Multi-Center, Randomized, Control, Phase IV Trial to Compare the Efficacy & Safety of Ursoplus® Capsules (UDCA 250mg & Silymarin 140mg) Versus UDCA Alone Versus Placebo Among Compensated Chronic Liver Diseased Patients
Phase: PHASE4
Conditions: Chronic Liver Disease
Sponsor: MinaPharm Pharmaceuticals

CONFIDENTIAL            CRF – Version 2 - dated 17 Aug 22                     Page 1 of 30 
 
CONFIDENTIAL 
Case Report Form 
 
Clinical Trial Protocol No. URSO – 003 
Version 2, dated 17 August 2022 
 
Multi-Center, randomized, control, phase IV trial to compare the efficacy & 
safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus 
UDCA alone versus Placebo among Compensated Chronic Liver Diseased 
Patients 
 
 
Please use a ball point Blue pen 
Investigator’s Name and Address: 
 
 
 
 
Patient's Nº: 
 
 
 
 
 
Patient’s 
Initials:  
 
 
 
 
 
Property of Minapharm Pharmaceuticals 
 
May not be used, divulged, published or otherwise disclosed  
Without the prior consent of Minapharm Pharmaceuticals 
 
 
Center Nº: 
  

Patient's 
Nº: 
 
 
 
 
 
Patient’s 
Initials: 
 
 
 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 2 of 30 
General instructions: 
 
1- A CRF must be completed for each study participant who is successfully 
enrolled (successfully screened) 
 
2- Please write legibly upper case/capital letter is preferred e.g. CASE REPORT 
FORM 
 
3- . All entries must be made preferably in blue ballpoint pen 
 
4-  Do not leave any question unanswered.   
            If the answer to a question is unknown/ for missing information.  
            Please enter: 
NA - if data is not applicable or not 
available. 
 
NK - if information is unknown. 
 
ND - if procedure not done 
5-  If you make an error, please strike through original entry (e. g. ORIGINAL), 
re- enter the data immediately above the old entry, and initial and date the 
correction.  However, If you make an error on the description for adverse 
event or medication / non – drug therapy, please strike through original entry. 
Re-enter the data in the space below the start date, and initial and date the 
correction. Please do not use white – out or obliterate information. 
 
6-  Patient should be identified by patient number and initials in the CRF. If 
reports or clinic /hospital records are attached to the CRF, the patient name 
must be blocked over completely with a black marker and the patient number 
and initials entered.  
 
7-  Use leading "0's" to complete entire field. 
 
8-  All CRF pages must be reviewed and signed by the investigator participating 
in the study. 
9- All text and explanatory comments should be brief 
 
10- Answer every question explicitly; do not use ditto marks 
I am confident that the information supplied in this case record form is complete 
and accurate data.  I confirm that the study was conducted in accordance with the 
protocol and any protocol amendments and that written informed consent was 
obtained prior to the study. 
 
Investigator’s Signature:                                                       Date of signature:  

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL            CRF – Version 2 - dated 17 Aug 22                     Page 3 of 30 
Numeric fields 
1- Enter only 1 digit in each box, with a leading 0 when necessary 
2- Record all values in the unites indicated on the CRF 
Confidentiality 
 Patients must only be identified by the subject identification ID (Center number, 
Patient number  
Adverse Event Log/Concomitant Medication Log 
If additional pages of adverse event and / or concomitant medication log are required, 
please make a photocopy of a blank adverse Event log / concomitant medication log 
and complete the information. The original page will be sent to data management and 
a photocopy retained at Minapharm and investigator site 
Dates 
1-  
All dates are to be reported in the format DD/MMM/YYYY 
2-  
The month is to be reported as the first three characters of the month, e.g. 
01/AUG/2012 the month abbreviations are as follows: 
 
January 
= 
Jan 
 
May 
= 
May 
 
September 
= 
Sep 
February 
= 
Feb 
 
June 
= 
Jun 
 
October 
= 
Oct 
March 
= 
Mar 
 
July 
= 
Jul 
 
November 
= 
Nov 
April 
= 
Apr 
 
August 
= 
Aug 
 
December 
= 
Dec 
3- In the absence of a precise date for an event or therapy that precedes the 
participant’s inclusion into the study, a partial date may be recorded by recording 
“NK” in the fields that are unknown e.g. where the day and month are not clear, the 
following may be entered into the CRF:   
0 
0 
M A R 
2 
0 
0 
9 
DD 
MMM 
YYYY 
 
Center Numbering: 
Enter the center number (2 digits),  
➢ Research Center of Air Force Specialized Hospital = 01 
➢ Helwan University Hospital = 02 
e.g. 
Center Nº: 
  0 
  1 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL            CRF – Version 2 - dated 17 Aug 22                     Page 4 of 30 
Patients’ Numbering; 
Enter Patients’ Group (A, B, or C), then patient’s number (from 001 to 297), e.g.  
Patient’s No 
A 
0 
0 
5 
 
No Carbon Required (NCR) CRF 
The White original and the pink NCR CRF Will be retrieved by Minapharm personnel 
during his / her visit to the center. The yellow NCR card will be retained by 
investigator folder at the site 
 
 
 
Yellow 
 
NCR 
 
CRF 
 
 
 
Pink 
 
NCR 
 
CRF 
 
 
 
White 
 
NCR 
 
CRF 
 
 
 
 
       Copy to be retained By 
Copy to be kept by         Original to be sent to  
 
   Investigator 
 
   MINAPHARM             data management 
 
A study population of 297 patients with compensated chronic Liver Disease, will be 
randomized according to fibroscan in screening visit into 2 groups: 
• Group 1: with non-cirrhosis, F0, F1 and F2. 
• Group 2: with advanced fibrosis and cirrhosis, F3 and F4 
Subjects will be randomized into the 3 treatment groups with a balanced ratio of 1:1:1 
➢ Group A (Experimental group), will receive Ursoplus® capsules (UDCA 250mg 
& Silymarin 140mg) = 99 subjects  
➢ Group B (Control group 1), will receive Ursofalk® capsules (UDCA 250mg) = 
99 subjects  
➢ Group C (Control group 2), will receive Placebo = 99 subjects 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL            CRF – Version 2 - dated 17 Aug 22                     Page 5 of 30 
Child-Pugh Score Calculation: 
The score employs five clinical measures of liver disease. Each measure is scored 
1-3, with 3 indicating most severe derangement. 
Measure 
1 point 
2 points 
3 points 
Total bilirubin, μmol/l (mg/dl) 
<34 (<2) 
34-50 (2-3) 
>50 (>3) 
Serum albumin, g/dl 
>3.5 
2.8-3.5 
<2.8 
Prothrombin time prolongation 
(secs) 
<4.0 
4.0-6.0 
> 6.0 
Ascites 
None 
Mild 
Moderate to Severe 
Hepatic encephalopathy 
None 
Grade I-II (or suppressed with 
medication) 
Grade III-IV (or 
refractory) 
In primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC), the bilirubin 
references are changed to reflect the fact that these diseases feature high conjugated bilirubin 
levels. The upper limit for 1 point is 68 μmol/l (4 mg/dl) and the upper limit for 2 points is 170 
μmol/l (10 mg/dl). 
Chronic liver disease is classified into Child-Pugh class A to C, employing the added score 
from above.  
 
 
 
 
 
 
 
 
Child Pugh Score
Class A: 5-6
Class B: 7-9
Class C: 10-15

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 6 of 30 
Screening Visit 
Date of Screening:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Informed Consent: 
Date patient signed 
written consent form:
 
 
__ __ / __ __ __ / __ __ __ __                             (DD  /   MMM  / YYYY) 
 
Inclusion/ Exclusion Criteria 
 
Inclusion Criteria 
Yes 
No 
The following criteria MUST be answered YES for participant to be 
included in the trial: 
1. 
Male or female patient aged ≥ 18 
 
 
2. 
Subjects with Compensated Chronic Liver Disease, defined as 
child 5-7. 
 
 
3. 
Patients with mild disturbance of liver biochemical profile 
(Elevated Total Serum Bilirubin ≤ 3 mg/dl, or elevated Direct 
Serum Bilirubin ≤ 2 mg/dl, or elevated one or more of liver 
enzymes up to 3 times of the normal level (Alanine Transaminase 
(ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase 
(ALP) & Gamma Glutamyl Transpeptidase (GGT)).  
 
 
4. 
Non-diabetic subjects and subjects with Co 
ntrolled DM-type 1 and 2 patients, HbA1C up to 7.5% 
 
 
5. 
Non-pregnant or lactating female patients 
 
 
6. 
Subjects who are willing to sign Informed Consent Form and 
ready to comply with the protocol for the duration of the study 
 
 
 
Exclusion Criteria 
Yes 
No 
The following criteria MUST be answered NO for participant to be 
included in the trial: 
1. 
Subjects with a history of hypersensitivity to any of the 
ingredients of the medication being studied 
 
 
2. 
Subjects with positive PCR in the past 6 months 
 
 
3. 
Subjects with positive Hepatitis B surface antigen (HBsAg) 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 7 of 30 
4. 
Subjects with elevated liver enzymes more than 3 times of the 
normal 
level 
(Alanine 
Transaminase 
(ALT), 
Aspartate 
Aminotransferase (AST), Alkaline Phosphatase (ALP) & 
Gamma Glutamyl Transpeptidase (GGT)). 
 
 
5 
Subjects with Primary Biliary Cirrhosis (PBC) and Primary 
Sclerosing Cholangitis (PSC) 
 
 
6 
Subjects with Child Pugh Score more than 7 
 
 
7 
Subjects with history of bleeding varices 
 
 
8. 
Subjects having uncontrolled Diabetes (HbA1c above 7.5 %)  
 
 
9. 
Subjects with any medical condition require the usage of 
medication may interfere with the absorption, distribution, 
metabolism or excretion of the drugs such as: 
1- Bile acid sequestering agents such as cholestyramine and 
colestipol, 
2- Antacids containing aluminum hydroxide. 
3- Drugs affecting lipid metabolism such as estrogens, oral and 
hormonal contraceptives, and clofibrate (and perhaps 
other lipid-lowering drugs) 
 
 
10. Subjects who are receiving other liver support drugs (including 
drugs of the study), 1 month before study initiation. 
 
 
11 
Subjects with auto immune liver disease taking corticosteroid or 
immune suppressant 
 
 
12. Pregnant or breast-feeding women 
 
 
13 
Use of oral contraceptives in child bearing ladies 
 
 
 
 Demographic Data & Vital Signs 
 
Patient Demography & Vital Signs: 
Gender:        Male   
                Female 
 
Birthdate:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Weight: ____ ___ ___ Kg                                                  Height:  ____ ___ ___ cm 
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 8 of 30 
 
 Habits 
 
Smoking Habits: 
Does the subject smoke or use tobacco products?           
 Yes                        
 No 
 
How many cigarettes per day?                              
 
Others, specify: ……………………………………… 
 
Alcohol Consumption: 
Does the subject consume alcohol?                 
 Yes                              
 No 
 
If yes, how many units per week? 
 
*Please fill the relevant forms of adverse events in case any abnormal or untoward event is 
noticed 
 
 
Medical History 
 
Has the patient had any relevant medical history? 
 No               
 Yes, Complete below 
 Physical Examination 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 9 of 30 
Condition / illness /surgical procedure 
Start date 
(DD/MMM/YYYY) 
Stop date 
(DD/MMM/YYYY) 
Or tick if 
ongoing   ? 
 
____/_____/____ 
____/_____/_____ 
 
 
____/_____/____ 
____/_____/_____ 
 
 
____/_____/____ 
____/_____/_____ 
 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
 Abdominal Ultrasound 
 
Date of Ultrasound: __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Liver 
Normal 
 
Abnormal 
 
If abnormal, 
findings: 
………………………………………………………………………………………... 
………………………………………………………………………………………... 
 
  Portal Vein Diameter:   ………….mm (N. up to 14mm) 
 
  Ascites:     
 No           
 Yes       If yes, Amount: ………… 
Spleen 
Normal 
 
Abnormal 
 
If abnormal, 
findings: 
………………………………………………………………………………………... 
………………………………………………………………………………………... 
 
 Splenic Vein Diameter:………………mm  
 
Gall Bladder 
Normal 
 
Abnormal 
 
If abnormal, 
findings: 
………………………………………………………………………………………... 
………………………………………………………………………………………... 
 
Common Bile Duct (CBD) Diameter: …………mm (N. up to 6mm) 
 
 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 10 of 30 
 
 Vibration-controlled transient elastography with CAP (Fibroscan) 
 
 
Date of Fibroscan: __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Liver 
Liver stiffness measurement  
Fibroscan score 
 
 F0/F1          
 F2 
 F3               
 F4              
If abnormal, 
findings: 
………………………………………………………………………………………... 
………………………………………………………………………………………... 
 Safety Laboratory Tests 
 
Date of Laboratory Tests:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Laboratory Parameter 
Value 
Unit 
If parameter indicated as 
out of normal range on 
report, please check if 
clinically significant: 
ALT 
 
 
 No        
 Yes 
AST 
 
 
 No        
 Yes 
Alkaline Phosphatase (ALP) 
 
 
 No        
 Yes 
Gamma-GT 
 
 
 No        
 Yes 
Total Bilirubin 
 
 
 No        
 Yes 
Direct bilirubin 
 
 
 No        
 Yes 
S Albumin 
 
 
 No        
 Yes 
PT 
 
 
 No        
 Yes 
HbA1c for diabetic patients 
 
 
 No        
 Yes 
PCR/ Antibody for hepatitis C 
 
 
 No        
 Yes 
HBs Ag 
 
 
 No        
 Yes 
Serum β-HCG (for Females in 
child bearing period) 
 
 
 No        
 Yes 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 11 of 30 
 Assessment for quality of life (The RAND 36-Item Health Survey) 
Completed                        
 
Not Completed                         
 
 
 End of Screening Visit 
 
End of Screening Visit Checklist: 
Yes 
No 
1. 
Does the participant meet the inclusion and exclusion criteria to 
date? 
 
 
2. 
Have all Screening Visit procedures been completed? 
 
 
3. 
Have the Medical History and Concomitant Medication pages 
been completed? 
 
 
 
Participant’s eligibility: 
Is the participant eligible to take part in the Clinical Study? 
 Yes 
 No, Please give reason for screen failure below 
Reason(s) for screen failure: 
1. 
2. 
Investigator Sign-Off 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________  Date : __ __ / __ __ __ / __ __ __ __                                          
                                                                                                                                         (DD / MMM / YYYY) 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Screening Visit 
Initiation Visit 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 12 of 30 
Randomization 
 
Group A            
 
Group B           
 
Group C         
 
 
Drug Dispense 
 
Date of Drug Dispense:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Drugs are dispensed for the patient to be sufficient for 30 days of treatment 
The subject is asked to take the treatment daily and come next visit with the empty 
blisters after 30 days, with a window of 7 days. 
 
Drug Dispense 
Number of Capsules 
Number of Blisters 
 
Drug A, B, or C
 
 
 
 
 
Investigator’s Name:       __________________ 
 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __                                                             
 
(DD / MMM / YYYY) 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Visit 2 (Week 4) 
Follow Up Visit 
1 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 13 of 30 
Visit 2 (Week 4) (may be done by phone call)  
 
Date of Visit 2:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that 
occurred since last visit, whether it is believed to be related to the study drug or not. 
 
 
Drug Dispense 
 
Date of Drug Dispense:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Drug Dispense 
Number of Capsules 
Number of Blisters 
 
Drug A, B, or C
 
 
 
 
 
 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Visit 2 (Week 4) 
Follow Up Visit 
1 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 14 of 30 
 
Drugs are dispensed for the patient to be sufficient for 30 days of treatment 
The subject is asked to take the treatment daily and come next visit with the empty 
blisters after 30 days, with a window of 7 days. 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
 
Is the participant had any Adverse Events 
 
The investigator shall ask probing questions, allowing 
the patient to tell about any untoward or unusual event 
that occurred since the last visit, whether he/she (the 
patient) believes it is related to the study drug or not? 
(including abnormal physical examination/ laboratory 
results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, 
severity and outcome and confirm that, to the best of my knowledge, it accurately reflects the 
study information obtained for this participant: 
 
 
 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 (DD / MMM / YYYY) 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Visit 3 (Week 8) 
Follow Up Visit 2 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 15 of 30 
Visit 3 (Week 8) (may be done by phone call) 
 
 
Date of Visit 3:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that 
occurred since last visit, whether it is believed to be related to the study drug or not. 
 
 
Drug Dispense 
 
Date of Drug Dispense:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Drug Dispense 
Number of Capsules 
Number of Blisters 
 
Drug A, B, or C
 
 
 
 
 
 
 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Visit 3 (Week 8) 
Follow Up Visit 2 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 16 of 30 
Drugs are dispensed for the patient to be sufficient for 30 days of treatment 
The subject is asked to take the treatment daily and come next visit with the empty 
blisters after 30 days, with a window of 7 days. 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
 
Is the participant had any Adverse Events 
 
The investigator shall ask probing questions, allowing 
the patient to tell about any untoward or unusual event 
that occurred since the last visit, whether he/she (the 
patient) believes it is related to the study drug or not? 
(including abnormal physical examination/ laboratory 
results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, 
severity and outcome and confirm that, to the best of my knowledge, it accurately reflects the 
study information obtained for this participant: 
 
 
 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 (DD / MMM / YYYY)

Patient's 
Nº: 
 
 
 
 
 
Patient’
s 
Initials: 
 
 
 
   
Visit 4 (Week 12) 
Follow Up Visit 3 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 17 of 30 
Visit 4 (Week 12)  
 
Date of Visit 4:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that 
occurred since last visit, whether it is believed to be related to the study drug or not. 
 
 
 Assessment for quality of life 
 
 The RAND 36-Item Health Survey 
Completed                        
 
Not Completed                         
 
 
 
 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 
Patient’
s 
Initials: 
 
 
 
   
Visit 4 (Week 12) 
Follow Up Visit 3 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 18 of 30 
Drug Dispense 
 
Date of Drug Dispense:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Drug Dispense 
Number of Capsules 
Number of Blisters 
 
Drug A, B, or C
 
 
 
 
 
Drugs are dispensed for the patient to be sufficient for 30 days of treatment 
The subject is asked to take the treatment daily and come next visit with the empty 
blisters after 30 days, with a window of 7 days. 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
 
Is the participant had any Adverse Events 
 
The investigator shall ask probing questions, allowing 
the patient to tell about any untoward or unusual event 
that occurred since the last visit, whether he/she (the 
patient) believes it is related to the study drug or not? 
(including abnormal physical examination/ laboratory 
results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, 
severity and outcome and confirm that, to the best of my knowledge, it accurately reflects the 
study information obtained for this participant: 
 
 
 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 (DD / MMM / YYYY) 

Patient's 
Nº: 
 
 
 
 
 
Patient’
s 
Initials: 
 
 
 
   
Visit 5 (Week 16) 
Follow Up Visit 4 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 19 of 30 
 
Visit 5 (Week 16) (may be done by phone call) 
 
Date of Visit 5:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that 
occurred since last visit, whether it is believed to be related to the study drug or not. 
 
 
Drug Dispense 
 
Date of Drug Dispense:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Drug Dispense 
Number of Capsules 
Number of Blisters 
 
Drug A, B, or C
 
 
 
 
 
 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 
Patient’
s 
Initials: 
 
 
 
   
Visit 5 (Week 16) 
Follow Up Visit 4 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 20 of 30 
 
Drugs are dispensed for the patient to be sufficient for 30 days of treatment 
The subject is asked to take the treatment daily and come next visit with the empty 
blisters after 30 days, with a window of 7 days. 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
 
Is the participant had any Adverse Events 
 
The investigator shall ask probing questions, allowing 
the patient to tell about any untoward or unusual event 
that occurred since the last visit, whether he/she (the 
patient) believes it is related to the study drug or not? 
(including abnormal physical examination/ laboratory 
results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, 
severity and outcome and confirm that, to the best of my knowledge, it accurately reflects the 
study information obtained for this participant: 
 
 
 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 (DD / MMM / YYYY) 

Patient's 
Nº: 
 
 
 
 
 
Patient’
s 
Initials: 
 
 
 
   
Visit 6 (Week 20) 
Follow Up Visit 5 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 21 of 30 
 
Visit 6 (Week 20) (may be done by phone call) 
 
Date of Visit 6:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that 
occurred since last visit, whether it is believed to be related to the study drug or not. 
 
 
Drug Dispense 
 
Date of Drug Dispense:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Drug Dispense 
Number of Capsules 
Number of Blisters 
 
Drug A, B, or C
 
 
 
 
 
 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 
Patient’
s 
Initials: 
 
 
 
   
Visit 6 (Week 20) 
Follow Up Visit 5 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22                     Page 22 of 30 
 
Drugs are dispensed for the patient to be sufficient for 30 days of treatment 
The subject is asked to take the treatment daily and come next visit with the empty 
blisters after 30 days, with a window of 7 days. 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
 
Is the participant had any Adverse Events 
 
The investigator shall ask probing questions, allowing 
the patient to tell about any untoward or unusual event 
that occurred since the last visit, whether he/she (the 
patient) believes it is related to the study drug or not? 
(including abnormal physical examination/ laboratory 
results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, 
severity and outcome and confirm that, to the best of my knowledge, it accurately reflects the 
study information obtained for this participant: 
 
 
 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 
 
 
 
 
 
    (DD / MMM / YYYY) 

Patient's Nº: 
 
 
 
 
 
Patient’s 
Initials: 
 
 
 
   
End of Study Visit 
(Week 24) 
 
CONFIDENTIAL  
            CRF – Version 2- dated 17 Aug 22                     Page 23 of 30 
 
End of study  
 
Date of End of study visit:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that occurred 
since last visit, whether it is believed to be related to the study drug or not. 
 
 
 Assessment for quality of life 
 
 The RAND 36-Item Health Survey 
Completed                        
 
Not Completed                         
 
 
 
 
Physical Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's Nº: 
 
 
 
 
 
Patient’s 
Initials: 
 
 
 
   
End of Study Visit 
(Week 24) 
 
CONFIDENTIAL  
            CRF – Version 2- dated 17 Aug 22                     Page 24 of 30 
 
Safety Laboratory Tests 
 
Date of Laboratory Tests:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
Laboratory Parameter 
Value 
Unit 
If parameter indicated as out of 
normal range on report, please 
check if clinically significant: 
ALT 
 
 
 No        
 Yes 
AST 
 
 
 No        
 Yes 
Alkaline Phosphatse (ALP) 
 
 
 No        
 Yes 
Gamma-GT 
 
 
 No        
 Yes 
S.Albumin 
 
 
 No        
 Yes 
Total Bilirubin 
 
 
 No        
 Yes 
Direct bilirubin 
 
 
 No        
 Yes 
Serum β-HCG (for Females 
with child bearing potential 
only) 
 
 
 No        
 Yes 
 
 
 Vibration-controlled transient elastography with CAP (Fibroscan) 
 
Date of Fibroscan: __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Liver 
Liver stiffness measurement  
Fibroscan score 
 
 
 F0/F1                     
 
 F2 
 
 F3 
 
 F4 
If abnormal, findings: 
………………………………………………………………………………………... 
………………………………………………………………………………………... 
………………………………………………………………………………………... 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 

Patient's Nº: 
 
 
 
 
 
Patient’s 
Initials: 
 
 
 
   
End of Study Visit 
(Week 24) 
 
CONFIDENTIAL  
            CRF – Version 2- dated 17 Aug 22                     Page 25 of 30 
If Yes: Complete Concomitant Medication Page 
26 
 
Is the participant had any Adverse Events 
 
The investigator shall ask probing questions, allowing the 
patient to tell about any untoward or unusual event that 
occurred since the last visit, whether he/she (the patient) 
believes it is related to the study drug or not? (including 
abnormal physical examination/ laboratory results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, severity and 
outcome and confirm that, to the best of my knowledge, it accurately reflects the study information 
obtained for this participant: 
 
 
 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 
 
 
 
 
 
    (DD / MMM / YYYY

Patient's Nº: 
 
 
 
 
 
                                                                    Patient’s Initials: 
 
 
 
 
CONFIDENTIAL  
            CRF – Version 2- dated 17 Aug 22                     Page 26 of 30 
 
Concomitant Medication Form  
 
Medication 
(Record Generic or  
trade name) 
Reason for use 
(Medical History 
diagnosis or other 
reason, e.g. 
Prophylaxis) 
Dose 
and 
units 
Frequency 
 
Route 
Start Date 
(DD/MMM/YYYY) 
Stop Date 
(DD//MMM/YYY) 
Or tick 
if 
ongoing    
1. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
2. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
3. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
4. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
5. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
6. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
7. 
 
 
 
 
____/_____/_____ 
____/_____/_____ 
 
 
PI signature _______________________________ _________________ 
 Date: _________________________  
 

Patient's Nº: 
 
 
 
 
 
                                                                    Patient’s Initials: 
 
 
 
 
CONFIDENTIAL  
            CRF – Version 2- dated 17 Aug 22                     Page 27 of 30 
 
Adverse Events (1/2) 
 
AE 
No 
Event Name  
(Please give Diagnosis if 
known) 
Start date 
(DD/MMM/YYYY) 
Stop date 
(DD/MMM/YYYY) 
Serious? 
Con-
comitant 
Medication 
given 
Severity 
0 - Mild 
1- Mode-
rate 
2 - Severe 
Study 
Drug 
Action 
0 - None 
1 - 
Temporarily 
Interrupted 
2 - 
permanently 
withdrawn 
Outcome 
1- Death related to 
AE 
2- Not resolved/Not 
recovered 
3- Resolved/ 
Recovered  
4- Resolved/ 
Recovered with 
Sequelae 
5- Resolving/ 
Recovering 
6- Unknown  
Relationship to  
Study Drug  
0 - Certain 
1 – Probable/Likely 
2 - Possible 
3 - Unlikely 
4 – Conditional/ 
Unclassified 
5 - Un-assessable/ 
Unclassifiable 
 
1 
 
____/____/____ 
 
 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
2 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
3 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
4 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
5 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
I have reviewed the AEs on this page and have assessed them for seriousness, causality, severity and outcome and confirm that, to the best of my 
knowledge, it accurately reflects the study information obtained for this participant: 
 
PI signature _______________________________ _________________ Date: _________________________  
 

Patient's Nº: 
 
 
 
 
 
                                                                    Patient’s Initials: 
 
 
 
 
CONFIDENTIAL  
            CRF – Version 2- dated 17 Aug 22                     Page 28 of 30 
Adverse Events (2/2) 
AE 
No 
Event Name  
(Please give Diagnosis if 
known) 
Start date 
(DD/MMM/YYYY) 
Stop date 
(DD/MMM/YYYY) 
Serious? 
Con-
comitant 
Medication 
given 
Severity 
0 - Mild 
1- Mode-
rate 
2 - Severe 
Study 
Drug 
Action 
0 - None 
1 - 
Temporarily 
Interrupted 
2 - 
permanently 
withdrawn 
Outcome 
1- Death related to 
AE 
2- Not resolved/Not 
recovered 
3- Resolved/ 
Recovered  
4- Resolved/ 
Recovered with 
Sequelae 
5- Resolving/ 
Recovering 
6- Unknown  
Relationship to  
Study Drug  
0 - Certain 
1 – Probable/Likely 
2 - Possible 
3 - Unlikely 
4 – Conditional/ 
Unclassified 
5 - Un-assessable/ 
Unclassifiable 
 
1 
 
____/____/____ 
 
 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
2 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
3 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
4 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
 
5 
 
____/_____/____ 
____/_____/____ 
 No 
 Yes 
 No 
 Yes 
 
 
 
 
I have reviewed the AEs on this page and have assessed them for seriousness, causality, severity and outcome and confirm that, to the best of my 
knowledge, it accurately reflects the study information obtained for this participant: 
 
PI signature _______________________________ _________________ Date: _________________________  
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Unscheduled Visit 
 
CONFIDENTIAL                CRF – Version 2- dated 17 Aug 22                  Page 29 of 30 
Unscheduled Visit 
Date of Unscheduled Visit:  __ __ / __ __ __ / __ __ __ __     (DD / MMM / YYYY) 
 
Vital Signs 
 
Vital Signs & Weight: 
Weight: ____ ___ ___ Kg                                                   
Blood Pressure (Systolic/Diastolic):    ___ ___ ___ / ___ ___ ___ mmHg 
 
 Physical Examination 
*Please fill the relevant forms of adverse events in case any untoward or unusual event that 
occurred since last visit, whether it is believed to be related to the study drug or not. 
 
Is the participant taking any 
concomitant medications? 
 No        
 Yes 
If Yes: Complete Concomitant Medication 
Page 26 
Is the participant had any Adverse Events 
 
 
The investigator shall ask probing questions, allowing 
the patient to tell about any untoward or unusual event 
that occurred since the last visit, whether he/she (the 
patient) believes it is related to the study drug or not? 
(including abnormal physical examination/ laboratory 
results) 
 No        
 Yes 
If Yes: Complete 
Page 30 
 
I have updated the AEs on page …….. And have assessed them for seriousness, causality, 
severity and outcome and confirm that, to the best of my knowledge, it accurately reflects the 
study information obtained for this participant: 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________ Date: __ __ / __ __ __ / __ __ __ __            
 
 
 
 
 
 
 
    (DD / MMM / YYYY) 
Physical 
Examination 
Normal 
 
Abnormal 
 
Findings 
 
 
………………………………………………………………………………………....... 
 
…………………………………………………………………………………………... 
 
…………………………………………………………………………………………... 
 
 

Patient's 
Nº: 
 
 
 
 
 Patient’s 
Initials: 
 
 
 
   
Study Completion 
page 
 
CONFIDENTIAL             CRF – Version 2- dated 17 Aug 22               Page 30 of 30 
Study Completion  
 
Did participant complete the trial? 
 Yes, Please provide date of last day: 
     __ __ / __ __ __ / 2 0 __ __                          (DD / MMM / YYYY) 
 No, Please provide date of withdrawal and complete below: 
     __ __ / __ __ __ / 2 0 __ __                          (DD / MMM / YYYY) 
Early Withdrawal: please tick most appropriate reason for participant not completing the 
trial:   
  Adverse Events related: please state related AE: ____________________________________ (add details to 
AE page) 
 Participant’s decision, specify: __________________________ 
 Investigator’s decision, specify: __________________________ 
 Sponsor’s decision 
 Lost to follow up 
 Patient deceased 
 Ineligibility (either arising during the study or retrospective having been overlooked at 
screening) 
 Significant protocol deviation 
 Significant non-compliance with treatment regimen or study requirements 
 Disease progression which requires discontinuation of the study medication or results in 
inability to continue to comply with study procedures 
 Consent withdrawn. 
 Pregnancy or discontinuation of contraception 
 Other, specify: __________________________ 
Investigator Sign off 
Investigator’s Name:       __________________ 
Investigator’s Signature: __________________  Date : __ __ / __ __ __ / __ __ __ __     
                                                                                                                      (DD / MMM / YYYY)