Clinical trial NCT04625114
Conditions: Covid19
Keywords: antiviral
Sponsor: University Hospital, Ghent
Start date: 2020-11-04; Completion date: 2022-07-12
Enrollment: 108 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators are conducting a pilot trial where they will study safety, efficacy and compliance in a cohort of ambulatory patients in the Ghent region with confirmed COVID-19 infection, in both an early stage of disease, defined as less than 5 days of symptoms and who at presentation do not meet any criteria for hospitalisation as well as asymptomatic individuals with a PCR CT value below 30.

The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load.

The aim of the study is to assess whether Camostat, a serine protease inhibitor available in an oral formulation has the potential to be studied as an antiviral drug in a large scale ambulatory setting to prevent transmission by decreasing viral load, to prevent symptoms after exposure (PEP) in asymptomatic individuals or to prevent disease progression in the occurrence of early symptomatology.

Detailed description:
Core study After eligibility assessment participants will be randomized and will receive the study drugs. We will define D1 as the first dose of the medication which can be the morning, midday or evening dose. They will be treated for 5 consecutive days.

In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4), the treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive days: D6 and D10).

Follow-up will be as follows:

* D1-\>D14 (D28): The study participants will be asked to fill in daily questionnaires assessing symptoms (cfr daily self-score). They will receive a kit enabling to monitor heart rate (HR), respiratory rate (RR), temperature and oxygen saturation 3 times per day (every 4-8 hours, preferentially at the timing of medication intake at D1 to D5 or D10).
* Compliance and tolerance will be assessed during the treatment period, D0-\>D5 (or D0-\>D10 if the treatment is prolonged).
* During the study D1-D28: If indicated in the opinion of the investigator, a physical exam and biochemistry will be performed through a consultation at the clinic. This can be requested at any time during the study based on clinical symptoms or signs.
* Consultation at D0, D5, (D10) and D28 at our COVID consultation facility. This will be done by a study nurse and/or a study physician.

Arms: arm 1: camostat 100mg 3 tablets 3x/day D1-\>D5 (+ possible extension D6-\>D10) arm 2: Placebo 3 tablets 3x/day D1-\>D5 (+ possible extension D6-\>D10)
Interventions: intervention 1: Camostat intervention 2: Placebo intervention 3: Camostat intervention 4: Placebo
Intervention descriptions: intervention 1: Standard of care (SOC) + Camostat mesilate (Foipan) 100mg 3 tablets 3 times a day for 5 consecutive days (D1-\>D5); intervention 2: SOC + placebo 500 mg 3 tablets 3 times a day for five consecutive days (D1-\>D5). intervention 3: Standard of care (SOC) + Camostat mesilate (Foipan) 100mg 3 tablets 3 times a day for 5 consecutive days (D6-\>D10); intervention 4: SOC + placebo 500 mg 3 tablets 3 times a day for five consecutive days (D6-\>D10).

Protocol documents:
Prot_SAP_000.pdf: 
COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
1/63 
The potential of oral Camostat in early COVID-
19 disease in an ambulatory setting to reduce 
viral load and disease burden.  
 
Acronym / Protocol code 
 
 
 
COV-AAT 
Protocol version and date 
 
 
 
version 3.0 dd. 04JUN2021 
Phase  
 
 
 
 
 
Phase 2 
EudraCT n° 
 
 
 
 
 
2020-003475-18 
Sponsor 
 
 
 
 
 
Ghent University Hospital  
Financial/Material Support: 
 
 
 
Ono Pharmaceutical LTD 
 
 
 
 
 
 
 
Byteflies  
 
Coordinating Investigator: 
 
 
 
Steven Callens 
 
 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
2/63 
The potential of oral Camostat in early COVID-
19 disease in an ambulatory setting to reduce 
viral load and disease burden.  
 
 
Protocol Coordinating Investigator signature page 
 
 
 
 
I certify that I will conduct the study in compliance with the protocol, any amendments, GCP 
and the declaration of Helsinki, and all applicable regulatory requirements. 
 
 
Investigator: 
 
 
Name: 
 
 
Function: 
 
 
Institution: 
 
 
 
Date:  
 
 
 
 
 
Signature: 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
3/63 
Protocol Amendment History: 
 
Version
Date
Description of amendment
1.2
13OCT2020
Initial version as approved by the Ethics Committee and 
the Federal Agency for Medicines and Health Products. 
2.0
26NOV2020
1. Change of PI/CI to Prof Steven Callens
2. Some changes concerning follow-up and analysis 
methods:  
- 
Extra recruitment materials en methods have 
been added, section 7.2 
- 
Trial conduct in case of hospitalization has been 
adjusted from patient withdrawal to further study 
follow-up, section 8.1.4 and 8.2.4 
- 
Patient home monitoring period was adjusted 
from 14 days to the period of intake of study 
medication (5 or 10 days), section 9.2.1 
- 
Protocols for analysis were adjusted based on 
current practice for PCR and PK/PD, section 10.3 
- 
The gradation of AEs was detailed and references 
were added 
3. Clarifications have been added in the section about 
safety reporting, section 13 
2.1
02FEB2021
Clarification was given concerning the discontinuation of 
treatment and its implication on study follow-up 
compared to study withdrawal, section 7.1.2 
3.0
04JUN2021
1. The option to conduct an interim analysis has been
added to the protocol, section 11.4.  
2. Recruitment strategy has been further explained in 
section 7.2 to tackle potential pitfalls. The COVID-19 
test centre at Ghent University Hospital added the 
possibility to question patients on their consent to be 
contacted by the study team, flyers are available in 
the test centre and when patients that tested positive 
for COVID-19 are called to inform them about their 
results, study interest is interrogated.  
3. Clarification on the possibility of simultaneity of the 
time-points D0 and D1, section 9.2.1.  
4. The role of the PI concerning verification of data input 
of the eCRF has been modified based on clinical 
practice, section 12.1.1.  
5. The option of serum HCG testing to exclude pregnancy 
has been added, section 6.2. 
6. Premature closure of the substudies is being reported, 
sections 9.2.2, 9.2.3 and 9.2.4.  
 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
4/63 
TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS .......................................................................................................................... 8 
1. 
Protocol Summary ......................................................................................................................... 10 
1.1. 
Protocol specifics ................................................................................................................... 10 
1.2. 
Study Type and Study Phase ................................................................................................. 10 
1.3. 
Aim of the study (including primary endpoints) ................................................................... 10 
1.3.1. 
Number of subjects ....................................................................................................... 11 
1.3.2. 
Target group .................................................................................................................. 11 
1.4. 
Inclusion and exclusion criteria ............................................................................................. 11 
1.5. 
Study Interventions ............................................................................................................... 13 
1.5.1. 
IMPs and dosage............................................................................................................ 13 
1.5.2. 
Schematic overview of the data collection & interventions ......................................... 13 
1.6. 
Study duration ....................................................................................................................... 17 
1.6.1. 
For an individual subject ............................................................................................... 17 
1.6.2. 
For the whole study ....................................................................................................... 17 
2. 
Rationale and background............................................................................................................. 18 
2.1. 
Rationale ................................................................................................................................ 18 
2.2. 
Background ............................................................................................................................ 20 
2.3. 
Risk/Benefit Assessment ....................................................................................................... 22 
2.4. 
Limitations ............................................................................................................................. 23 
3. 
Objectives ...................................................................................................................................... 23 
3.1. 
Primary Objectives ................................................................................................................ 23 
3.2. 
Secondary Objectives ............................................................................................................ 23 
4. 
End Points and Time Points ........................................................................................................... 24 
4.1. 
Primary End Points and Time Points ..................................................................................... 24 
4.2. 
Secondary End Points and Time Points ................................................................................. 24 
5. 
Study design .................................................................................................................................. 25 
5.1. 
Description of study design ................................................................................................... 25 
5.2. 
End of Study Definition .......................................................................................................... 26 
5.2.1. 
For an individual subject ............................................................................................... 26 
5.2.2. 
For the whole study ....................................................................................................... 26 
5.3. 
Estimated duration of the study ........................................................................................... 26 
5.3.1. 
For an individual subject ............................................................................................... 26 
5.3.2. 
For the whole study ....................................................................................................... 26 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
5/63 
6. 
Inclusion and Exclusion Criteria ..................................................................................................... 27 
6.1. 
Inclusion Criteria .................................................................................................................... 27 
6.2. 
Exclusion Criteria ................................................................................................................... 28 
6.3. 
Screen failures ....................................................................................................................... 28 
7. 
Target Population .......................................................................................................................... 28 
7.1. 
Subjects ................................................................................................................................. 28 
7.1.1. 
Number of subjects and planned recruitment rate ...................................................... 28 
7.1.2. 
Withdrawal and replacement of subjects ..................................................................... 28 
7.2. 
Method of recruitment ......................................................................................................... 29 
7.3. 
Screening ............................................................................................................................... 30 
8. 
Investigational Medicinal Product (IMP) ....................................................................................... 30 
8.1. 
Camostat Mesilate ................................................................................................................. 30 
8.1.1. 
Composition and active substance of the IMP .............................................................. 30 
8.1.2. 
Producer and Distributor of the IMP ............................................................................. 30 
8.1.3. 
Preparation + Dosage + administration of the IMP ....................................................... 30 
8.1.4. 
Permitted dose adjustments and interruption of treatment ........................................ 31 
8.1.5. 
Duration of treatment ................................................................................................... 32 
8.1.6. 
Packaging and Labeling of the IMP ................................................................................ 32 
8.1.7. 
Storage conditions of the IMP ....................................................................................... 32 
8.1.8. 
Known side effects of the medication ........................................................................... 33 
8.2. 
Placebo .................................................................................................................................. 33 
8.2.1. 
Composition of the placebo .......................................................................................... 33 
8.2.2. 
Producer and Distributor of the placebo ...................................................................... 33 
8.2.3. 
Preparation + Dosage + administration of the placebo ................................................ 33 
8.2.4. 
Permitted dose adjustments and interruption of treatment ........................................ 33 
8.2.5. 
Duration of treatment ................................................................................................... 34 
8.2.6. 
Packaging and Labeling of the placebo ......................................................................... 35 
8.2.7. 
Storage conditions of the placebo................................................................................. 35 
8.2.8. 
Known side effects of the medication ........................................................................... 35 
8.3. 
Concomitant / Rescue Medication ........................................................................................ 35 
9. 
Study Specific Procedures ............................................................................................................. 36 
9.1. 
Randomisation/blinding ........................................................................................................ 36 
9.1.1. 
Randomisation ............................................................................................................... 36 
9.1.2. 
Blinding .......................................................................................................................... 36 
9.1.3. 
Deblinding procedures .................................................................................................. 37 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
6/63 
9.2. 
Study specific interventions .................................................................................................. 37 
9.2.1. 
Core trial ........................................................................................................................ 37 
9.2.2. 
PK/PD substudy ............................................................................................................. 39 
9.2.3. 
Odor substudy: Odor sampling SARS-CoV-2 patients ................................................... 39 
9.2.4. 
COVIM2.0 substudy: Immunological and virological assessment ................................. 40 
9.2.5. 
Screening failures substudy ........................................................................................... 40 
9.3. 
Overview of collected data .................................................................................................... 40 
9.4. 
Schematic overview of the data collection & interventions ................................................. 41 
9.5. 
Restrictions for subjects during the study ............................................................................. 41 
10. Sampling ........................................................................................................................................ 42 
10.1. 
Types and number of samples .......................................................................................... 42 
10.2. 
Timepoints of sampling ..................................................................................................... 42 
10.3. 
Sample Handling & Analysis .............................................................................................. 42 
10.4. 
Sample Storage and/or shipping ....................................................................................... 46 
10.5. 
Future use of stored samples ............................................................................................ 47 
11. Statistical Considerations .............................................................................................................. 48 
11.1. 
Sample size calculation ...................................................................................................... 48 
11.2. 
Type of statistical methods ............................................................................................... 49 
11.3. 
Statistical analysis team .................................................................................................... 50 
11.4. 
Interim analysis ................................................................................................................. 50 
12. Data handling ................................................................................................................................ 51 
12.1. 
Method of data collection ................................................................................................. 51 
12.1.1. 
Case Report Form .......................................................................................................... 51 
12.1.2. 
Data directly collected in the CRF (no source available) ............................................... 51 
12.2. 
Data storage ...................................................................................................................... 51 
12.3. 
Archiving of data................................................................................................................ 52 
12.4. 
Access to data .................................................................................................................... 52 
13. Safety ............................................................................................................................................. 52 
13.1. 
Definitions ......................................................................................................................... 52 
13.2. 
Reporting requirements .................................................................................................... 54 
13.2.1. 
AE reporting ................................................................................................................... 54 
13.2.2. 
SAE reporting ................................................................................................................. 54 
13.2.3. 
SUSAR reporting ............................................................................................................ 54 
13.2.4. 
Other reporting requirements....................................................................................... 55 
13.3. 
List of contact details for safety reporting ........................................................................ 55 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
7/63 
13.4. 
Flowchart Reporting .......................................................................................................... 56 
13.5. 
Events, excluded from reporting ....................................................................................... 56 
13.6. 
Data Safety Monitoring Board (DSMB).............................................................................. 57 
13.7. 
Development Safety Update Report ................................................................................. 57 
14. Monitoring/Auditing/Inspection ................................................................................................... 57 
14.1. 
Monitoring ......................................................................................................................... 57 
14.1.1. 
General .......................................................................................................................... 57 
14.1.2. 
Monitoring team ........................................................................................................... 57 
14.1.3. 
Scope ............................................................................................................................. 57 
14.2. 
Inspection .......................................................................................................................... 58 
14.3. 
Protocol Deviation policy .................................................................................................. 58 
14.4. 
Serious breach to GCP and/or the protocol ...................................................................... 58 
15. Ethical and legal aspects ................................................................................................................ 58 
15.1. 
Good Clinical Practice ........................................................................................................ 58 
15.2. 
Informed Consent .............................................................................................................. 59 
15.3. 
Approval of the study protocol ......................................................................................... 60 
15.3.1. 
General .......................................................................................................................... 60 
15.3.2. 
Protocol amendments ................................................................................................... 60 
15.4. 
Confidentiality and Data Protection .................................................................................. 60 
15.5. 
Liability and Insurance ....................................................................................................... 61 
15.6. 
End of Study Notification ................................................................................................... 61 
16. Publication policy .......................................................................................................................... 61 
17. Reference List ................................................................................................................................ 61 
18. Appendices .................................................................................................................................... 63 
18.1. 
Appendix 1: Study Schedule .............................................................................................. 63 
18.2. 
Appendix 2: Questionnaire Daily self score ....................................................................... 63 
18.3. 
Appendix 3: Socio-demographic parameters .................................................................... 63 
18.4. 
Appendix 4: Emergency ward flow chart .......................................................................... 63 
18.5. 
Appendix 5: Byteflies manual ............................................................................................ 63 
18.6. 
Appendix 6: Parameter log ................................................................................................ 63 
18.7. 
Appendix 7: Medication log............................................................................................... 63 
18.8. 
Appendix 8: Proposed cut-offs for abnormal values ......................................................... 63 
18.9. 
Appendix 9: DSMB charter ................................................................................................ 63 
18.10. 
Appendix 10: Toxicity lab .................................................................................................. 63 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
8/63 
LIST OF ABBREVIATIONS 
 
AE 
 
= 
Adverse Event 
CI 
 
= 
Coordinating Investigator 
CT 
 
= 
Clinical Trial Unit 
CT 
 
=  
Cycle Threshold  
DSMB  
= 
Data Safety Monitoring Board 
DSUR  
= 
Development Safety Update Report 
EC 
 
= 
Ethics Committee 
eCRF 
 
= 
electronic Case Report Form 
EDC 
 
= 
Electronic Data Capture 
EPD 
 
= 
Electronic Patient Dossier 
FAMHP  
= 
Federal Agency for Medicines and Health Products 
FPI 
 
= 
First Patient In 
GCP 
 
= 
Good Clinical Practice 
GDPR  
= 
General Data Protection Regulation 
GMP 
 
= 
Good Manufacturing Practice 
HIRUZ  
= 
Health, Innovation and Research Institute UZ Ghent 
HR 
 
= 
Heart Rate  
IB 
 
= 
Investigator’s Brochure 
ICF 
 
= 
Informed Consent Form 
ICH 
 
= 
International Council for Harmonisation 
IMP 
 
= 
Investigational Medicinal Product 
IMPD  
= 
Investigational Medicinal Product Dossier 
LN 
 
= 
Liquid Nitrogen 
LVLS 
 
= 
Last Visit, Last Subject 
PD 
 
= 
Pharmacodynamics 
PI 
 
= 
Principal Investigator 
PK 
 
= 
Pharmacokinetics 
POC 
 
= 
Point of care  
RR  
 
= 
Respiratory rate  
SAE 
 
= 
Seriouse Adverse Event 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
9/63 
SmPC  
= 
Summary of Product Characteristics 
SOC 
 
= 
Standard of care  
SOP 
 
= 
Standard Operating Procedure 
SUSAR  
= 
Suspected Unexpected Serious Adverse Reaction 
TERENA 
= 
Trans-European Research and Education Networking Association 
TLS 
 
= 
Transport Layer Security 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
10/63 
1. Protocol Summary 
 
1.1. 
Protocol specifics 
 
Title: The potential of oral Camostat in early COVID-19 disease in an ambulatory setting to reduce viral 
load and disease burden.  
 
Protocolcode: COV-AAT 
 
EudraCT number: 2020-003475-18 
 
Sponsor: Ghent University Hospital 
 
1.2. 
Study Type and Study Phase 
 
Phase 2 clinical trial  
A randomized, placebo controlled, double blinded, prospective trial to assess the efficacy and safety 
of Camostat, by inhibiting S protein-initiated membrane fusion in the treatment of early phase COVID 
19 disease in an ambulatory setting. 
The trial is adaptive and can be adjusted if new data on PK/PD, safety or efficacy becomes available. 
Adjustments will only be implemented after written approval from the Ethics Committee and 
Competent Authority (if applicable). 
 
1.3. 
Aim of the study (including primary endpoints) 
 
We are conducting a pilot trial where we will study safety, efficacy and compliance in a cohort of 
ambulatory patients in the Ghent region with confirmed COVID-19 infection, in both an early stage of 
disease, defined as less than 5 days of symptoms and who at presentation do not meet any criteria for 
hospitalisation as well as asymptomatic individuals with a PCR CT value below 30.  
The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in 
respiratory (oropharyngeal swab RT-PCR) log10 viral load.  
The aim of the study is to assess whether Camostat, a serine protease inhibitor available in an oral 
formulation has the potential to be studied as an antiviral drug in a large scale ambulatory setting to 
prevent transmission by decreasing viral load, to prevent symptoms after exposure (PEP) in 
asymptomatic individuals or to prevent disease progression in the occurrence of early 
symptomatology.  
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
11/63 
1.3.1. Number of subjects 
We aim to include 150 participants. Symptomatic individuals will be included either directly through 
the emergency room at Ghent University Hospital or after referral from regional hospitals and general 
practitioners (general practitioners outposts) to the emergency room or the COVID consultation area 
at Ghent University Hospital. Asymptomatic individuals with positive PCR can be included through the 
COVID test centre at the Ghent University Hospital and at the COVID consultation. Inclusions will be 
done exclusively at Ghent University Hospital. The follow-up will be done through a monitoring tool 
provided by Byteflies, by phone and/or email and at the COVID consultation area that has been 
installed on the Ghent University Hospital Campus. 
 
1.3.2. Target group 
Patients will be selected either based on the presence of symptoms suggestive of COVID-19 disease 
based on clinical symptoms and signs or any asymptomatic individual that presents with a positive 
screening test with CT value below the threshold of 30. Inclusion will be based on a positive COVID 
screening by RT-PCR, gene expert, IgM antibody screening or any other comparable test confirming 
COVID infection and eligibility will be checked based on the flowchart used at the emergency 
department (appendix 4). Patients that need to be hospitalised or have a high risk of hospitalization, 
based on these criteria, will not be included.  
In case of negative screening test and suggestive clinical picture, the test can be completed with 
additional blood analysis, arterial blood gas and/or lung imaging to assess the probability of COVID-19. 
These additional tests are a decision of the treating physician and will only be performed if necessary 
for the patient’s standard of care. In this case the study physician can decide to rescreen the patient 
after minimum 24h and within the 5 days of occurrence of symptoms (with PCR).  
The medication will be initiated as soon as possible after inclusion and randomisation. We will define 
D1 as the first dose of the study medication at whatever point of time during that day. Thus, D0 and 
D1 can coincide (if the participant starts taking medication on the day of inclusion). 
 
1.4. 
Inclusion and exclusion criteria 
 
Inclusion 
 
Aged ≥18  
 
Willing to participate and fill out a daily symptom diary  
 
Willing to take the parameters such as blood oxygenation and temperature 
 
Willing to attend follow-up visits both by phone as at the clinic 
 
Capable of understanding the commitment in the trial 
 
Signed informed consent  
 
Signs and symptoms suggestive of COVID disease in absence of hospitalization criteria as 
defined by the flowchart used at the emergency department at Ghent University Hospital 
(appendix 4), present for maximum 5 days and confirmed by PCR.  
 
 OR documented COVID-19 infection by PCR with CT value below the threshold of 30 in 
asymptomatic individuals.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
12/63 
 For women of childbearing potential*: they should be willing to use highly effective method 
of contraception during treatment and until the end of study defined as having a failure 
rate of less than 1% per year when used consistently and correctly.  
Such methods include: 
o combined (estrogen and progestogen containing) hormonal contraception 
o associated with inhibition of ovulation: oral, intravaginal or transdermal 
o progestogen-only hormonal contraception associated with inhibition of ovulation: 
oral, injectable or implantable  
o intrauterine device (IUD) and intrauterine hormone-releasing system (IUS)  
o bilateral tubal occlusion  
o vasectomised partner 
o sexual abstinence 
 
For men of reproductive potential**: condom should be used as contraception during 
treatment and until the end of study when having a partner of childbearing potential 
 
*a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until 
becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined 
as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone 
(FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women 
not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient. 
**a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
 
Exclusion 
 
Inability to make a decision to participate  
 
Pregnant or breast feeding 
 
Inability to take oral medication 
 
Inability to provide informed written consent 
 
Known hypersensitivity towards Camostat or other Serine protease inhibitors 
 
Any condition that, in the Investigator’s opinion, prevents adequate compliance with study 
therapy.  
 
Any COVID infection at risk for hospitalisation as described in the flowchart used at the 
emergency department (appendix 4) 
 
With regard to exclusion of women of child-bearing potential, women who tell us they 
know they are pregnant are excluded. All women of child-bearing potential who test 
positive for pregnancy by urine test or serum (if an early pregnancy cannot be excluded) 
at first visit are excluded.  
 
Severe chronic pancreatitis requiring suction of gastric juice, fasting or abstention from 
drinking. 
 
Postoperative reflux oesophagitis due to reflux of gastric juice 
 
Postoperative reflux oesophagitis (if improvement of symptoms is not observed).  
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
13/63 
1.5. 
Study Interventions 
 
1.5.1. IMPs and dosage 
Standard of care (SOC) + Camostat mesilate (Foipan) 100mg 3 tablets 3 times a day for 5 consecutive 
days (D1D5); 
versus  
SOC + placebo 500 mg 3 tablets 3 times a day for five consecutive days (D1D5). 
Randomisation 2:1 Camostat versus placebo.   
In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical 
symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4, the 
treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive 
days: D6D10). 
 
1.5.2. Schematic overview of the data collection & interventions 
1.5.2.1 Core study 
After eligibility assessment participants will be randomized and will receive the study drugs. We will 
define D1 as the first dose of the medication which can be the morning, midday or evening dose. They 
will be treated for 5 consecutive days. D0 and D1 can coincide, if the participant starts taking 
medication on the day of inclusion.  
In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical 
symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4), 
the treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive 
days: D6D10). 
Follow-up will be as follows:  
- 
D1D14: The study participants will be asked to fill in daily questionnaires assessing 
symptoms (cfr daily self-score). This will be extended to D28 if patients are still 
symptomatic at D14. 
- 
D1D5 (or D10): They will receive a kit enabling to monitor heart rate (HR), respiratory 
rate (RR), temperature and oxygen saturation 3 times per day (every 4-8 hours, 
preferentially at the timing of medication intake at D1 to D5 or D10). This can be extended 
after completion of the medication as SOC in presence of symptoms and for the period 
that symptoms persist.  
- 
Compliance and tolerance will be assessed during the treatment period, D0D5 (or 
D0D10 if the treatment is prolonged).  
- 
During the study D1-D28: If indicated in the opinion of the investigator, a physical exam 
and biochemistry will be performed through a consultation at the clinic. This can be 
requested at any time during the study based on clinical symptoms or signs.  
- 
Consultation at D0, D5, (D10) and D28 at our COVID consultation facility. This will be done 
by a study nurse and/or a study physician.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
14/63 
At D0 (screening and inclusion) a standardized history, clinical exam will be performed, including blood 
pressure (BP), heart rate (HR), respiratory rate (RR), blood oxygen saturation, temperature. Socio-
demographic parameters such as age, gender, treatment, smoking status, BMI, diabetes, race and 
comorbidities will be assessed. If unavailable, a COVID screening test will be performed to confirm 
COVID 19 infection. A baseline lab for toxicity will be done on D0 (max 21ml).  
In case of negative screening test and suggestive clinical picture as described above, the test can be 
completed with additional blood analysis, arterial blood gas and/or lung imaging to assess the 
probability of COVID-19. The additional tests are SOC. It is the treating physician who will decide 
whether these test are valuable. In this case the study physician can decide to rescreen the patient 
(with PCR) after minimum 24h and within the 5 days of occurrence of symptoms. 
The medication will be initiated as soon as possible after inclusion and randomisation. We will define 
D1 as the first dose of the study medication at whatever point of time during that day. Thus, D0 and 
D1 can coincide (if the participant starts taking medication on the day of inclusion). 
At D1 up to D14 (or until D28 if they still have symptoms at D14), participants will be asked for the 
presence of symptoms and signs by a questionnaire and to monitor temperature, blood oxygen 
saturation, heart rate and respiratory rate.  
If indicated in the opinion of the investigator, a physical exam and biochemistry will be performed 
through a consultation at the clinic. This can be requested at any time during the study based on clinical 
symptoms or signs. 
At D5 a scheduled study visit is planned with a clinical exam including BP, RR, HR, temperature, blood 
oxygen saturation. Nasopharyngeal (or combined nose/throat) swab will be taken for PCR. CRP can be 
assessed by point of care test or routine lab when clinically relevant as part of SOC. A toxicity screening 
will be performed through a venous blood draw (max 21ml). At the day of consultation the time point 
at the hospital will replace the monitoring measurement at home.  
At any given time between D1 and D28 an additional blood draw (max. 21 ml) can be asked by the 
study team to assess severity of infection (peripheral blood count, inflammation, electrolytes, kidney 
and liver function.) If CRP values are available at baseline and/or follow-up they will be analyzed as 
part of the study, however this will only be performed as SOC. If HRCT or a lung X ray are available at 
baseline or follow-up, they will be analyzed as part of the study, however they will only be performed 
as SOC.  
At D28 an additional blood draw (9 ml) will be done for neutralizing antibodies (Nabs) titer assessment. 
At D10 an additional study visit will be planned in individuals that are retested with positive PCR at D5 
and when treatment is prolonged after D5 up to D10. This will include a clinical exam including BP, RR, 
HR, temperature, blood oxygen saturation. At the day of consultation the time point at the hospital 
will replace the measurement at home. Also, a toxicity screening will be performed through a venous 
blood draw (max 21ml) if any significant abnormalities occurred at D5 (Grade 1-2 adverse events as 
defined by CTCAE1.  
At D10 and D28 an additional nasopharyngeal swab or combined nose/throat swab will be performed 
in individuals that still had a positive PCR result at day 5 and D10 respectively.   
                                                          
1 https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
15/63 
Questionnaires will be sent through email and can be filled in online and transferred directly to the 
eCRF or will be filled in on paper and handed to the study personnel at the time of consultation.  
Home monitoring of heart rate, respiratory rate, temperature and oxygen saturation will be done 
through a kit provided by Byteflies. A manual with usage instructions will be delivered to the patients. 
The patient will be asked to register these parameters 3 times a day through an online platform. If they 
are unable to register the parameters themselves, a back-up through email or phone can be proposed. 
If these parameters are not within normal range as defined by cut-off criteria (appendix 8), the system 
will ask either to remeasure or to contact the study-team based on the reported values. 
Participants that meet hospitalization criteria will not be considered drop-outs/withdrawals. These 
patients will no longer take any study medication but their outcomes will still be monitored for the 
duration of the study period. This means: 
- 
Study medication will be interrupted completely (and will not be reinitiated). 
- 
As long as the patient is submitted to the hospital (and maximum until D28): 
o No study-specific interventions (from the core study nor the substudies) will be 
performed. 
o Patient’s standard of care COVID-19 data will be collected. If the patient is 
hospitalized in Ghent University Hospital, the study team will consult the EPD. If 
the patient is hospitalized in another hospital, the study team will contact the 
treating physician or GP.  
- 
After the patient has been released from the hospital: 
o In case the patient has been discharged before D28, only some of the study-
specific interventions will be carried out: 
 
If the patient has been discharged before D14: the study participants will 
be asked to fill in daily questionnaires assessing symptoms (cfr daily self-
score) until D14. This will be extended to D28 if patients are still 
symptomatic at D14. 
 
If the patient has been discharged on or after D14 and if symptoms are 
still present at the time of discharge: the study participants will be asked 
to fill in daily questionnaires assessing symptoms (cfr daily self-score) until 
D28. 
 
The study visit on D28 will be performed as stipulated in the study 
protocol, except for the medication log check and the check on 
compliance and tolerance of the study medication, as this will no longer 
be applicable. 
 
Except for the PK/PD substudy, all substudies will be carried out as 
indicated in the protocol (only those for which the patient agreed on 
participating). 
o In case the patient has been discharged after D28, no further study-specific 
interventions (from the core study nor the substudies) will be performed. 
 
1.5.2.2 PK/PD substudy 
Participants will be asked to participate in a PK/PD substudy. We aim to include 50 patients samples in 
the Camostat treatment arm, therefore sampling approx. half of the participants in both arms. When 
we have 50 participants in the camostat arm, inclusions will be stopped. Drop-outs however will be 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
16/63 
replaced. If the participant agrees, PK/PD samples will be taken during the treatment phase between 
D1 and D5. 4 additional blood samples will be taken between two intakes of the study medication: at 
30’, 60’, 2-4h, and 4-8h (on the same day, between D1 and D5). The samples will be deblinded during 
the study by an unblinded person. After unblinding, only the samples from patients in the Camostat 
group will be sent for analysis. Samples that are not used for PK/PD analysis, will be stored in the 
prospective Biobank for future studies. 2x3ml of blood will be taken per sampling point =24ml.  
Update dd. 04JUN2021: This study was prematurely closed after a test phase due to logistic reasons.  
 
1.5.2.3 Odor substudy: Odor sampling SARS-CoV-2 patients 
All participants will be asked to participate in a substudy analysing odor samples from COVID 19 
infected individuals. The goal of this study is to take odor samples at the arm pit and between the legs, 
in order to train dogs to identify COVID-19 infected individuals. In this way, dogs can be trained to 
identify COVID 19 infected individuals in groups and avoid transmissions. If participants consent, at D5 
a cotton pad will be put in the arm pits and between the legs to capture the odors for approx 60 
minutes. The samples will be sent to the dog training centre (K9 Training Centrum, Brugsesteenweg 
105 8450 Bredene, responsible: Johan Weckhuyzen (CEO)) where they will be used to train dogs to 
identify COVID-19 infected individuals. These samples will be used one time and will be destroyed after 
usage at the training centre.  
Update dd. 04JUN2021: This study ended at the end of May 2021 after having recruited a sufficient 
amount of participants and in the absence of budget to prolong the inclusions.  
 
1.5.2.4 COVIM2.0 substudy: Immunological and virological assessment  
Deep characterization of patients’ inflammatory profile offers a unique opportunity for comprehensive 
understanding of the pathophysiological mechanisms behind SARS-CoV2. All participants will be 
therefore asked for additional blood sampling at D0 and D28 (8X9ml). The lipidomics analysis will be 
performed at the laboratory of Dr. Jesmond Dalli. In addition, we will study immunological functions 
on the level of both adaptive and innate immunity by performing extensive immunophenotyping, 
cytokine analysis and RNA sequencing analysis. Biomarker analysis will be performed on protein and 
on RNA single cell level. Infectivity of different cell types including macrophages will performed. These 
analyses will be performed at the HCRC laboratory, the laboratory of Prof. Rafick-Pierre Sékaly and the 
VIB-UGent Center for Inflammation Research. To gain a deeper understanding of pathways potentially 
leading to severe disease courses, and also to chart where in the body there is tissue damage (apart 
from the lungs), we aim to analyze patient plasma samples with several other analytics technologies 
as well. Bacterial extracellular vesicles, due to microbial translocation after hyperinflammation, will be 
quantified from plasma in the laboratory of Experimental Cancer Research of Ghent University. 
Furthermore, normal cell turnover in tissues results in the release of some of their nucleic acid content 
into the blood. This can then be found as circulating free RNA and DNA (cfRNA and cfDNA). These 
analyses will be performed at the laboratory of Prof. Jo Vandesompele (Biogazelle). Virological 
evaluations will be based on nasopharyngeal (or nose-throat) swab samples, used to diagnose and 
quantify SARS-CoV2. In addition a swab will be taken to culture the SARS-CoV2 virus at D0. This will be 
repeated at D5, D10 and D28 if PCR is positive on these timepoints (an extra swab will be taken). On a 
selection of nasopharyngeal swab samples from patients whole genome sequencing of the SARS-CoV2 
virus will be performed to study the viral diversity and trace patterns of spread across multiple 
epidemiological scales. In addition, a viral metagenomics analysis using Nanopore sequencing will be 
used to reveal the presence of other viruses besides SARS-CoV2 (lab of Hans Nauwynck). 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
17/63 
Update dd. 04JUN2021: This substudy was not initiated due to the lack of availability of lab technicians.  
 
1.5.2.5 Screening failures substudy 
Asymptomatic individuals with positive PCR and high CT values that are not eligible for the clinical trial 
and drug administration, but who otherwise meet all in- and exclusion criteria, can participate in a 
substudy, where we want to see whether these individuals, despite their high CT values and therefore 
low viral load can carry viable virus and therefore can transmit the disease. This implicates whether or 
not they should be isolated. Furthermore, in individuals with low viral load there is a possibility that 
they do not develop antibodies against SARSCOV2. Therefore we want to 1) culture virus from 
throat/nose swabs from these individuals at D0 2) measure antibodies at D28.  
 
1.5.2.6 Flowchart 
Cfr appendix 1.  
 
1.6. 
Study duration 
 
1.6.1. For an individual subject 
The duration of the study will be 28 days of follow-up after inclusion, i.e. maximum 29 days in total for 
the patient.  
 
1.6.2. For the whole study 
We expect the whole study to take 2 years starting in November 2020. This is a rough estimation as 
we cannot predict when, how hard and how long the second and/or third wave of the COVID19 
epidemic will hit us.  
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
18/63 
2. Rationale and background 
 
2.1. 
Rationale 
 
Covid-19 is a new emerging disease causing severe respiratory symptoms in a substantial amount of 
people with an increased mortality especially in elderly and in men with cardio-vascular comorbidities 
(hypertension, obesity and diabetes) (Kunyu Yang et a., Clinical characteristics, outcomes, and risk 
factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, 
retrospective, cohort study, The Lancet Oncology, 2020). Due to its high contagiousness, the pandemic 
caused by this novel SARS-CoV-2 coronavirus poses a major threat to public health.  
So far, no therapeutic intervention has been proven to be efficient in the treatment of this disease and 
prevention of severe acute respiratory distress.  
We propose the use of Camostat, an antiviral drug with potential effects on viral entry of the SARS-
CoV-2 virus as shown by in vitro data (Hoffman et al, 2020). Camostat Mesilate is a serine protease 
inhibitor, licensed for the treatment of chronic pancreatitis in Japan. Camostat inhibits the host cell 
serine protease TMPRSS2, needed to prime viral protein S for cell entry. Besides Camostat, another 
drug in its class shows promising results. Nafamostat however is only available in iv formulation but 
phase I studies are being planned to see whether an oral formulation can be proposed as an alternative 
to Camostat, potentially reaching higher drug levels in serum and tissues.  
 
Figure 1: Viral entry of SARS-CoV-2 Illustrator: Hoffman Marcus 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
19/63 
An important point for the use of antiviral drugs in COVID-19 disease is that their effect is to be 
expected in the early stages of disease. By reducing viral replication early, we hypothesize that we can 
prevent progression towards the second phase of infection which is characterised by increase 
inflammation and cytokine release, mostly responsible for the bad outcome in infected patients 
(Dimitar Popov. “Treatment of Covid-19 Infection. A Rationale for Current and Future Pharmacological 
Approach”. EC Pulmonology and Respiratory Medicine 9.4 (2020): 38-58.). Therefore, it seems only 
logical to provide these antiviral drugs at the early stage of infection, preferentially in an outpatient 
setting.  
 
Figure 2: Disease stages  
 
We could also hypothesize that in a further stage, these drugs might be of interest to provide 
prophylaxis to highly exposed, non-immunised individuals eg family members, healthcare workers etc.  
The goal of this study is to provide substantial data on the efficacy (in terms of viral clearance), safety, 
compliance and pharmacokinetics of Camostat (and possibly other drugs of the same class). This will 
allow us to assess the interest of this drug in larger ambulatory trials.  
In a first phase, participants will be enrolled at the University Hospital in Ghent after presentation at 
the emergency room and can be referred to us by the general practitioners in the region around Ghent 
and other regional hospitals. They will be randomised (2:1) SOC + Camostat versus SOC + placebo. The 
trial will be placebo controlled, double blinded and adaptive based on our data or the data on efficacy 
and safety from other trials currently assessing these drugs (Ono pharmaceutical LTD, SPIKE-1 trial 
Oxford, CamoCO-19 Denmark, Yale University).   
The primary endpoint will be to assess the efficacy of the drug in terms of viral clearance based on 
nasopharyngeal (or combined nose/throat) PCR, the safety and compliance of the drug in ambulatory 
setting. Furthermore, we want to assess whether the administration of antiviral drugs has an effect on 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
20/63 
the presence of neutralising antibodies at D28. The secondary outcome will be to assess the efficacy 
of the antiviral drug in terms of clinical outcome, in terms of hospitalised participants at D14, the 
disappearance of symptoms and the clinical status will be assessed by collecting symptoms and using 
the daily clinical score. The emergence of viral resistance in response to therapy can be assessed in 
case of prolonged viral shedding. 
 
2.2. 
Background 
 
In April 2020 Hoffman et al. Published a paper showing how Camostat (orally) and Nafamostat (iv) have 
an effect on the entry of SARS-CoV-2 in the host cells (https://doi.org/10.1016/j.cell.2020.02.052, 
https://aac.asm.org/content/aac/64/6/e00754-20.full.pdf). Camostat Mesilate is a serine protease 
inhibitor, licensed for the treatment of chronic pancreatitis in Japan. Camostat inhibits the host cell 
serine protease TMPRSS2, needed to prime viral protein S for cell entry. It has the advantage to be a 
safe drug, which is licensed at 600mg daily dosing for the treatment of chronic pancreatitis in Japan. 
Due to its use in ambulatory care in Japan without major side effects, it is a good candidate in the 
setting of early COVID treatment and prevention. Therefore this drug was selected as a strong 
candidate for this pilot study and if we can confirm its efficacy and safety and the chosen dose, whether 
we can apply it in a large setting. 
 
Rationale for dose selection:  
The approved dose for Foipan is 100mg three times daily for postoperative reflux oesofagitis and 
200mg three times daily for symptomatic treatment of chronic pancreatitis. Much higher doses have 
been used in some smaller studies without any severe adverse effects up to 7,2g daily for severe oral 
carcinomas (Ohkoshi et al, J. Maxillofac Surgery 1984; 12:148-52). 
Camostat is a drug which is not detectable in blood or plasma after oral administration. PK data of its 
active metabolite 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA) are scarce and only available in 
healthy volunteers (ONO pharmaceutical LTD, not published).  
Although this dose is not used in clinical practice, this dosing regimen has been studied by Sato et al, 
1992 in a phase II trial in 62 patients with postoperative reflux esophagitis during 8 weeks of treatment. 
Three adverse reactions (edema, feeling of nasal congestion, and urticaria) occurred in 2 of 62 patients. 
No clinically meaningful events were reported. More recently ONO pharmaceuticals conducted a 
phase I trial with dosing schedules up to 2400mg/day and only report one adverse event 
(hyperuricemia) (unpublished data). 
The proposed regimen for this trial is based on simulations using population PK parameters from a 
Phase I healthy volunteer study (ONO Pharmaceuticals; dose 600 mg 4 times daily) and the recently 
reported in vitro  EC50 of antiviral activity of GBPA against the SARS Cov2. 
From these simulations, it can be derived that time above the EC50 equals 5.3 h per day if a dose of 
300 mg is administered three times daily in fasted condition. Results are presented in the Figure and 
Table below. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
21/63 
 
Figure 3: Simulated concentration-time profile using popPK parameters from a pilot Population PK model in healthy volunteers 
(ONO pharmaceuticals). The red dashed line represents the EC50 of the active metabolite of camostate mesilate (GBPA).  
 
 
Table 3. Time above the EC50 and average concentration per day of the active metabolite of camostate mesilate (GBPA) 
Studies in rat and dog revealed [14C]camostat in the lung to be 1- to 3.8-fold that in the plasma. If 
accumulation occurs in humans, this would result in an even higher time above EC50 using a 300 mg 3 
times daily dosing regimen. 
Data are currently lacking on the magnitude of accumulation in human lung tissue and the required 
tissue concentration for optimal efficacy, however we believe the above rationale provides enough 
support to select a 3 x 300mg dosing regimen in this phase II clinical trial.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
22/63 
A daily dose of 900mg is the highest dose for which enough safety data is available to be used in a 
phase II clinical trial. For compliance reasons, we preferred a 3 daily dosing regimen over a 4 daily 
dosing regimen. From their data in healthy volunteers, ONO pharmaceuticals also reported that food 
intake has a large impact on drug disposition and a fasting state should be recommended in future 
clinical trials.  Therefore, patients in our study will be taking their medication in a fasting state. 
We are aware that ONO pharmaceutical LTD and other research groups (Oxford University, Aarhus 
University, University of Vienna, Yale University) are launching a phase I/ II and III trial to assess safety 
and efficacy at lower and higher dosing regimens (up to 2400mg daily). Moreover, more data from in 
vitro and animal experiments are expected to be published in the coming months. If these data become 
available during the trial, this could be used to optimize the study dosing regimen in terms of efficacy, 
tolerability and patient compliance. Adjustments will only be implemented after written approval from 
the Ethics Committee and Competent Authority (if applicable). 
 
Rationale for duration of treatment:  
This is based on current guidelines for the treatment of lower respiratory tract infections with antiviral 
and antibacterial drugs. For influenza the treatment with oseltamivir (Tamiflu) is 5 days. For mild to 
moderate bacterial pneumonia recommendations are 5 days of antibiotics or even less 
(DOI:10.1056/NEJMoA1912400).  
If the PCR remains positive and above a CT value of <30, we will continue the treatment for an 
additional 5 days as we assess that these individuals are still infectious and therefore will benefit from 
prolonged treatment. Also in patients with persisting symptoms we will extend the treatment.  
 
Rationale for an outpatient trial in COVID-19:  
The rationale for enrolling patients in early phase of disease and with mild to moderate symptoms not 
requiring hospitalisation is to assess whether these antivirals can have an effect on symptom 
reduction, viral shedding and risk of disease progression. Our data can support a larger trial assessing 
the effect on clinical outcome but could also support their usage in PEP after exposure or to reduce 
transmission in co-housing (eg households or care facilities) due to their effect on viral shedding. 
Moreover, this drug has an interesting safety profile and therefore the potential benefits of Camostat 
on COVID-19 are likely to counter the low risk of significant adverse effects.  
 
2.3. 
Risk/Benefit Assessment 
 
A study-specific risk assessment plan (separate document) will be available to address, in detail, the 
most relevant potential risks and to specify the mitigation of those risks. Risks will be scaled into low, 
medium and high risks.  
 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
23/63 
2.4. 
Limitations 
 
The Belgian government has successfully reduced the incidence of COVID-19 to a low level 
transmission, with an R0 that has been estimated below 1 for several weeks now. However, the 7 day 
average number of diagnosis has remained stable and even increased at the end of June. We expect 
that due to the changing behavioral pattern of the population at risk of infection and the low level of 
immunity in the community, a second, albeit smaller, wave can occur. However, conversely to the first 
wave, more paucisymptomatic or asymptomatic people will be tested, thus increasing the number of 
eligible subject for this trial significantly.  
The numbers of participants we can include in this pilot trials will likely be underpowered to show an 
effect on clinical outcome and hospitalisation. Therefore, these results should be interpreted with 
caution as the risk exists that a valid drug candidate might be rejected based on these results when 
not put in the right perspective.  
 
3. Objectives  
 
3.1. 
Primary Objectives 
 
The aim of the study is to assess whether Camostat, a serine protease inhibitor available in an oral 
formulation, has the potential to be studied as an antiviral drug in a large scale ambulatory setting to 
prevent transmission by decreasing viral load, to prevent symptoms after exposure (PEP) in 
asymptomatic individuals or to prevent disease progression in the occurrence of early 
symptomatology. In this pilot we will assess efficacy of the drug in terms of viral load changes at D5 
compared to baseline in nasopharyngeal (or nose/throat) swabs. Cycle threshold values will be used 
as a surrogate for viral load.  
Descriptive objectives are to assess the safety and compliance of the drug in ambulatory setting. 
 
3.2. 
Secondary Objectives 
 
To estimate the clinical outcome of patients based on daily clinical scales.  
To estimate the effectiveness of the drug to prevent hospitalization, intensive care hospitalization, 
oxygenation and death at D14 and D28. 
Objectives substudies: 
- 
PK/PD substudy: quantify PK/PD parameters of camostat metabolite and interpatient 
variability in covid-19 infected patients.  
- 
Odor substudy: to estimate whether dogs can be trained to successfully detect covid 19 
positive individuals based on odor.   
- 
COVIM2.0 substudy: understanding of the pathophysiological mechanisms behind SARS-
CoV2. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
24/63 
- 
Screening failures substudy: to estimate whether asymptomatic COVID positive individuals 
with high CT values, not eligible for the drug administration, can transmit the virus and 
therefore should be isolated and whether they develop antibodies despite their mild 
infection.  
 
4. End Points and Time Points 
 
4.1. 
Primary End Points and Time Points 
 
The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in 
respiratory (oropharyngeal swab RT-PCR) log10 viral load.  
Descriptive endpoints are to assess the safety and compliance of the drug in ambulatory setting.  
 
4.2. 
Secondary End Points and Time Points 
 
- 
Days to clinical improvement from study enrolment, defined as no fever for at least 48 hrs 
AND improvement in other symptoms (e.g. cough, expectoration, myalgia, fatigue, or head 
ache) using a standardised symptom assessment scale modified from the FLU-PRO tool by 
DR. Vinetz, Yale University. Symptoms will be assessed daily from D1-D14 and up to D28 if 
patients are still symptomatic at D14 and compared to baseline using questionnaires and 
monitoring of temperature 4x daily, oxygen saturation, respiratory rate and heart rate.  
- 
Clinical status as assessed by the 7-point ordinal scale at day 0, 3, 5, 10 and 28 (Not 
hospitalized, no limitations on activities; Not hospitalized, limitation on activities; 
Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental 
oxygen; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, 
on invasive mechanical ventilation or ECMO; Death) 
- 
The effectiveness of the selected drug to prevent death at D14 and D28 
- 
The effectiveness of the selected drug to prevent hospitalization and oxygenation at D14 
and D28  
- 
The effectiveness of the selected drug to prevent intensive care hospitalization at D14 and 
D28  
- 
If available, the effect of the selected drug on pulmonary infiltrates by RX or HRCT will be 
assessed at D5 or D10 compared to baseline. The CO-RADS classification will be used to 
assess the findings.  
- 
If available, the effect of the selected drug on inflammatory parameters at D5 and D10 
compared to baseline.  
- 
The efficacy of the drug in terms of change from day 0 to day 10 in respiratory 
(oropharyngeal swab RT-PCR) log10 viral load in patients with positive PCR at D5.  
- 
The efficacy of the drug in terms of change from day 0 to day 28 in respiratory 
(oropharyngeal swab RT-PCR) log10 viral load in patients with positive PCR at D10.  
- 
The probability of finding viable virus after virus culture from swabs in COVID 19 infected 
individuals at D0 (and at D5, D10 and D28 if PCR remains positive).  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
25/63 
- 
The emergence of resistance for each of the selected drug regimens in case of prolonged 
viral shedding at D10 and D28 in individuals with positive PCR at these timepoints.  
- 
The presence of neutralising antibodies at D28. 
- 
Number of participant-reported secondary infection of housemates (and/or close 
contacts) at D28. 
Endpoints and timepoints of the substudies:  
 
PK/PD substudy: PK (volume of distribution, clearance, Cmax, Tmax) and PD (Emax and 
EC50) parameters of camostat metabolite and predictors for interpatient variability. 4 
additional blood samples. Between two drug administrations between D1 and D5: at 30’, 
60’, 2-4h, and 4-8h (on the same day). Efficacy parameters are collected on timepoints as 
described above from which Emax and EC50 and viral load decline parameters will be 
estimated. 
 
Odor substudy: to correctly distinct COVID 19 positive from negative individuals. 3 odor 
samples at 1 sampling timepoint at D5.  
 
COVIM2.0 substudy: to study the inflammatory patterns and virological characteristics of 
SARSCOV2. 1 additional blood sample (8x9ml) at D0 and D28. 1 additional swab at D0 and 
D5, D10 and D28 if PCR remains positive at these timepoints).  
 
Screening failures substudy: to see whether asymptomatic individuals with positive PCR 
but high CT values (>30) are carrying viable virus and whether these individuals produce 
neutralising antibodies and therefore have immunity against SARSCOV2. 1 additional swab 
at D0. 1 blood sampling at D28.  
 
5. Study design  
 
5.1. 
Description of study design 
 
Randomised, double blinded, placebo controlled 
Prospective  
The trial is adaptive and can be adjusted if new data on PK/PD, safety or efficacy becomes available. 
Adjustments will only be implemented after written approval from the Ethics Committee and 
Competent Authority (if applicable). 
Phase 2 clinical trial  
Monocentric in collaboration with regional hospitals and general practices (GPs) in the region of Ghent 
for referral of potential candidates. 
The trial is a pilot trial in order to provide information on Camostat, dosing, safety and efficacy, to 
support the roll-out of a possible multicentre trial with clinical outcomes.  
Medication will be provided orally in an ambulatory setting.  
Camostat or placebo will be taken for 5 consecutive days (D1D5) at a daily dose of 900mg (300mg 
TID) for the Camostat arm.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
26/63 
In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical 
symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4), 
the treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive 
days: D6D10). 
 
5.2. 
End of Study Definition 
 
5.2.1. For an individual subject 
The subject has completed the study if he or she has completed all phases of the study, including the 
last visit or the last scheduled procedures, as described in this protocol (see section “9. Study Specific 
Procedures”). 
 
5.2.2. For the whole study 
Overall, the end of the study is reached when the last study procedure for the last subject has occurred: 
last subject, last visit (LSLV). 
As soon as the whole study has ended (cfr the definition above), the Coordinating Investigator shall 
notify the HIRUZ Clinical Trial Unit, so that the Competent Authority and the Ethics Committee can be 
informed in a timely manner according to the regulatory requirements (within 90 days after end of the 
study, or if the study had to be terminated early, this period must be reduced to 15 days and the 
reasons should be clearly explained). 
The final study report will be submitted no later than 1 year after the end of the study.  
 
5.3. 
Estimated duration of the study 
 
5.3.1. For an individual subject 
The study will take maximum 29 days from initiation to completion (and minimum 28 days). 
 
5.3.2. For the whole study 
We expect the whole study to take 2 years starting in November 2020. This is a rough estimation as 
we cannot predict when, how hard and how long the second and/or third wave of the COVID19 
epidemic will hit us. 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
27/63 
6. Inclusion and Exclusion Criteria 
 
6.1. 
Inclusion Criteria 
 
 
Aged ≥18  
 
Willing to participate and fill out a daily symptom diary  
 
Willing to take the parameters such as blood oxygenation and temperature 
 
Willing to attend follow-up visits both by phone as at the clinic 
 
Capable of understanding the commitment in the trial 
 
Signed informed consent  
 
Signs and symptoms suggestive of COVID disease in absence of hospitalization criteria as 
defined by the flowchart used at the emergency department of our institution (appendix 4), 
present for maximum 5 days and confirmed by PCR.  
 
 OR documented COVID-19 infection by PCR with CT value below the threshold of 30 in 
asymptomatic individuals.  
 
 For women of childbearing potential*: they should be willing to use highly effective method 
of contraception during treatment and until the end of study defined as having a failure 
rate of less than 1% per year when used consistently and correctly. 
Such methods include: 
o combined (estrogen and progestogen containing) hormonal contraception 
o associated with inhibition of ovulation: oral, intravaginal or transdermal 
o progestogen-only hormonal contraception associated with inhibition of ovulation: 
oral, injectable or implantable  
o intrauterine device (IUD) and intrauterine hormone-releasing system ( IUS)  
o bilateral tubal occlusion  
o vasectomised partner  
o sexual abstinence 
 
 
For men of reproductive potential**: condom should be used as contraception during 
treatment and until the end of study when having a partner of childbearing potential 
 
*a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until 
becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined 
as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone 
(FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women 
not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient. 
**a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
28/63 
6.2. 
Exclusion Criteria  
 
 
Inability to make a decision to participate  
 
Pregnant or breast feeding 
 
Inability to take oral medication 
 
Inability to provide informed written consent 
 
Known hypersensitivity towards Camostat or other Serine protease inhibitors 
 
Any condition that, in the Investigator’s opinion, prevents adequate compliance with study 
therapy.  
 
Any COVID infection at risk for hospitalisation as described in the emergency department 
flowchart (cfr appendix 4) 
 
With regard to exclusion of women of child-bearing potential, women who tell us they know 
they are pregnant are excluded. All women of child-bearing potential who test positive for 
pregnancy by urine test or serum test (if an early pregnancy cannot be excluded) at first visit 
are excluded.  
 
Severe chronic pancreatitis requiring suction of gastric juice, fasting or abstention from 
drinking 
 
Postoperative reflux oesophagitis due to reflux or gastric juice 
 
Postoperative reflux oesophagitis (if improvement of symptoms is not observed).  
 
6.3. 
Screen failures 
 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of 
screen failure information will be kept to ensure transparent reporting of screen failure subjects.  
Individuals who do not meet the criteria for participation in this study (screen failure) can be 
rescreened after minimum 24h and within the 5 days of onset of symptoms. 
 
7. Target Population 
 
7.1. 
Subjects 
 
7.1.1. Number of subjects and planned recruitment rate 
We aim to include 150 participants in this study. Drop-outs will not be replaced. 
The patients will be randomised 2:1 into two study arms:  
- 
SOC + camostat 300mg 3x/d during 5 consecutive days 
- 
SOC + placebo 3x/d during 5 consecutive days 
It is expected that overall an accrual rate of 10 subjects per month is realistic in the whole study. 
 
7.1.2. Withdrawal and replacement of subjects 
Subjects are free to withdraw from participation in the study at any time upon request. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
29/63 
 
An investigator may discontinue the treatment in a subject from the study for the following reasons:  
• 
Pregnancy  
• 
If any clinical or biochemical adverse event (AE) (grade 3-4 according to the CTCAE 
classification), or other medical condition or situation occurs such that continued treatment in 
the study would not be in the best interest of the subject  
• 
Disease progression which requires discontinuation of the study intervention (including 
hospitalization as described in section 8.1.4 and 8.2.4). 
• 
If the subject meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further treatment (not including the need for hospitalization as 
defined in the flowchart (appendix 4), cfr. infra section 8.1.4 and 8.2.4).    
In case of study noncompliance or if the investigator decides for whatever reason that study 
participation of the subject is no longer advisable, the investigator can decide to withdraw the subject 
from the study at any time during the study. 
In all cases, the reason why subjects are being discontinued their treatment or withdrawn from the 
trial must be recorded in detail in the eCRF and in the subject’s medical records. 
A subject will be considered lost to follow-up if he or she fails to return for 1 scheduled visit and is 
unable to be contacted by the study site staff.  
The following actions must be taken if a subject fails to return to the clinic for a required study visit:  
• 
The site will attempt to contact the subject and reschedule the missed visit within 48 hours 
and counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain if the subject wishes to and/or should continue in the study.  
• 
Before a subject is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, 
a certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record or study file.  
• 
Should the subject continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up.  
 
7.2. 
Method of recruitment 
 
Participants will be recruited at the emergency department of Ghent University Hospital or the COVID 
consultation and test center at Ghent University Hospital after referral by the GPs in the region around 
Ghent and regional hospitals. Asymptomatic individuals with positive PCR can be referred directly to 
the COVID consultation or can be picked up after positive testing at the test center.  
A poster was designed by the Ghent University Hospital communication service and will be distributed 
to the above mentioned places of recruitment to inform care givers and potential participants of the 
study. The poster will also be used on social media and will be spread by snowball sampling via friends, 
colleagues, acquaintances, etc. of the study team. 
The COVID-19 test centre at Ghent University Hospital added the possibility to question patients on 
their consent to be contacted by the study team and flyers are available in the test centre. When 
patients that tested positive for COVID-19 are called to inform them about their results, study interest 
is being interrogated.  
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
30/63 
7.3. 
Screening 
 
Patients will be selected either based on the presence of symptoms suggestive of COVID-19 disease 
based on clinical symptoms and signs or any asymptomatic individual that has a positive screening test 
with CT value below the threshold of 30. Inclusion will be based on a positive COVID screening by RT-
PCR, gene expert, IgM antibody screening or any other comparable test confirming COVID infection.  
Eligibility will be checked based on the flowchart used at the emergency room (appendix 4).  
In case of negative screening test and suggestive clinical picture, the test can be completed with 
additional blood analysis, arterial blood gas and/or lung imaging to assess the probability of COVID-19. 
This is SOC and will be decided by the treating physician. In this case the study physician can decide to 
rescreen the patient (with PCR) after minimum 24h and within the 5 days of onset of symptoms.  
 
8. Investigational Medicinal Product (IMP) 
 
8.1. 
Camostat Mesilate 
 
8.1.1. Composition and active substance of the IMP 
Foipan 100 mg tablets, active substance camostat mesilate 100 mg 
 
8.1.2. Producer and Distributor of the IMP 
Ono Pharmaceutical LTD (Japan) 
 
8.1.3. Preparation + Dosage + administration of the IMP 
Camostat Mesilate (Foipan) 100mg, 3 tablets, 3 times a day (daily dose of 900mg). After inclusion the 
patient will receive medication for 5 days of treatment (= 45 tablets). The patient will take the 
medication at home. Oral administration. Fasting state (minimum 60 minutes before the next meal 
and 2 hours after the previous meal). At D5, the patient will bring the empty bottle and leftover tablets 
to the consultation visit.  
If the treatment is extended to 10 days, the patient will receive medication at D5 for 5 days of 
treatment (= 45 tablets). He will take the medication at home and orally in a fasting state (minimum 
60 minutes before the next meal and 2 hours after the previous meal). At D10, the patient will bring 
the empty bottle and leftover tablets to the consultation visit.  
The Foipan® (Camostat 100 mg) tablets will be used outside the conditions of the Summary of Product 
Characteristics: 
- 
The Foipan® (Camostat mesilate 100 mg) tablets are used in a phase II clinical trial to assess 
the efficacy and safety of oral serine protease inhibitors that inhibit S protein-initiated 
membrane fusion in the treatment of early phase COVID 19 disease in an ambulatory setting. 
This indication is not mentioned in the SmPC.   


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
31/63 
- 
The maximum dose mentioned in the SmPC is 600 mg of camostat mesilate daily in three 
divided doses. In this clinical trial a dose of 900 mg of camostat mesilate daily in three divided 
doses will be administered. The Foipan® tablets will be packaged conform Circular 596 (of the 
FAMHP) on the production and distribution activities for experimental medicines. 
 
8.1.4. Permitted dose adjustments and interruption of treatment 
Participants should take this medication 3 times a day during 5 consecutive days with a maximum of 4 
hours delay. If the patient forgets to take his medication within the 4 hours window, he will skip that 
dose and report it in the medication log. The time between two intakes should be at least 4 hours. So 
if one intake is delayed (with maximum 4 hours), the next intake should be adjusted, taken into account 
a minimum of 4 hours between each intake. A medication log will be available and should be filled in 
by the participants.  
If any clinical or biochemical adverse event (AE) (grade 3-4 according to CTCAE classification), or other 
medical condition or situation occurs such that continued participation in the study would not be in 
the best interest of the subject, treatment will be interrupted. 
The study medication will be interrupted in participants that meet hospitalization criteria, as defined 
in the flowchart used at the emergency department of Ghent University Hospital. Participants that 
meet hospitalization criteria will not be considered drop-outs/withdrawals. These patients will no 
longer take any study medication but their outcomes will still be monitored for the duration of the 
study period. This means: 
- 
Study medication will be interrupted completely (and will not be reinitiated). 
- 
As long as the patient is submitted to the hospital (and maximum until D28): 
o No study-specific interventions (from the core study nor the substudies) will be 
performed. 
o Patient’s standard of care COVID-19 data will be collected. If the patient is 
hospitalized in Ghent University Hospital, the study team will consult the EPD. If 
the patient is hospitalized in another hospital, the study team will contact the 
treating physician or GP.  
- 
After the patient has been released from the hospital: 
o In case the patient has been discharged before D28, only some of the study-
specific interventions will be carried out: 
 
If the patient has been discharged before D14: the study participants will 
be asked to fill in daily questionnaires assessing symptoms (cfr daily self-
score) until D14. This will be extended to D28 if patients are still 
symptomatic at D14. 
 
If the patient has been discharged on or after D14 and if symptoms are 
still present at the time of discharge: the study participants will be asked 
to fill in daily questionnaires assessing symptoms (cfr daily self-score) until 
D28. 
 
The study visit on D28 will be performed as stipulated in the study 
protocol, except for the medication log check and the check on 
compliance and tolerance of the study medication, as this will no longer 
be applicable. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
32/63 
 
Except for the PK/PD substudy, all substudies will be carried out as 
indicated in the protocol (only those for which the patient agreed on 
participating). 
o In case the patient has been discharged after D28, no further study-specific 
interventions (from the core study nor the substudies) will be performed. 
 
8.1.5. Duration of treatment 
Five consecutive days (D1D5). In patients with a positive PCR at D5 (CT value with threshold below 
30) and/or presence of clinical symptoms after exclusion of hospitalization criteria (flowchart 
emergency department appendix 4), the treatment will be extended up to D10 at the same dosage in 
both treatment arms for 5 consecutive days (D6D10). 
 
8.1.6. Packaging and Labeling of the IMP 
Repackaging, labeling, blinding and randomization will be performed by the Pharmacy of Ghent 
University Hospital. 
The Foipan® tablets will be repackaged per 45 tablets (5 consecutive dosing days). Primary packaging, 
blinding and randomization will be performed in accordance with Circular 596 (of the FAMHP) on the 
production and distribution activities for experimental medicines. Labelling will be performed 
compliant to Eudralex volume 4, annex 13. 
Protocol: COV-AAT
Apr.Commeyne S. UZ Gent 
Camostat Mesylate 100 mg/placebo 45 tabl 
Exp:    
0 
Lotnr:  
0 
Kit 
N°: 
1 
Trial subject :   
GEBRUIK/usage/gebrauch: 3 x 3 PER DAG/par jour/pro tag 5 dagen/jours/tagen 
ENKEL VOOR STUDIEGEBRUIK/Uniquement pour utilisation de l'essai clinique/Nur 
studiengebrauch klinischer. BUITEN HET BEREIK EN ZICHT VAN KINDEREN HOUDEN/Tenir 
hors de la vue et de la portée des enfants/Artznemittel für Kinder unzugänglich aufbewahren 
BEWAAR TUSSEN/ conserver entre/ Aufbewahrung zwischen 15-25°C 
ORAAL GEBRUIK/ voie oral/Orale anwendung 
  
Principal Investigator: prof. dr. S. Callens 
Sponsor: UZ GENT, C. Heymanslaan 10, 9000 Gent. België (09/33 22 793) 
 
8.1.7. Storage conditions of the IMP 
The Foipan® tablets must be shipped and stored under the recommended storage conditions (room 
temperature), locked with restricted access. Temperature excursion will be handled conform local 
procedures. After repackaging by the pharmacy, the tablets will be stored at the investigators site 
(internal medicine department) under the same conditions until they are given to the patients. IMP 
accountability and inventory logs will be kept up-to-date at the investigators site (internal medicine 
department). Patients are instructed to store the medication under the recommended storage 
conditions (room temperature). Reconciliation of used/unused IMP will be performed by the 
unblinded study nurse. At the end of the trial, unused IMP will be discarded conform local procedure 
by the study nurse. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
33/63 
8.1.8. Known side effects of the medication 
Hypersensitivity reactions including rash (0.4%), pruritus (0.2%), nausea (0.3%), abdominal discomfort 
(0.2%), abdominal fullness (0.2%).  
Increase in liver tests are reported (AST/ALT) (0,3%), diarrhea (0,2%) and nausea (0,1%).  
Besides hypersensitivity reactions, the SmPC also refers to potential complications such as 
thrombocytopenia, hyperkaliemia and increased liver enzymes (incidence not reported).  
 
8.2. 
Placebo 
 
8.2.1. Composition of the placebo 
Lactose tablets 500 mg 
 
8.2.2. Producer and Distributor of the placebo 
Fagron 
 
8.2.3. Preparation + Dosage + administration of the placebo 
Placebo tablets are used in the purchased form. There will be no additional preparation. Only 
repackaging will be conducted at the local pharmacy.  
Lactose 500 mg, 3 tablets, 3 times a day (daily dose of 4,5 g).  
After inclusion the patient will receive medication for 5 days of treatment (= 45 tablets). The patient 
will take the medication at home. Oral administration. Fasting state (minimum 60 minutes before the 
next meal and minimum 2 hours after the previous meal). At D5, the patient will bring the empty bottle 
and leftover tablets to the consultation visit.  
If the treatment is extended to 10 days, the patient will receive medication at D5 for 5 days of 
treatment (= 45 tablets). He will take the medication at home and orally in a fasting state (minimum 
60 minutes before the next meal and minimum 2 hours after the previous meal). At D10, the patient 
will bring the empty bottle and leftover tablets to the consultation visit.  
 
8.2.4. Permitted dose adjustments and interruption of treatment 
Participants should take this medication 3 times a day during 5 consecutive days with a maximum of 4 
hours delay. If the patient forgets to take his medication within the 4 hours window, he will skip that 
dose and report it in the medication log. The time between two intakes should be at least 4 hours. So 
if one intake is delayed (with maximum 4 hours), the next intake should be adjusted, taken into account 
a minimum of 4 hours between each intake. A medication log will be available and should be filled in 
by the participants.  
If any clinical or biochemical adverse event (AE) (grade 3-4 according to CTCAE classification), or other 
medical condition or situation occurs such that continued participation in the study would not be in 
the best interest of the subject, treatment will be interrupted.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
34/63 
The study medication will be interrupted in participants that meet hospitalization criteria, as defined 
in the flowchart used at the emergency department of Ghent University Hospital.  
Participants that meet hospitalization criteria will not be considered drop-outs/withdrawals. These 
patients will no longer take any study medication but their outcomes will still be monitored for the 
duration of the study period. This means: 
- 
Study medication will be interrupted completely (and will not be reinitiated). 
- 
As long as the patient is submitted to the hospital (and maximum until D28): 
o No study-specific interventions (from the core study nor the substudies) will be 
performed. 
o Patient’s standard of care COVID-19 data will be collected. If the patient is 
hospitalized in Ghent University Hospital, the study team will consult the EPD. If 
the patient is hospitalized in another hospital, the study team will contact the 
treating physician or GP.  
- 
After the patient has been released from the hospital: 
o In case the patient has been discharged before D28, only some of the study-
specific interventions will be carried out: 
 
If the patient has been discharged before D14: the study participants will 
be asked to fill in daily questionnaires assessing symptoms (cfr daily self-
score) until D14. This will be extended to D28 if patients are still 
symptomatic at D14. 
 
If the patient has been discharged on or after D14 and if symptoms are 
still present at the time of discharge: the study participants will be asked 
to fill in daily questionnaires assessing symptoms (cfr daily self-score) until 
D28. 
 
The study visit on D28 will be performed as stipulated in the study 
protocol, except for the medication log check and the check on 
compliance and tolerance of the study medication, as this will no longer 
be applicable. 
 
Except for the PK/PD substudy, all substudies will be carried out as 
indicated in the protocol (only those for which the patient agreed on 
participating). 
o In case the patient has been discharged after D28, no further study-specific 
interventions (from the core study nor the substudies) will be performed. 
 
8.2.5. Duration of treatment 
5 consecutive days (D1D5).  
In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical 
symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4), 
the treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive 
days (D6D10). 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
35/63 
8.2.6. Packaging and Labeling of the placebo 
Repackaging, labeling, blinding and randomization will be performed by the Pharmacy of Ghent 
University Hospital. 
The placebo tablets will be repackaged per 45 tablets (5 consecutive dosing days). Primary packaging, 
blinding and randomization will be performed in accordance with Circular 596 (of the FAMHP) on the 
production and distribution activities for experimental medicines. Labelling will be performed 
compliant to Eudralex volume 4, annex 13. 
Protocol: COV-AAT
Apr.Commeyne S. UZ Gent 
Camostat Mesylate 100 mg/placebo 45 tabl 
Exp:    
0 
Lotnr:  
0 
Kit 
N°: 
1 
Trial subject :   
GEBRUIK/usage/gebrauch: 3 x 3 PER DAG/par jour/pro tag 5 dagen/jours/tagen 
ENKEL VOOR STUDIEGEBRUIK/Uniquement pour utilisation de l'essai clinique/Nur 
studiengebrauch klinischer. BUITEN HET BEREIK EN ZICHT VAN KINDEREN HOUDEN/Tenir 
hors de la vue et de la portée des enfants/Artznemittel für Kinder unzugänglich aufbewahren 
BEWAAR TUSSEN/ conserver entre/ Aufbewahrung zwischen 15-25°C 
ORAAL GEBRUIK/ voie oral/Orale anwendung 
  
Principal Investigator: prof. dr. S. Callens 
Sponsor: UZ GENT, C. Heymanslaan 10, 9000 Gent. België (09/33 22 793) 
 
8.2.7. Storage conditions of the placebo 
The Placebo tablets must be shipped and stored under the recommended storage conditions (room 
temperature), locked with restricted access. Temperature excursion will be handled conform local 
procedures .After repackaging by the pharmacy, the tablets will be stored at the investigators site 
(internal medicine department) under the same conditions until they are given to the patients. 
IMP/placebo accountability and inventory logs will be kept up-to-date at the investigators site (internal 
medicine department). Patients are instructed to store the medication under the recommended 
storage conditions (room temperature). Reconciliation of used/unused study medication will be 
performed by the unblinded study nurse.  At the end of the trial, unused placebo will be discarded 
conform local procedure by the study nurse. 
 
8.2.8. Known side effects of the medication 
Lactose tablets can cause gastro-intestinal symptoms such as diarrhea when administered to people 
with lactose intolerance, although this most likely occurs when administered in higher dosing 
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586575/pdf/nutrients-07-05830.pdf).  
 
8.3. 
Concomitant / Rescue Medication 
 
There are no restrictions regarding concomitant medication.  
In case of hospitalization or unfavorable clinical evolution, participants will not be excluded from other 
protocols or SOC treatments for COVID.  
The study site will not supply rescue medication.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
36/63 
9. Study Specific Procedures 
 
9.1. 
Randomisation/blinding 
 
9.1.1. Randomisation 
A randomisation Plan generator (randomisation.com) is used to allocate in a blind manner. The 
Pharmacist (QC) performs a release of the randomisation plan. A transcription of this randomisation 
list in excel is reviewed and released by a second Pharmacist (QC) and stored in the pharmacy file. 
Printing of all the labels for the blinding is done before repackaging by an operator. Splitting of labels 
for active and placebo is performed by the same operator and checked and released by pharmacist 
(QC). 
Repackaging is performed with a copy of the transcripted randomisation list in excel and the labels 
(check of the labels by QC) – repackaging for active and placebo is performed separately. An operator 
does the repackaging, a pharmacist QC does the check. 
Repackaging records and copy of the transcripted randomisation list is filed in the pharmacy file, with 
no access for blinded staff. 
An unblinded study nurse will allocate the medication to each participant in a chronologic way, so that 
when treatment is to be prolonged, the participant remains in the same treatment arm. 
A sealed envelope will be available from the pharmacy with the transcripted excelsheets for the 
unblinded studynurse. He/she will sign for acceptance.  
 
9.1.2. Blinding 
This will be a double blinded study. The participant will be blinded. The study nurses and physicians 
that are in contact with the participants will be blinded. The pharmacy is unblinded and will deliver the 
randomization lists. At the investigator site (department of internal medicine) 2 study collaborators 
will be unblinded. There will be also be two back-ups assigned for this function. They will not be in 
contact with the participants. Only data that is relevant for them shall be shared. They will conduct the 
following procedures:  
- 
Deliver medication based on the randomization list both at D0 and at D5 in case of prolonged 
treatment.  
- 
Accountability of the tablets and destruction of the remaining tablets. 
- 
In case of AEs they will communicate the AEs in the Camostat group to ONO  
- 
In case for medical or safety reasons there is a need for urgent deblinding, they will break the 
code and pass this information to the treating physician of the participants. In this case, the 
physician treating the participant is preferentially not the same one as the study physician.  
- 
Deblind the PK/PD samples for analysis during the trial. Shipment of the PK/PD samples.  
To minimize the risk for unblinding the other (blinded) study personnel we will take the following 
measurements:  
- 
Two co-workers will be delegated as unblinded personnel at the clinic, in order to set up a 
back-up system. Another two collaborators will be assigned as back-up for the two co-workers.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
37/63 
- 
Unblinded personnel and their study activities will be clearly documented on the delegation 
log. 
- 
Unblinded personnel at the clinic have no contact with study participants in any way. 
- 
All communication between unblinded and blinded personnel concerning allocation of 
treatment will be traceable. 
 
9.1.3. Deblinding procedures 
Deblinding of the participants will take place after completion of the study (LPLV). The blinded study 
nurses and physicians will also stay blinded until that moment. 
The study code should only be broken for valid medical or safety reasons e.g. in the case of a severe 
adverse event where it is necessary for the investigator or treating health care professional to know 
which treatment the subject is receiving before he or she can be treated. If possible, other study team 
members should remain blinded. 
The code breaks for the study are held at the department of internal medicine. 
The CI/PI documents the breaking of the code and the reasons for doing so on the CRF/study 
documents, in the site file and medical notes. It will also be documented at the end of the study in any 
final study report and/or statistical report. 
The study team will notify the Sponsor in writing as soon as possible following the code break detailing 
the necessity of the code break. 
As the investigator is responsible for the medical care of the individual study subject (Declaration of 
Helsinki 3§ and ICH 4.3) the coding system in blinded studies should include a mechanism that permits 
rapid un-blinding (ICH GCP 5.13.4). The investigator cannot be required to discuss unblinding if he or 
she feels that emergent unblinding is necessary.  
PK/PD samples will be deblinded during the study. An unblinded collaborator of the study will deblind 
the samples and arrange for the shipment of samples from the Camostat arm and storage of the 
samples in the placebo arm.  
 
9.2. 
Study specific interventions 
 
9.2.1. Core trial 
After eligibility assessment participants will be randomized and will receive the study drugs. We will 
define D1 as the first dose of the medication which can be the morning, midday or evening dose. They 
will be treated for 5 consecutive days. D0 and D1 can coincide, if the participant starts taking 
medication on the day of inclusion. 
In patients with a positive PCR at D5 (CT value with threshold below 30) and/or presence of clinical 
symptoms after exclusion of hospitalization criteria (flowchart emergency department appendix 4), 
the treatment will be extended up to D10 at the same dosage in both treatment arms for 5 consecutive 
days: D6D10). 
Follow-up will be as follows:  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
38/63 
- 
D1D14: The study participants will be asked to fill in daily questionnaires assessing 
symptoms (cfr daily self-score). This will be extended to D28 if patients are still 
symptomatic at D14. 
- 
D1D5 (or D10): They will receive a kit enabling to monitor heart rate (HR), respiratory 
rate (RR), temperature and oxygen saturation 3 times per day (every 4-8 hours, 
preferentially at the timing of medication intake on D1 to D5 or D10). The home monitoring 
can be extended as SOC after termination of the medication, in presence of symptoms and 
for the period that symptoms persist.   
- 
Compliance and tolerance will be assessed during the treatment period, D0D5 (or 
D0D10 if the treatment is prolonged).  
- 
During the study D1-D28: If indicated in the opinion of the investigator, a physical exam 
and biochemistry will be performed through a consultation at the clinic. This can be 
requested at any time during the study based on clinical symptoms or signs.  
- 
Consultation at D0, D5, (D10) and D28 at our COVID consultation facility. This will be done 
by a study nurse and/or a study physician.  
At D0 (screening and inclusion) a standardized history, clinical exam will be performed, including blood 
pressure (BP), heart rate (HR), respiratory rate (RR), blood oxygen saturation, temperature. Socio-
demographic parameters such as age, gender, treatment, smoking status, BMI, diabetes, race and 
comorbidities will be assessed. If unavailable, a COVID screening test will be performed to confirm 
COVID 19 infection. A baseline lab for toxicity will be done at D0 (max 21ml.) 
In case of negative screening test and suggestive clinical picture as described above, the test can be 
completed with additional blood analysis, arterial blood gas and/or lung imaging to assess the 
probability of COVID-19. The additional tests are SOC. It is the treating physician who will decide 
whether these test are valuable. In this case the study physician can decide to rescreen the patient 
(with PCR) after minimum 24h and within the 5 days of occurrence of symptoms. 
The medication will be initiated as soon as possible after inclusion and randomisation. We will define 
D1 as the first dose of the study medication at whatever point of time during that day. Thus, D0 and 
D1 can coincide (if the participant starts taking medication on the day of inclusion). 
At D1 up to D14 (or until D28 if they still have symptoms at D14), participants will be asked for the 
presence of symptoms and signs by a questionnaire and to monitor temperature, blood oxygen 
saturation, heart rate and respiratory rate.  
If indicated in the opinion of the investigator, a physical exam and biochemistry will be performed 
through a consultation at the clinic. This can be requested at any time during the study based on clinical 
symptoms or signs. 
At D5 a scheduled study visit is planned with a clinical exam including BP, RR, HR, temperature, blood 
oxygen saturation. Nasopharyngeal (or combined nose/throat) swab will be taken for PCR. A toxicity 
screening will be performed through venous blood draw (max 21ml). At the day of consultation the 
time point at the hospital will replace the monitoring measurement at home.  
At any given time between D1 and D28 an additional blood draw (max. 21 ml) can be asked by the 
study team to assess severity of infection (peripheral blood count, inflammation, electrolytes, kidney 
and liver function.) If CRP values are available at baseline or during follow-up, they will be analyzed as 
part of the study, however they will only be performed as SOC. If HRCT or a lung X ray are available at 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
39/63 
baseline or follow-up, they will be analysed as part of the study, however they will only be performed 
as SOC.  
At D28 an additional blood draw (9 ml) will be done for neutralizing antibodies (Nabs) titer assessment. 
At D10 an additional study visit will be planned in individuals that are retested with positive PCR at D5 
and when treatment is prolonged after D5 up to D10. This will include a clinical exam including BP, RR, 
HR, temperature, blood oxygen saturation. At the day of consultation the time point at the hospital 
will replace the measurement at home. Also, a toxicity screening will be performed through venous 
blood draw (max 21ml) if any significant abnormalities occurred at D5 (Grade 1-2 adverse events 
according to CTCAE classification).  
At D10 and D28 an additional nasopharyngeal swab or combined nose/throat swab will be performed 
in individuals that still had a positive PCR result at day 5 and D10 respectively.   
Questionnaires will be sent through email and can be filled in online and transferred directly to the 
eCRF or will be filled in on paper and handed to the study personnel at the time of consultation.  
Home monitoring of heart rate, respiratory rate, temperature and oxygen saturation will be done 
through a kit provided by Byteflies. A manual with usage instructions will be delivered to the patients. 
The patient will be asked to register these parameters 3 times a day through an online platform. If they 
are unable to register the parameters themselves, a back-up through email or phone can be proposed. 
If these parameters are not within normal range as defined by cut-off criteria (appendix 8), the system 
will ask either to remeasure or to contact the study-team based on the reported values. The study 
medication will be interrupted in participants that meet hospitalization criteria as defined by the flow 
chart used at the emergency department of Ghent University Hospital (appendix 4). 
 
9.2.2. PK/PD substudy 
Participants will be asked to participate in a PK/PD substudy. We aim to include 50 patients samples in 
the Camostat treatment arm, therefore sampling approx. half of the participants in both arms. When 
we have 50 participants in the camostat arm, inclusions will be stopped. Drop-outs however will be 
replaced. If the participant agrees, PK/PD samples will be taken during the treatment phase between 
D1 and D5. 4 additional blood samples will be taken between two intakes of the study medication: at 
30’, 60’, 2-4h, and 4-8h (on the same day, between D1 and D5). The samples will be deblinded during 
the study by an unblinded person. After unblinding, only the samples from patients in the Camostat 
group will be sent for analysis. Samples that are not used for PK/PD analysis, will be stored in the 
prospective Biobank for future studies. 2x3ml of blood will be taken per sampling point =24ml.  
Update dd. 04JUN2021: This study was prematurely closed after a test phase due to logistic reasons. 
 
9.2.3. Odor substudy: Odor sampling SARS-CoV-2 patients 
Participants will be asked to participate in a substudy analysing odor samples from COVID 19 infected 
individuals. The goal of this study is to take odor samples at the arm pit and between the legs, in order 
to train dogs to identify COVID-19 infected individuals. In this way, dogs can be trained to identify 
COVID 19 infected individuals in groups and avoid transmissions. If participants consent, at D5 a cotton 
pad will be put in the arm pits and between the legs to capture the odors for approx 60 minutes. The 
samples will be send to the dog training centre (K9 Training Centrum, Brugsesteenweg 105 8450 
Bredene, responsible: Johan Weckhuyzen (CEO)) where they will be used to train dogs to identify 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
40/63 
COVID-19 infected individuals. These samples will be used one time and will be destroyed after usage 
at the training centre. 
Update dd. 04JUN2021: This study ended at the end of May 2021 after having recruited a sufficient 
amount of participants and in the absence of budget to prolong the inclusions.  
 
9.2.4. COVIM2.0 substudy: Immunological and virological assessment  
Deep characterization of patients’ inflammatory profile offers a unique opportunity for comprehensive 
understanding of the pathophysiological mechanisms behind SARS-CoV2. All participants will be 
therefore asked for additional blood sampling at D0 and D28 (8X9ml). The lipidomics analysis will be 
performed at the laboratory of Dr. Jesmond Dalli, In addition, we will study immunological functions 
on the level of both adaptive and innate immunity by performing extensive immunophenotyping, 
cytokine analysis and RNA sequencing analysis. Biomarker analysis will be performed on protein and 
on RNA single cell level. Infectivity of different cell types including macrophages will performed. These 
analyses will be performed at the HCRC laboratory, the laboratory of Prof. Rafick-Pierre Sékaly and the 
VIB-UGent Center for Inflammation Research. To gain a deeper understanding of pathways potentially 
leading to severe disease courses, and alsoto chart where in the body there is tissue damage (apart 
from the lungs), we aim to analyze patient plasma samples with several other analytics technologies 
as well. Bacterial extracellular vesicles, due to microbial translocation after hyperinflammation, will be 
quantified from plasma in the laboratory of Experimental Cancer Research of Ghent University. 
Furthermore, normal cell turnover in tissues results in the release of some of their nucleic acid content 
into the blood. This can then be found as circulating free RNA and DNA (cfRNA and cfDNA). These 
analyses will be performed at the laboratory of Prof. Jo Vandesompele (Biogazelle). Virological 
evaluations will be based on nasopharyngeal swab samples, used to diagnose and quantify SARS-CoV2. 
In addition a swab will be taken to culture the SARS-CoV2 virus at D0. This will be repeated at D5, D10 
and D28 if PCR is positive on these timepoints (an extra swab will be taken). On a selection of 
nasopharyngeal swab samples from patients whole genome sequencing of the SARS-CoV2 virus will be 
performed to study the viral diversity and trace patterns of spread across multiple epidemiological 
scales. In addition, a viral metagenomics analysis using Nanopore sequencing will be used to reveal the 
presence of other viruses besides SARS-CoV2 (lab of Hans Nauwynck). 
Update dd. 04JUN2021: This substudy was not initiated due to the lack of availability of lab technicians. 
 
9.2.5. Screening failures substudy 
Asymptomatic individuals with positive PCR and high CT values that are not eligible for the clinical trial 
and drug administration, but who otherwise meet all in- and exclusion criteria, can participate in a 
substudy, where we want to see whether these individuals, despite their high CT values and therefore 
low viral load can carry viable virus and therefore can transmit the disease. This implicates whether or 
not they should be isolated. Furthermore, in individuals with low viral load there is a possibility that 
they do not develop antibodies against SARSCOV2. Therefore we want to 1) culture virus from 
throat/nose swabs from these individuals at D0 2) measure antibodies at D28.  
 
9.3. 
Overview of collected data 
 
 
Clinical exam including blood pressure, respiratory rate, heart rate, temperature and blood 
oxygen saturation: D0-D5-(D10)-D28. D10 additional visit will be planned if PCR is positive at 
D5 and treatment is prolonged. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
41/63 
 
At D0: Socio-demographic parameters such as age, gender, treatment, smoking status, BMI, 
diabetes, race and comorbidities will be assessed. 
 
Symptoms, signs, compliance and tolerance will be assessed by questionnaire daily D0D14 
and up to D28 in patients that still have symptoms at D14.  
 
A monitoring kit will be provided for self-assessment of temperature, HR, RR and saturation 
(D0D5 (or D10)).  
 
Clinical 7 points score: D0-D5-(D10)-D28  
 
Toxicity lab at D0-D5 (and D10 if necessary cfr. protocol) 
 
Optional: lung imaging (RX or HRCT): D0, D5 or D10 when clinically relevant and based upon 
availability.  
 
Optional : (POC) CRP: D0-D5 or D10  
 
Nasopharyngeal (or combine nose/throat) swab: D0-D5-(D10-D28 when positive at D5 or D10 
respectively) 
 
Neutralising Abs: D28  
 
Substudies:  
o PK/PD sampling between D1 and D5: 4 additional blood samples on the same day 
(2x3ml per timepoint =24ml)  
o Odor sampling: D5: 3 cotton pads  
o COVIM2.0:  
Peripheral blood draw: 
o Day 0: 8 EDTA tubes (9mL)  
o Day 28: 8 EDTA tubes (9mL) 
Swabs for SARS-CoV2 culture and infectivity 
o Day 0, day 5, day 10 and day 28: one additional swab (with viral transport medium) 
to culture virus in BSL3 lab if PCR is positive at these timepoints (an extra swab will be 
taken for the COVIM2.0 substudy).  
o Screening failures: additional swab for viral culture D0 and blood sample for 
neutralizing Abs D28 
At any given time between D1 and D28 an additional blood draw (max. 21 ml) can be asked by the 
study team to assess severity of infection and safety (peripheral blood count, inflammation, 
electrolytes, kidney and liver function.)  
 
9.4. 
Schematic overview of the data collection & interventions 
 
Appendix 1 
 
9.5. 
Restrictions for subjects during the study  
 
There are no extra restrictions for the subjects (apart from the restrictions from the government for 
COVID-19 positive patients). 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
42/63 
10. 
Sampling 
 
10.1. Types and number of samples 
 
 
Nasopharyngeal (or combined nose/throat) swab for COVID PCR: D0-D5 and D10-D28 if 
positive at D5 or D10 respectively 
 
Toxicity lab D0, D5 (and at D10 if necessary cfr. protocol) (max 21ml).  
 
Additional blood analysis can be performed at any given time during the study to assess the 
severity of infection, for follow-up or in case of the safety issues. This includes peripheral blood 
count, CRP, liver, renal function and electrolytes (max 21 ml).  
 
Additional: capillary blood for POC CRP or regular blood draw for CRP (max 6ml): D0-D5-D10  
 
Blood test for neutralizing Abs titer at D28 (max 9ml). 
 
Substudies  
o PK/PD: 4 additional blood draws (6ml 4x=24ml) between D1-D5 between 2 intakes of 
the medication (on the same day, at 30’, 60’, 2-4h, and 4-8h).  
o Odor sampling: 3 cotton (gauze) pads at D5 
o COVIM2.0:  
 
Peripheral blood draw: 
o Day 0: 8 EDTA tubes (9mL)  
o Day 28: 8 EDTA tubes (9mL),  
 
Swabs for SARS-CoV2 culture and infectivity 
o Day 0, day 5, day 10 and day 28: one additional swab (with viral transport 
medium) to culture virus in BSL3 lab if PCR is positive at these timepoints (an 
extra swab will be taken for the COVIM2.0 substudy) 
o Screening failure: 1 swab for viral culture at D0 and 1 blood sample (9ml) at D28 for 
neutralizing antibodies  
 
10.2. Timepoints of sampling 
 
D0-D5-(D10)-D28 
PK/PD substudy: between D1-D5, 4 timepoints between 2 drug administrations (30’, 60’, 2-4h, 4-8h) 
 
10.3. Sample Handling & Analysis 
 
Nasopharyngeal (or combine nose/throat) swab: PCR  
Gene expert Cepheid 
The Xpert Xpress SARS-CoV-2 test is an automated in vitro diagnostic test for qualitative detection of 
nucleic acid from SARS-CoV-2. The Xpert Xpress SARS-CoV-2 test is performed on GeneXpert 
Instrument Systems. The GeneXpert Instrument Systems automate and integrate sample preparation, 
nucleic acid extraction and amplification, and detection of the target sequences in simple or complex 
samples using real-time PCR assays. The systems consist of an instrument, computer, and preloaded 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
43/63 
software for running tests and viewing the results. The systems require the use of single use disposable 
cartridges that hold the RT-PCR reagents and host the RT-PCR process. Because the cartridges are self-
contained, cross-contamination between samples is minimized. For a full description of the systems, 
see the GeneXpert Dx System Operator Manual or the GeneXpert Infinity System Operator Manual. 
The Xpert Xpress SARS-CoV-2 test includes reagents for the detection of RNA from SARS-CoV-2 in 
nasopharyngeal, oropharyngeal, nasal, or mid-turbinate swab and/or nasal wash/aspirate specimens. 
A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge 
utilized by the GeneXpert instrument. The SPC is present to control for adequate processing of the 
sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also 
ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the 
amplification reaction and that the RT-PCR reagents are functional. The PCC verifies reagent 
rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge 
including monitoring for probe integrity and dye stability. The nasopharyngeal, oropharyngeal, nasal, 
or mid-turbinate swab specimen and/or nasal wash/aspirate specimen is collected and placed into a 
viral transport tube containing 3 mL transport medium or 3 mL of saline. The specimen is briefly mixed 
by rapidly inverting the collection tube 5 times. Using the supplied transfer pipette, the sample is 
transferred to the sample chamber of the Xpert Xpress SARS-CoV-2 cartridge. The GeneXpert cartridge 
is loaded onto the GeneXpert Instrument System platform, which performs hands-off, automated 
sample processing, and real-time RT-PCR for detection of viral RNA. 
 
Because of current limitation to perform these tests in house due to the high demand in the COVID 
epidemic, we looked for alternatives:  
- 
In house PCR based on the protocol of Corman et al. Eurosurveillance 2020 can be used: 
 
Real-time reverse transcription PCR, Extraction with Easymag from Biomérieux, 
amplification on CFX96 from Bio-Rad.  
 
Target = Egene 
 
Internal control (this is added to the sample before extraction; amplification of this 
signal is a sign of good extraction and succeeded PCR) Diagenode RNA extraction and 
inhibition Real-Time PCR 
 
Startvolume = 200µL/sample. 
- 
Besides PCR, we will perform Antigen testing on the NFS samples. RNA extracted from NFS 
samples will be shipped to Sciensano and both Antigen testing and 3 PCRS ( E-gen, CDC N1 
and N2 test and RdRP Pasteur assay) will be performed at Sciensano. This way we will have 
ample comparative data. Antigen ELISA SARS COV 2: test kitEQ 2606-9601 is used from 
Euroimmun. The test kit contains microplate strips each with 8 reagent wells coated with 
a monoclonal anti-SARS-CoV-2 antibody. Throat swabs and controls should be lysed before 
pipetting them into the reagent wells in the first incubation step. In the second incubation 
step, biotinylated anti-SARS-CoV-2 antibody is added to the sample which is then detected 
by streptavidin-bound horseradish peroxidase. The colour intensity is proportional to the 
SARS-CoV-2 antigen concentration in the sample. 
 
Neutralising AB test:  
A standard 3 or 5ml collection tube is enough to get about 1 to 2ml of serum, that would be more than 
sufficient and allow to repeat analysis if needed. 
After clotting it should be centrifuged (1,000–2,000 x g for 10 minutes ideally in a refrigerated 
centrifuge, but room temperature is also fine), transferred to a new tube and stored at -80°C before it 
is shipped. Serum samples should be stored at the clinical trial site at – 80°C and shipped to Sciensano 
on dry ice. There they will be stored at -80°C and analyzed when enough samples for a common 
seroneutralisation run are available. After analyses have been performed, all residual material will be 
destroyed by Sciensano. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
44/63 
Microneutralisation Assay: 
Vero-E6 cells are seeded in 96 well plate at 2.104 cells/well. The day after, 100 TCID50 of virus (strain 
BetaCoV/Belgium/S1871/2020) are incubated with serial 2-fold dilutions of sera, starting from 1:10, in 
100 μl of DMEM for 1 hour at 37°C. Mixes are then added to cells and incubated for 4-5 days at 37°C. 
Cytopathic effect (CPE) reading is performed by direct observation under the microscope and after cell 
coloration with crystal violet. Microneutralisation titers are expressed as the serum dilution for which 
50% neutralisation is observed.   
PK/PD substudy analyses:  
Blood (2x 3ml) is sampled on ice and collected in citrate tubes at 4 timepoints between 2 drug 
administrations at the Ghent University Hospital (between D1 and D5, on the same day: at 30’, 60’, 2-
4h, and 4-8h). 
The inhibitor diisopropylflurophosphat (DFP) (Sigma-Aldrich (Merck) cat. No. D0879-1G), dissolved in 
2-propanol at 1 M (184 mg/ml)10 ul of this solution added to 1 ml blood, ie. 30 ul in 1 citrate-tube that 
contains 3 ml blood. The solution will be added to the tube prior to use. These tubes are then 
transferred to the COVID consultation and kept on ice. After blood is drawn (via venous puncture or 
from a venous catheter that will remain in place for the 4 consecutive PK blood samples), blood will be 
aspirated using a syringe and the blood is transferred at the COVID consultation to the tubes containing 
the inhibitor and transferred immediately after on ice to the MRB2 lab. The blood sample is centrifuged 
at 1000-2000 g for 10-20 min at 4°C at Ghent University Hospital as soon as possible after the sampling. 
The plasma is stored within one hour at -80°C at HCRC lab until shipment for bio-analysis at the Aarhus 
University Hospital, Denmark (prof. Mads Fuglsang and team).  
PK/PD data analysis will be performed at the Heymans Institute of Pharmacology, Ghent university 
(Prof. dr. P. De Paepe and dr De Cock) and the Leiden Academic Centre of Drug Research, Leiden, The 
Netherlands (prof Coen van Hasselt and team).  
After analysis, all PK/PD residual material will be destroyed by the Aarhus University. 
Samples that are not shipped for PK/PD analysis, will be stored in the prospective Biobank HCRC for 
future studies. 
 
Odor sampling substudy:  
Sampling at hospital. 
Odor measurement is performed by means of a sterile cotton pad or gauze worn, rubbed or kept in 
the axilla and groin for approx. 60 min.  
 
Sterile cotton pads or gauze are put by the patient under the armpit for 60’ to capture the 
odor.  
 
After this time, the cotton pad is transferred by the patient into a sterile plastic bag.  
 
The caretaker then transfers the bag into an extra sterile plastic bag and stores the sample in 
the freezer (-20°C or -80°C). 
 
For long term storage, it is best to store the sample as cold as possible (-80°C or on dry ice).  
 
Transport of samples. 
 
A trained person transfers the samples in a closed container on dry ice to the dog training 
center (K9 Training Centrum, Brugsesteenweg 105 8450 Bredene, responsible: Johan 
Weckhuyzen (CEO))  
 
Ideally, the sample is kept in the cold chain until it reaches the training center.  
 
The container is marked with address of origin, address of final destination.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
45/63 
 
The box cannot be opened during transportation.  
 
The box is marked with the proper logo’s for these types of samples. 
 
Sampling at odor assessment location. 
 
The samples are opened by a trained person in a well-ventilated room. One skilled person is 
handling the samples, using gloves, plastic arm cover, labcoat and mouth mask. 
 
The cotton pads are presented to the dogs behind a wall so that there is no direct contact 
between nose of the dog and the cotton pad. There is a distance of min 15cm between cotton 
pad/gauze and the dogs nose. 
 
The odor containers are aluminum containers with a cone-like outlet. After odor assessment, 
the aluminum containers are sterilized using ethanol 70%.  
 
The cotton pads are destroyed after usage at the site (K9 Training Centrum) 
 
COVIM2.0 substudy  
Immunological assays that will be performed include lipidomics, immunophenotyping, single cell RNA 
seq, serologic testing and cytokine analysis. Novel mediators of the so-called immune resolution 
pathways have been recently identified, collectively described as “pro-resolution” factors that include 
lipoxins, resolvins, protectins and maresins. So far, their presence and their impact on adaptive 
immune responses controlling viral replication has rarely been studied, especially not in the context of 
the emerging SARS-CoV2 epidemic. Therefore, deep characterization of patients’ inflammatory profile 
offers a unique opportunity for comprehensive understanding of the pathophysiological mechanisms 
behind SARS-CoV2.  
- 
The lipidomics analysis will be performed at the laboratory of Dr. Jesmond Dalli (London, 
U.K.). Plasma (1ml) will be extracted from fresh blood samples and stored at -80°C until 
shipment.  
- 
In addition, we will study immunological functions on the level of both adaptive and innate 
immunity by performing extensive immunophenotyping, cytokine analysis and RNA 
sequencing analysis. Biomarker analysis will be performed on protein and on RNA single 
cell level. Infectivity of different cell types including macrophages will performed.  
These analyses will be performed at the HCRC laboratory, the laboratory of Prof. Rafick-
Pierre Sékaly (Cleveland, U.S.) and the VIB-UGent Center for Inflammation Research.  
PBMCS and plasma will be extracted from blood and stored at HCRC Biobank (PBMCs in 
liquid nitrogen, plasma at-80°C). 2ml of plasma and 10 million PBMCs will be shipped to 
the lab of Sekaly. The rest of the PBMCs and plasma will be stored at HCRC until they are 
being used.  
- 
To gain a deeper understanding of pathways potentially leading to severe disease courses, 
and also to chart where in the body there is tissue damage (apart from the lungs), we aim 
to analyze patient plasma samples with several other analytics technologies as well.  
* Bacterial extracellular vesicles, due to microbial translocation after hyperinflammation, 
will be quantified from plasma in the laboratory of Experimental Cancer Research of Ghent 
University.  
* Furthermore, normal cell turnover in tissues results in the release of some of their nucleic 
acid content into the blood. This can then be found as circulating free RNA and DNA (cfRNA 
and cfDNA). These analyses will be performed at the laboratory of Prof. Jo Vandesompele 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
46/63 
(Biogazelle nv). Plasma will be extracted from fresh blood and stored at -80°C. 1ml of 
plasma will be shipped for analysis. 
 
After analysis, all COVIM2.0 residual material of samples that were shipped, will be destroyed by the 
party that did the analysis. The samples that are stored in the HCRC Biobank and that are not used for 
studies described in COVIM2.0 will remain there for 25 years and can be used for future studies.  
Virological evaluations will be based on nasopharyngeal swab samples, used to diagnose and quantify 
SARS-CoV2. In addition a swab will be taken to culture the SARS-CoV2 virus at D0. This will be repeated 
at D5, D10 and D28 if PCR is positive at these timepoints (an extra swab will be taken). On a selection 
of nasopharyngeal swab samples from patients whole genome sequencing of the SARS-CoV2 virus will 
be performed to study the viral diversity and trace patterns of spread across multiple epidemiological 
scales. In addition,  viral metagenomics analysis using Nanopore sequencing will be used to reveal the 
presence of other viruses besides SARS-CoV2. These analyses will be performed at the HCRC 
laboratory, the Laboratory of Microbiology of Ghent University Hospital and the Laboratory of Virology 
of the Department of Veterinary Medicine of Ghent University. These analysis will be done on RNA 
extracted from the swab in the core study. 
Viral culture will be performed in collaboration with the Xavier Saelens lab (VIB). Viral swabs will be 
transferred immediately after sampling and put into culture in the lab.  
 
Screening failure substudy 
Blood analysis at D28 will be sent to Sciensano for antibody analysis cfr core study. An additional swab 
at D0 will be taken for viral culture cfr COVIM2.0 study.  
 
Additional blood analyses 
Monitoring of safety and severity of the infection : SOC laboratory analysis as described above  
POC CRP: Afinion CRP (immediate analysis on blood spot) or CRP through the routine lab: SOC 
laboratory analysis as described above 
 
10.4. Sample Storage and/or shipping  
 
Nasopharyngeal (or combined nose/throat) swabs: Storage at the microbiology department (Ghent 
University Hospital). RNA extraction. PCR. Because of limitations to perform these analysis in house, 
samples will be shipped to Sciensano for Antigen detection and 3 PCRS as described above.  
If available, samples will be stored for resistance analysis (-80°C). After analysis, samples will be kept 
at the biobank at Ghent University Hospital for future research. POC CRP: immediate analysis after 
capillary blood extraction through the Afinion platform. Sample is destroyed immediately after 
analysis. 
Nabs: 2ml of serum stored at -80° at HCRC Biobank. Batch shipment to Sciensano. After analysis, 
residual material will be destroyed by Sciensano. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
47/63 
Samples for PK/PD will be stored after centrifugation at -80°C until analysis at the Biobank HCRC. They 
will be shipped to Aarhus University for analysis. After analysis, residual material will be destroyed by 
Aarhus University. Samples that are not shipped for PK/PD analysis, will be stored in the prospective 
Biobank HCRC for future studies. 
COVIM2.0 samples: isolated PBMCs from blood and plasma will be stored at the Biobank at Ghent 
University Hospital. Plasma will be stored at -20°/-80°C and PBMCs will be transferred to Liquid 
nitrogen. 1ml plasma will be transferred to the lab of Jo Vandesompele (Biogazelle) for cell free RNA 
sequencing. 1ml of plasma will be shipped to the lab of Desmond Dalli for lipidomics study. 2ml plasma 
and 10 MIO PBMCs will be shipped to the lab of Raffick Sekaly. Selected samples of RNA extracted from 
the nasopharygeal swab will be shipped to the lab of Hans Nauwynck for whole genome sequencing 
(WGS) and metagenomics sequencing. After analysis, all COVIM2.0 residual material that was shipped, 
will be destroyed by the party that did the analysis. The samples that are stored in the HCRC Biobank 
and that are not used for studies described in COVIM2.0 will remain there for 25 years and can be used 
for future studies.  
 
The cotton pads for odor analysis are transferred to a sterile bag and stored in the freezer at Ghent 
University Hospital (-20-80°) until transfer to the dog training centre (K9 Training Centrum, 
Brugsesteenweg 105 8450 Bredene, responsible: Johan Weckhuyzen (CEO)). Samples for odor analysis 
will be destroyed after the analysis at the K9 training centre. 
Swabs from screening failure substudy: viral culture cfr COVIM2.0. Blood from screening failure 
substudy: Antibody analysis will be done by Sciensano, cfr core study.  
SOC blood analysis and toxicity labs will be performed by the routine lab and will be destroyed 
according to SOC.  
 
10.5. Future use of stored samples 
 
Samples that remain in Ghent will be stored for 25 years at Ghent University Hospital Biobank. 
Samples for neutralizing antibody detection and PK/PD samples will be destroyed after analysis in 
external laboratories we collaborate with (Sciensano; Aarhus University, Denmark). Plasma that will 
not be sent to these labs, will be stored at the UZ Ghent Biobank for 25 years, to be used in future 
clinical research.  
Nose/throat swabs will be stored in the UZ Ghent Biobank for 25 years, to be used in future clinical 
research.  
Samples for odor analysis will be destroyed after the analysis at the dog training centre.  
Samples for COVIM2.0 analysis that are sent to external collaborators will be destroyed after analysis. 
All COVIM2.0 residual material that was shipped, will be destroyed by the party that did the analysis. 
The samples that are stored in the HCRC Biobank and that are not used for studies described in COVIM 
will remain there for 25 years and can be used for future studies.  
Samples from the screening failure substudy (blood/swab): cfr neutralizing antibody detection 
Sciensano, viral culture COVIM2.0.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
48/63 
11. 
Statistical Considerations 
 
11.1. Sample size calculation 
 
This is a pilot trial where we want to assess the value of Camostat as a potential candidate for a larger 
trial in the ambulatory setting where the primary objective would be to prevent hospitalisation and to 
improve outcome in COVID infection if initiated in an early stage.  
This pilot will assess the efficacy of Camostat in terms of viral clearance, confirm its safety and look at 
the pharmacokinetic profile. Neutralising Abs will be assessed after 28 Days. The trial is adaptive and 
can be adjusted if new data on PK/PD, safety or efficacy becomes available.  
All tests performed will be tests of superiority. 
For the primary endpoint, we will test the hypothesis that camostat mesylate results in a significantly 
greater change from baseline (D0) to day 5 in respiratory (Nasopharyngeal (or combined nose/throat) 
swab RT-PCR) log 10 viral load compared to placebo. 
SAMPLE SIZE CALCULATION:  
The sample size calculation is based on the primary outcome of interest: change in log 10 respiratory 
(nasopharyngeal (or combined nose/throat) swab RT-PCR) viral load from baseline (D0) day 5 (D5) 
post-randomization. Given the limited data on the variability of the change in log 10 viral load, we have 
powered the study based on detecting a moderate standardized effect size of 0.3 using an analysis of 
covariance (ANCOVA), adjusting for baseline log 10 viral load. To put into context, one scenario that 
would produce a 0.3 standardized effect size would be a change of 4 in log 10 viral load in the camostat 
mesilate group compared to a change of 1 in log 10 viral load in the placebo group assuming a standard 
deviation of 5.0. 
(NOTE: For ANCOVA, the effect size is the standard deviation of the treatment means divided by the 
pooled standard deviations of the observations.) To be conservative we assume a R-squared of 0 
between the log 10 viral RNA at 2-days and baseline log 10 viral RNA. With a power of 90%, and a type 
I error rate of 5% (2-sided) and a 2:1 randomisation, we would be able to detect the hypothesized 0.3 
standardized effect size with 132 total patients - 88 patients versus 44 patients in 2:1 randomization. 
Increasing this sample size by 15%, 5% for an efficacy and futility look at 50% information (i.e. when 
half of the patients have been enrolled) and 10% to account for loss to follow up, gives a total of 150 
participants (100:50). 
POPULATIONS FOR ANALYSES 
Intention-to-Treat Analysis Dataset: Participants will be analyzed based on their treatment assignment. 
Per Protocol Analyses Dataset: All participants completing the study who complied with the protocol. 
Safety Analysis Dataset: all study participants. 
 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
49/63 
11.2. Type of statistical methods 
 
GENERAL APPROACH 
All primary analyses will be performed as intent-to-treat analyses with a type I error rate of 5% (two-
sided). Parametric distributional assumptions will be checked. If assumptions fail, other distributions 
will be considered prior to transformations and non-parametric methods. SAS (version 9.4) or the 
latest version of R (currently 3.6.3) will be used to analyze the data. 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
The primary analysis will be according to intent-to-treat and conducted using ANCOVA, adjusting for 
baseline log 10 viral load (or conversion from Ct value assuming 1 log 10 = 3.3 Ct units). We will use 
the t-statistic for the treatment effect to determine whether the treatment is statistically different 
from the placebo at the overall 10% level of significance, controlling for baseline log 10 viral load. 
Because of the interim analysis (see below), a p-value of 0.06 (2-sided), corresponding to an efficacy 
boundary value of 1.875 at the last look, will be used for the level of significance for the primary 
outcome at the final analysis. In sensitivity analyses, we will adjust for age and time since onset of 
symptoms. We will also conduct a per-protocol analysis as a secondary analysis. We will assess the 
missing mechanism and the impact of missing data. Sensitivity analyses under either missing at random 
or missing not at random will be considered, as appropriate. 
ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Secondary outcomes of interest include change of COVID-19 symptom score from baseline (day 0), as 
measured at D1D14 and D28. Linear mixed models will be used to describe trajectories of change in 
the symptom score. The models will include fixed effects for treatment, time and the interaction of 
treatment and time. An unstructured covariance pattern will allow for correlation between repeated 
observations. Differences in means at each timepoint will be estimated along with 90% confidence 
intervals. All statistical tests will be conducted at 5% level of significance (two-sided) with no 
adjustment for multiple testing. 
Monitoring tool + questionnaires for symptoms and signs. 
Time to complete absence of symptoms the components of the symptom assessment scale (e.g. nose, 
throat, cough); and hospitalization. Time to complete absence of symptoms will be analyzed using the 
Cox model and event-free rates determined by Kaplan-Meier. Individuals will be administratively 
censored at 28 days. Those who die will be censored at time of death. We will conduct sensitivity 
analyses using death as a semi-competing risk. Twenty-eight day hospitalization rates will be compared 
using an exact binomial distribution. We will also consider additional biomarkers (using similar 
methods as described for the primary and secondary outcomes) and the individual components of the 
symptoms (using similar methods as described above). 
SAFETY ANALYSES 
Safety will be reported by treatment arm using descriptive statistics (means and standard deviations 
or frequencies and counts) and assessed by comparing the adverse events in the treatment group using 
Type I error of 5% (2-sided); no control for multiplicity will be done for safety outcomes. We will 
consider Wilcoxon rank sum tests or two-sample t-tests for continuous outcomes and the exact 
binomial distribution for proportions. 
BASELINE DESCRIPTIVE STATISTICS 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
50/63 
Baseline characteristics (including demographic, lab, and clinical variables) will be presented by 
treatment group (camostat mesylate and placebo). Means and standard deviations will presented for 
continuous variables and frequencies and proportions will be presented for categorical variables. No 
inferential statistics will be presented. 
MISSING DATA 
Regarding missing data, we will try to limit the amount of missing data by setting up alarm systems to 
remind participants to adhere to these data collections. Regarding the parameters, the system of 
Byteflies can send a message through email or phone, to remind people to submit their data if this has 
not been done within the desired timeframe. For the questionnaire through the REDCap system, a 
daily email will be sent to the participants. We consider therefore that we can monitor and follow this 
up in a strict manner. 
The study nurse will pay attention that on the specific day of PK/PD-sampling, all parameters and 
questionnaires are submitted during the patient’s stay at the clinic.  
We realise that missing data in an ambulatory care trial is a potential problem and we will also evaluate 
this and see whether a daily monitoring system is feasible in routine clinical care, whether patients are 
motivated enough to do this so that we can adjust this for future trails or a broader roll-out. 
Concerning data analysis, we should primarily investigate the patterns of missing data in order to 
decide which technique(s) could be used to handle the missing data. In case of less than 5% 
missingness, this is ignorable and a complete-case analysis could be performed. Other options are 
single imputation, model-based methods for repeated measures (mixed models, generalised 
estimation equations) or multiple imputation. 
 
11.3. Statistical analysis team 
 
Dr. Wim Trypsteen, HCRC, wim.trypsteen@ugent.be  
 
11.4. Interim analysis 
 
An interim analysis will be performed if recruitment drops significantly (no inclusions for more than 2 
weeks) or there is an important decrease in patients that have a positive screening test for COVID, and 
after at least 2/3 of the intended total amount of participants have been recruited. An interim analysis 
will be conducted to see whether significance is reached and whether it seems useful to continue the 
trial based on efficacity or futility in 3 endpoints: viral outcomes, symptom control and safety. 
This interim analysis will be performed by an unblinded statistical team who will not perform any 
blinded tasks and/or have contact with participants. In case blinded study personnel becomes 
unblinded in order to perform the interim analysis, they will stay unblinded from that moment on and 
they cannot perform any more study related procedures which require being blinded. The interim 
analysis will be carried out as described above, in section 11.2. 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
51/63 
12. 
Data handling 
 
12.1. Method of data collection 
 
Subjects that are included in the study, will be assigned a unique study number upon their registration 
in REDCap. On all documents submitted to the coordinating centre, sponsor or CI, patients will only be 
identified by their study number. The subject identification list will be safeguarded by the site. The 
name and any other directly identifying details will not be included in the study database. 
12.1.1. Case Report Form 
An electronic data capture (EDC) system, i.e. REDCap, will be used for data collection. Data reported 
on each eCRF should be consistent with the source data. If information is not known, this must be 
clearly indicated on the eCRF. All missing and ambiguous data will be clarified.  
Only the data required by the protocol are captured in the eCRF. The eCRFs and the database will be 
developed, based on the protocol. The final eCRF design will be approved by the Coordinating 
Investigator. 
All data entries and corrections will only be performed by study site staff, authorized by the 
investigator. Data will be checked by trained personnel (monitor, data manager) and any errors or 
inconsistencies will be clarified.  
Before signing off the eCRF, the investigator must verify with the data manager that all data entries in 
the eCRF are accurate and correct. 
REDCap is provided and maintained by Vanderbilt University; a license for use was granted to the 
Health, Innovation and Research Institute (HIRUZ). REDCap is a web-based system.  
The study site staff is responsible for data entry in REDCap.  
 
12.1.2. Data directly collected in the CRF (no source available) 
Source documentation will be available for all information captured in the eCRF, except for the daily 
questionnaires which can be filled in directly through a link sent by email and transferred to the eCRF. 
 
12.2. Data storage 
 
The data is accessed through a web browser directly on the secure REDCap server. The server is hosted 
within the Ghent University Hospital campus and meets hospital level security and back-up 
requirements.  
 
Privacy and data integrity between the user's browser and the server is provided by mandatory use of 
Transport Layer Security (TLS), and a server certificate issued by TERENA (Trans-European Research 
and Education Networking Association). All study sites will have access to REDCap. Site access is 
controlled with IP restriction. 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
52/63 
12.3. Archiving of data 
 
The investigator and sponsor specific essential documents will be retained for at least 25 years. At that 
moment, it will be judged whether it is necessary to retain them for a longer period, according to 
applicable regulatory or other requirement(s). 
 
12.4. Access to data 
 
Direct access will be granted to authorised representatives from the Sponsor, host institution and the 
regulatory authorities to permit study-related monitoring, audits and inspections. 
Login in REDCap is password controlled. Each user will receive a personal login name and password 
and will have a specific role which has predefined restrictions on what is allowed in REDCap. 
Furthermore, users will only be able to see data of subjects of their own site. Any activity in the 
software is traced and transparent via the audit trail and log files. 
 
13. 
Safety  
 
13.1. Definitions 
 
Term
Definition
Adverse Event (AE)
Any untoward medical occurrence in a subject to whom a medicinal 
product has been administered, including occurrences which are not 
necessarily caused by or related to that product. 
Unexpected Adverse 
Event 
An adverse event, the nature or severity of which is not consistent with 
the applicable product information (e.g., Investigator's Brochure for an 
unapproved investigational product or package insert/summary of 
product characteristics for an approved product). 
Adverse Reaction (AR)
 
An untoward and unintended response in a subject to an investigational 
medicinal product which is related to any dose administered to that 
subject. 
The phrase "response to an investigational medicinal product" means 
that a causal relationship between a study medication and an AE is at 
least a reasonable possibility, i.e. the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional 
or the Sponsor as having a reasonable suspected causal relationship to 
the study medication qualify as adverse reactions. 
Serious Adverse Event 
(SAE) 
A serious adverse event is any untoward medical occurrence that:
 results in death 
 is life-threatening 
 requires inpatient hospitalisation or prolongation of existing 
hospitalisation 
 results in persistent or significant disability/incapacity 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
53/63 
 consists of a congenital anomaly or birth defect 
Other ‘important medical events’ may also be considered serious if they 
jeopardise the subject or require an intervention to prevent one of the 
above consequences. 
NOTE: The term "life-threatening" in the definition of "serious" refers to 
an event in which the subject was at risk of death at the time of the event; 
it does not refer to an event which hypothetically might have caused 
death if it were more severe. 
Serious Adverse 
Reaction (SAR) 
An adverse event that is both serious and, in the opinion of the reporting 
Investigator, believed with reasonable probability to be due to one of the 
study treatments, based on the information provided. 
Suspected Unexpected 
Serious Adverse 
Reaction (SUSAR) 
A serious adverse reaction, the nature and severity of which is not 
consistent with the information about the medicinal product in question 
set out: 
 in the case of a product with a marketing authorisation, in the 
summary of product characteristics (SmPC) for that product 
 we expect that the adverse events described in the SmPC of the IMP 
are relevant for our dosing schedule, despite the fact that we use a 
slightly higher dose than what is used in the SmPC. However, a 
study that used the same dosing schedule as we propose currently, 
did not report adverse events different from those described in the 
SmPC (Sato et al, 1992). Recently, ONO pharmaceuticals conducted 
a study where they tested dosing up to 2400mg daily. They did not 
report any AE except for one person presenting with grade 1 
hyperuricemia (unpublished data).  
 
Attribution definitions 
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable or definitive. 
 
Not related 
An adverse event which is not related to the use of the drug. 
 
Unlikely 
An adverse event for which an alternative explanation is more likely - e.g. concomitant drug(s), 
concomitant disease(s), and/or the relationship in time suggests that a causal relationship is unlikely. 
 
Possible 
An adverse event which might be due to the use of the drug. An alternative explanation - e.g. 
concomitant drug(s), concomitant disease(s), - is inconclusive. The relationship in time is reasonable; 
therefore the causal relationship cannot be excluded. 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
54/63 
Probable 
An adverse event which might be due to the use of the drug. The relationship in time is suggestive (e.g. 
confirmed by dechallenge). An alternative explanation is less likely - e.g. concomitant drug(s), 
concomitant disease(s). 
 
Definitely 
An adverse event which is listed as a possible adverse reaction and cannot be reasonably explained by 
an alternative explanation - e.g. concomitant drug(s), concomitant disease(s). The relationship in time 
is very suggestive (e.g. it is confirmed by dechallenge and rechallenge). 
 
13.2. Reporting requirements 
 
13.2.1. AE reporting 
AEs will be recorded from the first drug administration until the end of the study for the patient, as 
defined in section 5.2. The Institution and the Investigator shall record adverse events (serious and 
non-serious) on the Case Report Form from the time the subject has taken at least one dose of study 
treatment (D1) through the last visit of this subject (D28). 
Special attention will be given to those subjects who have discontinued the study treatment for an AE, 
or who experienced a severe or a serious AE. All AEs should be recorded in the patient’s file and in the 
CRF.  
 
13.2.2. SAE reporting 
SAEs occurring within a period of 30 days following the last intake of study medication will be reported 
as below. 
 
All serious adverse events (initial and follow up information) and pregnancies occurring during this 
study must be reported by the study team within 24 hours after becoming aware of the SAE to: 
- 
HIRUZ CTU of the Ghent University Hospital, who will report the SAE to the central ethics 
committee 
- 
The company that provides the IMP (as stipulated in the agreement with Ono Pharmaceutical 
LTD) 
 
This reporting is done by using the appropriate SAE form(s). For the contact details, see below. 
 
13.2.3. SUSAR reporting 
In case the Coordinating Investigator, in consultation with HIRUZ CTU, decides the SAE is a SUSAR 
(Suspected Unexpected Serious Adverse Reaction), HIRUZ CTU will report the SUSAR to the Central EC 
and the FAMHP within the timelines as defined in national legislation.  


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
55/63 
For fatal and life-threatening SUSARs the sponsor should report at least the minimum information as 
soon as possible and in any case no later than 7 calendar days after being made aware of the case. 
In case of a non life-threatening SUSAR the reporting process must be completed within 15 calendar 
days.  
 
13.2.4. Other reporting requirements 
- report to Ono pregnancy occurring from the start of Clinical Study drug treatment to the completion 
of the final tests (other than the determination of outcome) within twenty-four (24) hours of becoming 
aware of the pregnancy by email. As for the pregnancy, the Investigator shall follow up the pregnancy 
until delivery or the end of pregnancy; 
- provide Non-serious Adverse Events (NSAEs) to Ono by completing and signing a designated CIOMS 
II Line listing form** in English. Such Line listing shall be sent via email to [pmsmailbox@ono.co.jp] at 
the completion of the Clinical Study. NSAE means any Adverse Event that does not meet any of the 
“Serious” criteria described above. 
** See p.35 of final report of CIOMS Working Group II: 
https://cioms.ch/wp-content/uploads/2018/09/cioms-international-reporting-periodic-drug-safety-
update-summaries.pdf 
- cooperate with Ono and its affiliates in the case Ono or its affiliates needs the follow-up investigation 
on the concerned case. The Investigator shall respond to the queries made by Ono or its affiliates 
promptly after receiving them and forward the information to Ono by e-mail. Follow up may also be 
requested by Ono or its affiliates if an SAE information is considered to be incomplete or if Ono or its 
affiliates determines that additional follow up information is required. Follow-up information 
regarding the course of the pregnancy, including perinatal and neonatal outcome and, where 
applicable, offspring information shall be reported; and 
- cooperate with Ono and its affiliates to enable Ono and its affiliates to comply with their obligations 
in relation to the reporting of adverse effects under applicable laws, regulations and/or acts. 
 
13.3. List of contact details for safety reporting 
 
HIRUZ CTU : 
 
 
e-mail: hiruz.ctu@uzgent.be   
 
 
 
 
Tel: 
+3293320500 
 
Coordinating Investigator: 
email: steven.callens@uzgent.be 
 
 
 
 
Tel: 
+3293320171 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
56/63 
Marketing Authorisation Holder: 
Name: Ono Pharmaceutical Co., Ltd. (Osaka, Japan)  
 
 
 
 
 
e-mail: pmsmailbox@ono.co.jp  
 
 
 
Since the subjects are not under 24-hour supervision of the investigator or his/her staff (out-patients, 
volunteers), they (or their designee, if appropriate) must be provided with a "study card" indicating 
the name of the investigational product, the study number, the investigator's name and a 24-hour 
emergency contact number. 
 
13.4. Flowchart Reporting 
 
Type of Adverse Event
Action to be taken
AE
List all AEs per subject in the patient’s file and 
add this information to the CRF. 
 study team informs company that provides 
the IMP (of all NSAEs, only for patients in the 
Camostat arm) 
SAE
Notify to HIRUZ CTU within 24 hours after 
becoming aware of the SAE + add the SAE to a 
list that will be reported yearly (see section 13.7)
 HIRUZ CTU will submit to the central EC 
 study team informs company that provides 
the IMP (only for patients in the Camostat arm) 
SAR
Notify to HIRUZ CTU within 24 hours after 
becoming aware of the SAR 
 HIRUZ CTU will submit to the central EC 
 study team informs company that provides 
the IMP (only for patients in the Camostat arm) 
SUSAR
Notify to HIRUZ CTU within 24 hours after 
becoming aware of the SUSAR 
 HIRUZ CTU will submit to the central EC. 
 HIRUZ CTU will submit to the FAMHP 
 study team informs company that provides 
the IMP (only for patients in the Camostat arm) 
Pregnancy 
study team informs company that provides 
the IMP (only for patients in the Camostat arm) 
 
13.5. Events, excluded from reporting 
 
Not applicable. 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
57/63 
13.6. Data Safety Monitoring Board (DSMB) 
 
We will make use of the ‘DSMB COVID-19 trials Dept. Internal Medicine’ at Ghent University Hospital. 
Although the medication is current practice in Japan and no significant adverse effects have been 
reported in a clinical trial with the dosing that will be used, this dose is not registered (SmPC) and 
furthermore the drug itself is not licensed in Europe. This way we are providing  an additional safety 
evaluation of the Camostat dosing. The DSMB charter can be found as appendix 9.  
 
13.7. Development Safety Update Report 
 
The Coordinating Investigator will provide DSURs once a year throughout the clinical study, or on 
request, to the Competent Authority (FAMHP in Belgium), Ethics Committee and Sponsor. This DSUR 
will include all SAEs (who were not categorized as SARs and were not immediately reported to the EC). 
The report will be submitted within 60 days after one year after the start of the study (FPI), and will 
subsequently be submitted each year until the study is declared ended.   
HIRUZ CTU can provide a template that can be used to complete this DSUR. 
 
14. 
Monitoring/Auditing/Inspection 
 
14.1. Monitoring 
 
14.1.1. General 
Monitoring of the study will be performed in compliance with GCP E6(R2) and the applicable regulatory 
requirements. The study team will be trained in an initiation visit by the monitor. A detailed description 
of the monitoring tasks can be found in the latest version of the (study-specific) ‘Monitoring plan’. 
 
14.1.2. Monitoring team 
Monitoring services will be provided by HIRUZ CTU. All relevant contact details (e.g. primary contact 
person), can be found in the ‘Monitoring plan’. 
 
14.1.3. Scope 
Monitoring services will consist of the following (non-exhaustive list): 
- 
review of informed consents and the followed process 
- 
check on recruitment status 
- 
checking for protocol deviations/violations 
- 
checking GCP compatibility 
- 
check on safety reporting compliance 
- 
IMP handling and storage 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
58/63 
- 
review of study data 
- 
… 
 
14.2. Inspection 
 
This study can be inspected at any time by regulatory agencies during or after completion of the study. 
Therefore access to all study records, including source documents, must be accessible to the inspection 
representatives. Subject privacy must be respected at all times, in accordance to GDPR, GCP and all 
other applicable local regulations. 
The investigator/study team should immediately notify the sponsor if he or she has been contacted by 
a regulatory agency concerning an upcoming inspection. 
 
14.3. Protocol Deviation policy 
 
Sponsor and all investigators agree to take any reasonable actions to correct protocol 
deviations/violations noted during monitoring/inspection, in consultation with the monitoring team. 
All deviations must be documented on a protocol deviation log by the study team that is kept available 
at any time for monitoring/inspection purposes. Under emergency circumstances, deviations from the 
protocol to protect the rights, safety or well-being of human subjects may proceed without prior 
approval of the sponsor and the EC. 
 
14.4. Serious breach to GCP and/or the protocol 
 
Critical issues that significantly affect patient safety, data integrity and/or study conduct should be 
clearly documented and will be communicated with the Coordinating Investigator, HIRUZ CTU and 
possibly both the applicable Ethics Committee(s) and Competent authority. (Please contact HIRUZ CTU 
asap in case of a serious breach: hiruz.ctu@uzgent.be and/or +3293320500). 
Early termination of the study (in a specific center or overall) may be necessary in case of major non-
compliance. 
 
15. 
Ethical and legal aspects 
 
15.1. Good Clinical Practice 
 
The study will be conducted cfr the latest version of the ICH E6 (R2) GCP guidelines, creating a standard 
for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
59/63 
clinical studies that provides assurance that the data and reported results are accurate and that the 
rights, integrity and confidentiality of study subjects are protected. 
 
15.2. Informed Consent 
 
Eligible subjects may only be included in the study after providing written (witnessed, if needed) Ethics 
Committee-approved informed consent, or, if incapable of doing so, after such consent has been 
provided by a legally acceptable representative(s) of the subject. 
Informed consent must be obtained before conducting any study-specific procedures (as described in 
this protocol).  
 
Prior to entry in the study, the investigator must explain to potential subjects or their legal 
representatives the study and the implication of participation. Subjects will be informed that their 
participation is voluntary and that they may withdraw consent to participate at any time. Participating 
subjects will be told that their records may be accessed by competent authorities and by authorized 
persons without violating the confidentiality of the subject, to the extent permitted by the applicable 
law(s) and/or regulations. By signing the Informed Consent Form (ICF), the subjects or legally 
acceptable representatives are authorizing such access. 
After this explanation and before entry to the study, written, dated and signed informed consent 
should be obtained from the subject or legally acceptable representative. The ICF should be provided 
in a language sufficiently understood by the subject. Subjects must be given the opportunity to ask 
questions. 
The subject or legally acceptable representative will be given sufficient time to read the ICF and to ask 
additional questions. After this explanation and before entry to the study, consent should be 
appropriately recorded by means of either the subject's or his/her legal representative's dated 
signature or the signature of an independent witness who certifies the subject's consent in writing. 
After having obtained the consent, a copy of the ICF must be given to the subject. 
In case the subject or legally acceptable representative is unable to read, an impartial witness must 
attest the informed consent. 
The following information should be added to the electronic patient dossier (EPD):   
• 
which version of the ICF was obtained 
• 
who signed the ICF  
• 
if sufficient time has been given to consider participation into the study 
• 
which investigator obtained ICF with the date of signature 
• 
if a copy was provided to the patient 
• 
start and end of participation in the study 
 
 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
60/63 
15.3. Approval of the study protocol 
 
15.3.1. General 
The protocol has been reviewed and approved by the Ethics Committee of the Ghent University 
(Hospital), designated as the central Ethics Committee, and the Federal Agency for Medicine and 
Health Products (FAMHP). This study cannot start before both approvals have been obtained. 
 
15.3.2. Protocol amendments 
Any significant change or addition to the protocol can only be made in a written protocol amendment 
that must be approved by the Central Ethics Committee (and the FAMHP if applicable). 
Only amendments that are intended to eliminate an apparent immediate safety threat to patients may 
be implemented immediately. 
Notwithstanding the need for approval of formal protocol amendments, the investigators are expected 
to take any immediate action, required for the safety of any subject included in this study, even if this 
action represents a deviation from the protocol. These actions should always be notified to the 
sponsor. 
 
15.4. Confidentiality and Data Protection 
 
All study data will be handled in accordance with the law on General Data Protection Regulation (GDPR) 
and institutional rules [Belgian law dated on 30 July 2018 and 22 Aug. 2002]. 
 
The collection and processing of personal data from subjects enrolled in this study will be limited to 
those data that are necessary to fulfill the objectives of the study. These data must be collected and 
processed with adequate precautions to ensure confidentiality and compliance with applicable data 
privacy protection laws and regulations.  
Appropriate technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be put 
in place. Sponsor and site personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential. 
The informed consent obtained from the subject includes explicit consent for the processing of 
personal data and for the investigator/institution to allow direct access to his or her original medical 
records (source data/documents) for study-related monitoring, audit, Ethics Committee review and 
regulatory inspection. This consent also addresses the transfer of the data to other entities, if 
applicable. 
 
Privacy and confidentiality of data generated in the future on stored samples will be protected by the 
same standards applicable to all other clinical data. 
Stored samples will be pseudonymized throughout the sample storage and analysis process and will 
not be labeled with personal identifiers. 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
61/63 
15.5. Liability and Insurance 
 
The sponsor has taken a no fault insurance for this study, in accordance with the relevant legislation 
(article 29, Belgian Law of May 7, 2004). 
Sponsor: Ghent University Hospital 
Insurance Details: Allianz Global Corporate & Specialty, Uitbreidingstraat 86, 2600 Berchem, tel: +32 
33 04 16 00 
Polis number: BEL000862 
 
15.6. End of Study Notification 
 
If all subjects have completed the study, a notification of the end of the study should be submitted to 
the (Central) Ethics Committee and FAMHP. This notification should be made within 90 days of the end 
of the clinical study. In case of early termination (definition in CT-1, 4.2), this is reduced to 15 days. 
 
16. 
Publication policy 
 
Because of the global interest in finding antiviral drugs that can be used in the treatment of COVID-19, 
available data will be made public as soon as possible.  
We hope to have the publication data available as soon as possible but will be limited by the number 
of patients that are currently presenting with COVID-19.  
This study will be registered at ClinicalTrials.gov, and results information from this study will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals. 
 
17. 
Reference List 
 
https://dx.doi.org/10.1016%2Fj.ijantimicag.2020.105949 
https://doi.org/10.1101/2020.03.31.20048777 
Kunyu Yang et a.,Clinical characteristics, outcomes, and risk factors for mortality in patients with 
cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study, The Lancet 
Oncology, 2020 
Dimitar Popov. “Treatment of Covid-19 Infection. A Rationale for Current and Future Pharmacological 
Approach”. EC Pulmonology and Respiratory Medicine 9.4 (2020): 38-58 
https://doi.org/10.1016/j.cell.2020.02.052,  
https://aac.asm.org/content/aac/64/6/e00754-20.full.pdf 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
62/63 
Ohkoshi et al, J. Maxillofac Surgery 1984; 12:148-52 
https://doi.org/10.1101/2020.08.05.237651 
DOI:10.1056/NEJMoA1912400 
DOI:10.1148/radiol.2020200823 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_referen
ce_5x7.pdf 
 
 


COV-AAT 
 
 
Version 3.0 dd. 04JUN2021 
63/63 
18. 
Appendices 
 
18.1. Appendix 1: Study Schedule 
 
18.2. Appendix 2: Questionnaire Daily self score  
 
18.3. Appendix 3: Socio-demographic parameters 
 
18.4. Appendix 4: Emergency ward flow chart 
 
18.5. Appendix 5: Byteflies manual  
 
18.6. Appendix 6: Parameter log  
 
18.7. Appendix 7: Medication log  
 
18.8. Appendix 8: Proposed cut-offs for abnormal values  
 
18.9. Appendix 9: DSMB charter  
 
18.10. Appendix 10: Toxicity lab  

ICF_001.pdf: 
COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 1 of 30 
 
The potential of oral Camostat in early COVID-19 disease in 
an ambulatory setting to reduce viral load and disease 
burden. 
 
Official title of the trial:  
The potential of oral Camostat in early COVID-19 disease in an ambulatory setting to 
reduce viral load and disease burden. 
 
 
EU number: 2020-003475-18 
Trial number: COV-AAT 
Sponsor(s) of the trial: Ghent University Hospital  
 
Site name: Ghent University Hospital 
Main address of site: C. Heymanslaan 10, 9000 Ghent   
 
 
Document Revision History 
 
Version No. 
Version Date 
Revision description 
1.1 
13OCT2020 
Initial approved version 
2.0 
26NOV2020 
Change of PI/CI to Prof Steven Callens 
Trial conduct in case of hospitalization has been 
adjusted from patient withdrawal to further study 
follow-up. 
Patient home monitoring period was adjusted 
from 14 days to the period of intake of study 
medication (5 or 10 days)  
Study schedule was modified
2.1 
02FEB2021 
The 
difference 
between 
withdrawal 
and 
treatment stop with continuous follow-up was 
explained
3.0 
04JUN2021 
Information about substudies which are no longer 
applicable, has been removed.
 
 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 2 of 30 
 
Who can I contact in case of questions? 
 
Name 
Function 
In case of 
Contact details 
Callens Steven 
Principal 
Investigator of the 
site 
Information, 
problems or 
concerns 
09/3320171 
steven.callens@ugent.
be 
De Scheerder 
Marie-Angélique  
Caluwé Els 
Vanherreweghe 
Sophie 
The trial staff  
Information, 
problems, 
concerns 
09/3321349 
 
09/3322319 
09/3325414 
Infectioloog van 
wacht  
Emergency 
contact [not 
emergency 
department of 
hospital] 
Emergency 
0474494302 
Ombudsdienst UZ 
Gent 
http://www.uzgent.
be/nl/patienten/om
budsdienst/pagina
s/default.aspx 
Patient rights 
ombudsman 
Concerns 
relating to your 
rights as a 
participant in a 
trial 
09/3325234 
ombudsdienst@uzgent
.be 
Allianz Global 
Corporate & 
Specialty 
Insurance 
Company of the 
sponsor 
In case of 
disagreement 
or complaint 
on a damage 
claim 
Polisnr.BEL000862 
03/3041600 
Katya Van 
Driessche 
Data protection 
officer of the site 
Questions 
relating to the 
confidentiality 
of your data 
09/3320987 
dpo@uzgent.be 
Gegevens-
beschermings-
autoriteit (GBA) 
Belgian Data 
Protection 
Authority 
Complaints 
relating to the 
confidentiality 
of your data 
E-mail: contact@apd-
gba.be  
 
Version No: Version 3.0, dated 04JUN2021 
 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 3 of 30 
 
Table of contents 
THE TRIAL AT A GLANCE ....................................................................................... 5 
CHAPTER I – DESCRIPTION OF THE TRIAL AND YOUR RIGHTS WHEN 
PARTICIPATING ........................................................................................................ 8 
1. 
Why are we doing this trial ....................................................................................................... 8 
2. 
Why am I being asked to take part? ........................................................................................ 8 
3. 
Do I have to take part in a trial? ............................................................................................... 8 
4. 
What will happen during the trial? ........................................................................................... 8 
5. 
Will I benefit from the trial? .................................................................................................... 10 
6. 
What are the possible risks and discomforts of taking part? ............................................. 10 
6.1. 
What are the possible side effects of Camostat/placebo? ................................................ 10 
6.2. 
What are the possible risks or discomforts of the examinations during the trial? ............. 11 
6.3. 
Can I take other medicines during the trial? ...................................................................... 11 
6.4. 
Will my participation to the trial have an impact on my daily activities? ............................ 12 
6.5. 
Can my partner or I get pregnant or can I breastfeed during the trial? ............................. 12 
7. 
What If something goes wrong within the trial? .................................................................. 13 
8. 
What if other treatment options or new information on the IMP become available during 
the course of the trial? .................................................................................................................... 13 
9. 
Can my participation in the trial end prematurely? ............................................................. 13 
9.1. 
You decide to withdraw your consent ................................................................................ 14 
9.2. 
The investigator decides to end your trial participation ..................................................... 14 
9.3. 
Other entities may interrupt or end the trial ....................................................................... 15 
10. 
Which treatment will I get after my participation in the trial? ......................................... 15 
11. 
Will my participation in the trial involve extra costs for me? ......................................... 15 
11.1. 
Examinations and treatments paid by the sponsor ....................................................... 15 
11.2. 
Other expenses paid by the sponsor ............................................................................. 16 
12. 
Which data are collected about me during the trial and what will happen with them? 16 
12.1. 
Which data are collected and processed during the trial? ............................................ 16 
12.2. 
How will the investigator treat my personal data? ......................................................... 16 
12.3. 
What will happen to information about me collected during the trial? ........................... 16 
12.4. 
How will my data be handled? ....................................................................................... 17 
12.5. 
Do I have access to my data collected and processed during the trial and can I rectify 
them ? 
17 
12.6. 
Who, other than the Investigator and his staff, has access to my personal data? ........ 17 
12.7. 
What will happen to the results of the trial? ................................................................... 18 
12.8. 
Will my data be used for other purposes than for the trial in which I take part? ........... 19 
12.9. 
How long will my data be kept? ..................................................................................... 19 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 4 of 30 
 
13. 
Which biological samples are collected from me during the trial and what will happen 
with them? ........................................................................................................................................ 19 
13.1. 
Which biological samples are collected from me during the trial? ................................ 19 
13.2. 
What will happen to the collected biological samples? ................................................. 19 
13.3. 
How will my biological samples be handled? ................................................................ 20 
13.4. 
What happens with any remainders of biological samples once the analyses described 
in this document have been carried out? ...................................................................................... 20 
13.5. 
Will any additional biological samples be collected and used for additional research? 21 
14. 
Who has reviewed and approved the trial documents? .................................................. 21 
15. 
What happens in case of incidental findings? ................................................................. 21 
CHAPTER II – SUBSTUDY SCREENING FAILURES ............................................ 22 
CHAPTER III – INFORMED CONSENT ................................................................... 23 
PARTICIPANT ....................................................................................................................................... 23 
INVESTIGATOR ..................................................................................................................................... 26 
ANNEX: FLOWCHART OF THE STUDY ................................................................. 28 
GLOSSARY ............................................................................................................. 29 
REFERENCES ......................................................................................................... 30 
 
 
 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 5 of 30 
 
THE TRIAL AT A GLANCE 
 
Dear patient, 
 
I recently informed you that you have a COVID-19 infection. 
 
That is why we invite you to take part in a clinical trial (further referred to as "the trial") that is 
meant to evaluate an investigational medicinal product for the treatment of this infection.  
Before you agree to take part in this trial, we want to fully inform you about the trial and its 
implications in terms of organisation, and its possible risks and benefits, so you can decide 
for yourself if you want to take part. This process is known as giving "informed consent". 
This chapter will already give you an idea of what will happen during this trial, but we 
nevertheless ask you to read all the pages, even if it will take you a lot of time. It is important 
that you read and understand all the information. If you don't do this, you will take part in the 
trial without knowing what you’re signing up for. So ask all your questions to the trial staff. 
In this trial, the investigational medicinal product CAMOSTAT will be tested. This 
investigational product is being used in the treatment of diseases such as pancreatitis and 
esophagitis and has been on the market in Japan for over many years. It is known to have 
very little side effects and is well tolerated. It has not yet been proven that it can cure, improve 
or stabilise COVID infection. That is what we want to demonstrate with this trial, so it is 
uncertain at this point whether you will benefit from it. That is precisely what we want to 
find out: does the investigational medicinal product work, does it not work, or not enough. In 
the first place we want to find out whether Camostat can reduce the viral load in people 
infected with COVID-19, which would reduce the chance of transmission and potentially lead 
to a better outcome and faster cure in those infected.  
In concrete terms, this means that during the trial you will receive the standard care. If you 
take part in the trial, you will receive in addition the investigational medicinal product 
Camostat or placebo. You will take the investigational medicinal product in the form of 3 
tablets, 3 times a day during 5 days in a fasting state. You will take the medication and home 
and we will monitor you during the course of the study.  
 
If you agree to take part in the trial, we will carry out prior tests to check whether you meet 
all the conditions to be accepted for this trial. We will monitor your clinical symptoms during 
the first 14 days and will equip you with a home monitor tool so you can follow-up your 
temperature, oxygen saturation, heart rate and respiratory rate 3 times a day. If these values 
are abnormal, you will be asked to remeasure or to contact the trial staff. At D0 and D5 your 
blood will be checked to screen for adverse events. If necessary additional blood analysis 
can be proposed. At D5 we will check the presence of the virus by taking a nose/throat swab. 
On the last study visit (D28) we will check the presence of antibodies against COVID-19. If 
virus is still present at D5, we can decide to prolong the treatment with an additional 5 days. 
An additional control will then take place at D10.  
 
If at screening you do not meet the inclusion criteria for the main study (positive screening 
test but low viral load and absence of symptoms), you can exceptionally take part in a 
separate substudy (chapter II page 22). Here we want to analyse whether you can still 
transmit the virus to your close contacts by measuring viable virus in the nose/throat swab 
and to look whether patients with mild infections develop antibodies and immunity against 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 6 of 30 
 
SARSCOV2. Therefore an additional swab will be taken at D0 and a blood sampling will be 
done at D28. 
If you want you can participate in the main study without participating in the separate 
substudy. However, you cannot participate only in the substudy, if you are not willing to 
participate in the main study.  
The study will take in total (maximum) 29 days (D0->D28). I need to know how well the 
investigational medicinal product works for you, and how well you tolerate the treatment. You 
will also have to fill in questionnaires. Even after the period of administration of the 
investigational medicinal product has ended, you will remain in the trial and will be followed 
up during the consultations and by questionnaires by telephone and email, in order to find 
out how you are doing.  
 
It is also very important that you know that all medicinal products have side effects. 
Therefore, it is really important that you report any side effects or any new health problem 
to the trial staff.  
 
The sponsor of this trial, the Ghent University Hospital, has taken out insurance for this 
trial. 
 
You are not allowed to become pregnant or to get someone pregnant during the trial and 
for some time after it. I will discuss with you the appropriate method of contraception. 
All treatments and examinations that you will undergo or receive in the context of the trial will 
be free of charge for you. All other treatments or examinations that you would have 
undergone anyway if you did not take part in the trial, must be paid for by your health 
insurance and by yourself.  
 
The data collected during this trial will be treated confidentially.  
 
You should also know that within the framework of this trial, a number of biological samples
(e.g. blood) will be taken. These samples will be stored for a very long period of time. Me or 
my staff will give you clear information about this, and you will have to decide what you do 
or do not want. It is important to think about it carefully. 
 
If you are hospitalized during the trial, the study-medication will be stopped for the remainder 
of the study. You will not undergo any study specific procedures but we will continue to follow 
you for the time of study (=29days), using your patient file. If you are hospitalized in Ghent 
University Hospital, we ask your permission to consult your file. If you are admitted in another 
hospital we ask your permission to contact your GP or treating physician. Once you are 
discharged from the hospital, you will be invited to continue study specific intervention as 
described.  
 
There is one thing that I would like to emphasise very strongly: you are not obliged in 
any way to take part in this trial. Even if you have already started the trial, you can stop at 
any time. I will fully understand your decision, and will continue to take care of you as before.
The authorities and an ethics committee have evaluated this trial. It is not because they have 
approved this trial that you should feel obliged to take part. 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 7 of 30 
 
To be able to take part in this trial, you must, for your own safety, agree that I, the 
investigator, inform your treating physicians of your participation in this trial. You are not 
allowed to take part in another clinical trial at the same time without informing the 
researcher or the trial staff. We may refuse that participation to other trials for justified 
reasons. It is also very important that you cooperate and follow the instructions that the trial 
staff and I give you regarding the trial. You will receive an "emergency card", which says that 
you are taking part in a clinical trial. You must carry this card with you at all times; this is 
necessary for your safety should you have to undergo emergency treatment in a hospital 
where they don’t know you. 
If you agree to take part, you will need to sign the informed consent form. I will also sign the 
form and thereby confirm that you have received the necessary information about the trial. 
You will receive a signed and dated copy of the form.
 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 8 of 30 
 
CHAPTER I – DESCRIPTION OF THE TRIAL AND YOUR 
RIGHTS WHEN PARTICIPATING 
1. Why are we doing this trial 
This clinical trial (further on referred to as “trial”) will evaluate the investigational 
medicinal product (IMP), Camostat for the treatment of COVID-19. The purpose of this 
trial is to learn about the role of Camostat in the treatment of COVID-19 in ambulatory 
setting. We want to study whether Camostat has the potential to reduce the viral load 
and therefore reduce the risk of transmissibility, reduces the disease burden and the 
time to recovery.  
Camostat is a drug that has been used for a very long time in the treatment of 
pancreatitis in Japan and has a good tolerability profile. It is taken as a tablet and 
therefore can be easily taken at home.  
In vitro laboratory studies have shown the potential effect of Camostat on the entry of 
the SARSCOV-2 virus in the lung cells. Therefore a couple of studies are currently 
investigating whether this drug can be of use in fighting COVID-19.  
In this pilotstudy, we will look whether we see a difference in viral load between 
Camostat and placebo after treating COVID-19 infected individuals during 5 days. We 
will measure the virus in nose/throat swabs. By doing this we want to show the effect 
of Camostat on viral load and by consequence on transmissibility and potentially the 
clinical effects (time to recovery and milder symptoms).  
 
2. Why am I being asked to take part? 
You have been diagnosed with COVID-19 
You are being asked to take part in this trial because you are 18 years or older, in an 
early stage of COVID infection or not presenting any symptoms despite having tested 
positive and not requiring a hospitalisation.  
For your COVID infection, no treatment is currently available in Belgium that has been 
approved by the authorities.  
The investigator or trial staff will discuss with you the requirements to be allowed to 
enter the trial. 
 
3. Do I have to take part in a trial? 
Your participation in a trial is voluntary and must remain free of any coercion. This 
means that you have the right not to take part in the trial or to withdraw at any time 
without giving a reason, even if you previously agreed to take part. Your decision will 
not affect your relationship with the investigator or your treating physician nor will it 
affect the quality of your future medical care. 
 
4. What will happen during the trial?  
This trial aims to include 150 participants in Ghent.  


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 9 of 30 
 
This trial is a randomised, dubbel blinded, placebo controlled trial. Randomisation will 
take place 2 against one, giving you 2 times more chance of being treated with 
Camostat compared to placebo. You will only know which arm you are randomised in 
after completion of the study. Also the study physician will be blinded and will only 
know which treatment you received after all inclusions have been finalised.  
After screening and randomisation you will immediately start your medication. The first 
dose will be defined as D1. You will take the medication for 5 consecutive days, 3 times 
a day and 3 pills per intake. The drug will be taken orally. You will take the medication 
in a fasting state (Minimum 60 minutes before the meal and 2 hours after the previous 
meal). You will be asked to fill in a medication schedule reporting on the number of 
pills, hour of intake and relationship to the meals. If you forget a dose you can take it 
up to 4 hours after the time of intake. You have to take into account a minimum of 4 
hours between each dose, so consequently other doses should be shifted as well. If 
you cannot take the dose within 4 hours than this dose will be passed. This needs to 
be documented in the medication schedule. If you have questions regarding dosing, 
you can contact the trial staff. The medications needs to be conserved at room 
temperature.  
On day 0 and day 5 a blood analysis will be performed (max 21ml) to check for adverse 
events of the medication.  
You will be followed during this period through telephone, email and consultations and 
at the hospital. You will receive a kit to perform some analysis at home 3 times per day 
including temperature measurement, oxygen saturation, heart rate and respiratory 
rate. You will be asked to register these data into an online platform or by phone. If 
these values are abnormal, you will be asked to remeasure or contact the trial staff. 
You will be asked to fill in a questionnaire on a daily basis between D1 and D14 through 
email or on paper, which can be given to the study personnel at the hospital visit.  
The intensive monitoring phase will be prolonged up to 14 days after inclusion (D14). 
This period will be extended if patients still present symptoms at D14 until D28. The 
final visit is planned D28. In between a visit is planned at D5 to control the virus via 
nose/throat swab.  
If you still present symptoms at D5 or the swab remains positive, the study physician 
will decide to prolong your treatment for an additional 5 days. If your condition requires 
a hospitalization, the study will be interrupted. If the treatment is prolonged, you will 
continue the same medication (placebo or camostat) 5 consecutive days, 3 tablets, 3 
times per day, fasting. An additional visit will be planned on D10. This visit will include 
an additional swab. If the swab remains positive at D10, this will be repeated at D28.  
At the final visit D28, we will also check your blood for antibodies.  
If you are willing to participate in the main study but do not meet the inclusion criteria 
for the study (positive screening test but low viral load and absence of symptoms), you 
can exceptionally take part in a separate substudy. Here we want to analyse whether 
you can still transmit the virus to your close contacts, despite the low viral load by 
measuring viable virus in the nose/throat swab and to look whether patients with mild 
infections develop antibodies and immunity against SARSCOV2. Therefore an 
additional swab will be taken at D0 and a blood sampling will be done at D28. 10 
participants can be included.  
At any given time during the study you might be asked for an additional blood sampling 
to follow-up inflammatory parameters related to your COVID infection. This will always 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 10 of 30 
 
be discussed with the responsible physician and is part of standard of care. If an X ray 
or CT from the lungs is performed during the trial, these data will be analysed in the 
study. These exams will only be performed as SOC and the decision to perform them 
will rely on your treating physician.  
If these standard of care data are available, they will be analysed in the study.  
Attached you can find an overview of the exams and visits and which are study specific 
or standard of care.  
Overall, your participation in the trial will last 29 days and involve 3 or 4 visits.  
If you meet all the conditions required to be enrolled in the trial and agree to take part 
in the trial, you will undergo the above-mentioned tests and examinations. If you have 
any important side effects, the investigator might determine that it is necessary to 
perform additional tests which will be considered as specific to the trial. 
- 
If you are hospitalized during the trial, the study-medication will be stopped for 
the remainder of the study. You will not undergo any study specific procedures 
but we will continue to follow you for the time of study (=29days), using your 
patient file. If you are hospitalized in Ghent University Hospital, we ask your 
permission to consult your file. If you are admitted in another hospital we ask 
your permission to contact your GP or treating physician. Once you are 
discharged from the hospital, you will be invited to continue study specific 
intervention as described below: Discharge before D14: daily questionnaires 
until D14. If symptoms are still present at D14, this will be prolonged until D28.  
- 
Discharge after D14: if you still present symptoms, daily questionnaires will be 
continued until D28.  
- 
D28 study visit will be done as described above except when a patient is still 
hospitalised at that time.  
- 
If you leave the hospital after D28, you will not undergo any study specific 
interventions. In this case we ask you to use your medical file to collect data 
regarding your COVID infection as described above.  
 
We expect that you will use Camostat/placebo as described above.  
 
5. Will I benefit from the trial?  
The information obtained during a trial may contribute to a better understanding of the 
use of the investigational medicinal product (referred to as “IMP”) or to the development 
of a new medicinal product for the treatment of yourself or future patients. 
The IMP may or may not be beneficial in treating your COVID infection or relieving 
your symptoms. Even if it is beneficial to you, a potential return or worsening of 
symptoms, illness or disease is still possible.  
 
6. What are the possible risks and discomforts of taking part? 
6.1. 
What are the possible side effects of Camostat/placebo? 
Participation in a trial involves some risk. 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 11 of 30 
 
All medicinal products can have side effects. Some of these side effects are already 
known, and some are not known. Even if previous studies have shown that 
Camostat/placebo was/were normally well tolerated, you may still experience the 
following side effects:  
- Hypersensitivity reactions: rash (0.4%), pruritus (0.2%), nausea 
(0.3%), abdominal discomfort (0.2%), bloating (0.2%), diarrhea 
(0.2%) 
- Liver enzyme disturbances (0.2%), thrombopenia, hypokalaemia 
- The placebo contains lactose which might induce gastro-intestinal 
complaints in patients with lactose intolerance.  
Because this IMP is still under investigation, other currently unknown risks and 
discomforts could occur. Therefore, it is very important that you report any new or 
worsened health problems immediately to the investigator, regardless of 
whether or not you think it has to do with the trial (or to Camostat/placebo), and 
even when it is already described in this document. If you need to use other 
medication, discuss this with the investigator before taking it. If, for any reason, 
you consult another treating physician during the trial you must inform him/her 
that you are taking part in a trial and present your emergency card. This could 
be important in determining a diagnosis and giving you the correct treatment if 
needed. 
If you experience adverse effects of the medication, these will be registered and in 
function of severity we will decide whether you can continue the treatment.  
We do not know whether the drug will have an effect on your disease. During the trial 
you will get the same standard of care as people that are not involved in the trial. If 
your disease worsens, you will be admitted in the hospital. Your participation in this 
trial does not change this standard of care nor any treatments that might be available 
at that time for treating COVID-19.  
 
6.2. 
What are the possible risks or discomforts of the examinations 
during the trial? 
The examinations of the trial may cause the following discomforts and risks:  
The taking of blood to check for adverse events (max 21ml at D0 and D5) and the 
analysis of antibodies at D28 (9ml) may cause pain, bleeding, bruising or infection 
localised around the injection site. Similarly, some participants may feel dizzy or even 
faint during the procedure.  The staff who take the blood will do all they can to minimize 
these discomforts. 
The nose/throat swab can be experienced as uncomfortable.  
 
6.3. 
Can I take other medicines during the trial?  
Do not hesitate to ask your investigator for more explanation about the use of other 
medicines and food supplements. 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 12 of 30 
 
6.4. 
Will my participation to the trial have an impact on my daily 
activities?  
The fact that you are infected with COVID 19 might have an important effect on your 
daily activities, probably due to related symptoms and isolation measurements.  
We will ask you to complete questionnaires and to do home monitoring and transfer 
these data 3x/day. Therefore we will ask an additional effort from you besides taking 
the medication correctly. We will also ask you for 2 visits at the clinic.  
 
6.5. 
Can my partner or I get pregnant or can I breastfeed during the 
trial?  
This section is intended solely for participants with a potential to get pregnant or 
participants who may get their partners pregnant. 
Female participant: Because the effects of Camostat on an unborn child or infant are 
not known, you will not be allowed to take part in this trial if  
- 
you are pregnant,  
- 
wish to become pregnant in the near future or  
- 
if you are breastfeeding.  
It is also not allowed to do egg/ovum donation during your participation in the trial. 
If you take part in the trial, you must use one of the authorised methods of 
contraception, during the trial: abstinence, intra-uterin device with a fail ratio of less 
than 1%, sterilisation of the male partner, approved hormonal contraception. Please 
discuss this point with your investigator if this applies to you. Please inform the 
investigator in case you would decide during the trial to change your method of 
contraception.  
You will be required to have a pregnancy test (urine) at trial start before the first dose 
of Camostat/placebo. A repeated pregnancy test must be done if you miss any periods 
or your menstrual cycle becomes irregular.  
Nevertheless, if you become pregnant during the trial, you should inform immediately 
the investigator and your treating physician. (S)he will ask you to sign a specific 
informed consent (for the pregnant participant) to follow up your pregnancy and its 
outcome. Upon your approval we will follow-up the evolution of the pregnancy, birth 
and first months of your child. 
Male participant: 
Taking Camostat/placebo could have an effect on your sperm and could lead to an 
unknown risk for an unborn child.  
If you take part in the trial, you must use contraception and you should not be sperm 
donor for the duration of the trial. Please discuss this point with the investigator if this 
applies to you.  
You commit to inform your female partner of your participation in this trial and of the 
potential risk to an unborn child.  
Nevertheless, if your partner becomes pregnant during the trial, you should inform 
immediately the investigator. If you agree, (s)he will contact your partner to ask her to 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 13 of 30 
 
be followed up during her pregnancy and its outcome and to sign a specific informed 
consent (for the pregnant partner).  
 
7. What If something goes wrong within the trial? 
Even if there is no fault, the sponsor is liable for harm caused to you whether directly 
or indirectly related to your participation in the trial. The sponsor has taken an  
appropriate insurance (a so called “NO FAULT INSURANCE”) for this liability (Ref. 1). 
A copy of the insurance certificate can be obtained from the investigator or trial staff. 
If you (or in the event of death, your rightful claimants) seek compensation for a harm 
to your health as a direct or indirect result of participating in the trial, you must inform 
your investigator or trial staff promptly. 
If the investigator believes that a link between the new or worsened health problem(s) 
and the trial is possible, he/she will inform the trial sponsor. The sponsor will then 
immediately initiate the declaration procedure to its insurance company. If the 
company considers it necessary, it will appoint an expert to assess whether there is a 
link between your reported health problem(s) and the trial. The insurance does not 
cover the natural progression of your disease/condition or the known side effects of 
the treatment you would have received without taking part to the trial (that is your 
standard treatment). 
Whenever you feel it is appropriate or if you or your rightful claimants disagree either 
with the investigator or with the expert appointed by the insurance company, you may 
contact the insurance company or proceedings may be brought against the insurance 
company. You will find the contact details on the front page of this form. 
 
8. What if other treatment options or new information on the IMP become 
available during the course of the trial? 
During the course of the trial, important new information might become available, 
possibly affecting your decision to (further) participate. For example other treatments 
for your COVID 19 or important new information on the IMP may become available. It 
is the duty of the investigator to discuss this new information with you and to give you 
the opportunity to re-consider your participation in the trial. 
If you decide to stop taking part in the trial or if you are no longer able to participate, 
your investigator will see to it that you continue to receive the best possible medical 
care. 
 
9. Can my participation in the trial end prematurely? 
As explained in detail below, your trial participation will end prematurely when  
 you decide to withdraw your consent, 
 the investigator decides to end your trial participation or the stop the study 
treatment, or 
 other entities interrupt or end the trial. 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 14 of 30 
 
In any case, if your trial participation ends prematurely, the investigator will discuss 
your future medical care with you. The sponsor can continue to retain and use any 
data that have already been collected before the end of your participation. This is to 
avoid skewing / biasing results of the trial (as described in I. § 12.4., page 17). 
If you experience a side effect at the moment of stopping the IMP, the investigator may 
contact you in the future to see if it has resolved or not after the end of the trial 
participation.  
If you experience a new side effect after the end of your trial participation you may 
contact the investigator to ask for a follow-up. 
 
9.1. 
You decide to withdraw your consent 
You are entitled to withdraw your consent for any reason, at any time, without having 
to justify your decision. However, for your safety, you should inform the investigator of 
your decision. Although it is not mandatory, it may be useful for the investigator and 
for the sponsor to know the reason of your decision (for example side effects, 
frequency of clinical visits,…).  
 
If you withdraw your consent, this means you decide to stop  
 the treatment with the IMP, and  
 all trial-related visits and examinations. 
Please discuss with your investigator to evaluate the practical modalities of your 
withdrawal (in light of your situation), including any follow up-visits or procedures.  
In any case, no new data will be sent to the sponsor. 
If your biological samples (e.g. blood samples, urine samples) have already been used 
or analysed before the withdrawal of your consent, the sponsor still has the right to use 
the results from those tests.  
The biological samples that have been collected (but not tested) before the withdrawal 
of your consent and the data obtained from it, can also still be used by the sponsor. 
You may ask for a destruction of those samples. If this impacts the validity of the trial, 
the destruction may be postponed till the end of the trial.  
In case you have signed an additional consent form for the use of your samples in 
future research, and you choose not to withdraw this separate consent, your samples 
can still be used for this research. 
 
9.2. 
The investigator decides to end your trial participation.  
The investigator will end your trial participation because  
 you become pregnant during the trial, 
 it is better for your health, 
 he/she determines that you are not following the instructions given to 
participants, or 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 15 of 30 
 
any other reason that will be explained. 
The investigator can also decide to stop the treatment (eg in case of side effects). In 
this case, the investigators will continue to follow-up the outcome of your study 
participation. In this case all planned visits and sample collections can be continued 
conform the protocol.  
 
9.3. 
Other entities may interrupt or end the trial 
The sponsor and the competent Belgian health authorities may interrupt or end the trial 
because  
 the information gathered shows that the IMP is not effective (does not deliver a 
sufficient level of improvement in the health of the trial participants), 
 the IMP causes more (serious) side effects than anticipated, or  
 any other reason that will be duly motivated by such party. 
 
10. Which treatment will I get after my participation in the trial?  
After you stopped the treatment with the IMP, the investigator will assess your health. 
If necessary, he/she will prescribe you the best standard treatment available or refer 
you to another treating physician of your choice. 
 
11. Will my participation in the trial involve extra costs for me? 
11.1. 
Examinations and treatments paid by the sponsor 
The sponsor has arranged to compensate the hospital or site for 
 the time devoted to the trial by the investigator and the trial staff,  
 the visits/consultations and all scheduled examinations specific to the trial, 
 the investigational treatment (IMP and any other medication and material 
specifically used for the trial).  
 
In the annex to this ICF you will find the treatments or examinations that you will have 
to undergo, with the specifications which ones are trial specific and which ones are 
part of your standard care. The treatments and examinations that are trial specific will 
be paid by the sponsor and will not be charged to you. The standard procedures or 
examinations for your condition (i.e. standard of care) will be charged to you or your 
mutual insurance fund (Belgian social security). 
If you need more details or if you are not affiliated with a mutual insurance fund (Belgian 
social security), please contact the trial staff. 
The visits and treatments which are a consequence of a side effect are also considered 
as trial specific. 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 16 of 30 
 
11.2. 
Other expenses paid by the sponsor 
The study will provide the medication and monitoring kits. They will not reimburse any 
additional costs.  
 
12. Which data are collected about me during the trial and what will happen with 
them? 
12.1. 
Which data are collected and processed during the trial?  
The collected and processed personal data concern information about your health and 
medical condition. This includes your medical history, some of your background 
information (for example your age, sex, and ethnic origin) and the results of 
examinations required by the trial.  
 
12.2. 
How will the investigator treat my personal data? 
The investigator is bound by professional secrecy about the data collected. 
This means that he/she will never reveal your identity, including in a scientific 
publication or a lecture and that he/she will encode your data (that is by replacing your 
identity by an identification code in the trial) before sending them to the sponsor. 
Therefore, the investigator and the trial staff under the responsibility of the investigator, 
will be the only ones able to establish a link between your identity and the data 
transmitted during the trial, with the exceptions listed under section 12.6.  
The data transmitted to the sponsor will not allow the sponsor to identify you.  
 
12.3. 
What will happen to information about me collected during the 
trial? 
Your participation in the trial means that your personal data 
- 
are collected by the investigator, and 
- 
are used in an encoded form by the trial sponsor.  
The investigator and the sponsor can only use the encoded personal data for research 
purposes in connection with scientific publications within the context of the trial that 
you participate in, or for a broader use of the encoded data if described below. 
In addition, the sponsor may provide access to the encoded data to external 
researchers (that are not involved in this trial).  In the event an external researcher 
wants to use the data in a project not yet described in this document, this project will 
have to be approved by an Ethics Committee. If your encoded trial data are sold, you 
will not benefit from this. 
If side effects appear during the study that could be linked to the treatment with 
camostat, this information will be transferred to the company which provides this 
medication (Ono Pharmaceutical Co, Ltd.), without transferring personal data.  
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 17 of 30 
 
12.4. 
How will my data be handled? 
Your trial data will be processed in accordance with the General Data Protection 
Regulation (GDPR, Ref. 2) and the Belgian law on data protection of 30th July 2018 
(Ref. 3). The sponsor is responsible for this processing. 
Processing your personal data in this trial is allowed because we are conducting 
scientific research and  
• 
You have given your consent. 
 
12.5. 
Do I have access to my data collected and processed during the 
trial and can I rectify them ?  
You are entitled to ask the investigator what data are being collected about you and 
how those data will be used in connection with the trial.  
You have the right to withdraw your consent for the processing of personal data. 
However personal data collected before withdrawal will be kept to avoid skewing of 
results in the trial.  
 
Your right  
 to inspect and access these data  
 to ask for correction if they are incorrect  
is postponed for the following reasons, including to avoid skewing of results in the trials 
because of the blinded character of the study. This means that neither the study 
physician or yourself have information on which study arm you are randomised in. 
Access to the study data therefore might influence the interpretation of the study 
results. Please ask your investigator when you can have access to your personal data. 
 
It is not possible  
 to have all your data erased  
 to restrict the processing of your data.  
 to object to the processing of your personal data  
for the following reasons, including to avoid skewing of results in the trial. 
 
12.6. 
Who, other than the Investigator and his staff, has access to my 
personal data? 
To verify the quality of the trial, it is possible that your personal uncoded data or 
information in your medical records relevant for the trial, will be examined by people 
outside the trial staff but under the responsibility of the investigator. These persons 
must be subject to professional secrecy or a confidentiality agreement. The following 
might be considered: 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 18 of 30 
 
 the personnel designated by the sponsor of the trial (MONITORS and 
AUDITORS), and people or organisations providing services for or collaborating 
with the sponsor. They will however never transfer your name and contact 
details to the sponsor. 
 inspectors of competent health authorities worldwide 
 an independent audit group  
 people designated by the Ethics Committee 
 
For the needs of the trial, the encoded trial data may be sent to other EU and non-
EU countries and may be reviewed by 
 personnel (other than the inspectors) of competent health authorities of Belgium 
(Federal agency for medicines and health products, FAMHP) and other EU and 
non-EU countries,  
 the evaluating Belgian Ethics Committee(s),  
 external researchers, 
 the sponsor of the trial, personnel designated by the sponsor, and people or 
organisations providing services for or collaborating with the sponsor, and/or  
 group companies of the sponsor in Belgium, and in other EU and non-EU 
countries.  
The European regulation and the Belgian legislation on data protection have 
requirements for transferring data to non-EU countries. The sponsor must ensure 
equivalent guarantees regarding personal data protection standards before 
transferring the encoded data to non-EU countries. If for this purpose, there is a data 
protection agreement, a copy of this agreement may be obtained via the investigator. 
You can always contact your investigator to obtain more information about any such 
transfers. 
To register the parameters obtained by the monitoring tool that you receive, we are 
using a data platform provided by the company Byteflies. Your data will be linked to 
the sensor Dot ID and will be coded. The company therefore is not able to link this data 
to your person and cannot use the obtained data for other purposes than those 
mentioned in the study. We will provide you with a flyer including information on the 
correct usage of the monitoring kit and how the data should be transferred.  
We ask you to return the monitoring material in a good state.   
In this study, questionnaires will be asked to be filled in by providing a valid e-
mailadress. Only pseudomysed data will be used for the analysis of the data and in all 
reports or publication about the study.  
 
12.7. 
What will happen to the results of the trial? 
After trial closure, a description and the results of this clinical trial will be published in 
specialised medical journals. A copy of the scientific publication or a summary for 
laypersons can be obtained from the investigator or the trial staff. 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 19 of 30 
 
A description of the trial will also be available on https://www.Clinicaltrials.gov.  You 
can search these websites at any time using the trial number given on the front page 
of the informed consent form. The websites will include a summary of the results within 
1 year after the end of the trial (Ref. 4).  
These websites or publications will not include information that can identify you.  
 
12.8. 
Will my data be used for other purposes than for the trial in which 
I take part?  
The results of the trial will be used to answer the scientific questions of the trial. In 
addition, the sponsor would like to use your data obtained from this trial, in connection 
with other research and development activities (and the associated scientific 
publications). These activities may concern  
 the way Camostat and drugs of the same group work,  
 the disease/condition for which Camostat is evaluated in this trial or  
 other diseases and health problems which could benefit from Camostat, or from 
related diagnostic tests.  
Any additional research outside of the trial, must be approved by a Belgian recognized 
Ethics Committee. 
At the end of this form you agree or disagree to the use of your trial data for other 
purposes by ticking the appropriate check-box in Chapter III, page 23. 
 
12.9. 
How long will my data be kept?  
After the end of the trial your encoded data will be retained for at least 25 years (Ref. 5) 
to ensure the validity of the research. This will also be the case if you stopped trial 
participation prematurely.  
 
13.  Which biological samples are collected from me during the trial and what will 
happen with them?  
13.1. 
Which biological samples are collected from me during the trial? 
Biological samples are samples of human body material (for example blood, tissue, 
urine, faecal stool, ….)  
In this trial, the following biological sample(s) will be taken:  
- 
nose/throat swab (max 4 in the core study D0-D5-D10 and D28) 
- 
blood sampling (2x 21ml at D0 and D5 to screen for side effects, 1x9ml D28, 
additional blood sampling standard of care or tolerability 1x9ml, 3x6ml.  
 
13.2. 
What will happen to the collected biological samples? 
The collected biological samples will be managed and stored at the biobank Ghent 
University Hospital for 25 years. 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 20 of 30 
 
These biological samples will be analysed for the objectives of the trial. Some analysis 
will be performed by external partners. The viral load and the antibodies will be 
measured in the lab of Sciensano in Brussels. 
Leftover material from the samples send to external partners will be destroyed. 
Leftover samples from the analysis done at Ghent University and back-up samples will 
be stored at the Biobank HCRC. 
Genetic analyses will also be performed on your samples. The purpose of these 
analyses is to analyse the genetic material of the virus.   
These genetic analyses will deliver essential information for the trial. If you do not want 
these analyses to be conducted, you will not be allowed to participate in the trial.   
It may happen by chance and in addition to the trial objectives, that the results of the 
analysis of your biological samples reveal information that may be important to your 
health or the health of your blood relatives. These data are called ”incidental findings” 
and will be treated as described in Chapter I, § 15, page 21. 
 
13.3. 
How will my biological samples be handled? 
The procedure to encode your biological samples is the same as that used for your 
personal data (see I § 12.3, page 16, Ref. 6). Samples sent to the sponsor or to 
organisations working in collaboration with the sponsor, will  only be labelled with your 
trial identification code. 
As part of the trial, the sponsor might transfer (a part of) your samples to a laboratory 
that is working with them. This laboratory may only use your samples as specified in 
this document. The tracking of your samples will be ensured by the sponsor unless 
you have accepted anonymization of your samples. 
Your biological samples are deemed to be a “donation”. You will not receive any 
financial benefit associated with the development of new therapies derived from the 
use of your biological samples, and which may have commercial value. 
 
13.4. 
What happens with any remainders of biological samples once 
the analyses described in this document have been carried out? 
The sponsor shall use the biological samples within the context of the trial as described 
above.   
Since scientific progress in this area is constant, the sponsor would like to, with your 
consent retain a part of the remainders of your biological samples for 25 years. The 
sponsor will use them for future research, outside the trial that you will participate in, 
to better understand the disease, its treatment and the responses to this treatment, 
and Camostat. The retention of the remainders of your samples goes together with the 
retention of the accompanying encoded personal data. 
You agree or disagree to the retention of the remainders of your biological samples for 
future research by ticking the appropriate check-box in Chapter III, page 23.  
If you agree, any future research, additional to what is described above, may only be 
conducted according to the legislation on the use of human tissue material (Ref. 7) and 
with the approval of a Belgian recognized Ethics Committee. As a general rule, you will 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 21 of 30 
 
be asked to sign an additional informed consent form in which the additional research 
is specified. 
 
13.5. 
Will any additional biological samples be collected and used for 
additional research?  
In this trial, no additional biological samples will be collected. 
 
14. Who has reviewed and approved the trial documents? 
The documents of the trial have been reviewed by 
 The Belgian competent health authorities (FAMHP) or if applicable by the 
competent national health authorities of other EU members states and 
 An independent Belgian Ethics Committee 
It is the task of the competent health authorities and the Ethics Committees to protect 
people who take part in a trial. The health authorities will ensure that the trial is 
conducted in accordance with the applicable legislation. 
You should not under any circumstances take their approval as an incentive to take 
part in the trial. 
 
15. What happens in case of incidental findings? 
If by chance and in addition to the trial objectives a result is discovered during the trial 
that may be important to your health or the health of your blood relatives (called 
”incidental findings”), the sponsor will inform the investigator. With your consent the 
investigator will notify you and your treating physician about your results and potential 
consequences. If necessary, the investigator and/or the treating physician will advise 
you on the next steps. 
 
You agree or disagree to being informed of it by ticking the appropriate check-box in 
Chapter III, page 23. 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 22 of 30 
 
CHAPTER II – SUBSTUDY SCREENING FAILURES 
 
If after screening it appears that you are not eligible for the core study, you can still 
participate in a separate substudy.  
You are eligible for this study if you meet all the criteria for the core study except that 
your PCR value shows too little virus.  
The sponsor in this case will invite you to participate in a substudy to analyse COVID-
19 infection in patient without symptoms and with a low viral load to see whether these 
individuals present antibodies against COVID and whether they present a risk of 
transmissibility.  
Therefore, we would like to take an additional naso-pharyngeal (or nose-throat)swab 
at inclusion (D0), and a blood sample at D28. Besides these 2 interventions, there are 
no additional interventions planned in this substudy. You agree or disagree to being 
informed of it by ticking the appropriate check-box in Chapter III, page 23. 
 
 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 23 of 30 
 
CHAPTER III – Informed consent 
PARTICIPANT  
PREREQUISITES FOR YOUR PARTICIPATION IN THE TRIAL 
 I declare that I have been informed of and that I understand the purpose of the 
clinical trial, its duration, possible risks and discomforts, the precautions that I 
have to take and what is expected of me. My rights have been explained to me 
and I have understood those rights. 
 I have had enough time to think about taking part in this trial and to discuss it 
with a trusted person (for example friends, relatives, treating physician, …). 
 I have had the opportunity to ask any questions that came to mind and have 
obtained a satisfactory response to my questions. 
 I understand that my participation in this trial is voluntarily and free from any 
coercion and that I am free to stop at any time my trial participation.  
 I understand that data about me will be collected and that they will be treated 
confidentially.   
 I agree to my personal data being processed as described in Chapter I, § 12, 
page 16.   
 I agree that my email address is used to send the questionnaires related to the 
study.  
 I understand that the sponsor has taken out an insurance in case I should suffer 
any damage in connection with my participation in this trial. 
 I understand that when participating in this trial, I will not have any costs except 
those related to the standard of care treatment of my disease (as described in 
the annex). 
 I agree to my treating physician(s) being informed of my participation in this trial. 
 I agree not to take part in any other trial at the same time without first informing 
the investigator or the trial staff, who might not permit me to participate for a 
good  reason. 
 I understand that I need to cooperate and follow the investigator’s and trial staff’s 
instructions regarding the trial. 
 I understand that participation to the trial might end for me without my consent 
if I need other treatment, do not follow the trial plan, have a trial-related injury, 
or for any other justified reason. 
 I understand that genetic analysis will be conducted on my biological samples.  
 I certify that all the information I have given about my medical history is correct. 
I understand that my failure to inform the investigator or designee about any 
exclusion criteria may harm myself. 
 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 24 of 30 
 
USE OF THE MEASUREMENT KIT 
 I understand and accept that I have received the measurement kit provided to 
me in good condition and will ensure its correct use and preservation for the 
duration of the study. 
 I will return this kit to the study nurses at the last study visit (D28). 
 I understand and accept that in the event of late returns, damage, improper use 
or loss, the Ghent University Hospital reserves the right to recover the damage. 
 I understand and agree that the device should not be given to a third party under 
any circumstances. 
 I understand and agree that in the event of damage, it is strictly forbidden to 
send the device to third parties for repair. 
 
☐ I agree  
☐ I do not agree  
 
OPTIONAL 
CONSENTS 
WHICH 
ARE 
NO 
PREREQUISITE 
FOR 
YOUR 
PARTICIPATION IN THIS TRIAL. 
 
1. As specified in Chapter I, § 12.8, page 19, the sponsor would like to be able to use 
your data obtained from this trial in connection with other research and 
development activities (and the associated scientific publications) on the condition 
that such research purposes have been approved by a Belgian recognized Ethics 
Committee. 
Do you agree with the use of your data obtained in this trial for other research 
purposes?  
(Tick as appropriate. If you leave this question open, we assume the answer 
is ‘I do not agree’.) 
☐ I agree  
☐ I do not agree  
 
2. As specified in Chapter I, § 13.4, page 20, the sponsor would like to retain the 
remainders of your biological samples for 25 years for future research outside the 
trial that you will participate in. The samples will be used to better understand the 
disease, its treatment and the responses to this treatment, and [name of 
IMP(s)/comparator]. 
Do you agree with the retention of the remainders of your biological samples and 
the accompanying personal data for future research outside the trial? 
(Tick as appropriate. If you leave this question open, we assume the answer 
is ‘I do not agree’.) 
☐ I agree  
☐ I do not agree  
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 25 of 30 
 
3. As described in Chapter I, § 13, page 19, and § 15, page 21, it may happen that 
incidental findings are discovered that may be important to your health or the health 
of your blood relatives.  
If this happens: do you want the investigator to inform you (directly or via your 
treating physician) of this result? 
(Tick as appropriate. If you leave this question open, we assume the answer 
is ‘yes, I want to be informed’.) 
☐ No, I do not want to be 
informed  
☐ Yes, I want to be informed  
 
4. As described in Chapter II, page 22, the sponsor would like to invite you to 
participate in a substudy to analyse the COVID-19 infection in patient without 
symptoms and with a low viral load. Your participation in this substudy is not 
required for the core study and includes that you consent with additional sampling. 
You will not take any study medication, or undergo other analysis than those 
described in Chapter II.  
Do you agree to participate in this substudy (screening failures substudy)? 
(Tick as appropriate. If you leave this question open, we assume the answer 
is ‘I do not agree’.) 
☐ I agree  
☐ I do not agree  
 
 
----------------------------------------------------------------------------------------------------------------- 
I consent to take part in the trial, with the above restrictions and I have received 
a signed and dated copy of all pages of this document. 
 
Participant’s surname and first name: 
 
Date (DD/MMM/YYYY): 
Time: 
 
Participant’s signature: 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 26 of 30 
 
INVESTIGATOR 
 
I, the undersigned investigator, confirm that 
 the participant has been verbally provided with the necessary information about 
the trial, has been explained the content and has been given an original signed 
document.  
 I have verified that the participant has understood the trial. 
 I have given the participant sufficient time to agree to take part and to ask any 
questions. 
 no pressure was applied to persuade the participant to agree to take part in the 
trial. 
 I operate in accordance with the ethical principles set out in the latest version of 
the “Helsinki Declaration”, the “Good Clinical Practices” and the Belgian Law 
(Ref. 8). 
 
Investigator’s, Surname and first name:  
 
Date (DD/MMM/YYYY): 
Time: 
 
Investigator’s signature:  


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 27 of 30 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 28 of 30 
 
ANNEX: FLOWCHART OF THE STUDY 
 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 29 of 30 
 
GLOSSARY 
 
DPA: The Data Protection Authority ensures that personal data are handled with care 
and thoroughly protected, and that your future privacy also remains guaranteed. 
 
FAMHP: Federal agency for medicines and health products 
 
IMP: investigational medical product 
 
NO FAULT INSURANCE:  
The sponsor is liable for any injury or any damage that the participant has suffered, 
and which is directly or indirectly related to the clinical trial. You do not have to prove 
any mistake in this respect. 
 
MONITOR and AUDITOR 
Both the monitor and auditor work for the sponsor. The monitor takes care of a 
continuous quality check during the course of a trial. The  auditor performs a quality 
check after the trial. They verify if the trial is being/was conducted according to the 
protocol, if the reported data are liable and if the clinical trial was conducted according 
the applicable rules. 


COV-AAT 
Informed consent form version 3.0, dated 04JUN2021, page 30 of 30 
 
REFERENCES 
 
1 This is in accordance with Article 29 of the Belgian Law of 7 May 2004 related to experiments on 
humans. 
2 General Data Protection Regulation No 2016/679 of the European Parliament and of the council of 27 
April 2016 on the protection of natural persons with regard to the processing of personal data and on 
the free movement of such data, and repealing Directive 95/46/EC. 
3 The Belgian Law of 30 July 2018 on the protection of natural persons with regard to the processing of 
personal data. 
4 In accordance with section 4.3. of the Commission Guideline: Guidance on posting and publication of 
result-related information on clinical trials in relation to the implementation of Article 57(2) of Regulation 
(EC) No 726/2004 and Article 41(2) of Regulation (EC) No 1901/2006 - (2012/C 302/03). [From the 
moment the Clinical trial regulation enters into force : In accordance with article 37 of the Clinical trial 
regulation No 536/2014 of the European Parliament and of the council of 16 April 2014 on clinical trials 
on medicinal products for human use, and repealing Directive 2001/20/EC; sponsor have to provide 
summary results of clinical trials in a format understandable to laypersons.] 
5 In accordance with article 58 of the Clinical trial regulation No 536/2014 of the European Parliament 
and of the council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing 
Directive 2001/20/EC. 
6 Belgian Law of 19 December 2008 on the acquisition and use of human body material with a view to 
medical application to humans or scientific research, and the applicable royal decrees. 
7 This is in accordance with Article 21 of the Belgian Law of 19 December 2008 on the acquisition and 
use of human body material with a view to medical application to humans or scientific research, and the 
applicable royal decrees. 
8 Belgian Law of 7 May 2004 related to experiments on humans, and the applicable royal decrees.