Clinical trial NCT03835481
Conditions: Psoriasis
Sponsor: Boehringer Ingelheim
Start date: 2019-03-18; Completion date: 2021-07-27
Enrollment: 165 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To assess long-term safety, tolerability, and efficacy of BI 730357 in patients with moderate to severe chronic plaque psoriasis.

Detailed description:

Arms: arm 1: 25 mg BI 730357 + placebo under fasted conditions. arm 2: 50 mg BI 730357 + placebo under fasted conditions. arm 3: 100 mg BI 730357 + placebo under fasted conditions. arm 4: 200 mg BI 730357 + placebo under fasted conditions arm 5: 400 mg BI 730357 + placebo under fasted conditions.
Interventions: intervention 1: BI 730357 intervention 2: Placebo to match BI 730357
Intervention descriptions: intervention 1: Film-coated tablet intervention 2: Film-coated tablet

Protocol documents:
Prot_000.pdf: 
001-MCS-40-106-RD-03 (15.0) / Saved on: 30 Nov 2017
Clinical Trial Protocol
TITLE PAGE
Document Number:
c22181693-04
EudraCT No.
EU Trial No.
2018-003487-31
BI Trial No.
1407-0005
BI Investigational
Medicinal Product(s)
BI 730357
Title
Phase II long-term extension study to assess the safety, tolerability, 
and efficacy of BI 730357 in patients with moderate-to-severe 
plaque psoriasis
Lay Title
A study to test how well patients with plaque psoriasis tolerate BI 
730357 over a longer period and how effective it is
Clinical Phase
Phase II
Clinical Trial 
Monitor
Phone: 
Fax:  
Coordinating
Investigator
Phone:  
Status
Final Protocol (Revised Protocol based on Global Amendment 
3.0)
Version and Date
Version: 4.0
Date: 06 Oct 2020
Page 1 of 84
Proprietary confidential information.
2020 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
Protocol date
05 Dec 2018
Revision date
06 Oct 2020
BI trial number
1407-0005
Title of trial
Phase II long-term extension study to assess the safety, tolerability, 
and efficacy of BI 730357 in patients with moderate-to-severe 
plaque psoriasis
Coordinating 
Investigator
Trial sites
Multi-centre trial 
Clinical phase
II
Trial rationale
To provide patients with extended access to a potentially beneficial
oral psoriasis intervention and gain long-term safety information.
Trial objectives
To assess long-term safety, tolerability, and efficacy of BI 730357 in 
patients with moderate to severe chronic plaque psoriasis.
Trial endpoints
Primary endpoint:
• The occurance of treatment emergent adverse events (TEAEs)
up to Week 288. 
Secondary endpoints:
• Achievement of Psoriasis Area and Severity Index (PASI)50/
PASI75/PASI90/ PASI100 at Week 24
• Achievement of Static Physician’s Global Assessment (sPGA) 
clear or almost clear at Week 24
• Achievement of sPGA clear at Week 24
• Time to loss of PASI50/PASI75/PASI90/PASI100 for patients 
who achieve the response up to Week 288
• Time to loss of sPGA clear or almost clear for patients who 
achieve the response up to Week 288
• Time to loss of sPGA clear for patients who achieve the 
response up to Week 288
Trial design
Double blind (double dummy), placebo-controlled, parallel design 
comparison of 5 treatment groups for 12 weeks, followed by open 
label treatment of 2 treatment groups
Total number of patients 
entered
Up to approximately 270 patients
Number of patients on 
each treatment
To be determined by response in the preceding study and the number 
of patients that participate in the extension study. Approximate 
possible ranges provided.


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Patients entering extension trial from Part 1 of trial 1407-0030
(Fasted) double blind treatment period until Week 12:
• 25 mg (0 to 40 patients)
• 50 mg (0 to 80 patients)
• 100 mg (0 to 80 patients)
• 200 mg (40 to 100 patients)
• placebo (0 to 20 patients)
(Fasted) open label treatment period: 
• 100 mg (80 to 140 patients)
• 200 mg (60 to 100 patients)
Patients entering extension trial from Part 2 of trial 1407-0030
(Fed) open label treatment period: 
• 400 mg (0 to 90 patients)
Diagnosis
Patients with moderate-to-severe plaque psoriasis who have 
completed treatment in the preceding trial
Main in- and exclusion 
criteria
• Have completed treatment in the preceding trial without early 
discontinuation, agree to continue treatment in 1407-0005, and
o
for patients entering from Part 1 of trial 1407-0030

≥PASI50 response upon completing the trial 
1407-0030 Week 24 end-of-treatment visit
o
for patients entering from Part 2 of trial 1407-0030

≥PASI50 response upon completing the trial 
1407-0030 Week 12 end-of-treatment visit 
or perceived patient improvement, at the 
discretion of the Investigator.
• Women of childbearing potential (WOCBP) must be ready to 
use highly effective methods of birth control 
• Have not developed any of the exclusion criteria of the 
preceding trial, including relevant chronic or acute infections
• Must agree to continue to avoid intake of any restricted 
medication
• No plan to receive a live vaccination during trial conduct 
• Must agree to continue to adhere to the rules of UV-light 
protection 
• No ongoing AEs related to trial medication (including gastric 
intolerance) from 1407-0030
Test product(s)
BI 730357
dose
25 mg, 50 mg, 100 mg, 200 mg, 400 mg BI 730357 per day
method and route of 
administration
Oral (p.o.)


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Comparator product(s)
Placebo to BI 730357 (for patients entering from Part 1 of trial 
1407-0030, 12 week double blind period only)
dose
Not applicable
method and route of
administration
p.o.
Duration of treatment
Approximately 6 years
Statistical methods
Descriptive statistics include exposure adjusted rate of patients 
reporting a TEAE, responder analysis, and time to loss of response.  


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FLOW CHART
Trial Periods
Screening/
Double Blind 
Treatment
Open Label Treatment 
Visit
11, 2
1.13
1.23 1.33
2
2.13
3
4
5
6
7
8
9
10
11
12
13
14
Week
(Day 1)
2
4
8
12
14
24
36
48
60
72
84
96
108
120
132
144
156
Visit window (days)
±7
±7
±7
±7
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Informed consent
x
Demographics 
x
Medical history 
x
Smoking/alcohol history
x
Baseline conditions
x
In-, ex-criteria
x
Concomitant therapy
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Body weight
x1
x
x
x
Vital signs
x1
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical examination
x1
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Resting 12 lead ECG
x1
x
x
x
Pregnancy testing4
x1
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Adverse Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Contact IRT 
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Dispense study 
medication
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Collect study medication
x
x
x
x
x
x
x
x
x
x
x
x
x
PASI, sPGA 
x1
x
x
x
x
x
x
x
x
x
x
x
x
x
 
 
 


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Trial Periods
Screening/
Double Blind 
Treatment
Open Label Treatment 
Visit
11, 2
1.13
1.23 1.33
2
2.13
3
4
5
6
7
8
9
10
11
12
13
14
Week
(Day 1)
2
4
8
12
14
24
36
48
60
72
84
96
108
120
132
144
156
Visit window (days)
±7
±7
±7
±7
±3
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Columbia-Suicide 
Severity Rating Scale 
(C-SSRS)7
x1
x
x
x
x
x
x
x
x
x
x
x
x
x
Safety laboratory samples
x2
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Biomarker samples 
(serum)
x1
x
x
Whole blood (PBMC) 
for flow cytometry 
(pre-dose) 8
x1
x
x
Termination of trial 
medication
Trial completion10, 11
Vital status collection13


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Trial Periods
Open Label Treatment
Follow-Up
Visit
15
16
17
18
19
20
21
22
23
24
EOT12
EOO11
Week
168
180
192
204
216
228
240
252
264
276
288
292
Visit window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
+7
Informed consent
Demographics 
Medical history 
Smoking/alcohol history
Baseline conditions
In-, ex-criteria
Concomitant therapy
x
x
x
x
x
x
x
x
x
x
x
x
Body weight
x
x
x
Vital signs
x
x
x
x
x
x
x
x
x
x
x
x
Physical examination
x
x
x
x
x
x
x
x
x
x
x
Resting 12 lead ECG
x
x
x
Pregnancy testing4
x
x
x
x
x
x
x
x
x
x
x
x
Adverse Events
x
x
x
x
x
x
x
x
x
x
x
x
Contact IRT
x
x
x
x
x
x
x
x
x
x
x
Dispense study medication
x
x
x
x
x
x
x
x
x
x
Collect study medication
x
x
x
x
x
x
x
x
x
x
x
PASI, sPGA 
x
x
x
x
x
x
x
x
x
x
x
 
 
Columbia-Suicide Severity Rating Scale 
(C-SSRS)7
x
x
x
x
x
x
x
x
x
x
x
x
Safety laboratory samples
x
x
x
x
x
x
x
x
x
x
x
Biomarker samples (serum)
x
Whole blood (PBMC) 
for flow cytometry 
(pre-dose) 8
x


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Trial Periods
Open Label Treatment
Follow-Up
Visit
15
16
17
18
19
20
21
22
23
24
EOT12
EOO11
Week
168
180
192
204
216
228
240
252
264
276
288
292
Visit window (days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
+7
Termination of trial medication
x
Trial completion10, 11
x
Vital status collection13
x


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Flow Chart Footnotes:
1 Visit 1 will occur on the same day as End of Treatment (EOT) Visit in 1407-0030. Weight, vital signs, physical exam, ECG, pregnancy test, PASI, sPGA, 
 
, C-SSRS, biomarker samples, whole blood 
(PBMC) for flow cytometry and 
 are performed only once on that day as part of the EOT Visit in 1407-0030.  Visit 1 may be delayed up to 16 weeks if necessary for 
administrative reasons. If Visit 1 is delayed, these procedures will be done at Visit 1, except for PK, Biomarker and flow cytometry samples.
2 Safety laboratory samples will be taken twice in the same day as part of both the EOT Visit in 1407-0030 and for Visit 1 in 1407-0005.  Visit 1 collection is only for the following laboratory 
tests that are not assessed at EOT in study 1407-0030:  infection testing, glycosylated Hbc, LDL-cholesterol/HDL-cholesterol, cholesterol total, and triglycerides. If Visit 1 is delayed, then a 
sample will be taken at Visit 1 to include all tests included in the two samples and only one sample will be taken at EOT for 1407-0030.  
3For patients entering from Part 1 of trial 1407-0030, Visit 2.1 is a phone visit, with only adverse events and concomitant medication collected. Visits 1.1, 1.2 and 1.3 do not apply.
For patients entering from Part 2 of trial 1407-0030, Visits 1.1, 1.2 and 1.3 to be performed at the clinic with all procedures indicated, Visit 2.1 does not apply.
4 Only applicable for women of childbearing potential. Urine pregnancy tests will be performed at all visits prior to administration of study drug. In case of a positive urine pregnancy test, a 
serum pregnancy test will be done. More frequent testing should be done if required by the local regulation or per investigator judgment. 
 
7 C-SSRS ‘since last visit’ version used at all visits.
8 Whole blood Peripheral Blood Mononuclear Cell (PBMC) sampling should be taken approximately within 1 hour prior to administration of study drug.
10 Patients who discontinue trial treatment prematurely should undergo the EOT visit as soon as possible and the End of Observation (EOO) Visit 4 weeks thereafter. 
11 Patients switching to licensed BI 730357 upon completion of active treatment in this study should not complete a washout period.  Instead, their last trial visit will be EOT and trial completion 
will occur at that visit.  These patients will not return for EOO Visit.
12 Timing of the EOT visit is variable depending on when BI 730357 is approved and available on the market in the patient's country.  Study visits (performing Visit 24 assessments and 
procedures) may continue every 12 weeks until licensed BI 730357 becomes available or the trial is terminated.
13 For patients who discontinue trial treatment prematurely, vital status will be collected once a year by telephone call starting from the last trial visit performed until the end of the originally 
planned observation period.


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TABLE OF CONTENTS
TITLE PAGE ...........................................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................................2
FLOW CHART........................................................................................................................5
TABLE OF CONTENTS ......................................................................................................10
ABBREVIATIONS................................................................................................................13
1.
INTRODUCTION...............................................................................................15
1.1
MEDICAL BACKGROUND.............................................................................15
1.2
DRUG PROFILE................................................................................................16
1.3
RATIONALE FOR PERFORMING THE TRIAL.........................................21
1.4
BENEFIT - RISK ASSESSMENT.....................................................................21
2.
TRIAL OBJECTIVES AND ENDPOINTS......................................................25
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS........25
2.1.1
Main objectives....................................................................................................25
2.1.2
Primary endpoint................................................................................................25
2.1.3
Secondary endpoints...........................................................................................25
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.........................26
3.1
OVERALL TRIAL DESIGN AND PLAN .......................................................26
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)......................................................................................28
3.3
SELECTION OF TRIAL POPULATION .......................................................29
3.3.1
Main diagnosis for trial entry ............................................................................29
3.3.2
Inclusion criteria .................................................................................................29
3.3.3
Exclusion criteria ................................................................................................30
3.3.4
Withdrawal of patients from treatment or assessments..................................31
3.3.4.1
Discontinuation of trial treatment .........................................................................31
3.3.4.2
Withdrawal of consent to trial participation .........................................................32
3.3.4.3
Discontinuation of the trial by the sponsor...........................................................32
4.
TREATMENTS...................................................................................................33
4.1
INVESTIGATIONAL TREATMENTS ...........................................................33
4.1.1
Identity of the Investigational Medicinal Products..........................................33
4.1.2
Selection of doses in the trial and dose modifications......................................33
4.1.3
Method of assigning patients to treatment groups...........................................34
4.1.4
Drug assignment and administration of doses for each patient......................34
4.1.5
Blinding and procedures for unblinding...........................................................35
4.1.5.1
Blinding.................................................................................................................35
4.1.5.2
Unblinding and breaking the code ........................................................................36
4.1.6
Packaging, labelling, and re-supply...................................................................36


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4.1.7
Storage conditions...............................................................................................36
4.1.8
Drug accountability.............................................................................................36
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS ................................................................................................37
4.2.1
Other treatments and emergency procedures..................................................37
4.2.2
Restrictions ..........................................................................................................38
4.2.2.1
Restrictions regarding concomitant treatment ......................................................38
4.2.2.2
Restrictions on diet and life style..........................................................................40
4.2.2.3
Contraception requirements..................................................................................40
4.3
TREATMENT COMPLIANCE........................................................................41
5.
ASSESSMENTS..................................................................................................42
5.1
ASSESSMENT OF EFFICACY........................................................................42
5.2
ASSESSMENT OF SAFETY.............................................................................42
5.2.1
Physical examination ..........................................................................................42
5.2.2
Vital signs.............................................................................................................42
5.2.3
Safety laboratory parameters ............................................................................42
5.2.4
Electrocardiogram ..............................................................................................44
5.2.5
Other safety parameters.....................................................................................45
5.2.5.1
Suicidality .............................................................................................................45
5.2.5.2
Major Adverse Cardiovascular Event (MACE)....................................................45
5.2.6
Assessment of adverse events.............................................................................46
5.2.6.1
Definitions of AEs ................................................................................................46
5.2.6.2
Adverse event collection and reporting ................................................................49
 
5.5
BIOBANKING ....................................................................................................51
5.6
OTHER ASSESSMENTS...................................................................................52
5.7
APPROPRIATENESS OF MEASUREMENTS..............................................52
6.
INVESTIGATIONAL PLAN.............................................................................53
6.1
VISIT SCHEDULE.............................................................................................53
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS .................53
6.2.1
Screening period..................................................................................................54
6.2.2
Treatment period ................................................................................................54
6.2.3
Follow up period and trial completion..............................................................54
7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE......................................................................................................................56
7.1
STATISTICAL DESIGN - MODEL.................................................................56
7.2
NULL AND ALTERNATIVE HYPOTHESES ...............................................56
7.3
PLANNED ANALYSES.....................................................................................56
7.3.1
Primary endpoint analyses.................................................................................56


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7.3.2
Secondary endpoint analyses .............................................................................56
7.3.4
Safety analyses.....................................................................................................57
7.4
INTERIM ANALYSES ......................................................................................58
7.5
HANDLING OF MISSING DATA ...................................................................58
7.6
RANDOMISATION ...........................................................................................58
7.7
DETERMINATION OF SAMPLE SIZE .........................................................59
8.
INFORMED CONSENT, TRIAL RECORDS, DATA PROTECTION, 
PUBLICATION POLICY, AND ADMINISTRATIVE STRUCTURE ........60
8.1
TRIAL APPROVAL, PATIENT INFORMATION, INFORMED 
CONSENT ...........................................................................................................60
8.2
DATA QUALITY ASSURANCE ......................................................................61
8.3
RECORDS...........................................................................................................61
8.3.1
Source documents ...............................................................................................61
8.3.2
Direct access to source data and documents.....................................................62
8.3.3
Storage period of records ...................................................................................63
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS ..................................63
8.5
STATEMENT OF CONFIDENTIALITY AND PATIENT PRIVACY........63
8.5.1
Collection, storage and future use of biological samples and 
corresponding data .............................................................................................63
8.6
TRIAL MILESTONES.......................................................................................64
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL ...................................64
9.
REFERENCES....................................................................................................67
9.1
PUBLISHED REFERENCES............................................................................67
9.2
UNPUBLISHED REFERENCES......................................................................68
10.
APPENDICES.....................................................................................................69
10.1
PASI SCORE DEFINITION AND USE...........................................................69
10.2
STATIC PHYSICIAN GLOBAL ASSESSMENT (SPGA) ............................70
11.
DESCRIPTION OF GLOBAL AMENDMENT(S) .........................................75
11.1
GLOBAL AMENDMENT 1 ..............................................................................75
11.2
GLOBAL AMENDMENT 2 ..............................................................................78
11.3
GLOBAL AMENDMENT 3 ..............................................................................79


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ABBREVIATIONS
AE
Adverse Event
AESI
Adverse Event of Special Interest
AUC
Area under the Curve
BI
Boehringer Ingelheim
BSA
Body Surface Area
CI
Confidence Interval
Cmax
Maximum Concentration
CML
Clinical Monitor Local
CRA
Clinical Research Associate
CRF
Case Report Form, paper or electronic (sometimes referred to as “eCRF”)
CRO
Clinical Research Organisation
CRP
C-Reactive Protein
C-SSRS
Columbia-Suicide Severity Rating Scale
CTP
Clinical Trial Protocol
CTR
Clinical Trial Report
CYP
Cytochrome P450
DC
Dendritic Cell
DILI
Drug Induced Liver Injury
DMC
Data Monitoring Committee
ECG
ElectroCardioGraphy
EDC
Electronic Data Capture
EOO
End Of Observation
EudraCT
European Clinical Trials Database
GCP
Good Clinical Practice
HIV 
Human Immunodeficiency Virus
IB
Investigator’s Brochure
IBD
Inflammatory Bowel Disease
IC
Inhibitory Concentration
ICH
International Conference on Harmonisation
IHC
ImmunoHistoChemistry
ILC
Innate Lymphoid Cell
IL
InterLeukin
IEC
Independent Ethics Committee
IRB
Institutional Review Board
IRT
Interactive Response Technology
ISF
Investigator Site File
iSTAT
independent Statistician
LBD
Ligand Binding Domain
LoEE
List of Essential Elements 
LPLT
Last Patient Last Treatment 
LTE
Long Term Extension trial
LXR
Liver X Receptor
MACE
Major Adverse Cardiovascular Event
MCT
Melanin Containing Tissue


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MedDRA
Medical Dictionary for Drug Regulatory Activities
MRD
Multiple Rising Dose
MST
Medical Sub Team
NMSC
Non-Melanoma Skin Cancer 
NOAEL
No Observed Adverse Effect Level
OPU
Operative Unit
PASI
Psoriasis Area and Severity Index
PBMC
Peripheral Blood Mononuclear Cell
PD
Pharmacodynamics
PG
PharmacoGenetic
P-gp
P-glycoprotein
PK
Pharmacokinetics
p.o.
Oral
PoCC
Proof of Clinical Concept
PRO
Patient Reported Outcomes
PsA
Psoriatic Arthritis
PsO
(Plaque) Psoriasis
PXR
Pregnane X Receptor
q.d.
quaque die (once a day)
REP
Residual Effect Period
SAE
Serious Adverse Event
SIB
Suicidal Ideation and Behaviour
SMC
Safety Monitoring Committee
SmPC
Summary of Product Characteristics
sPGA
Static Physician’s Global Assessment
SRD
Single Rising Dose
SUSAR
Suspected Unexpected Serious Adverse Reactions
TCM
Trial Clinical Monitor
TEAE
Treatment Emergent Adverse Event
TDMAP
Trial Data Management and Analysis Plan
TMF
Trial Master File
TNF
Tumor Necrosis Factor
TSAP
Trial Statistical Analysis Plan
VEGF
Vascular Endothelial Growth Factor
WOCBP
Woman Of ChildBearing Potential


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1.
INTRODUCTION
1.1
MEDICAL BACKGROUND
Plaque psoriasis (PsO) is a chronic skin disease characterized by raised, well-demarcated, 
oval erythematous plaques covered in adherent silvery scale (R11-1257). Lesions are 
typically painful and/or itchy, and can be associated with a high degree of morbidity. PsO can 
affect extensive areas of skin; disease severity is in fact defined by body surface area (BSA) 
as mild (<3%), moderate (3-10%), and severe (>10%) (P20-07441). Approximately 25% of 
patients are classified as having moderate-to-severe disease. Disease severity correlates 
inversely with quality of life, as reported by patients with regard to symptom severity and 
disease impact on functionality and socialization (R16-4115, R11-1260, R03-1208, R16-
3072). Plaques on visible skin (e.g., scalp, face, hands) have particular impact on physical, 
sexual, psychosocial, and even economic status; disease severity is associated with reduced 
levels of employment and income (R16-3072). PsO is more than a superficial disease, with 
30% of patients having joint involvement, and a high correlation between PsO and obesity, 
diabetes, depression, metabolic syndrome, and cardiovascular risk (R16-4115).
Affecting approximately 2% of the global population, including 25 million North American 
and European patients, PsO is the most prevalent immune-mediated skin disease (R08-1089). 
Direct and indirect annual costs attributed to PsO in the US are estimated to be US $6,422 per 
patient on average, resulting in a total burden of US $35.2 billion. This cost is distributed, 
roughly in equal thirds, to medical costs, reduced quality of life, and productivity loss (R17-
1990). Across Germany, Italy, Spain, UK, and France the per-patient cost of PsO has been 
estimated to range from US $2,077 to $13,132 annually (R17-1989).
 
 
 
 
 
 
 
 
 
Mainstays of therapy for the treatment of PsO include topical agents, ultraviolet light-based 
therapies, traditional systemic agents (methotrexate, acitretin, cyclosporine), and more 
recently, targeted biologic and small-molecule therapies. Steroidal and non-steroidal topical 
agents (e.g., vitamin D analogues, retinoids, tar, anthralin, salicylic acid, tacrolimus) are 
efficacious, particularly for mild-to-moderate disease, but typically require long-term 
administration, and often provide only incomplete clearance. Long-term adherence to 
topically-prescribed therapies is often poor, and systemic absorption limits long-term usage 
of topical corticosteroids, particularly for large surface areas and for facial and genital 
lesions. Ultraviolet light-based therapies, often combined with the photosensitizing agent 


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psoralen, may be used to treat extensive areas of involved skin, but generally require long-
term therapy, and are associated with non-melanoma skin cancer (NMSC). Conventional 
systemic agents provide relatively inexpensive options to treat more severe or refractory 
disease, but long-term usage may be substantially limited by the risks of hepatotoxicity, bone 
marrow suppression, and pulmonary toxicity (methotrexate), teratogenicity (acetretin), and 
nephrotoxicity and hypertension (cyclosporine). 
 
 
 
 
 
 
 
 
 
 
1.2
DRUG PROFILE
 
Residual Effect Period
The Residual Effect Period (REP) of BI 730357 is 7 days. This is the period after the last 
dose with measurable drug levels and/or pharmacodynamic effects still likely to be present.
 
 
 
 
 
 
 
 
 
 


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1.3
RATIONALE FOR PERFORMING THE TRIAL
As described in Section 1.1, the treatment of patients with moderate-to-severe plaque 
psoriasis has been greatly enhanced by the introduction of biologic agents, and more options 
may be added to the armamentarium in the near future. However, these antibody drugs must 
be administered by subcutaneous injections, and long-term therapeutic effect may be limited 
by the formation of antidrug antibodies. There remains a medical need for the introduction of 
new, efficacious oral treatment options.
 
 
 
 
 
.
The preceding Phase II Trial 1407-0030 will allow for the investigation of safety, tolerability, 
and efficacy of BI 730357 in patients with moderate-to-severe plaque psoriasis. Favorable 
results of 1407-0030 will serve as a PoCC in the treatment of psoriasis, for refinement of 
Phase III dose selection, and to support further development in other disease indications. 
The aim of this extension Trial 1407-0005 is to provide additional safety and efficacy data of 
up to approximately six years treatment in up to approximately 270 patients treated with BI 
730357.  The trial is designed to gain long-term safety information to support registration 
submissions. Furthermore, the study will provide patients with extended access to a 
potentially beneficial intervention.
1.4
BENEFIT - RISK ASSESSMENT
Study participants are exposed to the risks of the study procedures and the risks related to the 
exposure to the trial medication.
Procedure-related risks
Blood sampling by venipuncture or through an indwelling venous catheter may be 
accompanied by mild bruising and also, 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 paresthesia, reduced sensibility, and/or pain for an indefinite 
period. 
No health-related risk is expected from the total planned blood withdrawal over 
approximately 6 years.
Drug-related risks and safety measures
As the nature of the target and the mechanism of action of BI 730357 are well understood, 
comparable compounds have been tested by other companies before, and the animal models 


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are believed to be predictive for the effects in humans, BI 730357 is not seen as a high risk 
compound.
The pharmacological effects of BI 730357 are dose dependent, and no evidence for prolonged 
or irreversible effects has been observed. Evaluation of BI 730357 dose levels selected for 
administration in this trial is supported by pre-clinical, as well as clinical safety data from 
Trial 1407.1 and 1407-0002 (see Section 1.2). 
Dose reassignments planned in this trial (refer to Section 3.1) will be contingent on an 
independent external Data Monitoring Committee (DMC) evaluation of all available data 
from Phase II Trial 1407-0030 regarding the safety of the dose levels proposed (refer to 
Section 8.7).
Since preclinical data indicate that BI 730357 has phototoxicity potential, patients in this trial 
will be advised to apply protection measures as described in Section 4.2.2.2. Solarium 
radiation, or treatment with ultraviolet light (e.g., PUVA) or use of medication with known 
phototoxicity potential (e.g., doxycycline) is prohibited during this clinical trial until the end 
of the follow-up period.
BI 730357 is confirmed as a sensitive cytochrome P450 (CYP) 3A substrate, based on 
clinical drug-drug interaction (DDI) evaluation with itraconazole, a CYP3A inhibitor, in trial 
1407-0014. Drugs or foods that are known CYP3A inhibitors or strong or moderate CYP3A 
inducers should not be co-administered in clinical trials with BI 730357. Based on in vitro 
data, BI 730357 could potentially induce CYPs 1A2, 2B6, 2C8, 2C9, or 2C19 in human. 
Sensitive substrates of CYPs 1A2, 2B6, 2C8, 2C9, or 2C19 for which a reduction in exposure 
could present a potential patient risk should not be given together with BI 730357. 
Additionally, based on in vitro data, BI 730357 may inhibit a number of transporters in 
human; based on the magnitudes of the in vitro inhibition, it is recommended that substrates 
of P-gp, BCRP, OATP1B1, OATP1B3, OAT3, OCT2, MATE1, and MATE2-K for which an 
increase in exposure could present a potential patient risk should not be given together with 
BI 730357.
As with other immune-targeted therapies, impaired host defense is a theoretical target-related 
toxicity, potentially resulting in increased risk of infection and/or malignancy. 
 
 
 
 
 
 
 
 
 
No evidence of an increased risk of lymphoma development or 
changes preceding lymphoma development has arisen based on the BI 730357 toxicology 
studies in rat and dogs up to 26- and 39-week duration, respectively. AEs and SAEs 
consistent with malignancy, and specifically those representing lymphoma, are to be 
evaluated throughout the BI 730357 clinical development program. Thus far, no clinical 
signal regarding malignancy has been identified in BI 730357 clinical trials.


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As with all drugs, the potential for hypersensitivity and allergic reactions has to be taken into 
consideration when BI 730357 is administered.
Although rare, a potential for drug-induced liver injury (DILI) is under constant surveillance 
by sponsors and regulators. Therefore, this trial requires timely detection, evaluation, and 
follow-up of laboratory alterations in selected liver laboratory parameters to ensure patients´ 
safety, see also Section 5.2.6, adverse events of special interest.
While there is no precedent clinical data implicating association between 
and important AEs such as Major Adverse Cardiovascular Events (MACE) and Suicidal
Ideation and Behaviour (SIB), these AEshave been associated with biological entities 
targeting PsO and other T
disease indications. In the interest of ensuring subject 
safety, these important AEs are to be evaluated throughout the BI 730357 clinical 
development program, and trial subjects will be proactively screened for SIB in accordance 
with available regulatory guidance.  Thus far no AEs consistent with MACE or SIB have 
been identified in the clinical program.
Even though gastritis development is not expected in humans, AE consistent with gastric
intolerance or gastritis are designated as AE of special interest (AESI), to ensure timely
characterization, monitoring and reporting of any such effects in this study (see Section 
5.2.6.1).
Patients with PsO receiving BI 730357 may experience improvement in disease severity. 
However, this is a newly-developed drug at an early stage of testing, therefore an individual 
benefit for patients cannot be guaranteed. Nonetheless, the results from toxicity and safety 
pharmacology studies demonstrated an acceptable profile for clinical trials with daily oral 
administration. The potential risks which are described above will be minimized by close 
monitoring and the involvement of a DMC evaluation. These risks are considered 
manageable and outweighed by the potential benefits of the study drug.
As with other immunomodulatory treatments, BI 730357 may potentially increase the risk of 
infections in patients participating in clinical trials. Therefore, risk mitigation measures (e.g., 
exclusion of patients with increased risk of infections, close monitoring of adverse events, 
provision of guidance pertaining to treatment and management of acute infections occurring 
during the trial) have been included. Any patient with suspected or diagnosed COVID-19 
infection should be treated according to standard of care, and interruption of trial medication 
should be considered.
Patients with the targeted BI 730357 indications may be at greater risk of cardiovascular disease 
and associated risk factors, comorbidities in which the likelihood of severe illness from COVID-
19 may be increased. Patients with evidence of a current or previous disease or medical condition 
(other than the target indication) that is clinically significant in the opinion of the investigator are 
excluded from participation in all trials with BI 730357. To prioritize the safety of patients, in 
areas with significant COVID-19 morbidity, remote visits will be permitted as needed to replace 
onsite patient visits in these trials. To ensure that patients may safely continue to participate in the 
clinical trial, remote visits will require, at a minimum, investigator assessment of new and 
ongoing adverse events, concomitant therapies, and patient compliance with the trial protocol and 


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study drug. The BI trial team will remain in close contact with the investigator during the 
execution of a remote visit.
Trial conduct and protocol-defined procedures do not impose additional risk to trial participants. 
To address potential risks associated with operational aspects related to the participation in 
clinical trials in the context of the COVID-19 pandemic, different risk mitigation measures are 
considered, based on local requirements and development of the pandemic. 
Recruitment of clinical trials will proceed when it is considered safe to do so in accordance with 
local public health guidance.


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2.
TRIAL OBJECTIVES AND ENDPOINTS
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS
2.1.1
Main objectives
The overall purpose of this extension trial is to assess long-term safety, tolerability, and 
efficacy of BI 730357 in patients with moderate to severe chronic plaque psoriasis.
2.1.2
Primary endpoint

The occurance of treatment emergent adverse events (TEAEs)

up to Week 288. 
2.1.3
Secondary endpoints

Achievement of Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/
PASI100 at Week 24

Achievement of Static Physician’s Global Assessment (sPGA) clear or almost clear at 
Week 24

Achievement of sPGA clear at Week 24

Time to loss of PASI50/PASI75/PASI90/PASI100 for patients who achieve the 
response up to Week 288

Time to loss of sPGA clear or almost clear for patients who achieve the response up to
Week 288

Time to loss of sPGA clear for patients who achieve the response up to Week 288 


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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN AND PLAN
Trial 1407-0005 is a multicentre, long-term extension trial in patients who have completed 
Phase II PoC/dose-ranging trial 1407-0030 with demonstrated improvement in disease 
severity and acceptable safety and tolerability of trial drug, as described below. The trial is 
designed to evaluate long-term safety and efficacy of BI 730357 in patients with moderate-to-
severe plaque PsO.
Two groups of patients are to be entered into this trial, including up to (approximately) 180 
patients entered in the original trial 1407-0030 protocol (now Part 1) and up to 
(approximately) 90 patients entered in an extended dose-ranging  segment, now Part 2 of the 
amended trial 1407-0030 protocol. Actual numbers of subjects entering the extension trial are 
to be determined by response in the preceding study and the number of patients that 
participate in the extension study.
In the first group (Part 1), patients will be considered eligible to participate in this long-term 
extension trial upon completing the trial 1407-0030 Week 24 end-of-treatment visit with a
≥PASI50 response. BI 730357 dose levels of up to 200 mg q.d.are to be administered under 
fasting conditions to patients in this group, reflecting the dose levels evaluated during Part 1 
of trial 1407-0030.

Patients entering the extension trial will remain on their blinded BI 730357 dose 
treatment from the preceding trial until the open label period of 1407-0005 begins at 
Visit 2/Week 12.

At Visit 2/Week 12, patients presently assigned to double blind treatment of placebo, 
25 mg, 50 mg, and 100 mg will be reassigned to the 100 mg open label dose, and 
patients presently assigned to the double blind treatment of 200 mg will be reassigned 
to 200 mg open label dose.  Refer to Figure 3.1: 1.
In the second patient group (Part 2), patients will be considered eligible to participate in this 
trial upon completing the trial 1407-0030 Week 12 end-of-treatment visit with a ≥PASI50
response or perceived patient improvement, at the discretion of the Investigator. Patients are 
to be considered eligible only if also without ongoing AEs consistent with intolerance of trial 
medication (including gastric intolerance) that in the opinion of the investigator would 
compromise the safety of the patient.
.

All patients entering the extension trial are to be assigned at Visit 1 to receive open-
label treatment with 400 mg q.d. (fed),  the anticipated therapeutic BI 730357 dose. 
Refer to Figure 3.1: 2.


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It is expected that Visit 1 of trial 1407-0005 will be performed on the same day of the EOT 
Visit of trial 1407-0030 in both patient groups. In the event that patients completing Part 2 of 
trial 1407-0030 are not able to be entered immediately into the extension trial due to 
administrative reasons (e.g., pending protocol approval, availability of trial medication), Visit 
1 of the extension trial may be delayed for no more than 16 weeks.In the event of a delay, the 
CTM should be consulted and refer to the Flow Chart for procedures to be conducted.
The treatment period is this trial will be approximately 6 years.
Figure 3.1: 1
Trial 1407-0005 dose assignment/reassignment for patients entering from 
Part 1 of trial 1407-0030
Figure 3.1: 2
Trial 1407-0005 dose assignment for patients entering from Part 2 and 
continuing from Part 1 of trial 1407-0030
Optional 
up titration 
100 mg BI 730357
200 mg BI 730357
200 mg BI 730357
400 mg BI 730357
open label


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Dose selection at Week 12 is based on the safety and tolerability data from the SRD Trial 
1407.1 and the MRD Trial 1407-0002, and will be contingent on DMC evaluation of all 
available data from Phase II trial 1407-0030.  For patients entering from Part 1 of trial 1407-
0030, if an unacceptable risk regarding the safety of the 200 mg dose level is reported by the 
DMC, the open label BI 730357 dose assignments beginning at Week 12, as shown in Figure 
3.1: 1, is to be altered to assign all patients to the 100 mg q.d. dose group.  For additional 
details and logistics, refer to Section 8.7.  Refer to Section 4.1.2 for dose selection rationale.
All patients entering from Part 2 of trial 1407-0030 are to receive the 400 mg q.d. dose, as 
long as no unacceptable risks are identified during Part 2 of trial 1407-0030. Once Part 2 
patients begin enrolling in this trial, existing patients receiving 100 mg q.d. in this trial will 
be given the option to titrate up to the 200 mg q.d. dose, if the investigator determines that the 
patients may benefit from the higher dose.
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP(S)
Trial 1407-0005 is designed as a long-term extension clinical trial, and is expected to 
generate additional safety information to support registration submissions. Therefore, the 
primary endpoint is focused on safety.  All patients who complete treatment with BI 730357 
or placebo in the preceding Trial 1407-0030 and achieve a PASI50 response at Week 24 of 
that trial will be invited to participate to receive long-term treatment. Our goal in this study is 
to obtain additional safety, tolerability and efficacy data following long-term drug 
administration 
For patients entering the extension trial from Part 1 of trial 1407-0030, the 12-week double 
blind treatment period (refer to Section 3.1) is intended to maintain the blind of the preceding 
trial while collecting additional data for the doses allocated at EOT in the preceding trial.  
After DMC review of all available safety data from 1407-0030 (refer to Section 8.7), the dose 
levels selected for the open label period of the extension trial will be confirmed and the long-
term assessment of the 100 mg q.d. and 200 mg q.d. dose groups will begin at Visit 2/Week 
12 (refer to Section 3.1).  Visit 2.1 will be conducted by telephone 2 weeks after this 
transition as a precaution to monitor patient safety. Trial 1407-0005 may include placebo 
patients who have achieved a PASI 75 at Week 12 of 1407-0030 and a PASI50 at Week 24 of 
1407-0030. Patients in this category that have meet these efficacy criteria would also need to 
be satisfied with their blinded treatment allocation at Week 24 of trial 1407-0030 and 
therefore selected to continue treatment by participating in the extension study.  These 
patients will begin active treatment of 100 mg BI 730357 at Visit2/Week 12 of the extension 
study. 
Based on safety and efficacy data from Part 1, Part 2 of trial 1407-0030 extends dose ranging 
of BI 730357 to 400 mg q.d. and 200 mg b.i.d., to be administered under fed conditions. 
Given that PoC efficacy has been demonstrated in Part 1 of trial 1407-0030, in the second 
patient group, patients are to be considered eligible to participate in 1407-0005 upon 
completing the trial 1407-0030 Week 12 end-of-treatment visit with >50% improvement in 
PASI50 or perceived patient improvement, at the discretion of the Investigator. Furthermore, 
given that patients in this group are to receive long-term BI 730357 at a substantially higher 
dose than in those in the first group, in the interest of safety, patients are to be considered 


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eligible only if also without ongoing AEs consistent with intolerance of trial medication
(including gastric intolerance), that in the opinion of the investigator would compromise the 
safety of the patient.
. Visits 1.1, 1.2 and 1.3 will be conducted in person for these patients to monitor patient 
safety, particularly as placebo patients may continue into this trial and receive active drug.
As a trial with an open label period, we realize that no powered or controlled analysis can be 
done. However, we will be able to evaluate initial tendencies and at the same time permit our 
early study participants an opportunity to maintain access to a therapy that has the potential to 
have clinical benefit. 
3.3
SELECTION OF TRIAL POPULATION
The trial is intended to provide extended access of BI 730357 to up to approximately 180
male and female patients in Part 1 and approximately 90 patients in Part 2 that complete Trial 
1407-0030 at approximately 30 study sites. 
A log of all patients enrolled into the trial (i.e. who have signed informed consent) will be 
maintained in the Investigator Site File (ISF) irrespective of whether they have been treated 
with investigational drug or not.
If a patient is enrolled in error (does not meet all inclusion criteria or meets one or more 
exclusion criteria on the day of enrolment), the sponsor should be contacted immediately.
3.3.1
Main diagnosis for trial entry
Patients with moderate-to-severe plaque psoriasis who have completed treatment in the 
preceding trial.
Please refer to Section 8.3.1 (Source Documents) for the documentation requirements 
pertaining to the in- and exclusion criteria.
3.3.2
Inclusion criteria
1. WOCBP1 must be ready and able to use highly effective methods of birth control per ICH 
M3 (R2) that result in a low failure rate of less than 1% per year when used consistently 
and correctly from date of screening until 4 weeks after last treatment in this trial. A list 
of contraception methods meeting these criteria is provided in the patient information. 
(1 A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until 
becoming post-menopausal unless permanently sterile. 
Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 
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.)
2. Patients with moderate-to-severe plaque PsO who have completed treatment in the 
preceding trial without early discontinuation, agree to continue treatment in 1407-0005, 
and

for patients entering from Part 1 of trial 1407-0030


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o
achieve a ≥PASI50 response upon completing the trial 1407-0030 Week 24 end-
of-treatment visit

for patients entering from Part 2 of trial 1407-0030
o
achieve a ≥PASI50 response upon completing the trial 1407-0030 Week 12 end-
of-treatment visit or perceived patient improvement, at the discretion of the 
Investigator
3. 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
Having developed any of the following exclusion criteria from the preceding study:
1. Nonplaque forms of PsO (including guttate, erythrodermic, or pustular), current drug-
induced PsO (including a new onset or exacerbation of PsO from, e.g., beta blockers, 
calcium channel blockers, lithium), active ongoing inflammatory diseases (including but 
not limited to inflammatory bowel disease (IBD)) other than PsO that might confound 
trial evaluations.
2. Previous enrolment in this trial.
3. Currently enrolled in another investigational device or drug trial or is receiving other 
investigational treatment(s) (with the exception of 1407-0030). 
4. Intake of any restricted medication as specified in Section 4.2.2.1 or any drug considered 
likely to interfere with the safe conduct of the trial.
5. Any plan to receive a live vaccination during the conduct of the trial.
6. Patients not expected to comply with the protocol requirements or not expected to 
complete the trial as scheduled.
7. Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes 
the patient an unreliable trial participant or unlikely to complete the trial.
8. Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
9. Any documented active or suspected malignancy, except appropriately treated basal cell 
carcinoma of the skin, squamous cell carcinoma of the skin, or in situ carcinoma of 
uterine cervix.
10. Relevant chronic or acute infections including human immunodeficiency virus (HIV), 
viral hepatitis, and tuberculosis. 
11. Evidence of a disease (including known or suspected IBD, cardiovascular disease), or 
medical finding that in the opinion of the Investigator is clinically significant and would 
make the study participant unreliable to adhere to the protocol or to complete the trial, 
compromise the safety of the patient, or compromise the quality of the data.
12. Any suicidal ideation, including grade 4 or 5 in the Columbia Suicide Severity Rating 
Scale (C-SSRS) in the past 12 months (i.e., active suicidal thought with intent but without 
specific plan), or active suicidal thought with plan and intent in the past.


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13. Unwillingness to adhere to the rules of UV-light protection as described in Section 
4.2.2.2.
14. Ongoing AEs consistent with intolerance of trial medication (including gastric 
intolerance) from 1407-0030, that in the opinion of the investigator would compromise 
the safety of the patient.
3.3.4
Withdrawal of patients from treatment or assessments
Patients 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.
Every effort should be made to keep the patients in the trial: if possible on treatment, or at 
least to undergo the procedures for early treatment discontinuation, follow up, and vital status 
collection.
Measures to control the withdrawal rate include careful patient 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 patient files and case report form (CRF). If the reason for 
discontinuation is death, this should be reported on the SAE form as well, regardless of 
causal relationship.
3.3.4.1
Discontinuation of trial treatment
An individual patient may be withdrawn from trial treatment if:

The patient wants to discontinue trial treatment, without the need to justify the decision. 

The patient 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 stick to the trial requirements in the future.

The patient experiences an intolerable increase of PsO, the trial medication will be 
discontinued and anti-psoriatic agents may be used as rescue medications (refer to Section 
4.2.1).

The patient needs to take concomitant drugs that interfere with the investigational product 
as listed in Table 4.2.2.1: 1.

The patient can no longer be treated with trial medication for other medical reasons (such 
as surgery, adverse events, other diseases, or pregnancy).

The patient develops suicidal ideation of type 4 or 5 in the C-SSRS (i.e., active suicidal 
thought with intent but without specific plan, or active suicidal thought with plan and 
intent). The patient should immediately be referred to a mental health professional for 
further work-up.

In addition to these criteria, the physician may discontinue subjects at any time based on 
his or her clinical judgment.
In case of a temporary reason, trial treatment should be restarted as early as possible if 
medically justified. 


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Even if the trial treatment is permanently discontinued, the patient remains in the trial and, 
given his/her agreement, will undergo the procedures for early treatment discontinuation, 
follow up, and vital status collection as outlined in the Flow Chart and Section 6.2.3.
For all patients, the reason for withdrawal from trial treatment (e.g. adverse events) must be 
recorded in the CRF. These data will be included in the trial database and reported.
If a patient becomes pregnant during a trial, the study medication needs to be discontinued.  
The patient will be followed up until birth or otherwise termination of the pregnancy.  The 
data of the patient will be collected and reported in the clinical trial report (CTR) until last 
patient visit and any events thereafter will be reported in the BI Pharmacovigilance database.
3.3.4.2
Withdrawal of consent to trial participation
Patients may withdraw their consent to trial participation at any time without the need to 
justify the decision.If a patient wants to withdraw consent, the investigator should be 
involved in the discussion with the patient 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 above.
3.3.4.3
Discontinuation of the trial by the sponsor
Boehringer Ingelheim 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. Emergence of any efficacy/safety information invalidating the earlier positive benefit-
risk-assessment that could significantly affect the continuation of the trial (refer to
Section 8.7 for DMC role in this process).
3. Violation of GCP, the trial protocol, or the contract impairing the appropriate conduct of 
the trial.
The investigator / the trial site will be reimbursed for reasonable expenses incurred in case of 
trial termination (except in case of the third reason).


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4.
TREATMENTS
4.1
INVESTIGATIONAL TREATMENTS
BI 730357 and Placebo to match BI 730357.  The placebo will only be given until the open 
label period of the extension trial begins.  
4.1.1
Identity of the Investigational Medicinal Products
Table 4.1.1: 1
Test product 1
Substance:
BI 730357
Pharmaceutical formulation:
Film-coated tablet
Source:
Boehringer Ingelheim Pharma GmbH & Co KG
Unit strength:
25 mg, 50 mg, 100 mg 
Posology
q.d.
Route of administration:
Per os
Substance:
Placebo to match BI 730357 (until open label drug 
supply is dispensed)
Pharmaceutical formulation:
Film-coated tablet
Source:
Boehringer Ingelheim Pharma GmbH & Co KG
Unit strength:
Not applicable
Posology
q.d.
Route of administration:
Per os
4.1.2
Selection of doses in the trial and dose modifications
The dose range for Part 1 of the preceding trial 1407-0030 was selected on the basis of the 
preclinical data, and on safety data obtained in first-in-human SRD trial 1407.1 and MRD 
trial 1407-0002, which respectively demonstrated that single BI 730357 dose levels of up to 
800 mg q.d. and multiple dose levels of up to 200 mg q.d. were well tolerated.  


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For patients entering from Part 1 of trial 1407-0030, BI 730357 doses of 25, 50, 100, and 200 
mg q.d. or placebo as assigned in the preceding Trial 1407-0030, will be continued for
patients in the extension trial 1407-0005 for the initial 12 week double-blind treatment 
period. At Visit 2/Week 12 patients will be assigned to either the 100 mg or 200 mg BI 
730357 (refer to Section 3.1). This change in treatment assignment will be supported by a 
DMC review of all available safety data from trial 1407-0030; if an unacceptable risk 
regarding the safety of the 200 mg dose level is reported by the DMC, a plan has been 
provided within the protocol for an alternative dosing scheme with all patients assigned to the 
100 mg BI 730357 open label treatment dose (refer to Section 8.7). Patients currently 
enrolled at the 100 mg q.d. dose at the time Part 2 begins will have the option of increasing to 
the 200 mg dose based upon investigator assessment that the increased dose could benefit the 
patient.
Based on PK-PD modeling developed to describe the concentration and PASI data obtained 
in Part 1 of trial 1407-0030, Part 2 of 1407-0030 extends dose ranging of BI 730357 to 400 
mg q.d. and 200 mg b.i.d., to be administered under fed conditions. The target human 
therapeutic efficacy exposures are currently based on 400 mg administered q.d. under fed 
conditions to patients with moderate-to-severe plaque PsO (P20-07441). Therefore, for 
patients entering from Part 2 of trial 1407-0030, BI 730357 400 mg q.d. is to be administered
to all eligible patients.
4.1.3
Method of assigning patients to treatment groups
For patients entering from Part 1 of trial 1407-0030, during visit 1, eligible patients will 
continue to receive their treatment allocation of BI 730357 received in the preceding study, in 
a blinded fashion, via Interactive Response Technology (IRT). Upon completion of Visit 
2/Week 12 the patients in this extension study will be assigned to an open label BI 730357 
dose, via IRT (refer to Section 3.1).
Patients entering from Part 2 of trial 1407-0030 will all be assigned to open label BI 730357 
400 mg q.d.
4.1.4
Drug assignment and administration of doses for each patient
Study medication will be dispensed at the investigational sites according to the Flow Chart. 
On days of scheduled patient visits, the study medication will be administered at the study 
site after the other visit procedures have been performed. On days with no scheduled study 
visit the patient will take their medication at home.
From the start of the treatment period patients will be instructed to take the trial medication
once daily with a glass of water. Patients must take the study medication after at least 6 hours 
fasting and should not eat for 30 minutes after drug administration.
Patients will receive four tablets per day from Visit 1 until Visit 2.  In Table 4.1.4: 1, the 
medication schedule for each treatment group is listed for continuation of the double-blind 
1407-0030 dose regimen until Visit 2/Week 12.
Upon the start of the open label treatment at Visit 2/Week 12, patients will be reassigned (see 
Section 3.1) via IRT to either the 100 mg treatment group or the 200 mg treatment group until 


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the End of Trial Visit. If a safety signal is identified by the DMC, an alternative dosing plan 
will be followed and all patients will be assigned via IRT to the 100 mg treatment group until 
the End of Trial Visit (see Section 3.1 and Section 8.7).
Placebo tablets will no longer be administered during the open label period.
Table 4.1.4: 1
Study medication dosing guide 
25 mg/placebo 
tablet
50 mg/placebo 
tablet
100 mg/placebo 
tablet
25 mg treatment group
1 active
1 placebo
2 placebo
50 mg treatment group
1 placebo
1 active
2 placebo
100 mg treatment group
1 placebo
1 placebo
1 active
1 placebo
200 mg treatment group
1 placebo
1 placebo
2 active
400 mg treatment group
0 placebo
0 placebo
4 active
Placebo group
1 placebo
1 placebo
2 placebo
To ensure a dose interval of about 24 hours, the medication should be taken in the morning at
approximately the same time every day. If a dose is missed by more than 12 hours, that dose
should be skipped and the next dose should be taken as scheduled. No double doses should 
be taken.
Patients should be instructed not to take their medication on the morning of trial visits as they
will be dosed in the clinic. 
During the COVID-19 pandemic or other unforeseen situations, physical visits to the sites 
may need to be restricted to ensure patient’s safety. Based on a thorough assessment of the 
benefits and risks, and consultation with the CTM, the investigator may still decide to 
continue the trial treatment and trial medication may be shipped to the patient’s home if 
acceptable according to local law and regulations.
4.1.5
Blinding and procedures for unblinding
4.1.5.1
Blinding
Double blind treatment period – Part 1 only
Patients, investigators and everyone involved in trial conduct or analysis will remain blinded 
with regard to the randomised treatment assignments during the double blind treatment period 
until Week 12 for each patient.  The randomisation code for this trial period will be kept 
secret by Clinical Trial Support up to database lock of the preceding trial. 
A trial independent statistician iSTAT will be assigned to prepare the summary reports for the 
DMC based on the agreed upon format and layout. All information, including adverse events, 
mortality, and laboratory parameters, will be provided in unblinded fashion. This will be 


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accomplished by using coded labels and providing the DMC members with the decoding 
information separately.
Open label period – Part 1 and Part 2
Please refer to Section 3.1 for open label treatment assignment beginning at Week 12 for Part 
1 and Day 1 for Part 2 and 3.2 for rationale.  In the open label period of this trial, treatment 
allocation will not be concealed. 
4.1.5.2
Unblinding and breaking the code
For the blinded period of this trial, emergency unblinding will be available to the investigator
via IRT. It must only be used in an emergency situation when the identity of the trial drug 
must be known to the investigator in order to provide appropriate medical treatment or 
otherwise assure safety of trial participants. The reason for unblinding must be documented in 
the source documents and/or appropriate CRF page along with the date and the initials of the 
person who broke the code.
Due to the requirements to report Suspected Unexpected Serious Adverse Reactions 
(SUSARs), it may be necessary for a representative from BI’s Pharmacovigilance group to 
access the randomisation code for individual patients during trial conduct. The access to the 
code will only be given to authorised Pharmacovigilance representatives and not be shared 
further. 
4.1.6
Packaging, labelling, and re-supply
The investigational products will be provided by BI or a designated clinical research 
organisation (CRO). They will be packaged and labelled in accordance with the principles of 
Good Manufacturing Practice (GMP).  Re-supply to the sites will be managed via an IRT 
system, which will also monitor expiry dates of supplies available at the sites.
For details of packaging and the description of the label, refer to the ISF.
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. Where 
necessary, a temperature log must be maintained for documentation
If the storage conditions are found to be outside the specified range, the local clinical monitor 
(as provided in the list of contacts) must be contacted immediately.
4.1.8
Drug accountability
The investigator or designee will receive the investigational drugs delivered by the sponsor 
when the following requirements are fulfilled:

Approval of the clinical trial protocol by the IRB/ethics committee,

Availability of a signed and dated clinical trial contract between the sponsor and the 
investigational site,

Approval/notification of the regulatory authority, e.g. competent authority,

Availability of the curriculum vitae of the Principal Investigator,

Availability of a signed and dated clinical trial protocol,


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
Availability of the proof of a medical license for the Principal Investigator, 

Availability of FDA Form 1572 (for US sites).
Investigational drugs are not allowed to be used outside the context of this protocol. They 
must not be forwarded to other investigators or clinics, if not site-to-site shipments are 
formally organized by the sponsor. Patients should be instructed to return unused 
investigational drug.
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 patient, and the return to the sponsor or warehouse / 
drug distribution centre or alternative disposal of unused products. If applicable, the sponsor 
or warehouse / drug distribution centre will maintain records of the disposal. 
These records will include dates, quantities, batch / serial numbers, expiry (‘use- by’) dates, 
and the unique code numbers assigned to the investigational product and trial patients. The 
investigator / pharmacist / investigational drug storage manager will maintain records that 
document adequately that the patients were provided the doses specified by the protocol and 
reconcile all investigational products received from the sponsor. At the time of return to the 
sponsor< and/or >appointed CRO, the investigator / pharmacist / investigational drug storage 
manager must verify that all unused or partially used drug supplies have been returned by the 
clinical trial patient and that no remaining supplies are in the investigator’s possession.
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS
4.2.1
Other treatments and emergency procedures
Stable doses of concomitant therapies for chronic conditions, for which neither the condition 
nor the treatment are judged to exclude the patient from participation (cf. Section 3.3) may be 
permissible. All concomitant medications should be carefully evaluated by the Investigator 
and the Clinical Monitor Local (CML) should be contacted when there are questions 
regarding concomitant medications.
In the event that a patient experiences an intolerable increase of PsO during the course of the 
trial, the trial medication will be discontinued and anti-psoriatic agents may be used as rescue 
medications.  Refer to Section 6.2.3 for early treatment and trial termination instructions.
In case of any AEs in need of treatment, symptomatic therapy according to investigator 
judgment will be permitted. All concomitant and/or rescue therapies will be recorded on the 
appropriate pages of the electronic case report form (eCRF).
Severe infections according to RCTC grading, serious infections, and opportunistic or 
mycobacterial infections:
Treatment of the infection should be initiated promptly according to local standard of care. 
Treatment with trial medication should be discontinued.


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Malignancies
In case of occurrence of malignant neoplasm other than appropriately treated basal cell 
carcinoma or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix, the 
investigator should discontinue treatment with the trial medication, and notify the CML. 
Diagnostics and treatment should be initiated according to local standard of care.
Suicidality
In case of signals of suicidal ideation the patient should be referred to a mental health 
professional for further work-up.
4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
The medications, classes of medications, and foods listed in Table 4.2.2.1: 1 must not be 
taken for the time periods as specified. Classes of antipsoriatic medications listed in Table 
4.2.2.1: 1 are likewise restricted, however may be permitted as rescue treatment, at the 
Investigator’s discretion, if a patient experiences an intolerable increase of PsO during the 
course of the trial and the patient is undergoing early treatment and trial termination. In such 
cases, the Investigator must notify the BI CML and document the details of the drug used and 
reason in the eCRF. A comprehensive list of restricted medications can be found in the ISF.


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Table 4.2.2.1: 1
Restricted antipsoriatic medications, concomitant treatments and food 
Medication or class of medications
Specified restriction time 
Drugs with known phototoxic or photoallergic 
potential
(e.g., tetracyclines, fluorchinolones)
One week prior to randomisation in preceding 
study until EOO in this study 
Drugs or foods (e.g., seville oranges, grapefruit, paw 
paw and their products) which are known inhibitors 
or moderate or strong inducers of CYP3A, or are 
sensitive substrates of CYP1A2 CYP2B6, or 
CYP2C8 , CYP2C9, or CYP2C19.
One week prior to randomisation in preceding 
study until EOO in this study
Drugs with narrow therapeutic windows which are 
substrates of P-gp, BCRP, OATP1B1, OATP1B3, 
OAT3, OCT2, MATE1, and MATE2-K
One week prior to randomisation in preceding 
study through EOO in this study
Investigational device or product (other than 
antipsoriatic drugs)
30 days prior to randomisationin preceding study 
through EOO in this study
Any drug known to interfere with or to aggravate PsO 
including but not limited to lithium and interferons
4 weeks prior to randomisation in preceding study 
through EOO in this study
BCG (Bacillus Calmette-Guérin) vaccine
1 year prior to randomisation in preceding study 
through 1 year after last administration of study 
drug in this study
Investigational antipsoriatic drugs
12 weeks prior to randomisation in preceding study 
through EOO in this study
 
 
 
Systemic anti-psoriatic medications or phototherapy
12 weeks prior to randomisation in preceding 
through EOO in this study
Other systemic immunomodulating treatments (e.g. 
methotrexate, cyclosporine A, corticosteroids1), 
apremilast (Otezla®1,cyclophosphamide, tofacitinib 
(Xeljanz))
1No restriction on corticosteroids with only a topical effect 
(e.g. inhalant corticosteroids to treat asthma or 
corticosteroid drops used in the eye or ear).
30 days prior to randomisation in preceding 
through EOO in this study
Other systemic psoriasis treatments (e.g., retinoids, 
fumarates, any other drug known to possibly benefit 
psoriasis)
30 days prior to randomisation in preceding 
through EOO in this study
Photochemotherapy (e.g., PUVA)
30 days prior to randomisation in preceding 
through EOO in this study
Phototherapy (e.g., UVA, UVB)
2 weeks prior to randomisation in preceding 
through EOO in this study


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Table 4.2.2.1: 1 (cont.) Restricted antipsoriatic medications, concomitant treatments and food 
cont’d
Medication or class of medications
Specified restriction time 
Topical treatment for psoriasis or any other skin 
condition (e.g. corticosteroids2, vitamin D analogues, 
vitamin A analogues, pimecrolimus, retinoids, 
salicylvaseline, salicylic acid, lactic acid, tacrolimus, tar, 
urea, andanthralin, α-hydroxy, fruit acids)
2Exception: Topical steroids of US class 6 (mild, such as 
desonide) or US class 7 (least potent, such as hydrocortisone) 
will be permitted for use limited to the face, axilla, and/or 
genitalia with a restriction of use within 24 hours prior to clinic 
visits where PASI is assessed
 2 weeks prior to randomisation in preceding 
through EOO in this study
4.2.2.2
Restrictions on diet and life style
The participants should take the medication after at least 6 hours fasting and should not eat 
for 30 minutes after drug administration.  
Foods which are known strong or moderate inhibitors of CYP 3A (e.g., seville oranges, 
grapefruit, paw paw and their products) should be avoided during the study participation.
Moisturizers/emollients containing retinoids and the use of tanning beds are not allowed 
during the study.
Throughout their participation in the study, patients should avoid prolonged exposure to
sunlight and artificial UV-light. When exposed to direct sunlight study participants should 
protect skin areas not covered by clothes by using sun-protection creams and lip balms with 
sun protection factor 30 or higher with protection against UV-A and UV-B. 
Patients should wear sunglasses when exposed to direct sun or other sources of UV-light.
These protection measures must be applied until the end of the follow-up periods.
4.2.2.3
Contraception requirements
WOCBP (for the definition please refer to Section 3.3.2) must use highly effective methods
of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year 
when used consistently and correctly during the study, and for a period of at least 28 days
after the last dose of study drug.
Highly effective methods include: 

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.

Vasectomised sexual partner with documented absence of sperm.


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Or WOCBP must abstain from male-female sex. This is defined as being in line with the 
preferred and usual lifestyle of the patient. 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
Patients are requested to bring all remaining trial medication including empty package 
material with them when attending visits.
Based on counts, treatment compliance will be calculated as shown in the formula below. 
Compliance will be verified by the Clinical Research Associate (CRA) authorised by the 
sponsor.
Treatment compliance (%) =
Number of  actually taken 100
     Number of  which should have been taken
If the number of doses taken is not between 80-120%, site staff will explain to the patient the 
importance of treatment compliance.


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5.
ASSESSMENTS
5.1
ASSESSMENT OF EFFICACY
The skin condition will be assessed by using the PASI and sPGA as described in Appendix 
10.1 and 10.2 and the ISF. 
 
5.2
ASSESSMENT OF SAFETY
5.2.1
Physical examination
A physical examination will be performed at the time points specified in the Flow Chart. It 
includes at a minimum general appearance, neck, lungs, cardiovascular system, abdomen, 
extremities, and skin. 
Measurement of body weight will be performed at the time points specified in the Flow Chart.
The results must be included in the source documents available at the site. 
5.2.2
Vital signs
Vital signs will be evaluated at the time points specified in the Flow Chart, prior to blood 
sampling.This includes systolic and diastolic blood pressure and pulse rate (electronically or 
by palpation count for 1 minute) in a seated position after 5 minutes of rest. The results must 
be included in the source documents available at the site.
5.2.3
Safety laboratory parameters
Safety laboratory parameters to be assessed are listed in Table 5.2.3: 1. For the sampling time 
points please see the Flow Chart.
All analyses will be performed by a central laboratory, the respective reference ranges will be 
provided in the ISF. 
Blood samples for safety will be drawn prior to drug administration, under fasted conditions.
Instructions regarding sample collection, sample handling/ processing and sample shipping 
are provided in the Laboratory Manual in the ISF. 
The central laboratory will send reports to the investigator. It is the responsibility of the 
investigator to evaluate the laboratory reports. Clinically relevant abnormal findings as 
judged by the investigator will be reported as adverse events (please refer to Section 5.2.6).
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 


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Electronic Data Capture (eDC) system). The amount of blood taken from the patient
concerned will be increased due to this additional sampling.
The central laboratory will transfer the results of the analysis to the sponsor.
Table 5.2.3: 1 
Safety laboratory tests
Category
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hbc (HbA1c)1
Red Blood Cell Count/ Erythrocytes
Reticulocyte Count
White Blood Cells / Leucocytes
Platelet Count/ Thrombocytes
Diff. Automatic
Neutrophils (relative and absolute count)
Eosinophils (relative and absolute count)
Basophils (relative and absolute count)
Monocytes (relative and absolute count)
Lymphocytes (relative and absolute count)
Diff. Manual (if Diff Automatic is abnormal)
Neutrophils, bands (Stabs)
Neutrophils, polymorphonuclear (PMN)
Eosinophils
Basophils
Monocytes
Lymphocytes
Coagulation
Activated Partial Thromboplastin Time (aPTT)
Prothrombin time (INR)
Fibrinogen
Enzymes
AST(GOT)
ALT(GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
CK-MB, only if CK is elevated
Gamma-Glutamyl Transferase (GGT/γ-GT)
Lactic Dehydrogenase (LDH)
Lipase
Amylase
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate
1 Only at Visit 1, Visit 5, Visit 9, Visit 13, Visit 17, Visit 21 and EOT Visit


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Table 5.2.3: 1 Safety laboratory tests Cont’d
Category
Test name
Substrates
Glucose
BUN
Uric acid
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Troponin (reflex in case of elevated CK)
Albumin
C-Reactive Protein (CRP, High sensitivity)
Cholesterol, total1
Triglycerides1
LDL-Cholesterol /HDL-Cholesterol1
Urine Pregnancy test (only for female patients of 
childbearing potential)
Human Chorionic Gonadotropin in the urine
Serum Pregnancy test (only if urine pregnancy test is 
positive) 
Human Serum Chorionic Gonadotropin 
Urinalysis with microscopic examination if urine 
analysis abnormal
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine Blood
Urine Leukocyte Esterase
Urine pH
Urine
Albumin (quantitative)
Creatinine
Infection testing
Hepatitis B Surface Antigen (qualitative)1
Hepatitis C Antibodies (qualitative)1
HIV-1 and HIV-2 Antibody (qualitative)1
QuantiFERON®-TB1
1 Only at Visit 1, Visit 5, Visit 9, Visit 13, Visit 17, Visit 21 and EOT Visit
5.2.4
Electrocardiogram
ECGs will be read and evaluated centrally. The 12-lead ECGs will be recorded as scheduled 
in the Flow Chart. ECGs may be repeated for quality reasons and the repeated recording used 
for analysis. 
If necessary, additional ECGs may be recorded for safety reasons. 
The digital ECG recordings will be transmitted to a vendor for central evaluation and the 
results will be reported to the site. 
Clinically relevant abnormal findings will be reported as AEs and will be followed up and/or 
treated as medically appropriate.


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5.2.5
Other safety parameters
5.2.5.1
Suicidality
Suicidal thoughts and behavior will be assessed by the C-SSRS (R08-1147). 
The C-SSRS is a semi-structured, 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 coordinator with C-SSRS training. It has a 
typical duration of five minutes, and causes only a low burden on subjects. 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. Free 
text entries are allowed for; the investigator has to directly evaluate the scale and write a 
report. In this trial paper forms will be used for the assessment of the C-SSRS® and results 
will be transcribed into the e-CRF.
The C-SSRS has been widely used in large multinational clinical trials. The C-SSRS was 
administered at Visit 1 of 1407-0030 (using the ‘baseline/ screening’ version) with the aim to 
exclude patients with active moderate or severe symptomatology within a specified time prior 
to the screening or screening visit of that trial. The lifetime and past year history of suicidal 
ideation and behavior was also recorded in 1407-0030.
After the screening visit, the assessment ‘since last visit’ version was performed at each visit
of 1407-0030 and will be administered at each visit of this extension trial. 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 or other 
mental health professional expert. If there is a confirmed positive report of suicidal behavior 
or suicidal ideation type 4 or 5 after start of trial, the investigator is to immediately interview 
the patient, and/or is to consult a mental health professional. If the positive report is 
confirmed, appropriate actions for the patient’s safety have to be initiated.
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, without suicidal intent’, standard AE / SAE reporting rules are 
to be applied.
For each negative report (suicidal ideation type 1, 2 or 3) after the start of the trial, the 
investigator is to decide based on clinical judgment whether it represents an Adverse Event 
(AE) as defined in the protocol, and if it is considered an AE then it must be reported 
accordingly.
5.2.5.2
Major Adverse Cardiovascular Event (MACE)
An independent adjudication committee will be used to adjudicate all observed cardio- and 
cerebro-vascular and thrombotic events reported during the conduct of the study to assure 
consistent assessment of MACE. See Section 8.7.


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5.2.6
Assessment of adverse events
5.2.6.1
Definitions of AEs 
5.2.6.1.1
Adverse event
An AE is defined as any untoward medical occurrence in a patient 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 as an AE in the CRF 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
A serious adverse event (SAE) is defined as any AE, which fulfils at least one of the 
following criteria:
-
results in death,
-
is life-threatening, which refers to an event in which the patient 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,
-
requires prolongation of existing hospitalisation,
-
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 patient and may require 
medical or surgical intervention to prevent one 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
AEs considered “Always Serious”
Cancers of new histology and exacerbations of existing cancer must be classified as a serious 
event regardless of the time since discontinuation of the drug and must be reported as 
described in Section 5.2.6.2, subsections “AE Collection” and “AE reporting to sponsor and 
timelines”.


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In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of further 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 
defined above.
The latest list of “Always Serious AEs” can be found in the eDC system. These events should 
always be reported as SAEs as described above.
5.2.6.1.4
Adverse events of special interest
The term adverse events of special interest (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:
Hepatic injury
A hepatic injury is defined by the following alterations of hepatic laboratory parameters: 

an elevation of AST (aspartate transaminase) and/or ALT (alanine aminotransferase) ≥3 
fold ULN combined with an elevation of total bilirubin ≥2 fold ULN measured in the 
same blood draw sample, or

aminotransferase (ALT, and/or AST) elevations ≥10 fold 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.
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.
Severe infections (according to RCTC grading)
Opportunistic and mycobacterial infections
These include pneumocystis jirovecii, BK virus disease including PVAN, CMV, post-
transplant lymphoproliferative disorder (EBV), progressive multifocal leucoencephalopathy, 
bartonellosis (disseminated only), blastomycosis, toxoplasmosis, coccidioidomycosis, 
histoplasmosis, aspergillosis (invasive only), candidiasis (invasive or pharyngeal), 
cryptococcosis, other invasive fungi (mucormycosis (zygomycosis, rhizopus, mucor, 
lichtheimia), scedosporium/pseudallescheria boydii, fusarium), legionellosis, listeria 
monocytogenes (invasive only), tuberculosis, nocardiosis, non-tuberculous mycobacterium, 
salmonellosis (invasive only), HBV reactivation, herpes simplex (invasive only), herpes 
zoster, strongyloides (hyperinfection syndrome and disseminated forms only), 


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paracoccidioides, penicillium marneffei, sporothrix schenckii, cryptosporidium species 
(chronic only), microsporidiosis, leishmaniasis (visceral only), trypanosoma cruzi infection 
(Chagas’ disease) (disseminated only), campylobacteriosis (invasive only),  shigellosis 
(invasive only), vibriosis (invasive due to vibrio vulnificus), HCV progression.
Gastric intolerance and gastritis:
Even though gastritis development is not expected in humans, AE consistent with gastric
intolerance or gastritis are designated as AESI to ensure timely characterization, monitoring 
and reporting of any such events in this study.
Not all gastrointestinal events will be considered AESI. Only events that are consistent with
the following definitions are considered AESI and will need to be reported accordingly:

Any adverse events of “nausea or vomiting” of moderate or worse severity (according to 
RCTC, OR of prolonged duration  (≥ 7 days), OR

Any adverse events of “gastritis” (regardless of duration or severity)
5.2.6.1.5
Intensity (severity) of AEs
The intensity grading of AEs will be performed according to Rheumatology Common 
Toxicity Criteria (RCTC) Version 2.0 developed by 
 (R13-3515). Refer to ISF 
for intensity/severity classification. Intensity options are:  
Grade 1 
mild
Grade 2 
moderate
Grade 3 
severe
Grade 4 
life-threatening
5.2.6.1.6
Causal relationship of AEs
Medical judgement should be used to determine the relationship, 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 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.

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).


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
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 drug 
concerned).

Continuation of the event despite the withdrawal of the medication, taking into 
account 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.

Additional arguments amongst those stated before, like 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
AE Collection
The investigator shall maintain and keep detailed records of all AEs in the patient files.
The following must be collected and documented on the appropriate CRF(s) by the 
investigator:
•
From signing the informed consent onwards until the individual patient’s end of trial: 
all AEs (serious and non-serious) and all AESIs.
•
After the individual patient’s end of trial: 
the investigator does not need to actively monitor the patient for new AEs but should only 
report any occurrence of cancer and related SAEs and related AESIs of which the 
investigator may become aware of by any means of communication, e.g. phone call.
Those AEs should however not be reported in the CRF.
Vital Status Collection
Patients who discontinue trial medication prematurely, who agree to be contacted further but 
do not agree to physical visits, should be followed up as described in Section 3.3.4.1, 
withdrawal from trial treatment. From then on until the individual patient’s end of the trial the 
investigator must report all deaths/fatal AEs regardless of relationship, related SAEs and 
related AESIs the investigator becomes aware of.
5.2.6.2.2
AE 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 via fax immediately (within 24 hours ) to the 
sponsor’s unique entry point (country specific contact details will be provided in the ISF). 
The same timeline applies if follow-up information becomes available. In specific occasions,


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the investigator could inform the sponsor upfront via telephone. This does not replace the 
requirement to complete and fax the BI SAE form.
With receipt of any further information to these events, a follow-up SAE form has to be 
provided. For follow-up information the same rules and timeline apply as for initial 
information.
5.2.6.2.3
Information required
All (S)AEs, including those persisting after individual patient’s end of trial must be followed 
up until they have resolved, have been assessed as “chronic” or “stable” , or no further 
information can be obtained.
5.2.6.2.4
Pregnancy
In rare cases, pregnancy might occur in a clinical trial. Once a patient 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 hours) by means of Part A of 
the Pregnancy Monitoring Form to the sponsor’s unique entry point.
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 Clinical Trials (Part B).
The ISF will contain the Pregnancy Monitoring Form for Clinical Trials (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 Clinical Trials and not the SAE form 
is to be completed. If there is an SAE and/or AESI associated with the pregnancy an SAE 
form must be completed in addition.
 
 
 
 
 
 
 
 


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5.5
BIOBANKING
Section not applicable.


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5.6
OTHER ASSESSMENTS
Section not applicable.
5.7
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements in PsO treatment 
trials and will be performed in order to monitor safety aspects or assess treatment response in 
an appropriate way.
Information about race should be obtained from all study participants as allowed by local 
regulations. This is because the prevalence and characteristics of psoriasis differ widely 
between patients of different racial origin. It will thus be worthwhile to assess if patients of 
different race will respond differently to the study treatment.


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6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
All patients are to adhere to the visit schedule as specified in the Flow Chart. Each visit date 
(with its window) is to be counted from Day 1. If any visit has to be rescheduled, subsequent 
visits should follow the original visit date schedule. Additional visits for the purpose of re-
testing of laboratory parameters or AE monitoring may be included as deemed necessary by 
the investigator.
Study procedures to be performed at each visit are listed in the Flow Chart and the respective 
protocol sections. Additional details on procedures at selected visits are provided below.
During COVID-19 or other exceptional circumstances, when it is impossible to conduct study 
visits at the study site, the study visit may be performed at the patient’s home or remotely (via 
telephone and/or internet based means of communication or by use of a home health nurse). 
The visit may also be performed as a hybrid of home and remote visit. All home/remote visits 
need to be discussed with and approved by the CTM.  Local regulatory and legal 
requirements of the participating country still apply.
If blood sampling for central lab at the trial site is not possible, safety lab analyses can be 
performed at a local lab. The results of the lab tests must be transferred to the investigator 
who ensures medical review and documents a clinically relevant safety issue as an adverse 
event. Use of a local lab must first be approved by the CTM.
All deviations from the original schedule of visits and procedures will be documented and the 
implications considered for the analysis of the trial data
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
PROs should be completed by the patient on his/her own in the pre-specified order in a quiet 
area/room before any other visit assessments or treatments, and, if possible, before any 
interaction with the investigator or other members of the study team.
The PSS will be completed by the patient at all visits, except V1, on a paper form.
The order of completion for PROs is as follows, as applicable for each PRO at relevant visits 
according to the Flow Chart:
(1) PSS 
The C-SSRS will be administered for eligibility confirmation and at all visits for assessment 
of suicidality (cf. Section 5.2.5.1).


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6.2.1
Screening period
No trial procedures should be done unless the patient has consented to taking part in the trial.
Once consented, the patient is considered to be enrolled in the trial and have started 
screening. The patient should be recorded on the enrolment log. The patient should be 
registered in IRT as a screened patient.
Re-screening will not be permitted. Patients who fail screening following Visit 1 assessments 
should be registered as a screen failure in IRT.
Re-testing for certain eligibility criteria can be performed once for abnormal laboratory, 
results.  
After the informed consent process is complete and written informed consent is obtained, the 
patients will be assessed for study eligibility including laboratory assessments as indicated in 
Section 5.2.6.  All other assessments will also be performed as summarized in the study Flow 
Chart.
6.2.2
Treatment period
The treatment period starts with Visit 1 and ends with the EOT visit. The patients will be 
fasted for each visit.
The patients will return to the clinic for regularly scheduled visits as specified in the Flow 
Chart. At these visits, the occurrence of safety and efficacy endpoints, trial medication 
compliance, concomitant therapy or intervention will be assessed.
At all treatment visits, the order of assessments (as applicable) should be followed:

Completion of the questionnaires

Physical examination, urine pregnancy, vital signs, and ECG 

Laboratory samples
All assessments must be performed before the medication is taken.
6.2.3
Follow up period and trial completion
For all randomised patients termination of trial medication and trial completion must be 
recorded on the corresponding eCRFs.
Early treatment and trial termination
If study medication is discontinued prior to the planned Flow Chart End of Treatment (EOT) 
Visit, the patient should undergo the EOT Visit as soon as possible and the End of 
Observation (EOO) Visit 4 weeks after last dose of study medication.
Vital status should be collected once a year by telephone call starting from the last trial visit 
performed until the end of the originally planned observation period.


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Trial completion
Patients who finish the treatment period will return to the clinic for EOT Visit. Trial 
completion is defined as patients having reached the EOT visit within the specified window 
per the Flow Chart. 
Patients switching to licensed BI 730357 upon completion of active treatment in this study 
should not complete a washout period.  Instead, their last trial visit will be EOT and trial 
completion will occur at that visit.  These patients will not return for EOO Visit.


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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
7.1
STATISTICAL DESIGN - MODEL
This is an extension trial of patients with moderate to severe chronic plaque psoriasis treated 
with BI 730357 after participation in preceding Trial 1407-0030. Descriptive statistics 
include exposure adjusted rate of patients reporting a TEAE, responder analysis (e.g., 
achievement of PASI75, sPGA of clear or almost clear, etc.), and time to loss of response 
(e.g. achievement of PASI75, sPGA of clear or almost clear, etc.).
This trial is designed to gain as much exposure as possible with adequate documentation of
safety, efficacy, and tolerability.
7.2
NULL AND ALTERNATIVE HYPOTHESES
There is no formal statistical hypothesis testing in this trial.
7.3
PLANNED ANALYSES
The descriptive analyses will be based on cumulative event incidence rates at critical 
timepoint, proportions of patients achieving a response (e.g., achieving PASI75, sPGA of 
clear or almost clear, etc.), and Kaplan Meier empirical survival curves to describe patterns of 
event incidence. 
The treated set (TS) in this trial for analyses is defined as: 

All patients who received at least one dose of treatment in the extension trial. It will 
be the main analysis set for presentation of safety and efficacy of the extension trial. 
Further analysis sets will be defined in the TSAP if necessary.
For all analyses, baseline refers to the baseline value in the 1407-0030 study.
7.3.1
Primary endpoint analyses
Refer to Section 7.3.4 for the description of safety analyses including that for the primary 
endpoint.
7.3.2
Secondary endpoint analyses
The rate of achievement of PASI50/PASI75/PASI90/PASI100 at Week 24 in the extended 
dosing period will be calculated. The same methods will be used to analyse other binary 
secondary endpoints, including achievement of sPGA clear or almost clear, sPGA clear. Time 
to loss of response (e.g. PASI75, sPGA of clear or almost clear, etc.) will be analysed 
descriptively by Kaplan Meier curves.
Additional information on these analyses will be provided in the TSAP.


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7.3.4
Safety analyses
Adverse events will be coded using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA). Standard BI summary tables and listings will be produced. All adverse events 
with an onset between start of treatment and end of the REP, a period of 7 days after the last 
dose of trial medication, will be assigned to the on-treatment period for evaluation.
All treated patients 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 adverse events will concentrate on treatment-emergent 
adverse events, i.e. all adverse events occurring between start of treatment and end of the 
REP. Adverse events that start before first drug intake and deteriorate under treatment will 
also be considered as ‘treatment-emergent’.
Exposure-adjusted adverse event incidence rates (per the primary endpoint) will be calculated 
using the following approach:

The incidence rate (per 100 subject years) of a selected adverse event (also known as
the incidence density rate or person-time incidence rate) is defined as the number of
subjects experiencing the adverse event per treatment group during the time at risk
divided by the total time of subjects at risk in that treatment group to contribute an 
event to the analysis multiplied by 100 (per 100 subject years), where:
Time at risk [subject years] = (date of onset of AE – study drug start date + 1)
/ 365.25
If, for a subject, no treatment emergent adverse event occurred, then the time at risk
will be censored at the minimum of (date of death; drug stop date + 28 days; last 
contact date).
For each AE, the incidence rate will therefore be calculated as:
Incidence rate [per 100 subject years (pt-yrs)] = 100 * number of subjects with
TEAE / Total TEAE-specific time at risk [subject years].
Exact 95% confidence intervals (CI) around the observed AE incidence rate will also be
provided.


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Frequency, severity, and causal relationship of adverse events will be tabulated by system 
organ class and preferred term after coding according to the current version of the Medical 
Dictionary for Drug Regulatory Activities (MedDRA) at database lock.
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 patients 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 to findings before start of treatment.
 
 
7.4
INTERIM ANALYSES
No interim analysis is planned. DMC will be in place with tasks as described in Section 8.7.  
Additionally, the efficacy analysis may be conducted by visit while the data collection for 
selected other analyses is still ongoing.
7.5
HANDLING OF MISSING DATA
Every effort should be made to collect complete data at all visits.
With respect to safety evaluations, it is not planned to impute missing values.
Missing items from the Quality of Life questionnaires will be handled according to the 
measure instructions. If there is no data for a particular visit, then it will be imputed following 
the same rules as described above.
More details will be included in the TSAP, if needed.
7.6
RANDOMISATION
There is no randomisation for this trial. The participants in this extension trial will be 
assigned with pre-specified treatment regimen and doses of BI 730357 as specified in Section 
3.1.


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7.7
DETERMINATION OF SAMPLE SIZE
The sample size will be up to approximately 270 patients. It will be determined by patients 
who have completed the randomized treatment period without early treatment discontinuation 
in 1407-0030 and are willing and able to continue treatment in this extension trial. Patients in 
the subsequent Psoriasis trials are expected to enroll in this extension trial, if applicable. 


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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 protocol, the ethical principles laid down 
in the Declaration of Helsinki, in accordance with the ICH Harmonized Guideline for Good 
Clinical Practice (GCP), relevant BI Standard Operating Procedures (SOPs), the EU 
regulation 536/2014 and other relevant regulations. Investigators and site staff must adhere to 
these principles.
Standard medical care (prophylactic, diagnostic and therapeutic procedures) remains the 
responsibility of the treating physician of the patient.
The investigator will inform the sponsor immediately of any urgent safety measures taken to 
protect the trial patients against any immediate hazard, as well as of any serious breaches of 
the protocol or of ICH GCP.
The Boehringer Ingelheim 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 rule, no trial results should be published prior to finalization of the Clinical Trial Report.
The certificate of insurance cover is made available to the investigator and the patients, 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 Institutional Review Board (IRB / Independent Ethics Committee 
(IEC and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to patient participation in the trial, written informed consent must be obtained from each 
patient (or the patient’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 and any additional patient-
information form retained by the investigator as part of the trial records. A signed copy of the 
informed consent and any additional patient information must be given to each patient or the 
patient’s legally accepted representative.”
The investigator or delegate must give a full explanation to trial patients based on the patient
information form. A language understandable to the patient should be chosen, technical terms 
and expressions avoided, if possible. 
The patient must be given sufficient time to consider participation in the trial. The 
investigator or delegate obtains written consent of the patient’s own free will with the 
informed consent form after confirming that the patient understands the contents. The 


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investigator or 
 delegate must sign (or place a seal on) and date the informed consent form. 
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.
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 subject protection and reliability of the results as well as 
identification and assessment of associated risks. An Integrated Quality and Risk 
Management Plan 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 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 patients will be provided by the sponsor. See Section 4.1.5.2 for rules 
about emergency code breaks. 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 patient. 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 patient 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 three documented attempts to 
retrieve previous medical records. If this fails, a verbal history from the patient, documented 
in their medical records, would be acceptable.


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During the site visit the sponsor’s CRA or auditor must be granted access to the original 
patient file (please see Section 8.3.2). 
The investigator must ensure that all patient identifiers (e.g. patient’s name, initials, address, 
phone number, social security number) have properly been removed or redacted from any 
copy of the patients’ source documents before sending them to the sponsor.
Copies of source documents necessary for adjudication assessment will be provided to the 
vendor upon request. Before sending or uploading those copies, the investigator must ensure 
that all patient identifiers (e.g. patient’s name, initials, address, phone number, social security 
number) have properly been removed or redacted from any copy of the patients’ source 
documents.
If the patient is not compliant with the protocol, any corrective action e.g. re-training must be 
documented in the patient file.
For the CRF, data must be derived from source documents, for example:

Patient identification: gender, year of birth (in accordance with local laws and 
regulations)

Patient participation in the trial (substance, trial number, patient number, date patient was 
informed)

Dates of patient’s visits, including dispensing of trial medication

Medical history (including trial indication and concomitant diseases, if applicable)

Medication history

Adverse events and outcome events (onset date (mandatory), and end date (if available))

Serious adverse events (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)

Completion of patient’s participation in the trial” (end date; in case of premature 
discontinuation document the reason for it).

Prior to allocation of a patient 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 patient or testing 
conducted specific for a protocol) to support inclusion/exclusion criteria does not make 
the patient eligible for the clinical trial.
8.3.2
Direct access to source data and documents
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 protocol and GCP.


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Remote source data verification is acceptable in rare cases where onsite monitoring visits 
cannot take place due to the COVID-19 pandemic or other unforeseen circumstances.  
Remote source data verification must first be approved by the CTM and must be aligned with 
local laws and regulations.
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 
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 PATIENT PRIVACY
Individual patient data obtained as a result of this trial is considered confidential and 
disclosure to third parties is prohibited with the exceptions noted in Section 8.7. 
Data protection and data security measures are implemented for the collection, storage and 
processing of patient data in accordance with the principles 6 and 12 of the WHO GCP 
handbook.
Personalised treatment data may be given to the patient’s personal physician or to other 
appropriate medical personnel responsible for the patient’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.
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 and future use of 
biological samples and clinical data, in particular

The BI-internal facilities storing biological samples from clinical trial participants as 
well as the external facility are qualified for the storage of biological samples 
collected in clinical trials.

An appropriate sample and data management system, incl. audit trail for clinical data 
and samples to identify and destroy such samples according to 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


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8.6
TRIAL MILESTONES
The start of the trial is defined as the date when the first patient in the whole trial signs 
informed consent.
The end of the trial is defined as the date of the last visit of the last patient in the whole trial
(“Last Patient Completed”).
The “Last Patient Last Treatment” (LPLT) date is defined as the date on which the last 
patient 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 protocol.
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.
The IEC / competent authority in each participating EU member state will be notified about 
the trial milestones according to the respective laws.
A final report of the clinical trial data will be written only after all patients have completed 
the trial in all countries (EU or non-EU) to incorporate and consider all data in the report.
The sponsor will submit to the EU database a summary of the final trial results within one 
year from the end of a clinical trial as a whole, regardless of the country of the last patient
(EU or non-EU).
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL
The trial is sponsored by Boehringer Ingelheim (BI).
A Coordinating Investigator is responsible to coordinate investigators at the different sites 
participating in this trial. Tasks and responsibilities are defined in a contract.
Data Monitoring Committee
A Data Monitoring Committee (DMC) will be established. Members of the DMC are 
independent of BI, they are physicians experienced in the treatment of the disease under 
investigation and a statistician. 
The DMC will evaluate safety data and efficacy data of the trial. The DMC will receive 
notification of urgent significant safety concerns including severe infections, suicidality 
reports, MACE and DILI cases for immediate evaluation. While DMC members may be 
unblinded, measures are in place to ensure the blinding for everyone else involved in the trial. 
Regular DMC meetings will be held at specified intervals. The DMC will recommend 
continuation, modification or termination of the trial as detailed in the DMC charter. DMC 
recommendations as well as the final BI decision will be reported to the appropriate 
RAs/HAs, IRBs/ECs, and to investigators as requested by local law. The tasks and 
responsibilities of the DMC are specified in a charter.


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Part 1
Prior to the first patient advancing to the open label phase of 1407-0005, the DMC will 
review all available 1407-0030 safety data.  The review will include data from a large 
fraction of patients that have completed Week 4, as well as, any patient safety data available 
beyond Week 4.  The DMC will evaluate the safety of the 100 mg and 200 mg dose levels 
proposed for the open label period and provide a recommendation regarding the acceptability
of proceeding with these doses.  After this review, the DMC will continue to review the 
accumulating safety data on an ongoing basis.  Details are specified in a charter.
If an unacceptable risk regarding the safety of the 200 mg dose level is reported by the DMC, 
the 100 mg and 200 mg BI 730357 dose groups planned for the open label treatment period 
will be changed to have all patients receive the 100 mg dose (Refer to Section 3.1).  If this 
alternative dosing scheme is required to be implemented due to identification of a safety 
signal, investigators will be informed by written communication from the Team Member 
Medicine and Clinical Trial Leader prior to the first patient reaching Week 12 in 1407-0005.  
IRT will be used to directly implement the changed dosing assignment and will require no 
additional actions by investigators or site staff.
Part 2
If an unacceptable risk regarding the safety of the 400 mg dose level is reported by the DMC 
prior to or during the implementation of Part 2, then Part 2 dosing may be amended as 
required.  If any changes to Part 2 are required due to identification of a safety signal, 
investigators will be informed by written communication from the Team Member Medicine 
and Clinical Trial Leader.  
During the conduct of the trial, the DMC will continue to review the accumulating safety data 
on an ongoing basis.  Details are specified in a charter.
MACE adjudication committee
An independent adjudication committee will be used to adjudicate all observed cardio- and 
cerebro-vascular and thrombotic events reported during the conduct of the study to assure 
consistent assessment of MACE.This review will be blinded to treatment allocation; the 
events that are to be adjudicated and the adjudication process will be detailed in the MACE 
Adjudication Committee Charter. 
Relevant documentation on the participating (Principal) Investigators (e.g. their curricula 
vitae) will be filed in the (Investigator Site File) ISF. The investigators will have access to the 
BI clinical trial portal (
 to facilitate document exchange and maintain electronic 
ISF. 
BI has appointed a Trial Clinical Monitor, 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,
-
ensure appropriate training and information of Local Clinical Monitors (CML), 
Clinical Research Associates (CRAs), and investigators of participating countries.


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The organisation of the trial in the participating countries will be performed by the respective 
local or regional BI-organisation (Operating Unit, OPU) in accordance with applicable 
regulations and BI SOPs, or by a Contract Research Organisation (CRO) with which the 
responsibilities and tasks will have been agreed and a written contract filed before initiation 
of the clinical trial.
Data Management and Statistical Evaluation will be done by BI according to BI SOPs.
Tasks and functions assigned in order 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.
A central laboratory service, a central ECG service and an IRT vendor will be used in this 
trial. Details will be provided in the IRT Manual, the ECG instructions and Central 
Laboratory Manual, available in the ISF.


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9.
REFERENCES
9.1
PUBLISHED REFERENCES
P20-07441
Menter A, Gelfand JM, Connor C, et al. Joint American Academy of 
Dermatology – National Psoriasis Foundation guideliens of care for the 
management of psoriasis with systemic nonbiologic therapies. J Am Acad 
Dermatol. 2020;82:1445-86.
R03-1208
NPF psoriasis score. Psoriasis Forum. 8:2. 2002
R05-2548
Finlay AQ, Khan GK. Dermatology Life Quality Index (DLQI) – a simple 
practical measure for routine clinical use. Joint Ann Mtg of the British 
Association of Dermatologists and the Canadian Dermatology Association, 
Oxford, 6-10 July 1993. Clin Exp Dermatol. 19. 210-216. 1994.
R08-1089
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of 
psoriasis. Nature. 445:7130. 866-873. 2007.
R08-1147
Posner K. State of the science: measurement of suicidal adverse events and 
the Columbia Suicide Severity Rating Scale. 47th NCDEU Ann Mtg, Boca 
Raton, 11 - 14 Jun 2007
R11-1257
Nestle FO, Kaplan DH, Barker J. Mechanisms of disease: psoriasis. N Engl 
J Med. 361:5. 496-509. 2009.
R11-1260
Griffiths CEM, Baker JNWN. Psoriasis 1: pathogenesis and clinical 
features of psoriasis. Lancet. 370. 263-271. 2007.
 
 
 
 
R13-3515
Woodworth T, Furst DE, Alten R, Bingham C, Yocum D, Sloan V, Tsuji 
W, et.al. Standardizing assessment and reporting of adverse effects in 
rheumatology clinical trials II: the Rheumatology Common Toxicity 
Criteria v.2.0. J Rheumatol 34:6. 1401-1414. 2007.
R14-3559
Revicki DA, Jin Y, Wilson HD, Chau D, Viswanathan HN Reliability and 
validity of the psoriasis symptom inventory in patients with moderate-to-
severe psoriasis. J Dermatol Treat 25 (1), 8 - 14 (2014)
R14-3562
Bushnell DM, Martin ML, McCarrier K, Gordon K, Chiou CF, Huang X,et 
al. Validation of the Psoriasis Symptom Inventory (PSI), a patient-reported 
outcome measure to assess psoriasis symptom severity. J Dermatol Treat. 
24(5): 356-360. 2013
R15-1219
Martin ML, McCarrier KP, Chiou CF, Gordon K, Kimball AB, Voorhees 
AS van, et al.. Early development and qualitative evidence of content 
validity for the Psoriasis Symptom Inventory (PSI), a patient-reported 
outcome measure of psoriasis symptom severity. J Dermatol Treat 24(4): 
255-260. 2013.


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R15-1410
Lebwohl M, Swensen AR, Nyirady J, Kim E, Gwaltney CJ, Strober BE. 
The psoriasis symptom diary: development and content validity of a novel 
patient reported outcome instrument. Int J Dermatol 53(6): 714-722. 2014.
R15-1411
Strober BE, Nyirady J, Mallya UG, Guettner A, Papavassilis C, Gottlieb 
AB, et al. Item-level psychometric properties for a new patient-reported 
psoriasis symptom diary. Value Health 16(6): 1014-1022. 2013.
R15-5200
Langley RGB, Feldman SR, Nyirady J, Kerkhof P van de, Papavassilis C. 
The 5-point Investigator's Global Assessment (IGA) scale: a modified tool 
for evaluating plaque psoriasis severity in clinical trials. J Dermatol Treat. 
26:1. 23-31. 2015.
 
.
R16-3072
Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl M. Association of 
patient-reported psoriasis severity with income and employment. J Am 
Acad Dermatol. 57:6. 963-971. 2007.
 
 
 
from manipulating the Th17 pathway. Eur J Immunol. 39. 667-669. 2009.
R16-4115
Mattei PL, Corey KC, Kimball AB. Cumulative life course impairment: 
evidence for psoriasis. Curr Probl Dermatol. 44. 82-90. 2013.
R17-1989
Burgos-Pol R, Martinez-Sesmero JM, Ventura-Cerda JM, Elias I, Caloto 
MT, Casado MA. The cost of psoriasis and psoriatic arthritis in 5 European 
countries: a systematic review. Actas Dermos Sifiliogr. Engl. Ed. 107:7. 
577-590. 2016.
R17-1990
Vanderpuye-Orgle J, Zhao Y, Lu J, et al. Evaluating the economic burden 
of psoriasis in the United States. J Am Acad Dermatol. 72:6. 961-967. 
2015.
R96-3541
Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new 
retinoid. Dermatologica. 157. 237-244. 1978.
9.2
UNPUBLISHED REFERENCES
c09228382
Investigators´s Brochure. BI 730357. Psoriasis (ankylosing spondylitis, 
psoriatic arthritis, asthma, inflammatory bowel disease). Current version.
n00250111
 Prediction of BI 730357 Pharmacokinetics and 
Therapeutic Dose in Human. Current version.
n00255738-02
BI 730357 Twenty-six-Weeks Oral (Gavage) Toxicity and Toxicokinetic 
Study in the Rat Followed by a Six-Week Recovery Period. BI Study 
Number 17R037. 05 December 2018
s00083382-01
BI 730357 Development Safety Update Report (DSUR). No. 03. 27 Jan 
2020.


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10.
APPENDICES
10.1
PASI SCORE DEFINITION AND USE
The PASI score is an established measure of clinical efficacy for psoriasis medications (R96-
3541).
The PASI is a tool which provides a numeric scoring for patients overall psoriasis disease 
state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin that is 
affected and the severity of erythema, infiltration, and desquamation over four body regions.
The endpoints used are based on the percent reduction from baseline, generally summarized 
as a dichotomous outcome based on achieving over an X% reduction (or PASI X), where X is 
50, 75, 90 and 100.
To calculate the PASI score, the four main body areas are assessed: head (h), trunk (t), 
upper extremities (u) and lower extremities (l). These correspond to 10, 30, 20 and 40% of 
the total body area respectively.
The area of psoriatic involvement of these four areas (Ah, At, Au, and Al) is given a 
numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 4 = 50 to 
<70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement.
The signs of severity, erythema (E), infiltration (I) and desquamation (D) of lesions are 
assessed using a numeric scale 0-4 where 0 is a complete lack of cutaneous involvement and 
4 is the severest possible involvement; scores are made independently for each of the areas, h, 
t, u and l and represents a composite score for each area. An illustration of judging erythema 
follows: 0 = no erythema, 1 = slight erythema, 2 = moderate erythema, 3 = striking erythema, 
and 4 = exceptionally striking erythema.
The PASI score is calculated according to the following formula:
PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 0.4(El+Il+Dl)Al


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10.2
STATIC PHYSICIAN GLOBAL ASSESSMENT (SPGA)
The sPGA used in this trial is a 5 point score ranging from 0 to 4, based on the physician’s 
assessment of the average thickness, erythema, and scaling of all psoriatic lesions (Table 
10.2: 1) (R15-5200). The assessment is considered “static” which refers to the patients 
disease state at the time of the assessments, without comparison to any of the subject’s 
previous disease states, whether at Baseline or at a previous visit.
A lower score indicates less body coverage, with 0 being clear and 1 being almost clear.
The Investigator (or qualified site personnel) scores the erythema, induration and scaling of 
all psoriatic lesions from 0 - 4 based on the following descriptors:
Erythema
0 Normal (post-inflammatory hyper/hypopigmentation may be present)
1 Faint, diffuse pink or slight red coloration 
2 Mild (light red coloration)
3 Definite red coloration (Dull to bright red)
4 Bright to Deep red coloration of lesions
Induration (plaque elevation)
0 None
1 Just detectable (slight elevation above normal skin) 
2 Mild thickening (slight but definite elevation, typically edges are indistinct or sloped)
3 Clearly distinguishable to moderate thickening (marked definite elevation with rough 
or sloped edges)
4 Severe thickening with hard edges (marked elevation typically with hard or sharp 
edges)
Scaling 
0 No scaling
1 Minimal focal scaling (surface dryness with some desquamation)
2 Predominately fine scaling (fine scale partially or mostly covering lesions)
3 Moderate scaling (coarser scale covering most or all of the lesions)
4 Severe /coarse scaling covering almost all or all lesions (coarse, non-tenacious scale 
predominates)
Scoring: a composite score is generated from the above data and the final sPGA is 
determined from this composite score as follows:
Clear 
0 = 0 for all three
Almost clear 1 = mean >0, <1.5
Mild 
2 = mean >= 1.5, <2.5
Moderate 
3 = mean >= 2.5, <3.5
Severe 
4 = mean >= 3.5


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Table 10.2: 1
sPGA Rating Scale for Overall Psoriatic Disease
Score
Short description
Detailed description
0
clear
No signs of psoriasis. Post-inflammatory hyperpigmentation 
may be present
1
almost clear
Normal to pink coloration
Just detectable (possible slight elevation above normal skin)
No to minimal focal scaling
2
mild
Pink to light red coloration
Mild thickening (slight but definite elevation, typically 
edges are indistinct or sloped)
Predominantly fine scaling
3
moderate
Dull to bright red coloration
Clearly distinguishable to moderate thickening
Moderate scaling
4
severe
Bright to deep dark red coloration;
Severe thickening with hard edges
Severe coarse scaling covering almost all or all lesions
 
 
 


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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
11.1
GLOBAL AMENDMENT 1
Date of amendment
21 May 2019
EudraCT number
EU number
2018-003487-31
BI Trial number
1407-0005
BI Investigational Product(s)
BI 730357
Title of protocol
Phase II long-term extension study to assess the 
safety, tolerability, and efficacy of BI 730357 
in patients with moderate-to-severe plaque 
psoriasis
Global Amendment due to urgent safety reasons
Global Amendment
Section to be changed
Title 
page
Synopsis
Coordinating Investigator
Coordinating Investigator
Description of change
Updated address.
Rationale for change
Correction.
Section to be changed
Synopsis
3.3.2
4.2.2.3
5.2.6.2.4
Main in- and exclusion criteria
Inclusion criteria
Contraception requirements
Pregnancy
Description of change
Removed the requirement for contraception in 
male study participants and use of a barrier 
method.  Aligned impacted sections.
Rationale for change
Based on nonclinical data (no genotoxicity 
demonstrated or suspected human 
teratogenicity/fetotoxicity at therapeutic 
systemic exposure levels) no measures are 
needed for contraception in male trial 
participants with a partner that is a WOCBP.  
Section to be changed
1.2
1.4
Drug profile
Benefit-risk assessment
Description of change
Information added that no drug-drug 
interactions of CYP3A4 substrates and 
BI 730357 as a perpetrator are to be expected.


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Rationale for change
To include results from a recently completed 
clinical multiple rising dose study with a 
midazolam micro-dose sub study.
Section to be changed
4.2.1
5.2.6.1.4
Other treatments and emergency procedures
Adverse events of special interest
Description of change
“Mycobacterium tuberculosis” replaced by “all 
mycobacterial infections”.
Rationale for change
To include and cover a more complete picture 
of opportunistic infections in the definition.
Section to be changed
4.2.2.1
Restrictions regarding concomitant treatment
Description of change
Revisions to table 4.2.2.1:1.
CYP3A4 substrates deleted from the list of 
restricted medications. 
Additional details and examples added.
Rationale for change
No drug-drug interactions of CYP3A4 
substrates are to be expected and text added for 
clarification.
Section to be changed
4.2.2.2
Restrictions on diet and life style
Description of change
Rephrased fasting instructions.
Rationale for change
For clarification.
Section to be changed
5.2.1
Physical examination
Description of change
Removed height.
Rationale for change
Height is not measured per trial flow chart.
Section to be changed
6.2.2
Treatment period
Description of change
Removed unnecessary ordering of assessments. 
Rationale for change
ECG may be performed in any order with the 
other assessments it is grouped with.
Section to be changed
1.2
7.3.4
Drug profile
Safety analysis
Description of change
Residual effect period reduced from 28 days to 
7 days.
Rationale for change
Correction. 
The follow-up period after end of treatment 
will remain at 28 days.
Section to be changed
1.4
3.1
3.1: 1
3.2
4.1.2
8.7
Benefit-risk assessment
Overall trial design and plan
Dose assignment in extension Trial 1407-0005
Discussion of trial design 
Selection of doses in the trial 
Administrative structure of the trial


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Description of change
Details added and refined regarding the timing 
and process for DMC review of 1407-0030 data 
prior to the start of open label dosing in 1407-
0005.
Rationale for change
DMC oversight wording revised to align with 
the charter.  
Section to be changed
1.2
1.4
4.2.2.2
5.2.3
5.2.5.1
5.2.5.2
5.3.4
8.7
Drug profile
Benefit – risk assessment
Restrictions on diet and life style
Safety laboratory parameters
Suicidality
Major adverse cardiovascular event (MACE)
Pharmacokinetic – pharmacodynamic 
relationship
Administrative structure of the trial
Description of change
Linguistic and stylistic errors corrected.
Rationale for change
Improved readability. 


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11.2
GLOBAL AMENDMENT 2
Date of amendment
04 Jun 2019
EudraCT number
EU number
2018-003487-31
BI Trial number
1407-0005
BI Investigational Product(s)
BI 730357
Title of protocol
Phase II long-term extension study to assess the 
safety, tolerability, and efficacy of BI 730357 
in patients with moderate-to-severe plaque 
psoriasis
Global Amendment due to urgent safety reasons
Global Amendment
Section to be changed
Title 
page
Version and date
Description of change
No changes to the content of the protocol have 
been made between Version 2.0 and 3.0.
Rationale for change
Technical update due to errors in the signature 
process for Version 2.0. 


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11.3
GLOBAL AMENDMENT 3
Date of amendment
06 Oct 2020
EudraCT number
EU number
2018-003487-31
BI Trial number
1407-0005
BI Investigational Product(s)
BI 730357
Title of protocol
Phase II long-term extension study to assess the 
safety, tolerability, and efficacy of BI 730357 
in patients with moderate-to-severe plaque 
psoriasis
Global Amendment due to urgent safety reasons
Global Amendment
Section to be changed
Title 
Page and 
synopsis
Title Page and synopsis
Description of change
Change title from Clinical Trial Monitor to 
Trial Clinical Monitor and change name
Rationale for change
New standard title and new monitor assigned.
Section to be changed
Synopsis
Synopsis
Description of change
Add description of Part 1 and 2. Add 
information describing Part 2 throughout 
synopsis.
Updated number of patients to add Part 2.
Changed wording for primary endpoint.
Added exclusion criterion for ongoing drug 
related adverse events from 1407-0030.
Rationale for change
Adding Part 2 to align with the addition of Part 
2 to trial 1407-0030 and allow those patients to 
roll over to this trial.


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Section to be changed
Flow 
Chart
Flow Chart
Description of change
Add Visits 1.1, 1.2 and 1.3 for Part 2 patients 
and clarification that Visit 2.1 is unchanged for 
Part 1 patients and not applicable for Part 2 
patients. Add an allowable administrative delay 
for Part 2 patients at Visit 1.
Rationale for change
Additional safety information to be collected 
during first 12 weeks for patients in Part 2 to 
ensure safety of placebo patients from 1407-
0030 rolling over and starting at the 400 mg 
q.d. dose.


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Section to be changed
1.1
Medical Background
Description of change
Add updated psoriasis background information 
and new reference, remove old reference.
Rationale for change
To provide most recent available information.
Section to be changed
1.2
Drug Profile
Description of change
Data from non-clinical and toxicology studies
has been updated, including the addition of 
gastritis finding in dogs.
Data from clinical studies has been updated to 
replace interim results from Phase 1 trials with
final results and add interim results from 
ongoing Trial 1407-0030.
Rationale for change
To provide most recent available information 
and align with current IB.
Section to be changed
1.3
Rationale for performing the trial
Description of change
Update the rationale to include information 
regarding Part 2.
Rationale for change
Provide information on the rationale for Part 2 
dosing and design.
Section to be changed
1.4
Benefit-Risk Assessment
Description of change
Added text on AESI of gastric intolerance or 
gastritis.
Information on DDI potential and malignancy 
has been updated.
Information regarding potential Cyp3A 
interactions has been updated.
Rationale for change
To provide background on why gastric AEs are 
added to AESIs.
To reflect the latest results from DDI and 
toxicology trials.
Section to be changed
2.1.2
Primary Endpoint
Description of change
Changed wording for primary endpoint.
Rationale for change
The definition of ‘an endpoint’ should be at 
individual level at one particular time point, 
and to make the wording consistent across 
protocols in the project.
Section to be changed
3.1
3.2
3.3
Overall trial design and plan
Discussion of trial design, including the choice 
of control groups
Selection of trial population
Description of change
Updated to describe original patient population 


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as Part 1 and add new patient population as Part 
2.
Describe the design and dosing paradigm for 
Part 2.
Rationale for change
Adding Part 2 to align with the addition of Part 
2 to trial 1407-0030 and allow those patients to 
roll over to this trial.
Section to be changed
3.3.2
Inclusion criteria
Description of change
Add criteria for Part 2 patients to roll over from 
1407-0030 trial to this trial.
Rationale for change
Adding Part 2 to align with the addition of Part 
2 to trial 1407-0030 and allow those patients to 
roll over to this trial.
Section to be changed
3.3.3
Exclusion criteria
Description of change
Remove candidiasis as an exclusion and add 
exclusion for ongoing drug related AEs.
Rationale for change
Candidiases is no longer considered an 
exclusion for BI 730357 and safety concern 
with drug related AEs over long term treatment.
Added exclusion criterion for ongoing drug 
related adverse events from 1407-0030.
Section to be changed
4.1.2
4.1.3
4.1.4
4.1.5
Selection of doses in the trial and dose 
modifications
Method of assigning patients to treatment 
groups
Drug assignment and administration of doses
Blinding
Description of change
Updated to describe original patient population 
as Part 1 and add new patient population as Part 
2.
Describe the design and dosing paradigm for 
Part 2.
Add option to allow patients from Part 1 on 100 
mg dose to up-titrate to 200 mg dose.
Rationale for change
Adding Part 2 to align with the addition of Part 
2 to trial 1407-0030 and allow those patients to 
roll over to this trial. Data from 1407-0030 trial 
indicates 100 mg dose is sub-optimal.
Section to be changed
4.1.4
Drug assignment and administration of doses
Description of change
Added language to 4.1.4 regarding options for 
limiting physical visits if needed due to Covid 
19.


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Rationale for change
Provide guidance to investigators to manage 
visit disruptions due to Covid 19.
Section to be changed
4.2.2.1
Restrictions regarding concomitant treatment
Description of change
Updated text to align with new DDI data..
Rationale for change
To ensure restrictions are current.
Section to be changed
5.2.3
Safety laboratory parameters
Description of change
Removed urine sediment as separate section, 
add to description of urinalysis. Update Urine 
RBC and WBC description
Rationale for change
Updated to correspond to current central 
laboratory standard tests and reporting.
Section to be changed
5.2.6.1:4
Adverse events of special interest.
Description of change
AE consistent with gastric intolerance or 
gastritis are designated as AESI.
Rationale for change
To ensure timely characterisation, monitoring 
and reporting of such effects.
Section to be changed
6.1
Visit schedule
Description of change
Add language to allow modifications to visits in 
response to Covid-19.
Rationale for change
Allow flexibility to monitor patient status 
during Covid 19 if in person visits are not 
possible.
Section to be changed
8.3.2
Direct access to source data and documents
Description of change
Add language regarding remote source data 
verification.
Rationale for change
Remote source data verification now permitted 
in certain circumstances.
Section to be changed
8.7
Administrative structure of the trial
Description of change
Add information regarding DMC review of Part 
2.
Rationale for change
Adding Part 2 to align with the addition of Part 
2 to trial 1407-0030 and allow those patients to 
roll over to this trial.
Section to be changed
9.1
Published references
Description of change
Add reference P20-07441 and delete reference 
R11-1259.
Rationale for change
To add new reference used in text and remove 
reference it replaced.
Section to be changed
9.2
Unpublished References


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Description of change
Reference DSUR s00083382-01 added.
Rationale for change
To add new reference used in added text.


 
 
 
 
APPROVAL / SIGNATURE PAGE 
 
Document Number: 
 
Technical Version Number:
 
Document Name: 
 
 
 
                                                                                                                 
 
Title: 
 
 
 
 
                                                                                                                   
 
Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c22181693
4.0
clinical-trial-protocol-version-4
Phase II long-term extension study to assess the safety, tolerability, and efficacy of
BI 730357 in patients with moderate-to-severe plaque psoriasis
Author-Clinical Trial Leader
07 Oct 2020 18:18 CEST
Author-Clinical Pharmacokineticist
08 Oct 2020 15:31 CEST
Approval-Biostatistics
08 Oct 2020 23:52 CEST
Approval-Therapeutic Area
09 Oct 2020 15:48 CEST
Approval-Team Member Medicine
09 Oct 2020 23:03 CEST
Verification-Paper Signature
Completion
12 Oct 2020 14:34 CEST


Boehringer Ingelheim 
Page 2 of 2
Document Number: 
 Technical Version Number:
 
 
 
(Continued) Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c22181693
4.0

SAP_001.pdf: 
TITLE PAGE
TRIAL STATISTICAL ANALYSIS PLAN
c35126725-01
BI Trial No.:
1407-0005
Title:
Phase II long-term extension study to assess the safety, tolerability, 
and efficacy of BI 730357 in patients with moderate-to-severe 
plaque psoriasis
Investigational
Product(s):
BI 730357
Responsible trial 
statistician(s):
 
Phone:
Date of statistical 
analysis plan:
03 MAR 2021 SIGNED
Version:
1 
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2021 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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1.
TABLE OF CONTENTS
TITLE PAGE............................................................................................................................1
1.
TABLE OF CONTENTS......................................................................................2
LIST OF TABLES ...................................................................................................................4
2.
LIST OF ABBREVIATIONS...............................................................................5
3.
INTRODUCTION.................................................................................................6
4.
CHANGES IN THE PLANNED ANALYSIS OF THE STUDY ......................7
5.
ENDPOINTS(S).....................................................................................................7
5.1
PRIMARY ENDPOINT(S)...................................................................................7
5.2 
SECONDARY ENDPOINTS ...............................................................................7
5.2.1
Key secondary endpoint(s) ...................................................................................7
5.2.2
Secondary endpoint(s)...........................................................................................7
6.
GENERAL ANALYSIS DEFINITIONS.............................................................9
6.1
TREATMENT(S) ..................................................................................................9
6.2
IMPORTANT PROTOCOL DEVIATIONS....................................................14
6.3
SUBJECT SETS ANALYSED ...........................................................................14
6.5
POOLING OF CENTRES..................................................................................15
6.6
HANDLING OF MISSING DATA AND OUTLIERS ....................................15
6.6.1
Efficacy data .......................................................................................................15
6.6.2
Safety data and other data.................................................................................16
6.6.3 
AE dates and times..............................................................................................16
6.6.5
Blood serum and plasma biomarker data.........................................................16
6.7
BASELINE, TIME WINDOWS AND CALCULATED VISITS....................16
7.
PLANNED ANALYSIS ......................................................................................19
7.1
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS .........20
7.2
CONCOMITANT DISEASES AND MEDICATION......................................20
7.3
TREATMENT COMPLIANCE ........................................................................21
7.4
PRIMARY ENDPOINT(S).................................................................................21
7.4.1
Primary analysis of the primary endpoint(s)....................................................21
 
7.5
SECONDARY ENDPOINT(S)...........................................................................22
7.5.1
Key secondary endpoint(s) .................................................................................22
7.5.2
(Other) Secondary endpoint(s)...........................................................................22
7.7
EXTENT OF EXPOSURE .................................................................................24
7.8
SAFETY ANALYSIS..........................................................................................24
7.8.1
Adverse Events ....................................................................................................25
7.8.2
Laboratory data...................................................................................................27
7.8.3
Vital signs.............................................................................................................27
7.8.4
ECG ......................................................................................................................28


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7.8.5
Others ...................................................................................................................28
8.
TIMEPOINT OF RELEASE OF TREATMENT INFORMATION .............29
9. 
REFERENCES ....................................................................................................30
11.
HISTORY TABLE..............................................................................................32


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LIST OF TABLES
Table 6.1: 1
Definition of Treatment Periods.......................................................................11
Table 6.7: 1
Time windows for patient visits .......................................................................17
Table 7.8.1: 1 User Defined Adverse Event Group Terms......................................................26
Table 11: 1
History table .....................................................................................................32


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2.
LIST OF ABBREVIATIONS
Term
Definition / description
AE
Adverse Event
CTC
Common Terminology Criteria
CTL
Clinical Trial Leader
CTP
Clinical Trial Protocol
CTR
Clinical Trial Report
DM&SM
Boehringer Ingelheim Data Management And Statistics Manual
DRA
Drug Regulatory Affairs
DMG
Dictionary Maintenance Group
EDC
Electronic Data Capture
EMEA
European Agency For The Evaluation Of Medicinal Products
FAS
Full Analysis Set
ICH
International Conference On Harmonisation
LOCF
Last Observation Carried Forward
MedDRA
Medical Dictionary For Regulatory Activities
MQRM
Medical Quality Review Meeting
PK
Pharmacokinetics
PPS
Per Protocol Set
PSTAT
Project Statistician
PT
Preferred Term
PV
Protocol Violation
RPM
Report Planning Meeting
Q1
Lower Quartile
Q3
Upper Quartile
SA
Statistical Analysis
SD
Standard Deviation
SMQ
Standardised MedDRA Query
SOC
System Organ Class
TESS
Treatment Emergent Signs And Symptoms 
ToC
Table of Contents
TMW
Trial Medical Writer
TSAP
Trial Statistical Analysis Plan


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3.
INTRODUCTION
As per ICH E9 (1), the purpose of this document is to provide a more technical and detailed 
elaboration of the principal features of the analysis described in the protocol, and to include 
detailed procedures for executing the statistical analysis of the primary and secondary 
variables and other data.
This TSAP assumes familiarity with the Clinical Trial Protocol (CTP), including Protocol 
Amendments. In particular, the TSAP is based on the planned analysis specification as written 
in CTP Section 7 “Statistical Methods and Determination of Sample Size”. Therefore, TSAP 
readers may consult the CTP for more background information on the study, e.g., on study 
objectives, study design and population, treatments, definition of measurements and variables, 
planning of sample size, randomization.
SAS® Version 9.4 will be used for all analyses.


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4.
CHANGES IN THE PLANNED ANALYSIS OF THE STUDY
There were no changes to the statistical analyses proposed in the study protocol. 
5.
ENDPOINTS(S)
5.1
PRIMARY ENDPOINT(S)
The primary endpoint is the occurrence of treatment emergent adverse events (TEAEs) up to 
Week 288.
5.2 
SECONDARY ENDPOINTS
5.2.1
Key secondary endpoint(s)
This section is not applicable as no key secondary endpoint has been specified in the protocol
5.2.2
Secondary endpoint(s)

Achievement of Psoriasis Area and Severity Index (PASI)50/PASI75/PASI90/ 
PASI100 at Week 24

Achievement of Static Physician’s Global Assessment (sPGA) clear or almost clear at 
Week 24 

Achievement of sPGA clear at Week 24

Time to loss of PASI50/PASI75/PASI90/PASI100 for patients who achieve the 
response up to Week 288

Time to loss of sPGA clear or almost clear for patients who achieve the response up to 
Week 288

Time to loss of sPGA clear for patients who achieve the response up to Week 288 
Details for scoring Psoriasis Area and Severity Index (PASI) and static physician global 
assessment are described in Section 10.1 and 10.2 of the CTP. The percent reduction from 
baseline is calculated by % PASI reduction from baseline = ((PASI at baseline - PASI at Visit 
X) / PASI at baseline) * 100, at all follow up visits. Achieving an X% or larger reduction 
from baseline PASI score is denoted as PASIX.


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6.
GENERAL ANALYSIS DEFINITIONS
6.1
TREATMENT(S)
All patients need to complete the preceding Phase II psoriasis Trial 1407-0030 and meet entry 
criteria for this study. 
Two groups of patients are to be entered into this trial, including up to (approximately) 180 
patients entered in the original trial 1407-0030 protocol (now Part 1) and approximately 90 
patients entered in an extended dose-ranging segment, now Part 2 of the amended trial 1407-
0030 protocol. Actual numbers of subjects entering the extension trial are to be determined 
by response in the preceding study.
In the first group (Part 1), patients will be considered eligible to participate in this long-term 
extension trial upon completing the trial 1407-0030 Week 24 end-of-treatment visit with a
≥PASI50 response. BI 730357 dose levels of up to 200 mg q.d.are to be administered under 
fasting conditions to patients in this group, reflecting the dose levels evaluated during Part 
1 of trial 1407-0030.

Patients entering the extension trial will remain on their blinded BI 730357 dose 
treatment from the preceding trial until the open label period of 1407-0005 begins 
at Visit 2/Week 12.

At Visit 2/Week 12, patients presently assigned to double blind treatment of placebo, 
25 mg, 50 mg, and 100 mg will be reassigned to the 100 mg open label dose, and 
patients presently assigned to the double blind treatment of 200 mg will be 
reassigned to 200 mg open label dose.
In the second patient group (Part 2), patients will be considered eligible to participate in this 
trial upon completing the trial 1407-0030 Week 12 end-of-treatment visit with a ≥PASI50 
response or perceived patient improvement, at the discretion of the Investigator. Patients 
are to be considered eligible only if also without ongoing AEs consistent with intolerance 
of trial medication (including gastric intolerance) that in the opinion of the investigator 
would compromise the safety of the patient.
.

All patients entering the extension trial are to be assigned at Visit 1 to receive 
open- label treatment with 400 mg q.d. (fed), the anticipated therapeutic BI 
730357 dose.
It is expected that Visit 1 of trial 1407-0005 will be performed on the same day of the EOT
Visit of trial 1407-0030 in both patient groups. In the event that patients completing Part 2 of 
trial 1407-0030 are not able to be entered immediately into the extension trial due to 
administrative reasons (e.g., pending protocol approval, availability of trial medication), Visit 
1 of the extension trial may be delayed for no more than 16 weeks.
The treatment period in this trial will be approximately 6 years.


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Figure 6.1: 1
Trial 1407-0005 dose assignment/reassignment for patients entering 
from Part 1 of trial 1407-0030
Figure 6.1: 2
Trial 1407-0005 dose assignment for patients entering from Part 2 and 
continuing from Part 1 of trial 1407-0030
open 
label
Dose selection at Week 12 is based on the safety and tolerability data from the SRD Trial 
1407.1 and the MRD Trial 1407-0002, and will be contingent on DMC evaluation of all 
available data from Phase II trial 1407-0030. For patients entering from Part 1 of trial 
1407- 0030, if an unacceptable risk regarding the safety of the 200 mg dose level is 
reported by the DMC, the open label BI 730357 dose assignments beginning at Week 12, 
is to be altered to assign all patients to the 100 mg q.d. dose group. 
Optional 
up titration
100 mg BI 730357
200 mg BI 730357
200 mg BI 730357
400 mg BI 730357


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All patients entering from Part 2 of trial 1407-0030 are to receive the 400 mg q.d. dose, as 
long as no unacceptable risks are identified during Part 2 of trial 1407-0030. Once Part 2 
patients begin enrolling in this trial, existing patients receiving 100 mg q.d. in this trial will 
be given the option to titrate up to the 200 g q.d. dose, if the investigator determines that the
Patients may benefit from the higher dose.
The first Part 2 patients enrolled in this study on December 10, 2020 and at that time all Part 1 
patients had been in the study more than 12 weeks and had titrated to 100 mg q.d. 
Subjects will be analyzed according to the treatment to which they were treated. The 
following study periods based on actual start and stop dates of study treatment administration 
are defined as follow.
Table 6.1: 1
Definition of Treatment Periods
Analysing Treatment 
Period
Start Date 
Stop Date
Screening#
NA
NA
On-treatment*
Date/Time of the first 
administration of trial treatment
Date of the last 
administration of trial 
treatment + REP
Follow-up
Date of the last administration of 
trial treatment + REP+1 day
Date of the last per protocol 
visit
# Patients in the 1407-0030 trial that fulfil the criteria for rollover will be asked to participate in this extension 
trial. Upon their agreement, they will immediately enter the treatment phase. Therefore, no screening period is 
defined in this trial.
* Within the On-treatment period, it can be divided into Period 1 (first 12 weeks) and Period 2 (after 12 weeks) 
for patients from part 1 of the 1407-0030 trial.
For the main safety analyses, Adverse Events (AEs) for patients who rolled over from Part 1 
of trial 1407-0030 will be classified to one of the following time periods: “first 12 weeks of 
treatment”, “second treatment period”, or “follow up”. Section 7.3.4 of the protocol specifies 
that, all AEs and laboratory assessments with an onset between start of treatment and end of
the residual effect period (REP), a period of 7 days after the last dose of trial medication for 
this trial, will be assigned to the “on-treatment” period for evaluation.
Detailed rules for assigning AEs to these time periods based on the onset dates of the AEs for 
patients who rolled over from Part 1 of the 1407-0030 trial are listed below (such AEs will be 
classified as new-onset TEAEs):

If date of Start of Treatment visit in  trial (1407-0005) ≤AE onset date < date of first 
intake after week 12 re-assignment, then the AE is assigned to “first 12 weeks of 
treatment”.
If an AE occurs on the day of week 12 visit, actual time between AE onset and study 
medication taken will be compared to determine AE time period (first 12 weeks, 
second treatment period).


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If the subject discontinues before the day of week 12 visit, date of first intake after 
week 12 re-assignment will be missing, the AE will still be assigned to “first 12 weeks 
of treatment”.

If date of first intake after week 12 re-assignment ≤ AE onset date ≤ date of last intake 
+ 7 days, then the AE is assigned to “second treatment period”.
Section 7.3.4 of the protocol specifies that adverse events that start before first drug intake 
and deteriorate under treatment will also be considered as ‘treatment emergent’. Worsening 
will be determined by a more severe grade according to Rheumatology Common Toxicity 
Criteria (RCTC) Version 2.0 Detailed rules for assigning such AEs of patients from Part 1 of 
the 1407-0030 trial to these time periods based on the onset dates and worsening dates  of the 
AEs are listed below (such AEs such be classified as worsening-severity TEAEs):

If AE onset date ≤ date of End of Treatment visit in the preceding trial (1407-0030) <
AE worsening date < date of first intake after week 12 re-assignment, then the AE is 
assigned to “first 12 weeks of treatment”.
If an AE worsening occurs on the day of week 12 visit, actual time between AE onset 
and study medication taken will be compared to determine AE time period (first 12 
weeks, second treatment period).
If the subject discontinues before the day of week 12 visit, date of first intake after 
week 12 re-assignment will be missing, the AE worsening will still be assigned to 
“first 12 weeks of treatment”.

If date of first intake after week 12 re-assignment ≤ AE worsening date ≤ date of last 
intake + 7 days, then the AE is assigned to “second treatment period”.
For patients who rolled over from Part 1 of the 1407-0030 trial if the onset date of an AE 
occurs prior to Week 12 and continues beyond Week 12 with a worsening RCTC grade after 
Week 12 then the AE will be captured as a TEAE both during  the firsr12-week period of 
1407-0005 (as a new-onset TEAE) and during the second treatment period (beyond Week 12, 
as a worsening-TEAE).  
Because there is no scheduled titration for patients who rolled over from Part 2 of trial 1407-
0030 adverse events will only be summarized for the entire treatment period and will not be 
summarized for the first 12 weeks and after 12 weeks for these patients. 
Due to differing doses, differing titration schedules and different timeframe for entering this 
study between patients from part 1 and part 2 of trial 1407_00030, several sets of adverse 
event analyses, each consisting of 11 summaries, will be presented:

Events up to 12 weeks for patients who rolled over from  Part 1 of trial 1407_00030
with treatment columns BI 25 mg, BI 50 mg, BI 100 mg and BI 200 mg

Events after 12 weeks for patients who rolled over from  Part 1 of trial 1407_00030


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with treatment columns BI 25 mg/BI 100 mg, BI 50 mg/BI 100 mg, BI 100 mg/BI 100 
mg and BI 200 mg/ BI 200mg.

All events for patients who rolled over from  Part 2 of trial 1407-0030 with treatment 
column BI 400 mg

All events from all patients who rolled over from trial 1407-0030 (part 1 and part 2 
combined) where events are classified under the treatment at onset in 1407-0005 with 
treatment columns BI 25 mg, BI 50 mg, BI 100 mg, BI 200 mg and BI 400 mg
Patients from part 1 of trial 1407_00030 who discontinue study treatment prior to Week 
12 will be excluded from the second and fourth sets of analyses above. Due to varying 
length of exposure to the various doses, exposure adjusted incidence rates will be 
presented in addition to number and percentage of patients with events in the fifth set 
above (classification by dose at onset).
For the analysis of other safety data (laboratory data, vital signs ,suicidal ideation) 
summaries will be presented for the entire study, for the first 12 weeks of the study and 
after 12 weeks on study. For these outputs data from patients who rolled over from Part 1 
and Part 2 of study 1407-0030 will be combined. In some of these data displays each 
treatment appears on a separate page. If deemed appropriate, additional displays showing 
descriptive statistics with figures for selected outcomes will be presented.
For efficacy summaries of response at Week 24 all patients from Part 1 of trial 1407-0030
will have data will be grouped as follows:

100 mg patients from part 1 of trial 1407-0030
o
25 mg/100mg
o
50 mg/100 mg
o
100 mg/100mg

200 mg patients from part 1 of trial 1407-0030

All patients from part 1 of trial 1407-0030

400 mg patients from part 2 of trial 1407-0030

All patients from part 1 and part 2 of trial 1407-0030 combined
For efficacy summaries of time to loss of response data will be grouped as follows:

100 mg patients from part 1 of trial 1407-0030 (combing 25 mg/100mg, 50 
mg/100 mg and 100 mg/100mg)

200 mg patients from part 1 of trial 1407-0030

400 mg patients from part 2 of trial 1407-0030
Efficacy response at Week 12 and 36 for patients from Part 2 of trial 1407-0030 will be 
summarized.


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6.2
IMPORTANT PROTOCOL DEVIATIONS
Handling of iPDs in analysis is included in the DV domain specifications and stored within 
the TMF in EDMS. 
A protocol deviation (PD) is important if it affects the rights or safety of the study subjects, 
or if it can potentially influence the primary outcome measurement(s) in a non-negligible 
way. Refer to Identify and Manage Important Protocol Deviations (iPD) (7). 
The documentation of the iPD categories and how to handle iPDs in the analysis are done in 
the DV domain.
Handling of iPDs in analysis is included in the DV domain specifications and stored within
the TMF in EDMS.
6.3
SUBJECT SETS ANALYSED
There are two patient sets defined in this trial:

Enrolled Set (ES) 
This patient set includes all patients who signed the informed consent form and were also 
enrolled, regardless whether the patient was treated with trial medication or not.

Treated Set (TS)
The TS includes all patients in the ES who received at least 1 dose of trial medication and 
is based on the actual treatment received at enrollment visit
The ES will be used for patient disposition.
The TS will be used for demographics, baseline characteristics, treatment exposure, analyses 
of all efficacy endpoints and safety analyses (including adverse events, laboratory 
measurements, vital signs, and ECG). 


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6.5
POOLING OF CENTRES
This section is not applicable because centre/country is not included in the statistical model.
6.6
HANDLING OF MISSING DATA AND OUTLIERS
Every effort should be made to collect complete data at all visits.
With respect to safety evaluations, it is not planned to impute missing values.
6.6.1
Efficacy data
An observed case analysis will be performed for the primary analysis of the secondary 
outcomes PASI 50, PASI 75, PASI 90, PASI100, and sPGA clear or almost clear endpoints at 
week 24. 
For the secondary outcome time to loss of PASI50/PASI75/PASI90/PASI100 for patients 
who achieve the response up to Week 288, patients who do not have the PASI assessment 
performed at a visit and maintained the PASI response at all scheduled visits prior to the 
missing visit  will be treated as censored at the day after the last visit where the PASI 
response was attained. 
For the secondary outcome time to loss of sPGA clear or almost clear for patients who 
achieve the response up to Week 288, patients who do not have the sPGA assessment 
performed at a visit and maintained the sPGA response at all scheduled visits prior to the 
missing visit will be treated as censored at the day after the last visit where the sPGA 
response was attained. 
For the secondary outcome time to loss of sPGA clear for patients who achieve the response 
up to Week 288, patients who do not have the sPGA assessment performed at a visit and 
maintained the sPGA response at all scheduled visits prior to the missing visit will be treated 
as censored at the day after the last visit where the sPGA response was attained. 
 
 
 


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If at any time a patient uses an inappropriate concomitant medication, then all future data will 
be excluded  for binary variables and for continuous variables and will not be implemented 
beyond the date of the prohibited medication..
6.6.2
Safety data and other data
In general, missing data will not be imputed and only observed values will be analyzed. 
6.6.3 
AE dates and times
Missing or incomplete AE dates will be imputed according to  “Handling of missing and 
incomplete AE dates” (3). 
 
 
6.6.5
Blood serum and plasma biomarker data
Missing blood serum and plasma biomarker data will not be imputed. Values below the limit
of quantification (BLQ) of the assay will be imputed to BLQ/2. Values above the limit of
quantification (ALQ) will be imputed to the ALQ.
6.7
BASELINE, TIME WINDOWS AND CALCULATED VISITS
For all analyses, baseline refers to the baseline value in the 1407-0030 study.
For laboratory safety measurements, the last measurements taken prior to the intake of BI 
730357 or placebo will be considered as baseline.
In general, measurements reported with a date only (and no time) and taken on the day of first 
administration of trial treatment will also be considered pre-treatment values.


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The visit schedule with accompanying details can be found in Flow Chart in the CTP.
Measurements taken after start of treatment will be considered either on- or off-treatment 
values based on definition in Table 6.1: 1.
On-treatment measurements for EOT and EOS visit for early discontinued patients will be 
allocated to visits by means of time windows with the limit between adjacent windows half-
way between the planned dates for the visits; the middle day is counted to the window of the 
later visit. Mutually exclusive relative day windows are defined below to provide derived 
visits that correspond to the post-baseline time points. For example, Visit 2 is planned on Day 
84 and Visit 3 is planned on Day 168. Therefore, the window of Visit 2 reaches until Day 125
while the window of Visit 3 starts on Day 126. The visit schedule with corresponding 
windows is given in the following table. 
Table 6.7: 1
Time windows for patient visits
  
Window 
No.
Window 
label
Nominal visit
Nominal 
day
Interval
1
Day 1
Visit 1
1
N/A
2
Week 12
Visit 2
84
[2, 125]
3
Week 24
Visit 3
168
[126, 209]
4
Week 36
Visit 4
252
[210, 293]
5
Week 48
Visit 5
336
[294, 377]
6
Week 60
Visit 6
420
[378, 461]
7
Week 72
Visit 7
504
[462, 545]
8
Week 84
Visit 8
588
[546, 629]
9
Week 96
Visit 9
672
[630, 713]
10
Week 108
Visit 10
756
[714, 797]
11
Week 120
Visit 11
840
[798, 881]
12
Week 132
Visit 12
924
[882, 965]
13
Week 144
Visit 13
1008
[966, 1049]
14
Week 156
Visit 14
1092
[1050, 1133]
15
Week 168
Visit 15
1176
[1134, 1217]
16
Week 180
Visit 16
1260
[1218, 1301]
17
Week 192
Visit 17
1344
[1302, 1385]
18
Week 204
Visit 18
1428
[1386, 1469]
19
Week 216
Visit 19
1512
[1470, 1553]
20
Week 228
Visit 20
1596
[1554, 1637]
21
Week 240
Visit 21
1680
[1638, 1721]
23
Week 252
Visit 22
1764
[1722, 1805]
24
Week 264
Visit 23
1848
[1806, 1889]
25
Week 276
Visit 24
1932
[1890, 1973]
26
Week 288
EOT
2016
[1974, 2029]
27
Week 292
EOS
2044
[2030, ∞]


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If there are multiple values for an efficacy endpoint in one window (visit), use the one from 
scheduled visit. If value from scheduled visit is not present, the visit closest to the nominal 
day will be selected for assessing endpoints at a particular visit and for by-visit displays. If the 
visits are equidistant from the nominal day, then the earlier visit will be selected. All 
measured values will be stored in analysis datasets.


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7.
PLANNED ANALYSIS
The format of the listings and tables will follow the standards defined in the BI corporate
guideline “Reporting of clinical trials and project summaries” .
The individual values of all patients will be listed, sorted by treatment, patient number and
visit. The listings will be included in Appendix 16.2 of the CTR.
For EoT tables, the set of summary statistics is: N / Mean / SD / Min / Median / Max.
For appendix tables, the set of summary statistics is: N / Mean / SD / Min / Q1 (lower
quartile) / Median / Q3 (upper quartile) / Max.
Tabulations of frequencies for categorical data will include all possible categories and will 
display the number of observations in a category as well as the percentage (%) relative to the 
respective treatment group. Percentages will be rounded to one decimal place. The category 
“missing” will be displayed only if there are actually missing values. Percentages will be 
based on all patients in the respective patient set no matter whether they have non-missing 
values or not.
No interim analysis is planned for this trial.
For patients from Part 1 of the 1407-0030 trial planned treatment for first 12 weeks of 
treatment is defined as treatment patient received at the end of 1407-0030. Planned 
treatment for after 12 weeks (Period 2) is defined as the treatment patient assigned from 
IVRS at week 12 visit (V2). For patients who titrate according to the protocol from  100 g 
q.d. dose to 200 g q.d. dose,if the investigator determines that the patient may benefit from 
the higher dose, 200 g q.d. dose will be the planned dose after the titration.
Subject data listings of data used in the analyses (i.e. demographic and baseline characteristics 
and key efficacy endpoints) will also be provided and included in Appendix 16.2 of the CTR.
Disposition of the patient population participating in the trial will be summarised by 
presentation of the frequency of patients screened, entered, screened but not entered, treated, 
entered but not treated. Within treated patients, data  for patients rolled over from Part 1 of 
trial 1407-00030 will be summarized by treatment periods (period 1 - first 12 weeks of 
treatment and period 2 – open label treatment after week 12) for treatment ongoing patients, 
patients complete planned treatment period and patients who are prematurely discontinued, by 
reason. 
Because there is no scheduled titration for patients from Part 2 of trial 1407-0030 disposition 
will be summarized without distinguishing the first 12 weeks from after 12 weeks for these 
patients. 


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7.1
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS
Only descriptive statistics are planned for this section of the report. Demographic parameters 
collected and to be presented include, but are not limited to, the following:

Gender (Male, Female)

Race and ethnicity (as defined in the eCRF)

Age [years]

Height [cm]

Weight [kg]

Body mass index [kg/m2] (defined as weight [kg]/(height [cm]/100)2)

Smoking history (Never-smoked, Ex-smoker, Currently smokes)

Alcohol History (Non-drinker, drinks – no interference, drinks – possible interference)

Region

PsA history (diagnosed, suspected, no PsA)

Prior biologic use for psoriasis (Yes/No)
Baseline disease characteristic to be presented include, but are not limited to, the following: 

PASI score 

Body surface area (affected by plaque psoriasis)

sPGA
 
Number (%) of patients with psoriasis therapy history will be summarized, including both 
non-topical drug therapy and non-drug therapy.
7.2
CONCOMITANT DISEASES AND MEDICATION
Only descriptive statistics are planned for this section of the report.
A table of the number (%) of patients with concomitant diagnoses from baseline condition by 
system organ class (SOC) and preferred term (PT) will be included along with a supporting 
listing. Concomitant diagnoses will be coded with the most recent version of MedDRA in 
effect at database lock.
Concomitant medication will be described as a table of number (%) of patients with on-
treatment medication use. On-treatment is defined as medication with a stop date after or on 
the day of first trial drug intake and before last trial drug intake + 7 days.


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7.3
TREATMENT COMPLIANCE
Treatment compliance will be reported based on calculation as described in CTP section 4.3. 
Only descriptive statistics are planned for this section of the report. Treatment non-
compliance is defined as any enrolled patients having taken at least one dose of study 
medication with an overall compliance rate not between 80% and 120% inclusive. Overall 
compliance is calculated based on unweighted average of study drug compliance rate at each 
visit during the treatment period. For the patients who discontinued the study treatment 
prematurely only the visits on or before premature discontinuation will be used for the 
calculation of overall compliance.
Summary statistics of overall compliance in the treated set will be given for the number of 
subjects as well as the corresponding percentage with compliance in the categories <80%, 
80% - 120%, >120%, missing.
7.4
PRIMARY ENDPOINT(S)
7.4.1
Primary analysis of the primary endpoint(s)
The primary endpoint is the occurrence of treatment emergent adverse events (TEAEs) up to 
Week 288. The primary analysis will be based on the exposure adjusted rate of patients 
reporting a treatment emergent adverse event (TEAE) up to Week 288.
Exposure-adjusted adverse event incidence rates will be calculated using the following 
approach:

The incidence rate (per 100 subject years) of a selected adverse event (also known as
the incidence density rate or person-time incidence rate) is defined as the number of
subjects experiencing the adverse event per treatment group during the time at risk
divided by the total time of subjects at risk in that treatment group to contribute an
event to the analysis multiplied by 100 (per 100 subject years), where for each subject 
and each TEAE preferred term:
Time at risk [subject years] = (date of first onset of AE – study drug start date + 1) / 
365.25
If, for a subject, no treatment emergent adverse event occurred for the preferred term, 
then the time at risk will be censored at the minimum of (date of death; drug stop date 
+ 7 days; last contact date).

For each AE, the incidence rate will therefore be calculated as:
Incidence rate [per 100 subject years (pt-yrs)] = 100 * number of subjects with
            TEAE / Total TEAE-specific time at risk [subject years].
Exact 95% confidence intervals (CI) around the observed AE incidence rate will also be
Provided using exact Poisson regression.


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7.5
SECONDARY ENDPOINT(S)
7.5.1
Key secondary endpoint(s)
This section is not applicable as no key secondary endpoint has been specified in the protocol.
7.5.2
(Other) Secondary endpoint(s)
For the convenience of writing and reviewing, all PASI and sPGA endpoints at different time 
points (secondary and further clinical endpoints) are first described generally in this section 
prior to addressing each secondary objective specifically.
Psoriasis Area and Severity Index (PASI)
Details for scoring Psoriasis Area and Severity Index (PASI) and its components are 
described in Section 10.1 of the CTP.  The percent reduction from baseline is calculated by % 
PASI reduction from baseline = ((PASI at baseline - PASI at Visit X) / PASI at baseline) * 
100, at all visits with PASI collected.  Achieving an X% or larger reduction from baseline 
PASI score is denoted as PASI X.  
Static Physician's Global Assessment (sPGA)
The sPGA is scored using the following levels of assessment:
0 - clear
1 - almost clear
2 - mild
3 - moderate
     4 - severe
Secondary Outcome Achievement of PASI50/PASI75/PASI90/PASI100 at Week 24
Descriptive statistics of the percentage of patients who achieve a PASI score of at least 50% 
(PASI 50), 75% (PASI 75), 90% (PASI90) and 100% (PASI100) reductions from baseline at 
Week 24 will be tabulated for each treatment group.  The number of patients, number of 
patients attaining the PASI response, percentage of patients attaining the PASI response at 
Week 24 with corresponding exact 95% confidence interval will be presented based on the 
Clopper Pearson method. 
The primary analysis of these secondary outcomes will be based on an observed case analysis. 
Secondary Outcome Achievement of sPGA clear or almost clear at Week 24
Descriptive statistics of the percentage of patients who achieve sPGA of clear or almost clear
(sPGA score of 0 or 1 ("clear or almost clear")) at Week 24 will be tabulated for each 
treatment group.  The number of patients, number of patients attaining the sPGA response, 
percentage of patients attaining the sPGA response at Week 24 with corresponding exact 95% 
confidence interval will be presented based on the Clopper Pearson method. 
The primary analysis of these secondary outcomes will be based on an observed case analysis.


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Secondary Outcome Achievement of sPGA clear at Week 24
Descriptive statistics of the percentage of patients who achieve sPGA of clear (sPGA score of 
0  ("clear ")) at Week 24 will be tabulated for each treatment group.  The number of patients, 
number of patients attaining the sPGA response, percentage of patients attaining the sPGA 
response at Week 24 with corresponding exact 95% confidence interval will be presented 
based on the Clopper Pearson method. 
The primary analysis of these secondary outcomes will be based on an observed case analysis. 
Secondary Outcome Time to Loss of PASI50/PASI75/PASI90/PASI100 for patients who 
achieve the response up to Week 288 
For the time to loss of response (PASI 50/ PASI 75/ PASI 90/ PASI 100) the time to event 
will be calculated as 
•
Time to first loss (with observed event) = [date of first loss] – [date of first visit with 
qualifying response] + 1
•
Time to first loss (censored) = [date of last visit with qualifying response] – [date of 
first visit with qualifying response] + 1
•
If a patient never attains PASI 50/ PASI 75/PASI 90/PASI 100 then the patient will 
not contribute to the analysis of this outcome.
Time to loss of response will be analysed descriptively by Kaplan Meier curves.  If at least 
50% of patients lose response, the median time to loss of response will be estimated median 
of time to loss with 95% confidence interval will be presented. 
Secondary Outcome Time to Loss of sPGA clear or almost clear at Week 24
for patients who achieve the response up to Week 288 
For the time to loss of response (sPGA clear or almost clear), the time to event will be 
calculated as: 
•
Time to first loss (with observed event) = [date of first loss] – [date of first visit with 
qualifying response] + 1
•
Time to first loss (censored) = [date of last visit with qualifying response] – [date of 
first visit with qualifying response] + 1
•
If a patient never attains sPGA clear or almost clear then the patient will not contribute 
to the analysis of this outcome.
Time to loss of response will be analysed descriptively by Kaplan Meier curves.  If at least 
50% of patients lose response, the median time to loss of response will be estimated median 
of time to loss with 95% confidence interval will be presented. 
Secondary Outcome Time to Loss of sPGA clear at Week 24
for patients who achieve the response up to Week 288 
For the time to loss of response (sPGA clear), the time to event will be calculated as: 


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•
Time to first loss (with observed event) = [date of first loss] – [date of first visit with 
qualifying response] + 1
•
Time to first loss (censored) = [date of last visit with qualifying response] – [date of 
first visit with qualifying response] + 1
•
If a patient never attains sPGA clear then the patient will not contribute to the analysis 
of this outcome.
Time to loss of response will be analysed descriptively by Kaplan Meier curves.  If at least 
50% of patients lose response the median time to loss of response will be estimated median of 
time to loss with 95% confidence interval will be presented. 
7.7
EXTENT OF EXPOSURE
Exposure will be presented as total days on treatment and total study medication intake 
assessed by actual treatment received. For example, a Placebo patient that switches to BI 
730357 100 mg at Week 12 should have 12 weeks of exposure under the Placebo column and 
their number of days on BI 730357 100 mg under BI 730357 100 mg column.
7.8
SAFETY ANALYSIS
All safety analyses will be performed on the treated set (TS). Analysis will be performed as 
defined in Section 7.3.4 of the CTP.


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7.8.1
Adverse Events
The analyses of adverse events will be descriptive in nature. All analyses of AEs will be based 
on the number of patients with AEs (not the number of AEs).
Unless otherwise specified, the analyses of AEs will be descriptive in nature. All analyses of
AEs will be based on the number of subjects with AEs and NOT on the number of AEs.
The analysis of AEs will be based on the concept of treatment emergent AEs. That means that
all AEs occurring between first drug intake till 7 days after last drug intake will be
assigned to the received treatment. All AEs occurring before first drug intake will be assigned 
to ‘screening’ and all AEs occurring after last drug intake + 7 days will be
assigned to ‘follow-up’ (for listings only). For details on the treatment definition, see Section
6.1.
According to ICH E3 (5), in addition to Deaths and serious adverse events, ‘other
significant’ AEs need to be listed in the clinical trial report. These will be any non-serious
adverse event that led to an action taken with study drug (e.g. discontinuation or dose
reduced or interrupted).An overall summary of adverse events will be presented.
The frequency of subjects with AEs will be summarised by treatment, primary system organ
class and PT using the version of MedDRA  at the database lock. Separate tables will be
provided for subjects with SAEs, AEs leading to treatment discontinuation  and related AEs.
The system organ classes will be sorted by default by decreasing frequency and PTs will be 
sorted by decreasing frequency within SOC.
For further details on summarization of AE data, please refer to the guideline 'Handling and 
summarization of adverse event data for clinical trial reports and integrated summaries' (4).
The severity of AEs will be summarised by the maximum intensity of the events each patient had 
(as indicated by the recorded RCTC version 2 grade). This will show the number and percent of 
patients who had at most mild, moderate, severe, and life threatening events. Severe adverse 
event is defined as an AE with RCTC grade equals to 3 (severe) or 4 (life threatening).
Groupings of adverse events and adverse events of special interest (AESI)
The AESI have been defined in the protocol.
Other user-defined special adverse event grouped term for BI 730357 specified in the 
following Table 7.8.1:1. 


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Table 7.8.1: 1 User Defined Adverse Event Group Terms
N
Term
Definition #
1
SMQ Drug Related Hepatic 
Disorders
SMQ Drug related hepatic disorders –
comprehensive search (20000006)
2
SMQ Opportunistic infections
MedDRA SMQ Opportunistic Infections (narrow)
3
Tuberculosis related terms
BIcMQ “Tuberculosis related terms” BIcMQ 
(30000107)(broad)
4
Severe infections
SOC “Infections and infestations” with eCRF 
severity grade >= Rheumatology Common Toxicity 
Criteria (RCTC) Grade 3
5
Gastritis related terms 
•
BIcMQ Gastritis (broad) [32008061]
# This column indicates whether the Term(s) provided in the  second column are 
MedDRA preferred terms (PT), Standardised MedDRA Queries (SMQ) or BI 
customised MedDRA Queries (BIcMQ).
In addition, adjudicated MACE (provided by 
 will be summarized by indication,  
treatment, primary system organ class and preferred term.
The user defined AE categories will be updated accordingly with Safety SAP updates. 
The following periods will be defined for assessing adverse events for patients from 
Part 1 of the 1407-0030 trial.:

First 12 weeks of treatment

Second treatment period
For patients from Part 1 of the 1407-0030 trial, AEs with onset date on day of week 12 visit, 
the AE onset time will be compared with first drug administration time of the dose dispensed 
at the Week 12 visit to determine AE period. The treatment label for second period will be a 
combination of actual treatment in first 12 weeks of treatment and second period treatment.  
Additionally an analysis including patients from both parts of the 1407-0030 trial will be 
performed in which adverse events are classified under the dose the patient was receiving at 
the onset of the TEAE. 
AE summaries
An overall summary of adverse events will be presented. The frequency of patients with 
adverse events will be summarized by treatment, primary system organ class and preferred 
term according to MedDRA. Separate tables will be provided for patients with:

Drug-related AEs

AESIs


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
AEs leading to discontinuation

Serious AEs

Other significant AEs 

AE by worst RCTC intensity

Investigator defined drug-related serious AEs

User defined AE categories
7.8.2
Laboratory data
The analyses of laboratory data will be descriptive in nature and will be based on BI standards
(6). The number and percent of patients with possibly clinically significant on treatment 
abnormalities as identified by use of clinically significant ranges for each laboratory 
parameter collected will be presented. The patients from both parts of   1407-0030 with 
possibly clinically significant abnormalities will be identified by actual treatment received at 
study entry. 
Each laboratory value will be graded using the RCTC (version 2.0) grading of laboratory 
abnormalities. A summary table of the baseline grade compared with the last available on 
treatment grade will display the number and percent of each type of transition in grade by 
laboratory parameter within each treatment period and treatment group. A second table will 
show the number and percent of patients with each type of transition from baseline to their 
worst on-treatment grade. 
A graphical summary highlighting potential cases of Hy’s Law by actual treatment received at 
study entry will be presented. The maximum on-treatment values of total bilirubin and ALT 
will be plotted each on a scale as multiples of the upper limit of normal. The figure will show 
areas that meet the criteria of cholestasis (total bilirubin > 2x ULN), Temple’s corollary (ALT 
> 3 x ULN) and Hy’s Law as the combination of these two factors. A similar figure using 
maximum AST values in place of ALT will be constructed. An accompanying listing will 
show by sample date and study day the full course of the total bilirubin, ALT, AST and 
alkaline phosphatase values for patients whose total bilirubin are > 2xULN or AST or ALT 
values > 3 x ULN at any time during the study (all treatment periods). The listing will indicate 
where the value meets the criteria, either falling in the cholestasis range, that for Temple’s 
corollary or where the combination meets that for Hy’s Law itself.
Laboratory measurements taken up to the residual effect period of 7 days after the last 
administration of study drug will be considered as on-treatment.
Study visits will be presented by the Visit labels in Table 6.7:1.
7.8.3
Vital signs
Only descriptive statistics are planned for this section of the report.


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7.8.4
ECG
Abnormal ECG recordings will be noted, and clinically relevant abnormal findings will be 
reported as AEs by the investigator.
7.8.5
Others


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8.
TIMEPOINT OF RELEASE OF TREATMENT 
INFORMATION
For patients rolled over from Part 1 of trial 1407-0030 the unblinded treatment information 
will be loaded into the trial database only after all patients have completed the blinded 12-
week treatment period.
For patients rolled over from Part 2 of trial 1407-0030 the treatment information will be 
loaded into the trial database upon entry into study 1407-0005.


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9.
REFERENCES
1.
CPMP/ICH/363/96: "Statistical Principles for Clinical Trials", ICH Guideline Topic E9, 
Note For Guidance on Statistical Principles for Clinical Trials, current version.
 
 
 
5.
CPMP/ICH/137/95: “Structure and Content of Clinical Study Reports”, ICH Guideline 
Topic E3; Note For Guidance on Structure and Content of Clinical Study Reports,
current version
 


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11.
HISTORY TABLE
Table 11: 1
History table
Version
Date
(DD-MMM-
YY)
Author
Sections 
changed
Brief description of change
1 
03-MAR-2021
None
This is the final TSAP