Clinical trial NCT02694523
Conditions: Psoriasis
Keywords: Psoriasis Skin Diseases Skin Diseases, Papulosquamous Adalimumab Anti-Inflammatory Agents ABBV-066 BI 655066 Risankizumab
Sponsor: AbbVie
Start date: 2016-03-01; Completion date: 2017-08-01
Enrollment: 684 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized double blind, double dummy, active comparator controlled, parallel design study that is performed to assess the safety and efficacy of BI 655066/ABBV-066 (risankizumab) compared to adalimumab to support registration for the treatment of moderate to severe chronic plaque psoriasis in adult patients.

Detailed description:
This study consists of 2 parts (Part A and Part B).

Part A:

* Participants were randomized to receive either risankizumab or adalimumab.

Part B:

* Participants who received risankizumab in Part A continued to receive risankizumab in Part B
* Adalimumab nonresponders (\<PASI 50 at Week 16) switched to risankizumab in Part B;
* Adalimumab responders (PASI 90 at Week 16) continued to received adalimumab in Part B;
* Adalimumab inadequate responders (PASI 50 to \<PASI 90) were rerandomized to receive either risankizumab or adalimumab in Part B.

Arms: arm 1: Participants randomized to receive double-blind (DB) adalimumab 80 mg by subcutaneous (SC) injection at Week 0, then 40 mg at Week 1 and every 2 weeks for 15 weeks (Part A). arm 2: Participants randomized to receive risankizumab at Weeks 0 and 4 (Part A).
Interventions: intervention 1: risankizumab intervention 2: adalimumab intervention 3: placebo for risankizumab intervention 4: placebo for adalimumab
Intervention descriptions: intervention 1: Risankizumab administered by subcutaneous (SC) injection intervention 2: Adalimumab pre-filled syringe, administered by subcutaneous (SC) injection intervention 3: Placebo risankizumab administered by subcutaneous (SC) injection intervention 4: Placebo for adalimumab pre-filled syringe, administered by subcutaneous (SC) injection

Protocol documents:
Prot_000.pdf: 
001-MCS-40-106-RD-03 (12 0) / Saved on: 30 Jan 2015
CLINICAL TRIAL PROTOCOL
 P
Document Number:
c03570610-04
EudraCT No.:
2015-003623-65
BI Trial No.:
1311.30
BI Investigational 
Product:
Risankizumab, BI 655066
Title:
BI 655066/ABBV-066 (risankizumab) versus adalimumab in a 
randoMized, double blind, parallel group trial in Moderate to 
severe plaque psoriasis to assess safety and efficacy after 16 
weeks of treatment and after inadequate adalimumab 
treatment response (IMMvent)
Brief Title:
BI 655066/ABBV-066 (risankizumab) compared to active 
comparator (adalimumab) in patients with moderate to severe 
chronic plaque psoriasis
Clinical Phase:
III
Trial Clinical 
Monitor:
Coordinating 
Investigator:
Status:
Revised Protocol
Version and Date:
Version: 4.0
Date: 17 Oct 2016
Page 1 of 102
Proprietary confidential information.
! 2016 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.
/$5


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CLINICAL TRIAL PROTOCOL SYNOPSIS
Name of company:
Boehringer Ingelheim 
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066 (risankizumab)
Protocol date:
10 December 2015
Trial number:
1311.30
Revision date:
17 October 2016
Title of trial:
BI 655066/ABBV-066 (risankizumab) versus adalimumab in a 
randoMized, double blind, parallel group trial in Moderate to severe 
plaque psoriasis to assess safety and efficacy after 16 weeks of 
treatment and after inadequate adalimumab treatment response 
(IMMvent)
Coordinating
Investigator:
Trial site(s):
Multi-centre trial
Clinical phase:
III
Objective(s):
The main objective of this study is to assess the safety and efficacy 
of BI 655066 (risankizumab) compared to adalimumab in patients 
with moderate to severe chronic plaque psoriasis
Methodology:
Active-controlled, double-blind, double dummy, randomized, 
parallel design comparison of BI 655066 and adalimumab over 44 
weeks
No. of patients: 
total entered:
600
each treatment:
300
Diagnosis :
Moderate to severe chronic plaque psoriasis
Main criteria
for inclusion:
-
Male or female patients with age ≥ 18 years at screening
-
Have a diagnosis of chronic plaque psoriasis (with or without 
psoriatic arthritis) for at least 6 months before the first 
administration of study drug.
-
Have stable moderate to severe chronic plaque psoriasis with or 


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Name of company:
Boehringer Ingelheim 
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066 (risankizumab)
Protocol date:
10 December 2015
Trial number:
1311.30
Revision date:
17 October 2016
without psoriatic arthritis at both Screening and Baseline 
(Randomisation):
∀
Have an involved body surface area (BSA) ≥ 10% and
∀
Have a Psoriasis Area and Severity Index (PASI) score
≥ 12 and
∀
Have a static Physician Global Assessment (sPGA) score 
of ≥ 3.
-
Must be candidates for systemic therapy or phototherapy for 
psoriasis treatment, as assessed by the investigator 
-
Must be a candidate for treatment with Humira® (adalimumab) 
according to local label.
Test product(s):
BI 655066
dose:
150mg (2 syringes à 75mg) at Weeks 0, 4 and every 12 weeks 
mode of 
administration:
subcutaneous
Comparator products:
Adalimumab
dose:
80mg at randomisation; then 40mg at Weeks 1, 3, 5 and every 
other week.
mode of 
administration:
subcutaneous
Duration of treatment:
44 weeks
Endpoints
Primary Endpoints
-
Achievement of ≥ 90% reduction from baseline PASI score 
(PASI 90) at Week 16,
-
Achievement of an sPGA score of clear or almost clear at 
Week 16
Key Secondary Endpoints: 
-
Achievement of ≥ 75% reduction from baseline PASI score 
(PASI 75) at Week 16
-
Achievement of 100% reduction from baseline PASI score 
(PASI 100) at Week 16
-
Achievement of ≥ 90% reduction from baseline PASI score 


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Name of company:
Boehringer Ingelheim 
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066 (risankizumab)
Protocol date:
10 December 2015
Trial number:
1311.30
Revision date:
17 October 2016
(PASI 90) at Week 44 for those patients who are re-randomized 
at Week 16
Other Secondary Endpoints 
∀
Achievement of an sPGA score of clear or almost clear
(0 or 1) at Week 44
∀
Achievement of sPGA score of clear (0) at Week 44
Further endpoints:
∀
Achievement of PASI 50 at all visits collected
∀
Achievement of PASI 75 at all visits collected
∀
Achievement of PASI 90 at all visits collected
∀
Achievement of PASI 100 at all visits collected
∀
Time until the first achievement of PASI 50, PASI 75, 
PASI 90, PASI 100 and sPGA 0 or 1
∀
Time until loss of PASI 75, PASI 90, PASI 100 and
sPGA 0 or 1 response
∀
Change and percent change from baseline in PASI at all 
visits collected
∀
Absolute PASI score of <3 at all visits collected
∀
Achievement of an sPGA score of clear or almost clear at all 
visits collected
∀
Achievement of an sPGA score of clear at all visits 
collected
∀
Change from baseline in Dermatology Life Quality Index 
(DLQI) at all visits collected
∀
Achievement of a DLQI score of 0 or 1 at all visits collected
∀
Achievement of a reduction of 5 or more points from 
baseline in DLQI score at all visits collected
∀
Change from baseline in Work Limitations Questionnaire 
(WLQ) at all visits collected
∀
Change and percent change from baseline in Nail Psoriasis 
Severity Index (NAPSI) at all visits collected


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Name of company:
Boehringer Ingelheim 
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066 (risankizumab)
Protocol date:
10 December 2015
Trial number:
1311.30
Revision date:
17 October 2016
∀
Change and percent change from baseline in Palmoplantar 
Psoriasis Severity Index (PPASI) at all visits collected
∀
Change and percent change from baseline in Psoriasis Scalp 
Severity Index (PSSI) at all visits collected
∀
Response to individual questions on the self-administration 
questionnaire at each visit where BI 655066 active or 
placebo is self-administered
∀
Change of metabolic risk factors from baseline (waist 
circumference, body weight, Homeostasis Model 
Assessment [HOMA] index)
Safety criteria:
Physical examination vital signs, 12-lead electrocardiogram (ECG),
laboratory tests, adverse events and tolerability
Statistical methods:
Co-primary analysis: The achievement of PASI 90 and sPGA of 
clear or almost clear at Week 16 are the co-primary endpoints and
are binary variables with values of 0 or 1. The difference in 
proportion responding between the BI 655066 arm and the 
adalimumab arm will be estimated and tested using the Cochran-
Mantel-Haenszel risk difference estimate stratified by the 
randomisation factors of weight (≤ 100 kg vs. >100 kg) and prior 
exposure to TNF antagonists (0 vs. ≥1) with weights proposed by 
Greenland & Robins.
Secondary analysis: The same methods for the primary analyses will 
be used to analyze binary key secondary endpoints. In particular, the 
achievement of PASI 90 at Week 44 for patients re-randomized to 
continue adalimumab or switch to BI 655066 will be compared 
using the methods described above.
The hypotheses comparing BI 655066 to adalimumab at Week 16 
will be tested in hierarchical order using two-sided tests with a 
type I error of 0.05. In addition, the comparison of the achievement 
of PASI 90 at Week 44 for the re-randomized patients will be tested 
separately with a type I error of 0.05.






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and for approximately 1 hour after the last injection at all other study visits with drug administrations.  Hypersensitivity reactions should be treated according to medical 
standards.
5.
Refer to table 5.3.3:1 for the list of infection screening tests and to Exclusion criterion 7 in section 3.3.3
6.
Serum pregnancy testing at screening and if urine pregnancy test is positive.  Urine pregnancy testing at randomization and will be continued as indicated in the Flow 
Chart (including EOT and EOO Visit) and should be done prior to administration of study drug in case there is dosing at study visits.
7.
Blood samples should be taken after patient has fasted for at least 8 hours prior (except Screening Visit).  If not fasted mark on laboratory requisition.
8.
On dosing visits, PK and ADA samples should be taken approximately within 1 hour prior to administration of study drug.
9.
Biomarker sampling should be done prior to administration of study drug at dosing visits.
10. Refer to section 5.3.5 for details on local tolerability assessment. 
11. Healthcare Resource Utilisation (HCRU): hospitalisations, emergency room visits and unscheduled outpatient or home visits will be captured (refer to Section 5.6.3). 
12. At selected study sites, voluntary skin biopsy assessment will be conducted after separate informed consent is given. Collection should be done prior to administration of 
study drug at dosing visits.  Refer to Section 5.5.1. 
13. Voluntary DNA Banking sample will be taken and stored after separate informed consent is given in accordance with local ethical and regulatory requirements. Refer to 
section 5.5.
14. At Week 16, patients treated with adalimumab and with >PASI 50 and <PASI 90 will be 1:1 re-randomized to continue on adalimumab or switch to BI 655066. 
Adalimumab patients below PASI 50 at Week 16 will be switched to BI 655066. Adalimumab patients with >PASI 90 at Week 16 will continue on adalimumab.
15. At Randomization (Visit 2) all study drugs will be administered by study personnel (2 injections BI 655066 active or placebo plus 2 injections adalimumab active or 
placebo). 
At Visits 3 and 4 (Weeks 1 and 3) the patient self-administers 1 injection adalimumab (active or placebo) under supervision of study personnel.
At Visit 5 (Week 4), Visit 8 (Week 16), Visit 9 (Week 20), Visit 11 (Week 28) and Visit 12 (Week 32) the patient self-administers 2 injections BI 655066 (active or 
placebo) under supervision of study personnel (Refer to Section 4.1.4 and Figure 3.1: 1).
16. Study personnel completes a questionnaire about self-administration of BI 655066 (active or placebo) by the patient (refer to section 4.1.4, 5.6.2 and Appendix 10.8)
17. Adalimumab (active or placebo) is dispensed to the patient for self-administration at home (at Weeks 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39 and
41). Time window for home administration should be ± 3 days.
18. Patients who complete the randomized treatment period of study 1311.30 will be offered to roll over into an open label extension (OLE) trial if they fulfill the in- and 
exclusion criteria for the OLE trial. Those patients will have no Follow-up Visit in study 1311.30. 
Patients who discontinue the randomized treatment period of study 1311.30 prematurely will complete EOT Visit procedures and return 16 (±1) weeks after their last 
BI 655066 (active or placebo) administration for End of Observation (EOO) Visit.
Patients who complete the randomized treatment period of study 1311.30, but will not (or cannot) be included in the OLE study will have their EOO Visit 4 (±1) weeks 
after their EOT Visit at Week 44 (this is at Week 48 ± 1 week).
19. For randomised patients who will not participate in the OLE study and who withdraw from the study prior to their planned EOO Visit, vital status should be collected at
48 (+1) weeks after the Randomisation Visit.
20. Patients that terminate trial medication early should remain in the trial if possible, and complete all remaining study visit procedures if possible. Termination of trial 
medication should be completed in the e CRF and treatment discontinuation registered in IRT. Refer to Section 6.2.3 for more details 


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TABLE OF CONTENTS
CLINICAL TRIAL PROTOCOL..........................................................................................1
TITLE PAGE ...........................................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................................2
FLOW CHART........................................................................................................................6
TABLE OF CONTENTS ........................................................................................................9
ABBREVIATIONS................................................................................................................13
1.
INTRODUCTION...............................................................................................16
MEDICAL BACKGROUND.............................................................................16
1.1
DRUG PROFILE................................................................................................16
1.2
2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK ASSESSMENT .....18
RATIONALE FOR PERFORMING THE TRIAL.........................................18
2.1
TRIAL OBJECTIVES........................................................................................18
2.2
BENEFIT - RISK ASSESSMENT.....................................................................18
2.3
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.........................20
OVERALL TRIAL DESIGN AND PLAN .......................................................20
3.1
3.1.1
Administrative structure of the trial .................................................................21
3.1.2
Data Monitoring Committee (DMC).................................................................22
3.1.3
MACE Adjudication Committee.......................................................................22
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
3.2
CONTROL GROUP...........................................................................................23
SELECTION OF TRIAL POPULATION .......................................................23
3.3
3.3.1
Main diagnosis for trial entry ............................................................................23
3.3.2
Inclusion criteria .................................................................................................23
3.3.3
Exclusion criteria ................................................................................................24
3.3.4
Removal of patients from therapy or assessments...........................................25
Removal of individual patients .............................................................................25
3.3.4.1
Discontinuation of the trial by the sponsor...........................................................26
3.3.4.2
4.
TREATMENTS...................................................................................................27
TREATMENTS TO BE ADMINISTERED.....................................................27
4.1
4.1.1
Identity of BI investigational product and comparator product....................27
4.1.2
Method of assigning patients to treatment groups...........................................29
4.1.3
Selection of doses in the trial..............................................................................30
4.1.4
Drug assignment and administration of doses for each patient......................31
4.1.5
Blinding and procedures for unblinding...........................................................35
Blinding.................................................................................................................35
4.1.5.1
Unblinding and breaking the code ........................................................................35
4.1.5.2
4.1.6
Packaging, labelling, and re-supply...................................................................35
4.1.7
Storage conditions...............................................................................................36
4.1.8
Drug accountability.............................................................................................36


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CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE  
4.2
TREATMENT.....................................................................................................36
4.2.1
Rescue medication, emergency procedures, and additional treatments........36
4.2.2
Restrictions ..........................................................................................................37
Restrictions regarding concomitant treatment ......................................................37
4.2.2.1
Restrictions on diet and life style..........................................................................38
4.2.2.2
Restrictions regarding women of childbearing potential ......................................38
4.2.2.3
TREATMENT COMPLIANCE........................................................................38
4.3
5.
VARIABLES AND THEIR ASSESSMENT ....................................................40
TRIAL ENDPOINTS..........................................................................................40
5.1
5.1.1
Primary Endpoint(s)...........................................................................................40
5.1.2
Secondary Endpoint(s) .......................................................................................40
5.1.3
Further Endpoints...............................................................................................40
ASSESSMENT OF EFFICACY........................................................................41
5.2
ASSESSMENT OF SAFETY.............................................................................41
5.3
5.3.1
Physical examination ..........................................................................................42
Waist circumference .............................................................................................42
5.3.1.1
Body weight ..........................................................................................................42
5.3.1.2
5.3.2
Vital Signs............................................................................................................42
5.3.3
Safety laboratory parameters ............................................................................43
5.3.4
Electrocardiogram ..............................................................................................45
5.3.5
Other safety parameters.....................................................................................46
5.3.6
Assessment of adverse events.............................................................................46
Definitions of AEs ................................................................................................46
5.3.6.1
5.3.7
Adverse event collection and reporting.............................................................48
DRUG CONCENTRATION MEASUREMENTS AND 
5.4
PHARMACOKINETICS...................................................................................50
5.4.1
Assessment of Pharmacokinetics.......................................................................50
5.4.2
Methods of sample collection .............................................................................50
Plasma sampling for pharmacokinetic analysis ....................................................50
5.4.2.1
Plasma sampling for ADA....................................................................................50
5.4.2.2
5.4.3
Analytical determinations ..................................................................................50
ASSESSMENT OF EXPLORATORY BIOMARKERS.................................51
5.5
5.5.1
Skin biopsy assessment.......................................................................................51
Methods of sample collection ...............................................................................51
5.5.1.1
Analytical determinations .....................................................................................51
5.5.1.2
5.5.2
Assessment of soluble protein biomarkers........................................................51
Methods of sample collection ...............................................................................51
5.5.2.1
Analytical determinations .....................................................................................52
5.5.2.2
5.5.3
Biomarker sample banking................................................................................52
5.5.4
DNA Banking.......................................................................................................52
Methods of sample collection ...............................................................................52
5.5.4.1
Analytical determinations .....................................................................................52
5.5.4.2
OTHER ASSESSMENTS...................................................................................52
5.6
5.6.1
Quality of Life Questionnaires DLQI and WLQ .............................................52


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5.6.2
Study drug self-administration questionnaire..................................................53
5.6.3
Health Care Resource Utilization (HCRU) Questionnaire .............................53
APPROPRIATENESS OF MEASUREMENTS..............................................53
5.7
6.
INVESTIGATIONAL PLAN.............................................................................54
VISIT SCHEDULE.............................................................................................54
6.1
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS .................54
6.2
6.2.1
Screening period..................................................................................................54
6.2.2
Treatment period ................................................................................................55
6.2.3
Follow Up Period and Trial Completion...........................................................56
6.2.3.1 
Early treatment and trial termination ....................................................................56
6.2.3.2 
Trial completion....................................................................................................56
6.2.3.3 
Vital Status............................................................................................................56
7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE
...............................................................................................................................58
STATISTICAL DESIGN - MODEL.................................................................58
7.1
NULL AND ALTERNATIVE HYPOTHESES ...............................................58
7.2
PLANNED ANALYSES.....................................................................................59
7.3
7.3.1
Primary endpoint analyses.................................................................................59
7.3.2
Secondary endpoint analyses .............................................................................61
7.3.3
Further endpoint analyses..................................................................................61
7.3.4
Safety analyses.....................................................................................................62
7.3.5
Pharmacokinetic analyses ..................................................................................62
7.3.6
Pharmacodynamic analyses ...............................................................................63
7.3.7
Biomarker analyses.............................................................................................63
INTERIM ANALYSES ......................................................................................63
7.4
HANDLING OF MISSING DATA ...................................................................63
7.5
RANDOMISATION ...........................................................................................64
7.6
DETERMINATION OF SAMPLE SIZE .........................................................64
7.7
8.
INFORMED CONSENT, DATA PROTECTION, TRIAL RECORDS........67
TRIAL APPROVAL, PATIENT INFORMATION, AND INFORMED 
8.1
CONSENT ...........................................................................................................67
DATA QUALITY ASSURANCE ......................................................................68
8.2
RECORDS...........................................................................................................68
8.3
8.3.1
Source documents ...............................................................................................68
8.3.2
Direct access to source data and documents.....................................................68
LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE EVENTS69
8.4
8.4.1
Listedness.............................................................................................................69
8.4.2
Expedited reporting of Adverse Events ............................................................69
STATEMENT OF CONFIDENTIALITY........................................................69
8.5
END OF TRIAL..................................................................................................69
8.6
9.
REFERENCES....................................................................................................70
PUBLISHED REFERENCES............................................................................70
9.1
UNPUBLISHED REFERENCES......................................................................72
9.2


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10.
APPENDICES.....................................................................................................73
PASI DEFINITIONS  AND  USE......................................................................73
10.1
STATIC  PHYSICIAN  GLOBAL  ASSESSMENT ( SPGA) ........................74
10.2
NAIL PSORIASIS SEVERITY INDEX (NAPSI)............................................76
10.3
PALMOPLANTAR  PSORIASIS  SEVERITY  INDEX  (PPASI)................77
10.4
PSORIASIS SCALP SEVERITY INDEX (PSSI)............................................78
10.5
DERMATOLOGY LIFE QUALITY INDEX (DLQI) ....................................79
10.6
WORK LIMITATIONS QUESTIONNAIRE (WLQ).....................................81
10.7
10.8 
SUPERVISING NURSE/HEALTH CARE PROFESSIONAL 
QUESTIONNAIRE – SELF-ADMINISTRATION OF BI 655066 ACTIVE 
OR PLACEBO ....................................................................................................92
11.
DESCRIPTION OF GLOBAL AMENDMENT(S) .........................................94


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ABBREVIATIONS
ADA
AE
Anti-drug antibodies
Adverse Event
AESI
ALT
AP
aPTT
AST
Adverse Event of Special Interest
Alanine transferase
Alkaline Phosphatase
Activated Partial Thromboplastin Time
Aspartate transferase
AUC
Area under the Curve
BIRDS
Boehringer Ingelheim Regulatory Documents for Submission
BLA
BUN
CCDS
Biologic Licensing Application
Blood urea nitrogen
Company Core Data Sheet
CI
Confidence Interval
CK
CK-MB
Cmax
CML
Creatine Kinase
Creatine Kinase Muscle Brain
Maximal concentration
Local Clinical Monitor 
CRA
Clinical Research Associate
CRF
Case Report Form
CTCAE
Common Terminology Criteria for Adverse Events
CTP
Clinical Trial Protocol
CTR
CV
DEDP
DILI
Clinical Trial Report
Cardiovascular
Drug Exposure During Pregnancy
Drug induced liver injury
DLQI
DNA
DMC
Dermatology Life Quality Index
Deoxyribonucleic Acid
Data Monitoring Committee
ECG
eCOA
eCRF
Electrocardiogram
Electronic clinical outcome assessment
Electronic Case Report Form
EDC
Electronic Data Capture
eGFR
ELISA
EOO
EOT
ePRO
Estimated glomerular filtration rate
Enzyme Linked Immunosorbent Assay
End of Observation
End of Treatment
Electronic Patient Reported Outcome
EU
EudractCT
European Union
European Clinical Trials Database
FAS
Full Analysis Set
FC 
Flow Chart
GCP  
Good Clinical Practice
gCV
GGT
Geometric mean of Coefficient Variation
Gamma-Glutamyl Transferase


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GOT
Hb
HCRU
Hct
HDL
HIPAA
HIV
HOMA
Glutamat Oxalacetate Transaminase
Hemoglobin
Health Care Resource Utilization
Hematocrit
High density lipoprotein
Health insurance portability and accountability act
Human immunodeficiency virus
Homeostatis model assessment
HPC
IB 
IC 
Human Pharmacology Centre
Investigator’s Brochure
Inhibitory concentration
ICH
IEC 
IFN
IgG
IL
INR
IQR
International conference on harmonisation
Independent Ethics Committee
Interferon
Immunogloblin G
Interleukin
International normalized ratio
Interquartile range
IRB 
Institutional Review Board
IRT 
Interactive Response Technology
ISF
Investigator Site File
i.v.
intravenous
IVRS
Interactive Voice Response System
IWRS
LDL
Interactive Web-based Response System
Low density lipoprotein
LOCF
LoEE
mAb
MACE
Last Observation Carried Forward
List of Essential Element
Monoclonal antibody
Major Adverse Cardiovascular Events 
MedDRA
Medical Dictionary for Drug Regulatory Activities
MMRM
MST
NAb
NAPSI
NOAEL
Mixed effect Model Repeat Measurement
Medical Sub team
Neutralizing Antibody
Nail Psoriasis Severity Index
No observed adverse effect level
NRI
OLE
OPU
PASI
No Response Imputation
Open label extension
Operative Unit
Psoriasis Area and Severity Index
Pbo
PD
Placebo
Pharmacodynamics
PK
Pharmacokinetics
p.o.
per os (oral)
PoCC
PPASI
PPD
Proof of Clinical Concept
Palmoplantar Psoriasis Area Severity Index
Purified Protein Derivative


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PPS
PSSI
Per Protocol Set
Psoriasis Scalp Severity Index
q.d.
RBC
RCTC
RDC
quaque die (once a day)
Red blood cells
Rheumatology Common Toxicity Criteria
Remote data capture
REP
Residual effect period, after the last dose of medication with measureable 
drug levels or pharmacodynamic effects still likely to be present
RNA
RRS-PPS
SAE
Ribonucleic Acid
Re-Randomized Per Protocol Set
Serious Adverse Event
SAF
s.c.
SD
SmPC
Safety Set
Subcutaneous
Standard deviation
Summary of product characteristics
SOPs
sPGA
SUSAR
TB
Standard Operating Procedures
Static Physician Global Assessment
Suspected unexpected serious adverse reaction
Tuberculosis
TCM
Trial Clinical Monitor
TMF
Trial Master File
TNF
Tumor Necrosis Factor
TSAP
Trial Statistical Analysis Plan
TSH
ULN
US PI
Thyroid Stimulating Hormone
Upper limit of normal
United States Product Information
VEGF
WBC
WLQ
Vascular endothelial growth factor
White blood cells
Work Limitations Questionnaire






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2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT
RATIONALE FOR PERFORMING THE TRIAL
2.1
Psoriasis is a chronic inflammatory disease affecting 2% of the world population with 
significant impact on patient quality of life and associated with significant systemic disease. 
IL-23 plays a key role in the pathophysiology of psoriasis through induction and maintenance 
of Th-17 type cells that secrete inflammatory cytokines. BI 655066 is a humanized 
monoclonal antibody that specifically neutralizes the IL-23 axis. Proof of clinical concept 
(PoCC) for BI 655066 was demonstrated in a single dose phase I trial in 39 patients with 
moderate to severe plaque psoriasis where 87% of patients achieved at least 75% reduction in 
Psoriasis Area and Severity Index (PASI 75) with no safety concerns (1311.1, c02434648).
The current trial is being performed to assess the safety and efficacy of BI 655066 to support 
registration for the treatment of moderate to severe chronic plaque psoriasis in adult patients.
TRIAL OBJECTIVES
2.2
The main objectives of this study are to assess the efficacy and safety of BI 655066 compared 
to adalimumab in patients with moderate to severe chronic plaque psoriasis. The primary 
efficacy evaluation will be performed at 16 weeks and an assessment of maintenance of 
response will be performed at 44 weeks. The study will also evaluate the efficacy of a 28 
week treatment with BI 655066 in patients who were initially treated with adalimumab for 16 
weeks, achieving insufficient or only partial response with adalimumab, and then switched to 
BI 655066 treatment from Week 16 to Week 44.
In addition, this trial will assess PK and the emergence of anti-drug antibodies (ADA) and 
their effect on efficacy and safety. Moreover, it will be explored how the use of BI 655066 
may influence gene and protein expression levels and disease specific protein markers.
Lastly, the influence of study treatment on some metabolic risk factors will be looked into.
BENEFIT - RISK ASSESSMENT
2.3
Participation in this study may help to generate future benefit for larger groups of patients 
with psoriasis if BI 655066 proves to be successful in treating this disease. BI 655066 has 
been studied in approximately 200 patients with moderate to severe plaque psoriasis. In these 
studies, the majority of patients receiving BI 655066 achieved 90% improvement of their 
disease. The most common adverse events reported in these trials were mild symptoms of the 
upper respiratory tract, including nasal stuffiness, sore throat, and influenza, and headache, 
that showed no dose dependency. These events were not considered to be related to drug 
treatment. Local reactions following subcutaneous administration of BI 655066 were 
uncommon, and limited to redness, swelling or induration at the injection site. No serious 
drug related adverse events were reported.


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As with many immune modulating agents, BI 655066 may impair immune function resulting 
in a risk of infection. This will be monitored by collection of all AEs during the treatment and 
observation periods. Patients with clinically important active infection will not be included in 
the study.
There is not enough information at this time to rule out a risk of cancer with BI 655066, but 
this risk is considered small with this type of compound as experience with the anti-IL 12/23
mAb ustekinumab has not suggested significant risk for cancer/serious infection.
Increases in major adverse cardiovascular events (MACE) including myocardial infarction, 
cerebrovascular accident, and cardiovascular death, reported initially with anti-IL-12/23 
agents, such as ustekinumab, have not been observed in longer term studies. While the 
likelihood of increased MACE is small, all suspected cardiovascular events, serious or non-
serious, observed in this study will be adjudicated by an independent MACE Adjudication 
Committee.
All patients will receive active treatment in this study, either BI 655066 or adalimumab; there 
is no placebo comparator in this trial. Adalimumab (Humira®) is used as an established 
treatment for patients with moderate to severe psoriasis and has been on the market in many 
countries for many years. Adalimumab has an acceptable safety profile.
Although rare, a potential for drug-induced liver injury 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 5.3.6.1.
In order to recognize any safety signals as early as possible, an independent Data Monitoring 
Committee (DMC) will monitor this study and all studies where patients are receiving BI 
655066. 
In conclusion, the benefit-risk profile is considered appropriate for this stage of clinical 
development.


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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
OVERALL TRIAL DESIGN AND PLAN
3.1
This confirmatory multi-national, randomized, double-blind, double dummy, active 
controlled, parallel design study compares BI 655066 with adalimumab. In total, 
approximately 600 patients with moderate to severe chronic plaque psoriasis will be 
randomized in this trial. 
Patients are included in the study once they have signed the informed consent. Patients 
suitable after screening will be eligible to participate in the 44 week treatment period and will 
be randomized at a ratio of 1:1 to one of 2 treatment arms (BI 655066 or adalimumab) shown 
in Figure 3.1: 1.
Patients initially randomized to BI 655066 will stay on BI 655066. 
At Week 16, patients initially on adalimumab and <PASI 50 will be switched to BI 655066.
At Week 16, patients initially on adalimumab and >PASI 90 will stay on adalimumab.
At Week 16, patients initially on adalimumab and >PASI 50 and <PASI 90 will be 
re-randomised 1:1 to receive either BI 655066 or adalimumab. 
Figure 3.1: 1 Trial design
Patients will be blinded to treatment. Patients in each dose group will receive the same 
injections (active or placebo) at each designated time point, in order to maintain blinding. 


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Patients starting and continuing with BI 655066 active drug will receive 2 syringes of 
BI 655066 active drug (2 x 75mg) at randomization, at Weeks 4, 16 and 28 and placebo 
adalimumab at randomization (2 syringes) and 1 placebo adalimumab syringe at Weeks 1, 3, 
5, 7, 9, etc. up to Week 41. These patients also receive 2 syringes of BI 655066 placebo at 
Weeks 20 and 32 to maintain blinding to the BI 655066 active treatment arm starting at 
Week 16 after adalimumab pre-treatment. BI 655066 active treatment always starts with a 
loading dose 4 weeks after the first injection.
Patients starting with active adalimumab and switching to active BI 655066 at Week 16 will 
receive 2 syringes active adalimumab at randomization (2 x 40mg) followed by 1 syringe 
active adalimumab (40mg) at Weeks 1, 3, 5, 7, 9, 11, 13, 15; and 1 placebo adalimumab 
syringe at Weeks 17, 19, 21, etc. up to Week 41 to maintain blinding. These patients also 
receive 2 syringes of BI 655066 placebo at randomization and Week 4 followed by two 
active BI 655066 injections (2 x 75mg) at Weeks 16, 20 and 32 as well as 2 placebo BI 
655066 injections at Week 28. 
Patients starting and continuing with adalimumab active drug will receive 2 syringes active 
adalimumab at randomization (2 x 40mg) followed by 1 syringe active adalimumab (40mg) 
at Weeks 1, 3, 5, 7, 9, etc. up to Week 41. These patients also receive 2 syringes of placebo 
BI 655066 at randomization and at Weeks 4, 16, 20, 28 and 32. 
Individual patient participation is concluded when the patient has completed the last planned 
visit. The “last-patient-last-visit-primary-endpoint” is the last scheduled primary endpoint 
visit at Week 16 completed by the last patient.  The end of the trial is defined as “last patient 
out”, i.e. last scheduled visit completed by last patient. 
Patients will be offered to roll over into an open label extension (OLE) trial if they have 
completed the study 1311.30 and meet the inclusion criteria for the OLE trial. 
Patients who terminate the study drug early in study 1311.30, will complete EOT Visit 
procedures instead of the planned treatment period visit and return 16 (±1) weeks after the 
last BI 655066 (active or placebo) administration for EOO Visit. Discontinuation of study 
medication should not necessarily lead to withdrawal from the study. If possible, the patient 
should be further followed up and complete all study visits and procedures until EOO.
Patients who complete the randomized treatment period of study 1311.30, but will not be 
included in the OLE study will have their EOO Visit 4 (±1) weeks after their EOT Visit at 
Week 44 (which is at Week 48 ±1 week).
3.1.1
Administrative structure of the trial
The trial is sponsored by AbbVie in the USA and Boehringer Ingelheim (BI) ex-US.
Boehringer Ingelheim has appointed a Trial Clinical Monitor (TCM), responsible for 
coordinating all required activities, in order to:
∀
manage the trial in accordance with applicable regulations and internal Standard 
Operating Procedures (SOPs),


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∀
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.
A Coordinating Investigator will be responsible to coordinate activities of investigators at 
different centres participating in this multicentre trial. Tasks and responsibilities will be 
defined in a contract. Relevant documentation on the participating investigators and other 
important participants, including their curricula vitae, will be filed in the ISF
Data Management will be done by BI according to BI SOPs and Statistical Evaluation will be 
done by AbbVie according to BI SOPs.
A central laboratory service and vendors for ECG, eCOA (electronic clinical outcome 
assessment) and IRT (interactive response technology) will be used in this trial. Details will 
be provided in the applicable manuals, available in ISF.
The organisation of the trial in the participating countries will be performed by the respective 
local BI-organisation (Operation Unit (OPU) 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. In each OPU participating in this study, a CML will be 
appointed responsible for coordinating the activities required in order to manage the trial in 
accordance with applicable regulations and internal SOPs in the countries covered by the 
respective BI OPU.
3.1.2
Data Monitoring Committee (DMC) 
A data monitoring committee (DMC), independent of the Sponsor will be established to 
assess the progress of the clinical trial, including unblinded safety assessments at specified 
intervals, and to recommend to the Sponsor whether to continue, modify, or stop the trial. 
Any efficacy data provided to the DMC will only be used for DMC’s obligation to assess the 
full benefit-to-risk of the treatments. Thus, no statistical penalty will be imposed since 
efficacy analyses will not be the basis for any potential early trial termination. Measures are 
in place to ensure blinding of the Sponsor and all other trial participants. The Sponsor will 
remain blinded until after the last patient completes the last study visit. The tasks and
responsibilities of the DMC will be specified in a charter. The DMC will maintain written 
records of all its meetings.
3.1.3
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 major adverse cardiovascular events (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.


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DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
3.2
CONTROL GROUP
This is a randomized double blind, double dummy and active controlled parallel design study. 
This design is appropriate for assessing the safety and efficacy of BI 655066 compared to 
adalimumab in patients with moderate to severe chronic plaque psoriasis. Patients will be 
followed up for a total of 44 weeks plus a residual effect period in order to assess the safety 
and maintenance of efficacy of BI 655066 compared to adalimumab.
A log of all patients enrolled into the trial (i.e. signed informed consent) will be maintained in 
the ISF at the investigational sites irrespective whether these patients have been treated with 
investigational drug or not.
SELECTION OF TRIAL POPULATION
3.3
A total of approximately 600 patients will be randomized in the current trial. A sufficient 
number of patients will be screened to meet this randomization goal. Patients will be
recruited at multiple investigative sites in multiple countries. Approximately 70 sites are 
planned with approximately 4 – 10 patients to be randomized per site. Recruitment will be 
competitive.
3.3.1
Main diagnosis for trial entry
Patients must have moderate to severe chronic plaque psoriasis, defined as ≥ 10% body 
surface area involvement, Psoriasis Area and Severity Index (PASI) score ≥ 12 and static 
Physician Global Assessment (sPGA) score ≥3. 
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. Male or female patients. Women of childbearing potential* 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. A list of 
contraception methods meeting these criteria is provided in the patient information.
*Women of childbearing potential are defined as:
∀
having experienced menarche and
∀
not postmenopausal (12 months with no menses without an alternative medical 
cause) and
∀
not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral 
oophorectomy or bilateral salpingectomy).
2. Age ≥ 18 years at screening
3. Have a diagnosis of chronic plaque psoriasis (with or without psoriatic arthritis) for at 
least 6 months before the first administration of study drug. Duration of diagnosis 
may be reported by the patient.


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4. Have stable moderate to severe chronic plaque psoriasis with or without psoriatic 
arthritis at both Screening and Baseline (Randomization):
a.
Have an involved body surface area (BSA) ≥ 10% and
b. Have a Psoriasis Area and Severity Index (PASI) score ≥ 12 and
c.
Have a static Physician Global Assessment (sPGA) score of ≥ 3.
5. Must be candidates for systemic therapy or phototherapy for psoriasis treatment, as 
assessed by the investigator
6. Must be candidates for treatment with adalimumab (Humira®) according to local label
as confirmed by the investigator.
7. Signed and dated written informed consent prior to admission to the study in 
accordance with GCP and local legislation
8. Patient must be able and willing to self-administer the study medication
3.3.3
Exclusion criteria
1. Patients with 
a.
non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)
b. current drug-induced psoriasis (including an exacerbation of psoriasis from 
beta blockers, calcium channel blockers, or lithium)
c. active ongoing inflammatory diseases other than psoriasis that might confound 
trial evaluations according to investigator’s judgment
2. Previous exposure to BI 655066 
3. Previous exposure to adalimumab (Humira®) 
4. Currently enrolled in another investigational study or less than 30 days (check also
with restricted medication table 4.2.2.1: 1) (from screening) since completing another 
investigational drug or device study.
5. Use of any restricted medication as specified in Table 4.2.2.1: 1 or any drug 
considered likely to interfere with the safe conduct of the study.
6. Major surgery performed within 12 weeks prior to randomization or planned within 
12 months after screening (e.g. hip replacement, removal aneurysm, stomach ligation).  
7. Known chronic or relevant acute infections, such as active tuberculosis, HIV or viral 
hepatitis. Confirmation of these diseases testing is required at screening.
QuantiFERON® TB test or PPD skin test will be performed according to local 
labelling for Humira®. If the result is positive, patients may participate in the study if 
further work up (according to local practice/guidelines) establishes conclusively that 
the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is 


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established, then treatment should have been initiated and maintained according to 
local country guidelines.
8. Any documented active or suspected malignancy or history of malignancy within 5 
years prior to screening, except appropriately treated basal cell or squamous cell 
carcinoma of the skin or in situ carcinoma of uterine cervix.
9. Evidence of a current or previous disease, medical condition (including chronic 
alcohol or drug abuse) other than psoriasis, surgical procedure (i.e., organ transplant), 
medical examination finding (including vital signs and ECG), or laboratory value at 
the Screening Visit outside the reference range 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.
10. History of allergy/hypersensitivity to a systemically administered biologic agent or its 
excipients
11. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
12. Previous enrolment in this trial
3.3.4
Removal of patients from therapy or assessments
Removal of individual patients
3.3.4.1
All patients have the right to withdraw from the study at any time without the need to justify 
their decision. The investigator has the right to remove patients from the study for non-
compliance, administrative or other reasons. It should be clearly understood that an excessive 
rate of withdrawals can render the study results uninterpretable. The sponsor reserves the 
right to remove any study patient from the trial for non-compliance.
An individual patient is to be withdrawn from trial treatment if:
∀
The patient withdraws consent for study treatment or study participation, without the 
need to justify the decision.
∀
The patient can no longer be treated with trial medication for other medical reasons 
(such as surgery, adverse events, other diseases, or pregnancy)
∀
Development of a toxicity or adverse event which warrants BI 655066 discontinuation 
including but not limited to SAEs or SUSARs
∀
If prohibited treatment is used during the study for any indication, the subject must 
discontinue use of the prohibited treatment if he/she wishes to continue in the 
study. In case of undue safety risk for the subject, the subject should discontinue 
study treatment at the discretion of the investigator. If the subject received a live virus 
vaccination during the study, the subject must discontinue study treatment.


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∀
If the patient experiences an intolerable increase of psoriasis during the course of the 
trial the patient will be discontinued from the trial to receive treatment as deemed 
appropriate by the investigator.
Of note: Discontinuation of study medication should not necessarily lead to withdrawal from 
the study. If possible the patient should be further followed up and complete all study visits 
and procedures as initially planned.
Given the patient’s agreement, the patient will undergo the procedures for early treatment 
discontinuation and follow up as outlined in the flow chart and section 6.2.3.
Patients who discontinue the trial after receiving the first dose of study medication at Visit 2 
will not be replaced.
For randomised patients leaving the study before the planned EOO, vital status should be 
collected at the date of the planned EOO Visit for a completed patient not going into the OLE 
study. Vital status assessment for discontinued patients should occur at 48 (±1) weeks after 
randomisation.
For all patients the reason for withdrawal (e.g. adverse events) must be recorded in the eCRF. 
These data will be included in the trial database and reported.
Discontinuation of the trial by the sponsor
3.3.4.2
AbbVie/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 that could significantly affect continuation 
of the trial or any other administrative reasons i.e. problems with availability of the study 
medication, discontinuation of development of BI 655066
3. Violation of GCP, the CTP, or the contract disturbing 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
TREATMENTS TO BE ADMINISTERED
4.1
Multiple doses of BI 655066, comparator drug adalimumab and matching placebos to both BI 
655066 and adalimumab will be administered subcutaneously. All products will be supplied 
by Boehringer Ingelheim.
4.1.1
Identity of BI investigational product and comparator product
Table 4.1.1: 1 Description of test product BI 655066
Substance:
BI 655066: Anti-human IL-23p19 mAb
Pharmaceutical form:
Injection solution of BI 655066, presented in a pre-filled 
syringe
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Chemical form:
Anti-human IL-23p19 mAb
Molecular weight
Approximately 148 kDa
Unit Strength:
75 mg BI 655066 in pre-filled syringe
Route of administration:
Subcutaneous injection
Posology:
2 injections à 75mg at randomization, at Weeks 4, 16 
and 28 for patients initially randomized to BI 655066
and who continue on BI 655066;
2 injections à 75mg at Weeks 16, 20 and 32 for patients 
crossing over from adalimumab to BI 655066 at 
Week 16
Duration of use:
28 weeks (from first to last administration) for 
BI 655066 arm
16 weeks (from first to last administration) for patients 
crossing over from adalimumab arm to BI 655066
Table 4.1.1: 2 Description of BI 655066 placebo
Substance:
Placebo to match BI 655066
Pharmaceutical form:
0.9% sodium chloride solution presented in a pre-filled 
syringe
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Chemical form:
Not applicable
Molecular weight
Not applicable


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Table 4.1.1: 2 Description of BI 655066 placebo (cont´d)
Unit Strength:
Not applicable
Route of administration:
Subcutaneous injection
Posology:
a) 2 injections at Week 20 and 32 for patients who start 
with BI 655066 and continue on BI 655066
b) 2 injections at randomization, Weeks 4 and 28 for 
patients switching from adalimumab to BI 655066 at 
Week 16
c) 2 injections at randomization, Weeks 4, 16, 20, 28, 
and 32 for patients who start with adalimumab and 
continue on adalimumab
Duration of use:
12 weeks or 28 weeks or 32 weeks from first to last 
administration for treatment arms a), b) and c), 
respectively
Table 4.1.1: 3 Description of test product adalimumab
Substance: 
Adalimumab (Brand Name Humira®)
Pharmaceutical form:
Injection solution of adalimumab, presented in a pre-
filled syringe
Source:
AbbVie Inc.
Chemical form:
recombinant human IgG1 monoclonal antibody specific 
for human tumor necrosis factor
Molecular weight
Approximately 148 kDa
Unit Strength:
40 mg adalimumab in a pre-filled syringe
Route of administration:
Subcutaneous injection
Posology:
2 injections à 40mg at randomization (80 mg loading 
dose), then 1 injection à 40mg at Weeks 1, 3, 5, 7, etc., 
every other week until Week 41 for patients who start 
with and continue on adalimumab; or only up to Week
15 for patients who switch from adalimumab to BI 
655066 at Week 16.
Duration of use:
41 weeks (from first to last administration) for patients 
who start and continue on adalimumab, or 15 weeks for 
patients who cross-over to BI 655066 at Week 16 


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Table 4.1.1: 4 Description of adalimumab placebo
Substance:
Placebo to match Adalimumab
Pharmaceutical form:
0.9% sodium chloride solution presented in a pre-filled 
syringe
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Chemical form:
Not applicable
Molecular weight
Not applicable
Unit Strength:
Not applicable
Route of administration:
Subcutaneous injection
Posology:
2 injections at randomization, followed by 1 injection at 
Weeks 1, 3, 5, 7 etc., every other week
Duration of use:
41 weeks (from first administration at randomisation to 
last administration at Week 41) for patients who start 
with and continue on BI 655066;
24 weeks (from first administration at Week 17 to last 
administration at Week 41) for patients who cross-over 
from active adalimumab to BI 655066 at Week 16
4.1.2
Method of assigning patients to treatment groups
Through the utilization of Interactive Response Technology/Tool (IRT), patients will be 
initially randomized to receive BI 655066 or adalimumab in a ratio of 1:1.
After the eligibility criteria are confirmed, the patient will be randomized 1:1 to either BI 
655066 or adalimumab on Day 1 (Visit 2) through IRT call or website entry. At visits where 
study medication is to be administered or dispensed to the patient, study sites will be required 
to complete the medication resupply module in the IRT. 
Patients initially randomized to adalimumab and with a PASI response of >PASI 50 and 
<PASI 90 at Week 16 will be re-randomised 1:1 to receive either BI 655066 or adalimumab
(refer to Section 3.1). Patients initially randomized to BI 655066 will stay on BI 655066. 
Patients initially randomized to adalimumab and >PASI 90 at Week 16 will continue on 
adalimumab. Allocation of patients to the three treatments (who continue on BI 655066 / who 
will be switched from adalimumab to BI 655066 / who will continue on adalimumab) from 
Week 16 onwards through EOT will be realized by the IRT. The study personnel will enter 
the PASI score into the IRT system at Visit 2 and at Visit 8 (Week 16).
Details regarding the use of the IRT are described in the site-user manual available in the ISF.






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following adalimumab (active or placebo) injections (at weeks 5, 7, 9, 11, etc. with a time 
window of ±3 days) will be self-administered by the patient at home. The study site should 
remind the patient by phone when each home administration is due. The patient is asked to 
record date and time of each home administration of adalimumab (active or placebo) in a 
paper diary.  
At Visit 5 (Week 4), Visit 8 (Week 16), Visit 9 (Week 20), Visit 11 (Week 28) and Visit 12 
(Week 32) the patient self-administers BI 655066 (active or placebo) at the study site under 
supervision of study personnel. The two injections at these dosing visits should be 
administered within approximately 5 minutes. The study personnel will complete a study 
drug self-administration questionnaire for the BI 655066 (active or placebo) self-
administrations by patients (refer to Section 5.6.2 and Appendix 10.8). 
BI 655066 (active and matching placebo) as well as adalimumab (active or matching 
placebo) will be administered as a subcutaneous injection in the abdomen (preferably lower 
abdomen) or thigh. The two BI 655066 (active or matching placebo) injections done 
subsequently within approximately 5 minutes should be at least 2 cm apart and should not be 
close to a vein. The injection sites should avoid sites of psoriasis involvement as well as sites 
where the skin is tender, bruised, erythematous, or indurated, and should be alternated to 
other areas for subsequent doses. Further information regarding injection details will be 
provided in the ISF. The dosing time to be entered in the eCRF is always the time of 
administration of the first syringe.  
For study site visits, investigators and patients are instructed to adhere to the regular allowed 
time window according to the Flow Chart (i.e. ±1 day at Visit 3; ±3 days at Visits 4 to 14 
and at EOT Visit; ±7 days at EOO Visit). In the rare event that a patient comes too late to a 
scheduled visit it must be decided whether the delayed visit should still be performed or 
should be skipped. Table 4.1.4: 1 shows the upper limits for extended time windows up to 
which study visits can still be performed
Table 4.1.4: 1 Upper Limits for extended time windows for study visits
Visit
Week
Scheduled 
Visit Day
Upper limit of 
delay (Days)
Upper limit 
(Day)
V3
Week 1
Day 8
+ 6
Day 14
V4
Week 3
Day 22
+ 6
Day 28
V5
Week 4
Day 29
+ 27
Day 56
V6
Week 8
Day 57
+ 27
Day 84
V7
Week 12
Day 85
+ 27
Day 112


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Table 4.1.4: 1 Upper Limits for extended time windows for study visits (cont´d)
Visit
Week
Scheduled 
Visit Day
Upper limit of 
delay (Days)
Upper limit 
(Day)
V8*
Week 16
Day 113
+ 13
Day 126*
V9
Week 20
Day 141
+ 27
Day 168
V10
Week 24
Day 169
+ 27
Day 196
V11
Week 28
Day 197
+ 27
Day 224
V12
Week 32
Day 225
+ 27
Day 252
V13
Week 36
Day 253
+ 27
Day 280
V14
Week 40
Day 281
+ 27
Day 308
*if Day 126 is exceeded, Visit 8 (Week 16) will be performed, but patient will continue their previous treatment 
There is an exception for Visit 8 (Week 16). This visit will not be skipped. If the upper limit 
of 126 days for Visit 8 (Week 16) is exceeded, Visit 8 will be performed, but the patient will 
continue with their previous treatment, irrespective of PASI score. 
Adalimumab (active or placebo) home administrations should occur with a time window of 
±3 days. The distance between two adalimumab (active or placebo) administrations should 
not be less than 11 days. The time window of ±3 days can be utilized for planning of home
administrations. If the minimum distance of 11 days cannot be adhered to, the respective 
administration should be skipped and the next scheduled dose should be administered. 
The injections at each visit, including dummy injections of placebo necessary in order to 
assure blinding are presented in Table 4.1.4: 2. 
Table 4.1.4: 2 Dosing Schedule
Dosing
Patients only on
BI 655066**
Patients starting with 
adalimumab and 
switching to 
BI 655066** at 
Week 16
Patients only on
Adalimumab
Randomisation
(Visit 2)
Active BI 655066 and
Placebo adalimumab*
Placebo 655066 and
Active adalimumab*
Placebo 655066 and
Active adalimumab*
Week 1 (Visit 3)
Placebo adalimumab
Active adalimumab
Active adalimumab


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Table 4.1.4: 2 Dosing Schedule (cont´d)
Dosing
Patients only on
BI 655066**
Patients starting with 
adalimumab and 
switching to 
BI 655066** at 
Week 16
Patients only on
Adalimumab
Week 3 (Visit 4)
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 4 (Visit 5)
Active BI 655066
Placebo 655066
Placebo 655066
Week 5
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 7
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 9
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 11
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 13
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 15
Placebo adalimumab
Active adalimumab
Active adalimumab
Week 16 (Visit 8)
Active BI 655066
Active BI 655066
Placebo 655066
Week 17
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 19
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 20 (Visit 9)
Placebo 655066
Active BI 655066
Placebo 655066
Week 21
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 23
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 25
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 27
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 28 (Visit 11)
Active BI 655066
Placebo 655066
Placebo 655066
Week 29
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 31
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 32 (Visit 12)
Placebo 655066
Active BI 655066
Placebo 655066
Week 33
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 35
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 37
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 39
Placebo adalimumab
Placebo adalimumab
Active adalimumab
Week 41
Placebo adalimumab
Placebo adalimumab
Active adalimumab


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* Two injections adalimumab (active or placebo) only at Visit 2 (adalimumab loading dose is 80mg); one injection 
    adalimumab (active or placebo) at Visits 3 and 4 and at all home administrations 
** BI 655066 (active or placebo) always two injections (two injections à 75mg for active drug)
4.1.5
Blinding and procedures for unblinding
Blinding
4.1.5.1
Patients, investigators and everyone involved in trial conduct or analysis or with any other
interest in this double-blind trial will remain blinded with regard to the randomized treatment 
assignments until after database lock.
The randomization code will be kept secret by Clinical Trial Support up to database lock.
The randomization codes will be provided to bioanalytics prior to last patient out to allow for 
the exclusion from the analyses of pharmacokinetic (PK) samples taken from placebo 
patients. Bioanalytics will not disclose the randomization code or the results of their 
measurements until the trial is officially unblinded. Serum drug levels and demographic data 
together with treatment assignments and dosing information may be made available to 
individuals outside of the trial team for the purpose of PK dataset generation and analysis in 
accordance with sponsor’s standard procedures.
Due to the requirements to report Suspected Unexpected Serious Adverse Reactions 
(SUSARs), it may be necessary for a representative from BI’s drug safety group to access the 
randomisation code for individual patients during study conduct via the IRT system. In such 
cases, access to the code will only be permitted by authorised drug safety representatives.  
Refer to Section 4.1.5.2 for rules of breaking the blinding code for an individual or for all 
patients in emergency situations
Unblinding and breaking the code
4.1.5.2
Emergency unblinding will be available to the Investigator / Pharmacist / investigational drug 
storage manager 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.
4.1.6
Packaging, labelling, and re-supply
BI 655066, adalimumab, and matching placebo supplies will be provided by Boehringer 
Ingelheim Pharma GmbH & Co KG, Biberach, Germany (see Section 4.1.1 for more details). 
Pre-filled syringes of study medication will be provided in individual boxes identified with 
the trial number, batch and medication number. Supply of study medication will be managed 
by the IRT.
For details of packaging and the description of the label, refer to the ISF.


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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. A
temperature log must be maintained for documentation.
If the storage conditions are found to be outside the specified range, the sponsor must be 
contacted immediately. Refer to the ISF.
Trial medication must be securely stored, e.g. in a locked refrigerator or at a pharmacy. The 
medication may only be dispensed to trial patients according to the CTP by authorized 
personnel as documented in the trial staff list.
4.1.8
Drug accountability
Drug supplies will be provided by the sponsor.
The Investigator and/or Pharmacist and/or investigational drug storage manager will receive 
the investigational drugs delivered by the Sponsor when the following requirements are 
fulfilled:
∀
Approval of the trial protocol by the IRB / ethics committee, 
∀
Availability of a signed and dated clinical trial contract between the Sponsor and the head 
of 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
∀
Availability of the proof of a medical license for the principal Investigator
∀
Availability of Form 1572 (for USA). 
All unused medication must be returned to the sponsor. Used medication will be destroyed 
per local guidelines. Account must be given for any discrepancies.
Receipt, usage, and return must be documented. Account must be given for any discrepancy.
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 CTP 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.
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
4.2
TREATMENT
4.2.1
Rescue medication, emergency procedures, and additional treatments
There are no special emergency procedures to be followed.


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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) are 
permissible. All concomitant medications should be carefully evaluated by the investigator,
and the CML should be contacted when there are questions regarding concomitant 
medications.
In the event that a patient experiences an intolerable increase of psoriasis, as deemed by the 
investigator, during the course of the trial the patient will be discontinued from the trial to 
receive rescue treatment. 
In case of adverse events 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 eCRF.
4.2.2
Restrictions
Restrictions regarding concomitant treatment
4.2.2.1
The medications (or classes of medications) listed in Table 4.2.2.1: 1 must not be taken for 
the time periods as specified.
Table 4.2.2.1: 1
Restricted medications 
Medication or class of medications
Restriction duration  
(through EOO Visit)
Guselkumab, tildrakizumab
Not allowed neither before nor 
during trial participation
Briakinumab, secukinumab (Cosentyx®), ustekinumab 
(Stelara®)
6 months prior to randomisation
Brodalumab, ixekizumab
4 months prior to randomisation
Infliximab (Remicade®)
Investigational products for psoriasis (non biologics)
12 weeks prior to randomisation
Etanercept (Enbrel®)
Live virus vaccinations
6 weeks prior to randomization


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Table 4.2.2.1: 1
Restricted medications (cont´d)
Medication or class of medications
Restriction duration  
(through EOO Visit)
Any investigational device or product (excludes 
psoriasis products)
Other systemic immunomodulating treatments, e.g. 
methotrexate, cyclosporine A, corticosteroids1, 
cyclophosphamide, tofacitinib (Xeljanz®), apremilast 
(Otezla®)
Other systemic psoriasis treatments (e.g. retinoids, 
fumarates, any other drug known to possibly benefit 
psoriasis)
Photochemotherapy (e.g., PUVA)
30 days prior to randomisation
Phototherapy (e.g., UVA, UVB)
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)
14 days prior to randomisation
1 No restriction on corticosteroids with only a topical effect (e.g. inhalative corticosteroids to treat asthma or corticosteroid 
drops used in the eye or ear).  
2 Exception:  Topical steroids of US class 6 (mild, such as desonide) or US class 7 (least potent, such as hydrocortisone) for 
use on the face, axilla, and/or genitalia with a restriction of use within 24 hours prior to trial visit in which PASI is assessed.
Restrictions on diet and life style
4.2.2.2
Patients should be fasted for at least 8 hours prior to collection of the safety laboratory 
samples, starting from Visit 2. Moisturizers/emollients containing retinoids and the use of 
tanning beds are not allowed during the study.
Restrictions regarding women of childbearing potential
4.2.2.3
Female patients of childbearing potential should use the contraception methods described in 
Section 3.3.2 and the patient information. 
TREATMENT COMPLIANCE
4.3
Study medication will be administered in accordance with the protocol. At Visit 2 
(randomisation) the study drugs will be administered by authorized study personnel (e.g. 
study nurse). At Visits 3 and 4 the adalimumab (active or placebo) injections will be self-
administered by the patient under supervision of study personnel. Any further adalimumab
administrations (active or placebo) will be self-administered by the patient at home. BI 
655066 (active or placebo) will be self-administered by the patient under supervision of the 


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study personnel at Visit 5 (Week 4) and at any later visit with BI 655066 (active or placebo) 
administration. 
The measured plasma concentrations will provide additional information about compliance.
Any missed dose has to be documented. The study site should remind the patient by phone 
about the adalimumab (active or placebo) injections to be self-administered by the patient at 
home. The patient will record date and time of each home administration in a paper diary.


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5.
VARIABLES AND THEIR ASSESSMENT 
TRIAL ENDPOINTS
5.1
None of the primary and secondary endpoints are considered safety issues.
5.1.1
Primary Endpoint(s)
There are co-primary endpoints to assess the efficacy of BI 655066 for the treatment of 
moderate to severe chronic plaque psoriasis. These are as follows:
∀
Achievement of ≥ 90% reduction from baseline PASI score (PASI 90) at Week 16
∀
Achievement of an sPGA score of clear or almost clear at Week 16
At the trial level, the co-primary endpoints will be the proportion of patients achieving 
PASI 90 and a sPGA score of clear or almost clear at Week 16 in each of the treatment 
groups.
5.1.2
Secondary Endpoint(s)
Key Secondary Endpoints:
The key secondary endpoints are as follows:
∀
Achievement of ≥75% reduction from baseline PASI score (PASI 75) at Week 16
∀
Achievement of 100% reduction from baseline PASI score (PASI 100) at Week 16
∀
Achievement of ≥90% reduction from baseline PASI score (PASI 90) at Week 44 for 
those patients who are re-randomized at Week 16
Other Secondary Endpoints: 
The other secondary endpoints are as follows:
∀
Achievement of an sPGA score of clear or almost clear (0 or 1) at Week 44
∀
Achievement of sPGA score of clear (0) at Week 44
5.1.3
Further Endpoints
The further endpoints are as follows:
∀
Achievement of PASI 50 at all visits collected
∀
Achievement of PASI 75 at all visits collected
∀
Achievement of PASI 90 at all visits collected
∀
Achievement of PASI 100 at all visits collected
∀
Time until the first achievement of PASI 50, PASI 75, PASI 90, PASI 100 and 
sPGA 0 or 1
∀
Time until loss of PASI 75, PASI 90, PASI 100 and sPGA 0 or 1 response


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∀
Change and percent change from baseline in PASI at all visits collected
∀
Absolute PASI score of <3 at all visits collected
∀
Achievement of an sPGA score of clear or almost clear at all visits collected
∀
Achievement of an sPGA score of clear at all visits collected
∀
Change from baseline in DLQI at all visits collected
∀
Achievement of a DLQI score of 0 or 1 at all visits collected
∀
Achievement of a reduction of 5 or more points from baseline in DLQI score at all 
visits collected
∀
Change from baseline in WLQ at all visits collected
∀
Change and percent change from baseline in Nail Psoriasis Severity Index (NAPSI) 
at all visits collected
∀
Change and percent change from baseline in Palmoplantar Psoriasis Severity Index 
(PPASI) at all visits collected
∀
Change and percent change from baseline in Psoriasis Scalp Severity Index (PSSI) at 
all visits collected
∀
Response to individual questions on the self-administration questionnaire at each 
visit where BI 655066 active or placebo is self-administered
∀
Change of metabolic risk factors from baseline (waist circumference, body weight, 
HOMA-index)
ASSESSMENT OF EFFICACY
5.2
∀
The skin condition will be assessed by using the PASI, sPGA, and other relevant 
scores as described in section 5.1.1 and the ISF.
∀
Symptoms, quality of life, and physical function will be assessed by the DLQI and the 
WLQ.
Details of the efficacy assessments are listed in the Appendix (Section 10).
ASSESSMENT OF SAFETY
5.3
Safety will be assessed descriptively based on: 
∀
Adverse events
∀
Serious adverse events
∀
Clinical laboratory values (haematology, clinical chemistry and urinalysis) 
∀
Intensity of adverse events assessed by Rheumatology Common Toxicity Criteria 
(RCTC) version 2.0 (refer to ISF for details).
∀
Physical examination
∀
Vital signs
∀
12-lead ECG
∀
Local tolerability 


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5.3.1
Physical examination
Complete and target physical examinations will be performed at visits as described in the 
flow chart. Complete physical examination will include vital sign assessment and general 
appearance as well as evaluation of all relevant organ systems. Targeted physical 
examination will include vital sign assessment and evaluation of organ systems associated 
with AE(s) symptoms or laboratory abnormalities.
Clinically relevant abnormal findings will be reported as baseline conditions or AEs.
Waist circumference
5.3.1.1
Waist circumference measurements should be made around a patient’s bare midriff, after the 
patient exhales while standing without shoes and with both feet touching and arms hanging 
freely. The tape should be placed perpendicular to the long axis of the body and horizontal to 
the floor and applied with sufficient tension to conform to the measurement surface. Waist 
circumference should be determined by measuring the midpoint between the lowest rib and 
the iliac crest.
Body weight
5.3.1.2
Body weight measurements should be done on the same scale for each patient. In order to get 
comparable body weight values, body weight measurements should be performed in the 
following way:
∀
fasting (except for the Screening Visit)
∀
after the urine sampling (body weight after bladder voiding)
∀
shoes and coat/jackets should be taken off
∀
pockets should be emptied of heavy objects (i.e. keys, coins etc)
5.3.2
Vital Signs
Vital signs evaluations will be performed at visits as shown in the flow chart. This includes 
temperature, pulse rate, systolic/diastolic blood pressure and respiratory rate. Respiratory 
rate, pulse rate, and blood pressure will be measured after patients have been sitting 
comfortably for at least five minutes. Measurement of vital signs should precede blood 
sampling to avoid the impact of blood sampling on the vital measurements. At dosing visits 
vital signs evaluations will be performed pre-dose and at Visit 2 and Visit 5 additional 
measurements will be performed approximately 5 minutes post-dose (5 min. after last 
injection) and approximately 60 minutes post-dose (60 min. after last injection).
Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for 
approximately 2 hours after the last injection at the Randomization Visit and for 
approximately 1 hour after the last injection at all other visits with drug administration.
Hypersensitivity reactions should be treated according to medical standards. Pre-medications
for further injections might be considered and will be agreed on between investigator and BI 
clinical monitor.


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5.3.3
Safety laboratory parameters
The laboratory tests listed in Table 5.3.3: 1 will be performed at the central laboratory service 
provider. Local laboratory may be used for selected tests in exceptional cases. Patients should 
be fasting for at least 8 hours prior to the blood sample being taken (except Screening Visit). 
Instructions regarding sample collection, sample handling/ processing and sample shipping 
are provided in the Laboratory Manual in the ISF. For time points of laboratory sampling, see 
Flow Chart. 
Laboratory results (i.e. all safety laboratory and clinical laboratory data relevant for current 
clinical practice) of the patients will be available in real time to the respective investigator 
(via laboratory reports) and to the sponsor (via the central laboratory website) and selected 
abnormal laboratory alerts will be flagged to the site and sent to sponsor in real time. 
Clinically relevant abnormal findings will be reported as baseline conditions or AEs. A 
clinically relevant value may be either in- or outside the reference range. Clinically relevant 
abnormal laboratory test results must be confirmed using an unscheduled visit laboratory kit 
and should be repeated until normalization or stabilization or until an alternative explanation 
has been found. Abnormal laboratory values will be also graded for intensity by using RCTC 
Version 2.0 criteria (R13-3515).
Table 5.3.3: 1 
Laboratory tests
Category
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hbc (HbA1c) 
Red Blood Cell Count/ Erythrocytes
Reticulocyte Count
White Blood Cells / Leukocytes
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


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Table 5.3.3: 1 
Laboratory tests (cont´d)
Category
Test name
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)
Amylase
Lipase
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate
Substrates
Glucose
BUN (blood urea nitrogen)
Uric acid
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Troponin I (reflex when CK is elevated)
Albumin
C-Reactive Protein (high sensitive)
Cholesterol, total
Triglycerides
LDL-Cholesterol (calculated by Friedewald 
formula)
HDL-Cholesterol
HOMA-IR (only at Visit 2, Visit 8, and 
EOT Visit)
Urine Pregnancy test (only for female 
patients of childbearing potential) at 
randomization and continued as indicated in 
the Flow Chart (including EOT and EOO 
Visit) (test done in clinic)
Human Chorionic Gonadotropin in the urine
(Dipstick not performed at central lab)
Serum Pregnancy test (only for female 
patients of childbearing potential) at 
screening and if urine pregnancy test is 
positive) 
Human Serum Chorionic Gonadotropin 
(quantitative)
Hormones (only at screening)
TSH, (free T3 and free T4 in case of 
abnormal TSH results)


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Table 5.3.3: 1 
Laboratory tests (cont´d)
Category
Test name
Autoantibodies (only at screening)
Rheumatoid Factor
Urinalysis (dipstick)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/ Erythrocytes
Urine WBC/ Leukocytes
Urine pH
Urine-Sediment (microscopic examination, 
only if urine analysis abnormal)
Urine Sediment Bacteria
Urine Cast in Sediment
Urine Squamous Epithelial Cells
Urine Sed. Crys., Unspecified
Urine Sediment RBC/ Erythrocytes
Urine Sediment WBC/ Leucocytes
Urine
Albumin (quantitative)
Creatinine
Albumin/creatinine ratio
Infections screening (only at screening and 
EOT Visit)
Hepatitis B Surface Antigen (qualitative)
Hepatitis C Antibodies (qualitative)
HIV-1, and HIV-2 Antibody (qualitative)
QuantiFERON®-TB1
1 There is the trial site option to perform a PPD skin test, although this will not be provided or performed at Central Lab.
5.3.4
Electrocardiogram
The 12-lead ECGs will be performed as scheduled in the Flow Chart.
ECGs will be recorded after the patients have rested for at least 5 minutes in a supine position 
and will always precede blood sampling. Six limb leads, as specified by Einthoven (I, II and 
III) and Goldberger (aVR, aVL, aVF), and six pre-cordial leads (V1–V6), according to 
Wilson, will be used. 
ECGs may be repeated for quality reasons and the repeat used for analysis. Additional ECGs 
may be collected for safety reasons. Clinically relevant, abnormal findings will be reported as 
AEs.
Information about the details of ECG collection and the parameters assessed will be provided 
in the ISF.
ECGs will be read and evaluated by a central vendor. The study site will be informed about 
the results of the assessment of the ECG obtained at screening and if there are findings that
would exclude the patient from study participation according to exclusion criterion #9.


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The electronic version of the ECG is regarded as source data. Dated and signed printouts will 
be stored in the patient’s medical file.
5.3.5
Other safety parameters
Local tolerability at the administration site of the subcutaneous injection will be assessed by 
the investigator according to “swelling”, “induration”, “heat”, “redness”, “pain”, or “other 
findings” at the specified visits as noted in the Flow Chart.  This assessment should be done 
pre-dose. 
5.3.6
Assessment of adverse events
Definitions of AEs 
5.3.6.1
Adverse event
An adverse event (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.
Serious adverse event
A serious adverse event (SAE) is defined as any AE which:
∀
results in death,
∀
is life-threatening,
∀
requires inpatient hospitalisation or prolongation of existing hospitalisation,
∀
results in persistent or significant disability or incapacity,
∀
is a congenital anomaly/birth defect,
or
∀
is to be deemed serious for any other reason if it is an important medical event when 
based upon appropriate medical judgment which may jeopardize the patient and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions.
Life-threatening in this context 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.
Every new occurrence of cancer must be reported as a serious event regardless of the duration 
between discontinuation of the drug and the occurrence of the cancer.
AEs considered “Always Serious”
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of AEs, which by their nature, can always be 


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considered to be “serious” even though they may not have met the criteria of an SAE as given 
above.
The latest list of “Always Serious AEs” can be found in the RDC These events should always 
be reported as SAEs. 
Adverse events of special interest (AESIs)
The term AESI relates to any specific AE that has been identified at the project level as being 
of particular concern for prospective safety monitoring and safety assessment within this trial, 
e.g. the potential for AEs based on knowledge from other compounds in the same class. AESI 
need to be reported to the Sponsor’s Pharmacovigilance Department within the same 
timeframe that applies to SAE, see Section 5.3.7.
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 and/or ALT >3 fold ULN combined with an elevation of total 
bilirubin >2 fold ULN measured in the same blood draw sample, and/or
∀
marked peak 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 ISF
and the RDC-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.
Intensity of AEs
The intensity grading of AEs will be performed according to Rheumatology Common 
Toxicity Criteria (RCTC) Version 2.0 developed by OMERACT (R13-3515). Refer to the
ISF for intensity/severity classification. Intensity options are: 
∀
Grade 1
mild
∀
Grade 2
moderate
∀
Grade 3 
severe
∀
Grade 4 
life threatening


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Causal relationship of AEs
Medical judgment 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.
Yes:
There is a reasonable causal relationship between the trial medication administered
and the AE.
No:
There is no reasonable causal relationship between the trial medication administered 
and the AE.
5.3.7
Adverse event collection and reporting
AE Collection
The following must be collected and documented on the eCRF by the Investigator (see Figure 
5.3.7: 1)
∀
From signing the informed consent onwards through the Residual Effect Period 
(REP), until individual patient’s end of trial; all AEs (serious and non-serious) and all 
AESIs must be collected
∀
After the individual patient’s end of trial: the investigator does not need to actively 
monitor the patient for AEs but should only report relevant SAEs and relevant AESIs 
of which the investigator may become aware of.
Figure: 5.3.7: 1 Adverse Events Collection
The REP is defined as 15 weeks after the last administration of BI 655066 (active or 
placebo). All AEs which occurred through the treatment phase and throughout the REP will 
be considered as on treatment; please see Section 7.3.4. Events which occurred after the REP 
will be considered as post treatment events.
AE reporting to 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). 


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The same timeline applies if follow-up information becomes available. In specific occasions 
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.
Information required
For each AE, the Investigator should provide the information requested on the appropriate 
eCRF pages and the BI SAE form, e.g. onset, end date, intensity, treatment required, outcome, 
seriousness, and action taken with the investigational drug(s). The Investigator should 
determine the causal relationship to the trial medication. 
The following should also be recorded as an (S)AE in the eCRF and 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 pre-exist prior trial inclusion they will be considered as 
baseline conditions.
All (S)AEs, including those persisting after individual patient’s end of trial must be followed 
up until they have resolved, have been sufficiently characterized, or no further information 
can be obtained.
Pregnancy
In the rare case that a female subject participating in this clinical trial becomes pregnant after 
having taken trial medication, the Investigator must report immediately (within 24 hours) the 
drug exposure during pregnancy (DEDP) to the Sponsor’s unique entry point (country-
specific contact details will be provided in the ISF). The Pregnancy Monitoring Form for 
Clinical Trials (Part A) should be used. 
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). 
As pregnancy itself is not to be reported as an AE, in the absence of an accompanying 
SAE/AESI, only the Pregnancy Monitoring Form for Clinical Trials and not the SAE form is 
to be completed. If there is an SAE/AESI associated with the pregnancy then the SAE/AESI
has to be reported on the SAE form in addition.
If a patient becomes pregnant during a trial, the study medication needs to be discontinued, 
and the patient will complete end of treatment as well as follow-up procedures.
The ISF will contain the Pregnancy Monitoring Form for Clinical Trials (Part A and B


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DRUG CONCENTRATION MEASUREMENTS AND 
5.4
PHARMACOKINETICS
5.4.1
Assessment of Pharmacokinetics
BI 655066 concentrations will be reported descriptively. No PK parameters will be 
calculated. PK data will be incorporated into a larger pharmacometric analysis with other 
trials of BI 655066 project. The relationship between PK and selected efficacy endpoints, 
biomarkers and AEs may be assessed. PK and demographic data together with treatment 
assignments and dosing information may be made available to individuals outside of the trial 
team for the purpose of PK dataset generation in accordance with sponsor’s standard 
procedures. 
Refer to Flow Chart for the time points of PK and ADA sample collection. Date and exact 
time of drug administration and PK and ADA sampling will be recorded on eCRFs. These 
actual administration and sampling times will be used for determination of PK parameters. 
On visits with study medication dosing, PK and ADA sampling should be collected prior to 
administration of study drug.
After completion of the study (i.e., clinical trial report archived), PK and ADA plasma 
samples may be used for further methodological investigations (e.g., stability testing).
5.4.2
Methods of sample collection
Plasma sampling for pharmacokinetic analysis 
5.4.2.1
For quantification of BI 655066 plasma concentrations, approximately 2.5 mL of blood will 
be taken at the time points listed in the Flow Chart under PK sampling. 
Detailed instructions for pharmacokinetic sampling, handling, and shipment of plasma 
samples are provided in the laboratory manual.
Plasma sampling for ADA
5.4.2.2
For ADA assessment, approximately 2.5 mL of blood will be taken at the time points listed in 
the Flow Chart under ADA assessment. 
Detailed instructions for ADA sampling, handling, and shipment of plasma samples are 
provided in the laboratory manual.
5.4.3
Analytical determinations
BI 655066 concentrations will be determined by a validated Enzyme Linked Immunosorbent 
Assay (ELISA).
The presence of ADA to BI 655066 will be assessed via a tiered approach using a validated 
electrochemiluminescence assay (screening, confirmatory, and titration analysis as 
appropriate). Samples that are confirmed positive may be further characterized in a validated 
neutralizing antibody (NAb) assay.


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ASSESSMENT OF EXPLORATORY BIOMARKERS
5.5
5.5.1
Skin biopsy assessment
Skin biopsies will be collected in a subset of patients at selected study sites to assess changes 
in gene and protein expression levels over time by treatment group. Biopsies are planned to 
be collected from approximately 75 patients. The biomarkers planned to be assessed by 
immunohistochemistry may include but not be limited to K16, Ki67 (on keratinocytes), S100 
A7 (on keratinocytes), lipocalin-2 (NGAL), β-defensin 2, CD3+ T lymphocytes, CD11+ and 
DC lamp (Dendritic Cells). Dermal and epidermal tissue will be evaluated. In addition, in situ 
hybridization analyses to identify changes in the proportion of select T cell sub-populations 
will be determined using expression of specific biomarkers (ie IL-23R on T17 cells and Fox 
P3 on T reg cells). RNA sequencing profiling of the skin biopsies will also be assessed to link 
changes in select pathways associated with IL-23 blockade and changes in the T cell sub-
populations. 
Methods of sample collection 
5.5.1.1
Skin biopsies will be performed at time points outlined in the Flow Chart and should be 
collected prior to administration of study drug at dosing visits. Participation of patients in 
skin biopsies requires their separate informed consent. At Visit 2 both non-lesional and 
lesional skin biopsies will be collected and at Visit 7 only lesional skin biopsies will be 
collected. Refer to ISF (Laboratory Manual) for biopsy, sample preparation and shipment 
instructions.
Analytical determinations
5.5.1.2
Immunohistochemistry will be performed as described in Section 5.5.1. RNA will be 
extracted from skin biopsies according to standard molecular genetics methods and analysed 
by RNA sequencing, TaqMan® or other standard gene expression technologies.
5.5.2
Assessment of soluble protein biomarkers
Serum will be collected pre and post treatment with BI 655066 to assess changes in protein 
levels of disease specific markers such as but not limited to #-defensin 2, neutrophil 
gelatinase associated lipocalin-2 (NGAL) and S-100 A8 protein over time by treatment 
group. Additionally, changes in levels of biomarkers related to metabolic syndrome such as 
leptin, resistin, TNFα, IL-6 and VEGF will be explored. 
Methods of sample collection 
5.5.2.1
Approximately 12.5 ml of blood will be collected at time points indicated in the Flow Chart.  
Samples should be collected prior to administration of study drug at dosing visits. For details 
on sample handling and logistics refer to the ISF (Laboratory Manual).


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Analytical determinations
5.5.2.2
These biomarkers are considered exploratory and respective assays will need to be qualified 
to meet the required performance criteria. 
5.5.3
Biomarker sample banking
After completion of the study any unused serum and tissue samples collected for biomarker 
sampling as listed in Section 5.5.1 and 5.5.2 may be used for further investigations (e.g. 
additional biomarkers for immunological & inflammatory diseases), if participation and the 
informed consent for biomarker sample banking is agreed upon by the patient.  
Declination to allow storage and use of these samples will not preclude participation in this 
study. The study samples will be stored for a maximum period of 15 years (under 
consideration of local legislation and if consented by the patient) upon archiving of the final 
study report after study completion.  
5.5.4
DNA Banking
Participation in the DNA banking sampling is voluntary and not a prerequisite for 
participation in the trial. The patient must provide informed consent for participation in this 
optional testing prior to any blood sampling used for DNA banking. The DNA banking 
sample will be stored in accordance with local ethical and regulatory requirements.
Methods of sample collection 
5.5.4.1
One blood sample for DNA banking will be taken at Visit 2. A maximum of 8.5 mL blood 
will be collected per PaxGene DNA blood sampling tube. For details on sample handling and 
logistics refer to the ISF (Laboratory Manual).
Analytical determinations
5.5.4.2
The DNA banking sample, derived from the original blood sample, will be stored at AbbVie
or a third party delegate (e.g. Boehringer Ingelheim Pharma GmbH & Co.KG; Birkendorfer 
Strasse 65, in 88397 Biberach, Germany). The stored DNA may be retrospectively analysed, 
e.g. to identify whether there are other genetic factors that could contribute to a better 
therapeutic outcome or a higher risk of developing treatment-related adverse drug reactions.
OTHER ASSESSMENTS
5.6
5.6.1
Quality of Life Questionnaires DLQI and WLQ
Dermatology Life Quality Index (DLQI) and Work Limitations Questionnaire (WLQ) are
questionnaires self-administered by patients at Visits 2, 8 and EOT. DLQI and WLQ will be 
used to assess quality of life, overall health and disability status, as well as work limitations
(see Appendix 10.6 and 10.7).


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5.6.2
Study drug self-administration questionnaire 
At study visits with self-administration of BI 655066 drug (active or placebo) by patients the 
trial site completes a questionnaire. This occurs at Visits 5, 8, 9, 11 and 12. The questionnaire 
captures information whether the patient did the injections of BI 655066 drug (active or 
placebo) correctly or not (see Appendix 10.8). 
5.6.3
Health Care Resource Utilization (HCRU) Questionnaire
For the purpose of a separate health economic analysis (such as cost-utility analysis), HCRU 
data will be collected at visits shown in the Flow Chart. Resource use data collected for 
calculating direct costs will include hospitalisations, unscheduled outpatient or home visits
and emergency room visits. The economic evaluation of the HCRU data will not be part of 
the Clinical Trial Report, but reported separately.
APPROPRIATENESS OF MEASUREMENTS
5.7
All measurements performed during this trial are standard measurements in psoriasis 
treatment trials and will be performed in order to monitor safety aspects or assess treatment 
response in an appropriate way. 
Therefore, the appropriateness of all measurements applied in this trial is given.
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
VISIT SCHEDULE
6.1
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 (randomization). If any visit has to be 
rescheduled, subsequent visits should follow the original visit date schedule from Day 1.  
Additional visits for the purpose of re-testing of laboratory parameters or AE monitoring may
be included as deemed necessary by the investigator.
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2
Study procedures to be performed at each visit are listed in the Flow Chart and the respective 
protocol sections. Refer to Section 5 and the Appendix Section 10 for explanations of 
procedures. Additional details on procedures at selected visits are provided below. 
Measurement of vital signs should precede blood sampling and be assessed pre-dose at 
dosing visits.
Self-administered patient questionnaires (DLQI, WLQ) 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 quality of life questionnaires (DLQI and WLQ) are self-administered by the patient using 
an electronic device. Also the Questionnaires to be completed by study site personnel (PASI,
sPGA, NAPSI, PPASI, PSSI, HCRU, and the BI 655066 (active or placebo) self-
administration questionnaire) will be completed using an electronic device, after the DLQI 
and WLQ have been completed by the patient. All questionnaires are detailed in 
Appendix 10. 
6.2.1
Screening period
After patients have been informed about the trial, written informed consent in accordance 
with GCP and the local legislation must be obtained prior to performing any study related 
procedures. A separate informed consent is required for optional study procedures which are 
DNA banking from blood samples, biomarker serum sample banking, skin biopsies and 
biomarker tissue sample banking from skin biopsies. 
Once they have consented, the patient is considered to be enrolled in the trial and have started 
screening. The patient should be recorded on the enrolment log and be registered in IRT as a 
screened patient. Patients will be assigned a patient number and enrolment must be recorded 
in the eCRF pages.


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Screening (Visit 1) should normally take place no more than 42 days before Visit 2 and be 
completed no less than 7 days prior to Visit 2. Screening procedures may be extended to 
more than 1 physical visit, if needed.
Re-screening will not be permitted. Patients who fail screening following Visit 1 assessments 
should be registered as a screen failure in IRT.
For the comprehensive list of the trial procedures required at the Screening Visit (Visit 1) 
please refer to flow chart.
Infection screening
See table 5.3.3: 1 for the list of infection screening tests that will be performed to verify 
exclusion criteria. Instructions regarding sample collection, sample handling/processing and 
sample shipping are provided in the Laboratory Manual in the ISF. See exclusion criteria 
Section 3.3.3 with study participation directive for patients with a positive QuantiFERON® or 
PPD skin test for TB.
Demographics
Informed consent date, HIPAA status (US patients only), sex, ethnicity and race (if allowed 
by local law) will be collected and reported in the eCRF. The patient’s smoking and alcohol 
history will also be assessed. 
Medical History
Cardiovascular (CV) History and CV risk factors will be collected and reported in the 
Medical History eCRF page. 
Baseline Conditions
Chronic diseases, current observable conditions, any new clinically relevant findings 
discovered from the physical examination, ECG, safety labs, and any condition requiring 
therapy (excluding psoriasis) will be reported on the Baseline Condition eCRF page.
IRT
All patients that are screened must be registered with IRT. If the patient results in a screen 
failure, IRT should be notified as soon as possible and within the 42 day screening period. 
Details of IRT procedures can be found in the IRT manual located in the ISF.
6.2.2
Treatment period
The treatment period is from Visit 2 to End of Treatment (EOT) Visit.  
Safety laboratory testing
Visits 2, 5, 8, 11, EOT and EOO should be performed in fasted state (8 hours no food and 
only water). This is not necessary at the Screening Visit. If a patient comes in non-fasted
where a fasting condition is required, the visit should be performed, the non-fasted condition 
documented on the laboratory requisition, and the patient reminded about the expected 
conditions. 


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Pregnancy testing
Urine pregnancy testing for all woman of child-bearing potential will be conducted on-site 
approximately every four weeks and must be negative to further treat the patient. The 
pregnancy testing should be done prior to administration of study drug. A positive urine test 
must be confirmed with a serum pregnancy test.
Randomization via IRT and administration of study medication should be the last activity at 
Visit 2.
Skin biopsies should be collected prior to administration of study drug at dosing visits.
Venipuncture (i.e. safety laboratories, PK, ADA, biomarkers) should be the last procedure 
prior to any study drug administration. On dosing visits PK and ADA samples should be 
taken approximately within 1 hour prior to administration of study drug. 
Patients should be closely monitored for signs and symptoms of hypersensitivity reactions for 
approximately 2 hours after the last injection at the Randomization Visit (Visit 2) and 
approximately 1 hour after the last injection at all other drug administration.
6.2.3
Follow Up Period and Trial Completion
For all randomized patients termination of trial medication and trial completion must be 
recorded on the corresponding eCRF.
6.2.3.1 
Early treatment and trial termination 
If study medication is discontinued prior to the planned Flow Chart visit EOT, every effort 
should be made to have the patient continue in the trial and complete all of the remaining trial 
visits and procedures including EOT and EOO Visit; with the EOO Visit to be performed 4 
weeks after the EOT Visit.
If a patient cannot or will not continue in the trial, the patient should complete EOT Visit
procedures instead of the next planned treatment period visit. These patients should be
registered as prematurely discontinued in IRT and return to the clinic for End of Observation 
Visit 16 (±1) weeks after their last administered dose of BI 655066 (active or placebo). 
Patients who discontinue from the trial prematurely will not have the option to participate in 
the open label extension (OLE) study. 
6.2.3.2 
Trial completion
Patients who complete the randomized treatment period and who qualify for the open-label 
extension (OLE) study will continue treatment with active BI 655066 and therefore will not 
have a Follow-up Visit in study 1311.30. 
6.2.3.3 
Vital Status
Randomised patients who do not participate in the OLE study and who withdraw from the 
study prior to their planned EOO Visit will be contacted for their vital status assessment 


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(alive / dead / lost to follow-up). In case the patient died, an SAE form should be completed 
by the site and forwarded immediately to the sponsor. Vital status assessment should occur at 
48 (±1) weeks after randomisation.


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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
STATISTICAL DESIGN - MODEL
7.1
This is a confirmatory, multicenter, randomized, double-blind and active comparator 
controlled 44 week study evaluating the efficacy and safety of BI 655066 in patients with 
moderate to severe chronic plaque psoriasis. The primary objective of this trial is to assess the 
safety and efficacy of BI 655066 in comparison to adalimumab in patients with moderate to 
severe chronic plaque psoriasis. The primary efficacy evaluation will be assessed at 16 weeks 
comparing treatment with BI 655066 to adalimumab. The study will also evaluate the 
efficacy of treatment with BI 655066 following insufficient or only partial response with 
adalimumab.
Baseline refers to the measurement recorded at randomisation (Visit 2); if data at Visit 2 is 
missing, then data from Visit 1 will be considered baseline. 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 PASI X.
Randomization will be stratified by weight (≤ 100 kg vs. >100 kg) and prior exposure to TNF 
antagonists (0 vs. ≥1). Based upon these design considerations and the binary nature of the 
co-primary endpoints of PASI 90 and sPGA 0 or 1, the trial will be analysed using the 
Cochran-Mantel-Haenszel risk difference estimate stratified by the randomisation factors 
mentioned previously.
NULL AND ALTERNATIVE HYPOTHESES
7.2
The primary hypotheses are that BI 655066 is different than adalimumab in achieving ≥ 90% 
reduction from baseline in the Psoriasis Area and Severity Index score (PASI 90) and sPGA 
score of clear(0) or almost clear(1) at Week 16 in participants with moderate to severe 
chronic plaque psoriasis. For the primary analyses, this study has 2 treatment arms (BI 
655066 and adalimumab [refer to Figure 3.1: 1]).
∀
Arm 1 – Patients randomised at Visit 2 to receive 150mg BI 655066 at Randomisation 
(Visit 2), Week 4 and then q12 weeks
∀
Arm 2 – Patients randomised at Visit 2 to receive 80mg adalimumab at Randomisation 
(Visit 2) and then 40mg adalimumab at Week 1 and then every other week
For the second part of the trial, patients randomised to receive adalimumab at Visit 2 and 
achieve a PASI 50 response but not PASI 90 at Week 16 will be re-randomised to one of the 
following treatment arms:
Arm A – Patients re-randomised to receive BI 655066 during the remaining treatment period 
of the trial


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Arm B – Patients re-randomised to continue to receive adalimumab during the remaining 
treatment period of the trial
The following null hypotheses will be tested in a hierarchical order using two-sided tests with 
a type I error of 0.05. The co-primary endpoints need to be significant simultaneously, 
therefore no alpha adjustment is necessary.
1. BI 655066 arm (Arm 1) is not different from adalimumab (Arm 2) with respect to 
PASI 90 or sPGA score of clear or almost clear (0 or 1) response at Week 16
2. BI 655066 arm (Arm 1) is not different from adalimumab (Arm 2) with respect to 
PASI 75 response at Week 16
3. BI 655066 arm (Arm 1) is not different from adalimumab (Arm 2)  with respect to 
PASI 100 response at Week 16
For the re-randomised patients, the following null hypothesis test will be performed with a 
type I error of 0.05. 
∀
BI 655066 arm (Arm A) is not different from adalimumab (Arm B) with respect to 
PASI 90 response at Week 44 for patients who are re-randomized at Week 16. 
PLANNED ANALYSES
7.3
The efficacy analyses will be based on the intent-to-treat principle, comprising all
participants who were randomised and received at least one dose during the trial. 
Misrandomized patients are by definition screening failures and therefore are not included in 
the intended to treat population. Efficacy analyses will be based on the planned treatment (i.e., 
the treatment assigned at randomization); this set of patients is called the Full Analysis Set 
(FAS). Safety analyses will be based on the actual treatment received at the Randomization 
Visit; this set of patients is called the Safety Set (SAF).
Important violations of the protocol will include key inclusion and exclusion violations, 
incorrect medications taken, compliance with study medication, incorrectly re-randomized or 
not re-randomized, concomitant use of restricted medications, and any other violations of the 
protocol deemed important by the study team. All decisions concerning important protocol 
violations will be made prior to unblinding of the database. A per-protocol set (PPS) will be 
defined excluding patients with violations that affect Week 16 efficacy. A secondary re-
randomized per-protocol set (RRS-PPS) will be defined excluding those patients with 
violations affecting the patients included in the Week 44 assessment of re-randomization.
The hypothesis tests as described in Section 7.2 will be repeated on the PPS or RRS-PPS 
populations, as appropriate.
7.3.1
Primary endpoint analyses
The achievement of PASI 90 at Week 16 is the first co-primary endpoint and is a binary 
variable with values of 0 or 1. The difference in proportion responding between the BI 
655066 arm and the adalimumab arm will be estimated and tested using the Cochran-Mantel-
Haenszel risk difference estimate stratified by the randomisation factors of weight (≤ 100 kg 


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vs. >100 kg) and prior exposure to TNF antagonists (0 vs. ≥1) with weights proposed by 
Greenland & Robins, which is calculated as follows:
 = ∑

 ∙


∑




, where
 = 

−

denotes the risk difference in stratum &, & = 1, ⋯, )

 =  ∙
 + 
denotes the weight of stratum &, & = 1, ⋯, )
 denotes the number of patients with event in treatmentin stratum i, & = 1, ⋯, )
 denotes the number of patients with event in treatment/in stratum i, & = 1, ⋯, )
 denotes the number of patients on treatmentin stratum i, & = 1, ⋯, )
 denotes the number of patients on treatment/in stratum i, & = 1, ⋯, )
The estimated variance of  is calculated as:
012
3 45 =
∑
6


(∑




)/
where 6 = ( −) 
9 + ( −) 
9
 ∙ ∙( + )/
, & = 1, ⋯, )
Assuming a normal distribution of  , an approximate 95% CI is given as follows, where 
:;.=>? is the 97.5% quantile of the standard normal distribution:
@A = B ± :;.=>? ∙D012
3 45E
Also, the approximate p-value can be calculated using the following:
pvalue = 2 ∙Pr
⎣
⎢
⎢
⎡
L > NN

D012
3 45
NN
⎦
⎥
⎥
⎤
, where L ~ S(0, 1)
If there is a stratum for a treatment group that has 0 patients in it, the 0 count will be replaced 
by 0.1 in order to prevent dividing by 0 in the above equations, as suggested in Greenland & 
Robins.  Comparisons of the BI 655066 arm and adalimumab arm will include both a p-value 
and 95% confidence interval. 
The achievement of a sPGA score of clear or almost clear at Week 16 is the second co-
primary endpoint and is a binary variable with values of 0 or 1. The analysis of the sPGA co-
primary endpoint will be identical to that of the PASI 90 co-primary endpoint detailed above.


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7.3.2
Secondary endpoint analyses
Key secondary endpoints:
The achievement of PASI 75 at Week 16 is a binary variable with values of 0 or 1. The 
analysis of this endpoint will be identical to that of the PASI 90 co-primary endpoint detailed 
in the Section 7.3.1.
The achievement of PASI 100 at Week 16 is a binary variable with values of 0 or 1. The 
analysis of this endpoint will be identical to that of the PASI 90 co-primary endpoint detailed 
in the Section 7.3.1.
The achievement of PASI 90 at Week 44 is a binary variable with values of 0 or 1. The 
analysis of this endpoint will be identical to that of the PASI 90 co-primary endpoint detailed 
in the Section 7.3.1. Note that this endpoint will only be analysed for patients who are re-
randomized at Week 16 (i.e., only for Arm A and Arm B defined in Section 7.2).
Other secondary endpoints:
Other secondary endpoints will be summarized descriptively.
7.3.3
Further endpoint analyses
Further endpoints will be summarized descriptively, with number and proportion of 
responders for dichotomous endpoints and mean, median, SD and IQR presented for 
continuous variables. 
Time to onset of Endpoint. The time to event will be calculated as:
∀
Time to first onset (with observed event) = [date of first onset] – [date of first active 
treatment] + 1
∀
If a patient never attains Endpoint (e.g. PASI 75 or PASI 90), then that patient’s time 
to first onset will be censored at the last visit where the Endpoint was measured (e.g. 
PASI). 
Time to Loss of Endpoint (from time of randomization), defined using the following 
algorithm:
a) Never attains Endpoint (Failure at time 0)
b) After achieving Endpoint, patient will be a failure if they subsequently do not 
achieve Endpoint and either discontinue from the study or switch therapy 
while still not achieving Endpoint. Time to failure will be calculated using 
date of first failure to achieve Endpoint.
c) Patients that take prohibited meds to treat Psoriasis will be counted as failures 
at the time when they add the prohibited med.
d) Patients that switch therapy while maintaining response will be censored at 
their last measurement prior to switching treatment. 


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e) Patients who maintain Endpoint throughout the study will be censored at their 
last measurement.
Time to Loss of Endpoint (from time of achieving Endpoint or from specific point in time) 
will be defined as above but only for those patients that have achieved Endpoint.
All Time to Event endpoints will be presented using Kaplan-Meier curves with comparisons 
made between treatment groups using stratified Log-Rank test. If needed, further information 
will be provided in the TSAP.
7.3.4
Safety analyses
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) coding dictionary. Standard AbbVie summary tables and listings will be 
produced. All adverse events with an onset between start of treatment and end of the residual 
effect period (REP), a period of 15 weeks after the last administration of BI 655066 (active or 
placebo), will be assigned to the 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 AbbVie standards. No hypothesis testing is planned.
Statistical analysis and reporting of adverse events will concentrate on treatment-emergent 
adverse events. To this end, all adverse events occurring between start of treatment and end 
of the residual effect period will be considered ‘treatment-emergent’.  The residual effect 
period is defined as 15 weeks. Adverse events that start before first drug intake and 
deteriorate under treatment will also be considered as ‘treatment-emergent’.
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).
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 highlighted in the 
listings. 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.
More information about the safety analysis will be provided in the TSAP.
7.3.5
Pharmacokinetic analyses
Descriptive statistics of BI 655066 concentration measurements by treatment group and visit 
will be provided.


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Pharmacokinetic data will be analysed using population pharmacokinetic approaches. For this 
purpose, data may also be combined with data from other trials. 
7.3.6
Pharmacodynamic analyses
No formal analysis of pharmacokinetic-pharmacodynamic relationships is planned. As the 
data from previous trials with BI 655066 suggest a pharmacokinetic (PK)-pharmacodynamic 
(PD) relationship for efficacy endpoints such as PASI, population PK-PD analyses will be 
performed. For this purpose, data may also be combined with data from other trials. Model-
based analyses will be planned and documented separately according to internal and external 
guidelines and SOPs. Other exploratory analyses of drug concentration, biomarker or safety 
data may be performed using data obtained as part of this trial. 
7.3.7
Biomarker analyses
Changes in serum protein, tissue protein and RNA biomarker levels over time will be 
described by treatment group. The details of these analyses will be included in the TSAP.
INTERIM ANALYSES
7.4
No interim analysis is planned for this study.
HANDLING OF MISSING DATA
7.5
Every effort should be made to collect complete data at all visits.
The following rules will be used to impute for missing data:
- For all non-binary endpoints, LOCF (Last Observation Carried Forward) will be used to
impute missing values
- For all binary endpoints (i.e. endpoints that are either 1 (patient responded) or 0 (patient did
  not respond)):
- If no data after that visit*, then impute as failure (NRI [No Response Imputation])
- If data at visits* before and after, only impute as success if both visits are successes;
             else impute as failure.
* Patients that take prohibited medications to treat psoriasis will be treated the same as those 
that discontinued from the trial – i.e. subsequent visits following start of prohibited 
medication will be considered as failure for binary endpoints.
Missing items from the Quality of Life questionnaires will be handled according to the 
measure instructions (cf. Appendix 10.6 and 10.7). If there is no data for a particular visit, 
then it will be imputed following the same rules as described above.
Sensitivity analyses to assess the robustness of the hypothesis testing results will include:
∀
LOCF (for binary endpoints)
∀
Logistic regression
∀
MMRM (for continuous endpoints)
∀
Multiple imputation (for binary endpoints)


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RANDOMISATION
7.6
At Visit 2, patients will be randomized in blocks to double-blind treatments, stratified by 
weight (≤ 100 kg vs. >100 kg) and prior exposure to TNF antagonists (0 vs. ≥1). Patients will 
be randomized to BI 655066 or adalimumab in a ratio of 1:1 within each level of 
stratification.
Patients originally randomized to BI 655066 150mg will stay on BI 655066 150mg.
Patients who are originally randomized to adalimumab will be separated into three groups at 
Week 16 depending on their Week 16 PASI score. Patients will be switched to BI 655066 if 
they don’t achieve PASI 50 at Week 16. Patients will continue on adalimumab if they achieve 
PASI 90 at Week 16. Patients will be re-randomized in a 1:1 ratio to either BI 655066 or 
adalimumab in a second double-blinded portion of the trial if they achieve PASI 50 but not 
PASI 90 at Week 16.
BI will arrange for the randomization and the packaging and labelling of trial medication. 
The randomization lists will be generated using a validated system, which involves a pseudo-
random number generator so that the resulting treatment will be both reproducible and non-
predictable. The block sizes will be documented in the CTR. Access to the codes will be 
controlled and documented.
DETERMINATION OF SAMPLE SIZE
7.7
This study is designed to show a benefit of BI 655066 over adalimumab in terms of PASI90 
response and sPGA scores of clear or almost clear at Week 16. This study is also powered to 
show a benefit in PASI 90 response at Week 44 between the patients randomized to continue 
on adalimumab vs patients randomized to BI 655066 at Week 16.
Based on the assumption that the Week 44 PASI 90 rate will be approximate 40% for 
adalimumab and 70% for BI 655066 for the patients who are re-randomized at Week 16, a
total of 120 patients will result in >90% power for the key secondary objective of the trial
using a type-I error rate at 5%. See Table 7.7: 1 sample size calculations for different 
scenarios. Assuming for those patients originally randomized to adalimumab the response 
rate at Week 16 for PASI 90 and PASI 50 are 45% and 85%, respectively, then this leaves 
approximately 40% of patients expected to fall in the more than or equal to PASI 50 and less 
than PASI 90 range and thus be eligible for re-randomisation. This requires that 300 (40% of 
300 = 120) patients be randomized to adalimumab at Randomisation. 
Based on the outcome from the trials 1311.1 and 1311.2, the PASI 90 response rate at 
Week 16 is assumed to be at least 65% in the BI 655066 arm. For the primary analysis 
comparing BI 655066 to adalimumab, sample sizes of 300 per arm will allow for > 90% 
power assuming 70% and 50% PASI 90 response rates for BI 655066 and adalimumab, 
respectively. See Table 7.7: 2 for more sample size calculations.


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Table 7.7: 1 Sample sizes for 90% power for testing against adalimumab using PASI 90 at re-
randomization
BI 655066 
rate
adalimumab 
rate
Delta
Re-randomisation ratio 
BI 655066: adalimumab = 
Total N 
65%
40%
25%
82:82 = 164
70%
45%
25%
80:80 = 160
70%
40%
30%
56:56 = 112
75%
45%
30%
54:54 = 108
80%
50%
30%
51:51 = 102
Table 7.7: 2 Sample sizes for 90% power for testing against adalimumab using PASI 90
BI 655066 
rate
adalimumab 
rate
Delta
Randomisation ratio 
BI 655066: adalimumab = 
Total N 
65%
50%
15%
226:226 = 452
70%
55%
15%
217:217 = 434
70%
50%
20%
124:124 = 248
75%
55%
20%
118:118 = 236
70%
45%
25%
80:80 = 160
75%
50%
25%
77:77 = 154
Based on the outcome from the trials 1311.1 and 1311.2, the achievement of sPGA clear or 
almost clear rate at Week 16 is assumed to be at least 85% in the BI 655066 arm. Assuming 
70% rate for the adalimumab arm, by using the PASI 90 required sample sizes, 300 patients 
per treatment arm will provide at least 90% power for sPGA endpoint. See Table 7.7. 3 for 
more sample size calculation.
As PASI 90 and sPGA are highly correlated, this trial will have >90% power for comparing 
BI 655066 arm to adalimumab arm on both of these endpoints.


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Table 7.7. 3 Sample sizes for 90% power for testing against adalimumab using sPGA clear or 
almost clear
BI 655066 
rate
adalimumab 
rate
Delta
Randomisation ratio 
BI 655066: adalimumab = 
Total N 
85%
72.5%
12.5%
223:223 = 446
85%
70%
15%
161:161 = 322
87.5%
72.5%
15%
148:148 = 296
87.5%
70%
17.5%
113:113 = 226
Calculations were performed using ADDPLAN Version 6.0.4.


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8.
INFORMED CONSENT, DATA PROTECTION, TRIAL
RECORDS
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 Tripartite Guideline 
for Good Clinical Practice (GCP), relevant BI Standard Operating Procedures (SOPs), and 
relevant regulations.
Standard medical care (prophylactic, diagnostic and therapeutic procedures) remains in 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 subjects against any immediate hazard, and also of any serious breaches of 
the protocol or of ICH GCP.
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 rights of the investigator / trial site and of the sponsor with regard to publication of the 
results of this trial are described in the investigator contract / trial site’s contract. As a general 
rule, no trial results should be published prior to finalisation 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 (Investigator Site File).
TRIAL APPROVAL, PATIENT INFORMATION, AND INFORMED 
8.1
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.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions. 


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DATA QUALITY ASSURANCE
8.2
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.
RECORDS
8.3
Electronic Case Report Forms (eCRF) 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
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site.
Data reported on the CRF must be consistent with the source data or the discrepancies must 
be explained. The Investigator may need to request previous medical records or transfer 
records, depending on the trial; current medical records must also be available.
For eCRFs all data must be derived from source documents.
8.3.2
Direct access to source data and documents
The Investigator / institution will permit trial-related monitoring, audits, IRB / IEC review 
and regulatory inspection, providing direct access to all related source data / documents. 
eCRF and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review by the Sponsor’s clinical trial 
monitor, auditor and inspection by health authorities (e.g. FDA). The Clinical Research 
Associate (CRA) / on site monitor and auditor may review all eCRF, and written informed 
consents. The accuracy of the data will be verified by reviewing the documents described in 
Section 8.3.1.
An adaptive approach to clinical trial monitoring will be utilised. This is initiated by an 
assessment of the risk associated with the trial combined with identification of critical data 
and processes. An Integrated Quality and Risk Management Plan documents the strategies 
involved with the implementation of onsite, offsite and central monitoring activities in order 
to direct focus to the areas of greatest risk which have the most potential impact to subject 
safety and data quality. Trial oversight is achieved by regular review of a report of risk which 
then influences any monitoring adaptations.


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LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE EVENTS
8.4
8.4.1
Listedness
To fulfil the regulatory requirements for expedited safety reporting, the Sponsor evaluates 
whether a particular adverse event is "listed", i.e. is a known side effect of the drug or not. 
Therefore, a unique reference document for the evaluation of listedness needs to be provided. 
For BI 655066 this is the current version of the Investigator’s Brochure (c02161217-10). For 
adalimumab this is the United States Product Information (US PI). 
The current versions of these reference documents are provided in the ISF. 
8.4.2
Expedited reporting of Adverse Events
BI is responsible to fulfil their legal regulatory reporting obligation and in accordance to the 
requirements defined in this CTP. 
STATEMENT OF CONFIDENTIALITY
8.5
Individual patient medical information obtained as a result of this trial is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers.
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 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.
END OF TRIAL
8.6
The end of the trial is defined as detailed in Section 6.2.3.
The IEC / competent authority in each participating EU member state will be notified about 
the end or early termination of the trial.


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9.
REFERENCES
PUBLISHED REFERENCES
9.1
R02-0127
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression scale. Acta
Psychiatr Scand 1983. 67:361-370.
R05-2548 
Finlay AY, 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 Jul 1993 Clin Exp Dermatol 1994. 19:210-216.
R07-1226
Herrmann C. International experiences with the Hospital Anxiety and
Depression Scale - a review of validation data and clinical results. J
Psychosom Res 1997. 42(1):17-41.
R08-1089 
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis.
Nature 2007; 445(7130):866-873.
R11-1257 
Nestle FO, Kaplan DH, Barker J. Mechanisms of disease: psoriasis. N Engl J 
Med 2009; 361(5):496-509.
R11-1259 
Menter A, Griffiths CEM. Psoriasis 2: current and future management of  
psoriasis. Lancet 2007; 370:272-284.
R11-1547
Smith RLI, Warren RB, Eyre S, Ho P, Ke X, Young HS, Griffiths CEM,  
Worthington J. Polymorphisms in the IL-12beta and IL-23R genes are 
associated with psoriasis of early onset in a UK cohort. J Invest Dermatol 
2008. 128:1325-1327.
R13-3515
Woodworth T, Furst DE, Alten R, Bingham C, Yocum D, Sloan V, Tsuji W, 
Stevens R, Fries J, Witter J, Johnson K, Lassere M, Brooks P. Standardizing 
assessment and reporting of adverse effects in rheumatology clinical trials II: 
the Rheumatology Common Toxicity Criteria v.2.0. J Rheumatol 2007. 
34(6):1401-1414.
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 2014. 25(1):8-14.
R14-3562
Bushnell DM, Martin ML, McCarrier K, Gordon K, Chiou CF, Huang X, 
Ortmeier B, Kricorian G. Validation of the Psoriasis Symptom Inventory 
(PSI), a patient-reported outcome measure to assess psoriasis symptom 
severity. J Dermatol Treat 2013. 24(5):356-360.


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R14-5159
Reich K, Puig L, Paul C, Kragballe K, Luger T, Lambert J, Chimenti S, 
Girolomoni G, Nicolas JF, Rizova E, Brunori M, Mistry S, Bergmans P, 
Barker J, TRANSIT Investigators. One-year safety and efficacy of 
ustekinumab and results of dose adjustment after switching from inadequate 
methotrexate treatment: the TRANSIT randomized trial in moderate-to-severe 
plaque psoriasis. Br J Dermatol 2014. 170(2):435-444.
R15-1219
Martin ML, McCarrier KP, Chiou CF, Gordon K, Kimball AB, Voorhees AS 
van, Gottlieb AB, Huang X, Globe D, Chau D, Viswanathan HN, Kricorian G. 
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 2013. 24(4):255-260.
R15-1393
Davidovici BB, Sattar N, Joerg PC, Puig L, Emery P, Barker JN, Kerkhof P 
van de, Stahle M, Nestle FO, Girolomoni G, Krueger JG, Psoriasis Education 
and Learning Syllabus (PEARLS). Psoriasis and systemic inflammatory 
diseases: potential mechanistic links between skin disease and co-morbid 
conditions. J Invest Dermatol 2010. 130(7):1785-1796.
R15-3846
Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of 
its history, issues, progress, and documentation. J Rheumatol 2003. 30(1):167-
178.
R15-3848
Lerner D, Amick BC, Rogers WH, Malspeis S, Bungay K, Cynn D. The work
limitations questionnaire. Med Care 2001. 39(1):72-85.
R15-3849
The Health Assessment Questionnaire (HAQ) and the improved HAQ 
(formerly called the PROMIS HAQ) (revised June 2009). 
http://aramis.stanford.edu/downloads/HAQ%20Instructions%20(ARAMIS)%2
06-30-09.pdf (access date: 15 July 2015) ; Stanford: Stanford University 
School of Medicine, Division of Immunology & Rheumatology 2009.
R15-3850
Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital
Anxiety and Depression Scale: an updated literature review. J Psychosom Res
2002. 52(2):69-77.
R15-3862
Langley RG, Feldman SR, Han C, Schenkel B, Szapary P, Hsu MC, Ortonne 
JP, Gordon KB, Kimball AB. Ustekinumab significantly improves symptoms 
of anxiety, depression, and skin-related quality of life in patients with 
moderate-to-severe psoriasis: results from a randomized, double-blind, 
placebo-controlled phase III trial. J Am Acad Dermatol 2010. 63(3):457-465.
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 2015. 
26(1):23-31.


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R16-2653
Tuong W, Armstrong AW. Scalp Psoriasis: Clinical Features and Assessment,
In: Adebajo A, Boehncke WH, Gladman DD, Mease PJ, editors. Psoriatic
Arthritis and Psoriasis: Pathology and Clinical Aspects. Cham: Springer, 139 --
141 (2016)
R16-2654
Rich P, Scher RK. Nail Psoriasis Severity Index: A useful tool evaluation of
nail psoriasis. J AM Acad Dermatol 49 (2), 206 -- 212 (2003)
R96-3541 
Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new 
retinoid. Dermatologica 1978; 157:238-244.
UNPUBLISHED REFERENCES
9.2
c02161217-10 Investigator’s Brochure BI 655066, Psoriasis, Crohn’s Disease, Ankylosing 
Spondylitis, Asthma, Psoriatic Arthritis
1311.P1/1311.P2/1311.P3/1311.P4/1311.P5.
c02434648
Summary report of analysis, Trial 1311.1. 26 Mar 2015.
c03272682-01 Summary report of interim analysis at Week 48, Trial 1311.2. 05 May 2015.


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10.
APPENDICES
PASI DEFINITIONS  AND  USE
10.1
The PASI 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 PASIX), where X is 
50, 75, 90 and 100.
To calculate the PASI, 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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STATIC  PHYSICIAN  GLOBAL  ASSESSMENT ( SPGA)
10.2
The sPGA 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 (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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NAIL PSORIASIS SEVERITY INDEX (NAPSI)
10.3
The NAPSI assesses how much of the fingernail is affected with psoriasis with scores ranging 
from 0 to 80 (R16-2654).
If a patient has nail psoriasis, the physician will assess the nail psoriasis at each protocol 
defined time point. Fingers (5) on each hand will be individually examined for two distinct 
assessments and are graded as follows:
Nail Matrix Assessment:
0 = None
1 = present in 1 quadrant of nail
2 = present in 2 quadrants of nail
3 = present in 3 quadrants of nail
4 = present in 4 quadrants of nail
Nail Bed Assessment:
0 = None
1 = present in 1 quadrant of nail
2 = present in 2 quadrants of nail
3 = present in 3 quadrants of nail
4 = present in 4 quadrants of nail
The sum of the scores will be added resulting a range of 0 to 80. If an individual finger 
assessment is missing (not done), the average of the remaining measured digits will be 
imputed and added to the sum. If < 50% of the finger assessments are missing the imputation 
will be performed. If more than 50% of the assessments are missing then the sum of the 
scores will be left as missing.


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PALMOPLANTAR  PSORIASIS  SEVERITY  INDEX  (PPASI)
10.4
The PPASI provides a numeric scoring for psoriasis affecting the hands and feet with scores 
ranging from 0 to 72. It is a linear combination of percent of surface area of hands and feet 
that are affected and the severity of erythema, induration, and desquamation. 
If a patient has palmoplantar psoriasis, the physician will assess the psoriasis at each protocol 
defined time point. Both palms and soles on each hand and foot will be individually assessed 
for erythema, induration, desquamation and percentage of area affected as follows:
∀
Erythema, Induration and Desquamation:
0 = None
1 = Slight
2 = Moderate
3 = Severe
4 = Very Severe
∀
Percent of Palm and Sole Area Covered:
0 = Clear
1 = <10%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
The PPASI is a composite score and will be computed for each palm and sole, left and right 
and is derived from the sum of the scores for erythema (E), induration (I) and desquamation 
(D) multiplied by the score recorded for the extent of palm and sole area involved. PPASI is 
calculated as follows: (sum of scores for E+I+D)*Area *0.2(location:right palm) + (sum of 
scores for E+I+D)*Area *0.2(location:left palm) + (sum of scores for E+I+D)*Area 
*0.3(location:right sole) + (sum of scores for E+I+D)*Area *0.3(location:left sole). The 
range is 0 to 72.


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PSORIASIS SCALP SEVERITY INDEX (PSSI) 
10.5
If a patient has scalp psoriasis, the physician will assess the erythema (redness), induration 
(hardness), desquamation (shedding of skin) and percent of scalp covered at each protocol 
defined time point (R16-2653).
∀
Erythema, Induration and Desquamation:
0 = None
1 = Slight
2 = Moderate
3 = Severe
4 = Very Severe
∀
Percent of Scalp Covered:
      1 = <10%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
The PSSI is a composite score derived from the sum of the scores for erythema, induration 
and desquamation multiplied by the score recorded for the extent of scalp area involved. The 
range is 0 to 72.


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DERMATOLOGY LIFE QUALITY INDEX (DLQI)
10.6
The DLQI is a subject-administered, ten-question, quality of life questionnaire that covers six 
domains including symptoms and feelings, daily activities, leisure, work and school, personal 
relationships and treatment (R05-2548). The DLQI has a one-week recall period. Response 
categories include “not relevant” (score of 0), “not at all” (score of 0), “a little” (score of 1), 
“a lot” (score of 2) and “very much” (score of 3). Question 7 is a “yes”/ “no” question where 
“yes” is scored as 3.
The DLQI will be self-administered by the patient at visits indicated in the flowchart. 
The DLQI will be analysed under six headings as follows (R05-2548): 
Domain
Question Number
Score                  
Symptoms and feelings
Questions 1 and 2
Score maximum 6
Daily activities
Questions 3 and 4
Score maximum 6
Leisure
Questions 5 and 6
Score maximum 6
Work and school
Question 7
Score maximum 3
Personal relationships
Questions 8 and 9
Score maximum 6
Treatment
Question 10
Score maximum 3
DLQI total score is calculated by summing the scores of each question resulting in a range of 
0 to 30 where 0-1 = no effect on subject’s life, 2-5 = small effect, 6-10 = moderate effect, 11-
20 = very large effect, and 21-30 = extremely large effect on subject’s life. The higher the 
score, the more the quality of life is impaired. If the answer to one question in a domain is 
missing, that domain is treated as missing. If 2 or more questions are left unanswered 
(missing), DLQI total score is treated as missing. A 5-point change from baseline is 
considered a clinically important difference.


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WORK LIMITATIONS QUESTIONNAIRE (WLQ)
10.7
The WLQ is a 25-item questionnaire that measures the degree to which health problems 
interfere with specific aspects of job performance and the associated health-related 
productivity loss (R15-3848). Respondents rate their level of difficulty or ability to perform 
specific job demands during the previous two weeks. The WLQ has four scales: time 
management, physical demands, mental-interpersonal demands and output demands. Item 
scores range from 0 (limited none of the time) to 4 (limited all of the time). Each scale is 
scored separately and scale scores are converted mathematically to 0 (no limitations) and 100 
(most limitations). Additionally, using an algorithm, WLQ scale scores can be converted into 
an estimate of productivity loss. The WLQ has been used in clinical trials in psoriasis (R15-
3862). The WLQ is not applicable to patients who are unemployed and have no paid job.






















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10.8 
SUPERVISING NURSE/HEALTH CARE PROFESSIONAL 
QUESTIONNAIRE – SELF-ADMINISTRATION OF BI 655066 ACTIVE OR 
PLACEBO
The following questions ask about whether the patient was able to successfully inject the BI 
655066 (active or placebo) medication. Please complete this questionnaire after the patient 
has self-injected both syringes. 
First syringe BI 655066 active or placebo medication
Question 1: Was the patient able to inject all of the liquid from the 
syringe into their body?
YES 
  /NO 
If “Yes”, proceed directly to Question 3. 
If “No”, continue with Question 2 below:
Question 2: Why was the patient unable to inject all of the liquid from 
the syringe into their body? (please check all that apply):
They were not able to remove the needle cap 
They were not able to fully push down the plunger 
They were not able to empty the syringe 
More than a drop of medication remained on their skin after they had completed the 
injection
The patient had some other problem injecting all of the liquid from the syringe. 
Please describe below:
  
  
  
  
Question 3: Which injection site was selected (check only one):
Left lower abdomen
Right lower abdomen
Left thigh
Right thigh
Question 4: Did you help the patient to administer the injection?
YES 
  /NO 
Second syringe BI 655066 active or placebo medication
Question 5: Was the patient able to inject all of the liquid from the 
syringe into their body?
YES 
  /NO 
If “Yes”, proceed directly to Question 7. 


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If “No”, continue with Question 6 below:
Question 6: Why was the patient unable to inject all of the liquid from 
the syringe into their body? (please check all that apply):
They were not able to remove the needle cap 
They were not able to fully push down the plunger 
They were not able to empty the syringe 
More than a drop of medication remained on their skin after they had completed the 
injection
The patient had some other problem injecting all of the liquid from the syringe. 
Please describe below:
  
  
  
  
Question 7: Which injection site was selected (check only one):
Left lower abdomen
Right lower abdomen
Left thigh
Right thigh
Question 8: Did you help the patient to administer the injection?
YES 
  /NO 


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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
Number of global amendment
1.0
Date of CTP revision
17 June 2016
EudraCT number
2015-003623-65
BI Trial number
1311.30
BI Investigational Product(s)
BI 655066 (risankizumab)
Title of protocol
BI 655066 (risankizumab) versus adalimumab in a 
randoMized, double blind, parallel group trial in 
Moderate to severe plaque psoriasis to assess 
safety and efficacy after 16 weeks of treatment and 
after inadequate adalimumab treatment response 
(IMMvent)
To be implemented only after 
approval of the IRB / IEC / 
Competent Authorities
To be implemented immediately 
in order to eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB / IEC / Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
Title page and synopsis
Description of change
Added risankizumab after BI 655066
Rationale for change
New name added for completeness
Section to be changed
Synopsis
Description of change
1. New further endpoint added:
Absolute PASI score of <3 at all visits collected.
2. Abbreviation for HOMA and ECG explained
Rationale for change
1. new further endpoint (update to original CTP).
2. explanation
Section to be changed
Flow Chart
Description of change
1. “Biologic therapy history” changed to “Psoriasis 
therapy history”
2. %BSA involvement at Visit 1 and 2 added as 
line item
3. ADA sampling at Week 4 added
4. Randomisation, Re-Randomisation at Visit 8: it 
should read footer 14 (not footer 13)


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5. Footer 4: Revised text to specify timing of vital 
sign measurements and hypersensitivity monitoring 
at dosing visits
6. Footer 15: It should read: At Visit 2 all study 
drugs will be administered by study personnel
7. New footer 20 to specify that patients who 
discontinue treatment should complete remaining 
study visits 
Rationale for change
1. and 2. Clarification
3. Request from Health Authorities
4. Correction
5. Clarification
6. Clarification
7. Update to original CTP
Section to be changed
Abbreviations
Description of change
Several new abbreviations explained
Rationale for change
Clarification
Section to be changed
1.2 Drug Profile
Description of change
Second sentence should read: The antibody has 
been engineered to reduce Fcγ receptor and 
complement binding and potential charge 
heterogeneity. 
Rationale for change
Correction
Section to be changed
2.3 Benefit – Risk Assessment 
Description of change
The third paragraph should read: There is not 
enough information at this time to rule out a risk of 
cancer with BI 655066, but this risk is considered 
small with this type of compound as experience 
with the anti-IL 12/23 mAb ustekinumab has not 
suggested significant risk for cancer/serious 
infection.
Rationale for change
To correct a typo (anti-IL12/23 mAb)
Section to be changed
2.3 Benefit – Risk Assessment
Description of change
The second to last paragraph should read: In order 
to recognize any safety signals as early as possible, 
an independent Data Monitoring Committee 
(DMC) will monitor this study and all studies 
where patients are receiving BI 655066.
Rationale for change
Clarification
Section to be changed
3.1 Overall Trial Design and Plan 
Description of change
1. Several text changes to better understand the 
treatment arms and blinding of the study
2. Discontiunation from Study medication should 
not necessarily lead to withdrawal from the study 
Rationale for change
1. Correction and Clarifications
2. Update original CTP


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Section to be changed
3.1.1 Administrative structure of the trial
Description of change
Abbreviations TCM and SOP explained
Rationale for change
Clarification
Section to be changed
3.1.2 Data Monitoring Committee (DMC)
Description of change
Clarification on how efficacy data will be used 
upon submission to the DMC as well as additional 
information on unblinding
Rationale for change
Clarification
Section to be changed
Section 3.1.3 MACE Adjudication Committee
Description of change
Added “thrombotic events”
Rationale for change
Clarification
Section to be changed
3.3 Selection of Trial Population
Description of change
Update on the approximate number of participating 
sites and number of patients per site
Rationale for change
Update to original CTP
Section to be changed
3.3.2 Inclusion criteria
Description of change
New inclusion criterion added: Patient must be able 
and willing to self-administer the study medication
Rationale for change
Update to original CTP
Section to be changed
3.3.3 Exclusion criteria
Description of change
Exclusion criteria number 4 and 7 slightly changed 
for better understanding and clarification
Rationale for change
Clarification
Section to be changed
3.3.4.1 Removal of individual patients
Description of change
Patients that discontinue study medication should 
complete all study visits and procedures as initially 
planned, if possible
Rationale for change
Update to original CTP
Section to be changed
4.1.2 Method of assigning patients to treatment 
groups
Description of change
Section revised to better understand assigning 
patients to the respective treatments
Rationale for change
Clarification
Section to be changed
4.1.3 Selection of doses in the trial
Description of change
Correction in the second to last paragraph
Rationale for change
Correction
Section to be changed
4.1.4 Drug assignment and administration of doses 
for each patient
Description of change
Revised text to specify timing of vital sign 
measurements and hypersensitivity monitoring at 
dosing visits; further information regarding drug 
injection details; additional description on what has 
to be done if the patient accidentally comes too late 
to a visit. 
Rationale for change
Clarification


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Section to be changed
4.2.2.1: 1 Restrictions regarding concomitant 
treatment
Description of change
1. Added tofacitinib (Xeljanz®) and apremilast 
(Otezla®)
2. Removed efalizumab (Raptiva®)
Rationale for change
1. Additional medication requiring washout
2. Medication not available
Section to be changed
5.1.3 Further endpoints
Description of change
Added: “Absolute PASI score of <3 at all visits 
collected”
Rationale for change
Update to CTP
Section to be changed
5.3.2 Vital Signs
Description of change
Revised text to specify timing of vital sign 
measurements and hypersensitivity monitoring at 
dosing visits
Rationale for change
Clarification
Section to be changed
5.3.3 Safety laboratory parameters
Description of change
Some laboratory parameters are better specified.
Added Albumin/creatinine ratio in urine 
Rationale for change
Clarification and Update to CTP
Section to be changed
5.3.4 Electrocardiogram
Description of change
Correction of wording in second to last paragraph
Rationale for change
Clarification
Section to be changed
5.6.1 Quality of Life Questionnaires DLQI and 
WLQ
Description of change
Abbreviations given
Rationale for change
Clarification
Section to be changed
6.2 Details of trial procedures at selected visits
Description of change
Removed: “At Visit 2 these questionnaires should 
be obtained after having the patient randomised”
Rationale for change
To match order of administration of patient 
reported outcome questionnaires DLQI and WLQ 
which should always come first (before any 
interaction with the investigator or other site 
personnel)
Section to be changed
6.2.1 Screening period
Description of change
1. New sentence: “Screening procedures may be 
extended to more than 1 physical visit, if needed.” 
2. Removed: “or local tolerability” from baseline 
conditions
Rationale for change
1. Patients may require more than 2 visits for 
screening procedures. 
2. Correction to original CTP
Section to be changed
6.2.2 Treatment period
Description of change
Last paragraph: Revised text to specify timing of 


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hypersensitivity monitoring at dosing visits
Rationale for change
Clarification
Section to be changed
6.2.3.1 Early treatment and trial termination
Description of change
Patients that discontinue study medication should 
complete all study visits and procedures as initially 
planned, if possible
Rationale for change
Update to original CTP
Section to be changed
7.2 Null and alternative hypotheses
Description of change
Treatment arms better described
Rationale for change
Clarification
Section to be changed
7.3 Planned analyses
Description of change
Clarifying the important protocol violations (IPVs), 
the intent-to-treat population, the per-protocol set 
(PPS) and the Re-randomised per-protocol set (RR-
PPS).
Hypothesis tests as described in Section 7.2 will be 
repeated on the PPS or RRS-PPS populations, as 
appropriate.  
Rationale for change
Response from Health Authorities
Section to be changed
7.3.3 Further endpoint analyses
Description of change
Added “Time to onset of Endpoint” definition.
Rationale for change
Update to CTP
Section to be changed
7.3.4 Safety analyses 
Description of change
Clarification of Residual Effect Period (REP)
Rationale for change
Clarification
Section to be changed
7.4 Interim analyses
Description of change
No interim analysis is planned for the study
Rationale for change
Clarification
Section to be changed
7.5 Handling of missing data 
Description of change
Explanations on sensitivity analyses
Rationale for change
Update to CTP
Section to be changed
9.2 Unpublished references
Description of change
The reference for the Investigator’s Brochure listed 
twice was deleted once
Rationale for change
Correction
Section to be changed
10.3 Nail Psoriasis Severity Index (NAPSI)
Description of change
Addition of Reference number
Rationale for change
Update to CTP
Section to be changed
10.4 Palmoplantar psoriasis severity index (PPASI)
Description of change
Correction of wording
Rationale for change
Correction
Section to be changed
10.5 psoriasis scalp severity index (PSSI) 
Description of change
Addition of Reference number


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Rationale for change
Update to CTP
Section to be changed
10.6 Dermatology life quality index (DLQI)
Description of change
Correction of response categories
Rationale for change
Correction
Section to be changed
10.7 Work Limitations Questionnaire (WLQ)
Description of change
The WLQ is not applicable to unemployed patients
Rationale for change
Clarification
Section to be changed
10.8 Supervising nurse/health care professional 
questionnaire – self-administration of BI 655066 
active or placebo 
Description of change
Update of the lay-out
Rationale for change
Correction


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Number of global amendment
2.0
Date of CTP revision
05 July 2016
EudraCT number
2015-003623-65
BI Trial number
1311.30
BI Investigational Product(s)
BI 655066 (risankizumab)
Title of protocol
BI 655066 (risankizumab) versus adalimumab in a 
randoMized, double blind, parallel group trial in 
Moderate to severe plaque psoriasis to assess 
safety and efficacy after 16 weeks of treatment and 
after inadequate adalimumab treatment response 
(IMMvent)
To be implemented only after 
approval of the IRB / IEC /
Competent Authorities
To be implemented immediately 
in order to eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB / IEC / Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
Section 11
Description of change
Ticked “To be implemented only after approval of 
the IRB / IEC / Competent Authorities”
Rationale for change
Clarification


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Number of global amendment
3.0
Date of CTP revision
17 Oct 2016
EudraCT number
2015-003623-65
BI Trial number
1311.30
BI Investigational Product(s)
BI 655066 (risankizumab)
Title of protocol
BI 655066 (risankizumab) versus adalimumab in a 
randoMized, double blind, parallel group trial in 
Moderate to severe plaque psoriasis to assess 
safety and efficacy after 16 weeks of treatment and 
after inadequate adalimumab treatment response 
(IMMvent)
To be implemented only after 
approval of the IRB / IEC / 
Competent Authorities
To be implemented immediately 
in order to eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB / IEC / Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
Section to be changed
Title page, Synopsis
Description of change
Changed BI drug or BI 655066 to refer to either 
names for this compound: BI 655066/ABBV-066 
(risankizumab)
Rationale for change
In February 2016, AbbVie entered into a license 
agreement with BI related to risankizumab, and in 
October 2016, the US IND for risankizumab 
transitioned from BI to AbbVie. This protocol 
change reflects that AbbVie will now be the 
Sponsor of this study in the USA, as well as the 
modifications to certain study conduct 
responsibilities as a result of that license agreement 
are listed as separate changes below. 
Section to be changed
Section 3.1.1
Description of change
1. Changed sponsor from Boehringer Ingelheim 
(BI) to AbbVie in the USA; BI remains the sponsor 
for all other participating countries. 
2. Changed text to specify Statistical Evaluation 


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will be done by AbbVie according to their SOPs. 
Rationale for change
Refer to rational for first change listed
Section to be changed
Section 3.3.4.2
Description of change
Updated text to “AbbVie/Boehringer Ingelheim 
reserves the right to discontinue the trial overall or 
at a particular trial site at any time for the following 
reasons”
Rationale for change
Refer to rational for first change listed
Section to be changed
Section 5.5.4.2
Description of change
Changed DNA banking sample storage from 
Boehringer Ingelheim to AbbVie or a third party 
delegate (e.g. Boehringer Ingelheim Pharma GmbH 
& Co. KG; Birkendorfer Strasse 65, 88397 
Biberach, Germany)
Rationale for change
Refer to rational for first change listed
Section to be changed
Section 5.5.1.1
Description of change
Skin biopsies will be collected only at Visit 2 
(lesional and non-lesional) and at Visit 7 (only 
lesional) as shown in the Flow Chart
Rationale for change
Correction
Section to be changed
Section 7.3.4 
Description of change
Changed text to specify that AbbVie summary 
tables and listings will be produced and analyses 
are based on AbbVie standards 
Rationale for change
Refer to rational for first change listed


 
 
 
APPROVAL / SIGNATURE PAGE 
Document Number: 
 
Technical Version Number:
Document Name: 
                                                                                                                 
 
Title: 
                                                                                                                   
Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c03570610
4.0
clinical-trial-protocol-version-04
BI 655066/ABBV-066 (risankizumab) versus adalimumab in a randoMized, double
blind, parallel group trial in Moderate to severe plaque psoriasis to assess safety and
efficacy after 16 weeks of treatment and after inadequate adalimumab treatment
response (IMMvent)
17 Oct 2016 15:23 CEST
17 Oct 2016 15:44 CEST
17 Oct 2016 15:58 CEST
17 Oct 2016 23:09 CEST
18 Oct 2016 10:21 CEST


Boehringer Ingelheim 
Page 2 of 2
Document Number: 
Technical Version Number:
(Continued) Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c03570610
4.0

SAP_001.pdf: 


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2.0
Table of Contents
1.0
Title Page ...............................................................................1
2.0
Table of Contents ..................................................................2
3.0
Introduction...........................................................................6
4.0
Study Objectives, Design and Procedures............................6
4.1
Primary Study Objective......................................................................... 6
4.2
Design Diagram ..................................................................................... 7
4.3
Sample Size............................................................................................ 9
4.4
Interim Analysis................................................................................... 11
5.0
Analysis Populations ........................................................... 12
5.1
Definition for Analysis Populations ...................................................... 12
5.2
Variables Used for Stratification of Randomization .............................. 15
6.0
Analysis Conventions .......................................................... 15
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications..............25
7.1
Demographic and Baseline Characteristics ........................................... 25
7.2
Medical History.................................................................................... 27
7.3
Previous Treatment and Concomitant Medications ............................... 28
7.4
Protocol Deviations .............................................................................. 28
8.0
Patient Disposition............................................................... 28
9.0
Study Drug Exposure and Compliance.............................. 29
10.0
Efficacy Analysis .................................................................31
10.1
General Considerations......................................................................... 31
10.1.1
Analyses of Categorical Variables ........................................................ 32
10.1.2
Analyses of Continuous Variables ........................................................ 33
10.1.3
Analyses of Time-to-Event Variables ................................................... 33
10.1.4
Missing Data Imputations..................................................................... 34
10.2
Primary Efficacy Analysis.................................................................... 36
10.3
Secondary Efficacy Analyses ............................................................... 37
10.3.1
Ranked Secondary Efficacy Analyses................................................... 37
10.3.1.1
Ranked Secondary Efficacy Analysis in Part A..................................... 37
10.3.1.2
Ranked Secondary Efficacy Analysis in Part B..................................... 38


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10.3.2
Other Secondary Efficacy Analysis ...................................................... 38
10.3.3
Further Endpoint Analyses ................................................................... 38
10.4
Handling of Multiplicity....................................................................... 39
10.5
Efficacy Subgroup Analysis ................................................................. 39
11.0
Safety Analysis.....................................................................40
11.1
General Considerations......................................................................... 40
11.2
Analysis of Adverse Events.................................................................. 40
11.2.1
Treatment-Emergent Adverse Events.................................................... 40
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 49
11.2.3
Safety Subgroup Analysis..................................................................... 49
11.3
Analysis of Laboratory Data................................................................. 49
11.3.1
Variables and Criteria Defining Abnormality........................................ 50
11.3.2
Statistical Methods ............................................................................... 52
11.4
Analysis of Vital Signs and Weight ...................................................... 55
11.4.1
Variables and Criteria Defining Abnormality........................................ 56
11.4.2
Statistical Methods ............................................................................... 56
11.5
Analysis of ECG Parameters ................................................................ 57
11.6
Local Tolerability................................................................................. 58
12.0
Pharmacokinetic Analysis...................................................58
13.0
Biomarkers Analysis ...........................................................58
14.0
Summary of Changes .......................................................... 58
14.1
Summary of Changes Between the Latest Version of Protocol and 
the Current SAP ................................................................................... 58
14.2
Summary of Changes Between the Previous Version and the 
Current Version of the SAP .................................................................. 59
15.0
Appendix.............................................................................. 59
16.0
References............................................................................59
17.0
List of Tables, Figures and Data Listings that Are to 
Be Programmed................................................................... 59


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List of Tables
Table 1.
Sample Sizes for 90% Power for Testing Against Adalimumab 
Using PASI 90 at Re-Randomization.................................................... 10
Table 2.
Sample Sizes for 90% Power for Testing Against Adalimumab 
Using PASI 90 ..................................................................................... 10
Table 3.
Sample Sizes for 90% Power for Testing Against Adalimumab 
Using sPGA Clear or Almost Clear ...................................................... 11
Table 4.
Visit Windows for PASI/sPGA and Vital Signs for Part A 
(ITT_A/PP_A/Safety_A Populations)................................................... 18
Table 5.
Visit Windows for Laboratory and ECG Parameters for Part A 
(Safety_A Population) .......................................................................... 18
Table 6.
Visit Windows for Other Efficacy Endpoints Only Collected at 
Week 16 in Part A (ITT_A Population) ................................................ 18
Table 7.
Visit Windows for Local Tolerability for Part A (Safety_A 
Population)........................................................................................... 19
Table 8.
Visit Windows for Analysis of PASI and sPGA in Part B 
(ITT_B_RR/ITT_B_R/ITT_B_NR/ITT_B_RZB/PP_B_RR 
Populations) ......................................................................................... 19
Table 9.
Visit Windows for Laboratory and ECG Parameters for Part B 
(Safety_B_RR Population) ................................................................... 20
Table 10.
Visit Windows for Vital Signs for Part B (Safety_B_RR 
Population)........................................................................................... 20
Table 11.
Visit Windows for Other Efficacy Endpoints Only Collected at 
Week 44 in Part B 
(ITT_B_RR/ITT_B_R/ITT_B_NR/ITT_B_RZB/PP_B_RR 
Populations) ......................................................................................... 21
Table 12.
Visit Windows for Local Tolerability for Part B (Safety_B_RR 
Population)........................................................................................... 21
Table 13.
Visit Windows for Laboratory and ECG Parameters for 
ALL_RZB Population .......................................................................... 21
Table 14.
Visit Windows for Vital Signs for ALL_RZB Population ..................... 22
Table 15.
Visit Windows for Local Tolerability Parameters for ALL_RZB 
Population............................................................................................ 22
Table 16.
Visit Windows for Summary of RZB Injections for Part A ................... 23


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Table 17.
Visit Windows for Summary of RZB Self-Administration 
Questionnaire in Part A ........................................................................ 23
Table 18.
Visit Windows for Summary of RZB Injections for Part B and 
RZB Self-Administration Questionnaire............................................... 23
Table 19.
Visit Windows for Summary of ADA Injections for Part A .................. 24
Table 20.
Visit Windows for Summary of ADA Injections for Part B .................. 24
Table 21.
Areas of Safety Interest ........................................................................ 45
Table 22.
Clinical Laboratory Tests ..................................................................... 51
Table 23.
Criteria for Potentially Clinically Important Chemistry Values ............. 53
Table 24.
Criteria for Potentially Clinically Important Hematology Values .......... 53
Table 25.
NCI CTCAE Grading........................................................................... 54
Table 26.
Criteria for Potentially Clinically Important Vital Sign Findings........... 56
List of Figures
Figure 1.
Trial Design ........................................................................................... 9


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3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Clinical Statistics Department for study Protocol 1311.30 dated 
10 December 2015.
This SAP will provide details to further elaborate statistical methods as outlined in the 
Protocol 1311.30 and will describe analysis conventions to guide the statistical 
programming work.  The SAP will be signed off before the study database is locked.
Analyses will be performed using SAS® version 9.4 (SAS Institute, Inc., Cary, NC 27513) 
or higher using the UNIX operating system.
4.0
Study Objectives, Design and Procedures
4.1
Primary Study Objective
The main objectives of this study are to assess the efficacy and safety of risankizumab 
compared to adalimumab in subjects with moderate to severe chronic plaque psoriasis.  
The primary efficacy evaluation will be performed at Week 16.  The study will also
evaluate the efficacy of a 28-week treatment with risankizumab in subjects who were 
initially treated with adalimumab for 16 weeks, achieving insufficient or only partial 
response with adalimumab, and then switched to risankizumab treatment from Week 16 to 
Week 44.
In addition, this trial will assess pharmacokinetics (PK) and the emergence of anti-drug 
antibodies (ADA) and their effect on efficacy and safety.  Moreover, it will be explored 
how the use of risankizumab may influence gene and protein expression levels and 
disease specific protein markers.  PK and ADA analyses, exploratory biomarker analyses, 
and metabolic risk factor analyses, will not be included in this SAP.


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4.2
Design Diagram
This confirmatory multi-national, randomized, double-blind, double dummy, active 
controlled, parallel design study compares risankizumab with adalimumab.  In total, 
approximately 600 subjects with moderate to severe chronic plaque psoriasis will be 
randomized in this trial.
Subjects are included in the study once they have signed the informed consent.  Subjects 
suitable after screening will be eligible to participate in the 44 week treatment period 
shown in Figure 1.
Subjects will be blinded to treatment.  Subjects in each dose group will receive the same 
injections at each designated time point, in order to maintain blinding.
Part A:
Part A is a 16-week, double-blinded, active-controlled treatment period during which 
subjects will be randomized at a 1:1 ratio to risankizumab or adalimumab.  The 
randomization will be stratified by weight (≤ 100 kg vs. > 100 kg) and prior exposure to 
TNF antagonists (0 vs. ≥ 1).  Subjects randomized to risankizumab will receive 2 syringes 
of risankizumab active drug (2 × 75 mg) at randomization and at Week 4, and 
adalimumab placebo at randomization (2 syringes) and 1 adalimumab placebo syringe at 
Weeks 1, 3, 5, 7, 9, etc. up to Week 15.  Subjects randomized to adalimumab will receive 
2 syringes adalimumab at randomization (2 × 40 mg) followed by 1 syringe adalimumab 
(40 mg) at Weeks 1, 3, 5, 7, 9, 11, 13 and 15.  These subjects will also receive 2 syringes 
of risankizumab placebo at randomization and at Week 4.
Part B:
At Week 16, subjects initially on risankizumab will stay on risankizumab.  These subjects 
will receive 2 syringes of risankizumab (2 × 75 mg) at Week 16 and 28, and 2 syringes of 
risankizumab placebo at Week 20 and 32.  They will also receive 1 syringe of 
adalimumab placebo at Weeks 17, 19, 21, 23, etc. up to Week 41.


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At Week 16, subjects initially on adalimumab and have < PASI 50 response (< 50% 
reduction in Psoriasis Area and Severity Index (PASI)) will be switched to risankizumab.  
These subjects will receive 2 syringes of risankizumab (2 × 75 mg) at Week 16, 20, and 
32, and 2 syringes of risankizumab placebo at Week 28.  They will also receive 1 syringe 
of adalimumab placebo at Weeks 17, 19, 21, 23, etc. up to Week 41.
At Week 16, subjects initially on adalimumab and ≥ PASI 90 will be stay on adalimumab.  
These subjects will receive 2 syringes of risankizumab placebo at Week 16, 20, 28 and 32.  
They will also receive 1 syringe of adalimumab at Weeks 17, 19, 21, 23, etc. up to 
Week 41.
At Week 16, subjects initially on adalimumab and ≥ PASI 50 and < PASI 90 will be 
re-randomized at a 1:1 ratio to risankizumab or adalimumab.  Subjects re-randomized to 
risankizumab will receive 2 syringes of risankizumab (2 × 75 mg) at Week 16, 20 and 32, 
and 2 syringes of risankizumab placebo at Week 28.  They will also receive 1 syringe of 
adalimumab placebo at Weeks 17, 19, 21, 23, etc. up to Week 41.  Subjects re-randomized 
to adalimumab will receive 2 syringes of risankizumab placebo at Week 16, 20, 28 and 
32.  They will also receive 1 syringe of adalimumab at Weeks 17, 19, 21, 23, etc. up to 
Week 41.


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Figure 1.
Trial Design
BI 655066 is risankizumab.
4.3
Sample Size
This study is designed to show a benefit of risankizumab over adalimumab in terms of 
PASI 90 response and static Physician Global Assessment (sPGA) of clear or almost clear 
(sPGA of 0 or 1) at Week 16.  This study is also powered to show a benefit in PASI 90 
response at Week 44 between the subjects re-randomized to continue on adalimumab vs. 
subjects randomized to risankizumab at Week 16. 
Based on the assumption that the Week 44 PASI 90 rate will be approximate 40% for 
adalimumab and 70% for risankizumab for the subjects who are re-randomized at 
Week 16, a total of 120 subjects will result in > 90% power for the primary efficacy 
analysis in Part B using a type-I error rate at 5%.  See Table 1 sample size calculations for 
different scenarios.  Assuming for those subjects originally randomized to adalimumab 
the response rate at Week 16 for PASI 90 and PASI 50 are 45% and 85%, respectively, 
then this leaves approximately 40% of subjects expected to fall in the more than or equal 


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10
to PASI 50 and less than PASI 90 range and thus be eligible for re-randomization.  This 
requires that 300 (40% of 300 = 120) subjects be randomized to adalimumab at 
randomization.
Based on the outcome from Trials 1311.1 and 1311.2, the PASI 90 response rate at 
Week 16 is assumed to be at least 65% in the risankizumab arm.  For the primary analysis 
comparing risankizumab to adalimumab, sample sizes of 300 per arm will allow for 
> 90% power assuming 70% and 50% PASI 90 response rates for risankizumab and 
adalimumab, respectively.  See Table 2 for more sample size calculations.
Table 1.
Sample Sizes for 90% Power for Testing Against Adalimumab 
Using PASI 90 at Re-Randomization
Risankizumab
Adalimumab
Delta
Re-Randomization Ratio
Risankizumab:Adalimumab = Total N
65%
40%
25%
82:82 = 164
70%
45%
25%
80:80 = 160
70%
40%
30%
56:56 = 112
75%
45%
30%
54:54 = 108
80%
50%
30%
51:51 = 102
Table 2.
Sample Sizes for 90% Power for Testing Against Adalimumab 
Using PASI 90
Risankizumab
Adalimumab
Delta
Randomization Ratio
Risankizumab:Adalimumab = Total N
65%
50%
15%
226:226 = 452
70%
55%
15%
217:217 = 434
70%
50%
20%
124:124 = 248
75%
55%
20%
118:118 = 236
70%
45%
25%
80:80 = 160
75%
50%
25%
77:77 = 154
Based on the outcome from Trials 1311.1 and 1311.2, the achievement of sPGA clear or 
almost clear rate at Week 16 is assumed to be at least 85% in the risankizumab arm.  


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Assuming 70% rate for the adalimumab arm, by using the PASI 90 required sample sizes, 
300 subjects per treatment arm will provide at least 90% power for sPGA endpoint.  See 
Table 3 for more sample size calculation.
As PASI 90 and sPGA are highly correlated, this trial will have > 90% power for 
comparing risankizumab arm to adalimumab arm on both of these endpoints.
Table 3.
Sample Sizes for 90% Power for Testing Against Adalimumab 
Using sPGA Clear or Almost Clear
Risankizumab
Adalimumab
Delta
Randomization Ratio
Risankizumab:Adalimumab = Total N
85%
72.5%
12.5%
223:223 = 446
85%
70%
15%
161:161 = 322
87.5%
72.5%
15%
148:148 = 296
87.5%
70%
17.5%
113:113 = 226
Calculations were performed using ADDPLAN Version 6.0.4.
4.4
Interim Analysis 
Unblinded data will be reviewed during the study by an independent data monitoring 
committee (DMC).  The membership, roles and responsibilities and activities of the DMC 
will be defined in a written charter.  The DMC will include representatives from external 
safety experts who do not directly involve in the study.  Clinical site personnel and the 
study team will remain blinded to the randomized treatment assignments during the 
course of the study.  Communications from the DMC to the study team will not contain 
information that could potentially unblind the study personnel.  Since there is no efficacy 
analyses for early stopping, no alpha adjustment is needed.
No other interim analyses are planned.


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5.0
Analysis Populations
5.1
Definition for Analysis Populations
Efficacy Population:
Intent to Treat (ITT) Populations:  The ITT Population in each period will be used for 
efficacy analyses.
●
The ITT Population in Part A (ITT_A) is defined as all subjects who are 
randomized at Baseline.
●
The ITT Population in Part B who are re-randomized (ITT_B_RR) is defined 
as all subjects who start with adalimumab at Baseline and are re-randomized at 
Week 16.
●
The ITT Population for PASI 90 responders at the entry of Part B (ITT_B_R) 
is defined as all subjects who start with adalimumab at Baseline and achieve 
PASI 90 at Week 16 and receive at least one dose of active adalimumab on or 
after Week 16.
●
The ITT Population for PASI 50 non-responders at the entry of Part B 
(ITT_B_NR) is defined as all subjects who start with adalimumab at Baseline 
and fail to achieve PASI 50 at Week 16 and receive at least one dose of active 
risankizumab on or after Week 16.
●
The ITT Population in Part B continuously receiving risankizumab 
(ITT_B_RZB) is defined as all subjects who start with risankizumab at 
Baseline and receive at least one dose of active risankizumab on or after 
Week 16.
The ITT Population will be analyzed by the treatment group as randomized and as 
re-randomized where applicable.
Per-Protocol (PP) Population:  To evaluate the impact of protocol deviations on the 
primary and ranked secondary endpoints, additional analyses will be performed on the 
Per-protocol Populations.  The Per-protocol Population will include those who were most 
compliant with the protocol in ways that could impact the primary and ranked secondary 


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endpoints.  Final results and the criteria for exclusion of subjects will be determined via 
classification prior to database lock for data pertaining to the DB period.  The PP 
population at Part A (PP_A) is defined as all ITT_A subjects meeting all the following 
criteria:
●
Subjects must receive at least 75% of planned risankizumab injections, as well 
as at least 75% of planned adalimumab injections, including dummy placebo 
injections, per randomized, in Part A.
●
Subjects must have either a PASI or sPGA assessment post-baseline in Part A.
●
Inclusion Criterion 4:  Subjects must have stable moderate to severe chronic 
plaque psoriasis baseline:
○
Have an BSA ≥ 10% and
○
Have a PASI ≥ 12 and
○
Have an sPGA ≥ 3.
Primary and ranked secondary efficacy endpoints at Week 16 will be analyzed on the 
PP_A Population.
The PP Population at Part B for re-randomized subjects (PP_B_RR) is defined as all 
subjects from the ITT_B_RR Population who meet all the following criteria:
●
Subjects must receive at least 75% of planned risankizumab injections, as well 
as at least 75% of planned adalimumab injections, including dummy placebo 
injections, per re-randomized, in Part B.
●
Subjects must have at least one PASI assessment post re-randomization in 
Part B.
●
Subjects must have a response of PASI 50 – < 90 at re-randomization.
The primary and ranked secondary efficacy endpoint at Part B at Week 44 will be 
analyzed on the PP_B_RR Population.
PP Populations will be analyzed by the treatment group as randomized (or 
re-randomized).


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Safety Populations (Safety):
The Safety Populations will be used for safety analyses in different study parts.
Each ITT Population will have a corresponding safety population (Safety) defined which 
require subjects to have at least one dose of active study drug during the analysis period.
Complete safety tables will be provided for the Safety_A Population and the 
Safety_B_RR population.  AE overview tables will be provided for other safety 
populations.
The Safety Population will be analyzed based on the actual treatment received at the 
randomization visit (Safety_A) and at the re-randomization visit (Safety_B_RR).
In addition, an All Risankizumab Treated Population (ALL_RZB) is defined as all 
subjects who receive at least one dose of risankizumab 150 mg in the study.  The 
ALL_RZB Population will be used for safety analyses.  Complete safety tables will be 
provided in the ALL_RZB Population.
Notations for Treatment Groups:
Part A:
●
ADA:  Subjects randomized to adalimumab 
●
RZB:  Subjects randomized to risankizumab 150 mg
Part B:
●
RZB/RZB:  Subjects randomized to risankizumab and continue with 
risankizumab
●
ADA/ADA:  Subjects randomized to adalimumab and stay with adalimumab at 
Week 16
●
ADA/RZB:  Subjects randomized to adalimumab and switched to 
risankizumab at Week 16


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ALL_RZB:
●
RZB:  Subjects who received at least one dose of risankizumab 150 mg
5.2
Variables Used for Stratification of Randomization
At Visit 2, subjects will be randomized in blocks to double-blind treatments, stratified by 
weight (≤ 100 kg vs. > 100 kg) and prior exposure to TNF antagonists (0 vs. ≥ 1).  
Subjects will be randomized to risankizumab or adalimumab in a ratio of 1:1 within each 
level of stratification.
Subjects patients initially on adalimumab and ≥ PASI 50 and < PASI 90 will be 
re-randomized at Week 16 in a 1:1 ratio to receive either risankizumab or adalimumab.  
Re-randomization will also be stratified by weight (≤ 100 kg vs. > 100 kg) and prior 
exposure to TNF antagonists (0 vs. ≥ 1).
6.0
Analysis Conventions
Definition of Baseline:
The last non-missing measure collected on or before the date of the first dose of study 
drug injection will be used as Baseline for summary of demographics and disease 
characteristics, efficacy analyses, and safety analyses in each period, with the exception 
that:
●
The last evaluation on or prior to the first dose date of risankizumab will be 
used for the safety analyses for ALL_RZB populations.
●
For all vital sign assessments, only assessments prior to first dose time will be 
considered, since vital signs are to be assessed both pre- and post-dose in some 
visits.
For subjects who are randomized but do not take any study drug during the study, the last 
non-missing measurement collected on or before the date of randomization will be used as 
Baseline.


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Definition of Final Observation (Applicable to Safety Analyses):
Final observation for the Part A is defined as:
●
The last non-missing observation collected within 105 days following the last 
dose of study drug in Part A for subjects who were not dosed in Part B.
●
The last non-missing observation collected on or before the first dose date of 
study drug on or after Week 16 and within 105 days following the last dose of 
study drug in Part A for subjects who were dosed in Part B.  For vital sign 
assessments, only assessments prior to the first dose of study drug injection in 
Part B will be included in the analysis for Part A.
Final observation in Part B and in the entire study is defined as the last non-missing 
observation collected within 105 days after the last dose of study drug.
Definition of Rx Days (Days Relative to the Date of First Dose of Study Drug)
Rx days are calculated for each time point relative to the date of first dose of study drug.  
They are defined as the number of days between the day of the first dose of study drug 
and the specific time point.  Rx days are negative values when the time point of interest is 
prior to the first study drug dose day.  Rx days are positive values when the time point of 
interest is on or after the first study drug dose day.  The day of the first dose of study drug 
is defined as Rx Day 1, while the day prior to the first study drug dose is defined as Rx 
Day –1 (there is no Rx Day 0). 
For analysis in each Part (A or B), the Rx Day is calculated relative to the first dose of 
study drug in the specific study Part.  For analysis across Part A and Part B, the Rx days 
are calculated relative to the date of first dose of study drug injection in Part A.
Definition of Analysis Windows
All time points and corresponding time windows are defined based on Rx Days.
For efficacy analyses, local tolerability, laboratory parameters, and vital sign variables, 
analysis windows are constructed using the following algorithm:


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●
Determine the nominal Rx day for each visit (e.g., Week 4 [4 weeks after 
Baseline visit] equals Rx Day 29).
●
In order to include all post baseline data, the first post-baseline interval starts 
on the first day after the first dose of study drug (Rx Day 2).
●
Determine the window around a specific nominal Rx day by adding or 
subtracting half of the interval between adjacent visits (e.g., days between 
Week 2 and Week 4 is 14).  The threshold between adjacent visits is 
determined by splitting the interval evenly between the visits.  If the resulting 
split is between Rx days, then the threshold is determined as the midpoint 
between the adjacent visits.  If the resulting split is on an Rx day, then the 
threshold is determined as being between that Rx day and the Rx day prior to it 
(e.g., the split between Week 2 and Week 4 would be between Rx Days 22 and 
23).
●
If more than one assessment is included in a time window the assessment 
closest to the nominal day will be used.  If there are two observations 
equidistant to the nominal day, the one after the nominal day will be used in 
analyses.  If more than one assessment is included on the same day, then the 
worst assessment on that day will be used in analyses, except those specified in 
Section 11.0.
The protocol specified visits and corresponding time windows used in the efficacy 
analyses, local tolerability, ECG, laboratory parameters, and vital sign variables, are 
presented in the following tables.


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Table 4.
Visit Windows for PASI/sPGA and Vital Signs for Part A 
(ITT_A/PP_A/Safety_A Populations)
Window Label
Target Day
Time Window
Baseline
1
≤ 1a
Week 4
29
[2, 43]
Week 8
57
[44, 71]
Week 12
85
[72, 99]
Week 16
113
[100, 127b]
Rx Day calculated relative to the first dose of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to randomization.
a.
If time is collected in vital signs, restrict to records prior to the first dose of study drug.
b.
The minimum of upper bound and first dose date of study drug on or after Week 16 (and within 105 days of last 
dose for safety analyses).  If time is collected in vital signs, restrict to records prior to the first dose of study drug 
on or after Week 16.
Table 5.
Visit Windows for Laboratory and ECG Parameters for Part A 
(Safety_A Population)
Window Label
Target Day
Time Window
Baseline
1
≤ 1
Week 4
29
[2, 71]
Week 16
113
[72, 155a]
Rx Day calculated relative to the first dose date of study drug.  For subjects randomized but not dosed, Rx Day 
calculated relative to randomization.
a.
The minimum of upper bound and first dose date/time on or after Week 16 (and within 105 days of last dose for 
safety analyses).
Table 6.
Visit Windows for Other Efficacy Endpoints Only Collected at 
Week 16 in Part A (ITT_A Population)
Window Label
Target Day
Time Window
Baseline
1
≤ 1
Week 16
113
[2, 225a]
Rx Day calculated relative to the first dose date of study drug.  For subjects randomized but not dosed, Rx Day 
calculated relative to randomization.
a.
The minimum of upper bound and first dose date of study drug on or after Week 16.


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Table 7.
Visit Windows for Local Tolerability for Part A (Safety_A 
Population)
Window Label
Target Day
Time Window
Week 1
8
[2,15]
Week 3
22
[16, 25]
Week 4
29
[26, 71]
Week 16
113
[72, 155a]
Rx Day calculated relative to the first dose of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to randomization.
a.
The minimum of upper bound and first dose date of study drug on or after Week 16 (and within 105 days of last 
dose for safety analyses) (and within 105 days of last dose for safety analyses).  If time is collected in vital signs, 
restrict to records prior to the first dose of study drug on or after Week 16.
Table 8.
Visit Windows for Analysis of PASI and sPGA in Part B 
(ITT_B_RR/ITT_B_R/ITT_B_NR/ITT_B_RZB/PP_B_RR 
Populations)
Window Label
Target Day
Time Window
Entry of B
1
≤ 1
Week 20
29
[2, 43]
Week 24
57
[44, 71]
Week 28
85
[72, 99]
Week 32
113
[100, 127]
Week 36
141
[128, 155]
Week 40
169
[156, 183]
Week 44
197
[184, 211]
Rx Day calculated relative to the first dose of study drug in Part B.  For subjects re-randomized but not dosed in Part B, 
Rx Day calculated relative to the IRT date of re-randomization evaluation.


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Table 9.
Visit Windows for Laboratory and ECG Parameters for Part B 
(Safety_B_RR Population)
Window Label
Target Day
Time Window
Entry of B
1
≤ 1
Week 28
85
[2, 141]
Week 44
197
[142, 211]
Week 48 (EOT + 4 Weeks)
225
[212, 239a]
Rx Day calculated relative to the first dose of study drug in Part B.  For subjects re-randomized but not dosed in Part B, 
Rx Day calculated relative to the IRT date of re-randomization evaluation.
a.
The minimum of upper bound and 105 days of last dose for safety analyses.
Table 10.
Visit Windows for Vital Signs for Part B (Safety_B_RR Population)
Window Label
Target Day
Time Window
Entry of B
1
≤ 1
Week 20
29
[2, 43]
Week 24
57
[44, 71]
Week 28
85
[72, 99]
Week 32
113
[100, 127]
Week 36
141
[128, 155]
Week 40
169
[156, 183]
Week 44
197
[184, 211]
Week 48 (EOT + 4 Weeks)
225
[212, 239a]
Rx Day calculated relative to the first dose of study drug in Part B.  For subjects re-randomized but not dosed in Part B, 
Rx Day calculated relative to the IRT date of re-randomization.
a.
The minimum of upper bound and 105 days of last dose for safety analyses.


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Table 11.
Visit Windows for Other Efficacy Endpoints Only Collected at 
Week 44 in Part B 
(ITT_B_RR/ITT_B_R/ITT_B_NR/ITT_B_RZB/PP_B_RR 
Populations)
Window Label
Target Day
Time Window
Entry of B
1
≤ 1
Week 44
197
[2, 393]
Rx Day calculated relative to the first dose of study drug in Part B.  For subjects re-randomized but not dosed in Part B, 
Rx Day calculated relative to the IRT date of re-randomization.
Table 12.
Visit Windows for Local Tolerability for Part B (Safety_B_RR 
Population)
Window Label
Target Day
Time Window
Week 28
85
[2, 141]
Week 44
197
[142, 253a]
Rx Day calculated relative to the first dose of study drug in Part B.  For subjects re-randomized but not dosed in Part B, 
Rx Day calculated relative to the IRT date of re-randomization.
a.
The minimum of upper bound and 105 days of last dose for safety analyses.
Note.
There is no local tolerability at re-randomization and after EOT.
Table 13.
Visit Windows for Laboratory and ECG Parameters for ALL_RZB 
Population
Window Label
Target Day
Time Window
Baseline
1
≤ 1
Week 4
29
[2, 71]
Week 16
113
[72, 155]
Week 28
197
[156, 253]
Week 44
309
[254, 323]
Week 48 (EOT + 4 Weeks)
337
[324, 351a]
Rx Day calculated relative to the first dose of risankizumab. 
a.
The minimum of upper bound and 105 days of last dose of risankizumab for safety analyses.


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Table 14.
Visit Windows for Vital Signs for ALL_RZB Population
Window Label
Target Day
Time Window
Baseline
1
≤ 1a
Week 4
29
[2, 43]
Week 8
57
[44, 71]
Week 12
85
[72, 99]
Week 16
113
[100, 127]
Week 20
141
[128, 155]
Week 24
169
[156, 183]
Week 28
197
[184, 211]
Week 32
225
[212, 239]
Week 36
253
[240, 267]
Week 40
281
[268, 295]
Week 44
309
[296, 323]
Week 48 (EOT + 4 Weeks)
337
[324, 351b]
Rx Day calculated relative to the first dose of risankizumab. 
a.
If time is collected in vital signs, restrict to records prior to the first dose of risankizumab.
b.
The minimum of upper bound and 105 days of last dose of risankizumab for safety analyses.
Table 15.
Visit Windows for Local Tolerability Parameters for ALL_RZB 
Population
Window Label
Target Day
Time Window
Week 1
8
[2, 15]
Week 3
22
[16, 25]
Week 4
29
[26, 71]
Week 16
113
[72, 155]
Week 28
197
[156, 253]
Week 44
309
[254, 323a]
Rx Day calculated relative to the first dose of risankizumab. 
a.
The minimum of upper bound and 105 days of last dose of risankizumab for safety analyses.
The time windows specified below will be used for the summary of study drug injections 
of each period. 


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Table 16.
Visit Windows for Summary of RZB Injections for Part A
Window Label
Target Day
Time Window
Week 0
1
≤ 1
Week 4
29
[2, 57a]
Rx Day calculated relative to the first dose of study drug.
a.
Before the first dose on or after Week 16.
Table 17.
Visit Windows for Summary of RZB Self-Administration 
Questionnaire in Part A
Window Label
Target Day
Time Window
Week 4
29
[2, 57a]
Rx Day calculated relative to the first dose of study drug.
a.
Before the first dose on or after Week 16.
Table 18.
Visit Windows for Summary of RZB Injections for Part B and RZB 
Self-Administration Questionnaire
Window Label
Target Day
Time Window
Week 16
1
≤ 1
Week 20
29
[2, 57]
Week 28
85
[58, 99]
Week 32
113
[100, 127]
Rx Day calculated relative to the first dose of study drug in Part B.


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Table 19.
Visit Windows for Summary of ADA Injections for Part A
Window Label
Target Day
Time Window
Week 0
1
≤ 1
Week 1
8
[2, 15]
Week 3
22
[16, 29]
Week 5
36
[30, 43]
Week 7
50
[44, 57]
Week 9
64
[58, 71]
Week 11
78
[72, 85]
Week 13
92
[86, 99]
Week 15
106
[100, 113]
Rx Day calculated relative to the first dose of study drug.
Table 20.
Visit Windows for Summary of ADA Injections for Part B
Window Label
Target Day
Time Window
Week 17
8
[1, 15]
Week 19
22
[16, 29]
Week 21
36
[30, 43]
Week 23
50
[44, 57]
Week 25
64
[58, 71]
Week 27
78
[72, 85]
Week 29
92
[86, 99]
Week 31
106
[100, 113]
Week 33
120
[114, 127]
Week 35
134
[128, 141]
Week 37
148
[142, 155]
Week 39
162
[156, 169]
Week 41
176
[170, 183]
Rx Day calculated relative to the first dose of study drug in Part B.


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Definition of Missing Data Imputation
No global imputation is taking place at the database level.  Efficacy related imputations 
are outlined in Section 10.0.  There is no imputation for missing values in the safety 
analyses.
Rounding of Numeric Results
Rounding will be performed for presentation of results.  No rounding will be performed 
before or during analyses.  The ROUND function of SAS will be used to round results. 
When dichotomizing continuous variables, associated continuous variables will be 
rounded to 9 decimal points before applying the cutoff point to determine the response 
status (for example, percent change from baseline in PASI score will be rounded to 
9 decimal places before comparing to 90%).
The mean and median will be rounded for presentation to 1 decimal more than the data 
entered into the database.  The standard deviation will be rounded to 2 decimal places 
more than the data entered into the database.  The minimum and maximum values will be 
presented as entered into the database.
Probabilities will be rounded to 3 decimal places before assignment of statistical 
significance and will be presented in rounded format.  Probabilities that round to zero or 
are reported by SAS as zero will be presented as "< 0.001."  Probabilities that round to 1 
or are reported by SAS as 1 will be presented as "> 0.999."
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
Demographics and Baseline characteristics will be summarized for each arm and for 
overall of the ITT populations.  Continuous variables will be summarized with the number 
of non-missing observations by mean, standard deviation, first quartile, median, 


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third quartile, minimum and maximum values.  Categorical data will be summarized using 
frequencies and percentages.  Statistical tests will be performed to assess the 
comparability of the two arms at Randomization on ITT_A and at Re-Randomization on 
ITT_B_RR.  Per Protocol Populations will only be summarized in the accountability 
table.  Treatment comparison will be made based on non-missing information.  
Continuous variables will be analyzed using one-way analysis of variance (ANOVA).  
Categorical variables will be analyzed using a two-sided Pearson's Chi-Square test (or an 
appropriate exact test if expected cell count < 5).
The following demographic and baseline parameters will be summarized. 
Subject Demographics
●
Sex (male, female)
●
Age (years), defined as the number of years from date of birth to date of 
first drug
●
Age categories (< 40 years, ≥ 40 – < 65 years, ≥ 65 years.)
●
Race (American Indian or Alaska Native, Asian, Black or African American, 
Native Hawaiian or Other Pacific Islander, White, Multi Race)
●
Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
●
Body weight (kg)
●
Body weight category (≤ 100 kg, > 100 kg)
●
Height (cm)
●
BMI (kg/m2)
●
BMI category (< 25, ≥ 25 – < 30, ≥ 30)
●
Prior exposure to TNF antagonists (0 versus ≥ 1)
General Baseline Characteristics
●
PASI (Psoriasis Area and Severity Index)
●
BSA (Body Surface Area)
●
sPGA (Static Physician Global Assessment)


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●
NAPSI (Nail Psoriasis Severity Index)
●
PSSI (Psoriasis Scalp Severity Index)
●
PPASI (Palmoplantar Psoriasis Area Severity Index)
●
Dermatology Life Quality Index (DLQI)
●
WLQ (Work Limitations Questionnaire)
Psoriasis and Cardiovascular History
●
Psoriatic arthritis (diagnosed, suspected, no)
●
Cardiovascular Diseases (myocardial infarction, angina pectoris, transient 
ischemic attack, stroke, deep vein thrombosis)
●
Cardiovascular Risk Factors (hypertension, hyperlipidemia, diabetes mellitus, 
obesity)
General Use
●
Smoking status (Never-smoked, Ex-smoker, Currently smokes)
●
Alcohol status (Non-drinker, drinks – no interference, drinks – possible 
interference)
Prior Treatment
●
Psoriasis Biologic Treatment History – by Response to Prior Treatment
●
Psoriasis Treatment – by Therapy Type (topical therapy, phototherapy, 
photochemotherapy, non-biologic systemic therapy, TNF antagonist, other 
biologic)
Also, Physical Exam and Pregnancy Test will be presented in listing format.
7.2
Medical History
Medical history will be summarized using body systems and condition/diagnosis as 
captured on the eCRF.  The body systems will be presented in alphabetical order and the 
conditions/diagnoses will be presented in alphabetical order within each body system.  


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The number and percentage of subjects with a particular condition/diagnosis will be 
summarized for each treatment arm.  Subjects reporting more than 
one condition/diagnosis within a body system will be counted only once for that body 
system.
7.3
Previous Treatment and Concomitant Medications
Prior and concomitant medications will be summarized by generic name.  A prior 
medication is defined as any medication taken prior to the first dose of study drug.  A 
concomitant medication is defined as any medication that started prior to the first dose of 
study drug and continued to be taken after the first dose of study drug or any medication 
that started after the first dose of study drug, but not after the last dose of study drug plus 
21 days.  The number and percentage of subjects who had taken medications will be 
summarized by generic drug name assigned by the World Health Organization (WHO) for 
both prior and concomitant medications.
7.4
Protocol Deviations
Number and percentage of subjects who reported at least one of the following protocol 
deviation categories will be provided.
●
Subject entered into the study even though she/he did not satisfy entry criteria
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded or prohibited concomitant treatment
8.0
Patient Disposition
The number of subjects for each of the following categories will be summarized, for 
overall and for each treatment group in the ITT_A population:
●
Number of subjects randomized


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●
Number of subjects treated during Part A
●
Number of subjects who completed Part A
●
Number of subjects who discontinued study drug during Part A
●
Number of subjects who prematurely discontinued from the Part A
The number of subjects for each of the following categories will be summarized, for 
overall and for each treatment group in the ITT_B_RR population:
●
Number of subjects re-randomized
●
Number of subjects treated during Part B 
●
Number of subjects who completed Part B
●
Number of subjects who discontinued study drug during Part B 
●
Number of subjects who prematurely discontinued from the Part B
In addition, the reasons for premature discontinuation will be summarized with 
frequencies and percentages. 
Disposition tables will also be summarized in the ITT_B_R, ITT_B_NR, and 
ITT_B_RZB Populations.
In addition to patient disposition, number of screening failures and reasons for screening 
failure will also be summarized among all screened subjects in a subject screening status 
table.
9.0
Study Drug Exposure and Compliance
Summary of study drug exposure will be provided for each treatment arm in each 
treatment part in the corresponding ITT populations.  Study drug compliance will be 
summarized in ITT_A, ITT_B_RR populations.
Study drug exposure (days) will be summarized using the sample size, mean, standard 
deviation, minimum, median and maximum for each treatment part.  In addition 


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cumulative exposure of RZB will be also summarized in the ALL_RZB Population.  
Study drug exposure will be summarized as follows:
Study Drug Exposure (in Days) in Each Part:
Part A:
●
For subjects who did not continue into Part B:
○
Date of last injection in Part A – Date of first injection in Part A + 14 days
(ADA)
○
Date of last injection in Part A – Date of first injection in Part A + 84 days
(RZB)
●
For subjects who continued into Part B:  the minimum of
○
Date of first injection in Part B – Date of first injection in Part A.
○
Date of last injection in Part A – Date of first injection in Part A + 14 days
(ADA)
○
Date of last injection in Part A – Date of first injection in Part A + 84 days
(RZB)
Part B:
●
Date of last injection in Part B – Date of first injection in Part B + 14 days
(ADA)
●
Date of last injection in Part B – Date of first injection in Part B + 84 days
(RZB)
ALL_RZB:
For study drug exposure during the administration of risankizumab in the ALL_RZB 
Population: 
●
Date of last injection of risankizumab – Date of first injection of risankizumab
+ 84 days.


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Compliance
There will be a summary of the number of subjects receiving study drug and dose at each 
scheduled study drug administration time point for adalimumab and for risankizumab, 
separately.  This will be repeated on the cumulative number of doses.  
When computing compliance at each scheduled time point, the denominator for each 
week will include all subjects in each analysis population who have not prematurely 
discontinued study drug (or prematurely discontinued from study) prior to the scheduled 
study drug injection.
Self-Administration of Risankizumab Questionnaire
There will be a summary of the self-administration of risankizumab questionnaire 
completed by supervising nurse/health care professional.
The following items will be summarized as-observed at each visit:
●
Patient able to inject all of the liquid (Yes/No)
●
Reason for unable to inject all of the liquid (Unable to remove the needle cap; 
Unable to fully push down the plunger; Unable to empty the syringe; More 
than a drop of medication remained on their skin; Other)
●
Injection site (Left lower abdomen; Right lower abdomen; Left thigh; Right 
thigh)
●
Helped by supervising personnel (Yes/No)
10.0
Efficacy Analysis
10.1
General Considerations
The treatment effect will be evaluated based on a two-sided significance level of 0.05 
(when rounded to three decimal places). 


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Efficacy variables will be summarized in all ITT populations.  The efficacy analysis will 
be conducted in the ITT_A and the ITT_B_RR populations.  Only the primary and ranked 
secondary variables will be analyzed for the per-protocol populations using primary 
approach to handle missing data as described below.
Subjects' actual weight category and prior TNF antagonist exposure will be used as the 
strata in the stratified analyses.
10.1.1
Analyses of Categorical Variables
For categorical variables, frequencies and percentages will be summarized.  The treatment 
groups will be compared using a Cochran-Mantel-Haenszel (CMH) test with stratification 
factors as strata for the analysis.  The CMH test will use weights proposed by Greenland 
& Robins, which is calculated as follows:
 =
∑

 ∙


∑




 , where
 = 

 − 

  denotes the risk difference in stratum &, & = 1, ⋯, )

 =  ∙
 + 
  denotes the weight of stratum &, & = 1, ⋯, )
 denotes the number of patients with event in treatmentin stratum i, & = 1, ⋯, )
 denotes the number of patients with event in treatment/in stratum i, & = 1, ⋯, )
 denotes the number of patients on treatmentin stratum i, & = 1, ⋯, )
 denotes the number of patients on  treatment/in stratum i, & = 1, ⋯, )
The estimated variance of  is calculated as:
012
3 45 =
∑
6


(∑




)/


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where 6 = ( −) 
9 + ( −) 
9
 ∙ ∙( + )/
 , & = 1, ⋯, )
Assuming a normal distribution of , an approximate 95% CI is given as follows, 
where :;.=>? is the 97.5% quantile of the standard normal distribution:
@A =  B  ± :;.=>? ∙D012
3 45E
Also, the approximate p-value can be calculated using the following:
pvalue =  2 ∙Pr
⎣
⎢
⎢
⎡
L > NN

D012
3 45
NN 
⎦
⎥
⎥
⎤
 , where L ~ S(0, 1)
If there is a stratum for a treatment group that has 0 subjects in any cell in the contingency 
table, all cells from the stratum will be added by 0.1 in order to prevent dividing by 0 in 
the above equations, as suggested in Greenland & Robins.
10.1.2
Analyses of Continuous Variables
For continuous variables, the model based mean and standard error will be presented.  The 
Baseline and visit means will also be presented for each treatment group for subjects who 
have both Baseline and post Baseline visit values.  The treatment groups will be compared 
using ANCOVA with treatment group, Baseline value, and stratification factors in the 
model.
10.1.3
Analyses of Time-to-Event Variables
Time to first achievement of endpoints will only be performed in ITT_A Populations up 
to Week 16.  The time to event will be calculated as:
●
Time to first achievement (with observed event) = [date of first achievement] –
[date of the first dose] + 1


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●
If a subject never attains Endpoint in Part A, that subject's time to 
first achievement will be censored at the last visit where PASI (or sPGA) was 
measured
Time to loss-of-response (and time to relapse) endpoints will only be performed in 
ITT_B_RR Population among those who achieved response at Re-Randomization.  The 
time to failure events will be calculated as:
●
Subjects will be a considered as failures if they subsequently lost the response, 
or discontinue from the study due to AE – "Worsening of disease under study."
●
Time to failure events = [date of failure] – [date of the first dose in Part B] + 1.
●
Subjects who maintain Endpoint throughout the study, or discontinued from 
the study due to reasons other than AE – "Worsening of disease under study," 
will be censored at their last measurement.
Both time to first achieving endpoints and time to loss-of-response endpoints will be 
analyzed using Kaplan-Meier estimates for each treatment group.  In the ITT_A and 
ITT_B_RR populations, treatments will be compared using stratified Log-rank test.
10.1.4
Missing Data Imputations
Missing data will be imputed using the following methods for the efficacy analyses: 
●
Non-Responder Imputation (NRI): the NRI analysis will categorize any 
subject who has a missing value at a specific visit as a non-responder for that 
visit.  The only exception is when the subject is a responder both before and 
after this specific visit window, within the same analysis period, then the 
subject will be categorized as a responder for the visit.  The NRI will be the 
primary approach in the analyses of categorical variables.
●
Last Observation Carried Forward (LOCF):  The LOCF analyses will use the 
completed evaluation from the previous visit within the particular analysis 
period for efficacy measures assessed to impute missing data at later visits in 
the same analysis period.  Baseline efficacy evaluations will not be carried 
forward.  Of note, post-baseline observations from Part A can be carried 


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forward to the ITT_B_RZB subjects since treatment is the same.  LOCF will 
be the primary approach in the analyses of continuous variables, and the 
secondary approach in the analyses of categorical variables.
●
As-Observed Cases (OC):  The as-observed analysis will not impute values for 
missing evaluations, and thus a subject who does not have an evaluation on a 
scheduled visit will be excluded from the as-observed analysis for that visit.  
As-observed analysis will be the secondary approach in the analysis of 
continuous variables.
●
Multiple Imputation (MI):  The MI analysis will be used as sensitivity 
approach to impute missing data in primary and ranked secondary endpoints.  
The variables to be included in the imputation model are listed below.  If MI is 
not applicable due to the nature of our data (e.g., MCMC algorithm does not 
converge), logistic regression or mixed effect model repeat measurement 
(MMRM) methods will be applied as sensitivity approach, whichever 
applicable.
The Multiple Imputation analysis will be carried out in three steps.
●
Imputation of missing data.  The imputation will be generated for each efficacy 
endpoint measurement.  The variables to be included in the imputation model 
are:  Baseline disease severity (PASI and sPGA), Baseline weight, treatment 
group, prior TNF exposure, and measurements at each visit from 
randomization (or re-randomization) up to the end of the analysis period.  For 
each endpoint, 20 'complete' datasets will be generated using SAS PROC MI.  
The imputed post-baseline measurements will be rounded to the same 
precision as the observed data before the determination of responder status 
(e.g., PASI 90).
●
Analysis of imputed data sets.  A CMH test, stratified by stratification factors, 
will be used to analyze categorical endpoints in each imputed dataset.
●
Synthesis of imputation and analysis results.  SAS PROC MIANALYZE will 
be used to generate the final inferences of the risk difference between 
treatment groups.


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Of note, subjects who discontinued due to AE – "Worsening of disease under study" will 
be counted as non-responders in all visits thereafter in the NRI and MI analyses, and will 
have their last observation prior to discontinuation carried forward in the LOCF analyses.  
10.2
Primary Efficacy Analysis
Primary Efficacy Analysis in Part A:
There are co-primary endpoints to assess the efficacy of risankizumab for the treatment of 
moderate to severe plaque psoriasis.  These are as follows:
●
Achievement of ≥ 90% reduction from baseline PASI score (PASI 90) at 
Week 16
●
Achievement of an sPGA of clear or almost clear (0 or 1) at Week 16
The primary null hypotheses are that risankizumab is not different from adalimumab in 
achieving ≥ 90% reduction from baseline in the Psoriasis Area and Severity Index score 
(PASI 90) and sPGA of clear (0) or almost clear (1) at Week 16.
The achievement of PASI 90 at Week 16 is the first co-primary endpoint and is a binary 
variable with values of 0 or 1.  The difference in proportion responding between treatment 
arms will be estimated and tested using the Cochran-Mantel-Haenszel risk difference 
estimate stratified by the randomization factors of baseline weight (≤ 100 kg versus 
> 100 kg) and prior exposure to TNF antagonists (0 versus ≥ 1).  
The achievement of a sPGA of clear or almost clear at Week 16 is the second co primary 
endpoint and is a binary variable with values of 0 or 1.  The analysis of the sPGA co-
primary endpoint will be identical to that of the PASI 90 co-primary endpoint detailed 
above.
The co-primary endpoints of PASI 90 and sPGA clear or almost clear need to be 
significant simultaneously.  Both endpoints compared to ADA will be tested using a 
two-sided test with a type I error of 0.05.


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The primary analysis will be carried out in the ITT_A Population and the PP_A 
Population.  Non-responder imputation will be used as the primary approach for missing 
values.  LOCF and MI will be performed as sensitivity analyses.
Primary Efficacy Analysis in Part B:
The primary endpoint in Part B is the achievement of PASI 90 at Week 44 for those 
subjects who are re-randomized at Week 16.  This endpoint will be tested independently 
with a type I error rate of 0.05, for the ITT_B_RR Population.  A sensitivity analysis will 
also be performed on the same endpoint for the PP_B_RR Population.
10.3
Secondary Efficacy Analyses
10.3.1
Ranked Secondary Efficacy Analyses
10.3.1.1
Ranked Secondary Efficacy Analysis in Part A
The ranked secondary endpoints in Part A are as follows:
1.
Achievement of ≥ 75% reduction from baseline PASI score (PASI 75) at Week 16
2.
Achievement of 100% reduction from baseline PASI score (PASI 100) at Week 16
Ranked secondary endpoints above will be analyzed in the ITT_A Population.  The same 
methods as discussed for the primary analyses will be used.  
The following null hypotheses will be tested in a hierarchical order using two-sided tests 
with a type I error of 0.05 only if the null hypothesis for the co-primary endpoints has 
been rejected:
1.
Risankizumab is not different from adalimumab with respect to PASI 75 response 
at Week 16
2.
Risankizumab is not different from adalimumab with respect to PASI 100 response 
at Week 16


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10.3.1.2
Ranked Secondary Efficacy Analysis in Part B
The ranked secondary endpoint for Part B is the achievement of 100% reduction from 
baseline PASI score (PASI 100) at Week 44.
This ranked secondary endpoint will be analyzed for the ITT_B_RR Population.  The 
same methods as discussed for the primary analyses will be used.
The null hypotheses below will be tested in a hierarchical order using two-sided tests with 
a type I error of 0.05 only if the null hypothesis for the primary endpoint in Part B has 
been rejected:
1.
Continuation of risankizumab is not different from switching to risankizumab with 
respect to PASI 100 response at Week 44.
10.3.2
Other Secondary Efficacy Analysis
The other secondary endpoints are as follows:
●
Achievement of an sPGA of clear or almost clear at Week 44
●
Achievement of sPGA of clear at Week 44
Other secondary endpoints will be analyzed for the ITT_B_RR Population.  
10.3.3
Further Endpoint Analyses
The further endpoints are as follows:
●
Achievement of PASI 50 at all visits collected
●
Achievement of PASI 75 at all visits collected
●
Achievement of PASI 90 at all visits collected
●
Achievement of PASI 100 at all visits collected
●
Time until the first achievement of PASI 50, PASI 75, PASI 90, PASI 100 and 
sPGA of clear or almost clear


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●
Time until loss of PASI 75, and sPGA of clear or almost clear
●
Change and percent change from baseline in PASI at all visits collected
●
Achievement of an sPGA of clear or almost clear at all visits collected
●
Achievement of an sPGA of clear at all visits collected
●
Change from baseline in DLQI at all visits collected
●
Achievement of a DLQI score of 0 or 1 at all visits collected
●
Achievement of a reduction of 5 or more points from baseline in DLQI score 
at all visits collected, among subjects with baseline DLQI ≥ 5
●
Change from baseline in WLQ at all visits collected
●
Change and percent change from baseline in Nail Psoriasis Severity Index 
(NAPSI) at all visits collected, in subjects with baseline NAPSI > 0
●
Change and percent change from baseline in Palmoplantar Psoriasis Severity 
Index (PPASI) at all visits collected, in subjects with baseline PPASI > 0
●
Change and percent change from baseline in Psoriasis Scalp Severity Index 
(PSSI) at all visits collected, in subjects with baseline PSSI > 0
10.4
Handling of Multiplicity
The statistical comparisons for the primary efficacy variables and the ranked secondary 
variables will be carried out in the hierarchical order.  This means that statistically 
significant results (P value ≤ 0.05) for the comparison in the higher rank (primary, then 
ranked secondary variables) are necessary to initiate the testing of the next comparison in 
the lower rank.  Since a step-down procedure is used, each comparison will be tested at a 
significance level of 0.05 and overall alpha level of 0.05 will be preserved. 
10.5
Efficacy Subgroup Analysis
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, summaries and analyses will be performed in the following subgroups for 
the primary efficacy endpoints in Part A and the primary efficacy endpoint in Part B.
●
Age group (< 40 years, ≥ 40 – < 65 years, ≥ 65 years);


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●
Sex (male, female);
●
Race (white, non-white);
●
Smoking (current, ex or never)
●
BMI (normal:  < 25, over weight:  ≥ 25 – < 30, obese:  ≥ 30);
●
Region (US, Asia, Other)
●
Baseline PASI score (by median);
●
Baseline sPGA (3, 4)
●
Psoriatic arthritis (yes [diagnosed or suspected], no)
●
Ps Therapy History (Phototherapy or Photochemotherapy, TNF Antagonist, 
Other biologics, Non-biologic systemic therapy, All biologics, Naïve to all)
11.0
Safety Analysis
11.1
General Considerations
Safety analyses will include adverse events, laboratory, local tolerability, ECG, and vital 
sign measurements.  Safety summaries will be provided using the safety population in 
each period as defined in Section 5.1.  Comparison between risankizumab group and 
adalimumab group will be performed in the Safety Population in Safety_A and 
Safety_B_RR populations.  Continuous variables will be analyzed using one-way 
ANOVA and categorical variables will be analyzed using Fisher's exact test.  For the 
analyses of AEs, only P values ≤ 0.100 when rounded to three digits will be presented. 
Missing safety data will not be imputed.
11.2
Analysis of Adverse Events
11.2.1
Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any event with an onset that 
is after the first dose of study drug and with an onset date within 105 days after the last 
dose of study drug in the analysis period, or prior to the first dose in the subsequent period 
for subjects who entered in to the subsequent period.  Events where the onset date is the 


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same as the study drug start date are assumed to be treatment-emergent, unless the adverse 
event start time is prior to the study drug start time.  If an incomplete onset date is 
collected for an adverse event, the event will be assumed to be treatment-emergent unless 
there is other evidence that confirms that the event is not treatment-emergent (e.g., the 
event end date is prior to the study drug start date).
Treatment-emergent adverse events (TEAE) for each safety population are defined as 
follows:
TEAEs of Safety_A:
For subjects who do not enter Part B, TEAEs are defined as any event with an onset after 
the first dose of study drug and no more than 105 days after the last dose of study drug.
For subjects who enter Part B, TEAEs are defined as any event with an onset after the 
first dose of study drug in Part A and before the first dose of study drug in Part B.
TEAEs of Safety_B_RR, Safety_B_R, Safety_B_NR:
TEAEs are defined as any event with an onset after the first dose of study drug in Part B 
and no more than 105 days after the last dose of study drug in the study.
TEAE of ALL_RZB:
TEAEs are defined as any event with an onset after the first dose of risankizumab and no 
more than 105 days after the last dose of risankizumab in the study.
The number and percent of subjects experiencing treatment-emergent TEAEs will be 
tabulated using the Medical Dictionary for Drug Regulatory Activities (MedDRA®) 
system organ class and preferred term. 


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Summary tables will be presented as follows:
1.
Adverse Event Overview
The number and percentage of subjects experiencing treatment-emergent adverse 
events will be summarized for the following adverse event categories:
●
Any AE
●
Any AE that was assessed as related to study drug by the investigator
●
Any severe AE
●
Any serious AE (SAE)
●
Any serious AE that was assessed as related to study drug by the investigator
●
Any AE leading to discontinuation of study drug
●
Any AE leading to death
●
Any deaths
●
Areas of Safety Interest
2.
Adverse Events by System Organ Class and Preferred Term
TEAEs will also be summarized and presented using primary Medical Dictionary 
for Regulatory Activities (MedDRA version 16.1 or later version) system organ 
classes (SOCs) and preferred terms (PTs).  The SOCs will be presented in 
alphabetical order, and the PTs will be presented in alphabetical order within each 
SOC.
Subjects reporting more than one adverse event for a given MedDRA preferred 
term will be counted only once for that term (most severe incident for the severity 
tables and most related incident for the relationship tables).  Subjects reporting 
more than one type of adverse event within a SOC will be counted only once for 
that SOC.  Subjects reporting more than one type of adverse event will be counted 
only once in the overall total.


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In addition, the number and percentage of adverse events with causal relationship 
between the events and the study drug will be summarized using the same 
conventions described above.
3.
Adverse Events by Maximum Severity
The severity grading of AEs follows Rheumatology Common Toxicity Criteria 
(RCTC).  
●
Grade 1 – mild
●
Grade 2 – moderate
●
Grade 3 – severe
●
Grade 4 – life threatening
Adverse events will also be summarized by maximum severity.  If a subject has an 
adverse event with unknown severity, then the subject will be counted in the 
severity category of "unknown," even if the subject has another occurrence of the 
same event with a severity present.  The only exception is if the subject has another 
occurrence of the same adverse event with the most extreme severity – ("Life-
threatening").  In this case, the subject will be counted under the "Life-threatening" 
category.  
4.
Adverse Events by Maximum Relationship
Adverse events will be summarized by maximum relationship to study drug, as 
assessed by the investigator.  Relationship of an AE to study drug is assessed by the 
investigator and collected in the CRF as 'Yes' or 'No.'  If a subject has an adverse 
event with unknown relationship, the subject will be counted in the relationship 
category of "unknown," even if the subject has another occurrence of the same 
event with a relationship of "No."  If the subject has another occurrence of the same 
adverse event with a relationship assessment of "Yes," the subject will be counted 
under the "yes" category.


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A listing of all pretreatment (i.e., events start prior to the first study drug injection) serious 
adverse events will be provided. 
The following tables are planned.
Treatment-emergent adverse events will be summarized as follows:
●
Grouped by SOC and PT
●
Grouped by SOC, PT and maximum relationship to study drug
●
Grouped by SOC, PT and maximum severity
Treatment-emergent serious adverse events will be summarized as follows:
●
Grouped by SOC and PT
●
A by-subject listing will be provided
Pre-treatment serious adverse events will be summarized as follows:
●
A by-subject listing will be provided
Treatment-emergent adverse events leading to death or premature discontinuation 
of study drug will be summarized as follows:
●
Grouped by SOC and PT
●
Separate listings by subject for deaths and premature terminations of study 
drug due to adverse events will be provided.
Treatment-emergent areas of safety interest will be summarized as follows:
●
Grouped by SOC and PT
●
A listing by subject will be provided.


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Areas of Safety Interest:
Areas of Safety Interest groupings are listed in Table 21.  These events are of interest due 
to a higher rate in the moderate to severe psoriasis population, or of interest for all Ig 
products or products in general (DILI).
The final list will be based on the most updated final version of risankizumab Product 
Safety Statistical Analysis Plan, which is consistent to the most updated risankizumab 
Risk Management Plan.
Table 21.
Areas of Safety Interest
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated CV 
Events
Major adverse 
cardiovascular 
events (MACE)
Adjudicated events
Display underlined terms 
defined by the following 
adjudicated terms:
!
CV Death which includes 
CETERM values:  Fatal 
CV, Fatal PE, Fatal Non-
Cardiac/Non-Neuro 
Arterial Thrombosis/ 
Thromboembolism, 
Undetermined Death, Not 
assessable death 
(cardiac/neuro/thrombotic), 
Fatal Stroke
!
Myocardial infarction
!
Stroke
Y
Extended 
MACE
Adjudicated events
Display underlined terms from 
MACE and underlined terms 
below:
!
Hospitalization for 
Unstable Angina
!
Coronary 
Revascularization 
Procedures
N


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Table 21.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated CV 
Events 
(continued)
Other CV 
events
Adjudicated events
Display underlined terms 
defined by the following 
adjudicated terms:  
!
Thrombotic events which 
includes CETERM values:  
Deep Vein Thrombosis, 
TIA, Pulmonary 
Embolism, Non-fatal Non-
Cardiac/Non-Neurological 
Arterial Thrombosis/ 
Thromboembolism, Other 
Venous Thrombosis, 
specified (non-fatal)
!
Cardiac arrhythmia which 
includes CETERM of:  
Clinically Significant 
Arrhythmia
!
Congestive heart failure
which includes CETERM 
of Heart Failure
!
Hypertensive emergency
N
Serious 
infections, TB, 
fungal and 
opportunistic 
infections 
(including 
herpes zoster)
Serious 
infections
Serious PTs of the 
CMQ (company 
MedDRA query) 
Infections 
(CMQ 80000018)
PTs
Y
TB
Tuberculosis 
(including 
Investigations) 
CMQ 
(code 80000033)
PTs
Y
Opportunistic 
infections
Opportunistic 
infections CMQ 
(code 80000073)
PTs
N


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Table 21.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Serious 
infections, TB, 
fungal and 
opportunistic 
infections 
(including 
herpes zoster) 
(continued)
Fungal 
infections
Fungal infections 
CMQ 
(code 80000063)
PTs
N
Herpes Zoster
Herpes zoster 
CMQ 
(code 80000175)
PTs
N
Malignancies
All possible 
malignancies
Narrow –
Malignancies 
(SMQ 20000090) 
PTs
N
Malignant 
Tumours
Narrow –
Malignant tumours 
(SMQ 20000194)
PTs
Y
Non-melanoma 
skin cancer
(NMSC)
Broad – Skin 
malignant tumours 
(SMQ 20000204) 
excluding terms 
identified by the 
Melanoma CMQ 
(code 80000119)
PTs
N
Malignant 
Tumours 
excluding 
NMSC
'Malignant 
Tumours excluding 
NMSC' is 
identified by the 
'Malignant 
Tumours' search 
excluding terms
identified by the 
'Non-melanoma 
skin cancer' 
(NMSC) search.
PTs
Y
Hypersensitivity 
Reaction
Hypersensitivity
Narrow –
Hypersensitivity 
(SMQ 20000214)
PTs
Y –
serious 
events 
only


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Table 21.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Hypersensitivity 
Reaction 
(continued)
Anaphylactic 
Reaction
Narrow –
Anaphylactic 
reaction 
(SMQ 20000021)
PTs
N
Hepatic Events
Hepatic Events
Broad – Hepatic 
failure, fibrosis and 
cirrhosis and other 
liver damage-
related conditions 
(SMQ 20000013) 
Broad – Hepatitis, 
non-infectious 
(SMQ 20000010) 
Broad –
Cholestasis and 
jaundice of hepatic 
origin 
(SMQ 20000009) 
Broad – Liver 
related 
investigations, 
signs and 
symptoms 
(SMQ 20000008) 
Narrow – Liver-
related coagulation 
and bleeding 
disturbances 
(SMQ 20000015)
PTs
N
Adverse Event per 100 Patient-Years of Exposure
Adverse events occurring during the entire study will be presented by event rate per 
100 patient-years. These will be presented for any TEAEs, serious adverse events, Areas 
of Special Interest. 


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AEs per 100 patient-years of exposure is defined as the number of AEs divided by the 
total exposure in 100 patient-years.  Note that one event per preferred term per day per 
subject will be counted in the calculation of the number of AEs (i.e., a preferred term will 
not be counted twice on the same day for the same subject).  See the calculation method 
below.
where total patient years is defined as the sum of the study drug exposure (defined as date 
of last dose – date of first dose + 105 days (5 half-lives)) of all subjects normalized by 
365.25, and rounded to one decimal place.
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Deaths and all SAEs will be presented in listing format.  In addition, SAEs and AE 
leading to study drug discontinuation will be summarized by System Organ Class and 
MedDRA Preferred Term.
11.2.3
Safety Subgroup Analysis
The AE overview and AE by SOC and PT in Safety_A and Safety_B_RR populations will 
also be analyzed with respect to the actual values of stratification factors:
●
Dichotomous weight (≤ 100 kg vs. > 100 kg)
●
Prior exposure to TNF antagonists (0 versus ≥ 1)
11.3
Analysis of Laboratory Data
For the assessments of laboratory data, values observed more than 105 days after the last 
dose of study drug will be excluded.
Years
Patient 
Total
TEAEs
of
Number 
100 ∀


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Listing and descriptive statistics of laboratory values over time, changes from baseline, 
and extreme abnormal value on treatment will be provided.  Extreme abnormal value is 
the value which is most significantly away from the reference range.  Frequency of 
subjects with transitions relative to reference range and listing of subjects with significant 
abnormal laboratory values will be presented as well.
Analyses will be conducted in the Safety_A Population, the Safety_B_RR Population, and 
the ALL_RZB Population.
11.3.1
Variables and Criteria Defining Abnormality
Clinical laboratory tests performed are listed below.


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Table 22.
Clinical Laboratory Tests
Category
Test Name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hbc (HbA1c)
White Blood Cells/Leukocytes
Platelet Count/Thrombocytes
Diff. Automatic
Neutrophils (relative count)
Eosinophils (relative count)
Lymphocytes (relative count)
Enzymes
AST(GOT)
ALT(GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
Gamma-Glutamyl Transferase (GGT/γ-GT)
Lactic Dehydrogenase (LDH)
Amylase
Lipase
Electrolytes
Calcium
Sodium
Potassium
Substrates
Glucose
BUN (blood urea nitrogen)
Uric acid
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Albumin
C-Reactive Protein (high sensitive)
Cholesterol, total
Triglycerides
LDL-Cholesterol
HDL-Cholesterol
Urinalysis (Stix)
Urine Protein
Urine Glucose


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11.3.2
Statistical Methods
Analysis of Quantitative Laboratory Parameters (Hematology and Chemistry)
Though the protocol indicates utilizing the Rheumatology Common Toxicity Criteria 
(RCTC) scale for grading laboratory values, given that the National Cancer Institute 
Common Toxicity Criteria for Adverse Events (NCI CTCAE) scale includes a more 
comprehensive list of laboratory values; the lab analyses based on the NCI CTCAE scale 
will be presented.  Changes from Baseline to each scheduled visit and to the final value in 
continuous laboratory parameters will be summarized with the mean, standard deviation 
and median.  The Baseline and visit/final value means will also be presented for subjects 
who have both the Baseline and visit/final values (see Section 6.0 for the definition of 
Baseline and final values).
If there are multiple post-baseline measurements on the same day, average value will be 
used.
Shift Tables
Shift tables for changes from Baseline according to the normal range will be provided for 
each hematology and clinical chemistry parameter.  Shifts from Baseline to the following 
endpoints will be considered:  minimum value, maximum value and final value.  
Categories of "low or normal" and "high or normal" will be included at Baseline in 
addition to the categories of "low," "normal," "high" and "missing." 
If there are multiple post-baseline measurements on the same day, the last value will be 
used.
Potentially Clinically Important Laboratory Values
Frequencies and percentages of subjects with post Baseline lab values meeting the 
following criteria will be summarized.  Of note, a post baseline value must be more 
extreme than the baseline value to be considered a potentially clinically important finding.


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Table 23.
Criteria for Potentially Clinically Important Chemistry Values
Definition of Potentially Clinically Important
Current (Version 4)
NCI CTCAE Grade 3 or Greater
Chemistry Variables
Units
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Sodium
mmol/L
< 130
> 155
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CPK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN
ALP
> 5.0 × ULN
Note:
A post baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.
Table 24.
Criteria for Potentially Clinically Important Hematology Values
Definition of Potentially Clinically Important
Current (Version 4) Grade 3 or Greater
Hematology Variables
Units
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
Note:
A post baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.


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A separate listing will be provided that presents all of the subjects and values that are NCI 
CTCAE toxicity grade 3 or above.  For each of these subjects, the whole course of the 
respective parameter will be listed.  The NCI CTCAE grading is shown in Table 25
below:
Table 25.
NCI CTCAE Grading
Test
Grade 1
Grade 2
Grade 3
Grade 4
SGPT/ALT 
increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
SGOT/AST 
increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
GGT increased
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
ALP increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
TBL increased
> ULN – 1.5 × ULN
> 1.5 – 3.0 × ULN
> 3.0 – 10.0 × ULN
> 10.0 × ULN
Creatinine 
increased
> ULN – 1.5 × ULN
> 1.5 – 3.0 × ULN
> 3.0 – 6.0 × ULN
> 6.0 × ULN
CPK increased
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 10.0 × ULN
> 10.0 × ULN
Hemoglobin 
decreased
< LLN – 100.0 g/L
< 100.0 – 80.0 g/L
< 80.0
Neutrophil 
count decreased
< LLN – 1.5 × 109/L
< 1.5 – 1.0 × 109/L
< 1.0 – 0.5 × 109/L
< 0.5 × 109/L
WBC decreased
< LLN – 3.0 × 109/L
< 3.0 – 2.0 × 109/L
< 2.0 – 1.0 × 109/L
< 1.0 × 109/L
Lymphocyte 
count decreased
< LLN – 0.8 × 109/L
< 0.8 – 0.5 × 109/L
< 0.5 – 0.2 × 109/L
< 0.2 × 109/L
If there are multiple post-baseline measurements on the same day, the worst value will be 
used.
Liver Function Tests
Additional summaries will be presented for liver function tests including ALT or serum 
glutamic-pyruvic transaminase (SGPT), AST or serum glutamic-oxaloacetic transaminase 
(SGOT), alkaline phosphatase, and total bilirubin.  Each laboratory value will be 
categorized as follows:


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●
< 1.5 × ULN
●
≥ 1.5 × ULN – < 3.0 × ULN
●
≥ 3.0 × ULN – < 5.0 × ULN
●
≥ 5.0 × ULN – < 10.0 × ULN
●
≥ 10.0 × ULN – < 20.0 × ULN
●
≥ 20.0 × ULN
Shift tables of Baseline to the maximum (relative to the normal range, i.e., the largest 
multiple relative to the upper limit of normal) values, and from Baseline to final value will 
be presented using these five categories.  A listing of potentially clinically important liver 
function laboratory values will be provided.  The listing will include all subjects who met 
any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or
●
Alkaline phosphatase ≥ 1.5 × ULN, or
●
Total bilirubin ≥ 2 × ULN.
A listing of possible Hy's Law cases, defined as those who meet all of the following 
conditions will be provided:
●
ALT > 3 × ULN or AST > 3 × ULN
●
Associated with an increase in bilirubin ≥ 2 × ULN
●
Alkaline phosphatase < 2 × ULN.
11.4
Analysis of Vital Signs and Weight
Analyses will be conducted in the Safety_A Population, the Safety_B_RR Population, and 
the ALL_RZB Population.


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11.4.1
Variables and Criteria Defining Abnormality
The following vital sign parameters will be assessed:  Systolic blood pressure [mmHg], 
Diastolic blood pressure [mmHg], Pulse [beats per minute], Respiratory rate [breaths per 
minute], Temperature [°C], Weight [kg].  The following table presents the Criteria for 
Potentially Clinically Important Vital Sign Findings.  Of note, a post baseline value must 
be more extreme than the baseline value to be considered a potentially clinically important 
finding.
Table 26.
Criteria for Potentially Clinically Important Vital Sign Findings
Vital Sign
Category
Criteria for Potential Clinically Important Vital Signs
Systolic Blood Pressure
Low Value
≤ 90 mmHg and decrease ≥ 20 mmHg from Baseline
High Value
≥ 160 mmHg and increase ≥ 20 mmHg from Baseline
Diastolic Blood Pressure
Low Value
≤ 50 mmHg and decrease ≥ 15 mmHg from Baseline
High Value
≥ 105 mmHg and increase ≥ 15 mmHg from Baseline
Pulse
Low Value
≤ 50 bpm and decrease ≥ 15 bpm from Baseline
High Value
≥ 120 bpm and increase ≥ 15 bpm from Baseline
Note:
A post baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.
11.4.2
Statistical Methods
Changes from Baseline to each visit and to the final value in vital sign parameters will be 
summarized with the mean, standard deviation and median.  The Baseline and final value 
means will also be presented for subjects who have both the Baseline and final values (see
Section 6.0 for the definition of Baseline and final values).
For baseline, if there are multiple measurements on the same day, the last measurement 
prior to the first dose of study drug will be used as the Baseline vital sign value.  If there 
are multiple post-baseline measurements on the same day, average value will be used.
For systolic blood pressure, diastolic blood pressure and pulse, a listing of all subjects
with any vital sign value meeting criteria for potentially clinically important values will be 


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provided.  For each of these subjects, the whole course of the respective parameter will be 
listed.  The number and percentage of subjects who have at least one value meeting 
criteria for potentially clinically important values will be provided for each selected vital 
sign parameter.
11.5
Analysis of ECG Parameters
The ECG parameters will be assessed as scheduled in the study protocol.
Summary statistics for mean change from baseline for corrected QT interval (QTc) using 
Bazett (QTcB) and Fridericia (QTcF) corrections will be provided by analysis visits.
●
Values for both QTcF and QTcB interval measurements will be categorized 
into the following:  ≤ 450 ms, > 450 ms, > 480 ms, > 500 ms, or missing.  For 
the scheduled visits, as well as baseline, the number and percentage of subjects 
within each category will be presented.  Additionally, for each category, the 
number and percentage of subjects with a maximum QTcF interval falling into 
the category will be presented; a similar summary will be presented for QTcB 
intervals.
●
For QTcF and QTcB intervals, the changes from baseline will be categorized 
into the following:  < 30 ms, 30 ≤ – < 60 ms, ≥ 60 ms, or missing.  For the 
scheduled visits, the number and percentage of subjects within each category 
will be presented.  Additionally, for each category, the number and percentage 
of subjects with a maximum change from baseline in the QTcF interval falling 
into the category will be presented; a similar summary will be presented for 
QTcB intervals.
Analyses will be conducted in the Safety_A Population, the Safety_B_RR Population, and 
the ALL_RZB Population.  


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11.6
Local Tolerability
Local tolerability of the subcutaneous injection will be assessed by the investigator 
according to 6 items:  swelling, induration, heat, redness, pain, and other findings.  
Proportion of subjects reporting each condition will be analyzed.
Analyses will be conducted in the Safety_A Population and the Safety_B_RR Population.  
In addition, the overall rate (with at least one occurrence) during the study will also be 
presented in the ALL_RZB Population. 
12.0
Pharmacokinetic Analysis
Pharmacokinetic analysis will not be covered in this SAP.
13.0
Biomarkers Analysis
Biomarker Analysis is not covered in this SAP.
14.0
Summary of Changes
Not applicable.  This is the first version of the SAP.
14.1
Summary of Changes Between the Latest Version of 
Protocol and the Current SAP
●
Defined analysis populations (including the Per-protocol population) in detail.
●
Clarified independent null hypothesis test hierarchy in the ITT Population in 
Part B consisting re-randomized subjects.
●
Added additional ranked secondary endpoint to the ITT Population in Part B 
consisting re-randomized subjects: achievement of 100% reduction from 
baseline PASI score (PASI 100) at Week 44.
●
Pre-specified Areas of Safety Interest.


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14.2
Summary of Changes Between the Previous Version and the 
Current Version of the SAP
Updated Table 23, Table 25, and Table 26 based on Integrated Summary of Safety SAP.
Updated the end day for inclusion concomitant medications, based on Integrated 
Summary of Safety SAP.
15.0
Appendix
None.
16.0
References
None.
17.0
List of Tables, Figures and Data Listings that Are to 
Be Programmed
To be provided in a separate document.