A Randomised, Double-blind, Placebo-controlled, Proof-of-concept, Dose-ranging Study of BI 655066/ABBV-066/Risankizumab in Patients With Active Psoriatic Arthritis
Phase: PHASE2
Conditions: Arthritis, Psoriatic
Sponsor: AbbVie

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001-MCS-40-106-RD-03 (12 0) / Saved on: 30 Jan 2015
CLINICAL TRIAL PROTOCOL
Document Number
c03416278-02
EudraCT No.:
2015-003625-34
BI Trial No.:
1311.5
Investigational 
Product:
BI 655066/ABBV-066/risankizumab
Title:
A randomised, double-blind, placebo-controlled, proof-of-
concept, dose-ranging study of BI 655066/ABBV-
066/risankizumab in patients with active psoriatic arthritis
Brief Title:
BI 655066/ABBV-066/risankizumab compared to placebo in 
patients with active psoriatic arthritis
Clinical Phase:
II
Trial Clinical 
Monitor:
Coordinating 
Investigator:
Status:
Final Protocol (Revised Protocol (based on global amendment 1)
Version and Date:
Version: 2.0
Date: 12 Oct 2016
Page 1 of 104
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! 2016 Boehringer Ingelheim International GmbH/AbbVie, Inc. or one or more of its affiliated companies. All rights 
reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission.
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CLINICAL TRIAL PROTOCOL SYNOPSIS
Name of company:
Boehringer Ingelheim (Sponsor 
for countries outside the United 
States)
AbbVie, Inc. (Sponsor 
United States Only)
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066/ABBV-
066/risankizumab
Protocol date:
15 Dec 2015
Trial number:
1311.5
Revision date:
12 Oct 2016
Title of trial:
A randomised, double-blind, placebo-controlled, proof-of-concept 
dose-ranging study of BI 655066/ABBV-066/risankizumab in 
patients with active psoriatic arthritis
Coordinating 
Investigator:
Trial sites:
Multi-centre, multi-national
Clinical phase:
II
Objectives:
To provide proof-of-concept and dose-ranging data of BI 
655066/ABBV-066/risankizumab in patients with active psoriatic 
arthritis
Methodology:
Randomised, parallel-design, dose-ranging, multiple-doses, placebo-
controlled, double-blind
No. of patients: 
total entered:
Approximately 180
each treatment:
40 each arm (150 mg BI 655066/ABBV-066/risankizumab Arms 1, 
2 and 3), 40 (placebo Arm 5), and 20 (75 mg BI 655066/ABBV-
066/risankizumab Arm 4)

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Name of company:
Boehringer Ingelheim (Sponsor 
for countries outside the United 
States)
AbbVie, Inc. (Sponsor 
United States Only)
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066/ABBV-
066/risankizumab
Protocol date:
15 Dec 2015
Trial number:
1311.5
Revision date:
12 Oct 2016
Diagnosis :
Active psoriatic arthritis
Main criteria
for inclusion:
1. Age ≥ 18 years at screening, males or females
2. Have psoriatic arthritis (PsA) symptoms for ≥6 months prior to 
screening, as assessed by the investigator
3. Have PsA on the basis of the Classification Criteria for Psoriatic 
Arthritis (CASPAR) with peripheral symptoms at screening 
visit, as assessed by the investigator
4. Have ≥5 tender joints and ≥5 swollen joints at screening and 
randomisation visits, as assessed by the investigator
5. At least one psoriasis (PsO) lesion or a documented personal 
history of PsO at screening, as assessed by the investigator
Test product:
BI 655066
dose:
Arm 1: 150 mg BI 655066/ABBV-066/risankizumab (2 syringes, 75
mg each) at Weeks 0, 4, 8, 12 and 16
Arm 2: 150 mg BI 655066/ABBV-066/risankizumab (2 syringes, 75
mg each) at Weeks 0, 4 and 16
Arm 3: 150 mg BI 655066/ABBV-066/risankizumab (2 syringes, 75
mg each) at Weeks 0 and 12
Arm 4: 75 mg BI 655066/ABBV-066/risankizumab (1 syringe, 75
mg) at Week 0
mode of 
administration:
Subcutaneous injection
Comparator products:
Placebo 
dose:
Arm 5: Placebo at Weeks 0, 4, 8, 12 and 16 
Arms 2, 3, 4 as needed for blinding

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Name of company:
Boehringer Ingelheim (Sponsor 
for countries outside the United 
States)
AbbVie, Inc. (Sponsor 
United States Only)
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066/ABBV-
066/risankizumab
Protocol date:
15 Dec 2015
Trial number:
1311.5
Revision date:
12 Oct 2016
mode of 
administration:
Subcutaneous injection
Duration of treatment:
16 weeks
Endpoints
Primary endpoint: Proportion of subjects achieving American College 
of Rheumatology (ACR) 20 response at Week 16
Safety criteria:
Physical examination, vital signs, 12-Lead ECG, laboratory tests, 
adverse events, serious adverse events, and local tolerability
Statistical methods:
The primary analyses will be based on the intent-to-treat principle, 
comprising all participants who were randomised and received at least 
one dose of assigned therapy during the trial. Safety analyses will be 
based on actual treatment received.
Sample size was determined on the basis of a one-sided comparison 
between the average ACR 20 response at Week 16 of Arm 1 and Arm 
2 versus placebo. With the assumed Week 16 ACR 20 response rate 
of 38% in the combined arms (Arm 1 and Arm 2) and of 15% in the 
placebo arm, 40 participants each for Arm 1, Arm 2 and placebo will 
provide 85% power to detect a 23% difference in proportion 
(combination of Arm 1 and Arm 2 versus placebo) using a one-sided 
test of 0.05 significance.
Randomisation is stratified based on prior TNF inhibitor experience
(naïve or experienced) and concurrent methotrexate use (yes or no) as 
determined at baseline. The difference in proportion of participants 
achieving ACR 20 at Week 16 between the combined arms of Arm 1 
and Arm 2 of BI 655066/ABBV-066/risankizumab and the placebo 
arm will be estimated and tested using the stratified Cochran-Mantel-
Haenszel risk difference estimate.
Pairwise comparisons of the BI 655066/ABBV-066/risankizumab
dose groups will be conducted using the same Cochran-Mantel-
Haenszel methods. There will be no adjustments for multiplicity in 

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Name of company:
Boehringer Ingelheim (Sponsor 
for countries outside the United 
States)
AbbVie, Inc. (Sponsor 
United States Only)
Name of finished product:
Not applicable
Name of active ingredient:
BI 655066/ABBV-
066/risankizumab
Protocol date:
15 Dec 2015
Trial number:
1311.5
Revision date:
12 Oct 2016
these analyses and nominal p-values of these comparisons will be 
provided.

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5. Vital signs will be assessed before study drug administration. In addition at Visits 2, 4 and 6 vital signs will be assessed at 5 and 60 minutes after study drug administration. Monitor for signs 
and symptoms of hypersensitivity reactions for approximately 2 hours after the first dose administered at Visit 2 and 1 hour following all other doses of study drug. Height and weight will be 
assessed at screening visit.
6. Background medications i.e. MTX, folic acid, systemic corticosteroids, NSAIDs and paracetamol/acetaminophen PRN medication will be recorded by patients in diaries provided and 
assessed by study staff.
7. Serum pregnancy testing for female patients of childbearing potential at screening and if urine pregnancy test is positive. Urine pregnancy testing will be done prior to administration of study 
drug at all dosing visits and at each follow-up visit.
8. Blood samples should be taken after patient has fasted for at least 8 hours (except screening visit). If not fasted mark on laboratory requisition form.
9. Biomarker sampling should be done prior to administration of study drug at dosing visits. Refer to Section 5.5.
10. PK and ADA (Anti Drug Antibody) samples at dosing visits should be taken pre-dose.
11. Voluntary DNA banking sample will be stored after separate informed consent is given in accordance with local ethical and regulatory requirements (Section 5.5.3).
12. HAQ-DI (Health Assessment Questionnaire Disability Index), LDI (Leeds Dactylitis Index), LEI (Leeds Enthesitis Index), SPARCC (Spondyloarthritis Research Consortium of Canada)
Enthesitis Index, PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), sPGA (Static Physician Global Assessment), mNAPSI (modified Nail Psoriasis Severity Index), 
BASDAI (Bath AS Disease Activity Index), SF-36 v2 (Medical Outcome Short Form Health Survey Version 2), FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue),. For 
details cf. Appendices 10. PASI and sPGA are assessed in patients with ≥ 3% BSA of psoriatic plaques at baseline and/or at current visit.
13. Assessed only in patients with baseline inflammatory spondylitis based on investigator judgement.
14. If X-Ray and/or Magnetic Resonance Imaging (MRI) are performed at screening, it does not need to be repeated at Week 0 (cf. Section 5.6).
. 

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TABLE OF CONTENTS
CLINICAL TRIAL PROTOCOL
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................................................................................17
1.2
2.
RATIONALE, OBJECTIVES, AND BENEFIT-RISK 
ASSESSMENT
19
RATIONALE FOR PERFORMING THE TRIAL.........................19
2.1
TRIAL OBJECTIVES .......................................................................19
2.2
BENEFIT-RISK ASSESSMENT ......................................................20
2.3
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
22
OVERALL TRIAL DESIGN AND PLAN.......................................22
3.1
3.1.1
Administrative structure of the trial............................................23
Data monitoring committee
24
3.1.1.1
MACE adjudication committee
24
3.1.1.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE 
3.2
OF CONTROL GROUP....................................................................25
SELECTION OF TRIAL POPULATION.......................................26
3.3
3.3.1
Main diagnosis for trial entry .......................................................26
3.3.2
Inclusion criteria............................................................................26
3.3.3
Exclusion criteria ...........................................................................27
3.3.4
Removal of patients from therapy or assessments......................29
Removal of individual patients
29
3.3.4.1
Discontinuation of the trial by the sponsor
30
3.3.4.2
4.
TREATMENTS
32
TREATMENTS TO BE ADMINISTERED.....................................32
4.1
4.1.1
Identity of BI investigational products ........................................32
4.1.2
Method of assigning patients to treatment groups......................33
4.1.3
Selection of doses in the trial.........................................................33
4.1.4
Drug assignment and administration of doses for each patient 35
4.1.5
Blinding and procedures for unblinding......................................36
Blinding
36
4.1.5.1
Unblinding and breaking the code
37
4.1.5.2
4.1.6
Packaging, labelling and re/supply...............................................37
4.1.7
Storage conditions..........................................................................37
4.1.8
Drug accountability .......................................................................38
CONCOMITANT THERAPY, RESTRICTIONS, AND RESCUE 
4.2
TREATMENT ....................................................................................38

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4.2.1
Rescue medication, emergency procedures, and additional 
treatments .......................................................................................38
4.2.2
Restrictions.....................................................................................40
Restrictions regarding concomitant treatment
40
4.2.2.1
Restrictions on diet and life style
42
4.2.2.2
Restrictions regarding women of childbearing potential
42
4.2.2.3
TREATMENT COMPLIANCE........................................................42
4.3
5.
VARIABLES AND THEIR ASSESSMENT
43
TRIAL ENDPOINTS .........................................................................43
5.1
5.1.1
Primary endpoint...........................................................................43
5.1.2
Secondary endpoints......................................................................43
5.1.3
Further endpoints ..........................................................................43
ASSESSMENT OF EFFICACY........................................................44
5.2
ASSESSMENT OF SAFETY ............................................................45
5.3
5.3.1
Physical examination .....................................................................46
5.3.2
Vital signs........................................................................................46
5.3.3
Safety laboratory parameters .......................................................46
5.3.4
Electrocardiogram.........................................................................49
5.3.5
Other safety parameters................................................................50
5.3.6
Assessment of adverse events........................................................50
Definitions of AEs
50
5.3.6.1
5.3.7
Adverse event collection and reporting........................................53
DRUG CONCENTRATION MEASUREMENTS AND 
5.4
PHARMACOKINETICS...................................................................55
5.4.1
Assessment of Pharmacokinetics..................................................55
5.4.2
Methods of sample collection ........................................................56
Plasma sampling for pharmacokinetic analysis
56
5.4.2.1
Plasma sampling for ADA
56
5.4.2.2
5.4.3
Analytical determinations .............................................................56
ASSESSMENT OF EXPLORATORY BIOMARKERS ................56
5.5
5.5.1
Assessment of soluble and cellular blood biomarkers and RNA57
Methods of sample collection
57
5.5.1.1
Analytical determinations
57
5.5.1.2
5.5.2
Biomarker sample banking...........................................................58
5.5.3
DNA banking..................................................................................58
Method of sample collection
58
5.5.3.1
Analytical determinations
58
5.5.3.2
OTHER ASSESSMENTS ..................................................................59
5.6
APPROPRIATENESS OF MEASUREMENTS..............................59
5.7
6.
INVESTIGATIONAL PLAN
60
VISIT SCHEDULE ............................................................................60
6.1
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS.60
6.2
6.2.1
Screening and run-in period .........................................................61
6.2.2
Treatment period ...........................................................................61
6.2.3
Follow-up Period and Trial Completion......................................61
Early treatment termination
62
6.2.3.1

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Trial completion
62
6.2.3.2
7.
STATISTICAL METHODS AND DETERMINATION OF 
SAMPLE SIZE
63
STATISTICAL DESIGN - MODEL.................................................63
7.1
NULL AND ALTERNATIVE HYPOTHESIS ................................63
7.2
PLANNED ANALYSES.....................................................................63
7.3
7.3.1
Primary endpoint analyses............................................................64
7.3.2
Secondary endpoint analyses ........................................................64
7.3.3
Further endpoint analyses.............................................................65
7.3.4
Safety analyses................................................................................65
7.3.5
Pharmacokinetic analyses .............................................................66
7.3.6
Pharmacodynamic analyses..........................................................66
7.3.7
Biomarker analyses........................................................................67
INTERIM ANALYSES......................................................................67
7.4
HANDLING OF MISSING DATA...................................................67
7.5
RANDOMISATION...........................................................................67
7.6
DETERMINATION OF SAMPLE SIZE.........................................67
7.7
8.
INFORMED CONSENT, DATA PROTECTION, TRIAL
RECORDS
69
TRIAL APPROVAL, PATIENT INFORMATION, AND
8.1
INFORMED CONSENT....................................................................69
DATA QUALITY ASSURANCE......................................................70
8.2
RECORDS...........................................................................................70
8.3
8.3.1
Source documents ..........................................................................70
8.3.2
Direct access to source data and documents................................70
8.3.3
Storage period of records ..............................................................71
LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE 
8.4
EVENTS ..............................................................................................71
8.4.1
Listedness........................................................................................71
8.4.2
Expedited reporting to health authorities and IEC/IRB............71
STATEMENT OF CONFIDENTIALITY .......................................71
8.5
END OF TRIAL..................................................................................72
8.6
PROTOCOL VIOLATIONS.............................................................72
8.7
COMPENSATION AVAILABLE TO THE PATIENT IN THE 
8.8
EVENT OF TRIAL RELATED INJURY........................................72
9.
REFERENCES
73
PUBLISHED REFERENCES ...........................................................73
9.1
UNPUBLISHED REFERENCES .....................................................77
9.2
10.
APPENDICES
78
CASPAR..............................................................................................78
10.1
JOINT ASSESSMENT.......................................................................79
10.2
ACR RESPONSE CRITERIA ..........................................................82
10.3
LEEDS DACTYLITIS INDEX (LDI)...............................................83
10.4
LEEDS ENTHESITIS INDEX (LEI) ...............................................84
10.5

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SPONDYLOARTHRITIS RESEARCH CONSORTIUM OF
10.6
CANADA (SPARCC) ENTHESITIS INDEX..................................85
MINIMAL DISEASE ACTIVITY....................................................86
10.7
DAS28 4V – CRP ................................................................................87
10.8
EULAR RESPONSE CRITERIA .....................................................88
10.9
PSARC RESPONSE...........................................................................89
10.10
PASI SCORE DEFINITIONS AND USE.........................................90
10.11
STATIC PHYSICIAN GLOBAL ASSESSMENT (SPGA)............91
10.12
MNAPSI – MODIFIED NAIL PSORIASIS SEVERITY INDEX .93
10.13
PATIENT REPORTED OUTCOMES.............................................95
10.14
10.14.1 Health Assessment Questionnaire Disability Index (HAQ-DI) .95
10.14.2 BASDAI (BATH AS DISEASE ACTIVITY INDEX) ................95
10.14.3 Medical Outcome Short Form Health Survey (SF-36) Version 2 
(Acute Form) ..................................................................................96
10.14.4 FUNCTIONAL ASSESSMENT OF CHRONIC ILLNESS 
THERAPY-FATIGUE (FACIT-F)...............................................96
10.14.5 Patient’s assessment of PsA pain intensity ..................................96
10.14.6 Patient’s global assessment of disease activity ............................97
CLINICAL CRITERIA FOR DIAGNOSIS OF ANAPHYLAXIS98
10.15
11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
99

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ABBREVIATIONS
ACR
American College of Rheumatology
ADA
Anti Drug Antibody
AE
Adverse Event
AESI
Adverse Event of Special Interest
ALT
Alanine Aminotransferase
Anti-CCP
Anti-Cyclic-Citrullinated Peptide
AST
Aspartate Aminotransferase
AUC
Area under the Curve
BASDAI
Bath AS Disease Activity Index
BI
Boehringer Ingelheim
BSA
Body Surface Area
CA
Competent Authority
CASPAR
ClASsification criteria for Psoriatic Arthritis
Cmax
Maximal Concentration
CML
Local Clinical Monitor 
CRA
Clinical Research Associate
CRO
Contract Research Organisation
CRP
C-Reactive Protein
CTP
Clinical Trial Protocol
DAS28
Disease Activity Score in 28 joints
DEDP
Drug Exposure During Pregnancy
DILI
Drug Induced Liver Injury
DIP
Distal Interphalangeal
DMARDs
Disease-Modifying Antirheumatic Drugs
DMC
Data Monitoring Committee
DN
Double Negative
DNA
Deoxyribonucleic Acid
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
ELISA
Enzyme Linked Immunosorbent Assay
EOS
End Of Study
EOT 
End Of Treatment
EudraCT
European Clinical Trials Database
EULAR
European League Against Rheumatism
FACIT-F
Functional Assessment of Chronic Illness Therapy-Fatigue
FACS
Fluorescence-Activated Cell Sorting
FAS
Full Analysis Set
FDA
Food and Drug Administration
FU
Follow-Up
GCP
Good Clinical Practice
HAQ-DI
Health Assessment Questionnaire-Disability Index
HIV
Human Immunodeficiency Virus
IB
Investigator’s Brochure
IC50
Half-maximal Inhibition

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IEC
Independent Ethics Committee
IFN
Interferon
IgG
Immunoglobulin G
IL
Interleukin
ILCs
Innate Lymphoid Cells
IP
Interphalangeal
IRB
Institutional Review Board
IRT
Interactive Response System
ISF
Investigator Site File
ITT
Intention-To-Treat
i.v.
intravenous
LDI
Leeds Dactylitis Index
LEI
Leeds Enthesitis Index
mAb
monoclonal Antibody
MACE
Major Adverse Cardiovascular Event 
MAR
Missing At Random
MCP
Metacarpalphalangeal
MDA
Minimal Disease Activity
MedDRA
Medical Dictionary for Drug Regulatory Activities
MMRM
Mixed Model Repeated Measures Model
mNAPSI
Modified Nail Psoriasis Severity Index
MRI
Magnetic Resonance Imaging
mTSS
Modified Total Sharp Score
MTX
Methotrexate
NGAL
Neutrophil Gelatinase Associated Lipocalin-2
nM
Nanomolar
NOAEL
No Observed Adverse Effect Level
NRI
Non-Responder Imputation
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
OLE
Open-Label Extension
OMERACT
Outcome Measures in Rheumatology
OPU
Operation Unit
PASI
Psoriasis Area and Severity Index
PD
Pharmacodynamic
PIP
Proximal Interpalangeal
PK
Pharmacokinetic
pM
Picomolar
PMN
Polymorphonuclear
PPD
Purified Protein Derivative
PRN
(Pro re nata) when necessary
PsA
Psoriatic Arthritis
PsAMRIS
Psoriatic Arthritis Magnetic Resonance Image Scoring System
PsARC
Psoriatic Arthritis Response Criteria
PsO
Psoriasis
PUVA
Psoralen and ultraviolet A
RCTC
Rheumatology Common Toxicity Criteria

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RDC
Remote Data Capture
REML
Residual Maximum Likelihood Method
REP
Residual Effect Period
RNA
Ribonucleic Acid
SAE
Serious Adverse Event
SF-36
Short Form-36 Health Survey
SJC
Swollen Joint Count(s)
SOP
Standard Operating Procedure
SPARCC
Spondyloarthritis Research Consortium of Canada
sPGA
Static Physician Global Assessment
SUSAR
Suspected Unexpected Serious Adverse Reaction
TB
Tuberculosis
TCM 
Trial Clinical Monitor
t.i.d.
ter in die (3 times a day)
TJC
Tender Joint Count(s)
TNF
Tumor necrosis factor
TNFi
Tumor necrosis factor inhibitor(s)
TSAP
Trial Statistical Analysis Plan
UV(A/B)
Ultraviolet (A/B)
VAS
Visual Analog Scale
W
Week
WBC
White Blood Count

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1.
INTRODUCTION
MEDICAL BACKGROUND
1.1
Psoriatic Arthritis (PsA) is a chronic seronegative spondyloarthritis characterized by 
peripheral synovitis, enthesitis, dactylitis and spondylitis (R14-4870; R15-1089). 
PsA is mostly associated with Psoriasis (PsO) and nail involvement (R15-1020). 
Prevalence estimates for PsA among PsO patients vary across studies, ranging from 
6 to 30% (R15-1003; R15-1002), with PsA affecting about 0.3 to 1% of the global 
population, equally men and women (R15-1020). The cause of PsA is not known, 
but hereditary factors, infection and physical trauma are frequently referred to as 
potential risk factors.
Although effective treatments for PsA are approved (traditional disease-modifying 
antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide), apremilast, 
tumour necrosis factor inhibitors (TNFi) (certolizumab pegol, adalimumab, 
etanercept, infliximab, golimumab), and anti-IL-12/23p40 (ustekinumab)), the 
unmet medical need remains for safer therapy that works more effectively on 
measures of signs and symptoms of PsA, prevention of structural damage and PsO 
and that maintains the efficacy over time, preferably with a new mode of action to 
provide more treatment options to patients who have already failed the currently 
approved therapies.
BI 655066/ABBV-066/risankizumab (risankizumab) is a humanized monoclonal 
antibody (mAb) directed against human IL-23 that specifically neutralizes this 
cytokine and prevents binding and signalling through the IL-23 receptor, expressed 
on Th17 cells as well as subset of ∀# T cells, NK cells, innate lymphoid cells (ILCs) 
and double negative (DN) entheseal-residing T cells. risankizumab has a potential 
for addressing some of the unmet needs in PsA.
PsO and PsA share common pathologies based on cellular pathways (T cells/ 
plasmacytoid dendritic cells), transcription factors (decreased AP-1), genetic 
susceptibility loci (CARD15/PSORAS1/NOD2, TNF gene polymorphism) and 
cytokines/ other mediators (TNF, type 1 interferon, amphiregulin) (R15-1030). Pro-
inflammatory mediators that act as drivers of PsO and PsA are released by a variety 
of cell types, including innate immune cells, adaptive immune cells and resident 
immune cells (R11-1257). Plasmacytoid dendritic cells are found in psoriatic skin 
and psoriatic synovium and activated dendritic cells present antigens and produce 
interferon (IFN)-α and pro-inflammatory mediators, such as IL-12 and IL-23. 
Antigen presented by myeloid dendritic cells to T-cells results in proliferation and 
differentiation into type 1 and type 17 T helper cells, which increase secretion of 
inflammatory cytokines (R11-1257; R15-1033).
The role of the IL-23/IL-17 axis in PsA is well documented in the literature (R14-
5175). IL-23 is expressed in the synovial tissue of patients with PsA (R15-1008). 

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Single nucleotide polymorphisms in this genetic pathway are related to genetic 
susceptibility to PsA (R15-1035; R15-0998). IL-23 has been shown to cause 
enthesitis (one of the key features of PsA) in a rodent model (R15-1070). The role 
of IL-23 (through its effect on Th17 cells) has been implied in bone erosion and 
dysregulated bone formation in PsA. IL-17 can cause cartilage degradation via 
effects on chondrocytes (R15-1066) In addition, IL-23 (independent of Th17) 
activates IL-23R+ entheseal resident lymphocyte cell population, which produces 
IL-22, and can promote entheseal and periosteal bone formation (R15-1070).
DRUG PROFILE
1.2
Risankizumab is a humanized monoclonal antibody (mAb) of the IgG1 subclass 
directed towards IL-23p19. 
 
 
 
 
 
 
The toxicology data suggest risankizumab can be safely administered to humans, as 
supported by chronic administration to monkeys for up to 
weeks. The monkey 
was identified as the most relevant toxicology species with a NOAEL (no observed 
adverse effect level) of 
mg/kg/dose (highest tested dose), corresponding to an 
exposure (combined sex) of 
μg/mL for the Cmax and 
μg*h/mL for 
AUC
, respectively.
Proof of clinical concept for risankizumab through IL-23/IL-17 pathway was 
demonstrated in a single rising dose Phase I trial in 39 patients with moderate to 
severe plaque PsO where 87% of patients achieved at least 75% reduction in 
Psoriasis Area and Severity Index (PASI 75) with no safety concerns (c02434648).
In a Phase II dose-ranging trial of risankizumab vs. ustekinumab, the primary 
endpoint of PASI 90 response at Week 12 was achieved by 32.6% (14/43), 73.2% 
(30/41), and 81.0% (34/42) of risankizumab patients in the 18 (single dose at Week 
0), 90, and 180 mg (dosed at Weeks 0, 4 and 16) groups, respectively, and 40.0% 
(16/40) of ustekinumab patients (dosed at Weeks 0, 4 and 16, weight based). A two-
sided Cochran-Mantel-Haenszel test of PASI 90 response at Week 12 between the 
18, 90, and 180 mg groups ofrisankizumab, and ustekinumab, gave p-values of 
0.4337, 0.0013, and <0.0001, respectively (c03272682). In addition, in this PsO 
trial, Pain Visual Analog Scale (pain-VAS [0-100 mm]) data over time was 
obtained from 46 patients who had concurrent diagnosed by rheumatologist or 
suspected PsA. The criterion of >50% decrease in pain-VAS (defined post hoc, as 
one of the potential domains contributing to ACR 50 response) at Week 24 was 
achieved in 16.7% (1/6), 81.8% (9/11), and 90.9% (10/11) of patients in 
risankizumab18, 90, and 180 mg dose groups, respectively, compared with 57.1% 

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2.
RATIONALE, OBJECTIVES, AND BENEFIT-RISK 
ASSESSMENT
RATIONALE FOR PERFORMING THE TRIAL
2.1
This trial is performed to provide proof-of-concept and dose-ranging data for 
risankizumab in patients with active PsA. The rationale for starting risankizumab 
development in PsA by performing this trial is based on the observed efficacy of 
risankizumab in PsO in Phase I and II trials (c02434648, c03272682) as well as 
pain-VAS data obtained from PsO patients with concurrent PsA in Phase II trial
(c03272682), supporting a role of IL-23p19 as a therapeutic target in PsA and 
supplementing the pre-clinical pharmacologic rationale for IL-23 pathway in this 
indication. In addition, positive Phase III data from approved and investigational 
anti-IL-12/23p40 and anti-IL-17 mAbs on various PsA domains confirm the role of 
IL-23/IL-17 pathway inhibition in treatment of active PsA patients.
TRIAL OBJECTIVES
2.2
The objectives of this study are to provide proof-of-concept and dose-ranging data 
of risankizumab in patients with active PsA to support dose selection for the pivotal 
program in this indication. The proof-of-concept will be achieved through the 
primary endpoint comparison (ACR 20 rates at Week 16) from the pooling of the 
two highest exposure arms versus placebo. The short-term utility of an additional 
dose at Week 4 will be evaluated by comparison of 150 mg at Weeks 0 and 12 
versus 150 mg at Weeks 0, 4, and 16. In addition, clinical efficacy (based on 
secondary and further endpoints) will be evaluated. Onset of response and 
assessment of duration of response will be assessed during treatment and through 
Week 32 follow-up, or until last visit prior to enrolling into the open label extension 
(OLE) study.
Safety of risankizumab will be evaluated during treatment and through Week 32 
follow-up. The effect of emergence of anti-drug antibodies (ADA) on safety and 
efficacy will be explored.
In addition, risankizumab PK exposure will be assessed to provide data for 
subsequent PK-PD modelling. The risankizumab exposure-response profile will be 
characterised through a relatively wide exposure range achieved by 150 mg every 4 
weeks to 75 mg single dosing.
Prevention of structural damage will be explored through X-ray endpoints at Week 
24 and MRI endpoints at Week 16. Influence of risankizumab on pathway gene and 
protein expression levels as well as disease specific protein markers will be 
explored.

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BENEFIT-RISK ASSESSMENT
2.3
Participation in this study may help generate future benefit for larger groups of 
patients with PsA if risankizumab proves to be successful in treating this disease to 
address an unmet medical need as described in Section 2.1. Risankizumab has been 
studied in 46 PsO patients who had concurrent diagnosed by rheumatologist or 
suspected by investigator PsA. The rates of patients with >50% reduction at Week 
24 (from baseline) in pain-VAS in the 90 mg and 180 mg of risankizumab arms 
were comparable with ustekinumab arm and numerically better than in 
risankizumab18 mg single dose arm. In addition, 70-80% of patients with moderate 
to severe PsO receiving 90 mg and 180 mg of risankizumab achieved PASI 90 in 
their skin disease.
However, no direct benefit for individual participants in this study can be assumed, 
because efficacy of risankizumab has not been confirmed in PsA and because some 
patients will be randomised to the placebo arm. Measures are in place to minimize 
administration of potentially sub-optimal treatment long-term. In particular, at 
Week 16, after last study drug administration and regardless of treatment arm, 
patients with reduction in both tender and swollen joint count of <20%, will be able 
to change their concomitant PsA medication according to investigator’s judgment 
and local standard of care, except addition of new biologic treatment (cf. Section 
4.2.1). Starting from Week 24 patients that are not enrolling in the OLE study can 
receive rescue treatment (cf. Section 4.2.1), including biologic treatment, according 
to investigator’s judgment and regardless of the degree of improvement in their 
symptoms. Patients will be continuing their follow-up procedures within this study 
regardless if they have started rescue treatment.
Risankizumab has been administered to approximately 350 patients with moderate 
to severe plaque PsO, ankylosing spondylitis and Crohn’s disease in completed or 
ongoing studies. The most common adverse events (AEs) reported in these trials 
were mild symptoms of the upper respiratory tract, including nasal stuffiness, sore 
throat, 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 risankizumab were uncommon, and limited to 
redness, swelling or induration at the injection site. No serious drug related AEs 
were reported. As with any immune modulating agent, risankizumab may impair 
immune function resulting in a risk of infection. This will be monitored by 
collection of any AEs during the treatment and observation periods. There is not 
enough information at this time to rule out a risk of cancer with risankizumab, 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. Patients will be monitored for signs and symptoms of malignancy at each 
visit.
Increases in major adverse cardiovascular events (MACE) including myocardial 
infarction, cerebrovascular accident, and cardiovascular death, reported initially 

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with anti-IL-12/23 agents, such as ustekinumab, have not been confirmed with 
longer observation times. 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.
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.
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 is a multi-national, randomised, parallel-design, dose-ranging, multiple-doses, 
placebo-controlled, double-blind Phase II study. Approximately 180 eligible 
patients with active PsA will be randomised at 2:2:2:1:2 ratio, stratified based on 
prior TNFi use and concurrent MTX use into five treatment arms shown in Figure 
3.1: 1. Patients with prior TNFi experience will be capped at approximately 70%.
Overall trial treatment duration is 16 weeks with additional 16 weeks follow-up.
Patients who have completed all doses of study drug and the Week 24 visit will 
have the option to enrol into a separate OLE study. The OLE study will be 
sponsored by AbbVie as part of a collaboration of the risankizumab development 
program.  Those patients rolling over to the OLE study, will not complete any 
remaining follow-up visits in this study and will follow the procedures in the OLE
study protocol.
Patients will receive risankizumab/placebo as described in Figure 3.1: 1. The overall 
dosing schedule will be the same in all treatment arms in order to keep the blind; 
this is further described in Section 4.1.4.
If patients have reduction in both tender and swollen joint count of <20% relative to 
baseline at the Week 16 assessment, they may alter their concomitant PsA treatment 
or start additional treatment, except biologics, according to investigator’s judgement 
and local standard of care, after receiving Week 16 study drug dose. After Week 24, 
patients that are not enrolling in the OLE study may start rescue treatment with local 
standard of care, including biologic treatment, if considered appropriate by the 
investigator, regardless of the joint count improvement. For details refer to Section 
4.2.1.
In addition to clinical endpoint assessments, patients will have X-rays performed at 
Weeks 0 and 24 for assessment of the modified total Sharp score (mTSS). 
Approximately 90 patients from selected sites with access to MRI will be included 
in the MRI sub-study, with MRI assessments performed at Weeks 0 and 16.
The analysis of the primary endpoint will be performed when the last patient 
completes the Week 16 visit, when the primary endpoint (ACR 20 at Week 16) is 
assessed. The trial will be unblinded to the sponsor for analysis, but patients and 
investigators will remain blinded until after the completion of the trial.
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 

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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.
Figure 3.1: 1
Trial design
3.1.1
Administrative structure of the trial
The trial is sponsored by Boehringer Ingelheim (BI) outside of the US and by 
AbbVie, Inc. in the US only. Boehringer Ingelheim will continue to manage the 
1311.5 study in all countries.
Boehringer Ingelheim has appointed a Trial Clinical Monitor, responsible for 
coordinating all required activities, in order to:
∃
manage the trial in accordance with applicable regulations and internal 
Standard Operating Procedures (SOPs),
∃
direct the clinical trial team in the preparation, conduct, and reporting of the 
trial,
∃
order the materials as needed for the trial; and

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∃
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 (Principal) 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 AbbVie SOPs.
A central laboratory service and an IRT (interactive response technology) vendor 
will be used in this trial. In addition, a centralised review of collected X-rays and 
MRI will be conducted by selected vendors. Details will be provided in IRT Manual 
and Central Laboratory Manual and other documentation, 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.
A list of responsible persons and relevant local information (as protocol reference, if 
applicable) can be found in the ISF.
Data monitoring committee
3.1.1.1
A data monitoring committee (DMC), independent of the Sponsor will be 
established to assess the progress of the clinical trial, including an unblinded safety 
and efficacy assessment at specified intervals, and to recommend to the Sponsor 
whether to continue, modify, or stop the trial. Measures are in place to ensure 
blinding of the Sponsor and all other trial participants. The tasks and responsibilities 
of the DMC will be specified in the DMC Charter. The DMC will maintain written 
records of all its meetings.
MACE adjudication committee
3.1.1.2
An independent adjudication committee will be used to adjudicate all observed 
cardio- and cerebro-vascular 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 adjudicated and 

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the adjudication process will be detailed in the MACE Adjudication Committee 
Charter.
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE 
3.2
OF CONTROL GROUP
This is a randomised double-blind, placebo-controlled, parallel-design study. This 
design is appropriate for providing proof-of-concept/dose-ranging and assessing the 
safety and efficacy of risankizumab compared to placebo in patients with active 
PsA. 
While there is a low rate of response with placebo treatment, it is important to have 
a placebo control to address potential confounding factors, such as placebo effect, 
potential investigator bias in safety and efficacy assessment or regression to the 
mean in endpoint scoring. Escape criteria are defined at Week 16 to ensure 
adjustment of treatment for all patients who have reduction in both tender and 
swollen joint count <20% at Week 16. In addition from Week 24, patients not 
enrolling in the OLE study can start rescue treatment with local standard of care, 
including biological treatment, as needed (i.e., without the need to meet any 
predefined escape criteria). The start of an alternative biologic treatment is delayed 
until Week 24, to allow for at least 8 weeks washout after the last dose of 
risankizumab in treatment Arms 1 and 2 for safety considerations. In addition, this 
delay will keep Week 24 assessments less biased considering the known significant 
efficacy of biologic treatments in PsA. The expectation of structural damage within 
Weeks 0 to 24 period (within which biologic treatment with proven effect on 
structural damage is restricted) is low (R15-1020). All patients, regardless if they 
have started rescue treatment need to be followed up to through EOS visit, if 
possible, except for patients who enrol in OLE studyto ensure safety follow-up
during Residual Effect Period (REP) as defined in Section 5.3.7. Those patients 
rolling over to the OLE study, will not complete the remaining follow-up visits in 
this study and will follow the procedures in the OLE study protocol.
Four active arms will be studied to provide a range of exposure. For primary 
analysis, primary endpoints from Arms 1 and 2 will be pooled for comparison with 
placebo with the aim of obtaining proof-of-concept in PsA patients at Week 16. 
Arm 2 will be compared to Arm 3 at Weeks 8 and 12 to assess the utility of the 
Week 4 dose in Arm 2. Arm 4 will provide what is expected to be a sub-optimal 
exposure for assessing a relatively wide exposure range that will be used in 
exposure-response profiling of risankizumab in PsA.
The reason for stratification based on prior TNFi experience is, that patients with 
prior TNFi experience may be more difficult to treat in comparison to others (R15-
1091, R15-3527, R15-5899). The number of patients with TNFi experience is 
capped at 70%, to have at least 30% TNFi naïve patients to allow for exploratory 
analysis of risankizumab efficacy in both sub-populations. Stratification based on 
concomitant MTX use is performed, because efficacy of risankizumab may be 

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different between patients with and without concomitant MTX use (i.e. concomitant 
MTX may provide additional efficacy).
SELECTION OF TRIAL POPULATION
3.3
A total of approximately 180 patients will be randomised in this trial. A sufficient
number of patients will be screened to meet this randomised goal. Patients will be 
recruited at approximately 70 sites in multiple countries. The planned number of 
patients per site is 2 – 3. Recruitment will be competitive.
A log of all patients enrolled into the trial (i.e. signed informed consent) will be 
maintained in the ISF at the investigational sites whether these patients have been 
treated with investigational drug or not.
3.3.1
Main diagnosis for trial entry
Patients with active PsA will be included. PsA will be diagnosed based on the 
Classification Criteria for Psoriatic Arthritis (CASPAR) that combine variable 
clinical patient characteristics and require inflammatory articular disease plus at 
least 3 points from different categories for a PsA diagnosis (Appendix 10.1). Active 
PsA will be defined by presence of ≥5 tender joints and ≥ 5 swollen joints.
Please refer to Section 8.3.1 (Source Documents) for the documentation 
requirements pertaining to the inclusion and exclusion criteria.
3.3.2
Inclusion criteria
1. Age ≥ 18 years at screening, males or females
2. Have PsA symptoms for ≥6 months prior to screening, as assessed by the 
investigator
3. Have PsA on the basis of the Classification Criteria for Psoriatic Arthritis 
(CASPAR) with peripheral symptoms at screening visit, as assessed by the 
investigator
4. Have ≥ 5 tender joints and ≥ 5 swollen joints at screening and randomisation 
visits, as assessed by the investigator
5. At least one PsO lesion or a documented personal history of PsO at 
screening, as assessed by the investigator
6. If patients receive concurrent PsA treatments, these need to be on stable 
doses as below: 

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For subjects receiving MTX: subject has received treatment for ≥ 3 months, 
with stable dose and stable route of administration (not to exceed 25 mg 
MTX per week) for ≥ 4 weeks prior to randomisation to Week 24; subjects 
on MTX should be taking folic acid supplementation according to local 
standard of care before randomisation and during the trial to minimize the 
likelihood of MTX associated toxicity
For subjects receiving oral corticosteroids: the subject must be on a stable 
dose (not to exceed the equivalent of 10 mg of prednisone per day) for ≥ 2
weeks prior to randomisation to Week 24
For subjects receiving non-steroidal anti-inflammatory drugs (NSAIDs) or 
paracetamol/acetaminophen PRN: the subject must be on stable dose for ≥ 2 
weeks prior to randomisation to Week 24
7. Active PsA that has been inadequately controlled by standard doses of 
NSAIDs administered for ≥ 4 weeks, or traditional DMARDs (including 
sulfasalazine) administered for ≥ 3 months, or TNFi agents, or subjects are 
intolerant to NSAIDs or DMARDs or TNFi agents, as assessed by the 
investigator
8. Signed and dated written informed consent prior to admission to the study in
accordance with Good Clinical Practice (GCP) and local legislation
9. 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 are
∃
not postmenopausal (12 months with no menses without an alternative 
medical cause) and are
∃
not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral 
oophorectomy or bilateral salpingectomy). 
3.3.3
Exclusion criteria
1. Major chronic inflammatory or connective tissue disease other than PsA
(e.g. rheumatoid arthritis, systemic lupus erythematosus, ankylosing 
spondylitis, Lyme disease, gout) and fibromyalgia, as assessed by the 
investigator
2. Has received any therapeutic agent directly targeted to IL-12/23 (including 
ustekinumab), IL-23 or IL-17 (including secukinumab)

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3. Prior use of more than two different TNFi agents
4. Use of the following treatments:
- TNFi agents (including, infliximab, adalimumab, certolizumab pegol or 
golimumab) within 12 weeks prior to randomisation 
- Etanercept within 8 weeks prior to randomisation
- Leflunomide without cholestyramine wash-out within 8 weeks prior to 
randomisation
- Systemic non-biologic medications for PsA or PsO (including apremilast 
and leflunomide with cholestyramine wash-out) and photochemotherapy 
within 4 weeks prior to randomisation
- Intraarticular injections (including steroids) and intramuscular or 
intravenous corticosteroid treatment within 4 weeks prior to randomisation
- Topical PsO medications and phototherapy within 2 weeks prior to 
randomisation
- Low and high potency opioid analgesics (e.g. methadone, hydromorphone, 
morphine) within 2 weeks prior to randomisation
5. Previous treatment with any cell-depleting therapies including but not 
limited to anti-CD20 (e.g. rituximab), investigational agents (e.g. 
CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)
6. Participation in another trial with an investigational drug or device within 4 
weeks (if the trial is for PsA treatment, within 12 weeks) or 5 half-lives 
(whichever is greater) prior to randomisation
7. 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, as assessed 
by the investigator
8. Plans for administration of live vaccines during the study period or within 6 
weeks prior to randomisation.
9. History of allergy/hypersensitivity to a systemically administered biologic 
agent or its excipients
10. Active systemic infections during the last 2 weeks (exception: common 
cold) prior to randomisation, as assessed by the investigator
11. Chronic or relevant acute infections including HIV (human 
immunodeficiency virus), viral hepatitis and (or) active tuberculosis. 
Patients with a positive QuantiFERON TB or PPD test 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 established, then tuberculosis treatment 
may be deferred until completion of the trial according to clinical judgment 
of investigator and local country guidelines.

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12. Any documented active or suspected malignancy or history of malignancy 
within 5 years prior to screening, except appropriately treated basal or 
squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix
13. Major surgery performed within 12 weeks prior to randomisation or planned 
within 32 weeks after randomisation (e.g. hip replacement, aneurysm 
removal, stomach ligation), as assessed by the investigator
14. Evidence of a current or previous disease, medical condition (including 
chronic alcohol or drug abuse) other than PsA and PsO, surgical procedure 
(i.e., organ transplant), medical examination finding (including vital signs 
and electrocardiogram (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.
15. Total white blood count (WBC) < 3,000/μL, or platelets < 100,000/μL or 
neutrophils < 1,500/μL, or  hemoglobin <8.5 g/dL at screening
16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x
the upper limit of normal, or serum direct bilirubin ≥ 1.5 mg/dL at screening
17. Positive rheumatoid factor or anti-cyclic-citrullinated peptide (anti-CCP) 
antibodies at screening
18. Women who are pregnant, nursing, or who plan to become pregnant while in 
the trial
19. Patients with cochlear implants, cardiac pacemakers, metallic foreign bodies 
in their eye or who have an aneurysm clip in their brain, and/or 
ferromagnetic surgical implants in the body or claustrophobia (MRI-sub-
study patients only)
20. Patients who are legally institutionalized
3.3.4
Removal of patients from therapy or assessments
Removal of individual patients
3.3.4.1
All patients have the right to discontinue the study treatment early and/or 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.
In order to minimize missing data in the evaluation of intention-to-treat “observed” 
data analysis, patients who discontinue study treatment early should complete early 
EOT visit as per Flow Chart at the first missed visit and continue to be followed for 

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all regularly scheduled follow-up visits (Visit 8, 9, 10 and EOS) for safety and 
efficacy assessments. These patients should be registered as early treatment 
discontinuations (treatment withdrawal) in IRT. If these patients do not agree to 
continue all scheduled visits, they need to be recommended to at least return to the 
clinic for EOS visit, 16 weeks after last dose of study medication for safety. Refer to 
Section 6.2.3. These patients are not eligible for the OLE study.
Early study treatment discontinuation is to be differentiated from study withdrawal. 
The only reasons for study withdrawal are patient withdrawal of consent to
contribute additional outcome information (including after early study treatment 
discontinuation) and loss to follow-up.
Study medication should be discontinued 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 risankizumab 
discontinuation including but not limited to SAEs or SUSARs.
∃
If the subject received a live vaccine during the study.
∃
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 study drug. In case of undue safety risk for the subject, the subject 
should discontinue study treatment at the discretion of the investigator.
∃
If the patient experiences an intolerable increase of PsA during the course of 
the trial treatment the patient will be discontinued from the trial treatment to 
receive rescue treatment as deemed appropriate by the investigator.
If a patient becomes pregnant, refer to Section 5.3.7 for instructions on treatment 
termination.
Patients who discontinue the trial after receiving the first dose of study medication 
at Visit 2 will not be replaced.
For all patients the reason for early study treatment discontinuation and study 
withdrawal must be recorded in the electronic case report form (eCRF). These data 
will be included in the trial database and reported.
Discontinuation of the trial by the sponsor
3.3.4.2
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,

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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 
ofrisankizumab, or
3. Violation of GCP, the Clinical Trial Protocol (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 and placebo to match BI 655066 will be administered
subcutaneously. All products will be supplied by Boehringer Ingelheim.
4.1.1
Identity of BI investigational products
Table 4.1.1: 1 Description of test product BI 655066
Substance:
BI 655066
Pharmaceutical form:
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,
concentration 90 mg/mL
Route of administration:
Subcutaneous injection
Posology:
Arm 1: 150 mg (two 75 mg syringes) at Week 0, 
4, 8, 12 and 16
Arm 2: 150 mg (two 75 mg syringes) at Week 0, 
4, 16
Arm 3: 150 mg (two 75 mg syringes) at Week 0 
and 12
Arm 4: 75 mg (one 75 mg syringe) at Week 0
Duration of use:
16 weeks 

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Table 4.1.1: 2 Description of test product placebo to BI 655066
Substance:
Placebo to BI 655066
Pharmaceutical form:
0.9% sodium chloride solution presented in a 1 
mL syringe pre-filled with 0.87 mL. Dispensed 
volume is 0.83 mL.
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:
Arm 5: Weeks 0, 4, 8, 12 and 16
Arms 2-4: cf. Table 4.1.4: 1
Duration of use:
16 weeks
4.1.2
Method of assigning patients to treatment groups
Through the utilisation of IRT, patients will be randomised to receive BI 655066 or 
placebo in a ratio of 2:2:2:1:2 stratified based on prior TNFi use (naïve or 
experienced) and concurrent MTX use (yes or no) in five treatment arms.
After the eligibility criteria are confirmed, the investigator or designee will 
randomise the patient on Day 1 (Visit 2) through IRT call or website entry.
Details regarding the use of the IRT are described in the site-user manual available 
in the ISF.
4.1.3
Selection of doses in the trial
There are four active dosing regimens in this Phase II trial as described previously 
in Figure 3.1: 1 and discussed below. The dose selection for this first BI 655066 
trial in patients with PsA considers all available BI 655066 safety and efficacy 
clinical data available from trials in other indications (PsO, Crohn’s disease and 
ankylosing spondylitis), as well as formulation and patient acceptability 
considerations.

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4.1.4
Drug assignment and administration of doses for each patient
An IRT will be used to allocate medication to patients through medication numbers. 
At visits where study medication is to be administered, study sites will be required 
to complete the medication resupply module in the IRT to receive assigned 
medication numbers. Site personnel will enter the medication numbers in the eCRF. 
Dosing visits are specified in the Flow Chart.
BI 655066 and/or matching placebo will be administered subcutaneously in a 
double blind fashion and are presented in Table 4.1.4: 1. At each dosing visit, two 
subcutaneous injections will be given.

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Table 4.1.4: 1
Dosing schedule 
Week
0
4
8
12
16
Arm 1: 150 mg W 0, 4, 8, 12, 16
2 x 75 mg
2 x 75 mg
2 x 75 mg
2 x 75 mg 
2 x 75 mg
Arm 2: 150 mg W 0, 4, 16  
2 x 75 mg
2 x 75 mg
2 x placebo
2 x placebo
2 x 75 mg
Arm 3: 150 mg W 0, 12
2 x 75 mg
2 x placebo
2 x placebo
2 x 75 mg
2 x placebo
Arm 4: 75 mg single dose W 0
1 x 75 mg
1 x placebo 
2 x placebo
2 x placebo
2 x placebo
2 x placebo
Arm 5: placebo
2 x placebo
2 x placebo
2 x placebo
2 x placebo
2 x placebo
Dose modifications or adjustments are not permitted. In exceptional cases of missed 
or delayed visits, study drug of the following visit should not be administered within 
7 days of the prior dose. There should be at least 7 days between two consecutive 
study drug administrations. The information on technique of injection and injection 
materials (syringes, needles) is provided in the ISF. Study medication will be 
administered exclusively at the study site, by authorised study personnel (e.g. study 
nurse).
BI 655066 and/or matching placebo will be administered as a subcutaneous 
injection in the abdomen and thighs. Injections 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.
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 
randomised treatment assignments until after 16-week primary analysis database 
lock. In addition, patients and investigators will further remain blinded until after 
the final database lock. After the last patient completes the 16-week visit, the 
database will be locked for analysis of the primary endpoint and BI study and 
project teams will become unblinded to treatment and dose assignments. 
The randomisation code will be kept secret by Clinical Trial Support up to the final 
database lock.
The randomisation 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 randomisation code or the 
results of their measurements until the trial is officially unblinded for primary 

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analysis. 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.
An independent DMC will provide an unblinded safety and efficacy assessment at 
specified interval, please refer to Section 3.1.1.1.
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 eCRF 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 and 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.
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 ISF.

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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 / pharmacist / 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 (only for US sites)
All unused medication must be returned to the sponsor. Receipt, usage, and return 
must be documented. Account must be given for any discrepancy. Used medications 
will be destroyed per local guidelines.
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 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.
All concomitant, and/or rescue therapies will be recorded on the appropriate pages 
of the eCRF.

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Stable doses of concomitant therapies for chronic conditions, for which neither the 
condition nor the treatment are judged to not 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 case of adverse events in need of treatment symptomatic therapy according to 
investigator judgment will be permitted.
If patients receive optional concurrent PsA treatment, these need to be on stable 
doses prior to randomisation to Week 24, as specified in Inclusion Criterion 6.
Methotrexate
Subjects taking MTX (up to 25 mg/week) must be on a stable dose and stable route 
of administration for at least 4 weeks before randomisation and maintained stable 
until Week 24.
Folic acid
Subjects on MTX must be taking folic acid supplementation according to local 
standard of care before randomisation and during the trial to minimize the 
likelihood of MTX associated toxicity.
Corticosteroids
Treatment with systemic corticosteroids is permitted up to a maximum daily dosage 
of 10 mg prednisone equivalent and if the dose was stable within the 2 weeks 
preceding randomisation. The subject should remain on a stable dose until Week 24.
Intra-articular corticosteroids are not permitted within the 4 weeks preceding 
randomisation and up to Week 24. 
Topical steroids of US class 6 (mild, such as desonide) or US class 7 (least potent, 
such as hydrocortisone) will be permitted for use limited to the face, axilla, and/or 
genitalia. These topical medications should not be used within approximately 24 
hours prior to visits requiring PASI assessment.
Non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol/ 
acetaminophen PRN
Subjects on regular use of NSAIDs or paracetamol/acetaminophen PRN (PRN 
referring to the latter only) should be on stable dose for at least 2 weeks before 
randomisation to allow inclusion. They should remain on a stable dose in the study 
up to Week 24; however, they have to refrain from any intake during at least 24 
hours before a visit with disease activity assessment.

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Rescue treatment 
If the patient experiences an intolerable increase in diseases activity of PsA during 
the course of the trial treatment the patient will be discontinued from the trial 
treatment to receive rescue treatment as deemed appropriate by the investigator.
These patients will complete early EOT visit and continue to be followed for all 
regularly scheduled follow-up visits for safety and efficacy assessments, as detailed 
in Section 3.3.4.1.
If patients have reduction in both tender and swollen joint count of <20% at the 
Week 16 assessment (escape criteria), they can start rescue treatment with local 
standard of care, except biologics, after receiving Week 16 study drug dose. For that 
purpose they can change the doses of concurrent medication and/or start new non 
biologic medication. These patients will continue with all scheduled follow-up
visits.
After Week 24, patients can start rescue treatment with local standard of care, 
including biologic treatment, if considered appropriate by the investigator, 
regardless of the joint count improvement. These patients too will continue with all 
scheduled follow-up visits.
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.

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Table 4.2.2.1: 1
Restricted medications
Investigational products not otherwise 
described below
4 weeks (if the trial is for PsA treatment, 12 
weeks) or 5 half-lives, whichever is greater 
prior randomisation and for the trial 
duration including the follow-up period
Investigational anti-IL-12/23, anti-IL-23, 
and anti-IL-17
Prior to the study and for the trial duration 
including the follow-up period
Cell-depleting therapies including but not 
limited to anti-CD20 (e.g. rituximab), 
investigational agents (e.g. CAMPATH, 
anti-CD4, anti-CD5, anti-CD3, anti-CD19)
Prior to the study and for the trial duration 
including the follow-up period
Ustekinumab and secukinumab
Prior to the study and within 24 weeks after 
randomisation
TNFi, except etanercept
12 weeks prior randomisation and within 
24 weeks after randomisation 
Etanercept 
8 weeks prior randomisation and within 24 
weeks after randomisation 
Apremilast or other PsA non biologic 
systemic treatment, including leflunomide 
with wash-out with cholestyramine*
4 weeks prior randomisation and within 24 
weeks after randomisation†
Leflunomide without wash-out with 
cholestyramine
8 weeks prior randomisation and within 24 
weeks after randomisation†
Intraarticular injections (including steroids)
4 weeks prior randomisation and within 24 
weeks after randomisation†
Intramuscular or intravenous corticosteroid 
treatment
4 weeks prior randomisation and within 24 
weeks after randomisation†
Oral or injectable PsO medications (not 
biologicals) including retinoids and 
fumarates, or any other drugs known to 
possibly benefit PsO
Photochemotherapy (e.g. PUVA)
Any drug known to interfere with or to 
aggravate PsO including but not limited to 
lithium and interferons
4 weeks prior randomisation and within 24 
weeks after randomisation
Phototherapy (e.g. UVA, UVB)
Topical PsO treatments such as steroids or 
other topicals as retinoids, vitamin D 
analogs, vitamin A analogs and anthralin
2 weeks prior randomisation and within 24 
weeks after randomisation (for exceptions 
cf. Section 4.2.1)
Low and high potency opioid analgesics 
(e.g. methadone, hydromorphone, 
morphine)
2 weeks prior randomisation and within 24 
weeks after randomisation†
Live vaccines 
6 weeks prior randomisation and for the 
trial duration including the follow-up 
period
* Stable doses of methotrexate, corticosteroids, NSAIDs, or paracetamol/acetaminophen PRN are allowed (cf. 
as specified in Inclusion Criterion 6 and Section 4.2.1)
† these treatments or their change are allowed from Week 16, if escape criteria are met (cf. Section 4.2.1, 
Rescue treatment)

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Leflunomide wash-out with cholestyramine
In case of leflunomide treatment, a drug wash-out of 8 weeks has to be performed. 
However, another wash-out procedure might be considered. Cholestyramine could 
be given orally to wash-out the drug at a dose of 8 g t.i.d. Cholestyramine reduced 
plasma levels of the active leflunomide metabolite by approximately 40 % in 24 
hours and by 49 % to 65 % in 48 hours in three healthy volunteers. Therefore, the 
administration of cholestyramine is recommended in subjects who require a drug 
elimination procedure. If a subject receives 8 g t.i.d. for 11 days he/she could be 
safely randomised 4 weeks after the beginning of the 11 days treatment period.
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.
In addition, both female patients of childbearing potential and male patients with 
female partners of childbearing potential, taking MTX as background medication, 
must follow the national regulatory guidelines regarding contraception while taking 
these medications.
TREATMENT COMPLIANCE
4.3
Study medication will be administered in accordance with the protocol by 
authorised study personnel (e.g. study nurse). The measured plasma concentrations 
will provide additional information about compliance.
Any missed dose has to be documented and reported to the CML.

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5.
VARIABLES AND THEIR ASSESSMENT
TRIAL ENDPOINTS
5.1
5.1.1
Primary endpoint
∃
ACR 20 response at Week 16
5.1.2
Secondary endpoints
∃
ACR 50 response at Week 16 
∃
ACR 70 response at Week 16
∃
Change in Tender Joint Count at Week 16 as compared to baseline
∃
Change in Swollen Joint Count at Week 16 as compared to baseline
∃
Change in HAQ-DI at Week 16 as compared to baseline
∃
Change in SF-36 at Week 16 as compared to baseline
∃
Change in Dactylitis count at Week 16 as compared to baseline (in patients 
with dactylitis at baseline)
∃
Change in SPARCC Enthesitis Index at Week 16 as compared to baseline
(in patients with enthesitis at baseline)
∃
Change in mNAPSI at Week 16 as compared to baseline (in patients with 
nail psoriasis)
∃
PASI90 response at Week 16 assessed in patients with a ≥ 3% baseline PsO 
BSA
5.1.3
Further endpoints
∃
ACR 20 and secondary measures at all other measured time points
∃
Change in Physician’s Global (VAS) at all measured time points as 
compared to baseline
∃
Change in Patient’s Pain (VAS) at all measured time points as compared to 
baseline
∃
Change in Patient’s Global Activity (VAS) assessments at all measured time 
points as compared to baseline 
∃
Change in C-Reactive Protein (CRP) at all measured time points as 
compared to baseline
∃
Change in minimal disease activity (MDA) at at all measured time points 
compared to baseline
∃
Change in DAS28-CRP at all measured time points as compared to baseline
∃
PsO endpoints assessed at all measured time points in patients with a ≥3% 
baseline PsO BSA: 
-
PASI75 response
-
Change in sPGA clear and almost clear 

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∃
EULAR (European League Against Rheumatism) response at all measured 
time points
∃
Change in PsARC (Psoriatic Arthritis Response Criteria) at all measured time 
points as compared to baseline
∃
Presence of dactylitis (yes/no) at all measured time points
∃
Change in LDI at all measured time points as compared to baseline (in 
patients with dactylitis at baseline)
∃
Change in LEI at all measured time points as compared to baseline (in 
patients with enthesitis at baseline)
∃
Change in FACIT-F at all measured time points as compared to baseline
∃
Change in BASDAI at Weeks 16 and 24 (in patient with baseline 
inflammatory spondylitis) as compared to baseline
∃
Change in mTSS at Week 24 as compared to baseline
∃
Change in PsAMRIS parameters at Week 16 as compared to baseline
ASSESSMENT OF EFFICACY
5.2
Table 5.2.1 presents clinical and patient reported efficacy endpoints assessed over 
the course of the study. Details of the efficacy assessments are listed in the 
Appendix (Section 10).
Assessments are completed in all patients as per Flow Chart except: 
∃
PASI and sPGA are assessed only in patients with ≥3% BSA of psoriatic 
plaques at baseline and/or with ≥3% BSA psoriatic plaques at the current 
visit. 
∃
BASDAI is assessed only in patients with baseline inflammatory spondylitis 
based on investigator judgement.

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Table 5.2: 1
Efficacy endpoint assessments 
ASSESSMENT OF SAFETY
5.3
Safety will be assessed descriptively based on:
∃
Adverse events
∃
Serious adverse events (SAEs)
∃
Clinical laboratory values (haematology, clinical chemistry and urinalysis) 
∃
Intensity of adverse events will be assessed by Rheumatology Common 
Toxicity Criteria (RCTC) version 2.0 (refer to ISF for details)
∃
Physical examination
∃
Vital signs
∃
12-lead ECG
Trial periods
Treatment
Follow-up
Visit
V2
V3
V4
V5
V6
V7
V8
V9
V10
EOS
Week
0
2
4
8
12
16
20
24
28
32
Tender Joint Count (68) 
x
x
x
x
x
x
x
x
x
x
Swollen Joint Count (66)
x
x
x
x
x
x
x
x
x
x
Patient’s assessment of pain (VAS)
x
x
x
x
x
x
x
x
x
x
Patient’s global assessment of disease 
activity (VAS)
x
x
x
x
x
x
x
x
x
x
Physician’s global assessment of 
disease activity (VAS)
x
x
x
x
x
x
x
x
x
x
HAQ-DI
x
x
x
x
x
x
x
x
x
x
CRP
x
x
x
x
x
x
x
x
x
x
Leeds Dactylitis Index, dactylitis
count, dactylitis presence
x
x
x
x
x
x
x
x
x
x
Leeds Enthesitis Index (0-6)
x
x
x
x
x
x
x
x
x
x
SPARCC Enthesitis Index (0-16)
x
x
x
x
x
x
x
x
x
x
BSA
x
x
x
x
x
x
x
x
x
x
PASI, assessed in patients with ≥3% 
BSA of psoriatic plaques at baseline
and/or at current visit
x
x
x
x
x
x
x
x
x
x
sPGA assessed in patients with ≥3% 
BSA of psoriatic plaques at baseline 
and/or at current visit
x
x
x
x
x
x
x
x
x
x
mNAPSI
x
x
x
x
x
x
x
x
x
SF-36 Version 2
x
x
x
x
FACIT-F
x
x
x
x
BASDAI, assessed only in patients 
with baseline inflammatory spondylitis 
based on investigator judgement
x
x
x
DAS28-CRP (calculated)
x
x
x
x
x
x
x
x
x
x
EULAR response criteria (calculated)
x
x
x
x
x
x
x
x
x
ACR 20, 50, 70 (calculated)
x
x
x
x
x
x
x
x
x
PsARC (calculated)
x
x
x
x
x
x
x
x
x
MDA (calculated)
x
x
x
x
x
x
x
x
x
x

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∃
Local tolerability
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 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.
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 Visits 2, 4 and 6 additional evaluations will be taken at 5 minutes post-dose 
and 60 minutes post-dose.
Patients should be closely monitored for signs and symptoms of hypersensitivity 
reactions for approximately 2 hours after the first dose administered and 1 hour 
following all other doses of study drug. 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.
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death 
(R11-4890). To be able to prospectively define and assess any potential cases of 
anaphylaxis, the clinical criteria for diagnosis of anaphylaxis defined in Section 
10.16 are to be considered.
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. A 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).

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Instructions regarding sample collection, sample handling/ processing and sample 
shipping are provided in the Laboratory Manual in 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 
AE’s. 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).

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Table 5.3.3: 1 Laboratory tests
Category
Test name
Haematology
Hematocrit (Hct)
Hemoglobin (Hb)
Glycosylated Hbc (HbA1c) (only at screening)
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
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) (only at 
screening)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Troponin (Reflex, in case of elevated CK) 
Protein, Total
Albumin
C-Reactive Protein (CRP) (high sensitivity)
Cholesterol, total
Triglycerides
LDL-Cholesterol
HDL-Cholesterol

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Table 5.3.3:1 Laboratory tests (cont.)
Category
Test name
Urine Pregnancy test (only for female patients of 
childbearing potential)
Human Chorionic Gonadotropin in urine
Serum Pregnancy test (only for female patients 
of childbearing potential at screening or if urine 
pregnancy test is positive)
Human Serum Chorionic Gonadotropin
Hormones (only at screening)
TSH (free T3 and free T4 in case of abnormal 
TSH result) 
Autoantibodies (only at screening)
Rheumatoid Factor
anti-CCP antibodies
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 (only at screening)
Albumin (quantitative)
Creatinine
Albumin/creatinine ratio
Infections screening (only at screening)
Hepatitis B Surface Antigen (qualitative)
Hepatitis C Antibodies (qualitative)
HIV-1, and HIV-2 Antibody (qualitative)
QuantiFERON®-TB1
PPD skin test1
1 QuantiFERON®-TB or PPD (Purified Protein Derivative) skin test may be performed.
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.

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The electronic version, if applicable, or dated and signed printouts of the ECG will 
be regarded as source data and 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.
Adverse reaction
An adverse reaction is defined as a response to a medicinal product which is 
noxious and unintended. Response in this context means that a causal relationship 
between a medicinal product and an adverse event is at least a reasonable possibility. 
Adverse reactions may arise from use of the product within or outside the terms of 
the marketing authorisation or from occupational exposure. Conditions of use 
outside the marketing authorization include off-label use, overdose, misuse, abuse 
and medication errors.
Serious adverse event
A serious adverse event (SAE) is defined as any AE which:
∃
results in death,
∃
is life-threatening, this refers to an event in which the patient was at risk of 
death at the time of the event; it does not refer to an event that hypothetically 
might have caused death if more severe.
∃
requires inpatient hospitalisation or
∃
prolongation of existing hospitalisation,
∃
results in persistent or significant disability or incapacity, or
∃
is a congenital anomaly/birth defect,
or

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∃
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.
Medical and scientific judgement should be exercised in deciding whether other 
situations should be considered serious reactions, such as important medical events 
that might not be immediately life threatening or result in death or hospitalisation 
but might jeopardise the patient or might require intervention to prevent one of the 
other outcomes listed above.
Examples of such events are intensive treatment in an emergency room or at home 
for allergic bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalisation or development of dependency or abuse. Any suspected transmission 
via a medicinal product of an infectious agent is also considered a serious adverse 
reaction.
For Japan only, the following events will be handled as “deemed serious for any 
other reason”. An AE which possibly leads to disability will be reported as an SAE.
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 considered to be “serious” even though they may not have met the criteria 
of an SAE as given above.
Cancers of new histology and exacerbations of existing cancer must be reported as a 
serious event regardless of the duration between discontinuation of the drug and the 
occurrence of the cancer.
The latest list of “Always Serious AEs” can be found in the Remote Data Capture 
(RDC) system. These events should always be reported as SAEs as described above.
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: 

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∃
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” (Drug 
Induced Liver Injury) 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
Causal relationship of AEs
The definition of an adverse reaction implies at least a reasonable possibility of a 
causal relationship between a suspected medicinal product and an adverse event. An 
adverse reaction, in contrast to an adverse event, is characterised by the fact that a 
causal relationship between a medicinal product and an occurrence is suspected.
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.
Arguments that may suggest that there is a reasonable possibility of a causal 
relationship could be:
∃
The event is consistent with the known pharmacology of the drug
∃
The event is known to be caused by or attributed to the drug class
∃
A plausible time to onset of the event relative to the time of drug exposure
∃
Evidence that the event is reproducible when the drug is re-introduced

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∃
No medically sound alternative aetiologies that could explain the event (e.g. 
pre-existing or concomitant diseases, or co-medications)
∃
The event is typically drug-related and infrequent in the general population 
not exposed to drugs (e.g. Stevens-Johnson syndrome)
∃
An indication of dose-response (i.e. greater effect size if the dose is 
increased, smaller effect size if dose is diminished).
Arguments that may suggest that there is no reasonable possibility of a causal 
relationship could be:
∃
No plausible time to onset of the event relative to the time of drug exposure 
is evident (e.g. pre-treatment cases, diagnosis of cancer or chronic disease 
within days / weeks of drug administration; an allergic reaction weeks after 
discontinuation of the drug concerned) 
∃
Continuation of the event despite the withdrawal of the medication, taking 
into account the pharmacological properties of the compound (e.g. after 5 
half-lives). Of note, this criterion may not be applicable to events whose 
time course is prolonged despite removing the original trigger.
∃
Additional arguments amongst those stated before, like alternative 
explanation (e.g. situations where other drugs or underlying diseases appear 
to provide a more likely explanation for the observed event than the drug 
concerned).
∃
Disappearance of the event even though the study drug treatment continues 
or remains unchanged.
For Japan only, the reason for the decision on causal relationship for unlisted AEs 
needs to be provided in the eCRF.
5.3.7
Adverse event collection and reporting
AE Collection
The following must be collected and documented on the eCRF by the Investigator:
∃
From signing the informed consent onwards through the Residual Effect Period 
(REP) until the end of a patient’s trial participation, all AEs (serious and non-
serious) and all AESIs.
∃
After the end of an individual patient’s trial participation 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.

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The REP is defined as 15 weeks after the last trial medication application. 
Therefore, EOS visit was selected to be at Week 32 (±7 days) (16 weeks of 
treatment plus 15 weeks of REP plus 1 week visit window). 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). 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.
For Japan only, all SAEs and AESIs must be reported immediately to the head of 
the trial site.
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

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∃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 patient 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 patient will be followed up until birth or otherwise termination of 
the pregnancy.
The ISF will contain the Pregnancy Monitoring Form for Clinical Trials (Part A and 
B).
DRUG CONCENTRATION MEASUREMENTS AND 
5.4
PHARMACOKINETICS
5.4.1
Assessment of Pharmacokinetics
Risankizumab concentrations will be tabulated and summary statistics will be 
provided by treatment group and visit and no PK parameters will be calculated. The 
concentration data generated in this will be incorporated into a pharmacometric 
analysis with other trials of risankizumab 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 

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be made available to individuals outside of the trial team for the purpose of PK 
dataset generation in accordance with sponsor’s standard procedures. ADA data will 
be reported as needed.
Detailed information on timing for dosing, PK and ADA sampling is provided in 
Flow Chart. Date and exact clock 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 will occur prior to the drug 
administration.
5.4.2
Methods of sample collection
Plasma sampling for pharmacokinetic analysis 
5.4.2.1
For quantification of analyte plasma concentrations, approximately 2.5 mL of blood 
will be taken at the time points listed in the Flow Chart under PK sampling (a 
nominal time of one hour pre-dose will be used). For details on sample handling and 
logistics refer to the ISF (Laboratory Manual).
After completion of the study, plasma samples may be used for further 
methodological investigations, e.g., stability testing. However, only data related to 
the analyte will be generated by these additional investigations. 
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. For details on sample 
handling and logistics refer to ISF (Laboratory Manual).
5.4.3
Analytical determinations
Risankizumab concentrations will be determined by a validated Enzyme Linked 
Immunosorbent Assay (ELISA).
The presence of ADA to risankizumab 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 assay.
ASSESSMENT OF EXPLORATORY BIOMARKERS
5.5
This section refers to exploratory biomarkers.

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5.5.1
Assessment of soluble and cellular blood biomarkers and RNA
Serum will be collected pre and post treatment. Samples may be used to to assess 
changes in protein levels of soluble biomarkers associated with inflammation (such 
as ß-defensin 2, neutrophil gelatinase associated lipocalin-2 (NGAL) and S-100 A8
protein), bone resorption (such as, MMP-3, cartilage oligomatrix protein, 
osteoprotegerin, RANKL) and bone formation (such as dickkopf 1, osteocalcin, 
bone morphogenetic protein 7, sclerostin). Samples for these assessments will be 
collected as per Flow Chart. 
RNA (Ribonucleic Acid) will be isolated from whole blood to assess changes in 
expression levels pre and post treatment with risankizumab at time points indicated 
in the Flow Chart. Please note that messenger RNA expression levels are dynamic 
and not comparable to a “static” pharmacogenetic test as only the amount and not 
the composition of RNA will be tested.
For cellular biomarker assessment, blood will be collected to evaluate markers 
including but not limited to IL-23R expression on specific cell types (i.e. T cell and 
monocyte subsets) utilizing FACS (fluorescence-activated cell sorting) analysis at 
time points indicated in the Flow Chart.
Evaluations performed with the above samples may also include analysing 
biomarkers related to the pathway(s) targeted by the study drug, believed to be 
related to the disease, or in the development of new therapies.
Methods of sample collection
5.5.1.1
For the assessment of soluble proteins, approximately 8.5 mL of blood will be 
collected from a vein 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).
For the assessment of RNA expression from whole blood, approximately 2.5 mL of 
blood will be collected from a vein in PAXgene RNA tubes 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).
For FACS analysis, approximately 8.5 mL of blood will be collected from a vein at 
the time points indicated in the Flow Chart. For details on sample handling and 
logistics refer to the ISF (Laboratory Manual).
Analytical determinations
5.5.1.2
These biomarkers are considered exploratory and respective assays will need to be 
qualified to meet the required performance criteria.

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5.5.2
Biomarker sample banking 
After completion of the study any unused serum, peripheral blood mononuclear 
cells (PBMCs), and RNA 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 and inflammatory diseases), if participation and 
informed consent for biomarker sample banking is agreed upon by the patient. The 
types of biomarkers to be analysed may include, but are not limited to: RNA 
proteins, lipids or metabolites.
Declining 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.
5.5.3
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.
Method of sample collection
5.5.3.1
Approximately 8.5 mL of blood will be taken at Visit 2. For details on sample 
handling and logistics refer to the ISF (Laboratory Manual).
Analytical determinations
5.5.3.2
The DNA banking sample, derived from the original blood sample, will be stored at
Boehringer Ingelheim, AbbVie or a third party delegate. 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.

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OTHER ASSESSMENTS
5.6
X-ray assessments 
The modified total Sharp score (mTSS) has been used to evaluate radiographic 
evidence of damage in rheumatoid arthritis and has been adapted to PsA, including 
distal interphalangeal joints (R15-1027). mTSS has been demonstrated to be 
sensitive enough to assess treatment effect over a short time (R15-1027). X-rays of 
hands, wrists and feet will be performed at the time points specified in the Flow 
Chart. Images will be read centrally for each patient at two time points (Weeks 0 
and 24) in a random order and without knowledge of time point, patient identity, or 
treatment assignment. If a patient has to be rescued by a biologic treatment after 
Week 12 and prior to Week 24, X-ray images need to be obtained prior to the start 
of rescue biologic treatment. If the rescue treatment is initiated prior to Week 12, 
post-treatment X-rays are not required. The details of X-ray collection and 
evaluation are provided in ISF.
MRI assessments 
The international “MRI in inflammatory arthritis” group of OMERACT (Outcome 
Measures in Rheumatology) has developed the OMERACT Psoriatic Arthritis 
Magnetic Resonance Image Scoring System (PsAMRIS) for evaluation of 
inflammatory and destructive changes in PsA hands and feet (R15-1026, R15-
5992). Hand (or foot, if no swollen joint is available in hands at baseline) MRI will 
be performed as presented in the Flow Chart in the first approximately 90 patients 
from the sites selected for MRI sub-study. Images will be read centrally for each 
patient at two time points (Weeks 0 and 16) in a random order and without 
knowledge of patient identity or treatment assignment. If a patient has to be rescued 
by a biologic treatment after Week 4 and prior to Week 16, MRI images need to be 
obtained prior to the start of rescue biologic treatment. If the rescue treatment is 
initiated prior to Week 4, post-treatment MRIs are not required. The details of MRI 
scanning and evaluation are provided in ISF.
APPROPRIATENESS OF MEASUREMENTS
5.7
All measurements performed during this trial are standard measurements in PsA
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.

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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. If any visit has to be 
rescheduled, subsequent visits should follow the original visit date schedule. 
Additional visits for the purpose of re-testing of laboratory parameters or AE 
monitoring may be included as deemed necessary by the investigator.
Regarding instructions for drug administration at missed or delayed visits, please 
refer to Section 4.1.4.
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 10 (Appendix) 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 all dosing visits.
Patient Reported Outcomes (PROs) should be completed by the patient on his/her
own in a 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 order of completion for PROs should be as follows, as applicable for each PRO 
at relevant visits according to the Flow Chart:
1) Patient’s global assessment of disease activity (VAS)
2) Patient’s assessment of pain (VAS)
3) HAQ-DI 
4) BASDAI
5) SF-36
6) FACIT-F
All visits starting from Visit 2 will be performed in fasted state (8 hours no food and 
only water). 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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6.2.1
Screening and run-in period
No trial procedures should be done unless the patient has consented to taking part in 
the trial.
Once consented, the patient is considered to be enrolled in the trial and has started 
screening. The patient should be recorded on the enrolment log and be registered in 
IRT as a screened patient.
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. Visit 1 procedures may be 
completed over two physical visits, if needed.
The time window for Visit 1 may be extended at the discretion of the CML in 
conjunction with the TCM (Trial Clinical Monitor) on a case by case basis or re-
screening is performed. Re-screening will be allowed once.  
Patients who have a laboratory test value that makes their participation uncertain
may have the test repeated once to determine eligibility; however, the result must be 
available prior to Visit 2 (Day 1). 
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.
6.2.2
Treatment period
After eligibility is confirmed, randomisation via IRT will be performed at Visit 2. 
The treatment period is from Visit 2 (Week 0) to 7 (Week 16/EOT, End of 
Treatment).
Urine pregnancy testing for all women of child-bearing potential will be conducted 
on-site prior to every dosing and must be negative to further treat the patient. A 
positive urine test must be confirmed with a serum pregnancy test.
Venipuncture (i.e. safety laboratories, PK, ADA, biomarkers) should be the last 
procedure prior to study drug administration.
6.2.3
Follow-up Period and Trial Completion
For all randomised patients termination of trial medication and trial completion 
must be recorded on the corresponding eCRFs.

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Early treatment termination
6.2.3.1
Patients who discontinue treatment prior to the planned Flow Chart visit schedule 
will complete early EOT procedures instead of the planned treatment period visit. 
These patients should be registered as withdrawn in IRT and return to the clinic for
all follow-up visits (Visits 8, 9, 10 and EOS). These patients will not be eligible to 
participate in the OLE study.
Trial completion
6.2.3.2
Patients who finish the randomised treatment period will return to the clinic for 
follow-up visits (Visits 8, 9, 10 and EOS). Completion is defined as a patient having 
reached the EOS visit, except for patients who enrol in the OLE study where study 
completion is defined as the final visit, on or after completion of Visit 9 (Week 24).

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7.
STATISTICAL METHODS AND DETERMINATION 
OF SAMPLE SIZE
STATISTICAL DESIGN - MODEL
7.1
This trial is a proof-of-concept, multi-center, randomised double-blind, placebo-
controlled, parallel-group Phase II dose-ranging study of risankizumab in patients 
with active PsA. The main objective of this trial is to show superior efficacy of 
treatment of risankizumab as compared to placebo for demonstration of proof-of-
concept. All eligible patients will be randomised in a 2:2:2:1:2 ratio at Week 0 to 
receive one of the four active regimens of risankizumab or placebo. There are five 
treatment arms as shown in Figure 3.1: 1. Randomisation is stratified based on prior 
TNFi experience (naïve or experienced) and concurrent MTX (yes or no) use as 
determined at baseline.
The statistical model for the binary endpoint is a stratified Cochran-Mantel-
Haenszel test with stratification factors of naïve or experienced to TNFi and 
concurrent MTX use (yes or no) as the stratification variables.
NULL AND ALTERNATIVE HYPOTHESIS
7.2
Null hypothesis: The proportion of participants who achieve ACR 20 at Week 16 is 
equal between the combined arms of Arm 1 and Arm 2 of risankizumab and 
placebo.
Alternative hypothesis: The proportion of participants who achieve ACR 20 at 
Week 16 in the combined arms of Arm 1 and Arm 2 of risankizumab is superior to 
placebo.
The overall level of significance is set to be alpha=0.05 (one-sided). The 
combination of Arm 1 and Arm 2 is simply for the primary inferential analyses, as 
these two arms represent the most intense regimens for the stated goal of achieving 
the proof-of-concept.
PLANNED ANALYSES
7.3
The primary analyses will be based on the intent-to-treat principle, comprising all 
participants who were randomised and received at least one dose of assigned 
therapy during the trial (full analysis set (FAS)). Safety analyses will be based on 
actual treatment received. Definitions of analysis sets will be specified in the TSAP.
The trial design incorporates multiple doses and dose frequencies; therefore, to 
obtain a proper evaluation of the effect of dose and dose frequency on ACR 
response, a systematic approach to the pairwise evaluation of treatment regimens 
must be undertaken. Although only the two most intense dose regimens (Arm 1 and 

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Arm 2) are considered for the evaluation of the pre-specified proof-of-concept at 
Week 16, Arm 3 and Arm 4 are expected to provide critical information on our dose 
selection objectives including the magnitude of maximum ACR response as well as 
the timing of maximum ACR response.
To address the dose response for the 75 mg dose, Arms 3 and 4 will be analysed at 
Weeks 8 and 12. Furthermore, to evaluate the effect of the loading dose, Arm 2 will 
be compared to Arm 3 at Weeks 8 and 12. If the loading dose shows response 
improvement (Arm 2 compared to Arm 3) then the examination of the possible need 
for a higher dose frequency can be evaluated by comparing Arm 1 against Arm 2 
from Week 12 onwards. Lastly, the achieved response of all regimens will be 
evaluated at Week 24. The aforementioned analyses along with the evaluation of 
ACR 20, ACR 50, and ACR 70 over time will be instrumental not only in dose 
regimen selection but also in establishing the time point for the primary endpoint 
assessment for Phase III.
Pairwise comparison will be carried out between risankizumab dose groups and 
nominal p-values of these comparisons will be provided.
7.3.1
Primary endpoint analyses
The proportion of patients who achieve ACR 20 at Week 16 is the primary endpoint. 
The difference in proportion of participants that achieve ACR 20 between the 
combined groups of risankizumab (Arm 1 and Arm 2) and the placebo arm (Arm 5) 
will be estimated and tested using the stratified Cochran-Mantel-Haenszel risk 
difference estimate. Pairwise comparisons of the risankizumab dose groups will be 
conducted using the same stratified Cochran-Mantel-Haenszel methods. There will 
be no adjustments for multiplicity in these analyses.
The primary analysis will be performed when the last patient completes the Week 
16 visit, when the primary endpoint (ACR 20 at Week 16) is assessed. The trial will 
be unblinded to the sponsor project and trial team to perform this analysis. Blinded 
treatment assignments will not be disseminated to the sites, investigators, and 
patients at this time. More details about the Week 16 analysis will be specified in 
the TSAP.
7.3.2
Secondary endpoint analyses
Binary endpoints will be analysed in a similar fashion as the primary endpoint.
Continuous endpoints will be analysed using a mixed model repeated measures 
model (MMRM) which is valid under the missing at random (MAR) assumption. 
Under the MMRM model, there’s no explicit imputation of missing data, rather, the 
future statistical behavior of those participants who drop out given their past 

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measurements is assumed to be the same as those who remain with the same 
history.
Specifically, for continuous endpoints, such as HAQ-DI at Week 16, a MMRM
which is valid under the missing at random (MAR) assumption will be 
implemented. In particular, between-treatment differences in the change in HAQ-DI 
at Week 16 (from baseline) will be evaluated using a MMRM with treatment 
regimen, clinical visit and stratification factors as fixed factors, and baseline HAQ-
DI score as a fixed continuous covariate. In addition, participants will be included in 
the model as a random effect. Furthermore, the treatment by clinical visit interaction 
will be included in the model. An unstructured covariance structure will be used to 
model the within-patient measurements. Parameter estimation of the MMRM will 
be based on the residual maximum likelihood method (REML). If all post-baseline 
values are missing then the missing value will not be imputed and the data for the 
respective participant will be removed from the analysis, thus, the total number of 
participants providing data for analysis could be smaller than the total number of 
participants in the FAS. If the analysis fails to converge, alternate covariance 
structures will be tested, details will be provided in the TSAP.
7.3.3
Further endpoint analyses
Analyses at Week 24 will be conducted in a similar fashion as for Week 16
endpoints. Further efficacy endpoints will be summarized descriptively. Continuous 
endpoints will be summarized with the use of box plots, while proportions will be 
displayed by histograms as appropriate. Additional further endpoints may be 
defined in the trial statistical analysis plan (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 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 (REP) will be considered ‘treatment-
emergent’. The REP is defined as 15 weeks after the last trial medication 
application and will include adverse events reported through EOS visit. Adverse 
events that start before first drug intake and deteriorate under treatment will also be 
considered as ‘treatment-emergent’.

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Frequency, severity, and causal relationship of adverse events will be tabulated by 
system organ class and preferred term after coding according to the current version 
of the Medical Dictionary for Drug Regulatory Activities (MedDRA).
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 risankizumab concentration measurements by treatment 
group and visit will be provided in clinical trial report. Pharmacokinetic data will 
also be analysed using population pharmacokinetic approaches. For this purpose,
data may also be combined with data from other trials and will be summarized as a 
stand-alone report.
7.3.6
Pharmacodynamic analyses
As the data from previous risankizumab trials, primarily in psoriasis, suggest a 
pharmacokinetic (PK)-pharmacodynamic (PD) relationship for efficacy endpoints,
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.
Model-based PK-PD analyses (PMx) will be part of a stand-alone report(s) and not 
part of the clinical trial report. Trial specific PK-PD analyses based on observed 
data will be reported in the clinical trial report, as appropriate. Other exploratory 
analyses of drug concentration, biomarker or safety data may be performed using 
data obtained as part of this trial.
In total, data from 40 patients in Arms 1, 2, 3 and 5 and 20 patients in Arm 4 (for a 
total of 180 patients) are considered sufficient to explore the exposure-response 
relationship through modelling.

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7.3.7
Biomarker analyses
Changes in cellular, serum, 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 handling of 
missing data for the primary endpoint and secondary endpoints for data up to Week 
24 will be handled as follows.
Participants that use protocol-prohibited medications, a non-responder imputation 
(NRI) will be used to impute their binary endpoint. Missing data due to loss of 
follow-up or due to the withdrawal of consent will be addressed by considering the 
participant a non-responder for their binary endpoint. For all other cases, regardless 
of the type of the endpoint, the de facto estimand, ITT (Intention-To-Treat), will be 
used. Namely, analyses will be conducted using the observed response regardless of 
adherence to treatment or early discontinuation. Hence, it is critical to continue 
collecting data on participants even if they withdraw from the study, except for the 
cases for which informed consent is withdrawn.
Details on the algorithm to impute mTSS will be described in TSAP.
RANDOMISATION
7.6
Eligible patients will be randomised to five parallel groups, Arm 1 – Arm 5, in a 
2:2:2:1:2 ratio, respectively. See Figure 3.1: 1 for a description of the study arms. 
Randomisation will be stratified with respect to naïve or experienced to TNFi
therapy and concurrent MTX (yes or no) use as determined at baseline.
The randomisation list will be generated using a validated system, which involves a 
pseudorandom number generator to guarantee the reproducibility of the assignments. 
This randomisation list will be checked by an independent statistician and used by a 
third-party. IRT system to assign randomisation numbers to eligible patients.
DETERMINATION OF SAMPLE SIZE
7.7

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Sample size was determined on the basis of a one-sided comparison between the 
average in ACR 20 response at Week 16 of Arm 1 and Arm 2 versus placebo. With 
the assumed Week 16 ACR 20 response rate of 38% in the combined arms (Arm 1 
and Arm 2) and of 15% in the placebo arm, 40 participants each for Arm 1, Arm 2 
and placebo will provide 85% power to detect a 23% difference in proportion 
(combination of Arm 1 and Arm 2 versus placebo) using a one-sided test of 0.05 
significance. Please see Table 7.7: 1 for the estimated power based on a range of 
possible placebo rates. Power analysis was conducted using the Chi-Square Test; 
the software used was ADDPLAN version 6.0.4.
Although not included in the hypothesis testing strategy, Arm 3 will have about 40 
participants. In addition, we plan to enrol 20 participants into Arm 4 for 
pharmacokinetic modelling. The total sample size for this study is therefore 180 
participants. Figure 3.1: 1 provides details on the study arms. This study is not 
powered to detect statistically significant differences between risankizumab 
treatment arms.
Table 7.7: 1
Power and sample size for the superiority test of ACR 20 at 
Week 16
Risankizumab
Placebo
Difference
1-sided 
type I error
Total 
sample size
Drop-out
rate 
Power
ACR 20 rate 
at Week 16
38%
15%
23%
0.05
120
0%
85%
40%
17%
84%
42%
19%
83%
44%
21%
82%
46%
23%
81%
48%
25%
80%
38%
17%
21%
78%
38%
19%
19%
69%

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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) and relevant BI Standard 
Operating Procedures (SOPs), the Japanese GCP regulations (Ministry of Health 
and Welfare Ordinance No. 28, March 27, 1997) 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 patients 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.
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 
8.1
INFORMED CONSENT
This trial will be initiated only after all required legal documentation has been 
reviewed and approved by the respective Institutional Review Board (IRB) / 
Independent Ethics Committee (IEC) and competent authority (CA) according to 
national and international regulations. The same applies for the implementation of 
changes introduced by amendments.
Prior to patient participation in the trial, written informed consent must be obtained 
from each patient (or the patient’s legally accepted representative) according to ICH 
/ GCP and to the regulatory and legal requirements of the participating country. 
Each signature must be personally dated by each signatory and the informed consent 
and any additional patient-information form retained by the Investigator as part of 
the trial records. A signed copy of the informed consent and any additional patient 
information must be given to each patient or the patient’s legally accepted 
representative.
For Japan only: The Investigator must give a full explanation to trial patients based 
on the patient information form. A language understandable to the patient should be 
chosen, technical terms and expressions avoided, if possible. The patient must be 
given sufficient time to consider participation in the trial. The Investigator obtains 
written consent of the patient’s own free will with the informed consent form after 

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confirming that the patient understands the contents. The Investigator must sign (or 
place a seal on) and date the informed consent form. If a trial collaborator has given 
a supplementary explanation, the trial collaborator also signs (or places a seal on) 
and dates the informed consent.
Re-consenting may become necessary when new relevant information becomes 
available and should be conducted according to the sponsor’s instructions. The 
consent and re-consenting process should be properly documented in the source 
documentation.
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 eCRF 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 (Food and Drug Administration)). The Clinical Research Associate (CRA) / 

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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.
8.3.3
Storage period of records
Trial sites:
The trial sites must retain the source and essential documents (including ISF) 
according to the national or local requirements (whatever is longer) valid at the time 
of the end of the trial.
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.
LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE 
8.4
EVENTS
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 the study drug risankizumab this is the current 
version of the Investigator’s Brochure (c02161217).
The current versions of these reference documents are provided in the ISF. No AEs
are classified as listed for matching placebo, trial design, or invasive procedures.
8.4.2
Expedited reporting to health authorities and IEC/IRB
Expedited reporting of serious adverse events, e.g. suspected unexpected serious 
adverse reactions (SUSAR) to health authorities and IEC / IRB, will be done 
according to local regulatory requirements.
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 

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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 in Section 6.2.3.
The Last Patient Visit Primary Endpoint is defined as last patient in the trial to 
complete Visit 7, Week 16 assessments.
The IEC / competent authority in each participating EU member state will be 
notified about the end or early termination of the trial.
For Japan only: When the trial is completed, the investigator should inform the head 
of the trial site of the completion in writing, and the head of the trial site should 
promptly inform the IRB and sponsor of the completion in writing.
PROTOCOL VIOLATIONS
8.7
For Japan only, the investigator should document any deviation from the protocol 
regardless of their reasons. Only when the protocol was not followed in order to 
avoid an immediate hazard to trial patients or for other medically compelling 
reason, the principal investigator should prepare and submit the records explaining 
the reasons thereof to the sponsor, and retain a copy of the records.
COMPENSATION AVAILABLE TO THE PATIENT IN THE 
8.8
EVENT OF TRIAL RELATED INJURY
For Japan only, in the event of health injury associated with this trial, the sponsor is
responsible for compensation based on the contract signed by the trial site.

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9.
REFERENCES
PUBLISHED REFERENCES
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Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, 
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American College of Rheumatology. Preliminary definition of 
improvement in rheumatoid arthritis. Arthritis Rheum 
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Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a 
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Ware JE, editor. SF-36 Health Survey: Manual and Interpretation 
Guide. Boston: The Health Institute, New England Medical Center 
(1993)
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Gestel AM van, Haagsma CJ, Riel PLCM van. Validation of 
rheumatoid arthritis improvement criteria that include simplified 
joint counts. Arthritis Rheum 1998; 41(10):1845-1850
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Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, 
Choy EHS, Sharp JT, Ory PA, Perdok RJ, Weinberg MA, 
Adalimumab Effectiveness in Psoriatic Arthritis Trial Study Group. 
Adalimumabfor the treatment of patients with moderately to severely 
active psoriatic arthritis: results of a double-blind, randomized, 
placebo-controlled trial.
Arthritis Rheum 52 (10), 3279 - 3289 (2005) 
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Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. 
Measuring fatigue and other anemia-related symptoms with the 
Functional Assessment of Cancer Therapy (FACT) measurement 
system. J Pain Symptom Manage 13 (2), 63 - 74 (1997)
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Webster K, Cella D, Yost K. The Functional Assessment of Chronic 
Illness Therapy (FACIT) Measurement System: properties, 
applications, and interpretation. Health Qual Life Outcomes 1, 79 
(2003)
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Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J 
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Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, 
Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli 
SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, 
Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, 
Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker 
WW. Second symposium on the definition and management of 
anaphylaxis: summary report - second National Institute of Allergy 
and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol 117 (2), 391 - 397 (2006)
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 34 (6), 1401 - 1414 (2007)
R14-4870
Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the 
management of PsO and psoriatic arthritis. Section 2. Psoriatic 
arthritis: overview and guidelines of care for treatment with an 
emphasis on the biologics. J Am Acad Dermatol. 2008; 58:851–64.
R14-5175
Frleta M, Siebert S, McInnes IB. The interleukin-17 pathway in 
psoriasis and psoriatic arthritis: disease pathogenesis and possibilities 
of treatment. Curr Rheumatol Rep 2014;16(4):414
R15-0998
Filer C, Ho P, Smith RL, et al. Investigation of association of the 
IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum 
2008; 58: 3705–09
R15-1001
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, 
Mielants H; CASPAR Study Group. Classification criteria for 
psoriatic arthritis: development of new criteria from a large 
international study. Arthritis Rheum 2006;54:2665-73
R15-1002
Zachariae H, Zachariae R, Blomqvist K, et al. Quality of life and 
prevalence of arthritis reported by 5,795 members of the Nordic PsO 
Associations. Data from the Nordic Quality of Life Study. Acta 
Derm Venereol. 2002;82:108-13
R15-1003
Prey S, Paul C, Bronsard V, et al. Assessment of the risk of psoriatic 
arthritis in patients with plaque PsO: a systematic review of the 
literature. J Eur Acad Dermatol Venereol. 2010; 24(Suppl. 2):31–5

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R15-1008
Celis R, Planell N, Fernandez-Sueiro JL, Sanmarti R, Ramirez J, 
Gonzalez-Alvaro I, Pablos JL, Canete JD. Synovial cytokine 
expression in psoriatic arthritis and associations with lymphoid 
neogenesis and clinical features. Arthritis Res Ther 14 (2), R93 
(2012)
R15-1020
Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic 
arthritis: epidemiology, clinical features, course, and outcome. Ann 
Rheum Dis 2005;64:Suppl 2:ii14-ii17
R15-1026
Ostergaard M, McQueen F, Wiell C, Bird P, Bøyesen P, Ejbjerg B, 
Peterfy C, Gandjbakhch F, Duer-Jensen A, Coates L, Haavardsholm 
EA, Hermann KG, Lassere M, O'Connor P, Emery P, Genant H, 
Conaghan PG. The OMERACT psoriatic arthritis magnetic 
resonance imaging scoring system (PsAMRIS): definitions of key 
pathologies, suggested MRI sequences, and preliminary scoring 
system for PsA Hands. J Rheumatol. 2009 Aug;36(8):1816-24
R15-1027
van der Heijde D, Sharp J, Wassenberg S, et al. Psoriatic arthritis 
imaging: a review of scoring methods. Ann Rheum Dis 
2005;64(Suppl 2):ii61–4
R15-1030
Ciocon DH, Kimball AB. Psoriasis and psoriatic arthritis: separate or 
one and the same? Br J Dermatol. 2007;157(5):850–60
R15-1033
Yawalkar N, Tscharner GG, Hunger RE, et al. Increased expression 
of IL-12p70 and IL-23 by multiple dendritic cell and macrophage 
subsets in plaque psoriasis. J Dermatol Sci. 2009;54(2):99–105
R15-1035
Liu Y, Helms C, Liao W, et al. A genome-wide association study of 
psoriasis and psoriatic arthritis identifies new disease loci. PLoS 
Genet 2008; 4: e1000041
R15-1066
Koshy PJ, Henderson N, Logan C, et al. Interleukin 17 induces 
cartilage collagen breakdown: novel synergistic effects in 
combination with proinflammatory cytokines. Ann Rheum Dis 
2002;61:704–13
R15-1070
Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces 
spondyloarthropathy by acting on ROR-γt+ CD3+CD4–CD8–
entheseal resident T cells. Nature Med 2012 18: 1069–76
R15-1089
Mease P. Psoriatic arthritis and spondyloarthritis assessment and 
management update. Current Opinion in Rheumatology. 25(3). 
2013:287-96

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Ritchlin C, Rahman P, Kavanaugh A, McInnes IB, Puig L, Li S, 
Wang Y, Shen YK,  Doyle MK, Mendelsohn AM, Gottlieb AB; 
PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 
p40 monoclonal antibody, ustekinumab, in patients with active 
psoriatic arthritis despite conventional non-biological and biological 
anti-tumour necrosis factor therapy: 6-month and 1-year results of 
the phase 3, multicentre, double-blind, placebo-controlled, 
randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014 Jun;73(6):990-
9.
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Coates LC, Fransen J, Helliwell PS. Defining minimal disease 
activity in psoriatic arthritis: a proposed objective target for 
treatment. Ann Rheum Dis 2010; 69:48–53
R15-1355
Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic 
arthritis: assessment of existing measures and development of an 
instrument specific to psoriatic arthritis. Arthritis Care Res 59 (5), 
686 - 691 (2008)
R15-3527
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, 
Rahman P, van der Heijde D, Landewé R, Conaghan PG, Gottlieb 
AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S; 
FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-
17A monoclonal antibody, in patients with psoriatic arthritis
(FUTURE 2): a randomised, double-blind, placebo-controlled, phase 
3 trial. Lancet. 2015 Sep 19;386(9999):1137-46.
R15-3846
Bruce B, Fries JF The Stanford Health Assessment Questionnaire: a 
review of its history, issues, progress, and documentation. J 
Rheumatol 30 (1), 167 - 178 (2003)
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(AR
AMIS)%206-30-09.pdf (access date: 15 July 2015) ; Stanford: 
Stanford University School of Medicine, Division of Immunology & 
Rheumatology (2009)
R15-4751
Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski 
WP, Wong RL, Sampalis J, Conner-Spady B. Development and 
validation of the Spondyloarthritis Research Consortium of Canada 
(SPARCC) Enthesitis Index. Ann Rheum Dis 68 (6), 948 - 953 
(2009)
R15-4755
Helliwell PS, Firth J, Ibrahim GH, Melsom RD, Shah I, Turner DE. 
Development of an assessment tool for dactylitis in patients with 
psoriatic arthritis. J Rheumatol 32 (9), 1745 - 1750 (2005)

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R15-5028
Helliwell PS, Fitzgerald O, Fransen J et al (2012) The development 
of candidate composite disease activity and responder indices for 
psoriatic arthritis (GRACE project). Ann Rheum Dis 2012 ;0:1–6
R15-5029
Cassell SE, Bieber JD, Rich P, Tutuncu ZN, Lee SJ, Kalunian KC, et 
al. The modified nail psoriasis severity index: validation of an 
instrument to assess psoriatic nail involvement in patients with 
psoriatic arthritis. J Rheumatol 2007;34:123–9
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
R15-5899
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van 
der Heijde D, Landewé R, Nash P, Pricop L, Yuan J, Richards HB, 
Mpofu S; FUTURE 1 Study Group. Secukinumab Inhibition of 
Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med. 
2015 Oct;373(14):1329-39.
R15-5992
Glinatsi D, Bird P, Gandjbakhch F, Mease PJ, Bøyesen P, Peterfy 
CG, Conaghan PG, Østergaard M. Validation of the OMERACT 
Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) 
for the Hand and Foot in a Randomized Placebo-controlled Trial. J 
Rheumatol. 2015 Nov 1. pii: jrheum.141010. [Epub ahead of print] 
PubMed PMID: 26523032
UNPUBLISHED REFERENCES
9.2
c02161217
Investigator’s Brochure BI 655066, Psoriasis, Crohn’s Disease, 
Ankylosing Spondylitis, 1311.P1/1311.P2/1311.P3
c02434648
Dorleacq N, Steimle-Goerttler C, Bai X, Joseph D; Safety, 
tolerability, efficacy, pharmacokinetics, and pharmacodynamics of 
single rising i.v. (Stage 1) and s.c. (Stage 2) doses of BI 655066 in 
male and female patients with moderate to severe psoriasis 
(randomised, double-blind, placebo-controlled within dose groups); 
Trial 1311.1, 26 Mar 2015
c03272682
Summary report of interim analysis at Week 48, Trial 1311.2. 05 
May 2015

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10.
APPENDICES
CASPAR
10.1
To meet the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria*, a 
patient must have inflammatory articular disease (joint, spine, or entheseal) with ≥3 
points from the following 5 categories (R15-1001):
1. Evidence of current psoriasis, a personal history of psoriasis, or a family 
history of psoriasis. 
%
Current psoriasis is defined as psoriatic skin or scalp disease present today 
as judged by a rheumatologist or dermatologist.† 
%
A personal history of psoriasis is defined as a history of psoriasis that may 
be obtained from a patient, family physician, dermatologist, rheumatologist, 
or other qualified health care provider. 
%
A family history of psoriasis is defined as a history of psoriasis in a first- or 
second-degree relative according to patient report.
2. Typical psoriatic nail dystrophy including onycholysis, pitting, and 
hyperkeratosis observed on current physical examination.
3. A negative test result for the presence of rheumatoid factor by any method 
except latex but preferably by enzyme-linked immunosorbent assay or 
nephelometry, according to the local laboratory reference range.
4. Either current dactylitis, defined as swelling of an entire digit, or a history of 
dactylitis recorded by a rheumatologist.
5. Radiographic evidence of juxtaarticular new bone formation, appearing as ill-
defined ossification near joint margins (but excluding osteophyte formation) on 
plain radiographs of the hand or foot.
* The CASPAR criteria have specificity of 98.7% and sensitivity of 91.4%.
† Current psoriasis is assigned a score of 2; all other features are assigned a score of 
1.

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Joint
Left
Right
Tender
Swollen
Tender
Swollen
Ankle
Mid-Tarsal
MTP1
MTP2
MTP3
MTP4
MTP5
IP of great toe
PIP of toes 2
PIP of toes 3
PIP of toes 4
PIP of toes 5
* Hip will only be assessed for TJC (Tender Joint Counts), not for SJC (Swollen 
Joint Count).
# Joints which will also count for DAS28-CRP evaluation.
Joint counts will be performed by assessor(s) who must be well trained and part of 
the site personnel. Whenever possible, the same evaluator should perform these
assessments at all visits.
Number of tender joints:
The 68 joints assessed for tenderness include the 2 temporomandibular, 2 
sternoclavicular, 2 acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 10
metacarpophalangeal, 10 proximal interphalangeal, 8 distal interphalangeal joints of 
the hands, the 2 hips, 2 knees, 2 ankles2 mid-tarsal, 10 metatarsophalangeal, and 10 
proximal interphalangeal joints of the feet.
Joints are be scored as either tender (1) or not tender (0)
Number of swollen joints:
The 66 joints to be examined for swelling are the same as those examined for 
tenderness, however excluding both hip joints.
Joints are to be scored as either swollen (1) or not swollen (0).

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Synovial fluid and/or soft tissue swelling but not bony overgrowth represents a 
positive result for swollen joint count. 
Data will be recorded for tender and swollen joints (right or left side), i.e. a box (no, 
yes or not applicable) needs to be ticked for all joints. The total number of tender 
and swollen joints (right and left) will be automatically calculated in the eCRF.

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ACR RESPONSE CRITERIA
10.3
ACR 20: 
•
At least 20% improvement in SJC* compared to baseline AND
•
At least 20% improvement in TJC* compared to baseline AND
•
At least 20% improvement in at least 3 out of the following 5 variables 
ACR 50:
•
At least 50% improvement in SJC* compared to baseline AND
•
At least 50% improvement in TJC* compared to baseline AND
•
At least 50% improvement in at least 3 out of the following 5 variables 
ACR 70: 
•
At least 70% improvement in SJC* compared to baseline AND
•
At least 70% improvement in TJC* compared to baseline AND
•
At least 70% improvement in at least 3 out of the following 5 variables 
1. Patient’s assessment of pain on VAS 
2. Patient’s global assessment of the disease on VAS
3. Investigator’s global assessment of the disease on VAS
4. Patient’s assessment of disability on HAQ
5. Acute phase reactant (serum CRP)
* SJC and TJC are evaluated according to the complete joint count (see Appendix 
10.2).
Reference: R96-2379
For Patient’s assessment of PsA pain intensity c.f. Section 10.14.5
For Patient’s global assessment of disease activity c.f. Section 10.14.6
Physician’s global assessment of disease activity
The physician’s global assessment of disease activity will be performed using 100 
mm VAS ranging from no disease activity to maximal disease activity, after the 
question "Considering all the ways the disease affects your patient, draw a line on 
the scale for how well his or her condition is today”. To enhance objectivity, the 
physician must not be aware of the specific patient’s global assessment of disease 
activity, when performing his own assessment on that subject.

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LEEDS DACTYLITIS INDEX (LDI)
10.4
The LDI basic measures the ratio of the circumference of the affected digit to the 
circumference of the digit on the opposite hand or foot, using a minimum difference 
of 10% to define a dactylitic digit. The ratio of circumference is multiplied by a 
tenderness score, using a modification of LDI which is a binary score (1 for tender, 
0 for non-tender). If both sides are considered involved, or the circumference of the 
contralateral digit cannot be obtained, the number will be compared to data 
provided in the standard reference tables (Table 10.4.1 and 10.4.2). This 
modification is referred to as LDI basic and will be applied in this study. The LDI
requires a finger circumference gauge or a tape measure to measure digital
circumference.
Dactylitis count
The dactylitis count is the number of fingers and toes with dactylitis, with a range of 
0-20.
Presence of dactylitis
If dactylitis is present with any finger or toe, the subject is counted as a subject with 
dactylitis.
Table 10.4.1. – Hands (in cm)
Digit
Men
Women
Thumb
7.0
5.8
Index
6.3
5.4
Middle
6.3
5.4
Ring
5.9
5.0
Little
5.2
4.4
Table 10.4.2. – Feet (in cm)
Digit
Men
Women
Central toe
8.2
7.2
Second
5.2
4.6
Middle
5.0
4.4
Fourth
5.0
4.4
Little
5.2
4.5
Reference: R15-4755

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LEEDS ENTHESITIS INDEX (LEI)
10.5
LEI is a validated enthesitis index that uses 6 sites for evaluation of enthesitis: 
lateral epicondyle humerus left and right, Achilles tendon insertion left and right
and medial condyle femur left and right. The LEI demonstrated substantial to 
excellent agreement with other scores in the indication of psoriatic arthritis.
Enthesitis count
Tenderness on examination is recorded as either present (1) or absent (0) for each of 
the 6 sites, for an overall score range of 0–6.
Presence of enthesitis
If enthesitis is present with any of the 6 sites (lateral epicondyle humerus left and 
right, Achilles tendon insertion left and right and medial condyle femur left and 
right), the subject is counted as a subject with enthesitis.
Reference: R15-1355

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SPONDYLOARTHRITIS RESEARCH CONSORTIUM OF
10.6
CANADA (SPARCC) ENTHESITIS INDEX
Enthesial sites examined include medial epicondyle (left and right), lateral 
epicondyle (left and right), supraspinatus insertion into greater tuberosity of 
humerus (left and right), greater trochanter (left and right), quadriceps insertion into 
superior border of patella (left and right), patellar ligament insertion into inferior 
pole of patella or tibial tubercle (left and right), Achilles tendon insertion into 
calcaneum (left and right), plantar fascia insertion into calcaneum (left and right).
Enthesitis count
Tenderness on examination is recorded as either present (1) or absent (0) for each of 
the 18 sites, for an overall score range of 0–16.
Reference: R15-4751

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MINIMAL DISEASE ACTIVITY
10.7
The proportion of subjects achieving minimal disease activity (MDA) will be 
analysed. A patient is classified as achieving MDA when meeting 5 of the 7 
following criteria are met:
∃
Tender joint count ≤ 1
∃
Swollen joint count ≤ 1
∃
PASI ≤ 1 or BSA ≤ 3 %
∃
Patient pain-VAS ≤ 15
∃
Patient global activity VAS ≤20
∃
HAQ-DI ≤ 0.5
∃
Tender entheseal points ≤ 1
Reference: R15-1218

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DAS28 4V – CRP 
10.8
Will be calculated taking the following variables into account:
•
TJC (on 28 joints, see Appendix 10.2)
•
SJC (on 28 joints, see Appendix 10.2)
•
Patient’s global assessment of the disease on VAS (0-100)
•
Serum CRP level (mg/L)
The formula used for DAS28 4v - CRP is: DAS28=0.56*√(TJC) + 0.28*√(SJC) + 
0.36 *Ln(CRP+1) + 0.014*VAS + 0.96
Reference: R00-0676

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EULAR RESPONSE CRITERIA
10.9
DAS28 at 
endpoint
Improvement in DAS28 from baseline:
> 1.2
> 0.6 and ≤ 1.2
≤ 0.6
≤ 3.2
Good
> 3.2 and ≤ 5.1
Moderate
> 5.1
None

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PSARC RESPONSE
10.10
A subject is defined as a PsARC responder if, and only if, they have an 
improvement in two of the following four factors (with at least one factor being a 
joint count) and no worsening in the remaining factors: 
∃
Patient global assessment of disease activity (0-100 mm VAS scale, 
improvement defined as decrease of ≥ 20 mm)
∃
Physician global assessment of disease activity (0-100 mm VAS scale, 
improvement defined as decrease ≥ 20 mm)
∃
Tender 68-joint count (improvement defined as decrease of ≥30%)
∃
Swollen 66-joint count (improvement defined as decrease of ≥30%)
Reference: R06-0073

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PASI SCORE DEFINITIONS AND USE 
10.11
The PASI score is an established measure of clinical efficacy for psoriasis 
medications (R96-3541).
The PASI is a tool which provides a numeric scoring for patients overall psoriasis 
disease state, ranging from 0 to 72. It is a linear combination of percent of surface 
area of skin that is affected and the severity of erythema, infiltration, and 
desquamation over four body regions. 
The endpoints used are based on the percent reduction from baseline, generally 
summarized as a dichotomous outcome based on achieving over an X% reduction 
(or PASIX), where X is 50, 75, 90 and 100.
To calculate the PASI score, the four main body areas are assessed: head (h), trunk 
(t), upper extremities (u) and lower extremities (l). These correspond to 10, 30, 
20 and 40% of the total body area respectively.
The area of psoriatic involvement of these four areas (Ah, At, Au, and Al) is given 
a numerical value: 0 = no involvement, 1 = <10%, 2 = 10 to <30%, 3 = 30 to <50%, 
4 = 50 to <70%, 5 = 70 to <90%, and 6 = 90 to 100% involvement.
The signs of severity, erythema (E), infiltration (I) and desquamation (D) of 
lesions are assessed using a numeric scale 0-4 where 0 is a complete lack of 
cutaneous involvement and 4 is the severest possible involvement; scores are made 
independently for each of the areas, h, t, u and l and represents a composite score 
for each area. An illustration of judging erythema follows: 0 = no erythema, 1 = 
slight erythema, 2 = moderate erythema, 3 = striking erythema, and 4 = 
exceptionally striking erythema.
The PASI score is calculated according to the following formula:
PASI = 0.1(Eh+Ih+Dh)Ah + 0.3(Et+It+Dt)At + 0.2(Eu+Iu+Du)Au + 
0.4(El+Il+Dl)Al

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STATIC PHYSICIAN GLOBAL ASSESSMENT (SPGA)
10.12
This 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 
(Table 10.12: 1) (R15-5200).
The assessment is considered “static” which refers to the patients disease state at the 
time of the assessments, without comparison to any of the patient’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 (possible 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:

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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
Table 10.12: 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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MNAPSI – MODIFIED NAIL PSORIASIS SEVERITY INDEX
10.13
Modified NAPSI Instructions
This tool will ask you to assess each abnormality for each of a subject’s fingernails. 
If you question which grade to give, your answer should be the lower of the grades. 
Three features or groups of features (pitting, onycholysis and oil-drop dyschromia, 
and crumbling) of each fingernail will be graded on a scale from 0 to 3, according to 
the directions below. Four features (leukonychia, splinter hemorrhages, 
hyperkeratosis, and red spots in the lunula) will be graded as either present or absent 
for each fingernail. 
1. Onycholysis: Separation of the nail plate from the nail bed. The separated part of 
the nail is opaque and can have white, yellow, or greenish tinge. If there is a piece 
of nail missing, estimate where the nail normally would have ended at the end of the 
nail bed, and count that missing part as involved in onycholysis.
Oil-drop (salmon patch) dyschromia: Reddish-brown discoloration under the nail 
plate.
Onycholysis and oil-drop dyschromia are considered together. When looking at the 
nail, combine the total percentage area of the nail that is affected by either and use 
that combined total to score the nail.
Score
Percent of nail with onycholysis or oil-drop dyschromia present
0
No onycholysis or oil drop dyschromia present
1
1-10% of the nail has onycholysis or oil-drop dyschromia
2
11-30% of the nail has onycholysis or oil-drop dyschromia
3
> 30% of the nail has onycholysis or oil-drop dyschromia
2. Pitting: Small, sharply defined depressions in the nail surface. Pits are discrete 
abnormalities (“ice-pick-like”). If there is nail plate crumbling that is confluent with 
pits, do not score for pits. If the pits are separate from crumbling, they may be 
scored regardless of whether crumbling is present or not.

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Score
Number of pits
0
0
1
1-10
2
11-49
3
> 50
3. Nail plate crumbling: Crumbling or fragmentation of friable nail plate which 
may be associated with confluent pitting. Crumbling involves alteration of the nail 
plate surface. Horizontal ridging of the nail, “wave-like” appearance, and horizontal 
lines are all features of crumbling.
Score
Percent of nail with crumbling present
0
No crumbling
1
1-25% of the nail has crumbling
2
26-50% of the nail has crumbling
3
> 50% of the nail has crumbling
The next 4 abnormalities are scored only by their presence or absence. A score of 1 
indicates present and a score of zero indicates not present.
1. Leukonychia: White spots in the nail plate due to psoriasis in the mid matrix. 
Leukonychia are just color changes. If it appears that there is depression or 
irregularity to the nail surface, this may be pitting or crumbling, not leukonychia. If 
the leukonychia is adjacent to, or confluent with crumbling or pits, it is counted as 
part of the crumbling or pitting and not as a separate abnormality.
2. Splinter hemorrhages: Small, longitudinal, linear, dark brown hemorrhage 
under the fingernail.
3. Nail bed hyperkeratosis: Thickened keratin in the nail bed.
4. Red spots in the lunula: Small pink or red macules in the lunula.
Reference: R15-5029

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PATIENT REPORTED OUTCOMES
10.14
10.14.1
Health Assessment Questionnaire Disability Index (HAQ-DI)
The HAQ-DI is a twenty-item patient reported outcome instrument that assesses 
current physical function/ disability. The HAQ-DI covers eight categories (dressing 
and grooming, hygiene, arising, reach, eating, grip, walking and common daily 
activities). There are four response options, ranging from 0 (no difficulty) to 3 
(unable to do). HAQ-DI score is reported as a mean score between 0 and 3 by 
dividing the total score by the number of items answered (R15-3849).
The HAQ-DI has been the most-widely used instrument to assess physical function 
clinical trials of treatments for rheumatoid and psoriatic arthritis and has extensive 
evidence of its validity and other psychometric properties in this context (R15-
3846). 
The HAQ-DI will be self-administered by the patient at visits indicated in the Flow 
Chart.
10.14.2
BASDAI (BATH AS DISEASE ACTIVITY INDEX)
Each question is answered on a 0 to 10 scale.  For questions 1-5, 0 means none and 
10 means very severe; for question 6, 0 means 0 hours and 10 means 2 or more 
hours. All questions refer to last week.
1.
How would you describe the overall level of fatigue/tiredness you have 
experienced?
2.
How would you describe the overall level of AS neck, back or hip pain you 
have had?
3.
How would you describe the overall level of pain/swelling in joints other 
than neck, back or hips you have had? 
4.
How would you describe the overall level of discomfort you have had from 
any areas tender to touch or pressure? 
5.
How would you describe the overall level of morning stiffness you have had 
from the time you wake up?
6.
How long does your morning stiffness last from the time you wake up?
Calculation of BASDAI: compute the mean of questions 5 and 6. Calculate the sum 
of the values of question 1–4 and add the result to the mean of questions 5 and 6. 
Divide the result by 5.

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10.14.3
Medical Outcome Short Form Health Survey (SF-36) Version 2 
(Acute Form)
The SF-36 is a widely used and extensively studied instrument to measure health-
related quality of life among healthy subjects and patients with acute and chronic 
conditions. It consists of eight subscales that can be scored individually: Physical 
Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social 
Functioning, Role-Emotional, and Mental Health (R97-1093). Two overall 
summary scores, the Physical Component Summary (PCS) and the Mental 
Component Summary (MCS) also can be computed (R96-1184). The SF-36 has 
proven useful in monitoring general and specific populations, comparing the
relative burden of different disease, differentiating the health benefits produced by 
different treatments, and in screening individual subjects.
The purpose of the SF-36 in this study is to assess the HRQoL of subjects. Given 
the acute nature of this disease, version 2, with a 1-week recall period, will be used 
in this study.
References: R97-1093, R96-1184
10.14.4
FUNCTIONAL ASSESSMENT OF CHRONIC ILLNESS 
THERAPY-FATIGUE (FACIT-F)
The FACIT-Fatigue is a 13-item questionnaire (Cella 1993; Yellen 1997) that 
assesses self-reported fatigue and its impact upon daily activities and function.
The purpose of FACIT-Fatigue in this study is to assess the impact of fatigue on 
subjects with PsA.
Number of items: 13 items.
Response options/scale: Answers are based on a 5-point Likert scale. Responses of 
“not at all”, “a little”, “somewhat”, “quite a bit”, and “very much” are available for
each question, and correspond to scores of 0, 1, 2, 3, and 4, respectively.
Recall period for items: 7 days.
Reference: R10-6433, R07-4311
10.14.5
Patient’s assessment of PsA pain intensity
The pain-VAS will be self-administered by the patient at visits indicated in the Flow 
Chart.
The patient’s assessment of pain will be performed using a horizontal 100 mm 
visual analog scale (VAS), ranging from 0 (no pain) to 100 (severe pain) after the 
question:
“Please indicate with a vertical mark ( | ) through the horizontal line the most pain 
you had from your psoriatic arthritis today”.

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10.14.6
Patient’s global assessment of disease activity
The patient global assessment VAS will be self-administered by the patient at visits 
indicated in the Flow Chart.
The patient’s global assessment of disease activity will be performed using a 
horizontal 100 mm VAS, ranging from 0 (very well) to 100 (very poor) after the 
question:
"Considering all the ways psoriatic arthritis affects you, please indicate with a 
vertical mark ( | ) through the horizontal line how well you are doing today”.

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CLINICAL CRITERIA FOR DIAGNOSIS OF ANAPHYLAXIS
10.15
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled:
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal 
tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], 
syncope, incontinence)
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen 
lips-tongue-uvula)
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence)
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours):
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in 
systolic BP*
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
person's baseline
PEF, Peak expiratory flow; BP, blood pressure.
*Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, 
less than (70 mm Hg + [2 × age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years.
Reference: R11-4890

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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
Number of global 
amendment
1
Date of CTP revision
12 October 2016
EudraCT number
2015-003625-34
BI Trial number
1311.5
Investigational Product
BI 655066/ABBV-066/risankizumab
Title of protocol
A randomised, double-blind, placebo-
controlled, proof-of-concept, dose-ranging 
study of BI 655066/ABBV-
066/risankizumab in patients with active 
psoriatic arthritis
To be implemented only 
after approval of the 
IRB/IEC/Competent 
Authorities
X
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, CLINICAL TRIAL PROTOCOL 
SYNOPSIS, and all sections

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Number of global 
amendment
1
Description of change 1
Add information for BI 655066/ABBV-
066/risankizumab and AbbVie. 
All instances of BI drug or BI investigational 
product or BI 655066 found within the 
protocol refers to either names for this 
compound:   BI 655066 or ABBV-066 or 
risankizumab except where outside
documents or previous BI studies are
referenced and only refers to BI 655066
(e.g., Investigator’s Brochure, Study Manual,
references, investigational drug product
labels).
All instances of BI, Boehringer Ingelheim,
Boehringer Ingelheim International GmbH or 
Boehringer Ingelheim Pharmaceuticals, Inc
found within the protocol are changed to 
Boehringer Ingelheim/AbbVie.
Rationale for change 1
The protocol has been amended to inform 
sites of a change in sponsor of the 1311.5 
study in the US, and of an open label 
extension (OLE) study for 1311.5 study 
patients.  
The extension study will be sponsored by 
AbbVie as part of collaboration between 
Boehringer Ingelheim and AbbVie in the 
development of BI-665066/ABBV-066.
The purpose of this amendment is to 
incorporate the changes summarized below 
as well as editorial changes.
Risankizumab is the name of the compound.
Section to be changed
FLOW CHART
Description of change 2
Revision to visit schedule for OLE 
participants.
Rationale for change 2
Subjects that elect to enrol in the extension 
study may complete the 1311.5 study at V9
or V10 and therefore it is necessary to revise 
the visit schedule and the assessment period.
Section to be changed
ABBREVIATIONS
Description of change 3
Add abbreviation.

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Number of global 
amendment
1
Rationale for change 3
This is an administrative change to add an 
abbreviation.
Section to be changed
2.2 TRIAL OBJECTIVES
Description of change 4
Addition of instruction in the assessment 
period for OLE study patients.
Rationale for change 4
Subjects that elect to enrol in the extension 
study may complete the 1311.5 study at V9
or V10 and therefore it is necessary to revise 
the visit schedule and the assessment period.
Section to be changed
2.3 BENEFIT – RISK ASSESSMENT
Description of change 5
Addition of rescue therapy instruction for 
patients that enrol in OLE.
Rationale for change 5
Therapy restriction required to maintain 
eligibility for OLE study.
Section to be changed
3.1 OVERALL TRIAL DESIGN AND 
PLAN
Description of change 6
Eligibility for OLE study and revision of 
study diagram.
Rationale for change 6
Explanation of open label study basic 
eligibility criteria and revised visit schedule
and visual representation of trial design.
Section to be changed
3.1.1 ADMINISTRATIVE STRUCTURE 
OF THE TRIAL
Description of change 7
Update of sponsorship of the study. Update 
of administrative structure of the study.
Rationale for change 7
Administrative structure of the trial was 
updated to reflect AbbVie as sponsor in the 
US only and to reflect that data management 
will be done by BI according to BI SOPs and 
the statistical evaluation will be done by 
AbbVie according to AbbVie SOPs.
Section to be changed
3.2 DISCUSSION OF TRIAL DESIGN, 
INCLUDING THE CHOICE OF CONTROL 
GROUP
Description of change 8
Revision of assessment period and visit 
schedule for patients that enrol in OLE.
Rationale for change 8
Explanation of revised assessment period 
and visit schedule for patients that enrol in 
OLE.
Section to be changed
3.3.4.1 Removal of individual patients
Description of change 9
Clarification and addition of eligibility 
instruction for OLE patients.

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Number of global 
amendment
1
Rationale for change 9
Added to describe eligibility restrictions for 
participation in OLE.
Section to be changed
4.1.2 METHOD OF ASSIGNING 
PATIENTS TO TREATMENT GROUPS
Description of change 10
Added description of stratification within the 
study.
Rationale for change 10
Further clarification of study stratification.
Section to be changed
5.2 ASSESSMENT OF EFFICACY
Description of change 11
Correct table 5.2: 1, follow-up period starts 
at visit 8.
Rationale for change 11
This is an administrative change to correct 
table. 
Section to be changed
5.3.3 SAFETY LABORATORY 
PARAMETERS
Description of change 12
Some laboratory parameters are better 
specified. Added Albumin/creatinine ratio in 
urine. Correct typos.
Rationale for change 12
Update to correct table.
Section to be changed
5.3.4 ELECTROCARDIOGRAM
Description of change 13
Source data for ECG is better specified.
Rationale for change 13
Update information for source data of ECG.
Section to be changed
5.4.1 ASSESSMENT OF 
PHARMACOKINETICS
Description of change 14
PK assessments revised to describe how 
summary statistics will be provided.
Rationale for change 14
Update to PK assessment.
Section to be changed
5.5.1 ASSESSMENT OF SOLUBLE AND 
CELLULAR BLOOD BIOMARKERS AND 
RNA
Description of change 15
Added additional types of analyses to be 
performed on samples.
Rationale for change 15
Update to clarify the additional types of 
cellular biomarker analyses that could be 
performed on the blood samples.
Section to be changed
5.5.2 BIOMARKER SAMPLE BANKING
Description of change 16
Added additional type of samples to be 
banked and additional analyses to be 
performed.
Rationale for change 16
Update to include PBMC samples and 
additional scope of sample analysis.
Section to be changed
5.5.3.2 Analytical determinations

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12 Oct 2016
BI Trial No.: 1311.5
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Number of global 
amendment
1
Description of change 17
Update information for DNA banking 
samples.
Rationale for change 17
Updated protocol to reflect that DNA 
banking samples will be stored at Boehringer 
Ingelheim, AbbVie or third party delegate.
Section to be changed
5.6 OTHER ASSESSMENTS
Description of change 18
Update information for central read of MRI 
images.
Rationale for change 18
Update protocol to clarify that MRI images 
will be read in random order.
Section to be changed
6.2 DETAILS OF TRIAL PROCEDURES 
AT SELECTED VISITS
Description of change 19
Clarify when patient reported outcomes 
(PROSs) are to be done.
Rationale for change 19
Update protocol to clarify that PROs have to 
be done first at a visit. 
Section to be changed
6.2.3.1 Early treatment termination
Description of change 20
Description of eligibility for patients that 
enrol in OLE
Rationale for change 20
To ensure appropriate patients are enrolled in 
the OLE study
Section to be changed
6.2.3.2 Trial completion
Description of change 21
Added description of completion for patients 
that enrol in OLE
Rationale for change 21
Study completion revised for OLE patients.
Section to be changed
7.3.1 PRIMARY ENDPOINT ANALYSES
Description of change 22
Moved paragraph from section 7.4 to section 
7.3.1.
Rationale for change 22
To accurately reflect the analysis process.
Section to be changed
7.3.4 SAFETY ANALYSES
Description of change 23
Safety analyses section update to reflect that 
AbbVie will produce summary tables and 
listings and to indicate that safety analyses 
will be based on AbbVie standards.
Rationale for change 23
Due to collaboration agreement.
Section to be changed
7.4. INTERIM ANALYSES
Description of change 24
Moved paragraph from section 7.4 to section 
7.3.1. To inform that no interim analysis will 
be done.
Rationale for change 24
To accurately reflect the analysis process.
Section to be changed
10.2 JOINT ASSESSMENT
Description of change 25
Update instructions for joint count.

Boehringer Ingelheim
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BI Trial No.: 1311.5
c03416278-02
Trial Protocol
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companies
.
001-MCS-40-106-RD-03 (12 0) / Saved on: 30 Jan 2015
Number of global 
amendment
1
Rationale for change 25
Clarify that there is no extra rule for joint 
count of dactylitic digits.
Section to be changed
10.10 BASDAI (BATH AS DISEASE 
ACTIVITY INDEX)
Description of change 26
Moved from section 10.10 to section 10.14.2.
Rationale for change 26
To move information for BASDAI to the 
correct section.
Section to be changed
10.13 MNAPSI – MODIFIED NAIL 
PSORIASIS SEVERITY INDEX
Description of change 27
Update instruction of mNAPSI.
Rationale for change 27
Clarify that visual analog scale for global 
assessment of fingernails will not be done.
Section to be changed
10.14.2 BASDAI (BATH AS DISEASE 
ACTIVITY INDEX)
Description of change 28
Moved from section 10.10 to section 10.14.2.
Rationale for change 28
To move information for BASDAI to the 
correct section.

 
 
 
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