Phase Ib Trial to Assess Safety and Tolerability of Multiple Subcutaneous Doses of BI 3006337 in Patients With Overweight or Obesity and Hepatic Steatosis
Phase: PHASE1
Conditions: Non-alcoholic Fatty Liver Disease, Obesity
Sponsor: Boehringer Ingelheim

001-MCS-40-106_RD-03 (20.0) / Saved on: 20 Apr 2021
Clinical Trial Protocol
TITLE PAGE
Document Number:
c39013879-05
BI Trial No.
1466-0002
BI Investigational
Medicinal Product
BI 3006337
Title
Phase Ib trial to assess safety and tolerability of multiple
subcutaneous doses of BI 3006337 in patients with overweight
or obesity and hepatic steatosis
Lay Title
A study to test how well different doses of BI 3006337 are 
tolerated by people with overweight or obesity and with fatty 
liver disease
Clinical Phase
Phase Ib
Clinical Trial Leader
Phone: 
Fax: 
Coordinating 
Investigator
Phone: 
 
Current Version and 
Date
Version 5.0, 08 Feb 2024
Original Protocol 
Date
17 Mar 2023
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2024 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission.

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CLINICAL TRIAL PROTOCOL SYNOPSIS
Company name
Boehringer Ingelheim
Original Protocol 
date
Latest revision date
17 Mar 2023
08 Feb 2024
BI trial number
1466-0002
Title of trial
Phase Ib trial to assess safety and tolerability of multiple dosing of 
BI 3006337 in patients with overweight/obesity and hepatic
steatosis.
Coordinating 
Investigator
NA
Trial sites
Multi-centre trial
Clinical phase
Phase Ib
Trial rationale
BI 3006337 is a dual glucagon-like peptide 1 (GLP-1)/fibroblast 
growth factor 21 (FGF21) receptor agonist being developed for the 
treatment of compensated cirrhosis due to non-alcoholic
steatohepatitis (NASH). Cumulative data for BI 3006337 from non-
clinical disease models demonstrate treatment effects across multiple 
pathological aspects of relevance to patients with NASH 
compensated cirrhosis including weight loss, improved lipid profile, 
insulin sensitivity, liver steatosis, hepatic lobular inflammation, and 
reduced hepatocyte injury and liver fibrosis. This multiple rising 
dose and proof of clinical principle (PoCP) trial will assess safety, 
tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), 
and signs of efficacy of BI 3006337 in trial participants with 
overweight/obesity and hepatic steatosis.
Benefit-risk 
assessment and 
ethical 
considerations
In the context of the unmet medical need in NASH, the anticipated 
benefit-risk of this trial is expected to be favourable, given the 
available preclinical and clinical information generated to date and 
the extensive safety monitoring planned in this trial.
Trial objectives
The objective of this trial is to assess the safety, tolerability, PK, and 
PD of 3 multiple rising dose levels and of the highest tolerated dose
(repeated in a separate group) by subcutaneous (s.c.) injection of up 
to 
 BI 3006337 over 12 weeks in comparison with placebo in 
trial participants with overweight/obesity and hepatic steatosis. The 
main objective is to descriptively assess the frequency (N [%]) of 
trial participants with drug-related AEs. Secondary objectives are to 
descriptively assess the PK parameters for BI 3006337 and to 
explore superiority of clinical efficacy vs. placebo for BI 3006337 at 
the highest tolerated dose.

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Trial endpoints
Primary endpoint:
Occurrence of drug-related adverse events occurring between first 
administration of trial medication (BI 3006337 or placebo) and end 
of study (EOS)
Secondary endpoints:
PK

AUCτ,ss (area under the concentration-time curve of the 
analyte in serum over the dosing interval tau at steady state)
after the last dose in Week 12

Cmax,ss (maximum measured concentration of the analyte in 
serum at steady state after the last dose in Week 12)

tmax,ss (time from dosing to the maximum measured 
concentration of the analyte in serum at steady state) after the 
last dose in Week 12
Efficacy

Relative percentage change in liver steatosis (as measured by 
MRI-PDFF) from baseline after 12 weeks of treatment
Trial design
Single-blind and randomised within dose groups, placebo-controlled
trial with 3 treatment groups over 12 weeks
Total number of 
trial participants
randomised
Approximately 56 trial participants (40 on BI 3006337 and 16 on 
placebo; including repetition of the highest tolerated dose level for 
PoCP analysis). Number of randomised trial participants will not 
exceed 72 in total.
Number of trial 
participants per
treatment group
14 trial participants (10 on BI 3006337 and 4 on placebo) in dose 
group 1-3. Number of trial participants in dose group 4 will not 
exceed 30 in total.
Diagnosis, 
main inclusion and 
exclusion criteria
Trial participants with overweight/obesity and steatosis
Inclusion:

Male or female patients ≥18 years and ≤75 years of age at 
time of consent

25≤BMI<40 kg/m2

Liver fat fraction ≥8% as measured by MRI-PDFF
Main exclusion criteria:

Any of the following liver-related conditions: significant 
alcohol consumption (past or present), intake of medications 
associated with liver injury, hepatic steatosis, or 
steatohepatitis for more than 14 consecutive days within 
12 weeks prior to screening, any acute or chronic disease 
other than simple steatosis, suspicion, confirmed diagnosis or 
history of hepatocellular carcinoma, treatment with vitamin E 

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or pioglitazone within 90 days before screening, and liver 
stiffness >10 kPa as measured by Fibroscan

Any of the following metabolic conditions: history of type 1 
diabetes, use of GLP-1 receptor agonists within 3 months 
before screening, use of glucose lowering or weight loss 
medication within 30 days before screening, bariatric surgery 
or treatment with weight-loss device in the past or planned 
during the trial, unstable body weight within the last 12 
months.

ALT and/or AST >5x ULN at the screening visit

Any major surgery (major according to Investigator’s 
assessment) performed within 12 weeks prior to 
randomization or planned during trial conduct

A marked prolongation of QT/QTc (Fridericia) interval that 
is greater than 450 ms for men or 470 ms for women at 
Visit 1 or any other abnormal clinically significant ECG 
finding at Visit 1 (e.g. type 2 second-degree AV block (Type 
Mobitz II) or third-degree AV block)
Trial intervention 
and 
test product
BI 3006337 solution for injection
Placebo for BI 3006337 solution for injection
Dose and mode of 
administration
BI 3006337 will be given s.c. once weekly.
Comparator 
product
Placebo
Dose and mode of 
administration
Matching the doses and mode of administration of BI 3006337
Duration of 
treatment
12 weeks
Statistical methods
Descriptive statistics will be calculated for all endpoints.

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FLOW CHART
Table 1
Flow Chart: Overall schedule
1.
Including SARS-CoV-2, hepatitis B and C testing
2.
3.
Serum pregnancy test at screening visit (test performed at central lab), and urine pregnancy test at the study site for other 
visits. Menstrual cycle status (not delayed or missed period) should be checked before the first dose (Visit 2). Applicable 
to only women of childbearing potential.
4.
Local tolerability: see Section 5.2.5.1
5.
C-SSRS, Columbia-Suicide Severity Rating Scale questionnaires will be administered at Visit 1 using the 
“baseline/screening” version. The “since last visit” version will be used at the following visits. Paper forms will be used 
for the assessment of C-SSRS (refer to Section 5.2.5.3).
Trial Periods
SCR
Treatment period
EOS
Visit
1
2
3
4
5
6
7
8
9
10 11 12 13 14
15
16 17
Days 
-48 to -4 -1 to 3 4
8 15-17 18 22 29
36
43 50 57 64 71 78-80 81 85
99
Informed consent
X
Randomisation
X
BW & waist circumference
X
X
X
X
X
X
Height
X
Demographics
X
Relevant medical history
X
Concomitant therapy
X
X
Review of inclusion and exclusion 
criteria
X
Drug administration 
X
X
X
X
X
X
X X X X X
X
Local tolerability at injection site4
X
X X
X
X X
X
X
X X X X X
X
AE collection
X
X
X X
X
X X
X
X
X X X X X
X
X
X
X
Safety laboratory
X1
X
X X
X
X X
X
X
X X X X X
X
X
X
C-SSRS completion5
X
X
X X
X
X X
X
X
X X X X X
X
X
X
BI 3006337 in serum (PK)
X
X X
X
X X
X
X
X X X X X
X
X
X
X
Glucose bedside test
X
X X
X
X X
X
X
X X X X X
X
X
X
12-lead ECG 
X
X
X
X X
X
X
X X
X
X
Vital signs
X
X
X X
X
X X
X
X
X X X X X
X
X
X
X
Physical examination
X
X
MR imaging2
X
X
Pregnancy testing3
X
X
X
X
X
X

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6.
Blood sample should be collected before administration of trial medication.
7.
8.

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Table 2
Flow Chart: Detailed schedule
Visit
Day
Planned time (relative to 
trial activities 8) [h:min] 
Approximate clock time 
of actual day [h:min]
Event and comment
Safety laboratory
BI 3006337 in serum6
Glucose bedside test
12-lead ECG
C-SSRS examination12
Vital signs (Temperature, 
BP, PR)
Questioning for AEs and 
concomitant therapy5
1
-48 to -
4
SCR1, 2
x3, 4
x
x
x
2
-1
-26:00
07:00
Admission to trial site,
Randomisation10
x4
x
x
x
x
x
-25:10
07:50
Liquid meal
-24:45
08:15
-24:30
08:30
-24:15
08:45
-24:00
09:00
x
x
-23:30
09:30
-23:00
10:00
240 mL fluid intake9
x
x
-22:00
11:00
-21:00
12:00
Lunch9
x
x
x
-20:00
13:00
-19:00
14:00
-17:00
16:00
Snack (voluntary)
-15:00
18:00
x
-14:00
19:00
Dinner
1
-1:00
08:00
BW & waist 
circumference  
x
x
x
x
x
x
0:00
09:00
s.c. injection of
BI 3006337 or placebo
x
x17
2:00
11:00
Local tolerability at 
injection site11
240 mL fluid intake9
3:00
12:00
x
x
x
x
x
4:00
13:00
Lunch9
7:00
16:00
Snack (voluntary)9
x
x
x
x
10:00
19:00
Dinner
11:00
20:00
x
x
x
x
15:00
24:00
x
x
2
22:00
07:00
x
x
x
x
x
x
22:50
07:50
Liquid meal
23:15
08:15
23:30
08:30
23:45
08:45
Local tolerability at 
injection site11
24:00
09:00
x
x
24:30
09:30
25:00
10:00
240 mL fluid intake9
x
x

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Visit
Day
Planned time (relative to 
trial activities 8) [h:min] 
Approximate clock time 
of actual day [h:min]
Event and comment
Safety laboratory
BI 3006337 in serum6
)
Glucose bedside test
12-lead ECG
C-SSRS examination12
Vital signs (Temperature, 
BP, PR)
Questioning for AEs and 
concomitant therapy5
26:00
11:00
27:00
12:00
Lunch9
x
x
x
x
28:00
13:00
29:00
14:00
31:00
16:00
Snack (voluntary)9
x
x
x
x
33:00
18:00
x
34:00
19:00
Dinner
35:00
20:00
x
x
x
39:00
24:00
x
x
3
46:00
07:00
Local tolerability at 
injection site11
x4
47:00
08:00
Breakfast (voluntary)9,
Discharge from trial site
x
x
x
x
x
x
3
4
72:00
09:00
Ambulatory visit, local 
tolerability at injection 
site11
x4
x
x
x
x
x
4
8
168:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
170:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
5
15
335:00
08:00
Admission to trial site, 
BW & waist 
circumference16
x
x
x
x
x
x
336:00
09:00
s.c. injection of
BI 3006337 or placebo
x
x17
338:00
11:00
Local tolerability at 
injection site11
240 mL fluid intake9
339:00
12:00
x
x
x
x
x
340:00
13:00
Lunch9
343:00
16:00
Snack (voluntary)9
x
x
x
x
346:00
19:00
Dinner
347:00
20:00
x
x
x
x
351:00
24:00
x
x
16
358:00
07:00
x
x
x
x
359:00
08:00
x
359:30
08:30
Local tolerability at 
injection site11
360:00
09:00
x
x
361:00
10:00
x
x
363:00
12:00
Lunch9
x
x
x
x
367:00
16:00
Snack (voluntary)9
x
x
x
x
369:00
18:00
x
370:00
19:00
Dinner
371:00
20:00
x
x
x
375:00
24:00
x
x
17
382:00
7:00
Local tolerability at 
injection site11
x4

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Visit
Day
Planned time (relative to 
trial activities 8) [h:min] 
Approximate clock time 
of actual day [h:min]
Event and comment
Safety laboratory
BI 3006337 in serum6
)
Glucose bedside test
12-lead ECG
C-SSRS examination12
Vital signs (Temperature, 
BP, PR)
Questioning for AEs and 
concomitant therapy5
383:00
8:00
Breakfast (voluntary)9,
discharge from trial site
x
x
x
x
x
x
6
18
408:00
09:00
Ambulatory visit, local 
tolerability at injection 
site11 BW & waist 
circumference16
x
x
x
x
x
x
x
7
22
504:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
506:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
x
8
29
672:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
674:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
x
9
36
840:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
842:00
11:00
Local tolerability at 
injection site
x
x
x
x
x
x
10
43
1008:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
1010:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
x
11
50
1176:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
1178:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
x
12
57
1344:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
1346:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
13
64
1512:00
09:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
1514:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
14
71
1680:00
9:00
Ambulatory visit16
s.c. injection of
BI 3006337 or placebo
x
x17
1682:00
11:00
Local tolerability at 
injection site11
x
x
x
x
x
15
78
1847:00
08:00
Admission to trial site, 
x
x
x
x
1848:00
09:00
s.c. injection of
BI 3006337 or placebo
x
x17

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Visit
Day
Planned time (relative to 
trial activities 8) [h:min] 
Approximate clock time 
of actual day [h:min]
Event and comment
Safety laboratory
BI 3006337 in serum6
Glucose bedside test
12-lead ECG
C-SSRS examination12
Vital signs (Temperature, 
BP, PR)
Questioning for AEs and 
concomitant therapy5
1850:00
11:00
Local tolerability at 
injection site11
240 mL fluid intake9
1851:00
12:00
x
x
x
x
x
1852:00
13:00
Lunch9
1855:00
16:00
Snack (voluntary)9
x
x
x
x
1858:00
19:00
Dinner
1859:00
20:00
x
x
x
x
1863:00
24:00
x
x
79
1870:00
07:00
Local tolerability at 
injection site11
x4
x
x
x
x
1870:50
7:50
Liquid meal
1871:15
08:15
1871:30
08:30
Local tolerability at 
injection site11
1871:45
08:45
1872:00
09:00
x
x
1872:30
09:30
1873:00
10:00
240 mL fluid intake9
x
x
1874:00
11:00
1875:00
12:00
Lunch9
x
x
x
x
1876:00
13:00
1877:00
14:00
1879:00
16:00
Snack (voluntary)9
x
x
x
x
1881:00
18:00
x
1882:00
19:00
Dinner
1883:00
20:00
x
x
x
1887:00
24:00
x
x
80
1894:00
07:00
Local tolerability at 
injection site11
x4
1895:00
08:00
Breakfast (voluntary)9,
discharge from trial site
x
x
x
x
x
x
16
81
1920:00
09:00
Ambulatory visit
x
x
x
x
x
x
17
85
2016:00
09:00
Ambulatory visit BW & 
waist circumference16
x
x
x
EO
S
99
2352:00
09:00
Ambulatory visit BW & 
waist circumference16
x
x
x
x
x
x
1.
Trial participants must be informed and written informed consent obtained prior to starting any SCR procedures. At 
SCR, the medical examination will include demographics, height, and BW, smoking and alcohol history (results not 
mandatory to be entered into CRF or to be reported), relevant medical history and concomitant therapy, review of 
inclusion and exclusion criteria, review of vital signs (Temperature, BP, PR), 12-lead ECG, laboratory tests, and a 
physical examination. Additionally, an MRI-PDFF and 
must be performed. If a trial 
participant misses an appointment (ambulatory visits and site admission visits), it will be rescheduled if possible. A time 
window of ± 1 day would be acceptable (see Section 6.1)
2.
A PCR test on SARS-CoV-2 will be performed at Visit 1.
3.
Including hepatitis B and C testing, HIV-1 and HIV-2 antibody and HIV-1 p24 Antigen. Tests will be done at screening 
and then if needed during the study (refer to section 5.2.3).

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4.
In addition, urine drug screening will be performed at this time point.
5.
AEs and concomitant therapies will be recorded throughout the trial but will be specifically asked for at the time points 
indicated in the Table 1 (Flow Chart).
6.
Sampling times and periods may be adapted based on information obtained during the trial (e.g. preliminary PK data) 
including addition of samples and visits as long as the total blood volume taken does not exceed 1050 mL per trial 
participant. A front and a back-up sample will be collected.
7.
8.
Planned time relative to administration of BI 3006337 or placebo at Visit 1.
9.
If several actions are indicated at the same time point, the intake of meals or liquids will be the last action. Only 
exception is the liquid meal for the acetaminophen absorption test which must be performed according to the flow chart.
10. Randomisation will be done following enrolment and the latest prior to administration of trial medication (BI 3006337 or 
placebo) at Visit 2 Day 1.
11. Local tolerability: see Section 5.2.5.1
12. C-SSRS completion (refer to Section 5.2.5.3).
13. BM samples (refer to Section 5.4.2)
14. Only plasma/serum samples for biobanking will be collected at EOS visit
15.
16. For ambulatory visits, kits assignment must be performed the day before the visit, otherwise the IMP will not be ready 
for administration.
17. At dosing visits for subcutaneous drug administration, vital signs evaluations (BP, PR) will be performed pre-dose and at 
30 min. after the end of drug administration.

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TABLE OF CONTENTS
TITLE PAGE ...........................................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................................2
FLOW CHART........................................................................................................................5
TABLE OF CONTENTS ......................................................................................................12
ABBREVIATIONS AND DEFINITIONS...........................................................................16
1.
INTRODUCTION...............................................................................................21
1.1
MEDICAL BACKGROUND.............................................................................21
1.2
DRUG PROFILE................................................................................................22
1.2.3
Nonclinical pharmacokinetics............................................................................23
1.4
BENEFIT - RISK ASSESSMENT.....................................................................26
1.4.1
Benefits.................................................................................................................26
1.4.2
Risks .....................................................................................................................26
1.4.3
Discussion.............................................................................................................29
2.
TRIAL OBJECTIVES AND ENDPOINTS......................................................31
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS........31
2.1.1
Main objectives....................................................................................................31
2.1.2
Primary endpoint................................................................................................31
2.1.3
Secondary endpoints...........................................................................................31
2.2.2.1
Safety and tolerability...........................................................................................32
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.........................35
3.1
OVERALL TRIAL DESIGN.............................................................................35
3.1.1
Staggered conduct of dose escalation ................................................................37
3.1.2
Dose Escalation Committee (DEC) – Operations and Safety Review............37
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP...........................................................................................38
3.3
SELECTION OF TRIAL POPULATION .......................................................39

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3.3.1
Main diagnosis for trial entry ............................................................................40
3.3.2
Inclusion criteria .................................................................................................40
3.3.3
Exclusion criteria ................................................................................................40
3.3.4
Discontinuation of trial participants from treatment or assessments............43
3.3.4.1
Discontinuation of trial treatment .........................................................................43
3.3.4.2
Withdrawal of consent to trial participation .........................................................45
3.3.4.3
Discontinuation of the trial by the sponsor...........................................................45
3.3.5
Replacement of patients......................................................................................46
4.
TREATMENTS...................................................................................................47
4.1
INVESTIGATIONAL TREATMENTS ...........................................................47
4.1.1
Identity of the Investigational Medicinal Products..........................................47
4.1.2
Selection of doses in the trial and dose modifications......................................48
4.1.3
Method of assigning trial participants to treatment groups ...........................48
4.1.4
Drug assignment and administration of doses for each trial participant......48
4.1.5
Blinding and procedures for unblinding...........................................................49
4.1.5.1
Blinding.................................................................................................................49
4.1.5.2
Emergency unblinding and breaking the code......................................................50
4.1.6
Packaging, labelling, and re-supply...................................................................50
4.1.7
Storage conditions...............................................................................................50
4.1.8
Drug accountability.............................................................................................50
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS ................................................................................................51
4.2.1
Other treatments and emergency procedures..................................................51
4.2.2
Restrictions ..........................................................................................................53
4.2.2.1
Restrictions regarding concomitant treatment ......................................................53
4.2.2.2
Restrictions on diet and lifestyle...........................................................................54
4.2.2.3
Contraception requirements..................................................................................54
4.3
TREATMENT COMPLIANCE........................................................................55
5.
ASSESSMENTS..................................................................................................56
5.1
ASSESSMENT OF EFFICACY........................................................................56
5.1.1
Magnetic Resonance Imaging for Proton Density Fat Fraction.....................56
5.2
ASSESSMENT OF SAFETY.............................................................................57
5.2.1
Physical examination ..........................................................................................57
5.2.2
Vital signs.............................................................................................................57
5.2.3
Safety laboratory parameters ............................................................................57
5.2.4
Electrocardiogram ..............................................................................................62
5.2.4.1
12-lead resting electrocardiogram.........................................................................62
5.2.5
Other safety parameters.....................................................................................64
5.2.5.1
Local tolerability...................................................................................................64
5.2.5.2
Monitoring for hypersensitivity reactions.............................................................64
5.2.5.3
Suicidal risk assessment and reporting .................................................................64
5.2.6
Assessment of adverse events.............................................................................65
5.2.6.1
Definitions of adverse events................................................................................65
5.2.6.1.1
Adverse event........................................................................................................65

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5.2.6.1.2
Serious adverse event............................................................................................65
5.2.6.1.3
Adverse events considered “Always Serious”......................................................66
5.2.6.1.4
Adverse events of special interest.........................................................................66
5.2.6.1.5
Intensity (severity) of adverse events....................................................................68
5.2.6.1.6
Causal relationship of adverse events...................................................................69
5.2.6.2
Adverse event collection and reporting ................................................................70
5.2.6.2.1
Adverse event collection.......................................................................................70
5.2.6.2.2
Adverse event reporting to the sponsor and timelines..........................................71
5.2.6.2.3
Pregnancy..............................................................................................................71
5.2.6.2.4
Hypoglycaemia .....................................................................................................72
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS...................................................................................72
5.3.1
Assessment of pharmacokinetics .......................................................................72
5.3.2
Methods of sample collection .............................................................................72
5.3.2.1
Blood sampling for BI 3006337 pharmacokinetic analysis..................................72
5.4
ASSESSMENT OF BIOMARKERS.................................................................74
5.4.2
Methods of sample collection .............................................................................75
5.5
BIOBANKING ....................................................................................................76
5.5.1
Methods and timing of sample collection..........................................................76
5.6
OTHER ASSESSMENTS...................................................................................76
5.7
APPROPRIATENESS OF MEASUREMENTS..............................................76
6.
INVESTIGATIONAL PLAN.............................................................................77
6.1
VISIT SCHEDULE.............................................................................................77
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS .................77
6.2.1
Screening period..................................................................................................78
6.2.2
Treatment period ................................................................................................78
6.2.3
Trial completion ..................................................................................................79
7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE......................................................................................................................80
7.1
NULL AND ALTERNATIVE HYPOTHESES ...............................................80
7.2
PLANNED ANALYSES.....................................................................................80
7.2.1
General considerations .......................................................................................80
7.2.2
Handling of Intercurrent Events .......................................................................81
7.2.3
Primary objective analyses.................................................................................81
7.2.3.1
Sensitivity Analyses..............................................................................................81
7.2.3.2
Subgroup Analyses ...............................................................................................81
7.2.3.3
Supplementary Analyses.......................................................................................81

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7.2.4
Secondary objective analyses.............................................................................82
7.2.6
Safety analyses.....................................................................................................85
7.2.7
Pharmacokinetic analyses ..................................................................................86
7.2.9
Interim analysis...................................................................................................89
7.3
HANDLING OF MISSING DATA ...................................................................89
7.3.1
Safety....................................................................................................................89
7.3.2
Pharmacokinetics................................................................................................89
7.4
RANDOMIZATION...........................................................................................90
7.5
DETERMINATION OF SAMPLE SIZE .........................................................90
8.
INFORMED CONSENT, TRIAL RECORDS, DATA PROTECTION, 
PUBLICATION POLICY, AND ADMINISTRATIVE STRUCTURE ........91
8.1
TRIAL APPROVAL, PATIENT INFORMATION, INFORMED 
CONSENT ...........................................................................................................91
8.2
DATA QUALITY ASSURANCE ......................................................................92
8.3
RECORDS...........................................................................................................92
8.3.1
Source documents ...............................................................................................92
8.3.2
Direct access to source data and documents.....................................................93
8.3.3
Storage period of records ...................................................................................94
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS ..................................94
8.5
STATEMENT OF CONFIDENTIALITY AND TRIAL PARTICIPANT 
PRIVACY ............................................................................................................94
8.5.1
Collection, storage, and future use of biological samples and 
corresponding data .............................................................................................94
8.6
TRIAL MILESTONES.......................................................................................95
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL ...................................95
9.
REFERENCES....................................................................................................97
9.1
PUBLISHED REFERENCES............................................................................97
10.
APPENDICES...................................................................................................102
10.1
TRIAL PARTICIPANT FEEDBACK............................................................102
10.2
INSTRUCTIONS FOR USE............................................................................102
10.3
COVID-19 RISK ASSESSMENT....................................................................102
10.4
DIAGNOSIS OF ANAPHYLAXIS .................................................................104

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ABBREVIATIONS AND DEFINITIONS
AE
Adverse event
AESI
Adverse event of special interest
ALP
Alkaline phosphatase
ALT
Alanine transaminase
API
Active pharmaceutical ingredient
AST
Aspartate transaminase
AUCτ,ss
Area under the concentration-time curve of the analyte in serum over the 
dosing interval tau at steady state
AV
Atrioventricular
BI
Boehringer Ingelheim
BMI
Body mass index
BP
Blood pressure
BW
Body weight
CA
Competent Authority
CCS
Canadian Cardiovascular Society
CI
Confidence interval
CK
Creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
Cmax,ss
Maximum measured concentration of the analyte in serum at steady state

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COVID-19
Coronavirus disease 2019
CPL
Clinical Program Leader
CRA
Clinical research associate
CRF
Case report form, paper or electronic (sometimes referred to as “eCRF”)
CRO
Contract Research Organization
C-SSRS
Columbia Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
CTL
Clinical Trial Leader
CTP
Clinical trial protocol
CTR
Clinical trial report
DEC
Dose Escalation Committee
DEXA
Dual energy X-ray absorptiometry
DG
Dose group
DILI
Drug-induced liver injury
DIO
Diet-induced
DSMB
Data and Safety Monitoring Board
ECG
Electrocardiogram
eDC
Electronic data capture
eGFR
Estimated glomerular filtration rate
ELISA
Enzyme-linked immunosorbent assay
EMA
EOS
European Medicines Agency
End of study
EOT
End of treatment
FC
Fragment crystallizable
FDA
Food and Drug Administration
FGF
Fibroblast growth factor
FGF21
Fibroblast growth factor 21
GCP
Good Clinical Practice
GLP
Good Laboratory Practice

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GLP-1
Glucagon-like peptide 1
GLP1R
Glucagon-like peptide 1 receptor
GGT
Gamma-glutamyltransferase
GOT
Glutamic oxaloacetic transaminase
GPT
Glutamic pyruvic transaminase
HbA1c
Glycosylated haemoglobin A1c
HbsAg
Hepatitis B virus surface antigen
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HIV
Human immunodeficiency virus
HR
Heart rate
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
Ig
Immunoglobulin
IMP
Investigational medicinal product
INR
International normalized ratio
IRB
Institutional Review Board
IRT
Interactive Response Technology
ISF
Investigator site file
i.v.
Intravenous
kDa
Kilodalton
kPa
Kilopascal
MDA
Methylenedioxyamphetamine
MDMA
Methylenedioxymethamphetamine
MedDRA
Medical Dictionary for Drug Regulatory Activities
MEN 2
Multiple endocrine neoplasia syndrome type 2
micro-CT
Micro-computer tomography

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MRD
Multiple rising dose
MRI
Magnetic resonance imaging
MRI-PDFF
Magnetic resonance imaging proton density fat fraction
MTC
Medullary thyroid carcinoma
NAFLD
Non-alcoholic fatty liver disease
NASH
Non-alcoholic steatohepatitis
NASH-CRN
NASH Clinical Research Network
NOAEL
No observed adverse effect level
NYHA
New York Heart Association
PCR
Polymerase chain reaction
PD
Pharmacodynamic(s)
PK
Pharmacokinetic(s)
PoCP
Proof of clinical principle
PP
Polypropylene
PR
Pulse Rate or time between start of the P-wave and start of the QRS 
complex in an electrocardiogram
q2 d
Every second day
qd
Daily (once daily)
QRS
Time between start of the Q-wave and the end of the S-wave in an 
electrocardiogram
QT
Time between start of the Q-wave and the end of the T-wave in an 
electrocardiogram
QTc
QT interval corrected for heart rate using the method of Fridericia (QTcF) 
or Bazett (QTcB)
qw
Weekly (once a week)
RBC
Red blood cell
REP
Residual effect period
RNA
Ribonucleic acid
RR
Time between 2 R-waves in an electrocardiogram
SAE
Serious adverse event
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

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s.c.
Subcutaneous
SCR
Screening
SGOT
Serum glutamic-oxaloacetic transaminase
SGPT
Serum glutamic-pyruvic transaminase
SOP
Standard operating procedure
T-BIL
Total bilirubin
TAA
Thioacetamide
TB
Total bilirubin
TC
Total cholesterol
TG
Triglycerides
TGFß
Transforming growth factor beta
tmax,ss
Time from dosing to the maximum measured concentration of the analyte 
in serum at steady state
TMF
Trial master file
TSH
Thyroid stimulating hormone
TSTAT
Trial statistician
ULN
Upper limit of normal
vs.
Versus
WBC
White blood cell
XTC
Ecstasy

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1.
INTRODUCTION
1.1
MEDICAL BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of about 20 to 30% in the 
general population of Western countries and is rapidly becoming the most common liver 
disease worldwide [R15-5365]. While simple hepatic steatosis can have a benign non-
progressive course, about 10% of patients with NAFLD progress to non-alcoholic 
steatohepatitis (NASH). As the disease progresses, significant fibrosis develops in 37 to 41% 
of patients within 15 years. According to the National Institute of Health, NASH is believed 
to be the most common cause of liver cirrhosis [R15-6070], and the 12th leading cause of 
death in the United States [R15-6057]. Patients with NASH are also at increased risk of 
hepatocellular carcinoma, even in the absence of cirrhosis [R15-5365]. By 2023, about 
13 million patients are projected to have NASH with advanced stages of fibrosis. The risk of
liver-related death in Western patients with NASH ranges from 10% over 13.7 years to 18% 
over 18.5 years [P13-02280].
Neither approved NASH-targeted therapy nor effective disease modifying regimens are 
currently available. Treatment is focused on addressing comorbidities from metabolic 
syndrome. Moreover, while lifestyle modifications – including weight loss and exercise – are 
recommended across different phenotypes and considered the mainstay initial treatment for 
NASH, they are difficult to achieve and maintain.
The test product BI 3006337 is a long-acting dual GLP-1 and FGF21 receptor agonist. By 
combining activities of GLP-1 and FGF21 in one molecule (dual GLP-1/FGF21 receptor 
agonist), BI 3006337 is expected to address multiple disease-related components of NASH 
by:

Reducing liver cell injury (steatosis, oxidative stress) and hepatic inflammation

Reducing fibrosis and

Improving glucose metabolism and insulin resistance
GLP-1 is a gut-derived incretin hormone with glucose-lowering features achieved by 
inducing insulin secretion and reducing the production of glucagon. It also suppresses 
appetite and retards gastric emptying.
GLP1R agonists are one of the newer classes of medications for the treatment of adults with 
type 2 diabetes and/or obesity. The GLP1R agonist class first became available in 2005 in the 
United States with the approval of short-acting exenatide by the FDA. There are now several 
GLP1R agonists (mostly for s.c. application) available for the treatment of type 2 diabetes 
and obesity. In clinical studies in patients with NASH, liraglutide, a long-acting GLP-1
agonist, achieved resolution of NASH without worsening of fibrosis in 39% (9/23) of patients 
compared with 9% (2/22) in the placebo group after 48 weeks of treatment. Improvements in 
steatosis and hepatocyte ballooning were greater in the liraglutide group, but no differences 
were seen in lobular inflammation and overall non-alcoholic fatty liver disease (NAFLD)
activity score [R16-3177].
The FGF family of hormones mediates metabolic functions and tissue repair and 
regeneration. FGF21, a non-mitogenic hormone, is a key regulator of energy metabolism. It 
increases energy expenditure, reduces hepatic triglyceride, and improves insulin sensitivity 
[R19-2360].

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Several FGF21-class molecules have been tested in humans, and several are still in different 
stages of clinical development for the treatment of type 2 diabetes or NASH. In clinical 
studies involving patients with NASH, pegbelfermin s.c. showed beneficial effects of FGF21 
on steatosis, injury, and fibrosis markers. Pegbelfermin significantly reduced the absolute 
hepatic fat fraction in the groups receiving either 10 mg daily (-6.8% vs. -1.3%) or 20 mg 
once a week (qw) (-5.2% vs. -1.3%), compared with the placebo group. It also decreased 
ALT and AST, and reduced the serum fibrosis biomarker Pro-C3 in both treatment groups
(-30%, 10 mg qd; -19%, 20 mg qw) relative to the placebo group [R20-0507].
Dual GLP-1/FGF21 receptor agonism is therefore expected to reduce liver cell injury 
(steatosis, oxidative stress, and release of aminotransferases) and hepatic inflammation. 
While sustained resolution of steatohepatitis could result in subsequent reduction of fibrosis, 
a dual agonist is also expected to have direct anti-fibrotic effects via FGF21 mediated 
attenuation of TGFß signalling and hepatic stellate cell activation as recently described 
[R20-0498]. In addition, a dual GLP-1/FGF21 receptor agonist should improve insulin 
resistance as a root cause of liver steatosis and inflammation.
Overall, the clinical data available from literature on the separate components (GLP-1 and 
FGF21 agonists) are supportive for the development of BI 3006337 in patients with NASH.

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1.2.2
Toxicology
In summary, the toxicology package did not indicate any adverse systemic toxicities nor 
embryo-foetal toxicity with sufficient margins to the exposures expected at the dose levels in 
this MRD trial. Therefore, the nonclinical safety data support the chronic administration of 
BI 3006337 to men and women with childbearing potential.
For details, please see IB Sections 5.3 and 8.3.
1.2.3
Nonclinical pharmacokinetics
Two enzyme-linked immunosorbent assay (ELISA) assays were designed to measure full 
length and therefore active components of the molecule (GLP-1 and FGF21). The 
pharmacokinetics (PK) of BI 3006337 was dose linear after i.v. and s.c. dosing in mice, rats, 
Cynomolgus monkeys, and minipigs. The ka and bioavailability (F) in non-clinical animals 
were species-dependent during the single dose PK studies. BI 3006337 is expected to be 
primarily distributed to blood and interstitial fluid. Dedicated metabolism studies have not 
been performed. BI 3006337 is expected to undergo protein catabolism in animals and 
humans to peptides and amino acids. The molecular weight of BI 3006337 is 104 kDa, which 
is above the renal filtration cut-off threshold (around 60 kDa). BI 3006337 is not expected to 
have significant renal filtration. Differential PK profiles were observed in mice and 
Cynomolgus monkeys only. Mice showed a slightly higher exposure to active GLP-1 than to 
active FGF21. Monkeys showed a substantially shorter PK profile for active GLP-1 than for 

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active FGF21. The cause of the discrepancies in the exposure between GLP-1 and FGF21 is 
unknown.

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1.4
BENEFIT - RISK ASSESSMENT
1.4.1
Benefits
Potential benefits of treating overweight or obese trial participants with BI 3006337 may
result in the resolution of liver steatosis and may prevent the progression to NASH with 
significant fibrosis. This is important because NASH can eventually lead to cirrhosis, liver 
cancer, liver transplantation and death. Additionally, the treatment may not only reduce 
weight but also ameliorate insulin resistance and improve the patient lipid profile, which may 
directly translate into relevant improvements for patients’ morbidity, mortality, and quality of 
life.
Trial participants may also benefit from more frequent clinical monitoring during the trial.
1.4.2
Risks
The trial participants are exposed to the risks of the trial procedures and the risks related to 
the trial medication.

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Procedure-related risks
The use of an indwelling venous catheter for the purpose of blood sampling may be 
accompanied by mild bruising and, in rare cases, by transient inflammation of the wall of the 
vein. In addition, in rare cases a nerve might be injured while inserting the venous catheter, 
potentially resulting in paraesthesia, reduced sensibility, and/or pain for an indefinite period. 
The same risks apply to venepuncture for blood sampling.
The total volume of blood withdrawn during the entire trial per trial participant will not 
exceed the volume of 1050 mL. No health-related risk to the trial participants is expected 
from this blood withdrawal.
In the usual Phase I settings, the trial participants stay on site in small groups for several days 
and there is a potential risk for spreading SARS-CoV-2 across the trial participant group or 
site staff. Some trial procedures, e.g. collecting blood samples, recording of ECGs, or 
assessing vital signs, may not allow keeping the recommended distance of 1.5 to 2 meters to 
prevent the transmission of SARS-CoV-2. A risk management procedure has been set up at 
the sites detailing specific cautionary measures (e.g. hygiene rules, wearing of face masks,
and physical distance), which is filed in the investigator site file (ISF). The local requirements 
may be subject to change and the trial procedures will be adapted accordingly, if applicable.
Drug-related risks and safety measures
The core safety pharmacology endpoints (cardiovascular, respiratory, and neurological 
function) were evaluated as part of a 26-week GLP repeat dose toxicity study in monkeys.
No mortality or adverse findings were associated with BI 3006337 administration in the 
neurological or respiratory function. Although a trend of BI 30063367 related increase in the 
heart rate was detected, it was considered non-adverse based on the lack of apparent dose-
related relationship and associated effects on other ECG parameters. This and other 
BI 3006337 related non-adverse effects were fully reversible after the 12-week recovery 
period.
The most prominent treatment-related effects were gastrointestinal effects including body 
weight loss and decreased body weight gain, which were associated with the reduced food 
consumption. In monkeys, the extent of the effect on the body weight was the most 
pronounced during the first 5 weeks of the treatment period and during the recovery period, 
marked body weight gain was observed. Similar effects including emesis have been shown 
with other GLP-1 agonists, and the up-titration method has been used to improve tolerability 
in the clinical trials.
Based on the injection site reactions observed in monkeys, local irritation in humans is 
possible. Monitoring the injection site is recommended in human trials.
Assuming linear and dose-proportional pharmacokinetics, an accumulation of +10%  with 
once weekly dosing (based on a half-life of 52 h) and based on the observed preliminary 

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single dose parameters Cmax (1290 µg/L) and AUC0-∞(80500 µg*h/L) at 150 mg in 
trial 1466-0001, the steady state parameters at 150 mg are predicted as 
Cmax,ss =1290 µg/L* 1.1 = 1419 µg/L and AUCτ,ss = 80500 µg*h/L. Hence, these predicted 
exposures at the proposed dose levels in this MRD trial are covered by sufficient margins in 
the toxicity studies (IB Section 5.3 and 8.3).
. Due 
to the s.c. administration, local intolerabilities may occur. Trial participants are exposed to 
risks of trial procedures and risks related to the exposure to the trial medication.
Non-clinical safety pharmacology studies with BI 3006337 have neither identified adverse 
effects on respiratory nor cardiovascular function that would imply an increased risk in 
context of the COVID-19 pandemic. Based on the mechanism of action, BI 3006337 is not 
expected to promote malfunction of the immune system resulting in an increased risk of 
progression of COVID-19 infection.
It is unlikely that there will be an additional risk to trial participants with a BMI ≥25 kg/m2 
(overweight to obesity) and steatosis by the application of BI 3006337. However, due to the
underlying common co-morbidities (obesity, diabetes) the NAFLD/NASH population is at 
increased risk for severe illness from COVID-19.
The following safety measures will be applied in this trial in order to minimize the risk for 
the trial participants:

Careful dose selection (refer to Section 4.1.2)

Preliminary measurement of BI 3006337 serum concentrations and preliminary 
determination of PK parameters

Patients with conditions that may pose a safety risk in the trial will be excluded (refer 
to Section 3.3.3)

An extensive safety laboratory will be performed with special focus on full blood 
exam also including bone turnover biomarkers

For safety reasons, each dose group of 14 trial participants (10 on BI 3006337 and
4 on placebo) will be divided into 3 cohorts: cohort 1 of 3 trial participants (2 on 
BI 3006337 and 1 on placebo), cohort 2 of 3 trial participants (all on BI 3006337),
and cohort 3 of 8 trial participants (5 on BI 3006337 and 3 on placebo). The drug 
administrations of these three cohorts will be separated by at least 72 h (between last 
trial subject in the current cohort and first trial participant of the next cohort) to cover 
the period of highest risk/peak effect. 

A thorough ECG monitoring during in-house days and additionally on selected 
ambulatory visits


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1.4.3
Discussion
In summary, BI 3006337 has the potential to become a s.c. treatment for NASH. Based on the 
mode of action, the pharmacological targets, the clinical experience of the separate 
components, and the nonclinical toxicology data as well as the implemented safety measures 
described above, trial participants who with overweight/obesity and steatosis will not be 
exposed to undue risks in relation to the important information expected from this trial as a 
basis for further clinical development of this compound. 
 

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2.
TRIAL OBJECTIVES AND ENDPOINTS
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS
2.1.1
Main objectives
The main objectives of this trial are to assess the safety, tolerability, PK, and PD of 3 multiple 
rising dose levels by s.c. injection of up to 150 mg BI 3006337 over 12 weeks in comparison 
with placebo in trial participants with overweight/obesity and steatosis. The primary objective 
is to descriptively assess the frequency (N [%]) of trial participants with drug-related AEs. 
Secondary objectives are to descriptively assess the PK parameters for BI 3006337 and to 
explore superiority of clinical efficacy vs. placebo for BI 3006337 at the highest tolerated 
dose.
2.1.2
Primary endpoint
The primary endpoint for the assessment of safety and tolerability of BI 3006337 is the 
occurrence of drug-related AEs between the first administration of trial medication 
(BI 3006337 or placebo) and end of study (EOS).
2.1.3
Secondary endpoints
The following PK parameters of BI 3006337 will be determined if feasible:

AUCτ,ss (area under the concentration-time curve of the analyte in serum over the 
dosing interval tau at steady state) after the last dose in Week 12

Cmax,ss (maximum measured concentration of the analyte in serum at steady state) after 
the last dose in Week 12

tmax,ss (time from dosing to the maximum measured concentration of the analyte in 
serum at steady state) after the last dose in Week 12
The following efficacy endpoints will be assessed:

Relative percentage change in liver steatosis (as measured by MRI-PDFF) from 
baseline after 12 weeks of treatment.
Trial participants who do not complete 12 weeks of treatment due to disruption related to 
COVID-19 will be replaced to achieve up to 100% sample size in each dose group; the main 
PoCP efficacy analysis will exclude these trial participants, 
 
; drop-outs due to other reasons will not be replaced and will be 
included in all analyses.

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2.2.2.1
Safety and tolerability
Safety and tolerability of BI 3006337 will be assessed during the on-treatment period, i.e. 
occurring between first administration of trial medication (BI 3006337 or placebo) and EOS 
based on:

AEs (including clinically relevant findings from the physical examination)

Safety laboratory tests including glucose

12-lead ECG

Vital signs (Temperature, BP, PR)

Local tolerability at the injection site

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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN
This MRD and PoCP Phase Ib trial is designed as single-blind (within each dose group) and
randomised trial with placebo matching the dose of BI 3006337 as comparator. Treatment 
allocation will be performed within each dose group in a 5:2 ratio (BI 3006337 to placebo).
The trial will consist of a screening period of up to 6 weeks to assess trial participant 
eligibility, a treatment period of 12 weeks and a follow up period of 3 weeks.
It is planned to include approximately 56 trial participants in the trial. In total the number of 
trial participants will not exceed 72. This sample size considers the investigation of three 
dose levels and the repetition of the highest tolerated dose level for the PoCP analysis with 
14 trial participants per group in DG 1-3 and 14 to 30 trial participants in DG 4:




Within dose group 1-3, 10 trial participants will receive BI 3006337 and 4 will receive 
placebo once weekly. For safety reasons, each dose group will consist of 3 cohorts. The first 
two cohorts are in fixed order and randomization will only be performed in Cohort 3 in a 5:3 
ratio (BI 3006337 to placebo).
The trial medication will be administered in the following order:

Cohort 1 (fixed order: ‘active – active – placebo’): 2 trial participants on BI 3006337 
and 1 on placebo (in total 3 trial participants)

Cohort 2 (fixed order: ‘active – active – active’): 3 trial participants on BI 3006337
(in total 3 trial participants)

Cohort 3 (randomised): 5 trial participants on BI 3006337 and 3 on placebo (in total 
8 trial participants)

For cohort 3 in DG 4: At least 8 trial participants will be randomised. The number of 
24 randomised trial participants in cohort 3 of DG 4 will not exceed.
In cohort 1 and 2, the 3 trial participants will be dosed sequentially. 72 h will elapse between 
the last trial participant of cohort 1 and the first trial participant of cohort 2, which is based on 
the time to reach peak concentrations of BI 3006337 (median tmax 7 to 61.5 h) and is expected 
to cover the period of highest risk/peak effect. The first 2 cohorts will be dosed in a single-
blinded, fixed sequence fashion ‘active – active – placebo’ (cohort 1) and ‘active – active –
active’ (cohort 2). First dosing in cohort 3 can only start after all trial participants in the 
previous cohorts have completed 72 h. 
An overview of the trial design is presented in Table 3.

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Table 3
Overview of the trial design
Doses/Weeks
Dose 
group
1
2
3
4
5
6
7
8
9
10
11
12
1
*Repetition of the highest tolerated dose level for PoCP analysis
A trial participant will be in the trial for up to 18 weeks in total (first screening until EOS). 
The overall treatment duration will be 12 weeks. A trial participant who completes the 
planned treatment or terminates treatment prematurely should undergo a follow-up visit (EOS
examination; see Flow Chart).
Trial participants who do not complete 12 weeks of treatment due to disruption related to 
COVID-19 will be replaced to achieve up to 100% sample size in each dose group; the main 
PoCP efficacy analysis will exclude these trial participants, 
 
; drop-outs due to other reasons will not be replaced and will be 
included in all analyses.
A Dose Escalation Committee (DEC), including but not restricted to Patient Safety Physician, 
Clinical Project Lead who is the medical expert representative with extensive hepatology 
expertise (CPL), Trial Statistician (TSTAT), Principal Investigators (PI), Clinical Trial Lead 
(CTL) and independent members experienced in treatment of liver disease or endocrine 
disease, will decide on the dose escalation. Target for releasing the next dose level is planned 
after 14 trial participants (100%) in the dose group completed 7 weeks of dosing. Two
additional weeks are to be needed for preparing the DEC. The decision to proceed to the next 
dose group will be based upon the safety and tolerability of the preceding dose groups. The 
next dose group will only be treated if no safety concerns have arisen in the preceding dose 
groups, and if none of the pre-specified trial-specific stopping criteria have been met (refer to
Section 3.3.4.1). In addition, dose group 3 will only be treated after the complete PK results 
of dose group 1 are available. Details will be defined in the DEC charter.
In addition to safety, tolerability and PK parameters, the trial will be performed to investigate 
PD parameters like fasting plasma glucose or insulin (see Section 2.2.2.4). As needed, 
additional safety, efficacy, and PK/PD analyses may be performed during the trial.
The end of the trial will be the date of the last visit of the last trial participant in the whole 
trial (at trial participant level: the date of the follow-up visit).
No formal interim analysis is planned. Unblinded exploratory analyses on the safety and 
tolerability will be performed during the conduct of the trial to evaluate dose escalations.
For definitions and handling of blinding, refer to Section 4.1.5.1.

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An overview of all relevant trial activities is provided in the Flow Chart. For visit schedules 
and details of trial procedures at selected visits, refer to Sections 6.1 and 6.2, respectively.
3.1.1
Staggered conduct of dose escalation
For safety reasons dose escalation will be performed in a staggered manner. The escalation of 
BI 3006337 within the escalation schedule to a higher dose level than given in the previous 
titration schedule will only be performed after a safety review meeting (refer to Section
3.1.2). An additional safety review will be performed when expanding the cohort on the 
highest dose level. Safety review meetings will start on Week 9 of treatment (see Figure 1).
3.1.2
Dose Escalation Committee (DEC) – Operations and Safety Review
A documented Safety Review must take place prior to each dose escalation. Furthermore, an 
unscheduled safety review meeting can be requested anytime for any reasonable cause by the 
Principal Investigator (or an authorised deputy) or the sponsor of the trial, e.g. because of any 
unforeseen AEs, etc. Proceeding to the next dose group will only be permitted if no safety 
concerns exist in the opinion of the DEC members. In summary, the implementation of the 
DEC and safety monitoring measures as described in this CTP are considered adequate to 
ensure trial participant safety in this Phase Ib trial.
Safety review meetings are either major (at the end of each dose group) or minor (within a 
dose group prior to escalating to the next dose group at the time points indicated in Figure 1). 
In general, dose escalation decisions will be taken based on safety data (and PK data, if 
applicable, see Section 7.2.7).
Minimum data set for review in minor safety review meetings.
Every effort should be made to recruit a complete DG with 14 patients. At a minimum, data 
from a minimum dataset of 8 patients on active drug and a minimum dataset of 2 patients on 
placebo (in case of dropouts until Week 7, see Section 3.3.5) in each dose group need to be 
available for escalation to a higher dose. For the minimum dataset with regards to preliminary 
PK data, see Section 7.2.7. The minimum data set for review consists of the following:

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
AEs in the current and preceding dose groups up to at least Week 7, including 
clinically relevant findings from ancillary safety testing listed below (Note: AEs may 
be ongoing at the time of Safety Reviews and AE information may be patient to 
change prior to Database Lock)

Results from 12-lead ECG 

Vital signs in the current and preceding dose groups up to at least Week7

Clinical laboratory tests in the current and preceding dose groups up to at least Week7

Assessment of local tolerability

Preliminary PK data as described in Section 7.2.7

Check of criteria for stopping trial participant treatment as per Section 3.3.4.1
Minimum data set for review in major safety review meetings
Major safety meetings should take place within of 3 weeks after data cut off on week 12. For 
major safety review meetings, the same minimum requirements as for minor safety review 
meetings apply. In addition, dose group 3 will only be treated after the complete PK results of 
dose group 1 are available.
The decision to escalate the dose will be made by the DEC members after in-depth analysis 
of all available safety data, especially serious AEs (SAEs, if occurred), AEs, and out-of-range 
laboratory results (if considered clinically significant). For the purpose of safety evaluation 
and decision taking at completion of each dose level in this trial, the Principal Investigator 
will provide
assessment based on
direct clinical experience in the use of the
investigational compound; because decisions in this Phase Ib dose escalation trial are taken 
based on safety observations of the trial participant cohorts, the view of the investigator on 
individual trial participants is considered essential for the overall safety assessment. In 
addition, and depending on the results and findings, suitable experts from the sponsor (e.g. 
TSTAT) or external institutions may be consulted on an as needed basis. In these cases,
expert recommendations will be documented in the minutes of the Safety Review and 
considered for the decision making. Decision of the DEC must be made unanimously.
Safety Reviews can be conducted face-to-face or by video/telephone conference. The CTL is 
responsible for the organisation and minutes of the reviews. Minutes will be signed off by the 
Principal Investigator (or an authorised deputy) and CTL (or an authorised deputy) and will 
be filed in the ISF and TMF.
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP
This will be an MRD trial with implementation of a DEC to decide on dose escalation, which 
is appropriate for the exploration of safety, tolerability, PK, and PD. The trial will be 
randomised and single-blind within each dose group to allow unbiased comparison with 
placebo.
Based on the expected mechanism of action of BI 3006337 and the studied population, the 
reduction of liver fat content measured by MRI-PDFF will be used as primary efficacy 
endpoints in this MRD trial. Liver steatosis is the main imaging and histologic finding 
common to all forms and stages of NAFLD/NASH. MRI-PDFF is a quantitative imaging 
biomarker that enables accurate, repeatable, and reproducible quantitative assessment of liver 
fat over the entire liver [R22-0898]. Thus, the technique has become the gold-standard for 

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assessing treatment response regarding liver fat reduction in NASH trials [R21-3294].
Reductions in liver fat content as measured by MRI-PDFF have been consistently associated 
to histologic response in subjects with NASH [R22-0900].
The trial will include an option for participants to complete questionnaires to provide 
feedback on their clinical trial experience (see Section 10.1). Providing this feedback is not 
required for trial participation, and information collected from these questionnaires will not 
be analysed as part of the clinical data for the trial.
3.3
SELECTION OF TRIAL POPULATION
The MRD 1466-0002 trial for BI 3006337 will include a population of participants with
overweight/obesity and steatosis (i.e. without clinically significant degrees of hepatic 
necroinflammation or fibrosis). This MRD trial is planned to be conducted without the use of 
biopsies for either eligibility or efficacy assessments. The overall eligibility goal will be to 
include participants with a clinically sound diagnosis of NAFLD, with steatosis confirmed 
and quantified by MRI-PDFF, and with exclusion of participants with clinically significant 
degrees of hepatic necroinflammation or fibrosis made with non-invasive tests. 
The trial will include approximately 56 trial participants (40 on BI 3006337 and 16 on 
placebo) and
 
Screening of trial participants for this trial is competitive, i.e., screening for the trial will stop 
at all sites at the same time once a sufficient number of trial participants has been screened to 
deliver the required number of patients randomized into each DG. Investigators will be 
notified about screening completion and will then not be allowed to screen additional trial 
participants for this trial. Trial participants already in screening at this time will be allowed to 
continue to randomization if eligible.
After14 participants have been randomized into DG3, the additional patients confirmed 
eligible, may be randomized into DG4. The total number of participants in DG4 should not 
exceed 30 patients.
A log of all trial participants enrolled into the trial (i.e. who have signed informed consent) 
will be maintained in the ISF irrespective of whether they have been treated with 
investigational drug or not.
Even for screen failure participants, a minimum of information will be collected: participant 
number, visit date, demographics, eligibility criteria, information on AEs (if applicable), and 
concomitant treatment relevant for the AE. Re-screening is allowed once, patients will 
receive a new ID number. When re-screening will be performed within the screening period 
all tests which have been already done can be used. Every test performed outside the 
screening window needs to be assessed again.
If retrospectively it is found that a trial participant has been randomized in error (=did not 
meet all inclusion criteria or met 1 or more exclusion criteria), the sponsor or delegate should 

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be contacted immediately. Based on an individual benefit-risk assessment, a decision will be 
made whether continued trial participation is possible or not.
3.3.1
Main diagnosis for trial entry
The trial will be performed in participants with overweight/obesity and steatosis.
Please refer to Section 8.3.1 for the documentation requirements pertaining to the in- and 
exclusion criteria.
3.3.2
Inclusion criteria
Trial participants will be eligible if they meet all the following inclusion criteria at screening:
1. Male or female trial participants ≥18 years and ≤75 years of age at time of consent. 
Women of child-bearing potential (WOCBP1) must be willing and able to use 2 forms 
of effective contraception where at least 1 form is a highly effective method of birth 
control per ICH M3 (R2) that results in a low failure rate of less than 1% per year 
when used consistently and correctly. Male trial participants must be willing and able 
to use condom if their partner is a WOCBP (Section 4.2.2.3)
2. BMI ≥25-<40 kg/m2
3. Liver fat fraction ≥8% as measured by MRI-PDFF
4. Signed and dated written informed consent in accordance with ICH-GCP and local 
legislation prior to admission to the trial
3.3.3
Exclusion criteria
Trial participants will NOT be eligible if they meet any the following exclusion criteria:
1. Current or past significant alcohol consumption (daily alcohol consumption in women 
should not exceed more than one standard drink per day and two drinks per day for 
men, whereby one standard drink is equivalent to 12 oz beer [5% alcohol]; 5 ounces 
of wine [12% alcohol], 1.5 ounces of 80 proof [40% alcohol]) or inability to reliably 
quantify alcohol consumption based on Investigator judgement within the last 5 years. 
The Alcohol Use Disorders Identification Test (AUDIT) shall be used a standardized 
screening tool for alcohol use disorder
2. Intake of medications historically associated with liver injury, hepatic steatosis, or 
steatohepatitis (e.g. oral or intravenous corticosteroids, methotrexate, valproic acid, 
tamoxifen, tetracycline, amiodarone) for more than 14 consecutive days within 
12 weeks prior to the screening visit
1A woman is considered of childbearing potential, i.e. fertile, following menarche, and until becoming post-
menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilisation. A 
postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

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3. Presence of any form of acute or chronic liver disease other than simple steatosis (e.g. 
viral hepatitis, autoimmune liver disease, primary biliary sclerosis, primary sclerosing 
cholangitis, Wilson’s disease, hemochromatosis, alpha-1 antitrypsin deficiency). 
Chronic viral hepatitis parameters that would be considered exclusionary for the 
participation to this trial are (hepatitis B and C testing will be done at the screening 
visit):
a.
HBV: trial participants with positive HbsAg
b. HCV: trial participants with positive HCV RNA. Trial participants treated for 
hepatitis C must have a negative RNA test at screening and also be HCV RNA 
negative for at least 3 years prior to screening in order to be eligible for the 
trial
4. Liver stiffness >10kPa as measured using Fibroscan. In patients with a non-valid 
Fibroscan measurement, a Fib-4 score >1.3 should be considered exclusionary.
5. Suspicion, confirmed diagnosis, or history of hepatocellular carcinoma
6. Treatment with vitamin E (at a minimum dose of 800 IU/day) or pioglitazone not 
stable (in the opinion of the Investigator) within 90 days before screening
7. History of type 1 diabetes
8. Use of GLP1-receptor agonists within last 90 days before screening
9. Use of glucose lowering or weight loss medication not stable (in the opinion of the 
Investigator) within 30 days before screening
10. Bariatric surgery or treatment with weight-loss device, prior to or planned during trial 
conduct; except gastric-band surgery more than 2 years prior to screening (including 
adjustments) with a stable BW within the last 12 months
11. Unstable BW (gain or loss) of more than 10% within 12 weeks before screening
12. Known history of HIV infection and/or acute SARS-CoV-2 infection at screening 
visit (confirmed by PCR test)
13. Abnormal laboratory values as listed below:
a.
eGFR <50 mL/min/1.73 m2 at the screening visit (CKD-EPI formula)
b. Bilirubin level >1.5x ULN at the screening visit (except for known Gilbert’s 
disease with a conjugated bilirubin of <0.3 mg/dL)
c.
ALT and/or AST >5x ULN at the screening visit
d. HbA1c ≥9.5% at the screening visit
14. Diagnosis of a serious or unstable disease including hepatic (other than steatosis), 
renal, gastrointestinal, respiratory, cardiovascular (including ischemic heart disease), 
endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease and 
other conditions that, in the clinical judgment of the Investigator, are likely to 
interfere with the analyses of safety and efficacy in this trial. Trial participants with an 
expected life expectancy of less than 2 years are also excluded.

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15. Any documented active or suspected malignancy or history of malignancy within 
5 years prior to screening, except appropriately treated basal cell carcinoma of the 
skin or in situ carcinoma of the uterine cervix
16. Any major surgery (major according to Investigator’s assessment) performed within 
12 weeks prior to randomization or planned during trial conduct
17. Personal or family history of medullary thyroid carcinoma or multiple endocrine 
neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit 1
18. History of chronic or acute pancreatitis or elevation of serum lipase/amylase >2x
ULN, or fasting serum triglyceride levels of >500 mg/dL (>5.65 mmol/L) at screening
19. History of fracture, bone surgery (including joint or hardware replacement, bone 
grafting, or amputation), or clinically significant bone trauma within 12 weeks of 
screening.
20. Any lifetime history of suicidal behaviour, any suicidal ideation of type 2 to 5 on the 
C-SSRS in the past 12 months prior to Visit 1
21. Resting HR >100 bpm and/or BP ≥160/95 mmHg at Visit 1. BP measurement should 
be repeated 10 min apart. Trial participant should be excluded only if the second 
measurement confirms a BP ≥160/95 mmHg.
22. A marked prolongation of QT/QTc (Fridericia) interval that is greater than 450 ms for 
men or 470 ms for women at Visit 1 or any other abnormal clinically significant ECG 
finding at Visit 1 (e.g. type 2 second-degree AV block (Type Mobitz II) or third-
degree AV block)
23. History of ventricular tachycardia, type 2 second-degree AV block (Type Mobitz II), 
third-degree AV block or congestive heart failure NYHA III-IV
24. Heart rhythm disturbances (e.g. bradycardia with baseline HR <50 bpm, in the 
absence of HR lowering medications), tachycardia or tachyarrhythmia (e.g. atrial 
fibrillation, atrial flutter, or ventricular tachycardia), considered by the Investigator 
indicative of relevant cardiac disease or with abnormalities that may interfere with the 
interpretation of changes in ECG intervals at Visit 1. Family history of long QT 
syndrome, use of prescription or over-the-counter medications known to significantly 
prolong the QT/QTc interval at Visit 1
25. Any of the following conditions or procedures within the last 6 months prior to 
Visit 1: myocardial infarction, unstable angina (e.g. CCS grading of Angina pectoris 
grade III and IV), artery bypass (e.g. coronary artery bypass graft, carotid bypass, 
peripheral artery bypass), percutaneous coronary intervention (diagnostic angiograms 
are permitted), transient ischemic attack, cerebrovascular accident (stroke), or 
decompensated congestive heart failure
26. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
27.

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3.3.4
Discontinuation of trial participants from treatment or assessments
Trial participants may discontinue trial treatment or withdraw consent to trial participation as 
a whole (“withdrawal of consent”) with very different implications; please see 
Sections 3.3.4.1 and 3.3.4.2 below.
However, if the trial participants agree, they should stay in the trial. Even if continued trial 
treatment is not possible, they should attend further trial visits to ensure their safety and to 
collect important trial data.
Measures to control the withdrawal rate include careful trial participant selection, appropriate 
explanation of the trial requirements and procedures prior to trial enrolment, as well as the
explanation of the consequences of withdrawal.
The decision to discontinue trial treatment or withdraw consent to trial participation and the 
reason must be documented in the trial participant files and CRF. If applicable, consider the 
requirements for AE collection reporting (please see Section 5.2.6.2).
If a trial participant is removed from or withdraws from the trial prior to the first 
administration of trial medication (BI 3006337 or placebo), the data of this trial participant
will not be entered in the CRF and will not be reported in the CTR. If a trial participant is 
removed from or withdraws from the trial after the first administration of trial medication, 
this will be documented and the reason for discontinuation must be recorded in the CRF; in 
addition, the data will be included in the CRF and will be reported in the CTR.
At the time of discontinuation, a complete EOS examination will be performed, if possible, 
and the information will be recorded in the CRF. If the discontinuation occurs before the end 
of the REP (see Section 1.2.5), the discontinued trial participant should if possible be 
questioned for AEs and concomitant therapies at or after the end of the REP in order to 
ensure collection of AEs and concomitant therapies throughout the REP, if not contrary to 
any consent withdrawal of the trial participant.
3.3.4.1
Discontinuation of trial treatment
An individual trial participant will discontinue trial treatment if:

The trial participant withdraws consent for trial treatment or trial participation, 
without the need to justify the decision

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
The trial participant has repeatedly shown to be non-compliant with important trial 
procedures and, in the opinion of both, the investigator and sponsor representative, is 
not willing or able to adhere to the trial requirements in the future

An AE (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or 
higher) occurred, and the AE was assessed by the Investigator as related to the trial 
treatment (Section 5.2.6.1.5 and 5.2.6.1.6).

An AE (CTCAE Grade 4 or higher) occurred, regardless of attribution to the trial 
treatment (Section 5.2.6.1.5 and 5.2.6.1.6).

The trial participant needs to take concomitant medication that interacts with the 
investigational medicinal product or other trial treatment

An AE or clinically significant laboratory change, or abnormality occurs that the 
investigator assesses as warranting discontinuation of treatment. This may include 
cases of sustained symptomatic hypotension (BP <90/50 mmHg) or hypertension 
(BP >180/100 mmHg), or clinically relevant changes in ECG requiring intervention 

The trial participant can no longer receive trial treatment for medical reasons such as 
surgery, other AEs, other diseases, or pregnancy (see Section 5.2.6.2.3)

The trial participant experiences a severe infection with SARS-CoV-2, (as confirmed 
by PCR test; test options outside the clinical trial to be considered if according to 
local requirements, see Section 5.2.3. The trial participant may resume trial treatment 
following recovery from SARS-CoV-2 infection if the participant is expected to 
derive clinical benefit, as agreed between the investigator and sponsor

Occurrence of:
o
Systemic hypersensitivity reaction (mild/CTCAE grade 1, moderate/CTCAE 
grade 2 or, or and severe/CTCAE grade 3, 4) to the investigational product
(Trial participants should be closely monitored for signs and symptoms of 
hypersensitivity reactions, please refer to Section 4.2.1)
o
DILI attributable to the trial drug (see section 5.2.6.1.4)  
o
Signs of suicidal behaviour or ideation (see section 5.2.5.3)
o
Pancreatitis
o
Any injection site reaction (ISR) with ulceration, necrosis, severe tissue 
damage or operative intervention (CTCAE grade 3, 4, 5) should prompt 
permanent discontinuation. ISR classified as moderate that meets three out of 
the five criteria on table in section 5.2.6.1.5 should also prompt treatment 
discontinuation. Continue to follow the patient in the trial per the schedule of 
assessment and until the ISR resolves, even if the investigational agent has 
been discontinued.
In addition to these criteria, the investigator may discontinue trial participants at any time 
based on his or her clinical judgment.
If the patient becomes pregnant during the trial medication must be stopped, the patient will 
be discontinued from the trial and followed up until birth or otherwise termination of the 
pregnancy. For further information, including the process for follow-up of the outcome of the 
pregnancy please see Section 5.2.6.2.3.

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If new efficacy/safety information becomes available, BI will review the benefit-risk-
assessment and, if needed, pause, or discontinue the trial treatment for all trial participants or 
take any other appropriate action to guarantee the safety of the trial participants.
Even if the trial treatment is discontinued, the trial participant remains in the trial and, given 
his/her agreement, will undergo the procedures for early treatment discontinuation and 
follow-up as outlined in the Flow Chart and Section 6.2.3.
Additional trial participants may be recruited during the trial to replace the trial participants 
who discontinued prematurely, please refer to Section 3.3.5 for details.
3.3.4.2
Withdrawal of consent to trial participation
Trial participants may withdraw their consent to trial participation at any time without the 
need to justify the decision.
If a trial participant wants to withdraw consent, the investigator should be involved in the 
discussion with the trial participant and explain the difference between trial treatment 
discontinuation and withdrawal of consent to trial participation, as well as explain the options 
for continued follow-up after trial treatment discontinuation; please see Section 3.3.4.1.
3.3.4.3
Discontinuation of the trial by the sponsor
BI reserves the right to discontinue the trial overall or at a particular trial site at any time for 
the following reasons:
1. Failure to meet expected enrolment goals overall or at a particular trial site
2. Violation of GCP, or the CTP by a trial site or investigator, or the contract with BI 
impairing the appropriate conduct of the trial
3. The sponsor decides to discontinue the further development of the investigational 
product
4. New toxicological findings, SAEs, or any safety information invalidating the earlier 
positive benefit-risk assessment
The investigator/the trial site will be reimbursed for reasonable expenses incurred in case of 
trial termination (except in case of the fourth reason).
The dose escalation/staggering and trial treatment will be stopped for all patients in the 
ongoing dose groups once the sponsor becomes aware of one of the following 3 scenarios: 
1. More than 50% of the patients at one dose level show drug-related and clinically relevant 
AEs of moderate (CTCAE grade 2) or severe (CTCAE grade 3 and 4) intensity
2. If at least 1 drug-related SAE is reported 
3. If severe non-serious AEs considered as drug-related by the investigator in 2 patients of 
the same dose group (14 patients) occur.

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These cases will be reviewed by the DEC considering individual patient and cumulative data, 
to decide on:
1. Proceeding with treatment and randomization in the ongoing dose groups 
2. Further randomization and enrolment for the next dose group
3. The discontinuation of the trial 
31. Details are described in the DEC charter.
32.
Further treatment and follow-up of trial participants affected will occur as described in 
Section 3.3.4.1.
3.3.5
Replacement of patients
If some patients do not complete the trial (including patients non-evaluable for PK), they may 
be replaced if considered necessary to reach the objective of the trial. The CTL together with 
the Trial Clinical Pharmacologist and the TSTAT are to decide if and how many patients will 
be replaced.
Additional trial participants may be recruited to replace trial participants who discontinue 
participation early for non-safety related reasons (e.g. unable to attend the protocol defined 
visits for personal reason) or trial disruption (e.g. measures to control the spreading of 
COVID 19). Trial participants may only be replaced prior to Week 7 and after an agreement 
with the sponsor. Trial participants who do not complete 12 weeks of treatment due to 
disruption related to COVID-19 will be replaced.
A replacement patient will be assigned a unique trial subject number and will be assigned to 
the same treatment as the patient he or she replaces. In case of patient replacement needed, 
previous cohort should be prioritized first, before continuing with randomization in following 
cohort to avoid missing patients in cohorts.

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4.
TREATMENTS
4.1.1
Identity of the Investigational Medicinal Products
Table 4 and Table 5 display the characteristics of the investigational medicinal products to be 
administered in this trial.

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4.1.2
Selection of doses in the trial and dose modifications
 have been selected in order to assess the 
safety, tolerability, PK, and PD of the novel dual GLP-1 and FGF21 receptor agonist 
BI 3006337 in trial participants with overweight/obesity and steatosis. The selected doses 
cover a safe starting dose in the sub-therapeutic range, the estimated therapeutic range, and 
potentially supra-therapeutic doses within the levels determined by toxicological 
investigations (see Section 1.2).
4.1.3
Method of assigning trial participants to treatment groups
After the assessment of all in- and exclusion criteria, each eligible patient will be assigned to 
treatment groups in a 5:2 ratio with IMP or placebo administration. Randomisation will be 
performed at Visit 2 using a randomisation centre and Interactive Response Technology 
(IRT) system to allocate patients to treatment groups. Note that the medication number is 
different from the patient number (the latter is generated during screening via the IRT 
system). If a patient withdraws from the trial, then the enrolment code cannot be re-used. For 
further details, refer to Section 7.4.
4.1.4
Drug assignment and administration of doses for each trial participant
The treatments to be evaluated in this trial are described in Section 3.1 and outlined in Table 
3. The dose volume for placebo corresponds to the dose volume of the respective dose level.
The syringes containing the s.c. solutions for administration (BI 3006337 or placebo) will be 
prepared by qualified medical trial personnel at the trial site under the responsibility of the 
investigator according to the Medication Handling Instruction provided by the sponsor. The 
investigator can decide at any time to discontinue dosing in case of intolerability or safety 
concerns.
On the treatment days (see Flow Chart), BI 3006337 or placebo will be administered by the 
investigating physician or authorised designee to the trial participant by s.c. injection into a 
lifted skin fold of the abdominal wall while lying in supine position. The injection needle has 
to be placed at a 45-degree angle and injected into the skin fold over at least 15 s. Skin is 
sanitized before injection. For administration, syringe sizes dependent on the administered 
volume 
, will be used). If the volume exceeds 
2 mL, the dose will be divided into 2 syringes and will be injected into 2 different injection 
sites on the same side of the abdomen wall. The subsequent doses should be administered on 
the alternate side of the abdominal wall. Following s.c. injection, the trial participant should 
remain in a supine position for at least 30 min. Injection sites will be specified by naming the 
quadrant of the abdomen in which the injection will be done (upper right quadrant; upper left 
quadrant; lower left quadrant; lower right quadrant).
For drug administration, the so-called four-eye principle (two-person rule) should be applied. 
For this, one authorised employee of the trial site should witness the administration of trial 
medication, and – if applicable – its preparation (e.g. reconstitution), if correct dosage cannot 
be ensured otherwise.
Administration of BI 3006337 or placebo will be performed by the investigator or authorised 
designee following an overnight fast, which is to start no later than 10 h before the scheduled 

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dosing until at least 1.5 h after dosing. Water may be consumed ad libitum except for 1 hour 
before and 1.5 h after drug administration. Predefined meals will be served as outlined in the 
Flow Chart. For restrictions with regard to diet see Section 4.2.2.2.
Trial participants will be kept under close medical surveillance until at least 48 h after drug 
administration during hospitalisation and until at least 2 h after drug administration at the 
ambulatory visits. Hypersensitivity reactions should be treated according to medical 
standards (see Section 4.2.1).
In the event of force majeure or other disrupting circumstances (e.g. pandemic, war, please 
see Section 6), physical participant visits to the sites may not be feasible or may need to be 
restricted to ensure participant safety. Based on a thorough assessment of the benefits and 
risks, the investigator may still decide to continue trial treatment. Where permitted by local 
law and regulations, trial medication may be shipped directly to the participants’ home. In 
agreement with the sponsor, a home visit service or telemedicine may assist the participant 
with medication administration.
Missed doses
If a dose is missed on the planned dosing day, subjects should take the planned dose within 
48 h. If more time has elapsed since the missed dose, subjects should wait to take the next 
planned dose.
The total number of skipped doses during the trial must not exceed 3 doses. Skipping more 
than 3 doses will be considered as non-compliance of trial medication, and the patient will 
have to discontinue the trial medication. In case of 3 consecutive skipped doses, treatment 
discontinuation may be considered, and the sponsor may be contacted for alternative options.
4.1.5
Blinding and procedures for unblinding
4.1.5.1
Blinding
The trial is designed as a single-blind. The treatments administered (BI 3006337 or placebo) 
will be blinded to the trial participants but will be known to the investigators (outcome 
assessors). Only the current dose level will be known to the trial participants due to the rising 
dose design (see Section 3.2).
A single–blind design is considered acceptable because the potential bias in this type of trial
seems to be low and according to trial procedures it is assured that the investigator's 
knowledge of the next treatment does not influence the decision to enter a trial participant.
All trial data will be handled open label. This means that trial functions of the sponsor are 
unblinded (including clinical monitor, data manager, statistician, bioanalyst, 
pharmacokineticist, pharmacometrician, drug metabolism scientist as well as dedicated 
personnel of the trial site). This is considered acceptable because the potential for bias seems 
to be low and does not outweigh practical considerations.
Within the central ECG lab, the staff involved with interval measurements and morphological 
analyses will be blinded with respect to the treatment and also with regard to the recording 
date and time as well as planned time points of the ECGs. The interval measurements for a 
given trial participant will be performed by board certified cardiologists.

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Also the staff of the central MRI lab will be blinded.
Access to the randomisation schedule will be controlled and documented.
4.1.5.2
Emergency unblinding and breaking the code
As this trial will be conducted in a single-blind design, the trial participants’ treatment 
assignments will be known to investigators. Therefore, no emergency envelopes will be 
provided.
4.1.6
Packaging, labelling, and re-supply
The investigational medicinal products BI 3006337 and placebo will be provided by BI. They 
will be packaged and labelled in accordance with the principles of Good Manufacturing 
Practice.
For details of packaging and the description of the labels, refer to the ISF.
The telephone number of the sponsor and the name, address, and telephone number of the 
trial site are provided in the patient information form. Re-supply to the sites will be managed 
via an IRT system, which will also monitor expiry dates of supplies available at the sites.
4.1.7
Storage conditions
Drug supplies will be kept in their original packaging and in a secure limited access storage 
area according to the recommended storage conditions on the medication label. If necessary, 
a temperature log must be maintained to make sure that the drug supplies are stored at the 
correct temperature.
If the storage conditions are found to be outside the specified range, the local CRA (as 
provided in the list of contacts) has to be contacted immediately.
4.1.8
Drug accountability
The investigator or designee will receive the investigational drugs from the sponsor when the 
following requirements are fulfilled:
1. Approval of the CTP by the IRB/ethics committee
2. Availability of a signed and dated clinical trial contract between the sponsor and the 
investigational site
3. Approval/notification of the regulatory authority, e.g. CA
4. Availability of the curriculum vitae of the Principal Investigator
5. Availability of a signed and dated CTP
6. Availability of FDA Form 1572 (if applicable)
Investigational drugs are not allowed to be used outside the context of this CTP. They must
not be forwarded to other investigators or clinics. Trial participants should be instructed to 
return unused investigational drugs.

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Only authorised personnel documented in the form ‘Trial Staff List’ may dispense medication 
to trial participants. The trial medication must be administered in the manner specified in this
CTP.
The investigator or designee must maintain records of the product’s delivery to the trial site, 
the inventory at the site, the use by each trial participant, and disposal of unused products.
These records will include dates, quantities, batch/serial numbers, expiry (‘use- by’) dates, 
and the unique code numbers assigned to the investigational medicinal product and trial
participants. The investigator or designee will maintain records that document adequately that 
the trial participants were provided the doses specified by the CTP and reconcile all 
investigational medicinal products received from the sponsor. At the time of disposal of 
remaining trial medication, the investigator or designee must verify that no remaining 
supplies are in the investigator’s possession.
All unused trial medication will be disposed of locally by the trial site upon written 
authorisation of the CTL. Receipt, usage, and disposal of trial medication must be 
documented on the appropriate forms. Account must be given for any discrepancies.
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS
4.2.1
Other treatments and emergency procedures
Except for acetaminophen administration to perform the acetaminophen absorption test (see 
Section 4.2.1.1), no additional treatment is planned. However, in case of AEs in need of 
treatment, the investigator can authorize symptomatic therapy. In those cases, trial 
participants will be treated as necessary and, if required, kept under supervision at the trial 
site or transferred to a hospital until all medical evaluation results have returned to an 
acceptable level.
Prolonged or severe GI events
There are no special emergency procedures to be followed. Most frequent AEs of 
GLP-1 and FGF21 receptor agonists are nausea and vomiting. In case of prolonged or severe 
vomiting, the investigator will monitor serum creatinine, if deemed necessary. If nausea or 
vomiting are not amenable to conservative management, anti-emetics (e.g. dimenhydrinate, 
metoclopramide, granisetron, or ondansetron) may be administered at the investigator’s 
discretion.
Hypoglycaemic events
Symptoms of mild to moderate hypoglycaemia, or blood glucose levels below 49 mg/dL 
(measured using a bedside glucose test) can be treated by ingestion of carbohydrates (e.g. 
stepwise in defined amounts of 10 g). Typical clinical signs of mild or moderate 
hypoglycaemia include cold sweats, cool pale skin, nervousness or tremor, anxious feeling, 
unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive 
hunger, temporary vision changes, headache, nausea, and palpitations. Severe hypoglycaemia 
may lead to unconsciousness. Trial participants experiencing hypoglycaemia should remain 
confined until the symptoms have improved and resolved, blood glucose is within or above 
the normal range, and the investigating investigator deems the trial participant safe for 
discharge.

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Hypoglycaemic events will be recorded as AEs if symptomatic, or if serum glucose levels 
(local safety laboratory) are below 54 mg/dL or blood glucose levels (bedside test) are below 
49 mg/dL (see Section 5.2.6.2.4).
Suicidality
In case of signals of suicidal ideation or behaviour, the Investigator should discontinue
treatment with the trial medication, notify the Sponsor and the patient should be referred to an
appropriate psychiatric clinic.
Systemic hypersensitivity
In case of any systemic hypersensitivity including anaphylactic reaction emerging during or
after injection(s) of trial medication, the investigator should:

Immediately stop further injections for this individual subject

Treat in accordance with severity of the reaction and local standard of care, with
systemic antihistamines, i.v. steroids, and in case of a severe allergic reaction (eg, 
anaphylactic reaction), epinephrine

Draw a blood sample for the evaluation of IgE, histamine, serum tryptase, and
complement components (see laboratory manual in the ISF)

When a delayed hypersensitivity reaction is suspected, please draw a blood sample for
laboratory assessment and evaluate for signs of extra-cutaneous organ involvement. The
decision to discontinue treatment and/or restart treatment after resolution of the reaction
should be based on reaction type and severity.

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4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
In principle, no concomitant therapy is allowed, except mentioned in Section 4.2.1. All 
concomitant or rescue therapies will be recorded (including time of intake on trial days) on 
the appropriate pages of the CRF. The following medications are prohibited during the entire 
duration of the trial (also during screening): 

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




While enrolled in this trial, trial participants must not participate in another investigational 
drug or device trial or receive other investigational treatment(s).
4.2.2.2
Restrictions on diet and lifestyle
While admitted to the trial site, the trial participants will be instructed not to consume any 
foods or drinks other than those provided by the staff. Predefined meals will be served at the 
times indicated in the Flow Chart.
For s.c. administration of the trial medication (BI 3006337 or placebo), the trial participant
will be fasting for at least 10 h before and 1.5 h after dosing. During this fasting period, liquid 
intake will be limited to water, which may be consumed ad libitum apart from 1 hour before 
and 1.5 h after drug administration.
Additionally:

Total fluid intake should be at least 1.5 litres and should not exceed 3.5 litres.

Alcoholic beverages consumption and smoking is not allowed during stay at the trial 
site.

Methylxanthine-containing drinks or foods (such as coffee, tea, cola, energy drinks,
and chocolate) are not allowed from 12 h before until 8 h after administration of trial 
medication (BI 3006337 or placebo).

Excessive physical activity (such as competitive sport) should be avoided starting 
5 days before the BI 3006337 application until the EOS examination.

Direct exposure to the sun or exposure to solarium radiation should be avoided during 
the entire trial.
4.2.2.3
Contraception requirements
WOCBP (for definition refer Section 3.3.2) and their male sexual partner must use two
medically approved methods of birth control during the treatment period and for a period of
at least 3 weeks after last trial drug intake. Male partner of a WOCBP trial participant who is
able to father a child must use a condom.
WOCBP (trial participant) must use a highly effective method of birth control per ICH M3
(R2) that results in a low failure rate of less than 1% per year when used consistently and

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correctly.

Combined (estrogen and progestogen containing) hormonal birth control that prevents 
ovulation (oral, intravaginal, transdermal)

Progestogen-only hormonal birth control that prevents ovulation (oral, injectable, 
implantable)

Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion

If male partner of a trial participant is vasectomised with documented absence of sperm, 
no further contraception methods are required
Male trial participants must refrain from donating sperm and use condom if their sexual 
partner is a WOCBP during the treatment period and until 3 weeks after the last dose of trial 
medication. As BI 3006337 is non-genotoxic, a time interval of the REP is considered 
sufficient. No contraception is required for the male participant’s partner.
Or
Trial participants must abstain from male-female sex. This is defined as being in line with the 
preferred and usual lifestyle of the trial participant. Periodic abstinence e.g. calendar, 
ovulation, symptothermal, post-ovulation methods; declaration of abstinence for the duration 
of exposure to study drug; and withdrawal are not acceptable.
4.3
TREATMENT COMPLIANCE
Compliance will be assured by administration of all trial medication in the trial centre under 
supervision of the investigating physician or a designee. The measured serum concentrations 
of trial medication will provide additional confirmation of compliance.
Trial participants who are non-compliant (for instance, who do not appear for scheduled visits 
or violate trial restrictions) may be removed from the trial and the CRF will be completed 
accordingly (for further procedures, please see Section 3.3.4.1).

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5.
ASSESSMENTS
5.1
ASSESSMENT OF EFFICACY
5.1.1
Magnetic Resonance Imaging for Proton Density Fat Fraction
MR imaging will be used to assess the liver fat content in the whole liver by way of proton 
density fat fraction (PDFF) at the time points specified in the Flow Chart. Therefore, sites must 
be equipped or collaborating with a site equipped with an MRI scanner from the following 
manufacturers: 
 Ideally the MRI scanner should be 
equipped with a manufacturer specific MRI-PDFF package also known as multi-echo, multi-
peak Dixon techniques. All imaging sites will undergo a quality assessment process prior to 
trial initiation based on a review of MRI hardware and software. 
Data transfer
All MR images will be transferred electronically to the central MR images lab 
 
for evaluation. For the screening visit the transfer has to be made as soon as 
possible to allow for a timely evaluation of the core lab.
 will conduct quality control 
to ensure adherence to the imaging protocol and sufficient image quality (e.g., correct MR 
sequences, appropriate liver coverage). If the images fail to meet the required standard, the 
site will be informed, and the participant will be asked to undergo a repeat scan within a 
reasonable timeframe. If the second MR scan fails quality control or the participant declines a 
repeat scan, the MR scan from that visit will be deemed unusable for analysis. It is essential 
to obtain MR scans correctly and promptly. 
Data transfer from the central MR images lab to the sponsor and the CRO is described in the 
ECG data transfer agreement (see TMF).

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5.2
ASSESSMENT OF SAFETY
At screening, the medical examination will include demographics, height, and BW, smoking 
and alcohol history (results not mandatory to be entered into CRF or to be reported), relevant 
medical history and concomitant therapy, review of inclusion and exclusion criteria, review 
of vital signs (temperature, BP, and PR), 12-lead ECG, laboratory tests, a physical 
examination and C-SSRS completion. At the EOS examination, it will include review of vital 
signs, 12-lead ECG, laboratory tests, a physical examination including determination of BW 
and potential injection site reactions as well as recording of AEs and concomitant therapies, 
and C-SSRS completion.
5.2.1
Physical examination
A complete physical examination will include at a minimum general appearance, neck, lungs, 
cardiovascular system, abdomen, extremities, and skin. The results must be included in the 
source documents available at the site. For the time points of the physical examination, refer 
to the Flow Chart.
5.2.2
Vital signs
Systolic and diastolic BPs as well as HR (HR is considered to be equal to PR) will be 
measured by a BP monitor at the times indicated in the Flow Chart. The measurement will be 
performed after trial participants have rested for at least 5 min in a supine position. All 
recordings should be made using the same type of BP recording instrument on the same arm, 
if possible. Body temperature will also be measured.
The results must be included in the source documents available at the site.
At dosing visits for subcutaneous drug administration, vital signs evaluations (BP, PR) will 
be performed pre-dose and at 30 min after the end of drug administration. Additional 
measurements will be also performed after the end of drug administration at the dosing visits. 
Any new clinically relevant abnormal findings should be recorded as AEs or SAEs and 
should be followed up and/or treated as medically appropriate per local standards.
See Sections 4.1.4 and 4.2.1 for the monitoring for signs and symptoms of hypersensitivity 
reactions
5.2.3
Safety laboratory parameters
For the assessment of laboratory parameters, blood and urine samples will be collected by the 
trial site at the times indicated in the Flow Chart after the trial participants have fasted for at 
least 10 h. For retests, at the discretion of the investigator or designee, overnight fasting is not 

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required. The parameters that will be determined are listed in Table 7 and Table 8 ranges will 
be provided in the ISF, Section 10 for parameters listed in Table 7.
Manual differential WBC count or urine sediment examinations will only be performed if 
there is an abnormality in the automatic blood cell count or in the urinalysis, respectively.
In case the criteria for hepatic injury are fulfilled, a number of additional measures will be 
performed (please see Section 5.2.6.1) and the DILI Checklist provided in the ISF or eDC 
system. The amount of blood taken from the trial participant concerned will be increased due 
to this additional sampling. Instructions regarding sample collection, sample
handling/processing, and sample shipping are provided in the Laboratory Manual.
The central laboratory will transfer the results of the analysis to the sponsor or delegate.
Table 7
Routine laboratory tests
Functional lab 
group
Test name
A
B
C
D
E
F
Haematology
Haematocrit
Haemoglobin
RBC Count/Erythrocytes 
Reticulocytes, absol.
WNC/Leucocytes 
Platelet Count/Thrombocytes (quant)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
--
X
X
X
X
X
X
--
--
--
--
--
Automatic WBC 
differential 
(relative and 
absolute)
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
X
X
X
X
X
--
--
--
--
Manual differential 
WBC (if automatic
differential WBC is 
abnormal)
Neut. Poly (segs); Neut. Poly (segs), relat.; 
Neutrophils Bands; Neutrophils Bands, relat.; 
Eosinophils/Leukocytes; Eosinophils, relat.; 
Basophils/Leukocytes; Basophils, relat.; 
Monocytes/Leukocytes; Monocytes, relat.; 
Lymphocytes/Leukocytes; Lymphocytes, relat.
X
X
X
--
X
--
Coagulation
Activated partial thromboplastin time 
Prothrombin time – (Quick and INR)
X
X
X
X
X
X
--
--
X
X
--
--
Enzymes
AST/GOT, SGOT 
ALT/GPT, SGPT
ALP
GGT 
CK
CK Isoenzyme MB [only if CK is elevated] 
Lactate Dehydrogenase 
Lipase
Amylase
Calcitonin
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
--
--
--
--
--
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
--
--
--
--
--
Hormones
TSH
X
--
--
--
--
X
Urinalysis (Stix)
Urine Nitrite (qual)
Urine Protein (qual)
Urine Glucose (qual)
Urine Ketone (qual)
Urobilinogen (qual)
Urine Bilirubin (qual)
Urine RBC/Erythrocytes (qual)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
--
--
X
X
X
X
X
X
X
--
--
--
--
--
--

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Functional lab 
group
Test name
A
B
C
D
E
F
Urine WBC/Leucocytes (qual)
Urine pH
X
X
X
X
X
X
--
--
X
X
--
--

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Table 7 (cont'd)
Routine laboratory tests 
Functional lab 
group
Test name
A
B
C
D
E
F
Substrates
Glucose (NaF plasma)
Insulin
HbA1c
Creatinine 
Bilirubin, Total 
Bilirubin, Direct
C-Peptide
Protein, Total
C-Reactive Protein (Quant)
Uric Acid 
Cholesterol, total 
Triglyceride
High density lipoprotein (HDL) cholesterol
Low density lipoprotein (LDL) cholesterol
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
--
--
--
--
--
--
--
X
X
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
--
--
--
--
--
--
--
--
Electrolytes
Calcium
Sodium
Potassium
Inorganic phosphate
X
X
X
X
X
X
X
X
X
X
X
X
--
--
--
--
X
X
X
X
--
--
--
--
Urine sediment 
(microscopic 
examination if 
erythrocytes, 
leukocytes nitrite 
or protein are 
abnormal in urine)
Only positive findings will be reported (for 
instance, the presence of sediment bacteria, casts 
in sediment, squamous epithelial cells, 
erythrocytes, leukocytes)
X
X
X
--
X
--
PCR Test
SARS-CoV-2
X
--
--
--
--
--
Serum pregnancy 
test (only for 
female participants 
of childbearing 
potential at Visit 1
and if urine 
pregnancy test is 
positive at other 
visits
Human Serum Chorionic Gonadotropin
X
--
--
--
--
--
Urine pregnancy 
test
Urine Chorionic Gonadotropin
--
--
--
--
--
X
A: parameters to be determined at Visit 1 (screening examination) 
B: parameters to be determined at Visit 2 on Day -1 (for time points refer to Flow Chart)
C: parameters to be determined at Visit 2 on Day 1, Day 2 and Day 3, Visit 3 on Day 4, Visit 4 on Day 8, Visit 5 on Day 15 
and Day 17, Visit 7 on Day 22, Visit 8 on Day 29, Visit 9 on Day 36, Visit 11 on Day 50, Visit 13 Day 64, 
Visit 15 Day 79 and Day 80 (for time points refer to Flow Chart)
D: parameters to be determined at Visit 2 on Day -1, Visit 3 on Day 4, Visit 5 on Day 15, Visit 6 on Day 18, Visit 7 on 
Day 22, Visit 10 on Day 43, Visit 12 on Day 57, Visit 14 on Day 71, Visit 16 on Day 81 (for time points refer to Flow 
Chart)
E: parameters to be determined at Visit 18 (EOS examination)
F: parameters to be determined at Visit 2 on Day-1, Visit 7 on Day 22, Visit 12 on Day 57, Visit 15 on Day 79 and Visit 18
(EOS examination)
In case of systemic hypersensitivity including anaphylactic reaction emerging during or the 
investigator should consider in accordance with severity of the reaction and local standard of 

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care to evaluate IgE, histamine, serum tryptase, and complement components (see Section 
4.2.1).
A bedside glucose test will be performed for safety reasons as indicated in the Flow Chart.  
For quantification of blood glucose, 1 drop (50 μL) of blood taken from a fingertip will be 
sufficient. The results will be listed in the trial report but will not enter statistical analysis.
The tests listed in Table 8 are exclusionary laboratory tests that may be repeated as required. 
The results will not be entered in the CRF/database and will not be reported in the CTR. 
Except for drug screening, it is planned to perform these tests at SCR only. Drug screening
will be performed at SCR and at the beginning of Visit 2, Visit 3, Visit 5 and Visit 15.
The investigator will use the exclusionary lab test results for the assessment of the 
participants’ eligibility for the trial. The lab results will not be reported to the sponsor.
Table 8
Exclusionary laboratory tests
Functional lab group
Test name 
Drug screening (urine)
Amphetamine/MDA
Barbiturates
Benzodiazepine
Cannabis
Cocaine 
Methadone
Methamphetamines/MDMA/XTC
Opiates 
Phencyclidine
Tricyclic antidepressants
Infectious serology (blood)
Hepatitis B surface antigen (qualitative)
Hepatitis B core antibody (qualitative)
Hepatitis C antibodies (qualitative)
HIV-1 and HIV-2 antibody and HIV-1 p24 Antigen (qualitative)
To encourage compliance with alcoholic restrictions, a breath alcohol test (e.g. Alcotest®
65107410 or 55106810,
 will be performed prior to the treatment 
period and may be repeated at any time during the trial at the discretion of an investigator or 
designee. The results will not be included in the CTR.
The laboratory tests listed in Table 7 and Table 8 will be performed at the central lab except 
for drug screening. Urine drug screening will be performed at central lab and either by local 
lab or the trial site. The SARS CoV 2 virus PCR test will be performed in the central lab or at 
local lab or trial site according to local requirements. 
Laboratory data will be transmitted electronically from the laboratory to the trial site.

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5.2.4
Electrocardiogram
5.2.4.1
12-lead resting electrocardiogram
Recording
Single standard twelve-lead resting ECGs (I, II, III, aVR, aVL, aVF, V1 - V6) will be 
recorded using a computerised electrocardiograph (ELI 150c,
) at the 
time points given in the Flow Chart.
Electrode placement will be performed according to the method of Wilson, Goldberger, and 
Einthoven at same locations within the subjects throughout the trial to allow proper 
comparisons of the ECGs.
To achieve a stable HR at rest and to assure high quality recordings, the site personnel will be 
instructed to assure a relaxed and quiet environment, so that all trial participants are at 
complete rest.
All ECGs will be recorded for a 10-second duration after trial participants have rested for at 
least 5 min in a supine position. ECG recording will always precede all other trial procedures 
scheduled for the same time point to avoid compromising ECG quality.
ECGs may be repeated for quality reasons for instance due to alternating current artefacts, 
muscle movements, or electrode dislocation. 
Additional (unscheduled) ECGs may be recorded for safety reasons. These ECGs are 
assigned to the prior scheduled time point in the sponsor’s database.
Storing
All ECGs will be stored electronically at the ECG core lab for a minimum of 30 years.
Data transfer
All ECGs will be transferred electronically to the central ECG lab 
for 
evaluation. For the screening and D-1 visits the transfer has to be made as soon as possible to 
allow for a timely evaluation of the core lab.
Unscheduled ECGs (for safety reasons) will be transferred to the central ECG lab but will not 
be included into the statistical analysis of interval lengths.
Data transfer from the central ECG lab to the sponsor and the CRO is described in the ECG 
data transfer agreement (see TMF).
Evaluation
a. Central ECG lab
The digital ECG recordings will be transmitted to the core lab for central reading by board 
certified cardiologists. This will include a semi-automated measurement of the cardiac 
intervals and a morphological interpretation.
The intervals RR, PR, QRS, and QT will be measured semi-automatically and on screen 
using the global superimposed 12 lead median beats in which each median beat is 
mathematically derived from the available 10 second-recording of the corresponding lead. 
The individual median beats are graphically displayed as temporally aligned and overlapped 
(or superimposed on) one on another. Global interval measurements are subsequently defined 
as the interval from the earliest onset of any viable lead to the latest offset of any viable lead.

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A mean RR interval will be assessed automatically from all the sinus node triggered
complexes recorded over the 10 s of the ECG. The cardiac QRS-axis will be assessed by the 
ECG machine’s algorithm.
HR and the QT interval corrected for HR (QTc e.g. QTcF and QTcB) will be determined by 
the sponsor (see Trial Statistical Analysis Plan for details).
The morphological interpretation of the ECGs will also be performed per ECG recording, 
independently of the quantitative measurement of the ECG parameters, and according to the 
coded list used by the ECG core lab and will include the following main categories rhythm 
analysis, ST segment morphology characterization, T and U wave morphology 
characterization. 
The ECG recordings will be evaluated and rated as normal, abnormal clinically significant / 
non clinically significant, or unable to evaluate, and the results will be reported to the site. 
The results will be made available for screening ECGs within 24 h after receipt of the ECGs 
at the core lab.
For blinding arrangements, see Section 4.1.5.1.
Evaluation of ECGs will comply with the ICH E14 guidance document and supplements 
[R07-4722, R16-0366] as well as the FDA requirements for annotated digital ECGs 
[R09-4830].
b. Trial site
V1 and V2/D-1 visits
At the screening visit V1 and at the visit V2/D-1, the investigator must perform a complete 
review of the ECG results from core lab to ensure the patient has met all the entry criteria for 
the study exclusion (see Section 3.3). Any pre-existing conditions should be recorded as 
baseline conditions. If the ECG is rated as abnormal, the investigator will have to determine 
if the abnormal findings are clinically significant. At the visit V2/D-1 an eligibility decision 
may be made based on the local reading of the ECG if the results of the central ECG have not 
been received, prior to randomisation visit.
V2/D1 pre dose visits
ECG recorded at the randomization visit V2/D1/pre dose should be evaluated by the 
investigator before the patient receives the first dose. If abnormalities are observed by the 
investigator for this ECG, it is strongly recommended that the investigator will wait until the 
results from central reading are available (after 24 h of receipt of the ECG), and the 
randomization visit should be rescheduled. To receive a fast feedback on this ECG it, again 
should be transferred to the core lab as soon as possible.
All other visits
All ECGs at the other scheduled visits should be also evaluated by the investigator who will 
have the responsibility of following up with the patient if there are any clinically significant 
findings present. It is strongly recommended to repeat 12-lead ECG recording and/ or a 
referral to a cardiologist and/or perform additional cardiac tests (e.g. cardiac enzymes) if 
there is an indication of significant abnormalities or in case of doubts.

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Abnormal findings, irrespective of whether they originate from central or local evaluation, 
will be reported as AEs (during the trial) or baseline conditions (at screening) if judged 
clinically relevant by the investigator.
Any ECG abnormalities will be monitored carefully and, if necessary, the trial participant 
will be removed from the trial and will be asked to see a medical specialist to receive the 
appropriate medical treatment.
5.2.5
Other safety parameters
5.2.5.1
Local tolerability
Assessment of the injection site should be performed after each s.c. drug administration as 
indicated in the Flow Chart and more frequently, if deemed necessary by the investigator. For 
assessment, the quadrant of the injection site will be captured in the eSource after injection. 
Local tolerability will be assessed by the investigator or authorised designee according to 
“swelling”, “induration”, “heat”, “redness”, “pain”, or “other findings” and will be captured 
in the eSource local tolerability page. Injection site reactions with clinically relevant findings 
must be recorded as AEs; specially, injection site reactions deemed as moderate as per the 
table in section 5.2.6.1.5 should be always recorded as AEs. For the severity of the AE please 
refer to Section 5.2.6.1.5. The diameter of the affected area will be measured. Digital 
photography (including a ruler to show the size in cm) should be used by the investigator to 
document clinically relevant injection site reactions.
5.2.5.2
Monitoring for hypersensitivity reactions
Trial participants will be kept under close medical surveillance until at least 48 h after drug 
administration during hospitalisation and until at least 2 h after drug administration at the 
ambulatory visits. Hypersensitivity reactions should be treated according to medical 
standards (see Section 4.2.1).
5.2.5.3
Suicidal risk assessment and reporting
The C-SSRS is an investigator-rated interview, developed by clinical experts in cooperation
with the FDA, assessing both suicidal behavior and suicidal ideation. It does not give a global
score but provides some categorical and some severity information specifically for behavior
and ideation.
The C-SSRS interview may be administered by any type of physician, psychologist, clinical
social worker, mental health counselor, nurse, or research coordinator with C-SSRS training.
It has a typical duration of five minutes and causes only a low burden on patients. At a
minimum, the interview consists of 2 screening questions related to suicidal ideation and 4 
related to suicidal behavior and may be expanded to up to 17 items in case of positive
responses. In this trial paper forms will be used for the assessment of the C-SSRS.
The C-SSRS has been widely used in large multinational clinical trials. The C-SSRS will be
administered at the screening visit (using the “baseline/screening” version) with the aim to
exclude subjects with a lifetime history of suicidal ideation and behavior. After the baseline
visit, the assessment “since last visit” will be performed at clinic visits as specified in the

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Flow Chart. The Investigator is to review positive and negative reports for plausibility and
clinical relevance. Doubtful reports may be repeated, or reports may be validated by a
consulting psychiatrist. If there is a positive report of suicidal behavior or suicidal ideation
type 4 or 5 after start of trial, the Investigator is to immediately interview the patient during
the clinic visits and advise the patient to consult with a psychiatrist. If the positive report is
confirmed, appropriate actions for the patient’s safety must be initiated. Treatment with trial
medication should be stopped, and patient should be discontinued from the trial (refer to 
section 3.3.4.1). Additionally, all C-SSRS reports of suicidal ideation type 4 or 5 and all 
reports of suicidal behavior must be reported as separate SAEs by the Investigator. For ‘Self-
injurious behavior, no suicidal intent’ (Type 11) standard AE / SAE reporting rules are to be 
applied. For each negative report (suicidal ideation type 1, 2 or 3) after start of the trial, the 
Investigator is to decide based on clinical judgment whether it represents an AE as defined in 
the protocol, and if it is considered an AE then it must be reported accordingly.
5.2.6
Assessment of adverse events
Data and information necessary for the thorough assessment of AEs, SAEs, and AESIs will 
be reported to the sponsor via eCRF. This may include specific data and information not 
prospectively specified in this protocol.
5.2.6.1
Definitions of adverse events
5.2.6.1.1
Adverse event
An AE is defined as any untoward medical occurrence in a trial participant or clinical 
investigation subject administered a medicinal product and which does not necessarily have 
to have a causal relationship with this treatment.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product.
The following should also be recorded on the appropriate eCRF(s) and BI SAE form (if 
applicable):
Worsening of the underlying disease or of other pre-existing conditions. Changes in 
vital signs, ECG, physical examination, and laboratory test results, if they are judged 
clinically relevant by the investigator
If such abnormalities already exist prior to trial inclusion, they will be considered as baseline 
conditions and should be collected in the eCRF only.
5.2.6.1.2
Serious adverse event
An SAE is defined as any AE, which fulfils at least 1 of the following criteria:

Results in death

Is life-threatening, which refers to an event in which the trial participant was at risk of 
death at the time of the event; it does not refer to an event that hypothetically might 
have caused death if more severe

Requires inpatient hospitalisation or prolongation of existing hospitalisation

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
Results in persistent or significant disability or incapacity

Is a congenital anomaly/birth defect

Is deemed serious for any other reason if it is an important medical event when based 
on appropriate medical judgement which may jeopardise the trial participant and may 
require medical or surgical intervention to prevent 1 of the other outcomes listed in 
the above definitions. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or 
convulsions that do not result in hospitalisation or development of dependency or 
abuse
5.2.6.1.3
Adverse events considered “Always Serious”
In accordance with the EMA initiative on Important Medical Events, BI has set up a list of 
AEs, which, by their nature, can always be considered to be ‘serious’ even though they may 
not have met the criteria of an SAE as described in Section 5.2.6.1.2.
The latest list of ‘Always Serious AEs’ can be found in the eDC system. A copy of the latest 
list of ‘Always Serious AEs’ will be provided upon request. These events should always be 
reported as SAEs as described in Section 5.2.6.2.2.
Cancers of new histology and exacerbations of existing cancer must be classified as a serious 
event regardless of the time since discontinuation of the trial medication and must be reported 
as described in Section 5.2.6.2, subsections ‘Adverse event collection’ and ‘Adverse event
reporting to sponsor and timelines’.
5.2.6.1.4
Adverse events of special interest
The term AESI relates to any specific AE that has been identified at the project level as being 
of particular concern for prospective safety monitoring and safety assessment within this trial, 
e.g. the potential for AEs based on knowledge from other compounds in the same class. 
AESIs need to be reported to the sponsor’s Pharmacovigilance Department within the same 
timeframe that applies to SAEs, please see Section 5.2.6.2.2.
The following are considered as AESIs:
Potential Severe DILI:
A potential severe Drug Induced Liver Injury (DILI) that requires follow-up is defined by any 
of the following alerts (alterations) of hepatic laboratory parameters:
For participants with abnormal aminotransaminase at baseline (defined as ALT or AST
>1.5x ULN):
A) Any one of the following alerts should trigger the DILI Checklist:
1. AST or ALT ≥2x baseline or ≥300 U/L (whichever occurs first); and concomitant TB 
>2x baseline
2. AST or ALT ≥2x baseline or ≥300 U/L (whichever occurs first); and concomitant 
INR >1.2x baseline
3. AST or ALT ≥2x baseline or ≥300 U/L (whichever occurs first) and any new or 
worsening signs and/or symptoms of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%)

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4. AST or ALT ≥3x baseline
These lab findings constitute a hepatic injury alert and the patients showing these lab 
abnormalities need to be followed up according to the DILI Checklist provided in the eDC 
system.
B) The following events should lead to immediate discontinuation of trial treatment
(active or comparator) in trial participants with abnormal AST and ALT at baseline:

Hepatic injury alerts number 1, 2 or 3

AST or ALT >5x baseline or >500 U/L (whichever occurs first)

Any magnitude of ALT or AST elevation above baseline and any new or worsening 
signs and/or symptoms of fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%)
For participants with normal/near normal levels of ALT and AST at baseline:
A) DILI checklist will be triggered by the following alterations of hepatic laboratory 
parameters: 
1. AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase) elevation ≥3x
ULN combined with an elevation of TB (total bilirubin) ≥2x ULN measured at the 
same visit, or in samples drawn within 30 days of each other, OR
2. Aminotransferase (ALT or AST) elevations ≥3x ULN and INR≥1.5x ULN measured 
at the same visit, or in samples drawn within 30 days of each other, OR
3. Aminotransferase (ALT or AST) elevations ≥3x ULN with new onset, or worsening 
of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%) OR
4. Aminotransferase (ALT or AST) elevations ≥5x ULN
These lab findings constitute a hepatic injury alert and the patients showing these lab 
abnormalities need to be followed up according to the DILI Checklist provided in the eDC 
system.
B) The following events should lead to immediate discontinuation of trial treatment
(active or comparator) in trial participants with normal AST and ALT at baseline:
•
Hepatic injury alerts number 1, 2 or 3
•
Hepatic injury alerts number 4, if persists >2 weeks
•
AST or ALT elevation >8x ULN
For participants with normal/near normal or abnormal aminotransaminase at baseline:
Following completion of the DILI Checklist, if the BI investigational drug cannot be 
excluded as a possible cause of DILI event, then discontinuation should be made 
permanent without rechallenge. If an alternative causality, e.g. acute viral hepatitis, is 
confirmed by the DILI Checklist evaluation, then BI investigational drug may be re-started if 
warranted.

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C) Further important considerations
In case of clinical symptoms of hepatic injury (icterus, unexplained encephalopathy, 
unexplained coagulopathy, right upper quadrant abdominal pain, etc.) without lab results 
(ALT, AST, total bilirubin) available, the investigator should make sure these parameters are 
analysed, if necessary, in an unscheduled blood test. Should the results meet the criteria of 
hepatic injury alert, the procedures described in the DILI checklist should be followed.
Additionally, with participants having a normal AST and ALT at baseline, the emergence 
of an isolated AST or ALT elevation between ≥3-fold and <5x ULN requires repeat testing 
within 72 h (AST, ALT, Total Bilirubin and INR). DILI Checklist is not required unless 
repeat testing triggers alerts 1, 2, 3, or 4.
Systemic hypersensitivity reactions including anaphylactic reaction
Any suspicion of severe systemic hypersensitivity reaction and of any potential cases of
anaphylaxis should be defined and assessed using the criteria discussed in the statement paper
from Sampson HA (Appendix 10.4; [R11-4890]). See Section 4.2.1 for procedures in case of
systemic hypersensitivity.
5.2.6.1.5
Intensity (severity) of adverse events
The intensity (severity) of adverse events should be classified and recorded in the eCRF 
according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 
released on 27 November 2017 [R18-1357]. 
The assessment of the injection site as per section 5.2.5.1 should be based on the following
criteria:

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Injection site reactions: (adapted from R08-1466 and R22-4429):
Injection site 
reaction
mild
moderate
severe
Erythema/redness1
2.5-5cm
5.1-10 cm
>10 cm
Induration/swelling1
2.5-5 cm and 
does not 
interfere with 
activity
5.1-10 cm or 
interferes with 
activity
>10 cm or prevents daily 
activity
Pruritus
itching 
localized to 
the injection 
site that is 
relieved 
spontaneously 
or in <48 h of 
treatment
itching beyond 
the injection 
site that is not 
generalized or 
itching 
localized to the 
injection site 
requiring >48 h
treatment
generalized itching causing 
inability to perform usual 
social and functional activities
Pain
does not 
interfere with 
activity
repeated use of 
non-narcotic 
pain reliever 
>24 h or 
interferes with 
activity
any use of narcotic pain 
reliever of prevents daily 
activity
Tenderness
Mild 
discomfort to 
touch
Discomfort 
with movement
Significant discomfort at rest
1Measured local reaction should be done at the greatest single diameter
5.2.6.1.6
Causal relationship of adverse events
Medical judgement should be used to determine the relationship between the AE and the BI 
investigational compound, considering all relevant factors, including pattern of reaction, 
temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant 
medication, concomitant diseases, and relevant history.
Arguments that may suggest that there is a reasonable possibility of a causal relationship 
could be:

The event is consistent with the known pharmacology of the trial drug

The event is known to be caused by or attributed to the drug class

A plausible time to onset of the event relative to the time of drug exposure

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
Evidence that the event is reproducible when the drug is re-introduced

No medically sound alternative aetiologies that could explain the event (e.g. pre-
existing or concomitant diseases, or co-medications)

The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome)

An indication of dose-response (i.e. greater effect size if the dose is increased, smaller 
effect size if dose is reduced)
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be:

No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days/weeks of 
drug administration; an allergic reaction weeks after discontinuation of the trial drug 
concerned)

Continuation of the event despite the withdrawal of the medication, considering the 
pharmacological properties of the compound (e.g. after 5 half-lives).
Of note, this criterion may not be applicable to events whose time course is prolonged 
despite removing the original trigger

There is an alternative explanation, e.g. situations where other drugs or underlying 
diseases appear to provide a more likely explanation for the observed event than the 
drug concerned

Disappearance of the event even though the trial drug treatment continues or remains 
unchanged
5.2.6.2
Adverse event collection and reporting
5.2.6.2.1
Adverse event collection
Upon enrolment into the trial, the trial participant’s baseline condition is assessed (e.g. by 
documentation of medical history/concomitant diagnoses), and relevant changes from 
baseline are noted subsequently.
Trial participants will be required to report any AEs and their time of onset and end, and 
intensity of these events. In addition, each trial participant will be regularly assessed by the 
medical staff throughout the clinical trial and whenever the investigator deems necessary. At
a minimum, trial participants will be questioned for AEs (and concomitant therapies) at the 
time points indicated in the Flow Chart. Assessment will be made using non-specific 
questions such as “How do you feel?”. Specific questions will be asked wherever necessary 
in order to describe an AE more precisely.
A carefully written record of all AEs shall be kept by the investigator in charge of the trial. 
Records of AEs shall include data on the time of onset, end time, intensity of the event, and 
any treatment or action required for the event and its outcome.
The following must be collected and documented:

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
From signing the informed consent onwards until the individual trial participant’s EOS
(please see Section 6.2.3):
all AEs (serious and non-serious) and all AESIs

After the individual trial participant’s EOS:
the investigator does not need to actively monitor the trial participant for new AEs but 
should only report any occurrence of cancer of new histology and trial drug related SAEs 
and trial drug related AESIs of which the investigator may become aware of by any 
means of communication, e.g. phone call. Those AEs should be reported on the BI SAE 
form (see Section 5.2.6.2.2), but not on the CRF
5.2.6.2.2
Adverse event reporting to the sponsor and timelines
The investigator must report SAEs, AESIs, and non-serious AEs which are relevant for the 
reported SAE or AESI, on the BI SAE form to the sponsor’s unique entry point immediately 
(within 24 h of becoming aware of the event, the country specific process will be described in
the ISF). The same timeline applies if follow-up information becomes available. In specific 
occasions, the investigator could inform the sponsor upfront via telephone in addition. This 
does not replace the requirement to complete and fax the BI SAE form.
With receipt of any further information on these events, follow-up reports have to be 
provided. For the follow-up information, the same rules and timeline apply as for the initial 
information. All (S)AEs, including those persisting after individual trial participant’s EOS,
must be followed up until they have resolved, have been assessed as ‘chronic’ or ‘stable’, or 
no further information can be obtained.
5.2.6.2.3
Pregnancy
In rare cases, pregnancy might occur in a clinical trial. Once a trial participant has been 
enrolled in the clinical trial and has taken trial medication, the investigator must report any 
drug exposure during pregnancy in a trial participant immediately (within 24 h) by means of 
Part A of the Pregnancy Monitoring Form to the sponsor’s unique entry point.
Similarly, potential drug exposure during pregnancy must be reported if a partner of a male 
trial participant becomes pregnant. This requires written consent of the pregnant partner.
Reporting and consenting must be in line with local regulations. The ISF will contain the trial 
specific information and consent for the pregnant partner.
The outcome of the pregnancy associated with the drug exposure during pregnancy must be 
followed up and reported to the sponsor’s unique entry point on the Pregnancy Monitoring 
Form for Studies (Part B).
The ISF will contain the Pregnancy Monitoring Form for Studies (Part A and B).
As pregnancy itself is not to be reported as an AE, in the absence of an accompanying SAE 
and/or AESI, only the Pregnancy Monitoring Form for Studies is to be completed. However,
an SAE and/or AESI associated with the pregnancy must be reported as described in 
Section 5.2.6.2.2.

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5.2.6.2.4
Hypoglycaemia
Hypoglycaemic events will be recorded as AEs if symptomatic, if serum glucose levels (local 
safety laboratory) are below 54 mg/dL or blood glucose levels (bedside glucose test) are 
below 49 mg/dL.
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
5.3.1
Assessment of pharmacokinetics
Date and clock times of drug administration and PK sampling will be recorded in the CRFs. 
PK sampling times and periods may be adapted during the trial based on information 
obtained during trial conduct (e.g. as a result of preliminary PK data), including addition of 
samples and visits, as long as the total blood volume taken per trial participant does not 
exceed 1050 mL. Such changes would be implemented via non-substantial CTP 
Amendments.
5.3.2
Methods of sample collection
5.3.2.1
Blood sampling for BI 3006337 pharmacokinetic analysis
For quantification of BI 3006337 concentrations in serum, 6.0 mL of blood will be drawn 
from an antecubital or forearm vein into a serum (SST_II_Advance_tube) blood drawing tube 
at the times indicated in the Flow Chart. Blood will be withdrawn by means of either an 
indwelling venous catheter or by venipuncture with a metal needle. The tube should be 
inverted 6 times (without shaking) and left upright at room temperature and undisturbed for 
30 to 60 min to allow the sample to thoroughly clot.
At a minimum, the sample tube labels should list BI trial number, trial participant number, 
visit, and planned sampling time. Further information such as matrix, analyte, and aliquot 
number may also be provided. The final instruction of blood sampling and processing will be 
written in a Laboratory Manual.
After completion of the trial, the samples may be used for further methodological 
investigations (e.g. for stability testing). However, only data related to the analyte (including 
, if applicable) will be generated by these additional investigations. The trial samples 
will be discarded after completion of the additional investigations, but not later than 5 years 
after the final CTR is archived.

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5.4
ASSESSMENT OF BIOMARKERS
This section refers to exploratory biomarkers. Established biomarkers of efficacy and safety 
are described and discussed in Sections 5.1 and 5.2. Further, 
 

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5.4.2
Methods of sample collection
For the measurement of the exploratory biomarkers, 13 mL of blood will be drawn from an 
antecubital or forearm vein at the time points indicated in the Flow Chart. Blood will be 
withdrawn by means of either an indwelling venous catheter or by venipuncture with a metal 
needle.
Detailed instructions for biomarker blood sampling, processing, storage, and shipment of the 
different biofluids are provided in a laboratory manual. All lab kit supplies will be provided 
by the central lab vendor designated by the sponsor.
All left over samples will be stored and used for not yet specified explorative investigations. 
Samples may be used for not yet specified biomarker analyses or method development. 
Results of these assessments will not be part of the CTR. The trial samples will be discarded 
after completion of any additional investigations but not later than 2 years after the CTR has 
been archived.
PD sampling times and periods may be adapted during the trial based on information 
obtained during trial conduct (e.g. as a result of preliminary PK/PD data), including addition 
of samples and visits, as long as the total blood volume taken from each trial participant does 
not exceed 1050 mL. Such changes would be implemented via non-substantial CTP 
Amendments.

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5.5.1
Methods and timing of sample collection
Detailed instructions on sampling, preparation, processing, shipment, and storage are 
provided in the laboratory manual. Samples will be collected prior to the IMP administration. 
For sampling timepoints, see Flow Chart.
Approximately 8.5 mL blood will be drawn for DNA, 10 mL for plasma and 8.5 mL serum 
banking purposes. Any analyses on DNA or plasma/serum samples will not be reported in the 
main CTR. Samples will be collected only in countries where all applicable local regulatory 
and ethics approvals have been obtained for biobanking.
5.6
OTHER ASSESSMENTS
Not applicable.
5.7
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements and will be 
performed in order to monitor safety aspects and to determine efficacy, PK, and PD markers 
of BI 3006337 in an appropriate way.

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6.
INVESTIGATIONAL PLAN
In the event of force majeure or other disruptive circumstances (e.g. pandemic, war) the 
execution of the investigational plan as per this CTP may not be feasible. With the consent of 
the trial participant, the sponsor and investigator may agree on alternative, back-up or rescue 
methodology which may include but will not be limited to virtual trial participant visits and 
assessments, home healthcare nurse visits, direct-to-participant/direct-from-participant
shipments of trial treatment or bio-sample pick up from the participant’s home. The 
implementation of these measures will depend on the trial participant’s consent, operational 
feasibility, local law, and regulations. If alternative methodology is implemented, the 
deviations from the original plan will be precisely documented.
6.1
VISIT SCHEDULE
The acceptable time window for the screening visit is provided in the Flow Chart. Exact 
times of measurements outside the permitted time window will be documented.
Trial measurements and assessments scheduled to occur ‘before’ trial medication 
administration are to be performed and completed within a 1-hour- or 2-hour- or 3-hour
period, respectively, prior to the trial drug administration (including blank values for PK and 
PD/biomarkers).
The acceptable deviation from the scheduled time for vital signs, ECG, and laboratory tests 
will be ± 30 min with exception for Visit 17 and EOS when a deviation from the scheduled 
time for all the planned trial activities of ± 120 min is acceptable.
The acceptable deviation from scheduled ambulatory and site admission visits will be ± 1 
day.
If several activities are scheduled at the same time point in the Flow Chart, the ECG should 
be the first and meal the last activity. Furthermore, if several measurements including 
venipuncture are scheduled for the same time, venipuncture should be the last of the 
measurements due to its inconvenience to the trial participant and possible influence on 
physiological parameters.
For planned individual serum and plasma concentration sampling times, refer to the 
Flow Chart. While these nominal times should be adhered to as closely as possible, the actual 
sampling times will be recorded and used for the determination of PK parameters.
If a trial participant misses an appointment (e.g. ambulatory visit), it will be rescheduled if 
possible. A time window of ± 1 day would be acceptable. The relevance of measurements 
outside the permitted time windows will be assessed no later than at the Report Planning 
Meeting. Remote visits may be performed in exceptional cases, please refer to Section 4.1.4
for details.
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
AEs and concomitant therapies will be recorded throughout the trial but will be specifically 
asked for at the time points indicated in the Flow Chart.

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6.2.1
Screening period
After having been informed about the trial at Visit 1, all trial participants will provide written 
informed consent in accordance with GCP and local legislation prior to enrolment in the trial. 
Additionally, a PCR test on SARS-CoV-2 will be performed. For information regarding 
physical examination, vital signs, laboratory tests (including drug and virus screening), and 
12-lead ECGrefer to Sections 5.2.1 to 5.2.4.
During the screening visit, demographics information will be collected. This includes:

Age on the day of informed consent (in years)

Sex (male, female in order to describe the trial participant`s sex at birth)

Gender identity (male, female, non-binary, not answered, or other in order to describe 
how the trial participant self-identifies, regardless of their genotypic or phenotypic 
sex) if 1) locally accepted (i.e. based on HA/EC/IRB acceptance, independent of 
acceptance by investigators or participants), 2) investigators are willing to ask, and 
3) participants are willing to reply

For women of childbearing potential, yes/no in order to characterize the trial 
participant population and as a basis for contraception 
6.2.2
Treatment period
On Day -1 of Visit 2, the trial participants will be admitted to the trial site and a urine drug 
screening will be done at this time point. 
and examination 
of laboratory parameters, 12-lead ECG as well as vital signs for the generation of baseline 
values will be performed. 
In the morning of Day 1 (i.e. the day with first administration of BI 3006337 or placebo), 
each trial participant will undergo the examination of laboratory parameters, 12-lead ECG, 
and vital signs prior to administration of BI 3006337 or placebo.
Each trial participant will receive weekly doses of trial medication (BI 3006337 or placebo) 
on Day 1 of Visit 2 (during hospitalization), Day 8 of Visit 4 (during ambulatory visit), 
Day 15 of Visit 5 (during hospitalization), Day 22 of Visit 7 (during ambulatory visit), 
Day 29 of Visit 8 (during ambulatory visit, Day 36 of Visit 9 (during ambulatory visit), 
Day 43 of Visit 10 (during ambulatory visit), Day 50 of Visit 11 (during ambulatory visit), 
Day 57 of Visit 12 (during ambulatory visit), Day 64 of Visit 13 (during ambulatory visit), 
Day 71 of Visit 14 (during ambulatory visit), and Day 78 of Visit 15 (during hospitalization
days) according to the randomized allocation.
The trial medication will be administered as s.c. injection by the investigating physician (or 
authorised designee). Details on treatments and procedures of administration are described in 
Section 4.1.4.
Trial participants will be kept under close medical surveillance for at least 48 h following s.c. 
administration of the trial medication during hospitalisation and for at least 2 h following s.c. 
administration of the trial medication during the ambulatory visits. The trial participants will 
then be allowed to leave the trial site after formal assessment and confirmation of their fitness 
by the investigator o
designee.

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For details on time points and procedures for collection of blood samples for PK analysis, 
analysis 
, refer to the Flow Chart and Section 5.3.2.
The safety measurements performed during the treatment period are specified in Section 5.2
and in the Flow Chart. For details on times of all other trial procedures, refer to the 
Flow Chart.
6.2.3
Trial completion
For physical examination, recording of vital signs, laboratory tests, recording of 12-lead 
ECGs, assessment of local tolerability at the injection site, and AE assessment during the 
EOS examination on Day 99 of Visit 18 (corresponding to the REP 3 weeks after the last 
administration of trial medication), see Sections 5.2.1 to 5.2.6.
Trial participants who discontinue before the end of the planned treatment period should 
undergo the EOS examination, see Flow Chart and Section 3.3.4.1.
A trial participant is considered to have completed the trial in case any of the following 
applies:

Completion of planned follow-up period (= EOS visit completed)

Lost to follow-up

Refusal to be followed-up

Death
If needed in the opinion of the investigator, after the EOS visit additional visits may be 
scheduled for continued safety monitoring.
All abnormal values (including laboratory parameters) that are assessed as clinically relevant 
by the investigator will be monitored using the appropriate tests until a return to a medically 
acceptable level is achieved. (S)AEs persisting after a trial participant’s EOS examination
must be followed until they have resolved, have been sufficiently characterized, or no further 
information can be obtained.

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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
The primary objective of this trial is to descriptively assess the frequency [N (%)] of trial 
participants with drug-related AEs. The primary endpoint is defined in Section 2.1.2.
The secondary objectives are to descriptively assess the PK parameters for BI 3006337 and to 
explore superiority of clinical efficacy versus placebo for BI 3006337 at the highest tolerated 
dose. Endpoints as specified in Section 2.1.3 will be analysed by descriptive statistics.
7.1
NULL AND ALTERNATIVE HYPOTHESES
Safety and tolerability of different dose groups of BI 3006337 are to be determined on the 
basis of the investigated parameters in comparison with placebo. It is not planned to test any 
statistical hypotheses with regard to these variables in a confirmatory sense. Instead, they will 
be described in their entirety and evaluated by descriptive statistical methods.
CIs will be computed and will have to be interpreted in the perspective of the exploratory 
character of the trial, i.e. CIs are considered as interval estimates for effects.
7.2
PLANNED ANALYSES
7.2.1
General considerations
The statistical analyses will be based on the following analysis sets.

Randomized set (RS): This trial participant set includes all randomised trial 
participants, whether treated or not.

Treated set (TS): The treated set includes all trial participants who were enrolled or 
randomised and treated with at least one dose of study drug. The treatment assignment 
will be determined based on the first treatment the trial participants received. The 
treated set will be used for safety analyses.

Pharmacokinetic parameter analysis set (PKS): This set includes all trial participants
in the treated set (TS) who provide at least one primary or secondary PK endpoint that 
was not excluded due to a protocol deviation relevant to the evaluation of PK or due 
to PK non-evaluability (as specified in the following subsection ‘Pharmacokinetics’). 
Thus, a trial participant will be included in the PKS, even if he contributes only one 
primary or secondary PK parameter value for one period to the statistical assessment. 
Descriptive and model-based analyses of PK parameters will be based on the PKS.

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Further analysis sets will be defined in the TSAP, if needed.
All individual efficacy, safety, and PK data will be listed.
Adherence to the protocol (such as inclusion/exclusion criteria, times of measurement, 
compliance with trial medication, treatment errors, prohibited concomitant medication, 
completeness, and consistency of data) will be assessed by the trial team. Important protocol 
deviation (IPD) will be identified no later than in the Report Planning Meeting, and the IPD 
categories will be updated as needed.
7.2.2
Handling of Intercurrent Events
The expected intercurrent events of interest in this trial are restricted to the Treatment Period 
and are defined as:

Premature treatment discontinuation of BI 3006337
The strategies for handling intercurrent events in this trial are as follows:
Treatment Policy: This is the effect of randomizing patients to a treatment arm regardless of
treatment actually being taken. All intercurrent events will be handled according to the
treatment policy approach as defined in ICH E9 (R1).
Each analysis will reference the strategy for handling intercurrent events that it will be
estimating. The estimand for each main analysis in this protocol is the combination of the
relevant detailed clinical objective from Section 2.1 and this strategy.
Handling of the intercurrent events that are not listed above will be decided by the review and
will be documented in the TSAP.
7.2.3
Primary objective analyses
The primary endpoint as specified in Section 2.1.2 will be derived according to BI standards.
Inferential statistics is not planned here. The analysis will be based on the treated set (TS) and
will be descriptive in nature. Refer to Section 7.2.6 for a description of the analysis of safety 
and tolerability, which are the primary objectives of this trial.
7.2.3.1
Sensitivity Analyses
Not applicable.
7.2.3.2
Subgroup Analyses
Not applicable.
7.2.3.3
Supplementary Analyses
Not applicable.

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7.2.4
Secondary objective analyses
The secondary endpoints (refer to Section 2.1.3) will be analysed descriptively.
Pharmacokinetic (PK) 
The PK parameters listed in Section 2.1 and 2.2 for BI 3006337 will be calculated using non-
compartmental analysis (see also Section 7.2.7). Noncompartmental PK parameters will be 
calculated based on actual sampling times using a validated PK software (e.g. Phoenix®
WinNonlin®).
Plasma concentration data and parameters of a trial participant will be included in the 
statistical PK analyses if they are not flagged for exclusion due to a protocol deviation 
relevant to the evaluation of PK (to be decided no later than in the Report Planning Meeting) 
or due to PK non-evaluability (as revealed during data analysis, based on the criteria 
specified below). Exclusion of a trial participant’s data will be documented in the CTR.
Relevant protocol deviations may be
•
Incorrect trial medication taken, i.e. the trial participant received at least one dose of 
trial medication the trial participant was not assigned to
•
Incorrect dose of trial medication taken
•
Use of restricted medications
Plasma concentrations and/or parameters of a trial participant will be considered as non-
evaluable, if for example
•
Missing samples/concentration data at important phases of PK disposition curve
Analysis will be evaluated of Pharmacokinetic parameter analysis set (PKS). Trial 
participants who are considered as not eligible for the PKS will be listed with their individual 
plasma concentrations and individual PK parameters, however, will not be included in 
descriptive statistics for plasma concentrations, PK parameters, or other statistical 
assessment.
Concentrations will be used for graphs and calculations in the format that is reported in the
bioanalytical report. Only concentrations within the validated concentration range will be
used for the calculation of PK parameters. Plasma concentrations will be plotted graphically 
versus time for all evaluable trial participants as listed in the drug plasma concentration
timetables. For the presentation of the mean profiles, the arithmetic mean and the planned
blood sampling times will be used.
The following descriptive statistics will be calculated for analyte concentrations as well as for
all PK parameters: N, arithmetic mean, standard deviation, minimum, median, maximum, 
arithmetic coefficient of variation, geometric mean, and geometric coefficient of variation. 
The data format for descriptive statistics of concentrations will be identical to the data format 
of the respective concentrations. The descriptive statistics of PK parameters will be 
calculated using the individual values with the number of decimal places as provided by the 

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evaluation program. Then the individual values as well as the descriptive statistics will be 
reported with three significant digits in the CTR.
Efficacy
Efficacy endpoints will be assessed: 
 
.
Trial participants who do not complete 12 weeks of treatment due to disruption related to 
COVID-19 will be replaced to achieve up to 100% sample size in each dose group; the main 
PoCP efficacy analysis will exclude these trial participants, 
 
; drop-outs due to other reasons will not be replaced and will be 
included in all analyses

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7.2.6
Safety analyses
Safety will be assessed from the further endpoints and parameters of interest listed in 
Section 2.2.2.1 based on the treated set (TS). Safety analyses will be descriptive in nature and 
will be based on BI standards.
For all analyses the treatment actually administered to the trial participant will be used (any 
deviations from the randomised treatment will be discussed in the minutes of the Report 
Planning Meeting).
Treatments will be compared in a descriptive way. Placebo group in the safety evaluation will 
consist of all trial participants treated with placebo, regardless of the dose group in which 
they were treated. The BI 3006337-treated groups will be compared with the placebo group 

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in a descriptive way. Tabulations of frequencies/proportions will be used for the evaluation of 
categorical (qualitative) data, and tabulations of descriptive statistics will be used to analyse 
continuous (quantitative) data.
Measurements (such as ECGs, vital signs, or laboratory parameters) or AEs will be assigned 
to treatments (see Section 4.1) based on the actual treatment at the planned time of the 
measurement or on the recorded time of AE onset (concept of treatment-emergent AEs). 
Therefore, measurements planned, or AEs recorded prior to first injection of trial medication 
will be assigned to the ‘screening’ period, those between the first trial medication injection 
and end of REP (see Section 1.2.5) will be assigned to the treatment period. Events occurring 
after the REP but prior to next injection or end of trial termination date will be assigned 
to ’follow-up’. These assignments including the corresponding time intervals will be defined 
in detail in the TSAP. Note that AEs occurring after the last per protocol contact but entered 
before database lock will be reported to Pharmacovigilance only and will not be captured in 
the trial database. Additionally, further treatment intervals (called analysing treatments) may 
be defined in the TSAP in order to provide summary statistics for other than above periods, 
such as combined treatments, on-treatment totals, or periods without treatment effects (such 
as screening and post-trial intervals).
AEs will be coded using MedDRA. All treated trial participants will be included in the safety 
analysis. In general, safety analyses will be descriptive in nature and will be based on BI 
standards. No hypothesis testing is planned.
Statistical analysis and reporting of AEs will concentrate on treatment-emergent adverse 
events, i.e. all AEs occurring between start of treatment and end of the REP. AEs that start 
before first drug intake and deteriorate under treatment will also be considered as ‘treatment-
emergent’.
Frequency, severity, and causal relationship of AEs will be tabulated by primary system 
organ class and preferred term. SAEs, AESIs (see Section 5.2.6.1.4) and other significant 
AEs (according to ICH E3) will be listed separately.
Laboratory data will be analysed both quantitatively as well as qualitatively. The latter will 
be done via comparison of laboratory data to their reference ranges. Values outside the 
reference range as well as values defined as clinically relevant will be summarised. Treatment 
groups will be compared descriptively with regard to distribution parameters as well as with 
regard to frequency and percentage of trial participants with abnormal values or clinically 
relevant abnormal values.
Vital signs, physical examinations, or other safety-relevant data observed at screening, 
baseline, during the course of the trial and at the end-of-trial evaluation will be assessed with 
regard to possible changes compared with findings before start of treatment.
7.2.7
Pharmacokinetic analyses
The pharmacokinetic parameters listed in Sections 2.1.3 and 2.2.2 for drug BI 3006337 will 
be calculated using non-compartmental analysis. Trial participant s who are not included in 

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the PKS (refer to Section 7.3.2) will be reported with their individual plasma and individual 
pharmacokinetic parameters; however, they will not be included in descriptive statistics for 
plasma pharmacokinetic parameters or other statistical assessment.
Only concentration values within the validated concentration range and actual sampling times 
will be used for the calculation of pharmacokinetic parameters. Noncompartmental PK 
parameters will be calculated based on actual sampling times using a validated PK software 
(e.g. Phoenix® WinNonlin®). Preliminary analysis will be based on planned sampling times 
(see Section 7.2.9). Concentrations used in the pharmacokinetic calculations will be in the 
same format provided in the bioanalytical report, (that is, to the same number of decimal 
places provided in the bioanalytical report).
The concentration taken before the first dose is generally below lower limit of quantification 
(BLQ). To perform a noncompartmental analysis, this concentration at time zero is set to 
zero. BLQ values in the lag-phase are also set to zero. The lag phase is defined as the period 
between time zero and the first time point with a concentration above the quantification limit. 
All other BLQ values are ignored, i.e. those occurring after a concentration above BLQ.
If a predose concentration value is greater than 5% of Cmax, the trial participant’s 
pharmacokinetic data will be not included in any statistical evaluations, in accordance with 
international guidance. The individual pharmacokinetic parameters of such a trial participant 
will be calculated and listed separately. If a predose concentration is above BLQ, but less 
than or equal to 5% of the trial participant’s Cmax value, the trial participant’s data without 
any adjustments will be included in all pharmacokinetic measurements and calculations. 
The area under the curve will be calculated using the linear up/log down algorithm: if a drug 
concentration is equal to or higher than the preceding concentration, the linear trapezoidal 
method is used. If the drug concentration is smaller than the preceding concentration, the 
logarithmic method is used.
The AUC,ss is calculated based on actual sampling times according to the following rules. If 
the dosing interval lies within the time frame of scheduled samplings but does not coincide 
with an observed sampling point, then a linear or logarithmic interpolation is done to estimate 
the corresponding drug plasma concentration at time t, according to the trapezoidal rule that 
applies. The prerequisite for this rule is plasma concentrations above the quantification limit. 
If the dosing interval goes beyond the time of the last quantifiable data observation and z 
cannot be estimated, various options may apply.
(1) No AUC,ss value is reported for this subject (not calculated = NC) 
(2) If reasonable, the pre-dose concentration at steady state may be used as concentration at 
the end of the dosing interval in order to determine AUC,ss.
(3) Alternatively, AUC0-tz,ss should be given instead (if reasonable for all subjects), where 
AUC0-tz,ss is the area under the concentration-time curve from the time point 0 after the 
last dose at steady state to the last quantifiable drug plasma concentration within the 
dosing interval . However, AUC,ss and AUC0-tz,ss should be considered as different 
parameters and should not be merged for combined descriptive statistics.

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Every effort should be made to include all concentration data in the PK and/or PD analysis. If 
not possible, a case-by-case decision is required whether the value should only be excluded 
from half-life estimation, descriptive statistics or the complete analysis. The excluded 
concentration will be listed in the PK/PD exclusion file and displayed in the concentration 
listings of the CTR with the respective flag. The following rules generally apply:
-
If a concentration is excluded from half-life determination only, it will be used for all 
parameter calculations, except the half-life determination, and it will be included for 
the calculation of descriptive statistics and for graphical presentation, 
-
If a concentration value is excluded from descriptive statistics, it is used for parameter 
calculation, but not included for calculation of descriptive statistics. The value may be 
presented graphically in displays that only show individual data based on actual times 
(timescale is based on planned time)., 
-
If a concentration value is excluded from further calculations, it is neither used for the 
calculation of parameters and descriptive statistics nor presented graphically in the 
CTR.
The decision to exclude a concentration value from the analysis should be justified in the 
CTR, and only the derived parameters obtained without the excluded concentration value 
should be presented throughout the CTR. However, in case of sensitivity analysis, derived 
parameters obtained with excluded concentration value may be presented as well with an 
appropriate flag.
Descriptive statistics of concentrations at specific time points are calculated by default when 
at least 2/3 of the individuals have concentrations within the validated concentration range. 
The overall sample size to decide whether the “2/3 rule” is fulfilled is based on the total 
number of samples that were drawn at the specific time point (i.e. BLQ, NOR, NOA and 
NOS are included).
 !"#$ %& '%'#($)( % *)+ #
(%()+  !"#$ %& )!,+#
≥2/3 (At a specific time point)
For assessment of dose proportionality, Linearity index and attainment of steady state, see 
Sections 7.2.4 and 7.2.5.
Graphical displays
To support the analyses of dose proportionality, linearity and attainment of steady state, 
graphical representations of the data might be created. These might include (but are not 
limited to) individual time-courses of trough plasma concentrations and the (geometric) mean 
plasma concentration time profiles.
Biomarker analysis
Intra-individual differences from baseline (Day -1 of Visit 2) will be calculated for all PD
endpoints (see Section 5.4). Data will be compared descriptively between DGs and placebo. 
The placebo group will consist of all subjects treated with placebo, regardless of the DG in 
which they were treated.
Additionally, for estimation purposes model-based analyses may be applied as appropriate:

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

More details will be provided in the TSAP.
7.2.9
Interim analysis
No interim analysis is planned. Unblinded exploratory analyses on the safety and tolerability, 
will be performed during the conduct of the trial to evaluate dose escalations.
A preliminary analysis of selected PK parameters of BI 3006337 (e.g. AUCτ,ss and Cmax,ss
after Week 3) as well as nausea/vomiting and HR provided as individual values and 
appropriate summary measures, will be performed for dose before proceeding to the next 
dose level or expanding the dose group on the highest tolerated dose level. Available 
concentration data up to at least Visit 6 will be used.
In contrast to the final PK/PD calculations, the preliminary analysis will be based on planned
sampling times rather than on actual times, regardless of whether actual times were within the
time windows. Therefore, minor deviations may occur between preliminary and final results.
The preliminary analysis will provide individual and mean concentration/effect-time profiles
and summary statistics of individual values without trial participant identification 
information. The preliminary results will be distributed to the investigator and the trial team.
Depending on the results of available preliminary PK/PD analyses and the tolerability and
safety of the compound, changes to the dosing schedule (e.g. additional intermediate doses),
and additional PK/PD preliminary analyses may be performed if requested by the Clinical
Trial Lead, the investigator or Trial Clinical Pharmacologist. Preliminary PK/PD results will 
not be reported in the CTR.
7.3
HANDLING OF MISSING DATA
7.3.1
Safety
It is not planned to impute missing values for safety parameters.
7.3.2
Pharmacokinetics
It is not planned to impute missing values for PK parameter calculations.

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PK parameters that cannot be reasonably calculated based on the available drug
concentration-time data will not be imputed.
7.4
RANDOMIZATION
Within each dose group, randomization will only be performed in Cohort 3 in a 5:3 ratio 
(BI 3006337 to placebo). The first two cohorts will follow fixed dosing.
BI will arrange for the randomisation and the packaging and labelling of trial medication. The 
randomisation list will be generated using a validated system, which involves a pseudo-
random number generator so that the resulting treatment will be both reproducible and non-
predictable. Specific parameters used for the creation of the randomization schedule (e.g.
block size or biasing coin probabilities) will be documented in the Clinical Trial Report. 
Access to the codes will be controlled and documented.
7.5
DETERMINATION OF SAMPLE SIZE
It is planned to enrol approximately 56 trial participants in this trial (the maximum number of 
trial participants will not exceed 72): the size of at least 14 trial participants per dose group 
(10 on BI 3006337 and 4 on placebo) is generally considered reasonable for the exploratory 
evaluation of multiple dose safety and PK.
Trial participants who cannot complete 12 weeks of treatment due to disruption related to 
COVID-19 will be replaced to achieve up to 100% sample size in each dose group.

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8.
INFORMED CONSENT, TRIAL RECORDS, DATA 
PROTECTION, PUBLICATION POLICY, AND
ADMINISTRATIVE STRUCTURE
The trial will be carried out in compliance with the CTP, the ethical principles laid down in 
the Declaration of Helsinki, in accordance with the ICH Harmonised Guideline for GCP,
relevant BI SOPs, the US Code of Federal Regulations, and other relevant regulations.
Investigators and site staff must adhere to these principles. Deviation from the CTP, the 
principles of ICH-GCP, or applicable regulations will be treated as ‘protocol deviation’.
Standard medical care (prophylactic, diagnostic, and therapeutic procedures) remains the 
responsibility of the treating physician of the trial participant.
The investigator will inform the sponsor immediately of any urgent safety measures taken to 
protect the trial participants against any immediate hazard, as well as of any serious breaches 
of the CTP or of ICH-GCP.
The BI transparency and publication policy can be found on the following web page: 
trials.boehringer-ingelheim.com. The rights of the investigator and of the sponsor with regard 
to publication of the results of this trial are described in the investigator contract. As a general 
rule, no trial results should be published prior to finalisation of the CTR.
The certificate of insurance cover is made available to the investigator and the trial 
participants and is stored in the ISF.
8.1
TRIAL APPROVAL, PATIENT INFORMATION, INFORMED CONSENT
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective IRB/IEC and CA according to national and international 
regulations. The same applies for the implementation of changes introduced by amendments.
Prior to participation in the trial, written informed consent must be obtained from each trial 
participant (or the trial participant’s legally accepted representative) according to ICH-GCP 
and to the regulatory and legal requirements of the participating country. Each signature must 
be personally dated by each signatory and the informed consent form, and any additional trial 
participant-information form retained by the investigator as part of the trial records. A signed 
copy of the informed consent and any additional trial participant information must be given to 
each trial participant or the trial participant’s legally accepted representative.
The trial participant must be given sufficient time to consider participation in the trial. The 
investigator or delegate obtains written consent of the trial participant’s own free will with 
the ICF after confirming that the trial participant understands the contents. The investigator or 
 delegate must sign (or place a seal on) and date the ICF. If a trial collaborator has given a 
supplementary explanation, the trial collaborator also signs (or places a seal on) and dates the 
informed consent.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions.
The consent and re-consenting process should be properly documented in the source 
documentation.

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8.2
DATA QUALITY ASSURANCE
A risk-based approach is used for trial quality management. It is initiated by the assessment 
of critical data and processes for trial participant protection and reliability of the results as 
well as identification and assessment of associated risks. An Integrated Quality and Risk 
Management Plan or alternative plan, in line with the guidance provided by ICH Q9 and 
ICH-GCP E6, documents the rationale and strategies for risk management during trial 
conduct including monitoring approaches, vendor management, and other processes focusing 
on areas of greatest risk.
Continuous risk review and assessment may lead to adjustments in the trial conduct, trial 
design, or monitoring approaches.
A quality assurance audit/inspection of this trial may be conducted by the sponsor, sponsor’s 
designees, or by IRB/IEC or by regulatory authorities. The quality assurance auditor will 
have access to all medical records, the investigator’s trial-related files and correspondence, 
and the informed consent documentation of this clinical trial.
8.3
RECORDS
CRFs for individual trial participants will be provided by the sponsor. For drug 
accountability, refer to Section 4.1.8.
8.3.1
Source documents
In accordance with regulatory requirements, the investigator should prepare and maintain 
adequate and accurate source documents and trial records that include all observations and 
other data pertinent to the investigation on each trial participant. Source data as well as 
reported data should follow the ‘ALCOA principles’ and be attributable, legible, 
contemporaneous, original, and accurate. Changes to the data should be traceable (audit trail).
Data reported on the CRF must be consistent with the source data or the discrepancies must 
be explained.
The current medical history of the trial participant may not be sufficient to confirm eligibility 
for the trial and the investigator may need to request previous medical histories and evidence 
of any diagnostic tests. In this case, the investigator must make at least 1 documented attempt 
to retrieve previous medical records. If this fails, a verbal history from the trial participant, 
documented in their medical records, would be acceptable.
Before providing any copy of the trial participants’ source documents to the sponsor, the 
investigator must ensure that all trial participant identifiers (e.g. trial participant’s name, 
initials, address, phone number, social security number) have properly been removed or 
redacted to ensure trial participant confidentiality.
If the trial participant is not compliant with the CTP, any corrective action (e.g. re-training)
must be documented in the trial participant file.
For the CRF, data must be derived from source documents, for example:

Trial participant identification: sex, year of birth (in accordance with local laws and 
regulations)

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
Trial participant participation in the trial (substance, trial number, trial participant
number, date the trial participant was informed)

Dates of trial participant’s visits, including dispensing of trial medication

Medical history (including trial indication and concomitant diseases, if applicable)

Medication history

AEs and outcome events (onset date [mandatory] and end date [if available])

SAEs (onset date [mandatory] and end date [if available])

Concomitant therapy (start date, changes)

Originals or copies of laboratory results and other imaging or testing results, with proper 
documented medical evaluation (in validated electronic format, if available)

ECG results (original or copies of printouts)

Completion of trial participant’s participation in the trial (end date; in case of premature 
discontinuation, document the reason for it, if known)

Prior to allocation of a trial participant to a treatment into a clinical trial, there must be 
documented evidence in the source data (e.g. medical records) that the trial participant 
meets all inclusion criteria and does not meet any exclusion criteria. The absence of 
records (either medical records, verbal documented feedback of the trial participant or 
testing conducted specific for a protocol) to support inclusion/exclusion criteria does not 
make the trial participant eligible for the clinical trial.
8.3.2
Direct access to source data and documents
The sponsor will monitor the conduct of the trial by regular on-site monitoring visits and 
inhouse data quality review. The frequency of site monitoring will be determined by 
assessing all characteristics of the trial, including its nature, objective, methodology, and the 
degree of any deviations of the intervention from normal clinical practice.
The investigator/institution will allow site trial-related monitoring, audits, IRB/IEC review,
and regulatory inspections. Direct access must be provided to the CRF and all source 
documents/data, including progress notes, copies of laboratory and medical test results, which 
must be available at all times for review by the CRA, auditor, and regulatory inspector 
(e.g. FDA). They may review all CRFs and informed consents. The accuracy of the data will 
be verified by direct comparison with the source documents described in Section 8.3.1. The 
sponsor will also monitor compliance with the CTP and GCP.
In the event of force majeure or other disrupting circumstances (e.g. pandemic, war; please 
see Section 6), site access may be restricted, thus limiting the ability to perform standard site 
monitoring activities on site such as on-site source data review and source data verification. 
Therefore, some of these activities may be performed remotely or replaced by centralized 
monitoring to the extent possible, based on a documented risk assessment and in alignment 
with local regulations.

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8.3.3
Storage period of records
Trial site(s):
The trial site(s) must retain the source and essential documents (including ISF) according to 
the contract or the local requirements valid at the time of the end of the trial (whatever is 
longer).
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS
BI is responsible to fulfil their legal and regulatory reporting obligation in accordance with
regulatory requirements.
8.5
STATEMENT OF CONFIDENTIALITY AND TRIAL PARTICIPANT
PRIVACY
Data protection and data security measures are implemented for the collection, storage, and 
processing of trial participant data in accordance with the principles 7 and 12 of the World 
Health Organization GCP handbook.
To ensure confidentiality of records and personal data, only pseudonymised data will be 
transferred to the sponsor by using a trial participant identification number instead of the trial 
participant’s name. The code is only available at the site and must not be forwarded to the 
sponsor. In case trial participant’s records will be forwarded e.g. for SAE processing or 
adjudication committees, personal data that can identify the trial participant will be redacted 
by the site prior to forwarding. Access to the trial participant files and clinical data is strictly 
limited: personalised treatment data may be given to the trial participant’s personal physician 
or to other appropriate medical personnel responsible for the trial participant’s welfare. Data 
generated at the site as a result of the trial need to be available for inspection on request by 
the participating physicians, the sponsor’s representatives, by the IRB/IEC, and the regulatory 
authorities.
A potential data security breach will be assessed regarding the implications for rights and 
privacy of the affected person(s). Immediate actions as well as corrective and preventive 
actions will be implemented. Respective regulatory authorities, IRBs/IECs, and trial 
participants will be informed as appropriate.
8.5.1
Collection, storage, and future use of biological samples and corresponding 
data
Measures are in place to comply with the applicable rules for the collection, biobanking, and 
future use of biological samples and clinical data, in particular

Sample and data usage must be in accordance with the separate biobanking informed 
consent

The BI-internal facilities storing biological samples from clinical trial participants as 
well as the external banking facility are qualified for the storage of biological samples 
collected in clinical trials

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
An appropriate sample and data management system, incl. audit trail for clinical data 
and samples to identify and destroy such samples according to the ICF is in place

A fit for the purpose documentation (biomarker proposal, analysis plan and report) 
ensures compliant usage

A fit for purpose approach will be used for assay/equipment validation depending on 
the intended use of the biomarker data

Samples and/or data may be transferred to third parties and other countries as 
specified in the biobanking ICF
8.6
TRIAL MILESTONES
The first act of recruitment representing the start of the trial is defined as the date when 
the first trial participant in the whole trial signs informed consent.
The end of the trial is defined as the ‘date of the last visit of the last trial participant in the 
whole trial’ (‘Last Trial Participant Completed’). At the trial participant level, this is the date 
of the follow-up visit. The “Last Trial Participant Last Treatment” (LPLT) date is defined 
as the date on which the last trial participant in the whole trial is administered the last dose of 
trial treatment (as scheduled per protocol or prematurely). Individual investigators will be 
notified of SUSARs occurring with the trial medication until 30 days after LPLT at their site.
Early termination of the trial is defined as the premature termination of the trial due to any 
reason before the end of the trial as specified in this CTP.
Temporary halt of the trial is defined as any unplanned interruption of the trial by the 
sponsor with the intention to resume it.
Suspension of the trial is defined as an interruption of the trial based on a Health Authority 
request.
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL
The trial is sponsored by BI Pharma GmbH & Co. KG, Germany.
A DEC will be established to decide on dose escalation (see Section 3.1).
Relevant documentation on the participating (Principal) Investigators (e.g. their curricula 
vitae) will be filed in the ISF.
BI has appointed a CTL, responsible for coordinating all required activities, in order to:

Manage the trial in accordance with applicable regulations and internal SOPs

Direct the clinical trial team in the preparation, conduct, and reporting of the trial
The BI investigational product BI 3006337 (test product) and the placebo (reference product) 
will be provided by the 
 
The trial will be conducted in 10 to 25 Phase I sites with access to MRI-PDFF measurements 
in the USA under the supervision of the Principal Investigators. The centres manage the trial 
in accordance with applicable regulations and internal SOPs.
Safety laboratory tests will be performed in a central laboratory and/or a dedicated CRO 
appointed by BI using validated assays.

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The analyses of BI 3006337 concentrations and ADAs/NAbs in serum will be performed at 
The analyses of acetaminophen will be performed at 
 
For investigation of PDs, serum adiponectin (HMW and total) and the bone biomarkers in 
serum will be measured in a central laboratory and/or a dedicated CRO appointed by BI using 
validated assays.
MR imaging to assess the liver fat content in the whole liver using proton density fat fraction 
(PDFF) will be performed at 
The digitally recorded 12-lead ECGs will be sent to a specialised CRO (
 
) for evaluation.
On-site monitoring will be performed by the CRO.
Data management responsibility is with an CRO according to BI´s FOT model and agreed 
contract with CRO. Statistical tasks and programming will be performed by a CRO. CRO 
works according CRO´s SOPs and BI´s SOPs/documents which are available in the BI 
procedural document list.
Tasks and functions assigned to organise, manage, and evaluate the trial are defined 
according to BI SOPs. A list of responsible persons and relevant local information can be 
found in the ISF. Responsibilities of the TSTAT will be filed in the TMF.

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9.
REFERENCES
9.1
PUBLISHED REFERENCES
P13-02280
Torres DM, Williams CD, Harrison SA. Features, diagnosis, and 
treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 
2012; 10(8); 837-858.
R07-4722
Guidance for industry: E14 clinical evaluation of QT/QTc interval 
prolongation and proarrhythmic potential for non-antiarrhythmic drugs.
Rockville: U.S. Department of Health and Human Services, Food and 
Drug Administration, Center for Drug Evaluation and Research (CDER), 
Center for Biologics Evaluation and Research (CBER), 2005.
R08-1466
Guidance for industry: toxicity grading scale for healthy adult and 
adolescent volunteers enrolled in preventive vaccine clinical trials 
(September 2007). Website: fda.gov/cber/guidelines.htm; 2007.
R09-4830
Brown BD, Badilini F. HL7 aECG implementation guide (March 21, 
2005).
R11-4890
Sampson HA et al. Second symposium on the definition and management 
of anaphylaxis: summary report - second National Institute of Allergy 
and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol; 117(2), p. 391-397; 2006.
R15-5365
Weston CJ, Shepherd EL, Claridge LC, et.al. Vascular adhesion protein-1
promotes liver inflammation and drives hepatic fibrosis. J Clin Invest 
2015; 125(2); 501-520.
R15-6057
Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital 
Stat Rep 2013; 61(4); 1-117.
R15-6070
Dharel N, Fuchs M. Nonalcoholic fatty liver disease - a major public 
health challenge for the 21 st century. JSM Gastroenterol Hepatol 2014; 
2(2); 1018.
R16-0366
E14 Implementation Working Group. ICH E14 guideline: the clinical 
evaluation of QT/QTc interval prolongation and proarrhythmic potential 
for non-antiarrhythmic drugs: questions & answers (R3) (current version 
dated 10 December 2015). Website: 
ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E
1 4/E14_Q_As_R3__Step4.pdf (access date: 29 January 2016); Geneva: 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (2015).
R16-3177
Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy 
in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, 
double-blind, randomised, placebo-controlled Phase II study. Lancet 
2016; 387(10019); 679-690.
R18-1357
U.S. Department of Health and Human Services - Common terminology 
criteria for adverse events (CTCAE) version 5.0

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R18-2829
Murphy KG, Bloom SR. Nonpeptidic glucagon-like peptide 1 receptor 
agonists: a magic bullet for diabetes? Proc Natl Acad Sci USA; 104(3), p. 
689-690; 2007.
R19-2360
Sonoda J, Chen MZ, Baruch A. FGF21-receptor agonists: an emerging 
therapeutic class for obesity-related diseases. Horm Mol Biol Clin Invest 
2017; 30(2).
R19-2365
Wei W, Dutchak PA, Wang X, et al. Fibroblast growth factor 21 
promotes bone loss by potentiating the effects of peroxisome proliferator-
activated receptor gamma. Proc Natl Acad Sci USA; 109(8), p. 
3143-3148; 2012.
R20-0498
Xu P, Zhang Y, Liu Y, et al. Fibroblast growth factor 21 attenuates 
hepatic fibrogenesis through TGF-beta/smad2/3 and NF-kappaB 
signaling pathways. Toxicol Appl Pharmacol 2016; 290; 43-53.
R20-0504
Xu J, Lloyd J, Hale C, et al. Fibroblast growth factor 21 reverses hepatic 
steatosis, increases energy expenditure, and improves insulin sensitivity 
in diet-induced obese mice. Diabetes; 58, p. 250-259; 2009.
R20-0506
Sarruf DA, Thaler JP, Morton GJ, et al. Fibroblast growth factor 21 
action in the brain increases energy expenditure and insulin sensitivity in 
obese rats. Diabetes; 59, p. 1817-1824; 2010.
R20-0507
Sanyal A, Charles ED, Neuschwander -Tetri BA, et al. Pegbelfermin 
(BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in 
patients with non-alcoholic steatohepatitis: a randomised, double-blind, 
placebo-controlled, Phase IIa trial. Lancet 2018; 392; 2705-2717.
R20-0508
Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel 
metabolic regulator. J Clin Invest; 115(6), p. 1627-1635; 2005.
R20-0509
Kim AM, Somayaji VR, Dong JQ, et al. Once-weekly administration of a 
long-acting fibroblast growth factor 21 analogue modulates lipids, bone 
turnover markers, blood pressure and body weight differently in obese 
people with hypertriglyceridaemia and in non-human primates. Diabetes 
Obes Metab 2017; 19; 1762-1772
R21-3294
Causs C, Reeder SB, Sirlin CB, et al. Noninvasive, quantitative 
assessment of liver fat by MRI-PDFF as an endpoint in NASH trials. 
Hepatology; 68(2), p. 763-772; 2018.
R22-0898
Bonekamp S, Tang A, Mashhood A, et al. Spatial distribution of MRI-
determined hepatic proton density fat fraction in adults with nonalcoholic 
fatty liver disease. J Magn Reson Imaging; 39, p. 1525-1532; 2014.
R22-0899
Harrison SA Ruane PJ Freilich BL Neff G Patil R Behling CA Hu C 
Fong E Temple B_de Tillman EJ Rolph TP Cheng A Yale K. 
Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-
blind, placebo-controlled, Phase IIa trial. Nature Med; 27, p. 1262-1271; 
2021.

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R22-0900
Patel J, Bettencourt R, Cui J, et al. Association of noninvasive 
quantitative decline in liver fat content on MRI with histologic response 
in nonalcoholic steatohepatitis. Ther Adv Gastroenterol; 9(5), p. 692-701;
2016.
R22-4307
Harrison SA Ruane PJ Freilich B Neff G Patil R Behling C et al. A 
randomized, double-blind, placebo-controlled Phase IIa trial of 
efruxifermin for patients with compensated NASH cirrhosis. JHEP Rep; 
2022.
R22-4429
National Institutes of Health. Division of AIDS (DAIDS) table for 
grading the severity of adult and pediatric adverse events (version 2.0, 
November 2014). Website: rsc.niaid.nih.gov/sites/default/files/daids-ae-
grading-table-v2-nov2014 .pdf (access date: 2022-12-16); 2014.
R23-0438
Trulicity (dulaglutide) injection, for subcutaneous use (Eli Lilly)
(U.S. prescribing information, revised: 11/2022). 2022.
R23-0766
TYLENOL For Children Plus Adults - acetaminophen suspension;
product information. Website: 
accessdata.fda.gov/spl/data/702a808 d-9376-4f67-89f8-d5dd43d5d793/7
02a808 d-9376-4f67-89f8-d5dd43d5d793.xml (access date: 
28 February 2023)
R23-1948
U.S. Department of Health and Human Services and U.S. Department of 
Agriculture, 2015-2020 Dietary Guidelines for Americans (8th ed, 
December 2015); 
R23-2478
Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias
JP, et al. Randomized, controlled trial of the FGF21 analogue
pegozafermin in NASH. N Engl J Med 2023.
R23-4413
Zepbound (tirzepatide) Injection, for subcutaneous use (Eli Lilly)
(U.S. prescribing information, revised: 11/2023). 2023.
R23-4564
Wegovy (semaglutide) injection, for subcutaneous use (Novo
Nordisk) (U.S. prescribing information, revised: 07/2023). 2023.
R24-0206
Ozempic (semaglutide) injection, for subcutaneous use (Novo
Nordisk) (U.S. full prescribing information, revised: 9/2023). 2023.
R24-0207
Victoza (liraglutide) injection, for subcutaneous use (Novo Nordisk)
(U.S. prescribing information, revised: 07/2023). 2023.
R24-0208
Saxenda (liraglutide) injection, for subcutaneous use (Novo Nordisk)
(U.S. prescribing information, revised: 04/2023). 2023.
R24-0209
Mounjaro (tirzepatide) injection, for subcutaneous use (Eli Lilly and
Company) (U.S. prescribing information, revised: 07/2023). 2023.

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R24-0216
Trulicity 0.75 mg, 1.5 mg, 3 mg, 4,5 mg solution for injection in prefilled
pen (Eli Lilly) (summary of product characteristics, manufacturers of the 
biological active substance and manufacturer responsible for batch 
release, conditions or restrictions regarding supply and use, other 
conditions and requirements of the marketing authorisation, conditions or 
restrictions with regard to the safe and effective use of the medicinal 
product, labelling and package leaflet, last updated: 16/03/2023). 2023.

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9.2
UNPUBLISHED REFERENCES

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10.
APPENDICES
10.1
TRIAL PARTICIPANT FEEDBACK
Optional Trial Participant Feedback Questionnaires:
This trial will include an option for participants to complete anonymized questionnaires, 
‘Trial Participant Feedback Questionnaire’, to provide feedback on their clinical trial 
experience. Individual participant level responses will not be reviewed by investigators. 
Responses will be used by the sponsor to understand where improvements can be made in the 
clinical trial process. These questionnaires will not collect data about the participant’s 
disease, symptoms, treatment effect, or AEs and therefore will not be part of the trial data or 
clinical trial report. The questionnaires will be implemented after local regulatory approval 
and after consent of the trial participant. Providing feedback is optional and not required for 
participation in the trial.
Optional Caregiver Feedback Questionnaires:
If applicable, this trial will include an option for caregivers to complete anonymized 
questionnaires, ‘Caregiver Feedback Questionnaire’, to provide feedback on the clinical trial 
experience. Individual caregiver level responses will not be reviewed by investigators. 
Responses will be used by the sponsor to understand where improvements can be made in the 
clinical trial process. These questionnaires will not collect data about the participant’s 
disease, symptoms, treatment effect, or AEs and therefore will not be part of the trial data or 
clinical trial report. The questionnaires will be implemented after local regulatory approval 
and after consent of the caregiver. Providing feedback is optional and not required for 
participation in the trial.
10.2
INSTRUCTIONS FOR USE
Not available.
10.3
COVID-19 RISK ASSESSMENT
Potential risks for trial participants due to the COVID-19 pandemic have been evaluated 
together with the Coordinating Investigator. The mode of action, available pharmacological, 
non-clinical and clinical data do not indicate an increased risk of contracting SARS-CoV-2 or 
aggravated clinical courses due to the treatment with BI 3006337 (e.g. effects on impaired or 
over- active immune-response). However, participants with NAFLD are at higher risk for 
severe illness from COVID-19 due to the underlying common co-morbidities (obesity, 
diabetes, CV disease).
Participants with active SARS-CoV-2 infection at the screening (e.g. confirmed by PCR test)
will be excluded from the trial (see Section 3.3.3). Rescreening of patients following the 
resolution of symptoms may be possible at the investigator´s discretion. In case of a 
diagnosed severe SARS-CoV-2 infection, trial treatment might be discontinued immediately 
and appropriate measures for monitoring, treatment and quarantine will be implemented. 
Trial treatment may be resumed after recovery as per Investigator´s discretion based on 
individual benefit-risk assessment on a case-by-case basis.

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Based on current data, the mode of action of BI 3006337 should not interfere with the 
immune system. Hence, effects of BI 3006337 on either the safety or efficacy of COVID-19
vaccines are considered unlikely.
The investigators will take the totality of information related to each single patient and the
local COVID-19 situation into consideration when performing the individual benefit-risk
assessment on a case-by-case basis. Considering all aspects, the investigator will decide upon
each patient’s (continued) participation in the planned trials. BI as the sponsor, if
required, will support the investigator in their decision finding. It is acknowledged that the
investigator may decide to implement protocol deviations where this protects the safety,
wellbeing and/or is in the best interest of the patient.

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10.4
DIAGNOSIS OF ANAPHYLAXIS
Clinical Criteria for diagnosing anaphylaxis [R11-4890]

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APPROVAL / SIGNATURE PAGE 
 
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Title: 
 
 
 
 
                                                                                                                   
 
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Meaning of Signature  
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c39013879
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clinical-trial-protocol-version-05
Phase Ib trial to assess safety and tolerability of multiple subcutaneous doses of BI
3006337 in patients with overweight or obesity and hepatic steatosis
Approval-Clinical Trial Leader
08 Feb 2024 21:06 CET
Approval-Clinical Program
09 Feb 2024 10:15 CET
Approval-Biostatistics
09 Feb 2024 16:27 CET
Verification-Paper Signature
Completion
14 Feb 2024 07:48 CET

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