Clinical trial NCT04524663
Conditions: Covid19
Sponsor: Stanford University
Start date: 2020-12-19; Completion date: 2021-05-15
Enrollment: 49 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate the efficacy of oral Foipan® (camostat mesilate) compared with the current standard of care in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with mild-moderate COVID-19 disease.

Patients will attend 4 study visits over a period of up to 28 days.

Detailed description:

Arms: arm 1: Patients will receive camostat mesilate for 10 days in addition to standard of care treatment. arm 2: Study participants will receive placebo to match camostat mesilate for 10 days in addition to standard of care treatment.
Interventions: intervention 1: Camostat Mesilate intervention 2: Placebo intervention 3: Standard of Care Treatment
Intervention descriptions: intervention 1: Camostat Mesilate administered as oral tablets intervention 2: Placebo to match camostat mesilate intervention 3: Standard of Care Treatment for COVID-19 Infection

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral 
Camostat Mesilate Compared to Standard of Care in Subjects With Mild-
Moderate COVID-19 
Study Protocol and Statistical Analysis Plan 
NCT04524663 
December 4, 2020 


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A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Camostat 
Mesilate Compared to Standard of Care in Subjects with Mild-Moderate COVID-19 
 
 
PROTOCOL NUMBER: 
IND 
 COPS-2003 
 
 
INVESTIGATIONAL 
camostat mesilate/camostat/Foipan 
PRODUCT: 
 
PROTOCOL VERSION 
Version 4.0 
/DATE: 
04 DEC 2020 
 
Amendment Version 3: 2 OCT 2020 
Amendment Version 2: 15 JUL 2020 
Amendment Version 1.2: 14 JUL 2020 
Original Version 1: 22 MAY 2020 
 
IND SPONSOR: Dr. Julie Parsonnet, M.D. 
CONTACT INFORMATION: 
Principal Investigator: 
Julie Parsonnet, MD, 
Professor, Stanford University, Division of Infectious Diseases and Geographic Medicine 
Lane Building, Suite L134, 300 Pasteur Drive, Stanford, CA 94305 
Email: parsonnt@stanford.edu 
Phone: 1-650-725-4561 
 
Chaitan Khosla, Ph.D. 
Baker Family co-Director, Stanford ChEM-H 
Professor of Chemistry and Chemical Engineering 
Email: khosla@stanford.edu 
Mobile phone: 
 
 
Sponsor’s Representative: 
 MS, RAC 
Director, Regulatory Affairs 
Pharmaceuticals & Healthcare 
Intertek Health Sciences Inc. 
 
Houston, Texas 
 
Email: 
 
Phone: 
 


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PROTOCOL SIGNATURE PAGE 
 
 
 
Protocol Title: A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral 
Camostat Mesilate Compared to Standard of Care in Subjects with Mild-Moderate 
COVID-19 
 
Protocol/IND Number: 
COPS-2003/
 
 
 
Protocol Version/Date: 
Version 4.0 / 04 DEC 2020 
 
 
Sponsor Name: Stanford University School of Medicine, Stanford, CA 94305 
 
 
Declaration of Investigator 
 
I confirm that I have read the above-mentioned protocol and its attachments. I agree to conduct the 
described trial in compliance with all stipulations of the protocol, regulations and ICH E6 Guideline 
for Good Clinical Practice (GCP). 
 
 
 
 
Principal Investigator Name:  
 
 
 
Principal Investigator Signature:  
 
 
 
Date:  
 
Date (MM/DD/YYYY) 


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TABLE OF CONTENTS 
1 
SYNOPSIS .............................................................................................................................. 6 
2 
INTRODUCTION ................................................................................................................ 13 
2.1 
Background Information ........................................................................................... 13 
2.2 
Preclinical and In Vitro Experiences ........................................................................ 13 
2.3 
Clinical Experience ..................................................................................................... 14 
2.4 
Phase 1 Study Steady State Exposure ........................................................................ 15 
2.5 
Rationale for 200 mg dose four times per day given one hour before meals ........ 16 
2.6 
Rationale for 10-day Dosing Regimen ...................................................................... 16 
2.7 
Rationale for the Current Study ............................................................................... 16 
3 
DESIGN ................................................................................................................................ 17 
4 
OBJECTIVES ...................................................................................................................... 17 
4.1 
Primary Objective .......................................................................................................17 
4.2 
Secondary Objectives ................................................................................................. 17 
5 
SUBJECT POPULATION ...................................................................................................18 
5.1 
Inclusion Criteria ........................................................................................................ 18 
5.2 
Exclusion Criteria ....................................................................................................... 19 
5.3 
Removal of Subjects from Treatment ....................................................................... 20 
6 
STUDY TREATMENT - CAMOSTAT MESILATE ........................................................ 21 
6.1 
Study Drug .................................................................................................................. 21 
6.2 
Administration of Camostat mesilate or placebo ..................................................... 21 
6.3 
Outpatient Camostat mesilate Dosing ...................................................................... 21 
6.4 
Drug Accountability ................................................................................................... 22 
6.5 
Treatment Compliance .............................................................................................. 22 
6.6 
Treatment Precautions ................................................................................................ 22 
6.7 
Clinically Significant Adverse Reactions .................................................................. 22 
6.8 
Other Adverse Reactions ............................................................................................22 
6.9 
Prohibited Concomitant Therapy ............................................................................. 23 
7 
STUDY PROCEDURES ...................................................................................................... 23 
7.1 
Day 1 (PRE-DOSE) .................................................................................................... 23 
7.2 
Day 1 (FIRST DOSE AND POST-DOSE) ................................................................ 24 
7.3 
Days 5, 10, 28 (Follow-up) or Early Termination .................................................... 24 
8 
EFFICACY, PHARMACOKINETICS AND SAFETY ASSESSMENTS ...................... 25 
8.1 
Efficacy Assessments .................................................................................................. 25 
8.2 
Required Resistance Testing ...................................................................................... 25 
8.3 
Safety Assessments ..................................................................................................... 25 
8.3.1 Adverse Events ................................................................................................. 26 


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8.3.2 Definition of an Adverse Event. ........................................................................ 26 
8.3.3 Evaluating and Reporting of Adverse Events ................................................... 27 
8.3.4 Serious Adverse Events (SAEs) ........................................................................ 28 
8.3.5 Definition of Serious Adverse Events ............................................................... 28 
8.3.6 SAE Reporting Requirements to the Sponsor ................................................... 28 
8.4 
Suspected Unexpected Serious Adverse Reactions (SUSARs) ................................. 29 
8.4.1 Reporting SUSARs to the FDA: IND Safety Reports ....................................... 29 
8.5 
Clinical Laboratory Abnormalities and Other Abnormal Assessments ................. 29 
8.6 
Handling of Overdose ................................................................................................. 30 
9 
STATISTICAL METHODS ................................................................................................ 30 
9.1 
General Considerations ............................................................................................... 30 
9.2 
Sample size justification .............................................................................................. 30 
9.3 
Demographic and Baseline Characteristics ............................................................... 30 
9.4 
Analysis Populations .................................................................................................... 31 
9.5 
Stratification, Subgroup Analysis and Pooled Analysis ............................................ 31 
9.6 
Efficacy Endpoint Analysis ......................................................................................... 31 
9.7 
Descriptive analyses ..................................................................................................... 31 
9.8 
Primary efficacy analysis ............................................................................................ 31 
9.9 
Secondary efficacy analyses ........................................................................................ 32 
9.10 Safety Analysis ............................................................................................................. 32 
10 DATA SAFETY MONITORING ........................................................................................ 33 
10.1 Data and Safety Monitoring Committee ................................................................... 33 
10.2 Interim Analysis ........................................................................................................... 34 
11 RECORDING AND COLLECTION OF DATA ............................................................... 34 
11.1 Case Report Form ....................................................................................................... 34 
11.2 Study Files and Subject Source Documents .............................................................. 35 
11.3 Monitoring ................................................................................................................... 35 
11.4 Audit ............................................................................................................................. 35 
11.5 Retention of Data ......................................................................................................... 36 
12 ETHICS ................................................................................................................................. 36 
12.1 Ethics Committee ........................................................................................................ 36 
12.2 Subject Information and Consent .............................................................................. 36 
13 GENERAL CONSIDERATIONS ........................................................................................ 36 
13.1 Discontinuation of the Study ...................................................................................... 36 
13.2 Use of Information and Publication ............................................................................ 37 
14 SCHEDULE OF ASSESSMENTS ....................................................................................... 38 
15 APPENDIX ............................................................................................................................ 38 


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List of Abbreviations 
ACE2 angiotensin-converting enzyme 2 
ADR adverse drug reaction 
AE adverse event 
ALP alkaline phosphatase 
ALT alanine aminotransferase 
AST aspartate aminotransferase 
CBC complete blood count 
CDC Centers for Disease Control and Prevention 
Cmax maximum plasma concentration 
CMC chemistry, manufacturing, and controls 
COVID-19 Coronavirus Disease 2019 
CTRU Clinical and Translational Research Unit 
CYP cytochrome P450 
DSMC Data and Safety Monitoring Committee 
ED emergency department 
FDA Food and Drug Administration 
FOY-251 4-(4-guanidinobenzoyloxy)phenylacetic acid 
GMP Good Manufacturing Practice 
HHS Department of Health and Human Services 
HPLC high performance liquid chromatography 
IC50 half maximal inhibitory concentration 
ICH International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
IND Investigational New Drug 
IRB Institutional Review Board 
IUPAC International Union of Pure and Applied Chemistry 
JP Japanese Pharmacopeia 
LD50 median lethal dose 
LFT liver function test 
NOAEL no-observed-adverse-effect level 
NOEL no-observed-effect level 
NSAID nonsteroidal anti-inflammatory drug 
p.o. oral (per os) 
PSUR Periodic Safety Update Report 
PTP press through packaging 
qPCR quantitative polymerase chain reaction 
RH relative humidity 
SAE serious adverse event 
SARS severe acute respiratory syndrome 
T1/2 half-life 
TID 3 times daily 
TLC thin layer chromatography 
U.S. United States 


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1 SYNOPSIS 
 
Title 
A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of 
Oral Camostat Mesilate Compared to Standard Supportive Care in 
Subjects with Mild-Moderate COVID-19 
Design 
This is a Phase 2 Double Blinded, Placebo Controlled Study evaluating 
the efficacy and safety of oral camostat mesilate in adult subjects with 
PCR-positive, mild-moderate COVID-19 infections. 
Subjects will be randomized to receive either camostat mesilate +current 
Standard of Care (SOC) or SOC + placebo. 
Study participants will be randomly assigned 1:1 to two tablets of oral 
camostat mesilate (100 mg/tablet) four times a day plus SOC or SOC plus 
placebo for 10 days. 
Subjects in the SOC arm will receive placebo. 
The total anticipated duration of the study for each patient is 28 days. 
Objectives 
Primary Objective 
To evaluate the efficacy of oral Foipan (camostat mesilate, 200 mg, four 
times a day for ten days) compared with placebo plus current standard of 
care in reducing the area under the curve (AUC) through day 10 of viral 
shedding of SARS-CoV-2 virus in patients with mild-moderate COVID- 
19. 
Secondary Objectives 
1. To evaluate the efficacy of oral camostat mesilate plus SOC 
compared with placebo plus current SOC in reducing the AUC up 
through day 28 of viral shedding of SARS-CoV-2 virus in patients 
with mild-moderate COVID-19. 
2. To evaluate the efficacy of oral camostat mesilate plus SOC 
compared with placebo plus current SOC in reducing the duration 
of viral shedding of SARS-CoV-2 virus in patients with mild- 
moderate COVID-19. 
3. To evaluate the efficacy of oral camostat mesilate plus SOC 
compared with placebo plus SOC in reducing the duration of 
symptoms, hospitalizations or ED visits, or mortality in patients 
with mild-moderate COVID-19. 
4. To evaluate the proportion of individuals with a negative SARS- 
CoV2 RT PCR test on days 7, 14 and 28. 
5. To assess the safety and tolerability of camostat mesilate in this 
subject population. 
6. To assess the development of antibodies against SARS-CoV-2 
7. To determine drug levels at one time point on day 5 using the 
current dosing scheme. 
Endpoints 
Primary Endpoint: 


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AUC of shedding of SARS-CoV-2 virus calculated using the RT-PCR 
measures of viral load from self-collected nasal swabs on days 1-10. 
Secondary Endpoints 
1. AUC of shedding of SARS-CoV-2 virus calculated using the RT- 
PCR measures of viral load from self-collected nasal swabs on 
days 1-10, 14, 21, and 28. 
2. Time until cessation of shedding of SARS-CoV-2 virus, defined as 
the time in days from randomization to the first negative RT-PCR 
result of self-collected nasal swabs that is followed by only 
negative results (i.e. no later positive results are observed). 
3. RT-PCR results from oropharyngeal swabs collected on Days 1, 5, 
10 and 28 
4. Clinical worsening of COVID-19 in symptomatic subjects 
(clinical worsening defined the development of respiratory distress 
or symptoms that require hospitalization) 
5. Adverse events AEs and clinical laboratory tests for systemic 
safety including hematology and clinical chemistry 
6. Mortality 
7. Development of antibodies to SARS-CoV-2 
8. Time until resolution of symptoms (resolution of symptoms 
defined as absence of moderate or severe symptoms for at least 24 
hours for those reporting moderate or severe symptoms at 
baseline). 
9. Drug level on day five, one hour after a dose taken on an empty 
stomach. 
Study Sites 
Stanford University School of Medicine 
Planned 
Enrollment 
120 (60 in the camostat mesilate + SOC group and 60 in the placebo + 
SOC group) 
Study Population 
Adults with confirmed SARS-CoV-2 who are experiencing mild- 
moderate symptoms 
Subject Entry 
Criteria 
Inclusion Criteria (all questions must be answered YES) 
1.  Adults (18-80) 
2. Diagnosis of COVID-19 disease: 
a. Presence of mild-moderate symptoms without signs of 
respiratory distress (as defined by SpO2 <=94% on room 
air, RR >=24, HR >=110), with FDA-cleared molecular 
diagnostic assay positive for SARS-CoV-2 within 72 hours 
from initial swab to the time of commencing informed 
consent: Disease is defined as having at least 2 of the 
following symptoms that are of moderate or 
higher severity as scored on the COVID Outpatient 
Symptom Scale (COSS): 
i. Fever (>98.7F) 


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ii. Cough 
iii. Shortness of breath 
iv. Fatigue 
v. Headache 
vi. Body ache 
vii. Joint pain 
viii. Chest pressure 
ix. Abdominal pain 
x. Sore throat 
xi. Nasal congestion 
xii. Chills 
xiii. Feeling hot or feverish 
xiv. Runny nose 
xv. Loss of taste 
xvi. Loss of smell 
xvii. Diarrhea 
xviii. Nausea 
xix. Vomiting 
xx. Rash 
b. The date of onset of the first of the above symptoms will 
be documented. 
3. Subject or their legal representative understands the requirements 
of the study and provides written informed consent prior to 
undergoing any treatment-related procedures. 
4. If male, subject must fulfill one of the following criteria: 
a. Be sterile (e.g., have had a vasectomy at least 6 months 
prior to Day 1 dosing), OR, 
b. Agree not to donate sperm during the study and for seven 
days following the last dose of study medication, AND, 
c. Agree to strictly adhere to the following contraceptive 
measures during the study and for seven days following the 
last dose of study medication: 
i. Abstain from sexual intercourse 
ii. Use a condom during sexual intercourse with a 
female of child-bearing potential. In addition, the 
female partner must use another form of 
contraception (e.g. intrauterine device [IUD], 
diaphragm with spermicide, oral contraceptives, 
injectable progesterone, or subdermal implants). 


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5. If female, subject must fulfill one of the following criteria: 
a. Be unable to bear children (have not had a period for ≥ 12 
consecutive months, have had her uterus or ovaries 
removed, or have had a tubal ligation), OR, 
b. Must ensure that their male partner is incapable of 
fathering a child (e.g., has had a vasectomy at least 6 
months prior to study entry), OR, 
c. If she is of childbearing potential will strictly adhere to the 
following contraceptive measures during the study and for 
seven days following the last dose of study medication: 
i. Abstain from sexual intercourse, OR, 
ii. Must ensure that their male partner agrees to use a 
condom during sexual intercourse and agree to use 
an approved method of contraception (e.g., IUD, 
diaphragm with spermicide, oral contraceptives, 
injectable progesterone, or subdermal implants). 
d. Agrees to stop breast-feeding prior to first dose of study 
drug and through seven days after completing therapy. 
e. Has a negative urine pregnancy test at screening. 
6. When such testing is available, subject will be confirmed to be 
SARS-CoV2 infected using a rapid (<30 minute) SARS-CoV2 
point-of-care test; if such a test is not available, this step of 
screening will be omitted. 
7. Subject agrees to maintain home or other quarantine as 
recommended by the study physician, except to visit the study site 
as required by the protocol. 
8. Subject agrees to take daily nasal swabs (anterior nares) for Day 1 
to Day 10 and Day 14, 21, and 28 using the study provided material 
and bring these to their follow up visits on days 5, 10 and 28. 
9. Subject agrees to record daily symptoms, temperature, and oxygen 
saturation using the study provided materials. 
10. Subject agrees to return to the study site for follow-up visits on Day 
5, 10 and 28. The study site will be staffed by trained healthcare 
providers wearing full personal protective equipment and study site 
equipment will be disinfected between patients according to the 
same protocols as a clinical setting. Subjects will be wearing masks, 
will be appropriately spaced, and the number of subjects assessed 
at each time will be limited. 
11. Members of the same household may participate in the study as long 
as the inclusion and exclusion criteria are met. 
Exclusion Criteria (all questions must be answered NO) 
12. Subject has a concomitant bacterial respiratory infection as 
documented by a respiratory culture with microbiologic growth. 


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NOTE: Subjects on empirical antibiotic treatment for possible 
but unproven bacterial pneumonia, but who are positive for 
SARS-CoV-2, are allowed in the study. 
13. Previous use of antiviral drugs that may be active against Covid- 
19. 
14. Subject is using adrenocorticosteroids (except topical or inhaled 
preparations or oral preparations equivalent to or less than 10 mg 
of oral prednisone) or immunosuppressive or immunomodulatory 
drugs (e.g., immunosuppressants, anticancer drugs, interleukins, 
interleukin antagonists or interleukin receptor blockers). 
NOTE: Treatment of study participants following 
institutional COVID-19 treatment policies or guidelines, 
including the use of immunomodulatory medications, is 
permitted. This excludes treatment with agents that have 
the potential for direct antiviral activity, including 
convalescent plasma and NO, and co-enrollment into other 
clinical studies that evaluate investigational agents for 
COVID-19. 
15. Subject has gout, a bleeding disorder, or a serious chronic disease 
(e.g., uncontrolled human immunodeficiency virus [HIV], cancer 
requiring chemotherapy within the preceding 6 months, and/or 
moderate or severe hepatic insufficiency). 
16. Subject uses an anticoagulant medication including heparin, 
coumadin, a factor Xa inhibitor (xarelto, apixaban) or a thrombin 
inhibitor (Pradaxa). Aspirin is not an indication for exclusion 
17. Has previously received camostat mesilate within the past 30 days. 
18. Has renal insufficiency requiring hemodialysis or continuous 
ambulatory peritoneal dialysis (CAPD). 
19. Has liver impairment greater than Child Pugh A. 
20. Has a history of alcohol or drug abuse in the previous 6 months. 
21. Has a psychiatric disease that is not well controlled where 
controlled is defined as: stable on a regimen for more than one 
year. 
22. Has taken another investigational drug within the past 30 days. 
23. Is deemed by the Investigator to be ineligible for any reason. 
Randomization 
Following consent, those subjects meeting all entry criteria will be 
randomized in a 1:1 ratio. 
Treatment Arm: camostat mesilate dose + SOC 
Control Arm: placebo + SOC 
Randomization will be stratified by age (>=50 and <50 years old) and sex 


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Treatment 
Regimen for 
Camostat mesilate 
(Standard dose) 
• 
Camostat mesilate and placebo tablets will be administered orally, 
one hour prior to eating, and at bedtime. 
• 
The total duration of treatment is expected to be 10 days. 
Duration of Study 
Participation 
The total anticipated duration of the study for each patient is 28 days. 
Statistical 
Methods 
To address our primary objective, the AUC SARS-CoV2 viral RNA 
levels during follow-up will be estimated using the linear trapezoidal 
method, and mean AUC levels compared between groups using a linear 
regression model regressing log(AUC) on treatment arm, site, age, and 
sex. The test will be performed at the two-sided alpha = 0.05 level of 
significance. 
Time until viral shedding cessation will be compared between the two 
treatment arms using a two-sided Wald test derived from a Cox 
proportional hazards model adjusted for age and sex. The test will be 
performed at the two-sided alpha = 0.05 level of significance. The hazard 
ratio for shedding cessation will be estimated, along with its 95% 
confidence interval, from a Cox proportional hazards model. We will use 
this same approach to model the secondary endpoints of clinical 
worsening and mortality. If the proportional hazards assumption is not 
met, we will consider an extended Cox model that relaxes the 
proportional hazards assumption. The log rank test will also be 
performed. 
The distribution of viral shedding cessation will be estimated using the 
Kaplan-Meier method, and Kaplan-Meier curves will be presented for 
each treatment arm. Median time to shedding cessation along with 95% 
confidence intervals will be presented for each treatment arm. 
Median time to resolution of symptoms will be estimated along with 95% 
confidence intervals by each arm. The frequency of adverse events and 
serious adverse events will be tabulated by type and by treatment arm. 
AEs will be compared by arm using the Chi-squared test or Fisher’s exact 
test, as appropriate, in the safety analysis set. 
An interim analysis for safety and overwhelming efficacy will be 
performed once 50% of patients have 24 hours of follow-up complete. 
Individual 
Stopping Rule 
A subject should be removed from camostat mesilate treatment if one of 
the following criteria is met: 
• 
AST or ALT > 8 x ULN 
• 
ALT or AST > 3 x ULN AND total bilirubin > 2X ULN 
• 
AST or ALT > 3 x ULN AND patient has right upper quadrant pain or 
eosinophilia 
• 
Platelet count <75,000 cells/mm3 


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• 
Absolute neutrophil count <800 cells/mm3 
• 
Hemoglobin <11 g/dL for women and <12 g/dL for men 
• 
Serum creatinine concentration ≥1.5× ULN 
• 
Confirmed creatinine clearance (CrCl) < 50 mL/min by Cockcroft- 
Gault 
• 
Hypersensitivity 
• 
Shock or anaphylactoid symptoms 
• 
Hepatic function disorder or jaundice (both incidences unknown). 
• 
Hepatic function disorder accompanied by remarkable increase of γ- 
GTP, Al-P, or jaundice. 
• 
Hyperkalemia (incidence unknown). Severe hyperkalemia may occur. 
A subject whose treatment is terminated should remain in the study for 
appropriate follow up assessments. 
Study 
Measurements: 
Efficacy, Safety 
Primary Measurement (Efficacy): 
1. Nasal swab for RT-PCR taken daily from Day 1 to Day 10, and 
Days 14, 21, and 28. 
Secondary Measurements (Safety and Efficacy): 
2. Symptom improvement or worsening: Subjects will fill in a diary 
daily, recording the following symptoms: 
a. Cough 
b. Sore throat 
c. Headache 
d. Nasal congestion 
e. Body aches and pains 
f. Fatigue 
g. Oral temperature taken at a consistent time each day and at 
least four hours after ingesting the most recent antipyretic 
(acetaminophen or NSAID) 
h. Dyspnea 
i. Shaking chills 
j. Loss of taste 
k. Loss of smell 
l. GI symptoms including nausea, vomiting, and/or diarrhea 
m. Chest pain 
3. Safety as assessed by: 
a. Observed and reported adverse events 
b. Clinical laboratory evaluations of blood on Days 1, 5, and 
10 
c. Physical Examination at screening (pre-dose Day 1), Days 
5, 10 and 28 
d. Daily vital signs: pulse oximetry, heart rate, and 
temperature. 


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4. Blood for determination of antibodies to SARS-CoV-2 will be 
obtained on Days 1 and 28. 
 
 
2 INTRODUCTION 
2.1 
Background Information 
Coronaviruses have been widely identified as causing respiratory and intestinal infections in 
humans after the outbreak of severe acute respiratory syndrome (SARS) in Guangdong, China in 
2002 and 2003 (Zhong et al., 2003; Cui et al., 2019; Khan et al., 2020). Recently, a novel 
coronavirus has been identified as the causative pathogen of a rapidly spreading infection 
associated with pneumonia and severe acute respiratory syndrome. COVID-19, originally 
identified in Wuhan in the Hubei province of China, has now spread across the globe and has been 
declared by the WHO as a global pandemic. While the majority of infected patients display mild 
symptoms if any, death rates of up to 4% due to development of severe acute respiratory syndrome 
(COVID-19 SARS), have been reported in patients with co-morbid conditions and in the elderly 
population. The only available treatment for COVID-19 illness is remdesivir but its use is currently 
limited to hospitalized patients with severe disease under an emergency use authorization from the 
FDA. With the unprecedented global health and economic threats imposed by COVID-19, 
development of therapies to suppress or eradicate this emerging pathogen has become an urgent 
unmet medical need. 
 
The mechanisms associated with the infectiousness of SARS-CoV-2 are not clear; however, 
structural analysis suggests it is likely entering human cells through the ACE2 receptor (Zhou et 
al., 2020). Considering the adverse outcomes of the current COVID-19 epidemic, developing 
effective therapeutic strategies is necessary to cope with the lack of effective drugs, high mortality 
rate, and the potential of the virus to cause further epidemics (Khan et al., 2020). 
 
2.2 
Preclinical and In Vitro Experiences 
The hypothesis that the transmembrane serine protease TMPRSS2 plays a critical role in the life 
cycle of SARS-CoV-2 is supported primarily by 2 lines of evidence. Using a panel of established 
human cell lines, Matsuyama et al. (2020) have shown that SARS-CoV-2 infection is enhanced by 
TMPRSS2 expression in a host cell. Independently, Hoffmann et al. (2020) have shown that 
SARS-CoV-2 cell entry depends on the ACE2 receptor and TMPRSS3 activity, the latter resulting 
from the ability of the protease to prime the viral spike (S) protein. The case for camostat as a 
pharmacologic inhibitor of TMPRSS2 also stems from 2 lines of evidence. In the same study cited 
above (Hoffmann et al., 2020), camostat was shown to block viral entry in vitro. Furthermore, 
because the same mechanism involving ACE2 and TMPRSS2 is also in the entry of the closely 
related SARS-CoV coronavirus in human cells, animal studies with this respiratory virus are also 
relevant to COVID-19 therapy. Zhou et al. (2015) have shown that camostat was effective in 
protecting mice against death due to a lethal infection by SARS-CoV, with a survival rate of ~60%. 
Together, these findings suggest that camostat may be an effective treatment and prophylactic for 
patients infected with SARS-CoV-2. The inhibitory effects of camostat on various proteases were 
compared with those of FOY-251 (the major metabolite of camostat). As compared to camostat, 
the inhibitory effect of FOY-251 on trypsin-catalyzed hydrolysis of TAMe was 1/2, that on 


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caseinolysis was 1/5, that on plasmin catalyzed fibrinogen degradation was 1/3, thrombin- 
catalyzed fibrin coagulation was equivalent, and those on plasma kallikrein and pancreatic 
kallikrein were 1/7 and 1/2, respectively. 
 
Decreased locomotor activity, convulsions, loss of righting reflex, external irritation, 
hypersensitivity, and dyspnea were observed in rats at extremely high doses of 3,000 mg/kg or 
higher orally (p.o.). However, no effects were observed on the central nervous system at doses up 
to 2,000 mg/kg, p.o., in mice, or on the autonomic nervous system at doses ranging between 100 
and 500 mg/kg, p.o., in rats. No changes in blood pressure were observed in rats at doses ranging 
between 10 and 1,000 mg, p.o. Inhibitory effects were observed in vitro on contraction of the 
isolated smooth muscles in the gastrointestinal tract, trachea, and blood. 
 
2.3 
Clinical Experience 
Camostat/Foipan has been extensively used in pancreatitis patients for more than 20 years in Japan. 
The clinical development program in Japan consisted of the following studies: 
• 
A Phase I tolerability study was conducted in which camostat mesilate was administered 
postprandially at doses of 50, 100, 200, 300, 400, and 600 mg to 6 healthy adult males aged 
between 24 and 39 years. Pulse rate, blood pressure and clinical symptoms were monitored 
every hour for 4 hours post-dose and at 24 hours post-dose. 
 
• 
A dose-response exploratory early Phase II study in remission of acute symptoms of 
chronic pancreatitis. This preliminary clinical study was conducted in which camostat 
mesilate 300mg/day and 600 mg/day was administered 3 times daily after each meal for 6 
consecutive weeks in patients with chronic pancreatitis. 
 
• 
A Phase II double-blind comparative study was conducted in which patients with 
postoperative reflux esophagitis received FOIPAN 300 mg/day (Group L), 600 mg/day 
(Group M), and 900mg/day (Group H) for 8 weeks. 
 
• 
A Phase II double-blind comparative clinical study was conducted in which patients with 
postoperative reflux esophagitis, subjective symptoms, endoscopically observed erosion, 
hemorrhage, ulcer, white film, redness, etc., received FOIPAN 300 mg/day (Group H) and 
90mg/day in unidentifiable tablets containing 30 mg of this product (Group L) for 8 weeks. 
 
• 
A Japanese double-blind controlled study for emission of acute symptoms of chronic 
pancreatitis was conducted using FOIPAN 600 mg/day (Group F) and placebo (Group P) 
in patients diagnosed with chronic pancreatitis by histological examination, morphologic 
examination, or pancreatic function test based on diagnostic criteria of the Japan Pancreas 
Society, and who had an elevated serum/urine amylase level and acute symptoms of upper 
abdominal pain and/or tenderness, and were capable of taking oral medication. The 
treatment period was 2 weeks and the observation period was 4 weeks until 2 weeks after 
the end of treatment. 
 
• 
A Japanese double-blind controlled study for emission of acute symptoms of chronic 
pancreatitis was conducted using FOIPAN 600 mg/day (Group F) and placebo (Group P) 
in patients diagnosed with chronic pancreatitis by histological examination, morphologic 


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examination, or pancreatic function test based on diagnostic criteria of the Japan Pancreas 
Society, and who had an elevated serum/urine amylase level and acute symptoms of upper 
abdominal pain and/or tenderness, and were capable of taking oral medication. The 
treatment period was 2 weeks and the observation period was 4 weeks until 2 weeks after 
the end of treatment. 
 
A Phase I study in 14 healthy young men of 2400 mg per day for seven days with the 
dose given 30 minutes or one hour pre-prandially. Fasting and non-fasting drug levels 
were compared and subjects were assessed for adverse events and to compare drug levels 
in fasting state, at 30 and 60 minutes before eating and with food. 
 
Implementation of a controlled study as a Phase III study was considered but based on the results 
of comparison of the Group H (300 mg/day) with the Group L (90 mg/day) in the Phase II double- 
blind controlled study, it was determined that a placebo-controlled study was not necessary. 
 
2.4 
Phase 1 Study Steady State Exposure 
Plasma concentrations of camostat mesilate were determined by HPLC after single dose of 200 
mg was orally administered with about 100 mL of water to 5 healthy adult male volunteers in a 
fasted state. The unchanged drug concentration in plasma was below the limit of quantitation, but 
the active metabolite 4-(4-guanidinobenzoyloxy)phenylacetic acid (hereafter abbreviated as FOY- 
251) was detected. The plasma concentration of the active metabolite FOY-251 reached a 
maximum at 40 minutes post-dose, with a maximum plasma concentration (Cmax) of 87.1 ng/mL 
and a half-life (T1/2) of approximately 100 minutes. The time course of the blood concentration 
of the active metabolite FOY-251 is provided below. 
Figure 3 Time Course of Blood Concentration of FOY-251 
 
 
 


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Data are presented as the mean ± standard deviation except that Tmax is shown as the median. 
 
 
2.5 
Rationale for 200 mg dose four times per day given one hour before meals 
In a recent study, the IC50 for camostat for coronavirus was found to be 4.3 nM (Hoffmann et al. 
2020 Preprint). In the presence of serum, however, camostat rapidly degrades to GBPA which has 
an IC50 of 70.3. This is similar to previous reports of an IC50 of 87. The Cmax of Camostat and 
GBPA in blood noted above (87.1 ng/ml) with a 200 mg dosing is thus barely sufficient to reliably 
inhibit the virus. There is precedent, however, in US for using a higher dose of 200 mg four times 
daily; a trial of camostat for Covid-19 currently underway at Mayo Clinic is using this 800 mg dose 
(NCT04470544). Moreover, providing the drug one hour before meals can maximize the Cmax as 
is evident in the figure below using a 600 mg dose. Thus, we feel the best dosage for Camostat is 
200 mg one hour before and two hours after meals and at bedtime. 
 
 
2.6 
Rationale for 10-day Dosing Regimen 
The indicated dose of camostat/Foipan has been extensively used in pancreatitis patients for 
more than 20 years in Japan. 
 
2.7 
Rationale for the Current Study 
There is a global pandemic caused by the SARS-CoV-2 virus, which threatens the lives of many 
and the economic stability of the world. Therapeutic approaches are badly needed, and an orally 
available, well tolerated small molecule agent could play a critical part in preventing and 
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People with COVID-19 who are or experiencing mild symptoms that do not require hospitalization 
have no proven option other than supportive care. The safety profile of camostat mesilate is well- 
established. It is generally safe and well-tolerated. Furthermore, reducing viral shedding may 
decrease household and community transmission of SARS-CoV2. Thus, the risk to benefit 
assessment of treatment with camostat mesilate in the face of COVID-19 is clearly in favor of 
potential study subjects. 
This study will assess the time course of cessation of viral shedding, and gather clinical benefit 
information, in patients with COVID-19 treated with camostat mesilate plus SOC as compared to 
placebo plus SOC. Data from this trial is expected to support a larger study which will demonstrate 
clinical benefit and serve as a pivotal trial for approval. The information gathered from this study 
will also help define the safety profile in this setting and enable expansion into other patient 
populations such as those who have been exposed but who are not yet ill. This could have a 
significant impact on public health. 
 
3 DESIGN 
This is a Phase 2 double blinded and placebo controlled randomized trial evaluating the efficacy 
and safety of camostat mesilate in adult subjects with PCR-positive, mild-moderate or COVID-19 
infections. 
Subjects will be randomized to receive either camostat mesilate + current Standard of Care (SOC) 
or SOC + placebo. 
Study participants will be randomly assigned 1:1 to two tablets of oral camostat mesilate (200 
mg) four times a day or current standard of care for 10 days. 
Subjects in the SOC arm will receive a placebo. The total anticipated duration of the study for each 
patient is 28 days. 
 
4 OBJECTIVES 
4.1 
Primary Objective 
To evaluate the efficacy of oral camostat mesilate plus SOC compared with placebo plus SOC in 
reducing the AUC through day 10 of shedding of SARS-CoV2 virus in patients with mild-moderate 
COVID-19 disease. 
 
4.2 
Secondary Objectives 
1. To evaluate the efficacy of oral camostat mesilate plus SOC compared with placebo plus 
current SOC in reducing the AUC up through day 28 of viral shedding of SARS-CoV-2 
virus in patients with mild-moderate COVID-19. 
2. To evaluate the efficacy of oral camostat mesilate plus SOC compared with placebo plus 
current SOC in reducing the duration of viral shedding of SARS-CoV-2 virus in patients 
with mild-moderate COVID-19. 
3. To evaluate the efficacy of oral camostat mesilate plus SOC compared SOC plus placebo 
in reducing the duration of symptoms, hospitalizations or ED visits, or mortality in patients 
with mild-moderate COVID-19 disease. 
4. To evaluate the proportion of individuals with a negative SARS-CoV2 RT PCR test on days 
7, 14 and 28. 


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5. To assess the safety and tolerability of camostat mesilate in this subject population. 
6. To assess the development of antibodies against SARSCoV-2 
7. To determine drug levels using the current dosing scheme. 
 
5 SUBJECT POPULATION 
5.1 
Inclusion Criteria 
All criteria must be confirmed as “YES”: 
1. Adults (18 to 80 years old inclusive) 
2. Diagnosis of COVID-19 disease: 
a. Presence of mild-moderate symptoms without signs of respiratory distress (as 
defined by SpO2 <=94% on room air, RR >=24, HR >=110), with FDA-cleared 
molecular diagnostic assay positive for SARS-CoV-2 within 72 hours from swab to 
the time of commencing informed consent. Mild-moderate disease is defined as 
having at least 2of the following symptoms that are of moderate or higher severity 
as scored on the COVID Outpatient Symptom Scale (COSS):: 
i. Fever (>98.7F) 
ii. Cough 
iii. Shortness of breath 
iv. Fatigue 
v. Headache 
vi. Body ache 
vii. Joint pain 
viii. Chest pressure 
ix. Abdominal pain 
x. Sore throat 
xi. Nasal congestion 
xii. Chills 
xiii. Feeling hot or feverish 
xiv. Runny nose 
xv. Loss of taste 
xvi. Loss of smell 
xvii. Diarrhea 
xviii. Nausea 
xix. Vomiting 
xx. Rash 
b. The date of onset of the first of the above symptoms will be documented. 
3. Subject or their legal representative understands the requirements of the study and provides 
written informed consent prior to undergoing any treatment-related procedures. 
4. If male, subject must: 


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a. Be sterile (e.g., have had a vasectomy at least 6 months prior to Day 1 dosing), OR, 
b. Agree not to donate sperm during the study and for seven days following the last dose of 
study medication, AND, 
c. Agree to strictly adhere to the following contraceptive measures during the study and for 
seven days following the last dose of study medication: 
i. Abstain from sexual intercourse. 
ii. Use a condom during sexual intercourse with a female of child-bearing potential. In 
addition, the female partner must use another form of contraception (e.g. intrauterine 
device [IUD], diaphragm with spermicide, oral contraceptives, injectable progesterone, 
or subdermal implants). 
5. 
If female, subject must: 
a. Be unable to bear children (have not had a period for ≥ 12 consecutive months, have had 
her uterus or ovaries removed, or have had a tubal ligation), OR, 
b. Must ensure that their male partner is incapable of fathering a child (e.g., has had a 
vasectomy at least 6 months prior to study entry), OR, 
c. If she is of childbearing potential will strictly adhere to the following contraceptive 
measures during the study and for seven days following the last dose of study medication: 
i. Abstain from sexual intercourse, OR, 
ii. Must ensure that her male partner agrees to use a condom during sexual intercourse and 
agree to use an approved method of contraception (e.g., IUD, diaphragm with 
spermicide, oral contraceptives, injectable progesterone, or subdermal implants). 
d. Agrees to stop breast-feeding prior to first dose of study drug and through seven days after 
completing therapy. 
e. Has a negative urine pregnancy test at screening. 
f. Has not had unprotected sexual intercourse within the past month. 
6. When such testing is available, subject will be confirmed to be SARS-CoV2 infected using a 
rapid (<30 minute) SARS-CoV2 point-of-care test; if such a test is not available, this step of 
screening will be omitted. 
7. Subject agrees to maintain home or other quarantine as recommended by the study physician, 
except to visit the study site as required by the protocol. 
8. Subject agrees to take daily nasal swabs (anterior nares) for Day 1 to Day 10 and Day 14, 21, 
and 28 using the study provided material and bring these to their follow up visits on days 5, 10 
and 28. 
9. Subject agrees to record daily symptoms, temperature, oxygen saturation, and pulse using the 
study provided materials. 
10. Subject agrees to return to the study site for follow-up visits on Day 5, 10 and 28. The study 
site will be staffed by trained healthcare providers wearing full personal protective equipment 
and study site equipment will be disinfected between patients according to the same protocols 
as a clinical setting. Subjects will be wearing masks, will be appropriately spaced, and the 
number of subjects assessed at each time will be limited. 
11. Members of the same household may participate in the study as long as the inclusion and 
exclusion criteria are met. 
 
5.2 
Exclusion Criteria 
All criteria must be confirmed as “NO”: 


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1. Subject has a concomitant bacterial respiratory infection, as defined by positive respiratory 
culture 
NOTE: Subjects on empirical antibiotic treatment for possible but unproven bacterial 
pneumonia, but who are positive for SARS-CoV-2, are allowed in the study. 
2. Previous use of antiviral drugs that may be active against COVID-19. 
3. Subject is using adrenocorticosteroids (except topical or inhaled preparations or oral 
preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or 
immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, 
interleukin antagonists or interleukin receptor blockers). 
NOTE: Treatment of study participants following institutional COVID-19 treatment 
policies or guidelines, including the use of immunomodulatory medications, is 
permitted. This excludes treatment with agents that have the potential for direct 
antiviral activity, including convalescent plasma and NO, and co-enrolment into 
other clinical studies that evaluate investigational agents for COVID-19. 
4. Subject has gout, a bleeding disorder, or a serious chronic disease (e.g., human 
immunodeficiency virus [HIV], cancer requiring chemotherapy within the preceding 6 months, 
moderate or severe hepatic insufficiency and/or unstable renal, cardiac, pulmonary, neurologic, 
vascular, or endocrinologic disease states requiring medication dose adjustments within the last 
30 days). 
5. Subject uses an anticoagulant medication including heparin, coumadin, a factor Xa inhibitor 
(xarelto, apixaban) or a thrombin inhibitor (Pradaxa). Aspirin is not an indication for 
exclusion 
6. Has previously received camostat mesilate within the past 30 days. 
7. Has renal insufficiency requiring hemodialysis or continuous ambulatory peritoneal dialysis 
(CAPD). 
8. Has liver impairment greater than Child-Pugh A. 
9. Has a history of alcohol or drug abuse in the previous 6 months. 
10. Has a psychiatric disease that is not well controlled where controlled is defined as: stable on a 
regimen for more than one year. 
11. Has taken another investigational drug within the past 30 days. 
12. Is deemed by the Investigator to be ineligible for any reason. 
 
5.3 
Removal of Subjects from Treatment 
The participation of a subject in the study or the administration of treatment may be terminated at 
any time for one of the following reasons: 
• 
The subject desires to discontinue study treatment. 
• 
The subject withdraws consent to participate in the study. 
• 
The subject is unwilling or unable to comply with the safety procedures. 
• 
The subject is discovered to be pregnant. 
• 
The subject experiences a medical emergency that necessitates withdrawal. 
• 
The subject is withdrawn at the discretion of the Investigator for medical reasons or non- 
compliance. 


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• 
AST or ALT > 8 x ULN 
• 
ALT or AST > 3 x ULN AND total bilirubin > 2X ULN 
• 
AST or ALT > 3 x ULN AND patient has right upper quadrant pain or eosinophilia 
• 
Hypersensitivity 
• 
Shock or anaphylactoid symptoms 
• 
Absolute neutrophil count <800 cells/mm3 
• 
Hemoglobin <11 g/dL for women and <12 g/dL for men 
• 
Serum creatinine concentration ≥1.5× ULN 
• 
Confirmed creatinine clearance (CrCl) < 50 mL/min by Cockcroft-Gault 
• 
Platelet count <75,000 cell/mm3. 
• 
Hepatic function disorder or jaundice (both incidences unknown). 
• 
Hyperkalemia (incidence unknown). Severe hyperkalemia may occur. 
A subject whose treatment is terminated should remain in the study for appropriate follow up 
assessments whenever possible. 
 
6 STUDY TREATMENT - CAMOSTAT MESILATE 
6.1 
Study Drug 
Camostat will be supplied as 100mg unprinted tablets to be stored at controlled room 
temperature (15°C to 30°C [59°F to 86°F]). Ono Pharmaceuticals has prepared matched placebo 
tablets, which they will also supply to us along with camostat tablets. Matching placebo will be 
provided in tablet form to be stored at controlled room temperature (15°C to 30°C [59°F to 
86°F]). 
Standard Dose 
Subjects randomized to the camostat mesilate + SOC arm will be administered. Day 1 is deemed to 
be the first 24 hours after enrollment into the study, with time 0 (time of first dose) occurring as 
soon as possible after the subject’s eligibility has been confirmed. 
Subjects randomized to the SOC + placebo arm will be administered. Day 1 is deemed to be the 
first 24 hours after enrollment into the study, with time 0 (time of first dose) occurring as soon as 
possible after the subject’s eligibility has been confirmed. 
 
6.2 
Administration of Camostat mesilate or placebo 
The tablets will be dispensed in appropriately sized amber prescription containers with child- 
resistant caps. The prescription container and caps are manufactured from PP (polypropylene 
plastic). 
Camostat mesilate is provided as 100 mg tablets and dosed orally. Subjects will be instructed to 
take their doses at least two hours after a meal and one hour before the next meal, and at bedtime. 
Subjects who vomit during or immediately after dosing, should not be re-dosed. 
 
6.3 
Outpatient Camostat mesilate Dosing 
Subjects in the camostat mesilate + SOC arm, will be dispensed sufficient camostat mesilate to 
ensure continued dosing until their next study visit. 


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Subjects will also be instructed that if they miss a dose, they should follow the guidelines: 
1) If more than 1/2 the time until their next dose has elapsed, they SHOULD NOT take the 
dose. They should just take the next dose at the normal scheduled time. 
2) If less than 1/2 the time until their next dose has elapsed, they should take the missed dose 
immediately. 
3) In both cases, they should then return to their regular dosing schedule. 
 
6.4 
Drug Accountability 
The Investigator must maintain adequate records showing the receipt, dispensation, or other 
disposition of camostat mesilate including the date, quantity and identification of subjects (study 
ID) who received camostat mesilate. Drug supplies will be inventoried and accounted. Unused 
supplies of all camostat mesilate will be returned to the Sponsor or destroyed on site in accordance 
with local procedures upon approval of the Sponsor. 
 
6.5 
Treatment Compliance 
The pharmacy will provide bottles of camostat mesilate for outpatient use (Exact dispensing 
instructions for outpatients will be described in the pharmacy instructions). Assessment for 
compliance with each dose will be monitored and recorded in accordance with site standard 
operating procedures. 
 
6.6 
Treatment Precautions 
An overdose is defined as any dose of study drug given to a subject or taken by a subject that 
exceeds the dose described in this document. In the event of an overdose, the subject’s symptoms 
should be treated, and the Sponsor informed. 
 
6.7 
Clinically Significant Adverse Reactions 
As indicated on the FOIPAN label (Japanese approved product), the below listed clinically 
significant adverse reactions may occur. Patients should be carefully monitored. If any 
abnormalities are observed, appropriate measures such as discontinuing the administration 
should be taken. 
 
• 
Shock or anaphylactoid symptoms (both incidences unknown). If any symptoms such as 
decreased blood pressure, dyspnea, and pruritus are observed, administration should be 
discontinued and appropriate measures be taken. 
• 
Thrombocytopenia (incidence unknown). 
• 
Hepatic function disorder or jaundice (both incidences unknown). 
• 
Hepatic function disorder accompanied by remarkable increase of AST (GOT), ALT 
(GPT), γ-GTP, Al-P, or jaundice may occur. 
• 
Hyperkalemia (incidence unknown). Severe hyperkalemia may occur. 
6.8 
Other Adverse Reactions 


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Incidence1/Adverse 
Reaction 
0.1%-0.5% 
<0.1% 
Unknown 
Hematologic 
Leukopenia, 
erythrocytopenia 
Eosinophilia 
Hypersensitivity2 
Rash, pruritus 
Gastrointestinal 
Nausea, abdominal 
discomfort, 
abdominal fullness, 
diarrhea 
Anorexia, vomiting, 
dry mouth, heartburn, 
abdominal pain, 
constipation 
Hepatic 
Increased AST 
(GOT), ALT (GPT), 
etc. 
Renal 
Increased BUN, 
increased creatinine 
Other 
Edema, 
hypoglycemia 
1 The incidences are calculated by including reports from the drug use surveillance 
2 If such symptoms are observed, administration should be discontinued. 
6.9 
Prohibited Concomitant Therapy 
The following may interact with camostat mesilate and risks and benefits should be carefully 
considered prior to treatment with the following: 
• 
Any other anti-viral medication whether investigational or approved. 
7 STUDY PROCEDURES 
Refer also to Section 14: Schedule of Assessments 
 
7.1 
Day 1 (PRE-DOSE) 
• 
Obtain informed consent. 
• 
Verify eligibility per the inclusion and exclusion criteria. (See Sections 5.1 and 5.2) 
o Review and record medical history to ensure there are no exclusionary illnesses. 
o Review and record concomitant medications for possible prohibited medications. (See 
Section 6.7) 
o Record date of onset of symptoms 
• 
If subject is female of child-bearing potential and meets inclusion criteria 5.e, obtain urine 
pregnancy test and proceed if result is negative. 
• 
Measure and record vital signs (BP, HR, Temp, Resp). 


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• 
Collect and record SPO2 by Finger Sensor 
• 
Perform Physical exam (may be done by the Principal Investigator or their designee) 
• 
Collect oropharyngeal swab for virologic testing by RT-PCR and resistance testing. 
• 
Collect blood samples for: 
o Antibodies to SARS-CoV-2. 
o Hematology and clinical chemistry laboratory analyses 
o Biobanking 
 
• Perform subject randomization (via EDC) to establish treatment arm (camostat mesilate + SOC 
or SOC + placebo). 
• Explain in home procedures for the study (self-sampling of nasal swabs, temperature, SPO2, 
completing the daily questionnaire). 
• Provide supplies to research subject and review the calendar of return visits 
7.2 
Day 1 (FIRST DOSE AND POST-DOSE) 
NOTE: Day 1 is deemed to be the first 24 hours after enrollment into the study, with time 0 (time 
of first dose) occurring as quickly as possible after the subject’s eligibility has been confirmed. 
• 
Administer first dose (200 mg camostat mesilate or placebo) at time 0. 
• 
Monitor patient for 30 minutes after their first dose. 
7.3 
Days 5, 10, 28 (Follow-up) or Early Termination 
• 
Conduct and record the results of a Physical Exam. 
• 
Review and record concomitant medications (Note: if there have been changes in concomitant 
medications during the study, determine whether the change is due to an AE). 
• 
Measure and record vital signs (BP, HR, Temp, Resp). 
• 
Collect and record SPO2 by Finger Sensor 
• 
Collect blood samples for: 
o Antibodies to SARS-CoV-2. (28) 
o Biobanking (Day 10 and Day 28) 
o Hematology and clinical chemistry laboratory analyses (Day 5, 10, 28) 
o Drug level one hour after dosing (Day 5) 
 
• 
Assess and record clinical status according to the following study-specific 7-point scale: 
1. Not hospitalized 
2. Hospitalized, not requiring hospital care due to lack of housing 
3. Hospitalized, not requiring supplemental oxygen 
4. Hospitalized, requiring supplemental oxygen 
5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 
6. Hospitalized, on invasive mechanical ventilation or ECMO 


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7. Death 
• 
Collect oropharyngeal swab for virologic testing (RT-PCR) and resistance analysis. 
• 
Collect and record adverse events (see Section 8.3 for detailed instructions). 
8 EFFICACY, PHARMACOKINETICS AND SAFETY ASSESSMENTS 
8.1 
Efficacy Assessments 
Primary Measurement (Efficacy): 
1.  Nasal swab for PCR taken daily from Day 1 to Day 10, and Days 14, 21, and 28. 
Secondary Measurements (Efficacy): 
1. Symptom improvement or worsening: Subjects will fill in a diary daily (see Appendix A2), 
recording the following symptoms: 
a. Cough 
b. Sore throat 
c. Headache 
d. Nasal congestion 
e. Body aches and pains 
f. Fatigue 
g. Oral temperature taken at a consistent time each day and at least four hours after 
ingesting the most recent antipyretic (acetaminophen or NSAID) 
h. Dyspnea 
i. Shaking chills 
j. Loss of taste 
k. Loss of smell 
l. GI symptoms including nausea, vomiting, and/or diarrhea 
m. Chest pain 
2. Blood for determination of antibodies to SARS-CoV-2 will be obtained on Days 1 and 28. 
3. Number of subject hospitalizations, emergency department visits, incidence of respiratory 
failure, deaths, and proportions of subjects alive, not hospitalized, and free of respiratory 
failure on day 28 
 
8.2 
Required Resistance Testing 
Resistance testing, as required in clinical trials of anti-viral drugs will be performed at each time 
point that oropharyngeal swabs are taken. 
 
8.3 
Safety Assessments 
Abnormal clinical laboratory values that are clinically significant and all reported adverse events 
will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) 
version 5.0. 
Safety will be assessed by the collection of observed and reported adverse events, physical exams, 
vital signs and the following clinical laboratory tests: 
• 
Hematology 


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Hemoglobin (Hgb) 
Hematocrit (Hct) 
Platelet count 
Red blood cell count 
White blood cell count with differential 
• 
Chemistry 
Blood Urea Nitrogen (BUN) 
Creatinine 
Total bilirubin 
Alkaline Phosphatase 
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Lactic dehydrogenase (LDH) 
Glucose 
Albumin 
Total protein 
Bicarbonate 
Sodium 
Potassium 
Chloride 
Calcium 
Urate 
C-reactive protein 
 
NOTES: 
• 
All clinical laboratory assessments listed above (hematology and chemistry) will be 
conducted at the Stanford University Medical Center clinical laboratory. 
• 
If coagulation assays are ordered as part of the SOC, the results should be added to the EDC. 
Including Clinical Laboratory Testing, subjects will undergo four planned venipunctures during 
this study. 
 
8.3.1 Adverse Events 
Treatment-emergent AEs will be defined as those occurring coincident with start of treatment 
through 28 days post-treatment. 
Subjects will be instructed to report AEs during the study and staff will query subjects regarding 
AEs throughout the study. The Investigator (and/or designee) must document all AEs reported 
through completion of the Day 28 visit. Any subject who is withdrawn from the study due to an AE 
shall be followed until the event has resolved or stabilized or, if in the camostat mesilate arm, 14 
days after last dose. The Investigator will document available follow-up information on the 
subject’s source documentation and CRF 
 
8.3.2 Definition of an Adverse Event 
The FDA Safety Guidance, referencing 21CFR312.32(a), defines an Adverse Event as follows: 
Adverse event means any untoward medical occurrence associated with the use of a drug 
in humans, whether or not considered drug related. 
An adverse event (also referred to as an adverse experience) can be any unfavorable and 
unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a drug and does not imply any judgment about causality. An 
adverse event can arise with any use of the drug (e.g., off-label use, use in combination with 
another drug) and with any route of administration, formulation, or dose, including an 
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Adverse Events are NOT: 
• 
Clinical events related to the progression of COVID-19. 
• 
Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion). 
The condition that leads to the procedure is the AE. 
• 
Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions). 
 
8.3.3 Evaluating and Reporting of Adverse Events 
All AEs (i.e. a new event or an exacerbation of a pre-existing condition) that occur after dosing 
with camostat mesilate and after completion of baseline assessments in the SOC + placebo arm, 
must be recorded as an AE or SAE (if applicable), on the Adverse Event eCRF and SAE form, as 
applicable. The Investigator must follow all AEs until the AE resolves, or until the Investigator 
and/or the Medical Monitor determine the event is chronic or clinically stable. If an AE remains 
unresolved at the conclusion of the study, the Investigator and Medical Monitor will make a clinical 
assessment to determine whether continued follow-up of the AE is warranted. All subjects who 
have received at least one exposure to study therapy will be evaluated for safety of study treatment. 
The Investigator should attempt to establish a diagnosis of the event based on signs, symptoms 
and/or other clinical information. In such cases, the diagnosis should be documented as the AE and 
not the individual signs/symptoms. 
All AEs must be promptly documented on the Adverse Event eCRF and assessed by the 
Investigator. Details of the event must include the dates of onset and resolution, severity, 
relationship to study drug, seriousness, and whether the event caused the subject to withdraw from 
the study, outcome and timing with regard to administration of the study drug. We will categorize 
the AES using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events. 
Severity: Severity should be graded and recorded as follows: 
• 
Grade 1 Mild: No or minimal interference with usual activities; intervention not indicated 
• 
Grade 2 Moderate: Greater than minimal interference with usual activity; intervention indicated 
• 
Grade 3 Severe: Inability to carry out usual activity, incapacitating; requires intervention or 
hospitalization 
• 
Grade 4 Potentially life-threatening: Inability to perform self-care; intervention indicated to 
prevent permanent impairment, disability or death 
• 
Grade 5 Death 
Relationship: The relationship of the Adverse Event to the study drug will be determined by the 
Principal Investigator, and assessed using the following definitions: 
• 
Related: There is a distinct temporal relationship between the event onset and administration 
of the study drug. There is a known reaction to agent or chemical group or predicted by known 
pharmacology. The event cannot be explained by subject’s clinical state or other factors. 
• 
Unrelated: Evidence exists that the AE has an etiology other than the study drug (e.g., pre- 
existing condition, underlying disease, intercurrent illness, or concomitant medication). 


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These criteria, in addition to good clinical judgment, should be used as a guide for determining the 
causal assessment. If it is felt that the event is not related to study drug therapy, then an alternative 
explanation should be provided. 
 
8.3.4 Serious Adverse Events (SAEs) 
All SAEs as defined below and that occur after the first dose of camostat mesilate and up to Day 
28 must be reported to the Sponsor as soon as the site becomes aware of them. Any SAEs occurring 
after Day 28 and considered at least possibly drug-related must also be reported. 
 
8.3.5 Definition of Serious Adverse Events 
An SAE is an AE from this study that results in any of the following outcomes: 
• 
Death (even if caused by COVID-19 all deaths are recorded as SAEs) 
• 
Life-threatening situation (subject is at immediate risk of death) 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant disability/incapacity 
• 
Congenital anomaly/birth defect in the offspring of a subject who received study drug 
NOTE: Important medical events that may not result in death, be immediately life-threatening, or 
require hospitalization, may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
A life-threatening AE is defined as any adverse experience that places the subject in the view of the 
Investigator, at immediate risk of death from the event as it occurred. This does not include an 
event that might have led to death, if it had occurred with greater severity. 
“Inpatient hospitalization” means the subject has been formally admitted to a hospital for medical 
reasons, for any length of time with a minimum one overnight stay. Presentation and care within 
an emergency department does not necessarily constitute an SAE. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization, it is an SAE. 
 
8.3.6 SAE Reporting Requirements to the Sponsor 
The procedure for reporting SAEs, regardless of causal relationship, is as follows: 
• 
Within 24 hours of the Investigator’s knowledge of an SAE, the site must notify the Sponsor 
by phone call to their site monitor, medical monitor or other Sponsor representative. They 
should also immediately complete the AE eCRF and select “Serious”. 
• 
This initial reporting of an SAE should contain as much information as is available to the 
Investigator. Submission of the SAE via the EDC should not be delayed in order to collect 
additional information to complete the form. 
• 
Follow-up SAE reports may be generated in cases in which additional information becomes 
available. Hospital records, autopsy reports, and other documents may become available and 
scanned copies can be provided to the Sponsor when applicable. The follow-up SAE report 
should describe whether the event has resolved or continues, if and how it was treated, whether 


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the blind was broken or not, and whether the subject continued or withdrew from study 
participation. 
• 
The Sponsor will distribute completed SAE forms, which may be used to notify the IRB when 
applicable, via a secure internet-based document depository. 
• 
The Investigator should notify the IRB of Serious Adverse Events occurring at the site and other 
adverse reports received from the Sponsor in accordance with local procedures. 
The Investigator must take all therapeutic measures necessary for resolution of the SAE. Any 
medications necessary for treatment of the SAE must be recorded onto the concomitant medication 
section of the subject’s eCRF. However, treatment medication should only be recorded in the 
narrative description section of the SAE form. 
 
8.4 
Suspected Unexpected Serious Adverse Reactions (SUSARs) 
A SUSAR carries specific and time-based reporting requirements for the Sponsor of a clinical trial. 
Thus, after an Investigator reports an SAE, the FDA expects the Sponsor will determine whether it 
meets the definition of a SUSAR. 
A SUSAR is defined according to 3 criteria: 
1. The AE is deemed a “suspected adverse reaction” if there is a reasonable possibility that the 
study drug caused the AE. A “reasonable possibility” means there is evidence to suggest a 
causal relationship between the drug and adverse event. 
2. The AE is “Serious” if it meets the definition of an SAE provided in section 8.3.5 
3. The AE is deemed “unexpected” if it is not listed in the Investigator’s Brochure (IB) or if in the 
IB, has not been reported at the severity observed. 
In cases where the Sponsor deems a SUSAR has occurred, it must file an IND Safety Report with 
the FDA. Sponsorwill require the assistance and cooperation of the Investigator and staff to provide 
accurate and complete information on the subject and observed SAE so that reporting requirements 
to the FDA can be met. 
 
8.4.1  Reporting SUSARs to the FDA: IND Safety Reports 
IND safety reports are used to submit reports of SUSARs to the FDA. There are 2 types of reports: 
• 
A “15-day report” is used when the reported SAE is a SUSAR and requires that as much 
information as is available to the investigator and the sponsor, be submitted to the FDA in on 
the appropriate form. For US trials, the appropriate form is the FDA Form 3500A also 
commonly known as a “MedWatch” form. 
• 
A “7-day report” is used when the SUSAR is considered to be fatal or life-threatening. 
The 7-day and 15-day timelines begin the day that the Investigator learns of the event and are 
counted in calendar days – not business days. Therefore, it is important that the investigator 
carefully follow the reporting requirements described in section 8.3.6. 
 
8.5 
Clinical Laboratory Abnormalities and Other Abnormal Assessments 
Laboratory abnormalities are usually not recorded as AEs unless considered to be clinically 
significant by the site clinician.  An abnormal laboratory result will be considered an AE if it 


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induces clinical signs or symptoms, if the abnormality is of a degree that requires active 
management (e.g. discontinuation of the study drug, dose modification) or when the event is 
requiring treatment or other therapeutic intervention (e.g. iron supplements, blood transfusion, etc.). 
The Investigator will evaluate the relationship of any significantly abnormal result to protocol 
treatment and clinical condition, if possible. All clinically significant abnormal laboratory results 
will be followed until they return to normal or become stabilized. 
 
8.6 
Handling of Overdose 
An overdose is defined as any dose greater than the highest daily dose included in this document. 
Any overdose must be recorded. If the overdose is associated with an AE, that AE must be recorded, 
assessed for seriousness, and reported as an SAE. 
 
9 STATISTICAL METHODS 
Complete details of all statistical analyses, including methods for handling missing data, will be 
included in a formal statistical analysis plan (SAP), to be completed as soon as possible. 
 
9.1 
General Considerations 
 
For the primary comparison, the following will be tested: 
 
• 
Null hypothesis: AUC of viral shedding through day 10 is equal in control and treatment; 
• 
Alternative hypothesis: AUC of viral shedding through day 10 differs between control and 
treatment. 
 
Hypothesis tests will be two sided and conducted at an overall alpha = 0.05 level of significance. 
 
The number of hospitalizations and emergency department visits will be estimated for each arm, 
with 95% confidence intervals. The frequency of adverse events and serious adverse events will be 
tabulated by type and by treatment arm. AEs will be compared by arm using the Chi-squared test 
or Fisher’s exact test, as appropriate, in the safety analysis set. 
 
9.2 
Sample size justification 
Approximately 120 patients will be enrolled. 
 
Assuming 1:1 randomization and the use of a two-sided log rank test at the alpha=0.04999 level of 
significance for the final analysis, 120 patients (60 per arm) events will provide 80% power to detect 
an effect size of 0.5 using two-sample t-test. This leaves alpha=0.00001 to check for overwhelming 
efficacy after 50% of participants have completed 24 hours of follow-up. 
 
9.3 
Demographic and Baseline Characteristics 
Summary statistics will be provided per treatment group for demographic (e.g., age, height, weight, 
body mass index [BMI], race, gender) and other initial subject characteristics (e.g., medical history, 


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concomitant diseases) will be provided per treatment group and for the total group. The ITT 
population will be used for the summaries. 
 
9.4 
Analysis Populations 
The following analysis populations will be defined for the study: 
The intent-to-treat (ITT) population will include all randomized patients. Patients will be analyzed 
according to their assigned treatment arm. All efficacy analyses will be completed in the ITT 
population. 
 
The safety population will include all patients who receive study treatment. Patients will be 
analyzed according to actual treatment received. All safety analyses will be completed in the safety 
population. 
 
9.5 
Stratification, Subgroup Analysis and Pooled Analysis 
Following consent, those subjects meeting all entry criteria will be randomized in a 1:1 ratio 
Treatment Arm: camostat mesilate + SOC 
Control Arm: placebo + SOC 
Randomization will be stratified by age (>=50 and <50 years old) and sex. 
Members of the same household may participate in the study as long as the inclusion and exclusion 
criteria are met. Because this is a double-blind, placebo-controlled trial, subjects from the same 
household will be randomized just as any other subject. 
 
9.6 
Efficacy Endpoint Analysis 
 
9.7 
Descriptive analyses 
Descriptive statistics (proportions for categorical variables, means, medians, standard deviations 
and interquartile ranges for continuous variables) will be reported for all key patient variables, 
including baseline and demographic characteristics, use of medications, compliance, and study 
completion status. Data that are missing on key patient characteristics and the outcome will be 
fully described, including any patterns of missingness (i.e., any relationships between missingness 
of a variable and patient characteristics). 
 
A CONSORT diagram displaying the number of patients screened, eligible, and consented along 
with reasons for ineligibility will be provided. Graphical tools such as histograms, boxplots, and 
scatterplots will be created to assess quality of data and to display patterns over time. 
 
9.8 
Primary efficacy analysis 
To address our primary objective, the AUC SARS-CoV2 viral RNA levels during follow-up will 
be estimated using the linear trapezoidal method, and mean AUC levels compared between 
groups using a linear regression model regressing log(AUC) on treatment arm, site, age, and sex. 
If more than 3 sites are included to address the objectives, we will employ a mixed effects 


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model, with a random effect for site. The test will be performed at the two-sided alpha = 0.05 
level of significance. 
 
9.9 
Secondary efficacy analyses 
Time until shedding cessation will be compared between the two treatment arms using a Cox 
proportional hazards model adjusted for site, age, and sex. Time of cessation will be defined as the 
first negative result that is followed only by negative results. If more than 3 sites are included to 
address the objectives, we will employ a stratified Cox model, stratified by site, allowing each site 
to have its own baseline hazard. The hazard ratio for shedding cessation will be estimated, along 
with its 95% confidence interval, from a Cox proportional hazards model. If the proportional 
hazards assumption is not met, we will consider an extended Cox model that relaxes the 
proportional hazards assumption 
 
The distribution of shedding cessation will be estimated using the Kaplan-Meier method, and 
Kaplan-Meier curves will be presented for each treatment arm. Time to shedding cessation at the 
end of the study period along with 95% confidence intervals will be presented for each treatment 
arm. 
 
The distribution of time to resolution of symptoms will be estimated using the Kaplan-Meier 
method, and Kaplan-Meier curves will be presented for each treatment arm. Time to resolution of 
symptoms at the end of the study period along with 95% confidence intervals will be presented for 
each treatment arm. The hazard ratio for resolution of symptoms will be estimated, along with its 
95% confidence intervals, from a Cox proportional hazards model. Time to resolution of symptoms 
will be determined by analysis of daily questionnaires (see Appendix A2). Resolution of symptoms 
requires that symptoms are mild or absent for at least 24 hours. The analysis of symptom resolution 
will be conducted on the symptomatic ITT population, i.e. participants who report moderate or 
severe symptoms at baseline. These analyses will be repeated in a second analysis considering only 
respiratory symptoms, i.e. fever, cough, shortness of breath, sore throat, headache, and nasal 
congestion/runny nose. This analysis will be performed on the subset of patients who report 
moderate or severe respiratory symptoms at baseline. 
 
The number of hospitalizations, emergency department visits, incidence of respiratory failure, 
deaths, and proportions of subjects alive, not hospitalized, and free of respiratory failure will be 
estimated for each arm, with 95% confidence intervals. Respiratory failure is defined as the need 
for mechanical ventilation, ECMO, non- invasive ventilation, or high-flow oxygen 
 
Our analyses will use multiple imputation methods that assume data are missing at random by 
including all baseline characteristics, treatment assignment, and reasons for missingness in the 
imputation model. This approach will be applied to any analysis involving endpoints or key 
variables where any missing data occurs in order to adhere to the ITT principle. Assumptions 
regarding missingness will be addressed in sensitivity analyses. 
 
9.10 Safety Analysis 


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The frequency of adverse events and serious adverse events will be tabulated by type and by 
treatment arm. AEs will be compared by arm using the Chi-squared test or Fisher’s exact test, as 
appropriate, in the safety analysis set. 
 
The original exact terms in the electronic data capture (EDC) system used by Investigators to 
identify AEs other than symptoms of COVID-19 will be fully described and coded according to the 
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs will be defined 
as those occurring coincident with start of treatment and through 28 days post-treatment. TEAEs 
will be summarized overall and by treatment group and by MedDRA body organ system and 
preferred term, severity, relatedness, and seriousness. 
An overall summary of TEAEs will be presented by treatment, with subject counts and percentages 
of subjects with the event. This summary will include subjects with any TEAE, any treatment- 
related TEAE, any serious TEAE, any treatment-related serious TEAE, TEAEs leading to study 
infusion discontinuation, treatment-related TEAEs leading to study infusion discontinuation, 
TEAEs leading to death, and treatment-related TEAEs leading to death. The difference in 
proportions between treatment groups in each of these categories will be calculated. 
 
Summaries of changes over time in laboratory parameters, as well as counts and percentages of 
laboratory parameters that are Low, Normal, and High compared to the reference ranges will be 
presented by treatment at each visit and time point. Shift tables will be presented for laboratory 
parameters with defined severity grades. 
 
10 DATA SAFETY MONITORING 
10.1 Data and Safety Monitoring Committee 
A DSMC will be established by the study team in cooperation with the sponsor to assess at 
intervals the progress of a clinical trial, safety data, and critical efficacy variables and 
recommend to the sponsor whether to continue, modify or terminate the trial. The DSMC will 
operate according to guidelines documented in a DSMC charter. Minutes will be taken to 
provide a written record of the DSMC meetings, including interim results; these will be available 
for review when the trial is complete. The DSMC will be a separate entity from the Institutional 
Review Board (IRB). The independence of the DSMC is intended to control the sharing of 
important comparative information and to protect the integrity of the clinical trial from adverse 
impact resulting from access to trial information. DSMC members will be external to Stanford 
University, will not participate in the study as investigators, and will not have conflicts of 
interest regarding the study or the investigational product. The composition of the DSMC will 
include at minimum: 
 
• 
DSMC Chair, having experience and expertise in clinical trials 
• 
Scientist with expertise in viral infectious diseases. 
• 
Biostatistician with expertise in clinical trials. 


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The DSMC will meet before the study and during an interim analysis to review progress of the 
clinical trial and safety data. A formal interim analysis for overwhelming efficacy is planned for 
the interim analysis. There are no plans to stop for futility. the DSMC may choose to stop 
enrollment on the basis of safety data observed. If safety concerns are found, further enrollment 
will not be allowed until issues are resolved. Any recommendation by the DSMC to stop the trial 
early will be based on a balanced review of safety and efficacy data and a consideration of 
whether an adequate amount of information is available to reach a conclusive decision. 
 
The study PI will distribute study information to the DSMC prior to a scheduled meeting. The 
DSMC may request additions and other modifications to this information on a one‑time or 
continuing basis. This information will consist of two parts: (1) information on study progress 
such as accrual, baseline characteristics, and other general information on study status and (2) 
any confidential data on study outcomes, including safety data. A formal report from the DSMC 
should be supplied to the PI within 3 days of each meeting. Each report should conclude with a 
recommendation to continue or to terminate the study. This recommendation should be made by 
formal majority vote. A recommendation to terminate the study should be transmitted to the PI 
and IRBs as rapidly as possible, by immediate telephone and fax if sufficiently urgent. In the 
event of a split vote in favor of continuation, a minority report should be contained within the 
regular DSMC report. 
 
10.2 Interim Analysis 
An interim analysis for safety and overwhelming efficacy will be performed once 50% of patients 
have 24 hours of follow-up complete. The DSMC will meet within a week after 50% enrollment is 
reached to review the safety data collected within the first 24 hours of follow-up on all enrolled 
patients. We additionally expect blood count labs collected at day 5 to be available in approximately 
25% of patients at the time of the DSMC review. 
 
The DSMC will also review the efficacy data on all randomized participants at this meeting. The 
interim efficacy analysis will use the same methods as are planned for the final analysis using the 
ITT analysis. Based on the results of the interim analysis, the DSMC will either recommend to the 
sponsor to terminate the study for overwhelming efficacy (p<0.00001 at the interim analysis), 
terminate the study for safety concerns, modify the study, or continue the study as planned. No 
formal stopping rules for futility are planned. 
 
11 RECORDING AND COLLECTION OF DATA 
11.1 Case Report Form 
The Investigator or designee will record all data collected on the electronic Case Report Form 
(eCRF) provided for that purpose. For this study, REDCAP cloud will be the eCRF. The site will 
be suitably trained on the use of the eCRF and appropriate site personnel will be provided electronic 
signatures. 


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All site entries will be made in a secured web site and the Principal Investigator will review the 
record for completeness. Upon completion of the review, the PI will sign electronically in the 
signature page of the eCRF. 
The Investigator or designee will make necessary eCRF corrections. The investigator must 
authorize the corrections to the entered data on eCRF. 
Specific instructions on use of the EDC system and guidelines for data entry and correction will be 
provided to the sites. 
 
11.2 Study Files and Subject Source Documents 
Subject confidentiality is strictly held in trust by the participating investigators, research staff, the 
Sponsor and their designees. This confidentiality is extended to cover testing of biological samples 
in addition to the clinical information relating to subjects. Authorized representatives of the 
Sponsor may inspect all documents and records required to be maintained by the Investigator, 
including but not limited to, medical records (office, clinic or hospital) and pharmacy records for 
the subjects in this study. Any data, specimens, forms, reports, and other records that leave the site 
will be identified only by a subject identification number to maintain confidentiality. 
The Investigator must maintain adequate and accurate records to enable the conduct of the study to 
be fully documented and the study data to be subsequently verified. These documents include 
Investigators’ Study Files and original subject clinical source documents generated at the study site. 
The term “original” means the first recording of the data. 
The Investigator will ensure the site master files are maintained, including the study protocol and 
its amendments, IRB and regulatory approvals with associated correspondence, informed consents, 
study drug records, staff curriculum vitae, all correspondence, and other appropriate documents. 
Subject clinical source documents may include, but are not limited to, subject hospital/clinic 
records, physicians’ and nurses’ notes, appointment books, laboratory reports, ECGs, radiographs, 
and consultant letters. The Investigator must assure that all original source documents are available 
to support monitoring activities. 
 
11.3 Monitoring 
Due to the restrictions imposed on clinical and hospital visits by the COVID-19 pandemic, all 
monitoring of this study will be conducted remotely. Monitors will work with the Study 
Coordinator at each site to determine times for “joint” remote monitoring – meaning that the 
monitor and the SC will review data together over the telephone. 
Remote monitoring will be conducted according to the applicable ICH and GCP guidelines to 
ensure protocol adherence, quality of data, drug accountability, compliance with regulatory 
requirements and continued adequacy of the investigational site and its facilities. The Investigator 
will cooperate in the monitoring process by ensuring the availability of the eCRFs, source 
documents and other necessary documents at the time of remote monitoring and by prompt attention 
to any matters brought to his/her attention by the monitor. 
 
11.4 Audit 
ICH guidelines for GCP require independent inspection of clinical program activities. Such 
inspections may be performed at any time - before, during and/or after the study. The Investigator 


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and study staff are responsible for maintaining the site master file containing all study-related 
regulatory documentation as outlined by the Sponsor that will be suitable for inspection at any time 
by the Sponsor, its designees, and/or regulatory agencies. The Investigator understands and agrees 
to give access to the necessary documentation and files. 
 
11.5 Retention of Data 
All records connected with this clinical study will be retained for at least two years following the 
date of an approved marketing application [21 CFR 312.62(c)]; or at least three years from the 
formal discontinuation of camostat mesilate development; or seven years from the end of the study, 
whichever is longer. All local laws regarding retention of records must also be followed. Study 
sites are required to retain all records until written notification allowing destruction is received from 
the Sponsor. 
 
12 ETHICS 
12.1 Ethics Committee 
A properly constituted, valid IRB/IEC must review the treatment plan and procedures, the 
Investigator’s informed consent document, and related subject information. It is the responsibility 
of the Investigator to ensure that all aspects of institutional review are conducted in accordance 
with current regulations governing the jurisdiction where the study is conducted. The Sponsor (or 
designee) must receive a letter documenting IRB/IEC approval that specifically identifies the title 
of the treatment plan, subject information sheet, and ICF. 
 
12.2 Subject Information and Consent 
It is the responsibility of the Investigator to ensure that written informed consent is obtained from 
the subject or legal representative before any activity or procedure is undertaken that is not part of 
routine care. The informed consent must comply with local regulations. 
The background of the study, the procedures, the potential benefits and risks of the treatment, and 
the fact that treatment is voluntary for the subject must be explained to the subject or legal 
representative. The subject or representative must be given sufficient time to consider whether to 
receive compassionate treatment. A copy of the ICF, signed and dated by the subject/representative 
and the Investigator (or designee), must be given to the subject/representative. Confirmation of a 
subject’s informed consent must also be documented in the subject’s medical record prior to any 
treatment with camostat mesilate. 
Each consent form should contain an authorization allowing the Investigator and the Sponsor (or 
designee) to use and disclose protected health information (PHI) (i.e., subject-identifiable health 
information) in compliance with local law. The signed consent form will be retained with the 
treatment records. 
 
13 GENERAL CONSIDERATIONS 
13.1 Discontinuation of the Study 
The Sponsor reserves the right to discontinue the study at any time for any reason. 


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13.2 Use of Information and Publication 
All information concerning camostat mesilate, Sponsor operations, patent applications, formulas, 
manufacturing processes, basic scientific data, formulation, and other information supplied by the 
Sponsor to the Investigator and not previously published is considered confidential and remains the 
sole property of the Sponsor. The Investigator agrees to use this information only to treat this patient 
and will not use it for other purposes without written consent of the Sponsor. 
The information obtained in this study will be used by the Sponsor in connection with the continued 
development and, if approved, commercialization of camostat mesilate. Thus, Sponsor may 
disclose such information as required to other clinical Investigators, contractors, and government 
regulatory agencies. 
 
Publication or other public presentation of results from this study and related information is subject 
to the provisions of the Clinical Trial Agreement between Sponsor and the Study Site. 


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14 SCHEDULE OF ASSESSMENTS 
 
Day 
of 
study 
Assessment in the study 
clinic (Physical Exam, 
Vital at each visit 
Clinical Status 7- 
scale,SPO2) 
Administration 
of study drugs 
Self- 
collected 
nasal swab 
and self- 
assessment 
Oropharyngeal 
swab 
Blood collected 
by phlebotomy 
for clinical labs 
(CBC, Chem 7, 
LFTs) 
Blood collected for 
drug level 
Blood collected by 
phlebotomy for 
biobanking/immunology 
studies 
1 
X 
X 
X 
X 
X 
X 
2 
X 
X 
3 
X 
X 
4 
X 
X 
5 
X 
X 
X 
X 
X 
X 
6 
X 
X 
7 
X 
X 
8 
X 
X 
9 
X 
X 
10 
X 
X 
X 
X 
X 
X 
14 
X 
21 
X 
28 
X 
X 
X 
X 
X 
 
 
 
 
 
 
15 APPENDIX 
 
 
 
 
 
 
 
 


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Appendix A: Subject Status 
 
1. ECOG Performance Status 
 
 
GRADE ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
light or sedentary nature, e.g., light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities; up an 
about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking hour 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 
5 
Dead 
 
*Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-655. 
 
 
2. Study Specific Daily Symptom Status Questionnaire 
 
COVID-19 Outpatient Symptom Scale (COSS): 
The below is a copy of a sample self-assessment a participant will be required to assess: 
Please take your oral temperature and 
assess your oxygen saturation with your 
pulse oximeter. 
Oral temperature.  
 F 
Time temperature was obtained.  
 AM/PM 
Blood oxygen saturation.  
 % 
Did you take a nasal swab today (study day 1-10,14,21,28)? Yes 
/ 
No 
Have you taken your study drug as prescribed in the last 24 
hours? (study day 1-10) Yes 
/ 
No 
If it is written on your schedule (clinic visit day 3, 14, 28): 
did you collect your stool sample for your next visit? 
Yes 
/ 
No 
daily. 
COVID-19 Outcome Symptom Scale (COSS) Daily Questionnaire 
The following questions are about how you feel and how things have been during the past 24 hours compared to 
your typical health. Give the one answer that comes closest to the way you have been feeling. Select "None" if you 
have not had this symptom. 
 
Cough? 
□ 
None 
□ 
Mild; just a few coughs 
per day 
□ 
Moderate; frequent but I can 
tolerate it 
□ 
Severe; I am very 
uncomfortable 
Shortness of breath (difficulty breathing)? 


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□ 
None 
□ 
Mild; just short of breath 
with exercise 
□ 
Moderate; I get short of breath 
doing daily activities 
□ 
Severe; I feel I can't get 
enough air even at rest 
Fatigue (low energy)? 
□ 
None 
□ 
Mild; I go about my day 
normally 
□ 
Moderate; I rest more and 
restrict activity 
□ 
Severe; I am staying in bed 
I'm so tired 
Headache? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; I need to take 
medication 
□ 
Severe; it is markedly 
limiting my life 
Body Ache? 
□ 
None 
□ 
Mild; I can ignore them 
□ 
Moderate; I need to restrict 
some activities 
□ 
Severe; they are markedly 
limiting my life 
Joint pain? 
□ 
None 
□ 
Mild; I can ignore them 
□ 
Moderate; I need to restrict 
some activities 
□ 
Severe; they are markedly 
limiting my life 
Chest pressure? 
□ 
None 
□ 
Mild; I feel it occasionally 
but can ignore it most of 
the time 
□ 
Moderate; I notice it a lot and 
it limits my activity 
□ 
Severe; I have bad pain and 
pressure that bothers me 
most of the time 
Abdominal pain? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; it is limiting my 
activities 
□ 
Severe; it hurts a lot. I may 
need to see a doctor 
Sore Throat? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; it is painful to 
swallow and speak 
□ 
Severe; it is limiting my 
ability to swallow or speak 
Nasal Congestion? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; I notice it a lot 
□ 
Severe; it is markedly 
limiting my life 
Chills? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; I notice it a lot 
□ 
Severe; I am very 
uncomfortable 
Feeling hot or feverish? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; I notice it a lot 
□ 
Severe; I am very 
uncomfortable 
Runny Nose? 
□ 
None 
□ 
Mild; I can ignore it 
□ 
Moderate; frequent but I 
can tolerate it 
□ 
Severe; I am very 
uncomfortable 
Taste? 
□ 
None 
□ 
Mild; tastes aren’t as 
strong as usual 
□ 
Moderate; I’ve noticed I can’t 
taste certain foods 
□ 
Severe; I cannot taste my 
food at all 
Smell? 
□ 
None 
□ 
Mild; smells aren’t as 
strong as usual 
□ Moderate; I’ve noticed I can’t 
smell certain odors 
□ 
Severe; I cannot smell 
anything at all 
Diarrhea? (loose or watery stools in 24 hours) 
□ 
None 
□ 
Mild; less than 3 times 
□ 
Moderate; 3-6 times 
□ 
Severe; more than 6 times 
Nausea (feeling like you want to throw up)? 
□ 
None 
□ 
Mild; I'm eating and 
ignoring it 
□ 
Moderate; I don't want to eat 
and can't ignore it 
□ 
Severe; I am feeling quite 
uncomfortable 


IND 
 COPS-2003 
Version 4.0/Date 04 DEC 2020 
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Vomiting? 
□ 
None 
□ 
Mild; only once or 
occasionally 
□ 
Moderate; 3-4 times per day 
□ 
Severe; I am having trouble 
keeping food down 
How many times have you vomited today? 
 
Do you have a rash? 
Yes 
/ 
No 
The rash is (check all that apply): 
□ 
No rash 
□ 
Covering a small amount of my body 
□ 
Extensive covering of my body 
□ 
Involving the inside of my mouth or 
lips 
□ 
Itchy 
□ 
Itchy with hives 
In the past 24 hours, have you returned to your usual health (before 
your COVID-19 illness)? 
Yes 
/ 
No 
 
 
 
16 REFERENCES 
 
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2019;17(3):181-92. doi: 10.1038/s41579-018-0118-9. PubMed PMID: 30531947; PMCID: 
PMC7097006. 
2. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, 
Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry 
Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. 
Cell. 2020;181(2):271-80.e8. Epub 2020/03/05. doi: 10.1016/j.cell.2020.02.052. PubMed 
PMID: 32142651; PMCID: PMC7102627. 
3. Hoffmann, M., Hofmann-Winkler, H., Smith, J. C., Krüger, N., Sørensen, L. K., Søgaard, O. S., 
Hasselstrøm, J. B., Winkler, M., Hempel, T., Raich, L., Olsson, S., Yamazoe, T., Yamatsuta, K., 
Mizuno, H., Ludwig, S., Noé, F., Sheltzer, J. M., Kjolby, M., & Pöhlmann, S. (2020). Camostat 
mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite 
GBPA exerts antiviral activity. bioRxiv : the preprint server for biology, 2020.08.05.237651. 
https://doi.org/10.1101/2020.08.05.237651 
4. Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, Bashir N, Xue M. Emergence of a Novel 
Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic 
Options. J Clin Microbiol. 2020;58(5). Epub 2020/04/23. doi: 10.1128/JCM.00187-20. PubMed 
PMID: 32161092; PMCID: PMC7180238. 
5. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, Nagata N, Sekizuka T, Katoh 
H, Kato F, Sakata M, Tahara M, Kutsuna S, Ohmagari N, Kuroda M, Suzuki T, Kageyama T, 
Takeda M. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad 
Sci U S A. 2020;117(13):7001-3. Epub 2020/03/12. doi: 10.1073/pnas.2002589117. PubMed 
PMID: 32165541; PMCID: PMC7132130. 
6. Zhong NS, Zheng BJ, Li YM, Poon, Xie ZH, Chan KH, Li PH, Tan SY, Chang Q, Xie JP, Liu 
XQ, Xu J, Li DX, Yuen KY, Peiris, Guan Y. Epidemiology and cause of severe acute respiratory 


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syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet. 
2003;362(9393):1353-8. doi: 10.1016/s0140-6736(03)14630-2. PubMed PMID: 14585636; 
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PMC7095418. 
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