreatin. Camostat mesilate is presented as a 
film-coated tablet that is white to yellowish white in appearance. Each tablet contains 100 mg 
camostat mesilate.  
All drug supplies will be provided by the Sponsor. Camostat mesilate will be manufactured in 
tablet form by Nichi-Iko Pharmaceutical Co., Ltd. (Japan). Placebo tablets will be manufactured 
by Stason Pharmaceuticals, Inc. (Irvine CA).  
Active Treatment Arm: two 100 mg tablets of camostat mesilate taken orally QID (total daily 
dose of 800 mg) 
Placebo Arm: 2 matching placebo tablets taken orally QID  
Study drug will be supplied in high density polyethylene (HDPE) bottles, each bottle containing 
112 tablets of active drug or matching placebo. Each bottle will be labeled with a randomized 
bottle number, the name and address of the Sponsor, expiration date, and other information 
required by the US Food and Drug Administration (FDA) regulations.  
Study drug must be stored at controlled room temperature (15℃ to 30℃; 59℉ to 86℉) in a limited 
access, secured storage area until dispensed. The storage conditions should be monitored daily. 
9.2 
Dosage Schedule 
Study drug is administered as 2 tablets taken orally QID for 14 days. Study drug should ideally 
be taken with a meal or snack (breakfast, lunch, dinner), but it is not required. Tablets should be 
taken 3 times during the day and the fourth dose should be taken in the late evening (bedtime), 
with the dosing spaced approximately 5 hours apart. If a subject misses a dose, there should be 
no less than 2 hours between doses. 
9.3 
Measures to Minimize Bias: Study Treatment Assignment and Blinding 
9.3.1 Method of Study Treatment Assignment 
Subjects will be screened and enrolled in the order they present to the study centers and will be 
assigned the next available sequential subject number.   
According to the randomization schedule as indicated in the Schedule of Assessments (Table 1), the 
investigator or designee will obtain the randomization number from the IWRS software.  The IWRS 
software will use the blinded study arm linked to the randomization number to select a bottle number 
containing the correct study product (active or placebo) which is known to the IWRS to be in the 
possession of the site. The pharmacist or designee will provide the assigned bottle to the subject. No 


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study site personnel, subjects, Sponsor personnel, or Sponsor designees will be unblinded to 
treatment assignment throughout the duration of the study unless unblinding is required. If an 
investigator becomes unblinded to a given subject’s study treatment, that subject will be discontinued 
from the study unless there are ethical reasons for that subject not to be discontinued; approval from 
the Sponsor’s Medical Monitor must be obtained in such instances. 
In the event that emergency unblinding is required for a given subject because of AEs or concerns for 
the subject’s safety or wellbeing, the IWRS software will perform the unblinding. The IWRS 
software limits access to the emergency unblinding function to designated personnel and records the 
date, time, and person performing the unblinding. The unblinding and its cause will also be 
documented on the eCRF via automated entry by the IWRS. 
9.3.2 Blinding 
This is randomized, double-blind, placebo-controlled study. Subjects will be randomized in a 2:1 
ratio to camostat mesilate:placebo. None of the investigators, study site personnel, Sponsor, or 
subjects will know to which treatment the subjects were randomized. To maintain the blind, 
camostat mesilate and placebo tablets will be indistinguishable from one another and are 
identified in distribution to study sites and dispensing to study subjects by a randomized number 
assigned to each bottle known only to the packager (Stason) and the IWRS.  
The labeling, shipment, and receipt of the bottles at the study sites are all recorded in the IWRS 
software, contributing to the blinding of the assigned product after study randomization by 
preventing site personnel from knowing the exact contents of bottles assigned to study subjects. 
The assignment of the blinded randomization number to a subject and selection of a bottle 
number for the corresponding blind-labeled product bottle are controlled by the IWRS with no 
visibility of underlying study arm or product assignment to any party. 
9.4 
Dosage Modification 
No dose modifications will be allowed. 
9.5 
Treatment Accountability and Compliance 
The pharmacist or other designated individual will maintain electronic records of study drug 
delivered to the study site, the inventory at the study site, the distribution to and use by each 
subject, and the return of materials to the Sponsor for storage or disposal. These records should 
include dates, quantities, batch/serial numbers, expiration dates, in-clinic temperature logs, and 
unique code numbers assigned to the product and study subjects. 
At each visit after initiation of treatment, study site personnel will record compliance. Subjects 
will be instructed to bring their unused/partially used bottles back for inspection at each study 
visit. Subjects are to be reminded of the importance of compliance with an emphasis on taking 
their study drug on schedule and maintaining the prescribed interval between doses. 
Investigators will maintain records that adequately document that the subjects were provided 
with the correct study treatment allocation and reconcile the products received from the drug 


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dispensing center. Used or unused Investigational product will be returned to Stason 
Pharmaceuticals, Inc. (drug packager) if not destroyed at the clinical site. 
Medication containers must be returned at the end of treatment visit, as compliance will be 
assessed by tablet counts. Noncompliance is defined as taking less than 80% of study drug. 
Discontinuation for noncompliance is at the investigator’s discretion and is to be noted on the 
eCRF. 
9.6 
Prior and Concomitant Therapies/Interventions 
9.6.1 Prior and Concomitant Medications 
Restricted prior therapies are provided in Section 8.2 and are prohibited within 30 days before 
the time of screening. All medications taken by or administered to the subject within 30 days of 
screening will be recorded on the eCRF.  
After the baseline visit, medication to treat minor treatment-emergent illness is generally 
permitted; however, the following therapies are expressly prohibited throughout the study:  
• Any antiviral medications, including but not limited to, hydroxychloroquine, 
lopinavir/ritonavir, tocilizumab, ivermectin, or remdesivir 
• Experimental drug or off-label use of any drug. 
• Antipyretics are not allowed with the exception of acetaminophen.  
Any medication or therapy that is taken by or administered to the subject during the course of the 
study must be recorded on the eCRF. The entry must include the dose, regimen, route, indication, 
and dates of use. 
Cough expectorants (e.g., guaifenesin) and cough suppressants (e.g., dextromethorphan) are 
allowed during the study.  
Acetaminophen for fever is allowed 
Antihistamines are allowed for congestion 
10 STUDY PROCEDURES 
Table 1 outlines the timing of procedures and assessments to be performed throughout the study. 
Section 12.3 specifies laboratory assessment samples to be obtained. See Section 11 and 
Section 12 for additional details regarding efficacy assessments and safety assessments, 
respectively. 
 
 


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Table 1. 
Schedule of Assessments 
Study Day:  
Screening/Baseline 
& D1a,b 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D 
10 
D 
11 
D 
12 
D 
13 
D 
14 
D 
15 
D 
21 
 
End of 
Study 
D 28 
Early 
Termination 
Assessment / 
Procedure 
Unscheduled 
Visiti 
Informed consenta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Verify notification 
of local COVID-
19 positive test 
result occurred 
within 72 hours of 
screeninga 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteriaa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographicsa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical historya 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medicationsa, 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
 
 
Urine pregnancy 
test (as 
applicable)a 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinic visitd 
X 
 
 
 
 
 
X 
± 1 
day 
 
 
 
 
 
 
 
X 
± 1 
day 
 
± 1 
day 
X 
 
± 1 day 
X 
± 1 day 
Height / Weighta 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization, 
assign subject ID, 
dispense study 
drugb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete 
eDiaryc,e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Vital signs (heart 
rate, blood 
pressure, SpO2)a 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
 
X 
Adverse eventsa,g, 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
 
X 
Laboratory 
assessmentsa,g 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 


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Study Day:  
Screening/Baseline 
& D1a,b 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D 
10 
D 
11 
D 
12 
D 
13 
D 
14 
D 
15 
D 
21 
 
End of 
Study 
D 28 
Early 
Termination 
Assessment / 
Procedure 
Unscheduled 
Visiti 
Sample for viral 
shedding by RT-
PCR 
(mid-turbinate 
swab) a 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
Body temperature 
assessmenta,c,h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Abbreviations: AE = adverse event; ALT = alanine transaminase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; COVID-
19 = coronavirus disease 2019; CRP = C-reactive protein; D = day; GGT = gamma-glutamyl transferase; ID = identification; LDH = lactate dehydrogenase; MCV = mean corpuscular volume; RBC = 
red blood cell; RT-PCR = reverse transcriptase – polymerase chain reaction; SAE = serious adverse event; SpO2 = peripheral capillary oxygen saturation; WBC = white blood cell.  
a Denotes a baseline assessment. Baseline is defined as before the first dose of study drug. Baseline assessments should be performed before administration of study drug. Subjects are enrolled 
following completion of eligibility requirements and who are randomized in the IWR. Subjects who are screened to determine eligibility, but do not undergo any baseline assessments are not 
considered enrolled. All eligible subjects must have documented COVID-19 infection diagnosed at the local level. 
b Study Day 1= first dose of study drug. 
c Assessments to be done daily. 
d X = clinic visit, 
 = telephone visit. All post-baseline visits are ± 1 day in the event a visit occurs on a weekend. 
e Subjects will be given access and instructions to complete their eDiary on Day 1 using the web portal. Subjects will complete their eDiary daily from Day 1 through Day 15, Data to be collected in 
the eDiary daily will include 1) the number of study medication doses taken/missed and 2) the highest temperature recorded over the past 24 hour period. 
f All AEs must be recorded from the time of administration of the first dose of study drug until the subject has completed the end of study or early withdrawal. Any study procedure-related SAE that 
occurs after the study participant has signed the informed consent form and prior to administration of the first dose of study drug will be considered as Medical History.  The study will collect only 
Treatment Emergent Adverse Events (TEAE). 
g Laboratory assessments including hematology (CBC including hemoglobin, hematocrit, WBC with differential, RBC, MCV, and platelet count) and clinical chemistry (albumin, ALT, ALP, AST, 
BUN, GGT, creatinine, electrolytes [sodium, potassium, carbon dioxide, chloride], glucose, total bilirubin, direct bilirubin, LDH, CRP) will be collected. Laboratory tests will be performed at the 
central laboratory. 
h Absence of fever is defined as ≤ 37.2°C oral. 
i The indicated assessments may be done at the investigators discretion but are not required. 
 


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10.1 Study Visits 
10.1.1 Screening/Baseline and Day 1 Visit 
The following procedures and assessments will be done at the onsite Screening/Baseline and 
Day 1 visit: 
• Verify subject has written notification from a local laboratory confirming COVID-19 
infection within 72 hours of randomization (i.e., Day 1). In most instances, the 
Screening/Baseline visit will occur on the same date as Day 1. If needed, the 
Screening/Baseline may occur before Day 1 as long as randomization can be completed 
within the 72-hour window. 
• Obtain informed consent 
• Review of inclusion/exclusion criteria, including urine pregnancy test, if applicable 
• Assign a subject ID number (ID number = XXX site number followed by 001, 002, 003 
subject number)  
• Obtain mid-turbinate nasal swab sample to be sent to the central laboratory to test for a 
baseline assessment and to test for viral shedding of COVID-19 by RT-PCR 
• Draw blood for central laboratory testing 
• Record demographics, medical history (including current COVID-19 symptoms), and 
concomitant medications 
• Obtain vital signs (height, weight, heart rate, blood pressure, SpO2) 
• Measure oral body temperature 
• Perform randomization and dispensing of study drug 
• Provide subject with instructions for accessing eDiary portal for collection of daily 
information 
• Administer first dose of study drug after all assessments are completed 
• Record of any TEAEs 
10.1.2 Onsite Visits on Day 7, Day 15, Unscheduled Visit, Early Termination Visits / 
Telephone Visits on Day 21, Day 28 
The following procedures and assessments will be done on Day 7, Day 15, Day 21, Day 28, and 
early termination by telephone or at onsite visits: 
• Verify subject compliance for completing daily eDiary entrees by accessing the web 
portal for the subject’s eDiary 
• Review concomitant medications and record any TEAEs 
• Assess vital signs (heart rate, blood pressure, SpO2) during on-site visits only 
• Measure oral body temperature 
• Draw blood for central laboratory testing (Day 15, Unscheduled Visit and Early 
Termination) during on-site visits only 


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• Obtain mid-turbinate nasal swab sample for viral shedding test (Day 7, Day 15, and Early 
Termination Visits) for central laboratory during on-site visits only 
10.1.3 Daily Assessments and Procedures by Subject 
The following procedures and assessments will be done daily by the subjects themselves: 
• Complete the daily eDiary entries using the web portal 
• Measure oral body temperature 
• Administer study drug QID 
 
10.2 Informed Consent 
Before performing any study-related procedures, the investigator (or designee) will obtain 
informed consent from the subject. 
10.3 Study Procedures 
Assessments and their timing are to be performed as outlined in the Schedule of Assessments 
(Table 1). Section 12.3 specifies laboratory assessment samples to be obtained.  
Assessments and procedures scheduled at a visit where study drug is administered should be 
performed before administration of study drug unless otherwise indicated in the Schedule of 
Assessments (Table 1). 
Efficacy assessments are described in Section 11 and include recording of hospitalization or 
death for any cause (if not hospitalized), resolution of fever, overall survival rate, and viral 
shedding. 
Safety assessments are described in Section 12 and include concomitant medications, vital signs, 
laboratory assessments, pregnancy test, and AEs. 
The investigator may, at his/her discretion, arrange for a subject to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or are considered by the 
investigator to be possibly related to the use of study drug. The unscheduled visit page on the 
eCRF must be completed.  
Study discontinuation procedures are described in Section 8.5. 
Follow-up of AEs and SAEs leading to study discontinuation is discussed in Section 8.5. 
11 EFFICACY ASSESSMENTS 
The Schedule of Assessments (Table 1) outlines the efficacy assessments to be performed 
throughout the study and their timing. 


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11.1 Subject eDiary 
• 
Subjects will be provided access to an eDiary and completion instructions at the baseline visit 
(Day 1). Adequate time should be allocated on Day 1 to ensure that the subject understands 
how to access the eDiary portal to complete the daily eDiary and is willing and able to do so 
every day throughout the study. NOTE: The objectives and endpoints for this study relies on 
subject reported data collected via the eDiary. It is critical that the Investigator and subject 
understand that accurate, complete, and contemporaneous eDiary data is required to meet the 
study primary objective. It is particularly important to ensure that each subject completes the 
eDiary every day. The eDiary will have reminders for subjects to take the study drug and to 
complete the eDiary daily. The site will check the portal to be sure the subject is completing 
the eDiary daily. It is suggested that the sites should call the subject on Day 2 about eDiary 
completion if it is felt the subject will not remember.  
Subjects will be asked to record the following details in their eDiary: 
• 
Number of doses taken in the previous 24 hours 
• 
Oral body temperature at the time of diary completion 
• 
Highest oral temperature obtained in the last 24 hours (if additional temperatures were 
obtained the previous day that were not recorded in the diary the day before) 
Information from the eDiary will be used directly for analysis of the secondary endpoints. The 
Investigator or designee will be required to monitor the subject’s eDiary entries and contact the 
subject to discuss any omissions or inaccurate entries. 
11.2 Hospitalization (Primary Efficacy Endpoint) 
Hospitalization is defined as the subject’s status changing from ambulatory care to COVID-19 
related hospitalization or death due to any cause before Day 28. Presenting to the emergency 
room is considered hospitalization. 
11.3 Resolution of Fever (Secondary Efficacy Endpoint) 
Body temperature will be measured orally and recorded daily. Oral temperature will also be 
collected by study staff at an onsite study visit. Subjects will be given an oral temperature device 
and instructed in the proper use of the device at the Day 1 visit. Temperatures are to be recorded 
in the eDiary every day from Day 1 through Day 15. 
11.4 Viral Shedding 
Subjects will have mid-turbinate nasal samples taken using flocked swabs at onsite study visits 
according to Table 1. Investigators and study site staff will be trained on proper mid-turbinate 
nasal sample collection and handling of the swab after the sample has been collected. The proper 
handling of the swab after the nasal sample has been collected are described in the laboratory 
manual. The procedure for collecting mid-turbinate swabs is also located in Appendix 2. The 
same nostril should be used for sampling each time it is done, and the nostril (right or left) 


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should be recorded on the eCRF. Processing samples should be performed according to the 
central lab manual instructions. 
Swab samples will be tested for COVID-19 virus using RT-PCR. Results will be reported as 
either yes or no for shedding the virus.  
12 SAFETY ASSESSMENTS 
Safety assessments (vital signs, AEs, SAEs, clinical laboratory results [routine hematology and 
biochemistry] are to be performed at protocol-specified visits, as specified in the Schedule of 
Assessments (Table 1).  
12.1 Medical History 
Medical history will be recorded at screening. Investigators should document the occurrence, 
signs, and symptoms of the subject’s preexisting and currently ongoing conditions, including 
comorbid conditions, present at the time when informed consent is given and up to the time of 
first dosing (Day 1). Medical history will include alcohol consumption and smoking history, if 
applicable. 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 12.4. All 
changes not present at baseline or described in the past medical history and identified as 
clinically noteworthy must be recorded as AEs. 
Additionally, demographic data will be collected for all subjects and include age, sex, race, and 
ethnicity. 
Prior and concomitant medications are to be recorded on the eCRF. Refer to Section 9.6.1 for 
details.  
12.2 Vital Signs and Body Temperature – On-Site Visits 
Vital signs (heart rate, systolic and diastolic blood pressure measurements, and SpO2) and body 
temperature will be evaluated at the visits indicated in the Schedule of Assessments (Table 1). 
All vital signs will be measured after the subject has been resting in a sitting position for at least 
5 minutes. Blood pressure measurements are to be taken in the same arm for the duration of the 
study. Body weight (without shoes) and height (without shoes) will be recorded at screening 
only. 
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur. Out-of-range blood pressure or heart rate measurements will be repeated at the 
investigator’s discretion.  
12.3 Laboratory Assessments 
Laboratory assessment samples (Table 2) to be obtained at designated visits as detailed in the 
Schedule of Assessments (Table 1). 


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Table 2. 
Laboratory Assessments 
Hematology 
Serum Chemistry 
Pregnancy Test 
Complete blood count:  
Hct 
Hb 
MCV 
Platelet count 
RBC count 
WBC count with differential 
Albumin 
ALT 
ALP 
AST 
GGT 
BUN 
Sodium  
Potassium  
Chloride  
Carbon dioxide  
Creatinine 
Glucose 
Total bilirubin 
Direct bilirubin 
LDH 
CRP  
A urine HCG pregnancy test will be 
performed on all women of childbearing 
potential at screening 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
BUN = blood urea nitrogen; CRP = C-reactive protein; GGT = gamma-glutamyl transferase; HCG = human 
chorionic gonadotropin; Hb = hemoglobin; Hct = hematocrit; LDH = lactate dehydrogenase; MCV = mean 
corpuscular volume; RBC = red blood cell; WBC = white blood cell. 
 
Blood will be analyzed at a central laboratory. A urine sample for pregnancy testing should be 
obtained for testing at the site using the provided test kits. All laboratory reports must be 
reviewed, signed, and dated by the investigator. A legible copy of all reports must be filed with 
the subject’s electronic source documents for that visit. Clinically significant abnormal values 
occurring during the study will be followed up until repeat test results return to normal, stabilize, 
or are no longer clinically significant. 
12.4 Adverse Events 
12.4.1 Adverse Events 
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
or, if present at screening, worsens during the study, regardless of the suspected cause of the 
event. All medical and psychiatric conditions (except those related to the indication under study) 
present at screening will be documented in the medical history eCRF. Changes in these 
conditions and new symptoms, physical signs, syndromes, or diseases should be noted on the AE 
eCRF during the rest of the study.  


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Subjects will be instructed to report AEs at each study visit. All AEs are to be followed up until 
resolution or a stable clinical endpoint is reached. 
Each AE is to be documented on the eCRF with reference to date of onset, duration, frequency, 
severity, relationship to study drug, action taken with study drug, treatment of event, and 
outcome. Furthermore, each AE is to be classified as being serious or nonserious. Changes in 
AEs and resolution dates are to be documented on the eCRF. 
For the purposes of this study, the period of observation for collection of AEs extends from the 
time the subject is administered study medication (Day 1) until Day 28 or early termination. 
Subjects with early termination will be followed up until Day 28. Follow-up of the AE, even 
after the date of therapy discontinuation, is required if the AE persists until the event resolves or 
stabilizes at a level acceptable to the investigator. 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the event should be noted. If the intensity category changes over a number of days, 
then those changes should be recorded separately (with distinct onset dates). 
Specific guidelines for classifying AEs by intensity and relationship to study drug are given in 
Table 3 and Table 4. 
Table 3. 
Classification of Adverse Events by Intensity 
MILD: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with 
everyday activities. 
MODERATE: An event that is sufficiently discomforting to interfere with normal everyday activities. 
SEVERE: An event that prevents normal everyday activities. 
 
 
 


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Table 4. 
Classification of Adverse Events by Relationship to Study Drug 
UNRELATED: This category applies to those AEs that are clearly and incontrovertibly due to extraneous 
causes (disease, environment, etc.). 
UNLIKELY: This category applies to those AEs that are judged to be unrelated to the study drug but for which 
no extraneous cause may be found. An AE may be considered unlikely to be related to study drug if or when it 
meets 2 of the following criteria: (1) it does not follow a reasonable temporal sequence from administration of 
the study drug; (2) it could readily have been produced by the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (3) it does not follow a known pattern of 
response to the study drug; or (4) it does not reappear or worsen when the drug is readministered. 
POSSIBLY: This category applies to those AEs for which a connection with the study drug administration 
appears unlikely but cannot be ruled out with certainty. An AE may be considered possibly related if or when 
it meets 2 of the following criteria: (1) it follows a reasonable temporal sequence from administration of the 
drug; (2) it could not readily have been produced by the subject’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the subject; or (3) it follows a known pattern of response to the 
study drug. 
PROBABLY: This category applies to those AEs that the investigator feels with a high degree of certainty are 
related to the study drug. An AE may be considered probably related if or when it meets 3 of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (3) it disappears or decreases on cessation or 
reduction in dose (note that there are exceptions when an AE does not disappear upon discontinuation of the 
drug, yet drug-relatedness clearly exists; for example, as in bone marrow depression, fixed drug eruptions, or 
tardive dyskinesia); or (4) it follows a known pattern of response to the study drug. 
DEFINITELY:  This category applies to those AEs that the investigator feels are incontrovertibly related to 
study drug. An AE may be assigned an attribution of definitely related if or when it meets all of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (3) it disappears or decreases on cessation or 
reduction in dose and recurs with reexposure to drug (if rechallenge occurs); and (4) it follows a known pattern 
of response to the study drug. 
Abbreviation: AE = adverse event. 
 
12.4.2 Serious Adverse Events 
In general for any clinical trial an SAE is any untoward medical occurrence, in the view of either 
the investigator or Sponsor, that: 
• results in death, 
• is life-threatening, 
• results in inpatient hospitalization or prolongation of existing hospitalization, 
• results in persistent or significant disability/incapacity, and/or 
• is a congenital anomaly/birth defect 
For the purposes of this study, death and inpatient hospitalization will not be considered as an 
SAE, as the primary end point of this study is the proportion of subjects requiring COVID-19 
related hospitalization (including emergency room visit) or who die due to any cause within 
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Other important non-COVID-19 medical events that may not be immediately life-threatening or 
result in death or hospitalization, based upon appropriate medical judgment, are considered SAEs 
if they are thought to jeopardize the subject and/or require medical or surgical intervention to 
prevent one of the outcomes defining an SAE. SAEs are critically important for the identification 
of significant safety problems; therefore, it is important to take into account both the 
investigator’s and the Sponsor’s assessment. If either the Sponsor or the investigator believes 
that an event is serious, the event must be considered serious and evaluated by the Sponsor for 
expedited reporting. 
12.4.3 Serious Adverse Event Reporting 
An SAE occurring from the first dose administered until Day 28 must be reported to 
EVERSANA Pharmacovigilance and will be communicated to the Sponsor. Any such SAE due 
to any cause, whether or not related to the study drug, must be reported within 24 hours of 
occurrence or when the investigator becomes aware of the event. Notification can be made using 
the dedicated fax line or email for the EVERSANA Pharmacovigilance group: 
EVERSANA Pharmacovigilance fax number: 1-510-295-6449 
EVERSANA Pharmacovigilance email address: sagentPV@eversana.com 
If the investigator contacts the EVERSANA Pharmacovigilance group by telephone, then a 
written report must follow within 24 hours and is to include a full description of the event and 
sequelae in the format detailed in the SAE reporting form. 
EVERSANA Pharmacovigilance telephone number: 1-510-595-8289 
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must be 
followed up by detailed descriptions later on, including clear and anonymized photocopies of 
hospital case reports, consultant reports, autopsy reports, and other documents when requested 
and applicable. SAE reports must be made whether or not the investigator considers the event to 
be related to the investigational drug. 
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed in order to 
determine the etiology of the problem. The investigator must report all additional follow-up 
evaluations to the EVERSANA Pharmacovigilance group within 24 hours of becoming aware of 
the additional information or as soon as is practicable. All SAEs will be followed up until the 
investigator and Sponsor agree the event is satisfactorily resolved. 
Any SAE that is not resolved by the end of the study or upon discontinuation of the subject’s 
participation in the study is to be followed up until it either resolves, stabilizes, returns to 
baseline values (if a baseline value is available), or is shown to not be attributable to the study 
drug or procedures. 


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12.4.4 Suspected Unexpected Serious Adverse Reactions 
Adverse events that meet all of the following criteria will be classified as suspected unexpected 
serious adverse reactions (SUSARs) and reported to the appropriate regulatory authorities in 
accordance with applicable regulatory requirements for expedited reporting: 
• serious 
• unexpected (i.e., the event is not consistent with the safety information in the IB) 
• there is at least a reasonable possibility that there is a causal relationship between the event 
and the study treatment 
The investigator will assess whether an event is causally related to study treatment. The Sponsor 
(or EVERSANA) will consider the investigator’s assessment and determine whether the event 
meets the criteria for being reportable as a 7-day or 15-day safety report. SUSARs that are life-
threatening must be reported to the regulatory authorities and the institutional review board 
(IRBs; where required) within 7 days after the Sponsor (or EVERSANA) has first knowledge of 
them, with a follow-up report submitted within a further 8 calendar days. Other SUSARs must be 
reported to the relevant regulatory authorities and the IRBs within 15 calendar days after the 
Sponsor (or EVERSANA) first has knowledge of them. 
The Sponsor (or EVERSANA) is responsible for reporting SUSARs and any other events 
required to be reported in an expedited manner to the regulatory authorities and for informing 
investigators of reportable events, in compliance with applicable regulatory requirements within 
specific timeframes. Investigators will notify the relevant IRBs of reportable events within the 
applicable timeframes. 
12.4.5 Pregnancy 
WOCBP must have a negative urine pregnancy test at screening. Following administration of 
study drug, any known cases of pregnancy in female subjects will be reported until the subject 
completes or withdraws from the study. The pregnancy will be reported immediately by 
faxing/emailing a completed pregnancy report to the Sponsor (or EVERSANA) within 24 hours 
of knowledge of the event. The pregnancy will not be processed as an SAE; however, the 
investigator will follow up with the subject until completion of the pregnancy and must assess 
the outcome in the shortest possible time but not more than 30 days after completion of the 
pregnancy. The investigator should notify the Sponsor (or EVERSANA) of the pregnancy 
outcome by submitting a follow-up pregnancy report. If the outcome of the pregnancy involved 
spontaneous or therapeutic abortion (any congenital anomaly detected in an aborted fetus is to be 
documented), stillbirth, neonatal death, or congenital anomaly, the investigator will report the 
event by faxing/emailing a completed pregnancy report form to the Sponsor (or EVERSANA) 
within 24 hours of knowledge of the event. 
If the investigator becomes aware of a pregnancy occurring in the partner of a subject 
participating in the study, the pregnancy should be reported to the Sponsor (or EVERSANA) 


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within 24 hours of knowledge of the event. Information regarding the pregnancy must only be 
submitted after obtaining written consent from the pregnant partner. The investigator will 
arrange counseling for the pregnant partner by a specialist to discuss the risks of continuing with 
the pregnancy and the possible effects on the fetus. 
Upon discontinuation from the study, only those procedures that would not expose the subject to 
undue risk will be performed. The investigator should also be notified of pregnancy occurring 
during the study but confirmed after completion of the study. In the event that a subject is 
subsequently found to be pregnant after inclusion in the study, any pregnancy will be followed to 
term, and the status of mother and child will be reported to the Sponsor after delivery. 
13 STATISTICAL ANALYSIS 
A statistical analysis plan (SAP) will be prepared after the protocol is approved and subsequently 
submitted to the Investigational New Drug application before completion of the study. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives. The SAP will serve as a companion document to the 
protocol and supersedes it in case of differences. 
The statistical evaluation will be performed using SAS® software version 9.4 or higher 
(SAS Institute, Cary, NC). All data will be listed, and summary tables will be provided. 
Summary statistics will be presented by treatment group. For continuous variables, data will be 
summarized with the number of subjects (N), mean, standard deviation, median, minimum, and 
maximum by treatment group. For categorical variables, data will be tabulated with the number 
and proportion of subjects for each category by treatment group.  
In general, all efficacy endpoints and major safety endpoints will be summarized using 
descriptive statistics (e.g., proportions for categorical data, means and standard deviations for 
continuous data, median for time-to-event data). The primary and key secondary efficacy 
endpoints will be analyzed using appropriate statistical models. 
A statistical analysis plan (SAP) will further describe the statistical analyses prior to unblinding 
of study and database lock. Missing data procedures will be described in the SAP.  
13.1 Determination of Sample Size 
Assuming that the proportions of outpatients who are hospitalized for COVID-19 related disease 
or die due to any reason within 28 days of randomization are 30% and 15% for placebo and 
camostat mesilate groups, respectively, based on the two-sided Fisher's Exact Test, at the target 
significance level of 5%, 275 outpatients (183 in camostat mesilate group and 92 in placebo 
group) are needed to achieve 80% power. Thus, approximately 300 outpatients (200 in the 
camostat mesilate group and 100 in the placebo group) will be randomized to account for subject 
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13.2 Analysis Populations 
Intent-to-Treat Population (ITT) 
The Intent-to-Treat (ITT) population will include all subjects who are randomized. Subjects will 
be analyzed according to their study treatment assignment, not according to the treatment 
actually received. The ITT population will be used for evaluating primary and secondary efficacy 
endpoints and subject characteristics. 
Per-Protocol Population (PP) 
The Per-Protocol (PP) population will include all subjects in the ITT population who complete 
the 28-day study and have no major protocol deviations. The PP population will be used for 
primary and secondary efficacy endpoints. 
Safety Population 
The Safety population will consist of subjects who receive at least 1 dose of study medication 
(camostat mesilate or placebo). The Safety population will be used for all summaries of safety 
and tolerability data. 
13.3 Efficacy Analysis 
13.3.1 Analysis of Primary Efficacy Endpoint 
The primary endpoint (the proportion of subjects requiring COVID-19 related hospitalization or 
who died due to any cause within 28 days of randomization) will be analyzed using the Fisher 
exact test in ITT and PP populations. The primary endpoint will also be analyzed using the 
Mantel-Haenszel (MH) test, and the 95% Clopper-Pearson confidence interval (CI) will be 
reported. In addition, the continuity-corrected Newcombe CI for the proportional difference 
between treatment groups will be reported. The logistic regression model with treatment group, 
sex, race, duration of symptoms prior to enrollment, age groups (< 65 versus ≥ 65 years) and 
other risk factors as covariates may be used to investigate the potential influences of 
demographic and baseline characteristics. The odds ratios and their 95% CIs will be estimated. 
A sensitivity analysis for the primary efficacy endpoint will be performed for central laboratory 
confirmed COVID-19 subjects in the ITT population. 
13.3.2 Analysis of Secondary Efficacy Endpoints 
Secondary analysis include: 
• The overall survival rate (the proportion of randomized subjects who survive up to 
Day 15 and Day 28) 
• Time to resolution of fever from randomization up to Day 28  
• Time to hospitalization or death following randomization up to Day 28 


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• Proportion of subjects with no viral shedding (yes/no) using RT-PCR at Day 7 and 
Day 15 
The overall survival rate up to Day 15 and Day 28 will be analyzed in ITT and PP populations 
similar to the primary analysis. 
Similar methods, as per the primary endpoint, will be used to analyze the proportion of subjects 
with no viral shedding at Day 7 and Day 15. Time to resolution of fever from randomization up 
to Day 28 and time to hospitalization or death will be summarized with Kaplan-Meier curves. A 
log-rank test will be used to analyze those time-to-event endpoints. The median event time and 
their corresponding 2-sided 95% CIs will be provided for each treatment arm. The Cox 
proportional hazard model with treatment group, sex, race, duration of symptoms prior to 
enrollment, age groups (< 65 versus ≥ 65 years) and other risk factors as covariates may be used 
to investigate the potential influences of demographic and baseline characteristics. The hazard 
ratios and their 95% CIs will be estimated. Additionally, the change from baseline in clinical 
symptoms and viral shedding will be summarized using shift tables. 
A sensitivity analysis for the secondary efficacy endpoints will also be performed for central 
laboratory confirmed COVID-19 subjects in the ITT population. 
13.4 Safety Analysis 
All reported AEs will be coded using the latest version of the Medical Dictionary for Regulatory 
Activities (MedDRA). The incidence of TEAEs will be included in incidence tables. Events with 
missing onset dates will be included as treatment-emergent. If a subject experiences more than 1 
occurrence of the same AE, the occurrence with the greatest severity and the closest association 
with the study drug will be used in the summary tables. SAEs, grade 3 or 4 TEAEs, and TEAEs 
causing discontinuation will be summarized using discrete summaries by system organ class and 
preferred term for each treatment group. All AEs will be listed by subject, along with 
information regarding onset, duration, relationship and severity to study drug, action taken with 
study drug, treatment of event, and outcome. TEAEs will be summarized by severity and 
relationship separately. 
Clinical laboratory data and vital signs will be summarized using descriptive statistics, including 
mean values and mean change from baseline values, as well as numbers of subjects with values 
outside limits of the normal range at each time point. 
Summary tables will be provided for concomitant medications initiated during the study period. 
13.5 Interim Analysis  
No interim analysis is planned. 
 
 


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14 STUDY MANAGEMENT 
14.1 Approval and Consent 
14.1.1 Regulatory Guidelines 
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and all relevant regulations as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of 
the United States Code of Federal Regulations (CFR), in compliance with International Council 
for Harmonisation (ICH) and GCP guidelines and according to the appropriate regulatory 
requirements in the countries where the study was conducted. 
14.1.2 Institutional Review Board 
Conduct of the study must be approved by an appropriately constituted IRB. Approval is 
required for the study protocol, protocol amendments (if applicable), IB, ICFs, recruitment 
material and subject information sheets, and other subject-facing material. 
14.1.3 Informed Consent 
For each study subject, electronic informed consent will be obtained before any protocol-related 
activities. As part of this procedure, the principal investigator (PI) or designee must explain 
orally the nature of the study, its purpose, procedures, expected duration, alternative therapy 
available, and the benefits and risks involved in study participation and this should be 
documented in the medical record. The subject should be informed that he/she may withdraw 
from the study at any time, and the subject will receive all information that is required by local 
regulations and guidelines for ICH. The PI will provide the subject with a copy of the fully 
executed ICF. The investigator will provide the Sponsor or its representative with a copy of the 
IRB-approved ICF before the start of the study. 
14.2 Data Handling 
Any data to be recorded directly on the eCRFs (to be considered as source data) will be 
identified at the start of the study. Data reported on the eCRF that are derived from source 
documents should be consistent with the source documents, or the discrepancies must be 
explained (See also Section 14.3).  
Clinical data will be entered by site personnel on eCRFs for transmission to the Sponsor. Data on 
eCRFs transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site, unless the study site makes direct data entry to the 
databases for which no other original or source documentation is maintained. In such cases, the 
study site should document which eCRFs are subject to direct data entry and should have in 
place procedures to obtain and retain copies of the information submitted by direct data entry. 
All study forms and records transmitted to the Sponsor must only include coded identifiers such 
that directly identifying personal information is not transmitted. The primary method of data 


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transmittal is via the secure, internet-based EDC. Access to the EDC system is available to only 
authorized users via the study’s internet website, where a user unique assigned username and 
password are required for access. 
Any changes made to data after collection will be made through the use of data clarification 
forms or the EDC system. Electronic CRFs will be considered complete when all missing and/or 
incorrect data have been resolved. 
14.3 Source Documents 
Source documents are considered to be all information in electronic copies of records of clinical 
findings, observations, data, or other activities in a clinical study necessary for the reconstruction 
and evaluation of the study. The investigator will provide direct access to electronic data in the 
facilitation of trial-related monitoring, audits, review by IRBs, and regulatory inspections. 
The investigator/institution should maintain adequate and accurate electronic source documents 
and trial records that include all pertinent observations on each of the site’s trial subjects. 
Electronic source data should be attributable, legible, contemporaneous, original, accurate, and 
complete. Changes to source data should be traceable, not obscure the original entry, and be 
explained if necessary. 
14.4 Record Retention 
Electronic study records and source documents must be preserved for at least 15 years after the 
completion or discontinuation of/withdrawal from the study, at least 2 years after the drug being 
studied has received its last approval for sale, or at least 2 years after the drug development has 
stopped, and in accordance with the applicable local privacy laws, whichever is the longer time 
period. 
The investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of subject health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 [HIPAA] Privacy Regulation). The 
investigator shall ensure that study subjects authorize the use and disclosure of protected health 
information in accordance with HIPAA Privacy Regulation and in a form satisfactory to the 
Sponsor. 
14.5 Monitoring 
The study will be monitored according to the clinical monitoring plan to ensure that it is 
conducted and documented properly according to the protocol, GCP, and all applicable 
regulatory requirements. 
Remote Monitoring visits and telephone contacts will be made at appropriate times during the 
study. The PI will assure he/she and adequate site personnel are available throughout the study to 
collaborate with clinical monitors. Clinical monitors must have direct access to electronic source 


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documentation in order to check the completeness, clarity, and consistency of the data recorded 
on the eCRFs for each subject. 
The investigator will make available to the clinical monitor all electronic source documents and 
medical records necessary to review protocol adherence and eCRFs. In addition, the investigator 
will work closely with the clinical monitor and, as needed, provide them appropriate evidence 
that the study is being conducted in accordance with the protocol, applicable regulations, and 
GCP guidelines. 
14.6 Quality Control and Quality Assurance 
The Sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the Sponsor lies with the investigator generating the data. 
The Sponsor may arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, standard operating procedures, 
GCP, and all applicable regulatory requirements. Audits will be independent of and separate 
from the routine monitoring and quality control functions. Quality assurance procedures will be 
performed remotely and during data management to assure that safety and efficacy data are 
adequate and well documented. 
14.7 Protocol Amendment and Protocol Deviation 
14.7.1 Protocol Amendment 
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no effect on 
the safety of subjects or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IRB for information only. The Sponsor will ensure that 
acknowledgement is received and filed electronically. Amendments that are classed as 
substantial amendments must be submitted to the appropriate regulatory authorities and the IRBs 
for approval and will not be implemented at sites until such approvals are received other than in 
the case of an urgent safety measure. 
14.7.2 Protocol Deviations 
Should a protocol deviation occur, the Sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the clinical study 
report. Reporting of protocol deviations to the IRB and in accordance with applicable regulatory 
authority mandates is an investigator responsibility. 
14.8 Ethical Considerations 
This study will be conducted in accordance with this protocol, the accepted version of the 
Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, 


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Subpart D, of Title 21 of the CFR; EU 536/2014, Annex 1, D, 17 (a); and in compliance with 
GCP guidelines. 
IRBs will review and approve this protocol and the ICF. All subjects are required to give 
electronic informed consent before participation in the study. 
14.9 Financing and Insurance 
Before the study commences, the Sponsor (or its designee) and the investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study. This agreement will 
be documented in a financial agreement that will be signed by the investigator (or the institution 
signatory) and the Sponsor (or its designee). 
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The Sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations. 
14.10 Publication Policy/Disclosure of Data 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters) generated by the investigator and others 
performing the clinical study will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the Sponsor or their designee. With respect to such rights, 
the Sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, investigators will be required to assign all such inventions either to their institution or 
directly to the Sponsor or its designee, as will be set forth in the clinical study agreement. 


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15 REFERENCES 
Abe M, Hara Y, Kuwano K et al. Use of FOY-305 for the treatment of pain attacks associated with 
chronic pancreatitis. New Horizons for Medicine (1980); 12 (Extra Edition) 233. 
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19-preliminary report. N 
Engl J Med. May 22, 2020. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/32445440/. Assessed 
15 June 2020. 
Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment 
Coronavirus (COVID-19). https[KC1]://www.ncbi.nlm.nih.gov/books/NBK554776. Accessed 13April 
2020. 
Centers for Disease Control and Prevention (CDC). Interim guidelines for collecting, handling, and 
testing clinical specimens for COVID-19. 22 May 2020. https://www.cdc.gov/coronavirus/2019-
ncov/lab/guidelines-clinical-specimens.html. Assessed 04 June 2020. 
Foipan® package insert. Oral protease inhibitor FOIPAN Tablets 100 mg <Camostat mesilate tables>. 
Revised August 2009. http://www.shijiebiaopin.net/upload/product/201272318373223.PDF. 
Accessed 28 April 2020. 
Fujiwara 5, Iwamoto K, Miyazaki A. Clinical experience with oral FOY-305 for pancreatitis. New 
Horizons for Medicine (1980); 12 (Extra Edition) 104.  
Gandhi RT, Lynch JB, del Rio C. Mild or moderate Covid-19. New England Journal of Medicine. April 
2020. https://www.nejm.org/doi/pdf/10.1056/NEJMcp2009249. Accessed 12 June 2020. 
Hayawaka T, Noda T, Kondo T et al. Effect of oral administration of FOY-305 on pancreatitis. New 
Horizons for Medicine (1980); 12 (Extra Edition) 236. 
[HMA] Heads of Medicines Agencies. Clinical Trial Facilitation Group page. Recommendations related 
to contraception and pregnancy testing in clinical trials. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. September 15, 2014. 
Accessed 27 May 2020. 
Hirayama A, Izumiyama S, Itagaki Y et al. Clinical investigation of FOY-305 against pancreatitis. New 
Horizons for Medicine (1980a); 12 (Extra Edition) 245.  
Hirayama A, Izumiyama S, Itagaki Y et al. Clinical analysis of FOY-305 for pancreatitis - A Small 
Double-blind Clinical Trial. New Horizons for Medicine (1980b); 12 (Extra Edition) 253. 
Hirono T. Clinical Experience with oral anti-enzyme agent FOY-305 for pancreatitis. New Horizons for 
Medicine (1980); 12 (Extra Edition) 215. 


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Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and 
TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:1-10. 
Horiguchi Y, Nakajima S, Ito M. Clinical experience with FOY-305 for pancreatitis. New Horizons for 
Medicine (1980); 12 (Extra Edition) 227. 
Ishii K, et al. Evaluation of the efficacy of FOY-305 in pancreatitis: multicenter, double-blind study. New 
Horiz Med. 1980;12:261. 
Kinami Y, Takita Y, Shinmura K et al. Clinical effect of FOY-305 on pancreatitis. New Horizons for 
Medicine (1980); 12 (Extra Edition) 108.  
Kubota Y, Meada S. Experience with FOY-305 in patients with pancreatitis. New Horizons for Medicine 
(1980); 12 (Extra Edition) 211. 
Ramsey ML, Nuttall J, Hart PA, TACTIC Investigative Team. A phase 1/2 trial to evaluate the 
pharmacokinetics, safety, and efficacy of NI-03 in patients with chronic pancreatitis: study protocol for a 
randomized controlled trial on the assessment of camostat treatment in chronic pancreatitis (TACTIC). 
Trials. 2019;20(1):501. 
Sagent Pharmaceuticals, Inc. Investigator Brochure Camostat mesilate Edition 1. Schaumburg, IL. 11 June 
2020. 
Tanaka N, Tsuchiya R. Clinical efficacy of FOY-305 in pancreatitis. New Horizons for Medicine (1980); 
12 (Extra Edition) 223. 
World Health Organization. https://www.who.int/blueprint/priority-diseases/key-action/novel-
coronavirus/en/Accessed 13-APR-2020.  
Wu C, Chen X, Cai, Y. Risk factors associated with acute respiratory distress syndrome and death in 
patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020; Published 
online March 13, 2020. doi:10.1001/jamainternmed.2020.0994. 


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16 APPENDICES 
APPENDIX 1 describes the contraception guidelines applicable for this study. 
APPENDIX 2 describes the proper collection method for mid-turbinate swab samples.


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16.1 APPENDIX 1 - CONTRACEPTION GUIDELINES 
Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP must 
use at least 1 highly effective method of contraception during the study and for 90 days after the 
last dose of study treatment.  
A woman is considered to be a WOCBP (fertile) following menarche and until becoming 
postmenopausal, unless she is permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is 
defined as no menses for 12 months without an alternative medical cause. A high 
follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal replacement 
therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient.  
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
Highly effective methods of contraception are those which have a failure rate of <1% (when 
implemented consistently and correctly) and include: 
• combined (containing estrogen and progestogen) hormonal contraception associated with 
inhibition of ovulation (administration may be oral, intravaginal, or transdermal) 
• progestogen-only hormonal contraception associated with inhibition of ovulation 
(administration may be oral, injectable, or implantable) 
• intrauterine device 
• intrauterine hormone-releasing system 
• bilateral tubal ligation or occlusion 
• vasectomy (provided that the male has a medical assessment of surgical success) 
• sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of risk in relation to the duration of the clinical trial, in line with the preferred and 
usual lifestyle of the subject) 
All subjects will be strongly advised that they (or the female partners of male subjects) should 
not become pregnant while on study treatment or for the above-specified period after the last 
dose. A female subject will be advised that she must report immediately to the study site for 
pregnancy testing and appropriate management in the event that she may be pregnant. 
(HMA, 2014) 
 


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16.2 APPENDIX 2 – GUIDELINES FOR NASAL TURBINATE SWAB COLLECTION 
PROCEDURE 
General Guidelines 
Proper collection of specimens is the most important step in the laboratory diagnosis of 
infectious diseases. A specimen that is not collected correctly may lead to false negative test 
results. The following specimen collection guidelines follow standard recommended 
procedures. These instructions are provided by the Centers for Disease Control and 
Prevention (CDC, 2020) 
A nasal mid-turbinate swab is to be collected by a healthcare provider using a flocked tapered 
swab. Use only synthetic fiber swabs with plastic or wire shafts. Do not use calcium alginate 
swabs or swabs with wooden shafts, as they may contain substances that inactivate some viruses 
and inhibit PCR testing. 
Collecting and Handling Specimens Safely 
For providers collecting specimens or within 6 feet of subjects suspected or known to be infected 
with SARS-CoV-2, maintain proper infection control and use recommended personal protective 
equipment (PPE), which includes an N95 or higher-level respirator (or facemask if a respirator is 
not available), eye protection, gloves, and a gown, when collecting specimens. 
For providers who are handling specimens, but are not directly involved in collection (e.g., self-
collection) and not working within 6 feet of the subject, follow standard precautions; gloves are 
recommended. Healthcare personnel are recommended to wear a form of source control 
(facemask or cloth face covering) at all times while in the healthcare facility. 
Collecting Mid-turbinate Swab Specimens 
Use a flocked tapered swab, and grasp only the distal end of the swab handle using gloved hands. 
Tilt subject’s head back 70 degrees. While gently rotating the swab, insert swab less than one 
inch (about 2 cm) into nostril until resistance is met at turbinates. Rotate the swab several times 
against nasal wall. In the subject eCRF, record the subject’s nostril used for sampling. Use the 
same nostril throughout the study each time a swab specimen is collected. 
Storage 
Swabs should be placed immediately into a sterile transport tube containing 2 to 3 mL of either 
viral transport medium (VTM), Amies transport medium, or sterile saline, unless using a test 
designed to analyze a specimen directly, (i.e., without placement in VTM), such as some point-
of-care tests.  
Label the specimen appropriately, including the subject ID, study number, specimen type (nasal 
mid-turbinate swab sample), and date and time of collection.  
Refer to the central laboratory manual for further processing of swab samples. 

SAP_001.pdf: 
 
1357 GARDEN ROAD, WYNNEWOOD, PA 19096 • (610) 645 5708 FAX: (484) 534 8570 • BSC@biomedstat.com • 
www.biomedstat.com 
Biomedical Statistical Consulting 
QUALITY IN DESIGN, IMPLEMENTATION, & PRESENTATION SINCE 1986 
 
Statistical Analysis Plan 
 
Protocol No.:  
NI03-CV19-001 
 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy of Camostat 
mesilate for the Treatment of Confirmed COVID-19 in Outpatients 
 
Sponsor: 
Sagent Pharmaceuticals 
1901 N. Roselle Road, Suite 450 
Schaumburg, IL 60195 
 
 
Version 2.0 
March 31, 2021 
 
Author: 
David Maislin 
Brendan Keenan 
Greg Maislin


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 2 of 56 
TABLE OF CONTENTS 
1 
PURPOSE AND SCOPE OF STATISTICAL ANALYSIS PLAN .............. 5 
2 
STUDY OBJECTIVES AND ENDPOINTS ................................................... 6 
2.1 
STUDY OBJECTIVES .............................................................................................................................. 6 
2.1.1 
Primary Objective ................................................................................................................................ 6 
2.1.2 
Secondary Objectives .......................................................................................................................... 6 
2.2 
PRIMARY ENDPOINT ............................................................................................................................ 6 
2.3 
SECONDARY ENDPOINTS .................................................................................................................... 6 
2.3.1 
Survival/Mortality ............................................................................................................................... 6 
2.3.2 
Clinical Improvement .......................................................................................................................... 6 
2.3.3 
Safety/Tolerability ............................................................................................................................... 6 
2.4 
RANDOMIZATION .................................................................................................................................. 7 
2.5 
ANALYSIS SETS ....................................................................................................................................... 7 
2.5.1 
Intent-to-Treat Population (ITT) ......................................................................................................... 7 
2.5.2 
Per-Protocol Population #1 (PP1)........................................................................................................ 7 
2.5.3 
Per-Protocol Population #2 (PP2)........................................................................................................ 7 
2.5.4 
Safety Population (SP) ........................................................................................................................ 8 
2.6 
BLINDING ................................................................................................................................................. 8 
3 
DESCRIPTION OF OUTCOME MEASURES ............................................. 9 
3.1 
PRIMARY ANALYSIS ............................................................................................................................. 9 
3.2 
SECONDARY ANALYSIS (PROTOCOL SPECIFIED) ....................................................................... 9 
3.3 
EXPLORATORY ANALYSIS ................................................................................................................ 10 
4 
ANALYSIS APPROACH ............................................................................... 12 
4.1 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT ................................................................ 12 
4.1.1 
Primary Efficacy Endpoint ................................................................................................................ 12 
4.1.2 
Primary Efficacy Hypotheses ............................................................................................................ 12 
4.1.3 
Testing of Primary Efficacy Hypothesis ........................................................................................... 12 
4.1.4 
Sample Size Determination for the Primary Efficacy Hypothesis ..................................................... 13 
4.1.5 
Heterogeneity of Treatment Effects .................................................................................................. 13 
4.1.6 
Handling of Baseline Differences ...................................................................................................... 13 
4.1.7 
Handling of Missing Data for the Primary Efficacy Test .................................................................. 14 
4.1.8 
Handling of Missing Data for the Secondary Endpoint of Fever resolution ..................................... 15 
4.2 
ANALYSES OF SECONDARY EFFICACY ENDPOINTS ................................................................ 15 
4.2.1 
Survival/Mortality ............................................................................................................................. 15 


 
 
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4.2.2 
Clinical Improvement ........................................................................................................................ 15 
4.3 
ANALYSES OF SAFETY/TOLERABILITY ....................................................................................... 15 
4.3.1 
Summary of Adverse Events ............................................................................................................. 16 
4.3.2 
Specific Adverse Events .................................................................................................................... 16 
4.3.3 
Severity of Adverse Events ............................................................................................................... 17 
4.3.4 
Comparisons Between Subjects with and without a TEAE ............................................................... 17 
4.3.5 
Safety Listings ................................................................................................................................... 17 
4.3.6 
Clinical Laboratory Values ................................................................................................................ 17 
4.3.7 
Vital Signs ......................................................................................................................................... 18 
4.3.8 
Compliance of Drug .......................................................................................................................... 18 
4.4 
SUBGROUP ANALYSES ....................................................................................................................... 18 
4.5 
EXPLORATORY ANALYSES .............................................................................................................. 18 
4.6 
POOLABILITY ....................................................................................................................................... 19 
4.6.1 
Site Poolability .................................................................................................................................. 19 
4.6.2 
Region Poolability ............................................................................................................................. 19 
4.7 
PROTOCOL DEVIATIONS ................................................................................................................... 19 
4.8 
PATIENT DISPOSITION ....................................................................................................................... 20 
4.9 
CHANGES TO THE ANALYSIS PLAN ............................................................................................... 20 
5 
APPENDIX: SHELL TABLES AND FIGURES ......................................... 21 
 




 
 
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1 PURPOSE AND SCOPE OF STATISTICAL ANALYSIS PLAN 
The purpose of this Statistical Analysis Plan (SAP) is to provide details regarding the analyses 
sets, endpoints, and statistical analysis methods to be used to meet the objectives of the NI03-
CV19-001 trial. When differences exist in descriptions or explanations provided in the 
Clinical Study Protocol and this SAP, the SAP prevails. This SAP will be finalized prior to 
unblinding of the treatment allocations codes.  
This document is designed to be a stand-alone document in terms of conveying essential 
statistical approaches to the analysis of the data. More definitions and details regarding 
variables collected are provided in the Clinical Study Protocol (version 4.0 at time of writing).  
Statistical approaches were developed to be consistent with accepted statistical and clinical 
trial principles including ICH E9, Statistical principals for clinical trials1. 
 
1 ICH E9 Expert Working Group. Statistical Principles for Clinical Trials: ICH Harmonized Tripartite Guideline. 
Statistics in Medicine 1999; 18:1905–1942. 


 
 
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2 STUDY OBJECTIVES AND ENDPOINTS 
Section 2.1, 2.2, and 2.3 summarize the sections of the Clinical Trial protocol NI03-CV19-
001 Version 4.0 and have been edited to provide additional clarity. As noted above in 
Purpose and Scope of Statistical Analysis Plan, this document was updated prior to the 
unblinding of treatment allocations and submitted to the FDA before database lock. 
2.1 STUDY OBJECTIVES 
2.1.1 Primary Objective 
The primary objective of this study is:  
To evaluate the clinical efficacy of Camostat mesilate (200 mg orally 4 times a day) in 
ambulatory subjects with confirmed COVID-19.  
2.1.2 Secondary Objectives 
The secondary objective of this study is: 
Evaluate the safety profile of Camostat mesilate (200 mg orally 4 times a day) in 
ambulatory subjects with confirmed COVID-19. 
2.2 PRIMARY ENDPOINT 
Proportion of subjects requiring COVID-19 related hospitalization (including emergency 
room visit) or who die due to any cause within 28 days of randomization.  
2.3 SECONDARY ENDPOINTS 
2.3.1 Survival/Mortality 
The overall survival rate (the proportion of randomized subjects who survive up to Day 15 
and Day 28). 
2.3.2 Clinical Improvement 
• (Protocol) Time to resolution of fever from randomization up to Day 28 among subjects 
presenting with Fever (Day 0 fever >= 100.4° F / 38.0° C, oral)  
• (Protocol) Time to hospitalization/ER visit or death following randomization up to Day 
28 (defined as time to disease progression from randomization to either 
hospitalization/ER visit or death). 
• (Protocol) Proportion of subjects with no viral shedding using RT-PCR at Day 7, Day 
15, and at early termination. 
2.3.3 Safety/Tolerability 
• Incidence of AEs and SAEs of any grade from randomization up to Day 28. 


 
 
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• Cumulative incidence of grade 3 and 4 AEs from randomization up to Day 28. 
• Incidence of discontinuation from study due to an AE/SAE (discontinued subjects will 
be followed up until Day 28). 
• Change from baseline in clinical laboratory parameters (including platelet counts, liver 
function tests, and potassium levels, etc.). 
• Change from baseline in vital signs (heart rate, blood pressure, peripheral capillary 
oxygen saturation [SpO2]). 
2.4 RANDOMIZATION 
Subjects will be randomized in a 2:1 ratio of Camostat mesilate: placebo. Approximately 
300 subjects are planned to be enrolled (200 subjects to Camostat mesilate and 100 subjects 
to placebo). 
One global computer generated, blocked randomization list with 2/3’s of the assignments 
will be to Camostat mesilate and 1/3 to placebo, in random order. Randomization block sizes 
will randomly vary in size 3 and 6. Labeling will be randomly varied as an additional 
masking feature.  
2.5 ANALYSIS SETS 
2.5.1 Intent-to-Treat Population (ITT) 
The Intent-to-Treat (ITT) population will include all subjects who are randomized. 
Subjects will be analyzed according to their study treatment assignment, not according to 
the treatment actually received. The ITT population is the primary population and will be 
used for evaluating primary and secondary efficacy endpoints and subject baseline 
characteristics. 
2.5.2 Per-Protocol Population #1 (PP1) 
The first Per-Protocol population (PP1) will include all subjects in the ITT population who 
complete the 14-day treatment period with 80% compliance with drug. Subjects will be 
analyzed according to the treatment actually received. 80% compliance of drug is 
determined by counting the number of pills returned at the end of the study. Subjects who 
do not return a bottle are assumed to have taken all doses. The primary and secondary 
efficacy endpoints will be evaluated in the PP1 population.  
2.5.3 Per-Protocol Population #2 (PP2) 
A second Per-Protocol population (PP2) will include all subjects in the ITT population who 
do not have major protocol deviations or clinically important intercurrent events thought 
to confound assessment of primary outcomes. The PP2 population will be provided for 
primary and secondary efficacy endpoints.  


 
 
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2.5.4 Safety Population (SP) 
The Safety Population (SP) will consist of ITT subjects who receive at least 1 dose of study 
medication (Camostat mesilate or placebo). Subjects will be analyzed according to the 
study treatment received. The Safety population will be used for all summaries of safety 
and tolerability data. 
2.6 BLINDING 
This is randomized, double-blind, placebo-controlled study. Subjects will be randomized in 
a 2:1 ratio to Camostat mesilate:placebo. None of the investigators, study site personnel, 
Sponsor, or subjects will know to which treatment the subjects were randomized. Additional 
details of the blinding are provided in the Clinical Study Protocol (NI03-CV19-001 Version 
4.0). 


 
 
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3 DESCRIPTION OF OUTCOME MEASURES 
This section provides definitions of specific variables and concepts relevant to this Statistical 
Analysis Plan for primary and second efficacy outcomes. Please refer to the Clinical Trial 
Protocol for additional details. 
3.1 PRIMARY ANALYSIS 
Disease Progression (Hospitalization): The Primary Efficacy Endpoint is defined as status 
changing from ambulatory care to COVID-19 related hospitalization, ER visit, or death due 
to any cause on or prior to Day 28. Presenting to the emergency room is considered 
hospitalization. Hospitalization/ER visit and Death are recorded on the End of Study (EOS) 
form and will support the primary endpoint analysis. All subjects who have an End of Study 
form with any Hospitalization/ER Visit or Death are assumed to be COVID-related and 
therefore analyzed as a failure of the primary endpoint. Subjects failing the primary endpoint 
will be described within the Clinical Study Report. 
3.2 SECONDARY ANALYSIS (PROTOCOL SPECIFIED) 
Time to Resolution of fever (existing at day 0): This analysis will be conducted in the 
subjects with Day 0 temperature >= 100.4° F/ 38.0° C. Time to resolution of fever is defined 
as the time (in days) from initiation of study treatment (active or placebo) until normalization 
of fever (< 100.4° F / 38.0° C oral) and sustained for at least 72 hours; this will only be 
assessed in subjects who experienced a fever within 24 hours of enrollment. In the analysis 
of time to resolution of fever, temperature is recorded everyday up to day 14. Occurrence of 
fever is recorded as a binary (yes/no) a fever (>= 100.4° F/ 38.0° C) was recorded on the 
following day using the e-diary. 
Time to Disease Progression (Hospitalization/ER visit or Death): Defined as time to 
disease progression from randomization to either COVID-19 related hospitalization/ER visit 
or death through Day 28. The primary endpoint is a binary endpoint of Disease Progression, 
this protocol specified analysis captures the temporal occurrence of the event. 
Viral shedding (Resolution): Participants will have Viral Shedding characterized and 
evaluated as having Viral shedding or not having Viral shedding for this secondary endpoint. 
Viral shedding will be collected using reverse transcriptase-polymerase chain reaction (RT-
PCR) at Day 7, Day 15, and at Day 28 or Early Termination. Subjects will have mid-turbinate 
nasal samples taken using flocked swabs at onsite study visits. The same nostril should be 
used for sampling each time it is done, and the nostril (right or left) should be recorded on 
the eCRF. Use of both nostrils is not to be a Major Protocol Deviation and therefore will 
have no bearing on the analysis populations. Details of collection method and laboratory 
requirements are defined in the Clinical Protocol. 


 
 
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3.3 EXPLORATORY ANALYSIS 
Time to Resolution of Existing fever (existing by day 3): This analysis will be conducted 
in the subjects with a fever on Day 0 or those who have a fever within 72 hours of first 
treatment with fever defined as temperature >= 100.4° F / 38.0° C. Time to resolution of 
fever is defined as the time (in days) from 72 hours of study treatment (active or placebo) 
until normalization of fever (< 100.4° F / 38.0° C oral) and sustained for at least 72 hours. In 
the analysis of time to resolution of fever, temperature is recorded everyday up to day 14.  
Time to Incidence of new fever: This analysis will be conducted in the subjects with Day 
0 temperature < 100.4° F/38.0° C. Time to incidence of new fever is defined as the time (in 
days) from initiation of study treatment (active or placebo) until a daily maximum fever >= 
100.4° F/38.0° C (oral). Daily fever is recorded dichotomously (yes/no) whether a fever of 
at least >= 100.4° F/38.0° C is measured in the e-diary. In the analysis of Time to Incidence 
of new fever, temperature is recorded everyday up to Day 14.  
Time to Resolution of new fever (occurring by Day 11): This analysis will be conducted 
in the subjects with a new fever defined as temperature >= 100.4° F / 38.0° C by Day 11. 
Time to resolution of new fever is defined as the time (in days) from 72 hours of study 
treatment (active or placebo) until normalization of fever (< 100.4° F / 38.0° C oral) and 
sustained for at least 72 hours. Occurrence by Day 11 is necessary to capture 72 hours of 
resolution within the data captured.  
Incidence of Fever (any Fever) after Day 0: This analysis will be conducted in the subjects 
with Day 0 temperature < 100.4° F/38.0° C. New fever is defined as a daily maximum fever 
>= 100.4° F/38.0° C (oral). Daily fever is recorded dichotomously (yes/no) whether a fever 
of at least >= 100.4° F/38.0° C is measured in the e-diary up to Day 14. 
Days with Fever: This analysis will be conducted in all subjects in the ITT population 
through day 14 completing 14 days. For each subject, the occurrence of fever (>= 100.4° F 
/ 38.0° C) will be recorded, 1 for yes, 0 for no. For any missing days of temperature data, 
the probability of fever on the missing data will be imputed as the mean of the non-missing 
days. For example, if a subject has 10 (of 14) days of temperature data, and 3 of those days 
had fever, each of the 4 missing days will be given a value of 0.3. Summary statistics 
(number of subjects, mean, SD, median, min and max) for the number of days with fever 
will be characterized. This analysis aims to explore the amount of fever present in time 
between subjects on IP and not on IP. 
Severity of Fever: Shift tables will be provided for the severity of Fever among subjects 
with a fever at Day 0 using the following classification scheme2: 
 
2 The grading for fever was adapted according to FDA categories used in COVID-19 vaccine studies (“U.S. 
Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and 
Research. September 2007. Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent 


 
 
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• None: < 100.4 
• Mild (Grade 1): >=38–38.4°C (>=100.4–101.1°F) 
• Moderate (Grade 2): >=38.5–38.9°C (>=101.2–102.0°F) 
• Severe (Grade 3): >=39–40°C (>=102.1–104.0°F) 
• Potentially Life Threatening (Grade 4): Over 40°C (>=104.0°F) 
A secondary descriptive analysis will be provided in which the status of fever at all points 
in time will be classified using the among Fever classifications without restricting to Fever 
at Day 0. 
 
 
Volunteers Enrolled in Preventive Vaccine Clinical Trials. https://www.fda.gov/media/73679/download Accessed 
30 March 2021 


 
 
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4 ANALYSIS APPROACH 
4.1 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT 
4.1.1 Primary Efficacy Endpoint 
The primary endpoint (the proportion of subjects requiring COVID-19 related 
hospitalization/ER visit or who died due to any cause within 28 days of randomization) 
will be analyzed using an unadjusted Pearson chi-squared test. If the expected number of 
events in either group is less than five (5), a Fisher’s exact test will be used.  
4.1.2 Primary Efficacy Hypotheses 
The primary efficacy hypothesis is that the probability of experiencing a COVID-19 related 
hospitalization/ER visit or death from any cause within 28 days of randomization is smaller 
among subjects randomized to the study drug relative to those subjects randomized to 
placebo.  Symbolically, these hypotheses may be represented as follows. 
Ho: πcm - πpl ≥ 0 
Ha: πcm - πpl < 0 
Where πcm and πpl are the probabilities of experiencing the primary endpoint as defined 
above among subjects randomized to Camostat mesilate and placebo, respectively. 
4.1.3 Testing of Primary Efficacy Hypothesis 
Primary results will include the numbers and percentages of subjects in each treatment 
group requiring COVID-19 related hospitalization/ER visit or who died due to any cause 
within 28 days of randomization. 
As noted in the next section, the study is statistically powered by assuming that πcm = 0.15 
and πpl = 0.30 and the number of subjects to be randomized are 186 and 93, in the active 
and placebo arms, respectively. Consequently, the expected number of subjects to 
experience the event is nearly 28 for both arms, with 158 and 65 subjects in the active and 
placebo arms, respectively, not expected to experience the primary endpoint. Therefore, an 
unadjusted chi-squared test (or exact test, if expected cell counts are < 5 in either group) 
will be used to test the primary efficacy hypotheses using a two-sided type 1 error of 0.05. 
Superiority will be concluded if p<0.05 and the proportion of subjects experiencing the 
event is smaller among subjects randomized to the active treatment. This is tantamount to 
specifying a one-sided type 1 error rate of α=0.025. 
In addition to determining the p-value for the primary efficacy hypothesis, results will also 
be expressed in terms of a two-sided normal based (asymptomatic) 95% confidence 
interval estimating the treatment group difference in 28-day COVID hospitalization or 
death. The upper bound of the confidence interval will be interpreted as the smallest 
treatment effect consistent with the study results.  
If the expected number of events in either group is less than five (5), a Fisher’s exact test 
and exact binomial intervals will be provided.  


 
 
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4.1.4 Sample Size Determination for the Primary Efficacy Hypothesis 
Sample size determination assumed event rates of 15% and 30% in the active and placebo 
groups, respectively, 2:1 randomization, and a two-sided type 1 error rate of α=0.05. Under 
these assumptions, an adjusted chi-square test will have 80% power for sample sizes of 
186 and 93 in the investigational and placebo arms, respectively (total sample size = 279). 
The sample size is increased by approximately 7.5% to allow for up to 200 and 100, 
respectively, to account for loss-to-follow-up.  
4.1.5 Heterogeneity of Treatment Effects 
Heterogeneity of treatment effects will be evaluated for the subgroups (see Subgroup 
Analyses). To this end, the estimated group difference in the probability of experiencing 
the event on the probability scale, along with its 95% confidence interval (CI) will be 
estimated within each subgroup. These results will be graphically displayed in a forest plot. 
4.1.6 Handling of Baseline Differences 
Group differences in baseline characteristics will be evaluated. Analyses will be performed 
to evaluate the treatment effect controlling for baseline covariates found to have clinically 
meaningful baseline differences. Clinically meaningful will be determined by the Sponsor 
Study Safety Monitor or Primary Investigator. This will be done using a generalized linear 
model with parameters estimated using SAS PROC GENMOD with distribution set to 
binomial and link set to logit. The adjusted probabilities and their standard errors are 
determined on the probability scale using the ilink option in a lsmeans statement with a 
diff option. This statement produces a test for the treatment group difference controlling 
for other covariates in the model. The model will include treatment group and each 
identified covariate one-at-a-time. The standard error on the probability scale for the 
difference in event rates will be determined as the square root of the sum of the treatment 
group specific squared standard errors and used in the determination of the 95% CI.  
As requested by FDA, multivariable analyses will be provided to the degree that sample 
size and number of observed events in each group allow. It is understood that a total of 10 
events per covariate is necessary for this modeling approach, which limits the number of 
covariates the model can support. The full model will consist of age, BMI, sex, and the 
number of days since first COVID-19 symptom (=<5 or >5 days), in addition to treatment 
group (sample size permitting). In addition to the full model, a forward stepwise procedure 
will be used to identify a set of covariates that each provide some independent association 
with the primary outcome. 
The totality of evidence (i.e., the clinical and statistical interpretations) will provide support 
for decision making regarding Phase III investigation. 


 
 
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4.1.7 Handling of Missing Data for the Primary Efficacy Test 
To provide a true ITT efficacy test, subjects lost-to-follow-up prior to Day 28 must be 
imputed.  A multiple imputation (MI) (Rubin and Schenker 1991)3  strategy will be used in 
the primary efficacy test followed by a completers analysis and a tipping point analysis as 
sensitivity analyses that examine the robustness of the Missing at Random (MAR) 
assumption necessary for valid application of MI.  
To implement the MI for primary efficacy testing, 20 imputed data sets will be constructed. 
If the pattern of missing data is not monotonic, a fully conditional (FCS) approach as 
implemented in SAS PROC MI (SAS Institute)4 will be utilized. If the pattern of missing 
data is monotonic, a regression approach may be used. The MI model will include age, 
BMI, sex, and the number of days since first COVID-19 symptom (<=5 or >5 days), as 
well as temperature at Day 7 and 14 taken at the clinic. Should the pattern of missing data 
be non-monotonic, an FCS model will be utilized. The estimated treatment group 
difference and standard error will be determined for each imputed data set and combined 
using Rubin’s rule as implemented in SAS PROC MIANALZE. The final treatment group 
difference will be the average of the multiple imputed datasets. The standard error, p-value, 
and width of the confidence interval will account for both within and between imputation 
error.  
The validity of the MI depends on the assumption of Missing at Random (MAR). MAR 
means that the likelihood of missingness does not depend on the unobserved event status. 
A tipping point analysis will be performed to evaluate the robustness of this assumption. 
First a completer’s analysis will be performed in which only subjects with complete 
endpoint status (that is, did not withdraw early or discontinue) are included. Then, all 
subjects with missing data are included in the analysis varying the numbers of subjects 
assumed to have experienced the event in both groups separately. This analysis includes 
the worst-case scenario in which all missing treated subjects are assumed to have 
experienced the event and all placebo subjects are assumed to have not experienced the 
event.  It also includes the best-case scenario, in which all missing treated subjects are 
assumed to have not experienced the event and all placebo subjects are assumed to have 
experienced the event. All other scenarios are similarly evaluated. Assuming superiority 
has been demonstrated, the percentage of scenarios in which the results change from 
rejecting the null hypothesis to not rejecting the null hypothesis is determined.  
If this percentage of scenarios in which study conclusions change is small (for example, 
less than 20%), then the superiority conclusion has been shown to be robust with regard to 
missing data. 
As requested by FDA, an additional sensitivity will be provided in which all missing data 
are treated as failures. 
If an exact test is necessary for the primary endpoint due to expected cell counts < 5 in 
either group, only the tipping point analysis based on the exact tests will be provided.  
 
3 Rubin DB and Schenker N. Multiple imputation in health-care databases: an overview and some applications.  
Statistics in Medicine 10: 585-598, 1991. 
4 Version 9.4, SAS Institute Inc, Cary, NC 


 
 
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4.1.8 Handling of Missing Data for the Secondary Endpoint of Fever resolution 
Three days of non-fever are required for the confirmation of fever resolution. If after a non-
fever is observed and the next 2 days are missing in the e-diary, then fever status (not the 
same day temperature) on the first non-missing will be used in the confirmation. That is, 
resolution of fever requires 3 sequential days of non-fever recorded in the e-diary, which 
may not be consecutive days, if there is missing data.  
4.2 ANALYSES OF SECONDARY EFFICACY ENDPOINTS 
4.2.1 Survival/Mortality 
The overall survival rate (the proportion of randomized subjects who survive up to Day 15 
and Day 28) will be summarized using the same approach as the primary outcome.  
4.2.2 Clinical Improvement 
Time to resolution of fever from randomization up to Day 28 will be analyzed with Kaplan 
Meier5 survival analyses. A log-rank test will be used to compare this time-to-event 
outcome between groups. The median event time and their corresponding 2-sided 95% CIs 
will be provided for each treatment arm. The analysis will treat subjects who die and have 
not yet had a fever resolve as having their fever having not been resolved at Day 28. A 
sensitivity analysis of this analytical approach will be performed, and the interpretation 
discussed in the Clinical Study Report. 
Time to COVID-19 related Hospitalization/ER visit or Death (disease progression) will be 
provided using a similar approach as to time to fever resolution. 
If needed, between group comparisons will be made accounting for covariates that may be 
associated with outcome which clinically significant baseline differences were observed 
despite randomization as determined by the Sponsor Safety Monitor and Principal 
Investigator using a proportional hazard (Cox) regression6.  
Proportion of subjects with no viral shedding (yes/no) using RT-PCR at Day 7, Day 15, 
and at early termination will be analyzed using the approach specified for the primary 
endpoint. 
4.3 ANALYSES OF SAFETY/TOLERABILITY 
As stated in the Clinical Protocol NI03-CV19-001 Version 4.0, all reported AEs will be 
coded using the latest version of the Medical Dictionary for Regulatory Activities 
(MedDRA). The incidence of Treatment Emergent Adverse Events (TEAEs) will be 
included in incidence tables. Events with missing onset dates will be included as treatment 
emergent. If a subject experiences more than 1 occurrence of the same AE, the occurrence 
 
5 Kaplan EL and Meier P. Nonparametric estimation from incomplete observations, Journal of the American 
Statistical Association, 53:457-481, 1959. 
6 Cox DR. Regression models with life-tables (with discussion), Journal of the Royal Statistical Society, B. 66:188-
90, 1972. 


 
 
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with the greatest severity and the closest association with the study drug will be used in the 
summary tables. SAEs, Common Terminology Criteria for Adverse Events (CTCAE) grades 
3, 4, or 5 TEAEs, and TEAEs causing discontinuation will be summarized using discrete 
summaries by system organ class and preferred term for each treatment group. All AEs will 
be listed by subject, along with information regarding onset (study day), duration, 
relationship and severity to study drug, action taken with study drug, treatment of event, and 
outcome.  
Treatment emergent adverse events (TEAEs) are defined as all adverse events that occur 
after first study treatment (either active or placebo). TEAEs will be summarized by severity 
and relationship separately. 
All adverse events that lead to death or are life threatening will be recorded as Serious 
Adverse Events in the SDTM datasets. Only non-COVID related Serious Adverse Event 
(SAE’s) will be included in the summaries provided below.  
4.3.1 Summary of Adverse Events 
All analyses of adverse events will be based on the Safety Population. A summary of the 
numbers and percentages of patients within each treatment group experiencing at least one 
treatment emergent-adverse event (TEAE) will be provided in tables. A treatment 
emergent-adverse event is any AE that occurs after any exposure to treatment.  
A Relative Risk comparison of the incidence in Camostat mesilate to Placebo will also be 
provided including a 95% Binomial Exact Confidence Interval when at least 3 subjects in 
both groups experienced the event. 
TEAEs will be defined as an AE occurring from Day 1 to end of study which is defined as 
Day 28. ‘Drug-related’ is defined as ‘possibly,’ ‘probably,’ or ‘definitely’ caused by the 
study medication. 
The AE endpoints summarized in this table are:   
• With one or more TEAE 
• With one or more drug-related TEAE 
• With one or more serious TEAEs 
• With one or more serious drug-related TEAE 
• With one or more severe TEAE 
• With one or more moderate or severe TEAE 
• TEAE with outcome of death 
• TEAE with outcome of drug related death  
• Discontinued study drug due to AE/SAE 
• Discontinued from study due to AE/SAE 
4.3.2 Specific Adverse Events 
The incidence rates (%) and event counts of TEAEs by system organ class (SOC) and by 
preferred term (PT) will be summarized by treatment group. The table will be organized 


 
 
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so that adverse event categories (SOC) are reported in upper case letters and specific 
adverse events (PT) are reported in lowercase.  
The incidence rates (%) and event counts of TEAEs by system organ class (SOC) and by 
preferred term (PT) will be summarized by treatment group restricted to events with at least 
5% incidence in either group. 
Tables will summarize the incidence rates (%) of specific TEAE PTs, sorted by descending 
incidence of PT in the active drug group.  
The incidence rates (%) and event counts of drug related TEAEs by SOC and by PT will 
be summarized by treatment group. 
The incidence rates (%) and event counts of serious drug related TEAEs by SOC and by 
PT will be summarized by treatment group. 
Tables will summarize the incidence rates (%) of serious TEAE PTs, sorted by descending 
incidence of PT in the active drug group.  
The incidence rates (%) and event counts of serious drug related TEAEs by SOC and by 
PT will be summarized by treatment group. 
4.3.3 Severity of Adverse Events 
The incidence rates (%) and event counts of severe TEAEs by SOC and by PT will be 
summarized by treatment group. 
Tables will summarize the incidence rates (%) of severe TEAE PTs, sorted by descending 
incidence of PT in the active drug group.  
Counts of drug related TEAEs in the active drug group will be summarized by severity, 
SOC and PT will be provided. Similarly, counts of drug related TEAEs in the placebo 
group will be summarized by severity, SOC and PT.  
4.3.4 Comparisons Between Subjects with and without a TEAE 
Tables will provide a comparison of demographic and baseline disease characteristics 
between patients in the active treatment group experiencing and not experiencing at least 
one Treatment Emergent Adverse Event.  
4.3.5 Safety Listings 
A comprehensive set of safety listings will be provided for all subjects in the Safety 
Analysis Set. Adverse event listings will include SOC, PT, relationship, severity, onset and 
resolution dates (and study days), and action taken. 
4.3.6 Clinical Laboratory Values 
Clinical Laboratory data at each timepoint and change from baseline will be summarized 
using descriptive statistics and shift tables (based on normative ranges). (See Protocol 
NI03-CV19-001 Section 12.3 Laboratory Assessments and PPD Lab Manual for normative 
ranges.) 


 
 
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4.3.7 Vital Signs 
Vital signs at each timepoint and change from baseline will be summarized using 
descriptive statistics. The Vital Signs collected include: Systolic/Diastolic Blood Pressure, 
pulse, temperature, and oxygen saturation. 
Temperature is collected in two ways within the e-diary. One involved a dichotomous 
variable indicating a fever the previous day was >= 100.4 degrees F, and if so, the 
temperature. In addition, the current temperature was recorded. The e-diary was only 
collected through Day 15 (i.e., maximum temperature reported is Day 14). In addition, 
temperature was collected on Day 15, 21, and 28 at clinic or phone visits.  
4.3.8 Compliance of Drug 
Subjects are instructed to take 112 of the Camostat mesilate 100 mg/Placebo tablets, 2 
tablets, 4 times per day, for 14 days. At the end of the study, subjects will return their bottle 
and the number of tablets returned will be counted. Subjects who do not return the bottle 
are assumed to have taken all the tablets, and therefore, return 0.    
Exposure to the drug will be characterized as number of tablets taken using descriptive 
statistics including number of subjects, mean, SD, Q1, median, Q3, minimum and 
maximum. 
4.4 SUBGROUP ANALYSES 
Exploratory pre-specified subgroup analysis will be performed. For these exploratory 
analyses, primary efficacy endpoint, selected secondary efficacy endpoints, and selected 
safety endpoints will be repeated and stratified according to the following classifications: 
1. Days from first COVID-19 symptom to the start of treatment, ≤ 5 days or > 5 
days 
2. Age, <55 and >=55 years 
3. Age, <65 and >=65 years 
4. Age, >=75 years 
5. Sex at birth 
6. Race, White vs. non-white 
7. Ethnicity, Hispanic vs. non-Hispanic 
8. Number of Risk Factors 
9. Site (see Site Poolability) 
10. Region (see Region Poolability) 
4.5 EXPLORATORY ANALYSES 
, The following analysis will be performed as exploratory e 
• Time to Resolution of fever (existing by day 3) 
• Time to Incidence of new fever 


 
 
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• Incidence of Fever (any Fever) after Day 0 
• Days with Fever 
• Severity of Fever 
4.6 POOLABILITY 
4.6.1 Site Poolability 
Site poolability of the primary endpoint will be evaluated using a random effects meta-
analysis approach using the R package metafor to implement the analysis7. Sites 
contributing less than 8 subjects will be pooled. After pooling (if needed), sites with 100% 
success will be given 0.5 subjects with failure and sites with 100% failure will be given 0.5 
subjects success. The True Effects will be evaluated on the logit scale and are assumed to 
be normally distributed with mean µ and variance τ2. By imposing a specified distribution 
on the site-to-site variability, i.e., a normal distribution with mean µ and variance τ2, 
sensitivity to small sample sizes in individual sites is reduced and the parameters reflecting 
the magnitude of site-to-site variability are naturally derived. The quantitative measure of 
the magnitude of heterogeneity is I2 8. I2 is the fraction of τ2 that is due to effect size 
heterogeneity (among sites), as opposed to sampling variance (within site). Fractions 25% 
and less are considered small (see reference 8). If there is significant site to site variability, 
the impact on this variability will be evaluated using a random effects logistic regression 
to test the null hypothesis that the likelihood of achieving the primary endpoint is the same 
for treated and placebo patients accounting for site-to-site heterogeneity in treatment 
effects.    
4.6.2 Region Poolability 
The distributions of regions will be summarized in the Baseline Demographic table 
According to the following four region breakdown:  
 
4.7 PROTOCOL DEVIATIONS 
The following Protocol Deviations (PD) will be captured for all subjects and recorded in the 
Protocol Deviation Log. The protocol Deviation log will capture deviations into the buckets 
 
7 Viechtbauer W. Bias and efficiency of meta-analytic variance estimators in the random-effects model. J Educ 
Behav Stat. 2005;30(3):261-293. 
8 Higgins JP, Thompson SG, Deeks JJ. Altman DG. Measuring inconsistency in meta-analyses. BMJ: 327(7414):557 


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shown in the ‘Deviation’ column of the following table. The bucketed deviations will be 
provided to the Sponsor Study Safety Monitors for review and classification per the 
Classification system outlined in Protocol Deviation Classifications. If a PD falls out of these 
categories, they will be handled on a case-by-case basis by sponsor medical monitors. 
Table 1: Protocol Deviation Classifications 
Deviation 
Classification 
Note 
Required procedure 
performed incorrectly 
Minor if not primary 
endpoint 
Required procedure not 
performed 
Minor if not primary 
endpoint 
This will not include missing e-diary temperatures. 
This will be addressed in the section in missing data 
for secondary endpoint of fever. 
Out of window visit 
Minor 
Missed Visit/Visit not 
performed 
Minor 
The window around the 72 hours from notification of 
positive COVID is +4 hours. Therefore, if notification 
occurs up to and including 76 hours, the deviation will 
be minor, otherwise, Major.  
Specimen temperature 
excursion 
Requires case by 
case via Sponsor 
Study product 
temperature excursion 
Requires case by 
case via Sponsor 
Study product not stable 
Requires case by 
case via Sponsor 
Blood not collected 
Minor 
Nasal swab not collected 
Minor 
Did not meet 
Inclusion/Exclusion 
criteria 
Major 
Informed consent 
deviations 
Major 
Incorrect study drug 
given per randomization: 
Major 
Subject fails to take 80% 
of study drug 
Major 
Subject is included in ITT and Safety Population (if at 
least one dose was taken) 
4.8 PATIENT DISPOSITION 
Patient disposition will be summarized according to Table 14.1.1.1.  
4.9 CHANGES TO THE ANALYSIS PLAN 
All revisions to the Analysis Plan will be documented in the Clinical Study Report. 


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5 APPENDIX: SHELL TABLES AND FIGURES 
This section displays mock-ups of the tables, listings, and figures that will be provided in the clinical study report.  
SAP TLF’s are provided to describe data presentations including examples of the Tables, Listings, and Figures.  
The following is a DRAFT set of Tables, Listings, and Figures. Table numbers, layouts, and units are subject to revision. 
Table 2: Listing of Tables, Listings, and Figures 
TLF Name 
TLF Number 
Popu- 
lation 
Accounting 
Table 14.1.1 - Subject Disposition by Treatment 
Table 14.1.1 
ITT 
Figure 14.1.1 – Subject Disposition by Treatment – Consort Diagram 
Figure 14.1.1 
ITT 
Baseline Demographics 
Table 14.1.2.1 - Summary of Demographic Characteristics by Treatment 
Table 14.1.2.1 
ITT 
Table 14.1.2.2 - Summary of Demographic Characteristics by Treatment 
Table 14.1.2.2 
PP1 
Table 14.1.2.3 - Summary of Demographic Characteristics by Treatment 
Table 14.1.2.3 
PP2 
Table 14.1.2.4 - Summary of Demographic Characteristics by Treatment 
Table 14.1.2.4 
SP 
Table 14.1.3 - Summary of Baseline Clinical Laboratory Data by Treatment 
Table 14.1.3 
ITT 
Table 14.1.4 - Summary of Baseline Vital Signs by Treatment 
Table 14.1.4 
ITT 
Primary/Secondary 
Table 14.2.1.1 - Primary Efficacy – Proportion of Subjects Requiring COVID-19 Hospitalization/ER visit 
Table 14.2.1.1 
ITT 
Table 14.2.1.2 - Secondary Efficacy – Proportion of Subjects Requiring COVID-19 Hospitalization/ER visit 
Table 14.2.1.2 
PP1 
Table 14.2.1.3 - Secondary Efficacy – Proportion of Subjects Requiring COVID-19 Hospitalization/ER visit 
Table 14.2.1.3 
PP2 
Table 14.2.1.4 – General Linear Model of COVID-19 Hospitalization/ER visit Adjusted by Covariates 
Table 14.2.1.4 
ITT 
Table 14.2.1.5 – General Linear Model of COVID-19 Hospitalization/ER visit Adjusted by Covariates 
Table 14.2.1.5 
PP1 
Table 14.2.1.6 – General Linear Model of COVID-19 Hospitalization/ER visit Adjusted by Covariates 
Table 14.2.1.6 
PP2 
Table 14.2.1.7 – Forest Plots of Group Difference in Primary Endpoint with 95% Confidence Intervals 
Stratified by Categorical Baseline Characteristics 
Table 14.2.1.7 
ITT 
Table 14.2.1.8 – Forest Plots of Group Difference in Primary Endpoint with 95% Confidence Intervals 
Stratified by Categorical Baseline Characteristics 
Table 14.2.1.8 
PP1 
Table 14.2.1.9 – Forest Plots of Group Difference in Primary Endpoint with 95% Confidence Intervals 
Stratified by Categorical Baseline Characteristics 
Table 14.2.1.9 
PP2 
Table 14.2.2.1 – Counts and Percentages Surviving to Days 15 and 28 Days by Treatment Group in ITT 
Table 14.2.2.1 
ITT 
Table 14.2.2.2 – Counts and Percentages Surviving to Days 15 and 28 Days by Treatment Group in PP1 
Table 14.2.2.2 
PP1 
Table 14.2.2.3 – Counts and Percentages Surviving to Days 15 and 28 Days by Treatment Group in PP2 
Table 14.2.2.3 
PP2 
Table 14.2.3.1 – Time to Resolution of Fever by Treatment in ITT Analysis Set 
Table 14.2.3.1 
ITT 
Table 14.2.3.2 – Time to Resolution of Fever by Treatment in PP1 Analysis Set 
Table 14.2.3.2 
PP1 
Table 14.2.3.3 – Time to Resolution of Fever by Treatment in PP2 Analysis Set 
Table 14.2.3.3 
PP2 
Figure 14.2.4.1 – Kaplan-Meier Time to Resolution of Fever in ITT 
Figure 14.2.4.1 
ITT 
Figure 14.2.4.2 – Kaplan-Meier Time to Resolution of Fever in PP1 
Figure 14.2.4.2 
PP1 
Figure 14.2.4.3 – Kaplan-Meier Time to Resolution of Fever in PP2 
Figure 14.2.4.3 
PP2 
Table 14.2.5.1 – Time to COVID-19 Hospitalization/ER visit or Death by Treatment in ITT 
Table 14.2.5.1 
ITT 
Table 14.2.5.2 – Time to COVID-19 Hospitalization/ER visit or Death by Treatment in PP1 
Table 14.2.5.2 
PP1 


 
 
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TLF Name 
TLF Number 
Popu- 
lation 
Table 14.2.5.3 – Time to COVID-19 Hospitalization/ER visit or Death by Treatment in PP2 
Table 14.2.5.3 
PP2 
Figure 14.2.6.1 – Kaplan-Meier Time to COVID-19 Hospitalization/ER visit by Treatment in ITT 
Figure 14.2.6.1 
ITT 
Figure 14.2.6.2 – Kaplan-Meier Time to COVID-19 Hospitalization/ER visit by Treatment in PP1 
Figure 14.2.6.2 
PP1 
Figure 14.2.6.3 – Kaplan-Meier Time to COVID-19 Hospitalization/ER visit by Treatment in PP2 
Figure 14.2.6.3 
PP2 
Table 14.2.7.1 – Proportion of Subjects with No Viral Shedding at Days 7, 15, and at Early Termination in ITT 
Table 14.2.7.1 
ITT 
Table 14.2.7.2 – Proportion of Subjects with No Viral Shedding at Days 7, 15, and at Early Termination in PP1 
Table 14.2.7.2 
PP1 
Table 14.2.7.3 – Proportion of Subjects with No Viral Shedding at Days 7, 15, and at Early Termination in PP2 
Table 14.2.7.3 
PP2 
Table 14.2.8.1 – Shift Table of Fever Severity Categories 
Table 14.2.8.1 
ITT 
Table 14.2.8.2 – Shift Table of Fever Severity Categories 
Table 14.2.8.2 
PP1 
Table 14.2.8.3 – Shift Table of Fever Severity Categories 
Table 14.2.8.3 
PP2 
Tables Safety 
  
  
Table 14.3.1.1 - Overall Summary of Adverse Events by Treatment 
Table 14.3.1.1 
SP 
Table 14.3.1.2 – Adverse Events Occurring in 5% of Subjects in Either Treatment Group by MedDRA System Organ Class and Preferred 
Term 
Table 14.3.1.2 
SP 
Table 14.3.1.3– Adverse Events Occurring in all Subjects by MedDRA System Organ Class and Preferred Term 
Table 14.3.1.3 
SP 
Table 14.3.1.4 - Incidence of Treatment Emergent Adverse Events 
Table 14.3.1.4 
SP 
Table 14.3.1.5 - Incidence of Treatment Emergent Serious Adverse Events 
Table 14.3.1.5 
SP 
Table 14.3.1.6 - Incidence of Related Treatment Emergent Adverse Events 
Table 14.3.1.6 
SP 
Table 14.3.1.7 - Incidence of Related Treatment Emergent Serious Adverse Events 
Table 14.3.1.7 
SP 
Table 14.3.1.8 - Incidence of Non-Serious Grade 3 or Grade 4 Treatment Emergent Adverse Events 
Table 14.3.1.8 
SP 
Table 14.3.1.9 - Incidence of Treatment Emergent Adverse Events Leading to Study Drug Discontinuation 
Table 14.3.1.9 
SP 
Table 14.3.1.10 to 29 Overall Summary of Adverse Events by Treatment by Subgroup 
Table 14.3.1.10 to 
29 
SP 
Listing 14.3.2.1 – Listing of Deaths 
Listing 14.3.2.1 
SP 
Listing 14.3.2.2 – Listing of Serious Adverse Events 
Listing 14.3.2.2 
SP 
Listing 14.3.2.3 – Listing of Non-Serious Grade 3 or Grade 4 Adverse Events 
Listing 14.3.2.3 
SP 
Listing 14.3.2.4 – Listing of Adverse Events Leading to Study Drug Discontinuation 
Listing 14.3.2.4 
SP 
Laboratory Assessment 
  
  
Table 14.3.4.1.1 - Summary of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment 
Table 14.3.4.1.1 
ITT 
Table 14.3.4.1.2 - Summary of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment 
Table 14.3.4.1.2 
SP 
Table 14.3.4.1.3 – Shift of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment 
Table 14.3.4.1.3 
ITT 
Table 14.3.4.1.4 – Shift of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment 
Table 14.3.4.1.4 
SP 
Figure 14.3.4.1.5 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alanine Aminotransferase (ALT) (U/L) 
Figure 14.3.4.1.5 
ITT 
Figure 14.3.4.1.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alanine Aminotransferase (ALT) (U/L) 
Figure 14.3.4.1.6 
SP 
Table 14.3.4.2.1 - Summary of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment 
Table 14.3.4.2.1 
ITT 
Table 14.3.4.2.2 - Summary of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment 
Table 14.3.4.2.2 
SP 
Table 14.3.4.2.3 - Shift of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment 
Table 14.3.4.2.3 
ITT 
Table 14.3.4.2.4 - Shift of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment 
Table 14.3.4.2.4 
SP 
Figure 14.3.4.2.5 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alanine Aminotransferase (ALT) (U/L) 
Figure 14.3.4.2.5 
ITT 
Figure 14.3.4.2.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alanine Aminotransferase (ALT) (U/L) 
Figure 14.3.4.2.6 
SP 
Table 14.3.4.3.1 - Summary of Alkaline Phosphatase (U/L) by Study Day and Treatment 
Table 14.3.4.3.1 
ITT 
Table 14.3.4.3.2 - Summary of Alkaline Phosphatase (U/L) by Study Day and Treatment 
Table 14.3.4.3.2 
SP 
Table 14.3.4.3.3 - Shift of Alkaline Phosphatase (U/L) by Study Day and Treatment 
Table 14.3.4.3.3 
ITT 
Table 14.3.4.3.4 - Shift of Alkaline Phosphatase (U/L) by Study Day and Treatment 
Table 14.3.4.3.4 
SP 
Figure 14.3.4.3.5 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alkaline Phosphatase (U/L) 
Figure 14.3.4.3.5 
ITT 
Figure 14.3.4.3.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alkaline Phosphatase (U/L) 
Figure 14.3.4.3.6 
SP 
Table 14.3.4.4.1 - Summary of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment 
Table 14.3.4.4.1 
ITT 


 
 
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TLF Name 
TLF Number 
Popu- 
lation 
Table 14.3.4.4.2 - Summary of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment 
Table 14.3.4.4.2 
SP 
Table 14.3.4.4.3 – Shift of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment 
Table 14.3.4.4.3 
ITT 
Table 14.3.4.4.4 – Shift of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment 
Table 14.3.4.4.4 
SP 
Figure 14.3.4.4.5 - Boxplots of Laboratory Parameters by Study Day and Treatment: Gamma-glutamyl Transpeptidase (GGT) (U/L) 
Figure 14.3.4.4.5 
ITT 
Figure 14.3.4.4.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Gamma-glutamyl Transpeptidase (GGT) (U/L) 
Figure 14.3.4.4.6 
SP 
Table 14.3.4.5.1 - Summary of Potassium (mmol/L) by Study Day and Treatment 
Table 14.3.4.5.1 
ITT 
Table 14.3.4.5.2 - Summary of Potassium (mmol/L) by Study Day and Treatment 
Table 14.3.4.5.2 
SP 
Table 14.3.4.5.3 - Shift of Potassium (mmol/L) by Study Day and Treatment 
Table 14.3.4.5.3 
ITT 
Table 14.3.4.5.4 - Shift of Potassium (mmol/L) by Study Day and Treatment 
Table 14.3.4.5.4 
SP 
Figure 14.3.4.5.5 - Boxplots of Laboratory Parameters by Study Day and Treatment: Potassium (mmol/L) 
Figure 14.3.4.5.5 
ITT 
Figure 14.3.4.5.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Potassium (mmol/L) 
Figure 14.3.4.5.6 
SP 
Table 14.3.4.6.1 - Summary of Platelets (109/L) by Study Day and Treatment 
Table 14.3.4.6.1 
ITT 
Table 14.3.4.6.2 - Summary of Platelets (109/L) by Study Day and Treatment 
Table 14.3.4.6.2 
SP 
Table 14.3.4.6.3 - Shift of Platelets (109/L) by Study Day and Treatment 
Table 14.3.4.6.3 
ITT 
Table 14.3.4.6.4 - Shift of Platelets (109/L) by Study Day and Treatment 
Table 14.3.4.6.4 
SP 
Figure 14.3.4.6.5 - Boxplots of Laboratory Parameters by Study Day and Treatment: Platelets (109/L) 
Figure 14.3.3.6.5 
ITT 
Figure 14.3.4.6.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Platelets (109/L) 
Figure 14.3.3.6.6 
SP 
Table 14.3.5.1.1 - Summary of Systolic Blood Pressure (mmHg) by Study Day and Treatment 
Table 14.3.5.1.1  
ITT 
Table 14.3.5.1.2 - Summary of Systolic Blood Pressure (mmHg) by Study Day and Treatment 
Table 14.3.5.1.2 
SP 
Figure 14.3.5.1.3 - Boxplots of Vital Signs by Study Day and Treatment: Systolic Blood Pressure (mmHg) 
Figure 14.3.5.1.3 
ITT 
Figure 14.3.5.1.4 - Boxplots of Vital Signs by Study Day and Treatment: Systolic Blood Pressure (mmHg) 
Figure 14.3.5.1.4 
SP 
Table 14.3.5.2.1 - Summary of Diastolic Blood Pressure (mmHg) by Study Day and Treatment 
Table 14.3.5.2.1 
ITT 
Table 14.3.5.2.2 - Summary of Diastolic Blood Pressure (mmHg) by Study Day and Treatment 
Table 14.3.5.2.2 
SP 
Figure 14.3.5.2.3 - Boxplots of Vital Signs by Study Day and Treatment: Diastolic Blood Pressure (mmHg) 
Figure 14.3.5.2.3 
ITT 
Figure 14.3.5.2.4 - Boxplots of Vital Signs by Study Day and Treatment: Diastolic Blood Pressure (mmHg) 
Figure 14.3.5.2.4 
SP 
Table 14.3.5.3.1 - Summary of Pulse Rate (beats/minute) by Study Day and Treatment 
Table 14.3.5.3.1 
ITT 
Table 14.3.5.3.2 - Summary of Pulse Rate (beats/minute) by Study Day and Treatment 
Table 14.3.5.3.2 
SP 
Figure 14.3.5.3.3 - Boxplots of Vital Signs by Study Day and Treatment: Pulse Rate (beats/min) 
Figure 14.3.5.3.3 
ITT 
Figure 14.3.5.3.4 - Boxplots of Vital Signs by Study Day and Treatment: Pulse Rate (beats/min) 
Figure 14.3.5.3.4 
SP 
Table 14.3.5.4.1 - Summary of Temperature (°C) by Study Day and Treatment 
Table 14.3.5.4.1 
ITT 
Table 14.3.5.4.2 - Summary of Temperature (°C) by Study Day and Treatment 
Table 14.3.5.4.2 
SP 
 


 
 
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DRAFT Table 14.1.2.1 
Subject Disposition by Treatment 
All Randomized Subjects 
 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=xxx) 
Subject Disposition 
n 
% 
n 
% 
n 
% 
Enrolled/Randomized 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Received Treatment 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Compliant with Study Drug (Received 80%) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Died 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Completed 28 Day Study Visitb 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Did not Complete 28 Day Study Visit 
 
 
 
 
 
 
Withdraw Reason 1 
 
 
 
 
 
 
… 
 
 
 
 
 
 
Withdraw Reason 10 
 
 
 
 
 
 
Analysis Populations 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Intent-to-Treat Population (ITT) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Per-Protocol Population #1 (PP1) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Per-Protocol Population #2 (PP2) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Safety Population 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Notes: N=Number of randomized subjects; n=Number of subjects with the specified event; NA = Not applicable. 
aA complete dose is 2 tablets 4 times a day for 14 days or 112 tablets. Compliance with study drug is subjects who finished the 14 days of treatment and took 90 or 
more tablets over 14 days. 
bThe 28-day visit is a telephone call. 
Program: xxxxx.sas                                                                          Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY 
 
 
 
 


 
 
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DRAFT Table 14.1.2.1.1 
Summary of Categorical Demographic Characteristics by Treatment 
Intent-to-Treat Population 
  
  
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=xxx) 
Variable 
Characteristic 
n 
% 
n 
% 
n 
% 
Sex at Birth 
  
Male  
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Female 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Age Group 1 
  
<55 Years 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
>=55 Years 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Age Group 2 
  
<65 Years 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
>=65 Years 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Age Group 3 
  
<75 Years 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
>=75 Years 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Time from Positive Covid-19  
Test to Randomization  
<= 5 days 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
>5 days 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Race 
  
  
  
  
  
  
White 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Black or African American 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Asian 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Native American or Alaska Native 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Native Hawaiian or Other Pacific Islander 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Multi-racial 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Unknown 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Race Group 1a 
  
White 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Non-White 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 


 
 
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DRAFT Table 14.1.2.1.1 
Summary of Categorical Demographic Characteristics by Treatment 
Intent-to-Treat Population 
Ethnicity 
  
  
Hispanic or Latino 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Not Hispanic or Latino 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Unknown 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Risk Factors 
  
  
  
  
Age 65 or Older 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Chronic Cardiac Conditions 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Chronic Liver Disease 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Chronic Lung Disease 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Diabetes Mellitus 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
 Risk Factors 
  
Hypertension 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Severe Obesity 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Number of Risk Factors 
  
  
  
  
  
1 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
2 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
3 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
4 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
5 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
6 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Northeast 
   
  
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site … 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
South 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site … 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 27 of 56 
DRAFT Table 14.1.2.1.1 
Summary of Categorical Demographic Characteristics by Treatment 
Intent-to-Treat Population 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
West 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site … 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Central 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site … 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
    Site xxx 
xxx 
xx.x 
xxx 
xx.x 
xxx 
xx.x 
Note: Denominator for percentages is the number of subjects in the intent-to-treat population for a group. 
aSubjects who did not report a race are not counted in Race Group 1. 
 
Program Source: xxxxx.sas                                                                                    Database Lock Date: DDMMMYYYY :   Run Date: DDMMMYYYY 
 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 28 of 56 
DRAFT Table 14.1.2.1.2 
Summary of Continuous Demographic Characteristics by Treatment 
Intent-to-Treat Population 
Variable 
Statistic 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=xxx) 
Age (yrs) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
Height (cm) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
Weight (kg) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
Body Mass Index (kg/mm2) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 29 of 56 
DRAFT Table 14.1.2.1.2 
Summary of Continuous Demographic Characteristics by Treatment 
Intent-to-Treat Population 
Number of Risk Factors 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 
Time from Positive Covid-19 Test to Randomization (hrs) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
Note: Denominator for percentages is the number of subjects in the safety population for a group. 
 
Program Source: xxxxx.sas                                                                           Database Lock Date: DDMMMYYYY :   Run Date: DDMMMYYYY 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 30 of 56 
DRAFT Table 14.2.1.1 
Numbers and percentages of subjects in each treatment group 
Requiring COVID-19 related hospitalization or who died due to any cause within 28 days of randomization 
ITT Analysis Set1 
  
Number and Percentage with Endpoint 
  
  
  
Camostat mesilate 
Placebo 
  
Difference and Confidence Interval 
(%)3 
Hospitalization/ER visit or death  
within 28 Days  
N 
n 
% 
N 
n 
% 
p-value2 
Diff. 
LB 
UB 
Multiple Imputation 
  
--- 
  
  
--- 
  
  
  
  
  
Completers 
  
  
  
  
  
  
  
  
  
  
Best Case 
  
  
  
  
  
  
  
  
  
  
Worse Case 
  
  
  
  
  
  
  
  
  
  
All Missing as Failure 
  
  
  
  
  
  
  
  
  
  
Notes: 
1 The Intent-to-Treat (ITT) population will include all subjects who are randomized. Subjects will be analyzed according to their study treatment assignment, not according 
to the treatment actually received (N=xxx).  
2 Unadjusted chi-square test 
3 Two-sided 95% CI 
Program Source [xxxxxxx.sas] 
 
 
Programming Note: This table will be repeated for the Per-Protocol populations(s). 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 31 of 56 
DRAFT Table 14.2.1.4 
Numbers and percentages of subjects in each treatment group 
Requiring COVID-19 related hospitalization or who died due to any cause within 28 days of randomization 
ITT Analysis Set1 
  
Number and Percentage with 
Endpoint 
  
  
  
Camostat 
mesilate 
Placebo 
  
Difference and Confidence 
Interval (%)3 
Hospitalization/ER visit or death  
within 28 Days  
N 
n 
% 
N 
n 
% 
p-
value2 
Diff. 
LB 
UB 
Adjusted for baseline covariates with clinically 
significant group differences4 
  
  
  
  
  
  
  
  
  
  
Adjusted for all covariates5 
  
  
  
  
  
  
  
  
  
  
Model identified by stepwise6 
  
  
  
  
  
  
  
  
  
  
Notes: 
1 The Intent-to-Treat (ITT) population will include all subjects who are randomized. Subjects will be analyzed according to their study treatment assignment, not according 
to the treatment actually received (N=295).  
2 Unadjusted chi-square test 
3 Two-sided 95% CI 
4 Variable list 
5 Variable list 
6 Variable list 
Program Source [xxxxxxx.sas] 
 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 32 of 56 
DRAFT Table 14.2.3 
Time to Resolution of Fever  
Intent-To-Treat Population 
Interval Pts at start #with event Censored 
Cumulative 
Resolution Rate SE‡ 
At Start 
 
 
 
 
 
Day 1 
 
 
 
 
 
… 
 
 
 
 
 
Day 14 
 
 
 
 
 
Notes: 
‡ SE Errors computed using the Peto method. No subjects died on or before Day14. 
 
Program source:  
 
 
Programming Notes: Time to Resolution of New Fever will be displayed in a similar manner. 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 33 of 56 
DRAFT Figure 14.2.4 
Kaplan-Meier Time to Resolution of Fever 
 Intent-to-Treat Population 
 
Note: This figure will include a number At-Risk Table detailing the number of subjects with events and censored for each day of 
the analysis. Day 0 will be included displaying the number of subjects in the analysis overall. 
Programming Notes: Kaplan-Meier Time to COVID-19 Hospitalization/ER visit will be displayed in similar manner. 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 34 of 56 
DRAFT Table 14.2.5 
Time to COVID-19 Hospitalization/ER visit or Death 
Intent-To-Treat Population 
Interval Pts at start #with event Censored Cumulative 
Rate 
SE‡ 
At Start 
 
 
 
 
 
Day 1 
 
 
 
 
 
… 
 
 
 
 
 
Day 28 
 
 
 
 
 
Notes: 
‡ SE Errors computed using the Peto method. 
 
Program source:  
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 35 of 56 
DRAFT Table 14.2.7 
Proportion of Subjects with No Viral Shedding at Days 7, 15, and at Early Termination 
Intent to Treat Population 
 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
 
 
n 
% 
n 
% 
Diff 
Day 7 
xxx 
xxx 
xxx 
xxx 
xxx 
Day 15 
xxx 
xxx 
xxx 
xxx 
xxx 
Day 28 or Early Termination 
xxx 
xxx 
xxx 
xxx 
xxx 
Program Source: xxxxx.sas                                              database Lock Date: DDMMMYYYY :   Run Date: DDMMMYYYY 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 36 of 56 
DRAFT Table 14.2.8.1 
Shift Table of Fever Severity Categories by Study Day and Treatment 
  
Camostat mesilate 
Placebo 
(N=xxx) 
(N=xxx) 
  
None 
Grade 1 
Grade 2 
Grade 3 
Grade 4  
Missing 
None 
Grade 1 
Grade 2 
Grade 3 
Grade 4  
Missing 
Study Day 
  
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
  
  
n 
  
  
% 
Day 0 
-- 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Day 1 
None 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Low grade 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Moderate 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
High-grade 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Hyperpyrexia 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Missing 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
… 
None 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Low grade 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Moderate 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
High-grade 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Hyperpyrexia 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Missing 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Day 14 
None 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Low grade 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Moderate 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
High-grade 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Hyperpyrexia 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 
Missing 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx 
xx.x 
xx.x 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 37 of 56 
DRAFT Table 14.1.3 
Summary of Baseline Clinical Laboratory Data by Treatment 
Intent-to-Treat Population 
Variable 
Statistic 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=xxx) 
Albumin (g/L) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
Alkaline Phosphatase (U/L) 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 
Alanie Aminotransferase (U/L) 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 
Aspartate Aminotransferase (U/L) 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 38 of 56 
DRAFT Table 14.1.3 
Summary of Baseline Clinical Laboratory Data by Treatment 
Intent-to-Treat Population 
Note: Continue for all Clinical laboratory tests: Bicarbonate, Chloride, Creatinine, Glucose, Direct Bilirubin, Total Bilirubin, GGT, LDH, Platelets, Potassium,  Sodium, 
Urea Nitrogen, White Blood Cells, Red Blood Cells, Hemoglobin, Hematocrit, Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Immature Granulocytes , 
MCV, CRP 
 
Program Source: xxxxx.sas                                                                database Lock Date: DDMMMYYYY :   Run Date: DDMMMYYYY 
 
Note: All units in the above Table are Subject to Change. 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 39 of 56 
DRAFT Table 14.1.4 
Summary of Baseline Vital Signs by Treatment 
Intent to Treat Population 
Variable 
Statistic 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=xxx) 
Temperature °C 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
Systolic Blood Pressure (mmHg) 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 
Diastolic Blood Pressure (mmHg) 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 
Pulse (breaths/mins) 
n 
xxx 
xxx 
xxx 
Mean   
x.x 
x.x 
x.x 
Standard Deviation 
x.xx 
x.xx 
x.xx 
Median 
x.x 
x.x 
x.x 
Minimum, Maximum 
x, x 
x, x 
x, x 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 40 of 56 
DRAFT Table 14.1.4 
Summary of Baseline Vital Signs by Treatment 
Intent to Treat Population 
Oxygen Saturation (%) 
n 
xxx 
xxx 
xxx 
Mean   
xx.x 
xx.x 
xx.x 
Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Minimum, Maximum 
xx, xx 
xx, xx 
xx, xx 
 
Program Source: xxxxx.sas                                                                                                                    database Lock Date: DDMMMYYYY :   Run Date: DDMMMYYYY 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 41 of 56 
DRAFT Table 14.3.1.1 
Overall Summary of Adverse Events by Treatment 
Safety Population 
 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
 
n 
% 
n 
% 
Subjects with at least onea: 
 
 
 
 
 
Treatment Emergent adverse event (TEAE)b 
xxx 
xx.x 
xxx 
xx.x 
 
Drug related TEAE 
xxx 
xx.x 
xxx 
xx.x 
 
Serious TEAE 
xxx 
xx.x 
xxx 
xx.x 
 
Serious drug related TEAE 
xxx 
xx.x 
xxx 
xx.x 
            Severe TEAE 
xxx 
xx.x 
xxx 
xx.x 
            Moderate or Severe TEAE 
xxx 
xx.x 
xxx 
xx.x 
 
TEAE with outcome of death 
xxx 
xx.x 
xxx 
xx.x 
 
TEAE with outcome of drug related death 
xxx 
xx.x 
xxx 
xx.x 
            Adverse event causing study drug withdrawal 
xxx 
xx.x 
xxx 
xx.x 
            Adverse event causing discontinuation from study 
xxx 
xx.x 
xxx 
xx.x 
Maximum severity for a subjectc: 
 
 
 
 
 
Mild (Grade 1) 
xxx 
xx.x 
xxx 
xx.x 
 
Moderate (Grade 2) 
xxx 
xx.x 
xxx 
xx.x 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 42 of 56 
DRAFT Table 14.3.1.1 
Overall Summary of Adverse Events by Treatment 
Safety Population 
 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
 
n 
% 
n 
% 
 
Severe (Grade 3) 
xxx 
xx.x 
xxx 
xx.x 
            Life-Threatening (Grade 4) 
xxx 
xx.x 
xxx 
xx.x 
            Death (Grade 5) 
xxx 
xx.x 
xxx 
xx.x 
Notes: N=Number of subjects in the Safety Population; n=Number of subjects with the specified event. 
aA subject is only counted once in each row category. 
bA subject is counted once at the maximum severity observed over all treatment-emergent adverse events. 
Program: xxxxx.sas                                                                      Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 43 of 56 
DRAFT Table 14.3.1.2 
Adverse Events Occurring in 5% of Subjects in Either Treatment Group by MedDRA System Organ Class and Preferred Term 
Safety Population 
SOC 
PT 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=X) 
 
 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Serious Adverse Events 
SOC1 
PT1 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
… 
… 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
Other (Non-serious) Adverse Events 
SOC1 
PT1 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
… 
... 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
N = number of subjects in the Safety Population.  
n = number of subjects reporting event.  
Events = total frequency of events reported. 
Program: xxxxx.sas                                                                                         Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY 
 
Programming Notes: 
Select all preferred terms/System organ classes where the % for any treatment group or overall is >= 5%.  Sort preferred terms by descending order of frequency 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
Confidential 
Page 44 of 56 
DRAFT Table 14.3.1.3.1 
Adverse Events Occurring in All Subjects by MedDRA System Organ Class and Preferred Term 
Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=X) 
 
 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Serious Adverse Events 
SOC1 
PT1 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
… 
... 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
Other (Non-serious) Adverse Events 
SOC1 
PT1 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
… 
… 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
N = number of subjects in the Safety Population.  
n = number of subjects reporting event.  
Events = total frequency of events reported. 
Program: xxxxx.sas                                                                                                                                              Database Lock Date: DDMMMYYYY:  Run Date: 
DDMMMYYYY 
 
Programming Notes: 
Select all preferred terms/System organ classes.  Sort preferred terms by descending order of frequency 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
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DRAFT Table 14.3.1.3.2 
Adverse Events Occurring in All Subjects by MedDRA Preferred Term 
Safety Population 
MedDRA Preferred Term 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=X) 
 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
PT1 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
... 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
… 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
xx 
xx.x 
xxx 
N = number of subjects in the Safety Population.  
n = number of subjects reporting event.  
Events = total frequency of events reported. 
Program: xxxxx.sas                                                               Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY 
 
Programming Notes: 
Select all preferred terms- Sort preferred terms by descending order of frequency in Active group. 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
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Page 46 of 56 
DRAFT Table 14.3.1.4 
Incidence of Treatment Emergent Adverse Events by MedDRA System Organ Class and Preferred Term 
Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
All Subjects 
(N=X) 
 
 
n 
% 
n 
% 
n 
% 
Any System Organ Class 
Any Preferred Term 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
SOC1 
Any Preferred Term 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
PT1 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
PT2 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
Continue for all PT 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
SOC2 
Any Preferred Term 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
PT1 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
PT2 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
Continue for all PT 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
N = number of subjects in the Safety Population.  
n = number of subjects reporting event.  
Program: xxxxx.sas                                                                                                                                              Database Lock Date: DDMMMYYYY:  Run Date: 
DDMMMYYYY 
 
Programming Notes: 
Sort by System organ class and preferred term 
 


 
 
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Page 47 of 56 
Table 14.3.1.5: Incidence of Treatment Emergent Serious Adverse Events 
Programming Notes:  Use the same layout as Table 14.3.1.4 – Select only Serious Adverse Events 
Table 14.3.1.6: Incidence of Related Treatment Emergent Adverse Events 
Programming Notes:  Use the same layout as Table 14.3.1.4 – Select only Adverse Events Related to Study Drug 
Table 14.3.1.7: Incidence of Related Treatment Emergent Serious Adverse Events 
Programming Notes:  Use the same layout as Table 14.3.1.4 – Select only Serious Adverse Events Related to Study Drug 
Table 14.3.1.8: Incidence of Grade 3 or Grade 4 or Grade 5 Treatment Emergent Adverse Events 
Programming Notes:  Use the same layout as Table 14.3.1.4 – Select only Treatment Emergent Adverse Events Graded as Grade 3 or Grade 4 or Grade 5  
Table 14.3.1.9: Incidence of Treatment Emergent Adverse Events Leading to Study Drug Discontinuation 
Programming Notes:  Use the same layout as Table 14.3.1.4 – Select only Treatment Emergent Adverse Events leading to study drug discontinuation 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
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Page 48 of 56 
DRAFT Table 14.3.2.1 
Listing of Deaths 
Subject 
ID 
Treatment 
Adverse Event 
Description 
Onset Date/ 
Resolution Date 
Study 
Day of 
Onset/ 
Duration 
Severity 
Relationship 
to Study 
Treatment 
Outcome 
Action Taken with 
Study Treatment 
MedDRA® 
System Organ 
Class 
MedDRA® 
Preferred 
Term 
xxxxxx 
Camostat 
mesilate  
xxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YY/ 
YY 
XXXXX 
XXXXXX 
XXXXXX 
XXXXXXX 
XXXXXXX 
XXXXXXX 
xxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YY/ 
YY 
XXXXX 
XXXXXX 
XXXXXX 
XXXXXXX 
XXXXXXX 
XXXXXXX 
xxxxxx 
Placebo 
xxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YY/ 
YY 
XXXXX 
XXXXXX 
XXXXXX 
XXXXXXX 
XXXXXXX 
XXXXXXX 
xxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
YY/ 
YY 
XXXXX 
XXXXXX 
XXXXXX 
XXXXXXX 
XXXXXXX 
XXXXXXX 
Program: xxxxx.sas                                                                                                                                                   Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY 


 
 
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Version 2.0 | March 31, 2021 
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Table 14.3.2.2: Listing of Serious Adverse Events 
Programming Notes:  Use the same layout as Table 14.3.2.1 – Select only Serious Adverse Events 
Table 14.3.2.3: Listing of Grade 3 or Grade 4 or Grade 5 Adverse Events 
Programming Notes:  Use the same layout as Table 14.3.2.1 – Select only Grade 3 or Grade 4 or Grade 5 Adverse Events 
Table 14.3.2.4: Listing of Adverse Events Leading to Study Drug Discontinuation 
Programming Notes:  Use the same layout as Table 14.3.2.1 – Select only Adverse Events leading to study drug discontinuation 
  
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
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Page 50 of 56 
DRAFT Table 14.3.4.1 
Summary of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment 
Intent-to-Treat Population 
  
Camostat mesilate (N=xxx) 
Placebo (N=xxx) 
Study Day 
Statistic 
Observed 
Change 
Observed 
Change 
Baseline (Day 1)a 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Std Deviation 
xxx.x. 
xxx.x. 
xxx.x. 
xxx.x. 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
Day 7 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Std Deviation 
xxx.x. 
xxx.x. 
xxx.x. 
xxx.x. 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
Day 15 
n 
xxx 
xxx 
xxx 
xxx 
Mean 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Std Deviation 
xxx.x. 
xxx.x. 
xxx.x. 
xxx.x. 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
Notes: N=Number of subjects in the Intent-toTreat Population; n=Number of subjects with an assessment at the specified time point. 
Change=Change from Baseline; aBaseline is the last value prior to treatment for a subject. It is used in the change from baseline. 
Program: xxxxx.sas           Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY                                                                                 
 


 
 
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Table 14.3.4.1.2: Summary of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.2 – change population to the safety population 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
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Page 52 of 56 
DRAFT Table 14.3.4.1.3 
Shift of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment 
 
Camostat mesilate 
(N=xxx) 
Placebo 
(N=xxx) 
 
Low 
Normal 
High 
Missing 
Low 
Normal 
High 
Missing 
Study Day 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Baseline 
--- 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
Day 15 
Low 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
Normal 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
High 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
Missing 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
xx 
xx.x 
Notes: N=Number of subjects in the Intent-to Treat Population;  
n=Number of subjects with an assessment at the specified time point. 
aBaseline is the last value prior to treatment for a subject.  
Program: xxxxx.sas                                                          Database Lock Date: DDMMMYYYY:  Run Date: DDMMMYYYY 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
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Table 14.3.4.1.4: Shift of Alanine Aminotransferase (ALT) (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 –  change population to the safety population 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
Version 2.0 | March 31, 2021 
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Page 54 of 56 
Alanine Aminotransferase (ALT) (U/L) 
DRAFT Figure 14.3.4.1.5 
Boxplots of Laboratory Parameters by Study Day and Treatment: Alanine Aminotransferase (ALT() (U) /L) 
Intent-to-Treat Population 
2000 
 
 
 
 
 
 
1500 
  
 
 
1000 
 
 
 
 
 
500 
 
 
 
 
0 
Baseline 
 
 
 
Treatment Group 
 
 
 
 
Study Day 
Camostat 
mesilate (N=xxx) 
 
 
 
       Day 15 
 
 
Placebo 
 
 
 


 
 
NI03-CV19-001: Statistical Analysis Plan 
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Figure 14.3.4.1.6: Boxplots of Laboratory Parameters by Study Day and Treatment: Alanine Aminotransferase (ALT) (U/L) – Safety 
Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.5 –  change population to the safety population 
Table 14.3.4.2.1 - Summary of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.1 –  Change ALT to AST 
Table 14.3.4.2.2 - Summary of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.1 –  change ALT to AST and population to the safety population 
Table 14.3.4.2.3 – Shift of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 –  Change ALT to AST 
Table 14.3.4.2.4 - Shift of Aspartate Aminotransferase (AST) (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 –  change ALT to AST and population to the safety population 
Figure 14.3.4.2.5 – Boxplots of Laboratory Parameters by Study Day and Treatment: Aspartate Aminotransferase (AST) (U/L) – ITT 
Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.5 –  Change ALT to AST 
Figure 14.3.4.2.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Aspartate Aminotransferase (AST) (U/L) – Safety 
Population 
Programming Notes:  Use the same layout as Table 14.3.4.1,5 –  change ALT to AST and population to the safety population 
Table 14.3.4.3.1 - Summary of Alkaline Phosphatase (U/L) by Study Day and Treatment – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.1 – Change ALT to AST 
Table 14.3.4.3.2 - Summary of Alkaline Phosphatase (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.1 – change ALT to AST and population to the safety population 
Table 14.3.4.3.3 – Shift of Alkaline Phosphatase (U/L) by Study Day and Treatment – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 – Change ALT to AST 
Table 14.3.4.3.4 - Shift of Alkaline Phosphatase (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 – change ALT to AST and population to the safety population 
Figure 14.3.4.3.5 – Boxplots of Laboratory Parameters by Study Day and Treatment: Alkaline Phosphatase  (U/L) – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.5 –  Change ALT to AST 
Figure 14.3.4.3.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Alkaline Phosphatase  (U/L) – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1,5 –  change ALT to AST and population to the safety population 


 
 
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Version 2.0 | March 31, 2021 
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Table 14.3.4.3.1 - Summary of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.1 – Change ALT to AST 
Table 14.3.4.3.2 - Summary of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.1 – change ALT to AST and population to the safety population 
Table 14.3.4.3.3 – Shift of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment – ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 – Change ALT to AST 
Figure 14.3.4.3.4 - Shift of Gamma-glutamyl Transpeptidase (GGT) (U/L) by Study Day and Treatment – Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.3 – change ALT to AST and population to the safety population 
Figure 14.3.4.3.5 – Boxplots of Laboratory Parameters by Study Day and Treatment: Gamma-glutamyl Transpeptidase (GGT) (U/L) – 
ITT Population 
Programming Notes:  Use the same layout as Table 14.3.4.1.5 – Change ALT to AST 
Figure 14.3.4.3.6 - Boxplots of Laboratory Parameters by Study Day and Treatment: Gamma-glutamyl Transpeptidase (GGT) (U/L) – 
Safety Population 
Programming Notes:  Use the same layout as Table 14.3.4.1,5 – change ALT to AST and population to the safety population