Clinical trial NCT02719171
Conditions: Arthritis, Psoriatic
Sponsor: AbbVie
Start date: 2016-04-01; Completion date: 2017-08-01
Enrollment: 185 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The overall purpose of this trial is to assess clinical efficacy and safety of different subcutaneous doses of BI 655066/ABBV-066/risankizumab in adult patients with psoriatic arthritis in order to select doses for further clinical trials.

Detailed description:

Arms: arm 1: Participants randomized to receive double-blind (DB) placebo for risankizumab by subcutaneous (SC) injection every 4 weeks for 16 weeks. arm 2: Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection every 4 weeks for 16 weeks. arm 3: Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0, 4, and 16. arm 4: Participants randomized to receive double-blind (DB) risankizumab 150 mg by subcutaneous (SC) injection at Weeks 0 and 12. arm 5: Participants randomized to receive double-blind (DB) risankizumab 75 mg by subcutaneous (SC) injection at Week 0.
Interventions: intervention 1: risankizumab intervention 2: placebo for risankizumab
Intervention descriptions: intervention 1: Risankizumab administered by SC injection intervention 2: Placebo for risankizumab administered by SC injection

Protocol documents:
Prot_000.pdf: 
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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
Proprietary confidential information.
! 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.
/$5


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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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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 
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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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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). 
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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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c03416278-02
Trial Protocol
Page 102 of 104
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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 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


Boehringer Ingelheim
12 Oct 2016
BI Trial No.: 1311.5
c03416278-02
Trial Protocol
Page 103 of 104
Proprietary confidential information © 2015 Boehringer Ingelheim International GmbH/Abbvie, Inc. or one or more of its affiliated 
companies
.
001-MCS-40-106-RD-03 (12 0) / Saved on: 30 Jan 2015
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
12 Oct 2016
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.


 
 
 
APPROVAL / SIGNATURE PAGE 
Document Number: 
 
Technical Version Number:
Document Name: 
                                                                                                                 
 
Title: 
                                                                                                                   
Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
c03416278
2.0
clinical-trial-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
12 Oct 2016 15:59 CEST
12 Oct 2016 16:03 CEST
12 Oct 2016 16:40 CEST
12 Oct 2016 16:53 CEST
12 Oct 2016 22:53 CEST
13 Oct 2016 09:05 CEST


Boehringer Ingelheim 
Page 2 of 2
Document Number: 
Technical Version Number:
(Continued) Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c03416278
2.0

SAP_001.pdf: 


Risankizumab (ABBV-066)
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3.0
Introduction
This document is an explanation of differences between the analysis performed after final 
database lock and those detailed in the SAP.
The changes include:
●
Section 6.4:  Updates to the visit window for mTSS.
Rationale:  Updated window more accurately encompasses observations 
appropriate to label as baseline.
●
Section 6.5:  mTSS and PsAMRIS removed from 6.5 Missing Data Handling.
Rationale:  No subject level imputation will be performed for continuous 
imaging data.
●
Section 7.1:  Removed statistical testing between placebo arm and the mixed 
two arms at baseline.
Rationale:  No statistical testing for baseline characteristics.
●
Section 9.0:  Planned number of visits when injection planned has been 
capped at 5.
Rationale:  No subject should have more than 5 planned visits.
●
Section 10.1:  Table 12 has been updated.
Rationale:  Some efficacy endpoints have been added and some analyses have 
changed.
●
Section 10.6 List of further efficacy endpoints has been updated.
Rationale:  Some efficacy endpoints have been added and some analyses have 
changed
●
Section 10.9.10:  The addition of a PASI LOCF sensitivity analysis.
Rationale:  Sensitivity analysis added due to the presence of PASI missing 
data.
●
Section 10.9.12:  Updates to what defines a dactylic digit.
Rationale:  Added a missing component of the definition of dactylitis.
●
Section 10.9.20:  Updates to the scoring and missing data rules for mTSS.
Rationale:  Two separate methods of analysis will be performed for mTSS.


Risankizumab (ABBV-066)
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●
Section 10.9.21:  Updated PsAMRIS analysis to be descriptive statistics only.
Rationale:  There are far too few observations with PsAMRIS data to provide 
a more detailed analysis.  Additionally hand and foot scores are not 
comparable.
●
Section 11.2:  Changed "Adverse Events by "Reasonably Possibly Related" 
Relationship" to "Adverse Events by Maximum Relationship."
Rationale:  Updates to the PSSAP.
●
Section 11.2:  Addition of unknown category to Adverse Events by Maximum 
Relationship.
Rationale:  Updates to the PSSAP.
●
Section 11.4:  Change of wording in Criteria for Potentially Clinically 
Significant Vital Sign Findings.
Rationale:  Updates to the PSSAP.
●
Various:  Several small editorial changes.
Rationale:  Various small updates to wording were made for clarity.
6.0
Analysis Conventions
6.4
Definition of Analysis Windows
Table 6 previously read:
Table 1.
Visit Windows for Analysis of mTSS
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
[–999, 13]
Week 24
VISIT 9
169
[14, 306]


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Table 6 now reads:
Table 1.
Visit Windows for Analysis of mTSS
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
[–999, 30]
Week 24
VISIT 9
169
[31, 306]
6.5
Missing Data Handling
This section no longer includes the subject level imputation method below:
Missing Data Handling for mTSS and PsAMRIS
The following imputation method on subject level will be used as the primary approach to 
impute missing mTSS and PsAMRIS:
●
Calculate average change from Baseline to follow-up visit (for example, 
Week 24 for mTSS and Week 16 for PsAMRIS) computed for all observed 
non-missing bones/joints data at both time points from a given subject.
●
If the Baseline score is available for a bone/joint, then the impute value at the 
follow-up visit will be the Baseline score plus the average change score from 
the other scored bone/joint locations.
●
If the Baseline visit is unavailable but the follow-up visit score is available, the 
imputed value at the Baseline will be computed from the follow-up time point 
score minus the average change, if the average change is smaller than the
follow-up time point score at that location.  Otherwise, the Baseline visit 
imputed value will use the most recent follow-up time point score carried 
backward.
●
If both Baseline and follow-up time point visit score values are missing for a 
bone/joint, no values will be imputed to either visit, and that joint's bone/joint 
contribution will be zero, which means assigning 0 to both baseline and the 
follow-up time point for that joint.


Risankizumab (ABBV-066)
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7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
The first paragraph in Section 7.1 previously read:
Demographics and Baseline characteristics will be summarized for each arm and for 
overall of the FAS populations.  Continuous variables will be summarized with the 
number of non-missing observations by mean, standard deviation, first quartile, median, 
third quartile, minimum and maximum values.  Categorical data will be summarized using 
frequencies and percentages.  Statistical tests will be performed to assess the 
comparability of the placebo arm and the mixed two arms at baseline.  Treatment 
comparison will be made based on non-missing information.  Continuous variables will 
be analyzed using one-way analysis of variance (ANOVA).  Categorical variables will be 
analyzed using Fisher's exact test.
The first paragraph in Section 7.1 now reads:
Demographics and Baseline characteristics will be summarized for each arm and for 
overall of the FAS populations.  Continuous variables will be summarized with the 
number of non-missing observations by mean, standard deviation, first quartile, median, 
third quartile, minimum and maximum values.  Categorical data will be summarized using 
frequencies and percentages.
PsA Medical History and Disease Characteristics at Baseline No Longer Includes:
●
Categorical:
○
PASI (Psoriasis Area and Severity Index) assessed in subjects with ? 3% 
BSA of psoriatic plaques
○
ContinousAnti-cyclic citrullinated peptide (Anti-CCP) (units)
PsA Medical History and Disease Characteristics at Baseline Now Includes:
●
Continuous:


Risankizumab (ABBV-066)
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○
PASI (Psoriasis Area and Severity Index) assessed in subjects with ≥ 3% 
BSA at baseline
○
PsA Disease duration based on diagnosis date in years
9.0
Study Drug Duration and Compliance
Compliance now includes:
The maximum number of visits where injections are supposed to be received will be 
limited to 5.


Risankizumab (ABBV-066)
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10.0
Efficacy Analysis
Summary of Efficacy Variables and Corresponding Analyses previously read:
Table 2.
Summary of Efficacy Variables and Corresponding Analyses
Efficacy Variables
Analysis Method
Binary Efficacy Endpoints:
!
Primary and Secondary Endpoints:
o
ACR20/50/70 responses at Week 16
o
PASI90 response at Week 16 in 
subjects with PsO BSA ≥ 3% at 
baseline
!
Point estimate and 90% CI of the response rate for 
each treatment group using exact method
!
Point estimate, 90% CI and p-value of the response 
rate difference between combined Arm 1 and Arm 2 
vs the placebo, as well as the response rate 
difference between combined Arm 2 and Arm 3 
using the stratified Cochran-Mantel-Haenszel test.
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted using the 
same stratified Cochran-Mantel-Haenszel methods. 
!
Histogram of response rates by treatment group
!
MCP-Mod to evaluate dose-response for 
ACR 20/50/70
!
Forest plot
!
No multiplicity adjustments.
!
Imputation:  NRI (primary), OC
Further Binary Endpoints:
At all measured time points except Week 16:
!
ACR20/50/70
At all measured time points:
!
PASI75 in subjects with a ≥ 3% 
baseline PsO BSA
!
PASI100 in subjects with a ≥ 3% 
baseline PsO BSA
!
sPGA Response (0 = clear and 
1 = almost clear) in subjects with a 
≥3% baseline PsO BSA
!
EULAR response
!
Presence of Dactylitis
!
MDA
!
PsARC
!
Point estimate and 90% CI of the response rate for 
each treatment group using exact method
!
Point estimate, 90% CI and p-value of the response 
rate difference between combined Arm 1 and Arm 2 
vs the placebo, as well as the response rate 
difference between combined Arm 2 and Arm 3 
using the stratified Cochran-Mantel-Haenszel risk 
difference estimate.
!
Pairwise comparisons of the risankizumab dose 
groups vs placebo will be conducted using the same 
stratified Cochran-Mantel-Haenszel methods.
!
Plot of ACR20/50/70 response rates overtime by 
treatment group
!
Ordinal Logistic Regression of EULAR response
!
Forest plot
!
Imputation:  NRI (primary), OC


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Table 2.
Summary of Efficacy Variables and Corresponding Analyses 
(Continued)
Efficacy Variables
Analysis Method
Continuous Efficacy Endpoints:
Secondary Endpoints:
Change from baseline at Week 16:
!
TJC68
!
SJC66
!
HAQ-DI
!
SF-36
!
Dactylitis Count in subjects with 
dactylitis at baseline
!
SPARCC in subjects with enthesitis 
at baseline
!
mNAPSI assessed in subjects with 
nail psoriasis at baseline
Further Continuous Endpoints:
Change from baseline at all measured time 
points:
!
Physician's Global (VAS)
!
Patient's Pain (VAS)
!
Patient's Global Activity (VAS)
!
CRP
!
DAS28(CRP)
!
LDI in subjects with dactylitis at 
baseline
!
LEI in subjects with Enthesitis at 
baseline
!
Presence of enthesitis
!
FACIT-F Change from baseline at 
Week 16 and 24:
!
BASDAI in subjects with baseline 
inflammatory spondylitis
!
Point estimate and 90% CI within each treatment 
group using mixed model repeated measures 
(MMRM) model;
!
Point estimate, 90% CI and p-value for the mean 
change difference  between combined Arm 1 and 
Arm 2 vs placebo, as well as the mean change 
difference between combined Arm 2 and Arm 3 
with mixed model repeated measures (MMRM) 
model
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted MMRM 
model
!
Box plots and change from baseline over time will 
be plotted for key continuous variables
!
For SF-36, spyderdiagram will be provided
!
Imputation:  OC (primary)


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Summary of Efficacy Variables and Corresponding Analyses currently reads:
Table 2.
Summary of Efficacy Variables and Corresponding Analyses 
(Continued)
Efficacy Variables
Analysis Method
Continuous Efficacy Endpoints (continued):
mTSS and PsAMRIS:
!
Change from baseline (CFB) at 
Week 24 in mTSS
!
Change from baseline (CFB) at 
Week 16 in PsAMRIS
!
Mean CFB and 90% CI within each treatment 
group;
!
Mean CFB , 90% CI and p-value for the difference 
between combined Arm 1 and Arm 2 and the 
placebo, as well as the difference between 
combined Arm 2 and Arm 3 using ANCOVA 
model
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted with 
ANCOVA model


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Table 3.
Summary of Efficacy Variables and Corresponding Analyses now 
reads:
Efficacy Variables
Analysis Method
Binary Efficacy Endpoints:
!
Primary and Secondary Endpoints:
o
ACR20/50/70 responses at Week 16
o
PASI90 response at Week 16 in 
subjects with PsO BSA ≥ 3% at 
baseline
!
Point estimate and 90% CI of the response rate for 
each treatment group using exact method
!
Point estimate, 90% CI and p-value of the response 
rate difference between combined Arm 1 and Arm 2 
vs placebo, as well as the response rate difference 
between combined Arm 2 and Arm 3 vs placebo 
using the stratified Cochran-Mantel-Haenszel test.
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo using the same stratified 
Cochran-Mantel-Haenszel test.
!
Bar plot of response rates by treatment group
!
MCP-Mod to evaluate dose-response for 
ACR 20/50/70
!
Forest plot 
!
No multiplicity adjustments.
!
Imputation:  NRI (primary), OC, LOCF additionally 
for PASI90
Further Binary Endpoints:
At all measured time points except Week 16:
!
ACR20/50/70
At all measured time points:
!
PASI75 in subjects with a ≥ 3% 
baseline PsO BSA
!
PASI100 in subjects with a ≥ 3% 
baseline PsO BSA
!
sPGA Response (0 = clear and 
1 = almost clear) in subjects with a 
≥3% baseline PsO BSA
!
EULAR response (Multinomial)
!
EULAR response (Binary)
!
Presence of Dactylitis
!
MDA
!
PsARC
!
No Progression of mTSS
!
Point estimate and 90% CI of the response rate for 
each treatment group using exact method
!
Point estimate, 90% CI and p-value of the response 
rate difference between combined Arm 1 and Arm 2 
vs the placebo, as well as the response rate 
difference between combined Arm 2 and Arm 3 vs 
placebo using the stratified Cochran-Mantel-
Haenszel risk difference estimate.
!
Pairwise comparisons of the risankizumab dose 
groups vs placebo will be conducted using the same 
stratified Cochran-Mantel-Haenszel methods.
!
Plot of ACR20/50/70 response rates overtime by 
treatment group
!
Ordinal Logistic Regression of EULAR 
multinomial response
!
Forest plot
!
Imputation:  NRI (primary), OC, LOCF additionally 
for PASI75/100


Risankizumab (ABBV-066)
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Version 1.0 – 16 October 2017
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Table 3.
Summary of Efficacy Variables and Corresponding Analyses 
(Continued)
Efficacy Variables
Analysis Method
Continuous Efficacy Endpoints:
Secondary Endpoints:
Change from baseline at Week 16:
!
TJC68
!
SJC66
!
HAQ-DI
!
SF-36
!
Dactylitis Count in subjects with 
dactylitis at baseline
!
SPARCC in subjects with enthesitis 
at baseline
!
mNAPSI assessed in subjects with 
nail psoriasis at baseline
Further Continuous Endpoints:
Change from baseline at all measured time 
points:
!
Physician's Global (VAS)
!
Patient's Pain (VAS)
!
Patient's Global Activity (VAS)
!
CRP
!
DAS28(CRP)
!
LDI in subjects with dactylitis at 
baseline
!
LEI in subjects with Enthesitis at 
baseline
!
Presence of enthesitis
!
FACIT-F Change from baseline at 
Week 16 and 24:
!
BASDAI in subjects with baseline 
inflammatory spondylitis
!
Point estimate and 90% CI within each treatment 
group using mixed model repeated measures 
(MMRM) model;
!
Point estimate, 90% CI and p-value for the mean 
change difference  between combined Arm 1 and 
Arm 2 vs placebo, as well as the mean change 
difference between combined Arm 2 and Arm 3 vs 
placebo with mixed model repeated measures 
(MMRM) model
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted MMRM 
model
!
Change from baseline over time will be plotted for 
key continuous variables
!
For SF-36, spyderdiagram will be provided
!
Imputation:  OC (primary)


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Table 3.
Summary of Efficacy Variables and Corresponding Analyses 
(Continued)
Efficacy Variables
Analysis Method
Continuous Efficacy Endpoints (continued):
mTSS:
!
Change from baseline  at Week 24 in 
mTSS
!
Point estimate and 90% CI within each treatment 
group;
!
Point estimate, 90% CI and p-value for the 
difference between combined Arm 1 and Arm 2 and 
the placebo, as well as the difference between 
combined Arm 2 and Arm 3 using ANCOVA 
model
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo using an ANCOVA model
PsAMRIS:
!
Change from baseline at Week 16 in 
PsAMRIS
!
Descriptive statistics at Week 16
!
Imputation:  OC
10.7
Further Efficacy Analysis
The last paragraph in Section 10.7 previously read:
Analyses at all measured time points will be conducted in a similar fashion as for 
Week 16 endpoints except for EULAR response, mTSS, and PSAMRIS.  EULAR 
response will be analysed using ordinal logistic regression with treatment group, prior 
TNFi use, and concurrent MTX use as main factors and baseline DAS value as a 
covariate.  mTSS and PSAMRIS will be analysed using ANCOVA with treatment group, 
prior TNFi use, and concurrent MTX use as main factors and baseline value as a 
covariate.  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.
The last paragraph in Section 10.7 now reads:
Analyses at all measured time points will be conducted in a similar fashion as for 
Week 16 endpoints except for mTSS and PSAMRIS.  Multinomial EULAR response will 
additionally be analysed using ordinal logistic regression with treatment group, prior 


Risankizumab (ABBV-066)
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TNFi use, and concurrent MTX use as main factors and baseline DAS value as a 
covariate.  mTSS will be analysed using ANCOVA with treatment group, prior TNFi use, 
and concurrent MTX use as main factors and baseline value as a covariate.  PsAMRIS 
will be described descriptively separately for hand and foot images as well as a 
descriptive analysis of the PsAMRIS feature scores, also separate for hand and foot 
images.  Further efficacy endpoints will be summarized descriptively.  Data will be 
displayed by graphics as appropriate.
10.9
Efficacy Variables Definition and Conventions
10.9.7
European League Against Rheumatism (EULAR) Response 
Criteria
This section now additionally includes:
EULAR response will also be analyzed as a binary variable with Good being defined as 
response and Moderate & None being defined as non-response.
For missing data use Non-Responder Imputation using the score of "None" as 
non-response.  For the binary response Good vs (Moderate & None) Non-Responder 
Imputation use Moderate & None as non-response.
10.9.10
Psoriasis Area and Severity Index (PASI) and Body Surface 
Area (BSA)
This section now includes:
An additional LOCF analysis will be performed, using last observation carried forward 
imputation for visits post-baseline with PASI70/90/100 response then being based on the 
imputed PASI score.


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10.9.12
Leeds Dactylitis Index (LDI)
This section previously read:
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.  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).
This section now reads:
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.  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), using a minimum difference of 10% to define a dactylitic 
digit.  When the difference is less than 10% the LDI for that digit is 0.
Dactylitis Count previously read:
The dactylitis count is the number of fingers and toes with dactylitis that are both affected 
and tender, with a range of 0 – 20.  If a site is not assessed assign it a value of "0."
Dactylitis Count now reads:
The dactylitis count is the number of fingers and toes with dactylitis, with a range of 
0 – 20.  If a site is not assessed assign it a value of "0."
10.9.20
Modified Total Sharp Score (mTSS)
This section now reads:
The radiographic outcome will be assessed and scored according to Sharp's method (Van 
der Heijde modification) centrally by two qualified physicians/radiologists who will be 
blinded to the site number, subject number, treatment allocation, time sequence and 
clinical response.


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Calculation of the Modified Total Sharp Score
To obtain the total mTSS score, scores for erosions and JSN in both the hands and feet 
will be added together.
The range of scores is summarized below.
Hands
Feet
Total 
(Hands and Feet)
Erosion Score Range
0-200
0-120
0-320
Joint Space Narrowing Range
0-160
0-48
0-208
mTSS Range for Erosion and JSN
0-360
0-168
0-528
The following joints will be examined for assessing Erosions:
Foota
Handb
1st IP
1st IP
3rd MCP
5th MCP
Ulnar
1st MTP
1st MCP
3rd DIP
5th DIP
MC1
2nd MTP
2nd PIP
4th PIP
Multangularc
3rd MTP
2nd MCP
4th MCP
Navicular
4th MTP
2nd DIP
4th DIP
Lunate
5th MTP
3rd PIP
5th PIP
Radius
a.
IP:  Inter-Phalangeal, MTP:  Metatarso-Phalangeal
b.
IP:  Inter-Phalangeal, PIP:  Proximal Inter-Phalangeal, MCP:  Metacarpophalangeal, DIP:  Distal Inter-Phalangeal
c.
Trapezium/Trapezoid as read as one unit-Multangular


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The following joints will be examined for assessing Joint Space Narrowing:
Foota
Handb
1st IP
1st MCP
3rd DIP
5th DIP
RC
1st MTP
2nd PIP
4th PIP
3rd CMC
1st IP
2nd MTP
2nd MCP
4th MCP
4th CMC
3rd MTP
2nd DIP
4th DIP
5th CMC
4th MTP
3rd PIP
5th PIP
MN
5th MTP
3rd MCP
5th MCP
CNL
a.
IP:  Inter-Phalangeal, MTP:  Metatarso-Phalangeal
b.
PIP:  Proximal Inter-Phalangeal, MCP:  Metacarpo-Phalangeal, CMC:  Carpo-Metcarpal, MN: Multangular-
Navicular, CNL:  Capitate-Navicular Lunate, RC:  Radio-Carpal, DIP:  Distal Inter-Phalangeal
For each Joint and Bone assessed scores range as follows:
●
Erosions:  0 – 5 (hands/wrists) or 0 – 10 (feet) to characterize the extent of 
erosions (where 0 denotes no erosion).
●
Joint Space Narrowing:  0 – 4 to characterize the extent of Joint Space 
Narrowing (JSN) (where 0 denotes no narrowing).
●
The categorical scores G and P could be possible for the entry for the 
following situation:
○
Osteolysis in the form of pencil-in-cup:  Osteolysis of proximal phalanx 
and the base of the distal phalanx resulting in a pencil like proximal 
phalanx covered by cup like base of the distal phalanx.  Pencil-in-cup will 
be scored as "P" where applicable.
○
Gross Osteolysis:  Osteolysis of the phalanx resulting a loss of the normal 
joint structure, ususlly accompanied by shorting of the length of the 
phalanx.  Gross osteolysis will be scored as "G" where applicable.
Erosion and JSN scores for each reader are calculated by taking the sum of the left and 
right joints as shown below.


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Right
Left
i
Reader 
Erosion
Erosion
Erosion
∀
#
Right
Left
i
Reader 
JSN
JSN
JSN
∀
#
for i = 1, 2.
Thus, the maximum erosion score for all 40 joints in hands/wrists is 200.  The maximum 
erosion score for all 12 joints in feet is 120.  Thus, the total erosion score for hands/wrists 
and feet is 320 assessed on total 52 erosion joints.
The maximum score for JSN in all 40 hand/wrist joints is 160.  The maximum score for 
JSN in all 12 feet joints is 48.  Thus, the total JSN score for hand/wrist and feet is 208 
based on total 52 JSN joints.
Since two independent readers evaluate each film, the mean score will be calculated for 
the two readers from the individual erosion and JSN scores as shown below:
2
Erosion
Erosion
Erosion
Reader2
Reader1 ∀
#
2
JSN
JSN
JSN
Reader2
Reader1 ∀
#
The mTSS for each reader is defined as the sum of the erosion and JSN scores:
TSSReader i = ErosionReader i + JSNReader i for i = 1, 2.
The mTSS from Erosion score plus JSN score will be used for all x-ray endpoint 
calculations.
.
JSN
Erosion
TSS
∀
#
Handling of missing joints in mTSS score calculation
For categorical score G and P, the maximum score per location should be assigned before 
any imputation.


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Missing joint score imputation will be performed for Erosion and JSN respectively.  If a 
score at a location/joint is missing then the methods described below will be used to 
calculate Erosion and JSN total score for that visit.
Method 1:
●
If the scores of more than 50% of JSN scoring locations are available 
(e.g., 27 or more JSN scoring locations out of 52 total JSN scoring locations), 
the total JSN score would be calculated as Total JSN Score = Avg of all 
available scores*52
●
If 50% or less (e.g., 26 or fewer JSN scoring locations out of 52 total JSN 
scoring locations) of the JSN scoring locations are readable, the Total JSN 
Score will not be calculated
●
If the scores of more than 50% of Erosion scoring locations are available 
(e.g., 27 or more Erosion scoring locations out of 52 total Erosion scoring 
locations), the total Erosion score would be calculated as Total Erosion 
Score = average of all available hand scores*40 + average of all available foot 
scores*12.
●
If 50% or less (e.g., 26 or fewer erosion scoring locations out of 52 total 
erosion scoring locations) of the erosion scoring locations are readable, the 
Total erosion Score will not be calculated
Method 2:
Missing joints for baseline will be imputed as 0 (denote no erosion or narrowing).
Missing joint score imputation will be performed for Erosion and JSN respectively.  If a 
score at any location/joint is missing for a post-baseline visit, and if there are >= 27 joints 
(i.e., more than 50%) in Erosion (or JSN) with non-missing change from baseline scores, 
the method described below will be used to impute the missing joint score for that visit.  
Otherwise, the erosion/JSN score will be missing so TSS is missing.


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●
Step 1:  Calculate average change from Baseline to follow-up visit (for 
example, Week 24) computed for all observed non-missing change from 
baseline scores for a given subject.
●
Step 2:  The imputed value at the follow-up visit will be the Baseline score 
plus the average change score from step 1.  If the imputed score exceeds the 
upper range of that bone/joint location, take the upper range to be the imputed 
value.
Adjudication process
Two reviewers will independently review the images.  Adjudication will occur for all 
subjects with pre-specified criteria for that study/indication between the two reviewers' 
mTSS change scores, in which case another reviewer, different from the reviewers who 
performed primary assessments, will make a third, independent assessment.
For the calculation of erosion and JSN total score, individual visit score of the 2 closest of 
the 3 readings (2 primary readers and adjudicator) will be used to determine the final 
score.  If one score is in the middle (equally close), take the middle score.  If one of 
3 readings is missing, take the average of two non-missing readings.  If two of 3 readings 
are missing, take the non-missing reading.  If all 3 readings are missing, 
erosion/JSN = missing and hence mTSS = missing.
No Progression
No progression of mTSS is defined as a change in mTSS score less than or equal to 0.
10.9.21
Psoriatic Arthritis Magnetic Resonance Image Scoring 
System (PsAMRIS)
Psoriatic Arthritis Magnetic Resonance Image Scoring System (PsAMRIS) 
previously read:
The PsAMRIS will be evaluated at Baseline and Week 16.  Change from baseline in 
PsAMRIS score at Week 16 will be summarized.  PSAMRIS will have six separate scores 


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for Synovitis (0 – 72), Tenosynovitis (0 – 72), Periaticular Inflammation (0 – 48), Osteitis 
(0 – 144), Bone Erosion (0 – 480), and Bone Proliferation (0 – 24).
Psoriatic Arthritis Magnetic Resonance Image Scoring System (PsAMRIS) now 
reads:
The PsAMRIS will be evaluated at Baseline and Week 16.  PSAMRIS will have 
six separate scores.  Four scores for Inflammation:  Synovitis, Tenosynovitis, Periaticular 
Inflammation, Osteitis.  Two scores for Damage, Bone Erosion, and Bone Proliferation.  
Descriptive statistics will be used to summarize Inflammation, Damage, and Total Scores 
for each visit separately for hands and feet.


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11.0
Safety Analysis
11.2
Analysis of Adverse Events
Table 20 for DILI previously read:
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Drug induced 
liver injury 
(DILI)
Drug induced 
liver injury 
(DILI)
Broad
Hepatic failure, fibrosis 
and cirrhosis and other 
liver damage-related 
conditions 
(SMQ 20000013)
Broad
Hepatitis, non-infectious 
(SMQ 20000010)
Broad
Cholestasis and jaundice 
of hepatic origin 
(SMQ 20000009)
Broad
Liver related 
investigations, signs and 
symptoms 
(SMQ 20000008)
Narrow
Liver-related coagulation 
and bleeding disturbances 
(SMQ 20000015)
PTs
N


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Table 20 now reads:
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Possible Drug 
induced liver 
injury (DILI)
Possible Drug 
induced liver 
injury (DILI)
Broad
Hepatic failure, fibrosis 
and cirrhosis and other 
liver damage-related 
conditions 
(SMQ 20000013)
Broad
Hepatitis, non-infectious 
(SMQ 20000010)
Broad
Cholestasis and jaundice 
of hepatic origin 
(SMQ 20000009)
Broad
Liver related 
investigations, signs and 
symptoms 
(SMQ 20000008)
Narrow
Liver-related coagulation 
and bleeding disturbances 
(SMQ 20000015)
PTs
N
4. Adverse Events by "Reasonably Possibly Related" Relationship has changed to 
read:
4.
Adverse Events by Maximum Relationship
Adverse events will be summarized by maximum relationship to study drug, as 
assessed by the investigator.  Relationship of an AE to study drug is assessed by 
the investigator and collected in the CRF as 'Yes' or 'No.'  If a subject has an 
adverse event with unknown relationship, the subject will be counted in the 
relationship category of "unknown," even if the subject has another occurrence of 
the same event with a relationship of "No."  If the subject has another occurrence of 


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the same adverse event with a relationship assessment of "Yes," the subject will be 
counted under the "yes" category.
11.3
Analysis of Laboratory Data
Table 21 used to read:
Table 21.
Criteria for Potentially Clinically Important Chemistry Values
Definition of Potentially Clinically Important Current 
(Version 3) NCI CTCAE Grade 3
Chemistry Variables
Units
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
ALP
U/L
> 5.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN


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Table 21 now reads:
Table 21.
Criteria for Potentially Clinically Important Chemistry Values
Definition of Potentially Clinically Important Current 
(Version 3) NCI CTCAE Grade 3 or greater
Chemistry Variables
Units
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
ALP
U/L
> 5.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN
Table 22 used to read:
Table 22.
Criteria for Potentially Clinically Important Hematology Values
Definition of Potentially Clinically Important 
Current (Version 3) Grade 3
Hematology Variables
Units
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0


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Table 22 now reads:
Table 22.
Potentially Clinically Important Hematology Values
Hematology Variables
Units
Definition of Potentially Clinically Important
Current (Version 4) CTCAE Grade 3 or greater
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
11.4
Analysis of Vital Signs and Weight
11.4.1
Variables and Criteria Defining Abnormality
Table 24 used to read:
Table 24.
Criteria for Potentially Clinically Significant Vital Sign Findings
Vital Signs
Category
Criteria for Potential Clinically Significant Vital Signs
Systolic blood pressure
Low
Value ≤ 90 mmHg or decrease ≥ 20 mmHg from Baseline
High
Value ≥ 180 mmHg or increase ≥ 20 mmHg from Baseline
Diastolic blood pressure
Low
Value ≤ 50 mmHg or decrease ≥ 15 mmHg from Baseline
High
Value ≥ 105 mmHg or increase ≥ 15 mmHg from Baseline
Pulse
Low
Value ≤ 50 bpm or decrease ≥ 15 bpm from Baseline
High
Value ≥ 120 bpm or increase ≥ 15 bpm from Baseline


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Table 24 now reads:
Table 24.
Criteria for Potentially Clinically Significant Vital Sign Findings
Vital Signs Variables
Criterion
Definition of Potentially Clinically Important
Systolic Blood Pressure 
(mmHg)
Low
Value ≤ 90 mmHg and decrease ≥ 20 mmHg from Baseline
High
Value ≥ 180 mmHg and increase ≥ 20 mmHg from Baseline
Diastolic Blood Pressure 
(mmHg)
Low
Value ≤ 50 mmHg and decrease ≥ 15 mmHg from Baseline
High
Value ≥ 105 mmHg and increase ≥ 15 mmHg from Baseline
Heart Rate (bpm)
Low
Value ≤ 50 bpm and decrease ≥ 15 bpm from Baseline
High
Value ≥ 120 bpm and increase ≥ 15 bpm from Baseline




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Version 1.0 – 12 May 2017
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1.0
Title Page
Statistical Analysis Plan
Boehringer Ingelheim Study 1311.5
(AbbVie Study M16-002)
A Randomized, Double-Blind, Placebo-Controlled 
Proof-of-Concept Dose-Ranging Study of 
Risankizumab in Subjects with Active Psoriatic 
Arthritis
Date:  12 May 2017
Version 1.0


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2.0
Table of Contents
1.0
Title Page ...............................................................................1
2.0
Table of Contents ..................................................................2
3.0
Introduction...........................................................................8
4.0
Study Objectives, Design and Procedures............................8
4.1
Objectives .............................................................................................. 8
4.2
Overall Trial Design and Plan................................................................. 9
4.3
Sample Size.......................................................................................... 11
4.4
Interim Analysis................................................................................... 12
4.5
Data Monitoring Committee (DMC)..................................................... 12
5.0
Analysis Populations ........................................................... 13
5.1
Definition for Analysis Populations ...................................................... 13
5.2
Variables Used for Stratification of Randomization .............................. 13
6.0
Analysis Conventions .......................................................... 13
6.1
Definition of Baseline........................................................................... 13
6.2
Definition of Final Observation (Applicable to Safety Analyses 
Other than Laboratory and Vital Signs) ................................................ 14
6.3
Definition of Rx Days (Days Relative to the First Dose of Study 
Drug).................................................................................................... 14
6.4
Definition of Analysis Windows........................................................... 14
6.5
Missing Data Handling......................................................................... 18
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications..............21
7.1
Demographic and Baseline Characteristics ........................................... 21
7.2
Medical History.................................................................................... 24
7.3
Previous Treatment and Concomitant Medications ............................... 24
7.4
Protocol Deviations .............................................................................. 25
8.0
Subject Disposition..............................................................26
9.0
Study Drug Duration and Compliance .............................. 27
10.0
Efficacy Analysis .................................................................28
10.1
General Considerations......................................................................... 28
10.2
Primary Efficacy Analysis.................................................................... 33


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10.3
Sensitivity Analysis of Primary Efficacy Variable ................................ 34
10.4
Dose Response Modelling .................................................................... 34
10.5
Secondary Efficacy Analyses ............................................................... 35
10.6
Further Efficacy Analysis..................................................................... 37
10.7
Handling of Multiplicity....................................................................... 38
10.8
Efficacy Subgroup Analysis ................................................................. 38
10.9
Efficacy Variables Definition and Conventions .................................... 39
10.9.1
ACR Criteria ........................................................................................ 39
10.9.2
Joint Evaluation.................................................................................... 42
10.9.3
Patient's Global Assessment of Disease Activity for Arthritis 
(PtGA) ................................................................................................. 43
10.9.4
Physician's Global Assessment of Disease Activity for Arthritis 
(PhGA)................................................................................................. 43
10.9.5
Patient's Assessment of Pain (VAS)...................................................... 43
10.9.6
Disease Activity Score Based on DAS28.............................................. 43
10.9.7
European League Against Rheumatism (EULAR) Response 
Criteria................................................................................................. 45
10.9.8
Minimal Disease Activity (MDA) in PsA ............................................. 45
10.9.9
Psoriatic Arthritis Response Criteria (PsARC) Response ...................... 46
10.9.10
Psoriasis Area and Severity Index (PASI) and Body Surface Area 
(BSA)................................................................................................... 46
10.9.11
Static Physician's Global Assessment (sPGA)....................................... 48
10.9.12
Leeds Dactylitis Index (LDI)................................................................ 49
10.9.13
Leeds Enthesitis Index (LEI) ................................................................ 50
10.9.14
Research Consortium of Canada (SPARCC) Enthesitis Index............... 51
10.9.15
Modified Nail Psoriasis Severity Index (mNAPSI) ............................... 52
10.9.16
Health Assessment Questionnaire-Disability Index (HAQ-DI) ............. 52
10.9.17
SF-36v2................................................................................................ 53
10.9.18
Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-F)............................................................................................ 55
10.9.19
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) .......... 56
10.9.20
Modified Total Sharp Score (mTSS)..................................................... 57
10.9.21
Psoriatic Arthritis Magnetic Resonance Image Scoring System 
(PsAMRIS) .......................................................................................... 60


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11.0
Safety Analysis.....................................................................63
11.1
General Considerations......................................................................... 63
11.2
Analysis of Adverse Events.................................................................. 63
11.3
Analysis of Laboratory Data................................................................. 71
11.3.1
Variables and Criteria Defining Abnormality........................................ 73
11.3.2
Statistical Methods ............................................................................... 75
11.4
Analysis of Vital Signs and Weight ...................................................... 78
11.4.1
Variables and Criteria Defining Abnormality........................................ 78
11.4.2
Statistical Methods ............................................................................... 78
11.4.3
Analysis of ECG Parameters ................................................................ 79
11.5
Local Tolerability................................................................................. 79
12.0
Biomarkers Analysis ...........................................................79
13.0
Pharmacokinetic Analysis...................................................79
14.0
Summary of Changes .......................................................... 79
14.1
Summary of Changes Between the Latest Version of Protocol and 
the Current SAP ................................................................................... 79
15.0
References............................................................................80
16.0
Appendix.............................................................................. 81
A1.
Standard Digit Reference Tables .......................................................... 81
A2.
Modified Nail Psoriasis Severity Index (mNAPSI) ............................... 82
A3.
PSAMRIS Joints .................................................................................. 85
A4.
Important Protocol Violations............................................................... 87
List of Tables
Table 1.
Power and Sample Size for the Superiority Test of ACR 20 at 
Week 16............................................................................................... 12
Table 2.
Visit Windows for Analysis of Efficacy Variables (ACR20/50/70, 
BSA, PSARC, MDA, TJC68 and SJC66, Patient's Assessment of 
Pain/Patient's Global and Physician's Global Assessment of 
Disease Activity, HAQ-DI, CRP, LDI, LEI, Dactylitis Count, 
Dactylitis Presence, SPARCC Enthesitis Index, PASI, sPGA) .............. 15
Table 3.
Visit Windows for Analysis of BASDAI .............................................. 16
Table 4.
Visit Windows for Analysis of SF-36 v2 and FACIT-F ........................ 16


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Table 5.
Visit Windows for Analysis of mNAPSI .............................................. 16
Table 6.
Visit Windows for Analysis of mTSS................................................... 16
Table 7.
Visit Windows for Analysis of PsAMRIS............................................. 17
Table 8.
Visit Windows for Local Tolerability ................................................... 17
Table 9.
Visit Windows for Analysis of Safety Laboratory Tests, and Vital 
Signs .................................................................................................... 17
Table 10.
Visit Windows for Summary of risankizumab Injections for 
Treatment Group Risankizumab 150 mg at Week 0, 4, 8, 12 and 
16......................................................................................................... 18
Table 11.
Overview of Efficacy Endpoint Assessments........................................ 28
Table 12.
Summary of Efficacy Variables and Corresponding Analyses............... 30
Table 13.
Candidate Models................................................................................. 35
Table 14.
Anatomical Joints Assessed for Calculation of Tender and 
Swollen Joint Counts (TJC68 and SJC66)............................................. 42
Table 15.
Anatomical Joints for DAS28(CRP) Calculation .................................. 44
Table 16.
Minimal Disease Activity (MDA) Criteria in Psoriatic Arthritis ........... 45
Table 17.
sPGA Rating Scale for Overall Psoriatic Disease.................................. 49
Table 18.
Enthesial Sites Examined for SPARCC Calculation.............................. 51
Table 19.
PsAMRIS Scoring Guidance ................................................................ 62
Table 20.
Areas of Safety Interest Listing............................................................. 67
Table 21.
Criteria for Potentially Clinically Important Chemistry Values ............. 72
Table 22.
Criteria for Potentially Clinically Important Hematology Values .......... 73
Table 23.
Laboratory Tests................................................................................... 74
Table 24.
Criteria for Potentially Clinically Significant Vital Sign Findings ......... 78
List of Figures
Figure 1.
Trial Design ......................................................................................... 10
Figure 2.
An Example of Spydergram of SF-36................................................... 54
Figure 3.
An Example of eDISH Plot .................................................................. 77


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List of Abbreviations
ACR
American College of Rheumatology
AE
Adverse Event
ASI
Areas of Special Interest
ALT
Alanine Aminotransferase
Anti-CCP
Anti-Cyclic-Citrullinated Peptide
AST
Aspartate Aminotransferase
BASDAI
Bath AS Disease Activity Index
BI
Boehringer Ingelheim
BSA
Body Surface Area
CASPAR
Classification criteria for Psoriatic Arthritis
CRP
C-Reactive Protein
DAS28
Disease Activity Score in 28 joints
DMARDs
Disease-Modifying Antirheumatic Drugs
DMC
Data Monitoring Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EOS
End Of Study
EOT
End Of Treatment
EULAR
European League Against Rheumatism
FACIT-F
Functional Assessment of Chronic Illness Therapy-Fatigue
FAS
Full Analysis Set
FU
Follow-Up
HAQ-DI
Health Assessment Questionnaire-Disability Index
HIV
Human Immunodeficiency Virus
IRT
Interactive Response System
i.v.
intravenous
LDI
Leeds Dactylitis Index
LEI
Leeds Enthesitis Index
MACE
Major Adverse Cardiovascular Event
MAR
Missing At Random
MDA
Minimal Disease Activity
MedDRA
Medical Dictionary for Drug Regulatory Activities


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MMRM
Mixed Model Repeated Measures Model
mNAPSI
Modified Nail Psoriasis Severity Index
MRI
Magnetic Resonance Imaging
mTSS
Modified Total Sharp Score
MTX
Methotrexate
NRI
Non-Responder Imputation
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
OLE
Open-Label Extension
OMERACT
Outcome Measures in Rheumatology
PASI
Psoriasis Area and Severity Index
PD
Pharmacodynamic
PK
Pharmacokinetic
PsA
Psoriatic Arthritis
PsAMRIS
Psoriatic Arthritis Magnetic Resonance Image Scoring System
PsARC
Psoriatic Arthritis Response Criteria
PsO
Psoriasis
RCTC
Rheumatology Common Toxicity Criteria
REML
Residual Maximum Likelihood Method
REP
Residual Effect Period
SAE
Serious Adverse Event
SF-36
Short Form-36 Health Survey
SJC
Swollen Joint Count(s)
SPARCC
Spondyloarthritis Research Consortium of Canada
sPGA
Static Physician Global Assessment
PtGA
Patient's Global Assessment of Disease Activity for Arthritis
PhGA
Physician's Global Assessment of Disease Activity for Arthritis 
TJC
Tender Joint Count(s)
TNF
Tumor necrosis factor
TNFi
Tumor necrosis factor inhibitor(s)
VAS
Visual Analog Scale
W
Week
WBC
White Blood Count


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3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Clinical Statistics Department for Boehringer Ingelheim (BI) Study 1311.5 
(AbbVie Study M16-002) dated 12 October 2016.  This study was sponsored by BI and 
data was collected using their internal SOPs.
This SAP will provide details to further elaborate statistical methods as outlined in the BI 
Protocol 1311.5 and will describe analysis conventions to guide the statistical 
programming work.  This SAP will be signed off before the study database is locked.
Analyses will be performed using SAS version 9.4 (SAS Institute Inc., Cary, NC  27513) 
under the UNIX operating system.
4.0
Study Objectives, Design and Procedures
4.1
Objectives
The objectives of this study are to provide proof-of-concept and dose-ranging data of 
risankizumab in subjects with active psoriatic arthritis (PsA) to support advancement and 
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.  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 for subjects enrolling into the open-label extension 
(OLE) Study M16-244.
The safety of risankizumab will be evaluated during treatment and through the Week 32 
follow-up, or through last visit for subjects enrolling into the OLE study.  The effect of 
emergence of anti-drug antibodies (ADA) on safety and efficacy will be explored.
In addition, risankizumab pharmacokinetic (PK) exposure will be assessed to provide data 
for subsequent pharmacokinetic- pharmacodynamic (PK-PD) modelling.  The 


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risankizumab exposure-response profile will be characterized 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 
magnetic resonance imaging (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.
4.2
Overall Trial Design and Plan
This is a multi-national, randomized, parallel-design, dose-ranging, multiple-dose, 
placebo-controlled, double-blinded Phase 2 study.  Approximately 180 eligible subjects 
with active PsA were randomized at 2:2:2:1:2 ratio, stratified based on prior tumor 
necrosis factor inhibitor(s) (TNFi) use and concurrent methotrexate (MTX) use into 
five treatment arms shown in Figure 1.  Subjects with prior TNFi experience were to be 
capped at approximately 70%. 
The overall trial treatment duration is 16 weeks with an additional 16 weeks follow-up 
period, or subjects who have completed all doses and Week 24 visit will potentially have 
the option to enroll into a separate OLE known as Study M16-244.  Subjects electing to 
participate in the OLE study will not complete any remaining visit in this study (BI 
Study 1311.5) after signing the OLE ICF and will solely follow the procedures in the OLE 
study protocol.
Subjects in Study 1311.5 will receive risankizumab/placebo as described in Figure 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 in the protocol. 


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Figure 1.
Trial Design
If subjects have a reduction in both tender and swollen joint count of < 20% relative to 
baseline at the Week 16 assessment, they were permitted to alter their concomitant PsA 
treatment or start an additional treatment, except biologics, according to investigator's 
judgment and local standard of care, after receiving Week 16 study drug dose.  After 
Week 24, subjects not enrolling in the OLE study are allowed to 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, please refer to 
protocol Section 4.2.1.
In addition to clinical endpoint assessments, subjects will have X-rays performed at 
Weeks 0 and 24 for assessment of the modified total Sharp score (mTSS).  Approximately 
90 subjects from selected sites will be included in the MRI sub-study, with MRI 
assessments performed at Weeks 0 and 16.


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The analysis of the primary endpoint (ACR 20) will be performed after the last subject 
completes the Week 16 visit.  The trial will be unblinded to the Sponsor, for analysis, but 
subjects and investigators will remain blinded until after the completion of the trial.
Individual subject participation is concluded when the subject has completed the last 
planned visit (Week 32 or early End of Study visit if a patient prematurely discontinues or 
the final visit prior to enrolling in the OLE study).  The "last-subject-last-visit-primary-
endpoint" is the last scheduled primary endpoint visit at Week 16 completed by the last 
subject.  The end of the trial is defined as "last subject out," i.e., last scheduled visit 
completed by last subject.
4.3
Sample Size
The sample size was determined on the basis of a one-sided comparison between the 
average rate of 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 (equivalent 
to two sided test of 0.1 significance).  Table 1 shows 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 enroll 20 participants into Arm 4 dose response 
modeling.  The total sample size for this study is therefore 180 participants.  Figure 1
provides details on the study arms.  This study is not powered to detect statistically 
significant differences between the different risankizumab treatment arms.


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Table 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 
of Arm 1 + 2 
and Placebo
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%
4.4
Interim Analysis
No interim efficacy analysis is planned for this study. 
The primary efficacy analysis will be performed once all subjects completed Week 16 
visits based on the interim locked database.  Unblinded group level results will be shared 
with the AbbVie internal study team.  No type I error adjustment will be done.
4.5
Data Monitoring Committee (DMC)
An independent DMC operating under a charter is responsible for reviewing safety data 
periodically to ensure subjects safety and to monitor the conduct of the trial and the 
integrity of the data.  An independent analytic team external to both BI and AbbVie will 
provide the unblinded results to the DMC.


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5.0
Analysis Populations
5.1
Definition for Analysis Populations
Full Analysis Set (FAS)
The FAS consists of all randomized subjects who have received at least one dose of study 
medication.  The subjects will be grouped by the treatment group assigned at the time of 
randomization regardless of the actual treatment they receive during the study.
All baseline and efficacy analyses will be based on FAS.
Safety Analysis Set
The Safety Analysis Set consists of all subjects who have received at least one dose of 
study medication.  For safety parameters, the treatment that was actually used by the 
subject will be applied in the analysis (an as-treated analysis).
5.2
Variables Used for Stratification of Randomization
Randomization will be stratified with respect to naïve or experienced to TNFi therapy and 
concurrent MTX use (yes or no) as determined at baseline.
6.0
Analysis Conventions
6.1
Definition of Baseline
The last non-missing measure collected on or before the day of the first dose of study drug 
injection for each randomized subject will be used as Baseline for summary of 
demographics, disease characteristics and safety analyses.  For efficacy endpoints except 
mTSS and PsAMRIS, the baseline is defined as the last non missing pre-treatment 
observation prior to first dose.  The Baselines for the modified total Sharp score (mTSS) 
and the MRI assessment, the imaging endpoints, are defined as the non-missing 
observation prior to Day 13 and closest to Day 1. 


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6.2
Definition of Final Observation (Applicable to Safety 
Analyses Other than Laboratory and Vital Signs)
Final observation is defined as:
●
The last non-missing observation collected within 105 days (15 weeks) 
following the last dose of study drug for subjects who did not enter the OLE. 
●
The last non-missing observation collected on or before the subjects signed the 
Informed Consent Form (ICF) for the OLE and entered the OLE.
6.3
Definition of Rx Days (Days Relative to the First Dose of 
Study Drug)
Rx days are calculated for each time point relative to the date of first dose of study drug.  
They are defined as the number of days between the date of the first dose of study drug 
and the specific time point.  Rx days are negative values when the time point of interest is 
prior to the first study drug dose day.  Rx days are positive values when the time point of 
interest is on or after the first study drug dose day.  The day of the first dose of study drug 
is defined as Rx Day 1, while the day prior to the first study drug dose is defined as Rx 
Day –1 (there is no Rx Day 0). 
6.4
Definition of Analysis Windows
All time points and corresponding time windows are defined based on Rx Days.
For efficacy analyses, laboratory parameters, and vital sign variables, analysis windows 
are constructed using the following algorithm:
●
Determine the nominal Rx day for each visit (e.g., Week 4 [4 weeks after 
Baseline visit] equals Rx Day 29).
●
In order to include all post baseline data, the first post-baseline interval starts 
on the first day after the first dose of study drug (Rx Day 2).
●
Determine the window around a specific nominal Rx day by adding or 
subtracting half of the interval between adjacent visits (e.g., days between 


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Week 2 and Week 4 is 14).  The threshold between adjacent visits is 
determined by splitting the interval evenly between the visits.  If the resulting 
split is between Rx days, then the threshold is determined as the midpoint 
between the adjacent visits.  If the resulting split is on an Rx day, then the 
threshold is determined as being between that Rx day and the Rx day prior to it 
(e.g., the split between Week 2 and Week 4 would be between Rx Days 22 and 
23).
●
If more than one assessment is included in a time window the assessment 
closest to the nominal day will be used.  If there are two observations 
equidistant to the nominal day, the one after the nominal day will be used in 
analyses.  If more than one assessment is included on the same day, then the 
worst assessment on that day will be used in analyses.
The protocol specified visits and corresponding time windows used in the various efficacy 
analyses, laboratory parameters, and vital sign variables, are presented in the following 
Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, and Table 9.
Table 2.
Visit Windows for Analysis of Efficacy Variables (ACR20/50/70, 
BSA, PSARC, MDA, TJC68 and SJC66, Patient's Assessment of 
Pain/Patient's Global and Physician's Global Assessment of Disease 
Activity, HAQ-DI, CRP, LDI, LEI, Dactylitis Count, Dactylitis 
Presence, SPARCC Enthesitis Index, PASI, sPGA)
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
< 1
Week 2
VISIT 3
15
[2, 22]
Week 4
VISIT 4
29
[23, 43]
Week 8
VISIT 5
57
[44, 71]
Week 12
VISIT 6
85
[72, 99]
Week 16
VISIT 7 (EOT)
113
[100, 127]
Week 20
VISIT 8
141
[128, 155]
Week 24
VISIT 9
169
[156, 183]
Week 28
VISIT 10
197
[184, 211]
Week 32
EOS
225
[212, 238]


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Table 3.
Visit Windows for Analysis of BASDAI
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
< 1
Week 16
VISIT 7 (EOT)
113
[2, 141]
Week 24
VISIT 9
169
[142, 196]
Table 4.
Visit Windows for Analysis of SF-36 v2 and FACIT-F
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
< 1
Week 4
VISIT 4
29
[2, 71]
Week 16
VISIT 7 (EOT)
113
[72, 141]
Week 24
VISIT 9
169
[142, 196]
Table 5.
Visit Windows for Analysis of mNAPSI
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
< 1
Week 4
VISIT 4
29
[2, 43]
Week 8
VISIT 5
57
[44, 71]
Week 12
VISIT 6
85
[72, 99]
Week 16
VISIT 7 (EOT)
113
[100, 127]
Week 20
VISIT 8
141
[128, 155]
Week 24
VISIT 9
169
[156, 183]
Week 28
VISIT 10
197
[184, 211]
Week 32
EOS
225
[212, 238]
Table 6.
Visit Windows for Analysis of mTSS
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
[–999, 13]
Week 24
VISIT 9
169
[14, 306]


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Table 7.
Visit Windows for Analysis of PsAMRIS
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
[–999, 13]
Week 16
VISIT 7 (EOT)
113
[14, 224]
Table 8.
Visit Windows for Local Tolerability
Window Label
Nominal Visit
Target Day
Interval
Week 2
VISIT 3
15
[1, 22]
Week 4
VISIT 4
29
[23, 43]
Week 8
VISIT 5
57
[44, 71]
Week 12
VISIT 6
85
[72, 99]
Week 16
VISIT 7 (EOT)
113
[100, 127]
Week 20
VISIT 8
141
[128, 155]
Table 9.
Visit Windows for Analysis of Safety Laboratory Tests, and Vital 
Signs
Window Label
Nominal Visit
Target Day
Interval
Baseline
VISIT 2
1
< 1
Week 2
VISIT 3
15
[2, 22]
Week 4
VISIT 4
29
[23, 43]
Week 8
VISIT 5
57
[44, 71]
Week 12
VISIT 6
85
[72, 99]
Week 16
VISIT 7 (EOT)
113
[100, 127]
Week 20
VISIT 8
141
[128, 155]
Week 24
VISIT 9
169
[156, 183]
Week 28
VISIT 10
197
[184, 211]
Week 32
EOS
225
[212, 238a]
a.
Within 105 days of last double-blind dose for safety analyses.
The same visit windows will be used for safety and laboratory assessments.
The time windows specified in Table 10 will be used for the summary of study drug 
injections. 


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Table 10.
Visit Windows for Summary of Risankizumab Injections for 
Treatment Group Risankizumab 150 mg at Week 0, 4, 8, 12 and 16 
Window Label
Nominal Visit
Target Day
Interval
Week 0
VISIT 2
1
N/A
Week 4
VISIT 4
29
[2, 43]
Week 8
VISIT 5
57
[44, 71]
Week 12
VISIT 6
85
[72, 99]
Week 16
VISIT 7 (EOT)
113
[100, 126]
6.5
Missing Data Handling
Missing data will be imputed for efficacy variables only for data up to Week 24.  Data 
after Week 24 will not be imputed and only be analyzed as observed.  Missing values can 
occur due to a missed visit or due to dropout from the study.  Data will be categorized "as 
observed" and "imputed" as deemed appropriate.  The following imputation approaches 
will be used to impute missing data:
●
For the binary variables, the Non-responder Imputation (NRI) approach will be 
used for imputing missing data. 
●
For the continuous variables, Last Observation Carried Forward (LOCF) 
approach will be used for imputing missing data.
Missing data up to Week 24 will be addressed by considering the participant a non-
responder for their binary endpoint regardless of adherence to treatment or early 
discontinuation. 
Modified Non-Responder Imputation (mNRI) Approach:
According to the non-responder imputation principle, any missing binary response at a 
given visit will be imputed as non-responders for that visit.  This imputation approach 
ensures the most conservative estimate for a response for active treatment arms. 
For composite categorical efficacy endpoint such as ACR20/50/70, PsARC, MDA:


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●
Step 1:  all missing components will be imputed using Last Observation 
Carried Forward (LOCF) first, and then calculate the composite score.
●
Step 2:  if the composite score still cannot be determined by Step 1, the 
composite score will be imputed as 0.  In addition, all subjects who 
prematurely discontinue from the study will be considered as non-responders 
for all subsequent visits up to Week 24 after the discontinuation date.
For categorical efficacy endpoint derived from a single component such as EULAR 
response, presence of dactylitis, the missing score will be imputed as non-responder.
For categorical efficacy endpoint derived from a single score such as PASI75 and sPGA 
Response that will only be measured at visits when BSA ≥ 3%:  The missing case will be 
imputed as a non-responder if the BSA ≥ 3%.  The missing case will instead be imputed 
as a responder if the BSA < 3% at visits after baseline.  If BSA is missing the missing 
case will be imputed as a non-responder.  PASI90/100 will follow this rule with the 
exception that if PASI is missing and BSA < 3% then PASI90/100 will be missing.
Last Observation Carried Forward (LOCF) Approach: 
The LOCF approach will be used for imputing missing data for continuous variables.
The LOCF analyses will use the completed evaluation from previous visit for efficacy 
measures assessed to impute missing data at later visits.  Only post-baseline value will be 
carried forward.  Baseline data will not be carried forward to post baseline visit.
For composite efficacy endpoint such as DAS28
●
Step 1:  all missing components will be imputed using LOCF carrying forward 
the most recent previous non-missing component value (excluding baseline 
values), and then a composite score will be calculated by following the "as 
observed" calculation.
●
Step 2:  if a composite score is still missing after Step 1, the composite score 
of the most recent previous visit with a non-missing composite score will be 
carried forward.


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For composite PROs such as HAQ-DI, BASDAI, SF-36, FACIT-F, scoring rule will be 
followed when missing component presents.  If the composite score still cannot be 
determined, then the entire composite score from the previous visit will be carried 
forward.
Observed Cases (OC)
The OC analysis will not impute values for missing evaluations, and thus a subject who 
does not have an evaluation on a schedules visit will be excluded from the OC analysis for 
that visit.
Missing Data Handling for mTSS and PsAMRIS
The following imputation method on subject level will be used as the primary approach to 
impute missing mTSS and PsAMRIS:
●
Calculate average change from Baseline to follow-up visit (for example, 
Week 24 for mTSS and Week 16 for PsAMRIS) computed for all observed 
non-missing bones/joints data at both time points from a given subject.
●
If the Baseline score is available for a bone/joint, then the impute value at the 
follow-up visit will be the Baseline score plus the average change score from 
the other scored bone/joint locations.
●
If the Baseline visit is unavailable but the follow-up visit score is available, the 
imputed value at the Baseline will be computed from the follow-up time point 
score minus the average change, if the average change is smaller than the 
follow-up time point score at that location.  Otherwise, the Baseline visit 
imputed value will use the most recent follow-up time point score carried 
backward.
●
If both Baseline and follow-up time point visit score values are missing for a 
bone/joint, no values will be imputed to either visit, and that joint's bone/joint 
contribution will be zero, which means assigning 0 to both baseline and the 
follow-up time point for that joint.


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7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
Demographics and Baseline characteristics will be summarized for each arm and for 
overall of the FAS populations.  Continuous variables will be summarized with the 
number of non-missing observations by mean, standard deviation, first quartile, median, 
third quartile, minimum and maximum values.  Categorical data will be summarized using 
frequencies and percentages.  Statistical tests will be performed to assess the 
comparability of the placebo arm and the mixed two arms at baseline.  Treatment 
comparison will be made based on non-missing information.  Continuous variables will 
be analyzed using one-way analysis of variance (ANOVA).  Categorical variables will be 
analyzed using Fisher's exact test.
The following demographic and baseline parameters will be summarized. 
Subject Demographics
●
Sex (male, female)
●
Ethnicity (Hispanic or Latino, Other)
●
Race (American Indian or Alaska Native, Asian, Black or African American, 
Native Hawaiian or Other Pacific Islander, White)
●
Age (years), defined as the number of years from date of birth to date of 
first drug
●
Age Categories (< 65, ≥ 65)
●
Body weight (kg) 
●
Body Weight Categories (< 100 kg, ≥ 100 kg)
●
Height (cm) 
●
Body Mass Index (BMI) (kg/m2)
●
Body Mass Index (BMI) Category (kg/m2) (BMI < 30 vs BMI ≥ 30) 


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PsA Medical History and Disease Characteristics at Baseline
●
Categorical:
○
MDA (Minimal Disease Activity) for PsA
○
PASI (Psoriasis Area and Severity Index) assessed in subjects with ≥ 3% 
BSA of psoriatic plaques 
○
sPGA (Static Physician Global Assessment) assessed in subjects with ≥ 3% 
BSA of psoriatic plaques 
○
Presence of Dactylitis (yes/no)
○
Presence of Enthesitis based on LEI (yes/no)
○
Presence of Enthesitis based on LEI and SPARCC (yes/no)
○
Presence of nail psoriasis (yes/no)
○
Body Surface Area (BSA) of psoriatic plaques:  ≥ 3% vs < 3%
○
Prior exposure to TNF antagonists (TNFi's; Experienced versus Naive)
○
Concurrent  exposure to Methotrexate (Concurrent use versus Non-
concurrent use)
○
Presence of inflammatory spondylitis (yes/no)
○
Duration of PsA Categories (≤ 5, [5, 10], > 10)
○
Anti-cyclic citrullinated peptide (Anti-CCP) status:  Positive or Negative 
○
Rheumatoid Factor (RF) status:  Positive (≥ 15) or Negative (< 15)
●
Continous
○
DAS28 (Disease Activity Score in 28 joints) – hsCRP
○
Dactylitis count in subjects with dactylitis at baseline 0 – 20
○
Leeds Dactylitis Index (LDI)in subjects with dactylitis at baseline 
○
Leeds Enthesitis Index (LEI) in subjects with enthesitis (based on LEI and 
SPARCC) at baseline (yes/no) 0 – 6
○
Duration of PsA in years
○
CASPAR classification criteria total score
○
SPARCC (Spondyloarthritis Research Consortium of Canada) Enthesitis 
Index in subjects with enthesitis


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○
mNAPSI (Modified Nail Psoriasis Severity Index) assessed in subjects 
with nail psoriasis at baseline 0 – 130
○
Anti-cyclic citrullinated peptide (Anti-CCP) (units)
ACR and/or DAS Components at Baseline
●
SJC (Swollen Joint Count(s) 66) 0 – 66
●
TJC (Tender Joint Count(s) 68) 0 – 68
●
SJC (Swollen Joint Count(s) 28) 0 – 28
●
TJC (Tender Joint Count(s) 28) 0 – 28
●
Patient's assessment of pain on VAS 0 – 100
●
Patient's global assessment of the disease on VAS 0 – 100
●
Physician's global assessment of the disease on VAS 0 – 100
●
HAQ-DI (Health Assessment Questionnaire-Disability Index) 0 – 3
●
High sensitivity C-Reactive Protein (hsCRP) mg/L 
Patient Report Outcomes at Baseline
●
SF-36v2 (Short Form-36 Health Survey) 
●
FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue) 0 to 52
●
BASDAI (Bath AS Disease Activity Index) (in subjects with baseline 
inflammatory spondylitis) 0 to 10
Imaging Characteristics at Baseline
●
mTSS (Modified Total Sharp Score) 0 – 528
○
Total Erosion Score 0 – 320
○
Joint Space Narrowing Score 0 – 208
●
PsAMRIS (Psoriatic Arthritis Magnetic Resonance Image Scoring System) 
○
Synovitis 0 – 72
○
Tenosynovitis 0 – 72
○
Periarticular Inflammation 0 – 48


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○
Osteitis 0 – 144
○
Bone Erosion 0 – 480
○
Bone Proliferation 0 – 24
Clinical Tests at Screening
●
Tuberculin PPD skin test (Negative/Positive/Undetermined), QuantiFERON 
TB Gold test,
●
Hepatitis Testing
●
Pregnancy test (Negative/Positive/Not Done/NA)
General Use 
●
Smoking status (Never-smoked, Ex-smoker, Currently smokes)
●
Alcohol status (Non-drinker, drinks – no interference, drinks – possible 
interference)
7.2
Medical History
Medical history other than psoriatic arthritis or cardiovascular diseases will be 
summarized using body systems and condition/diagnosis as captured on the eCRF.  The 
body systems will be presented in alphabetical order and the conditions/diagnoses will be 
presented in alphabetical order within each body system.  The number and percentage of 
subjects with a particular condition/diagnosis will be summarized for each treatment arm.  
Subjects reporting more than one condition/diagnosis within a body system will be 
counted only once for that body system.
7.3
Previous Treatment and Concomitant Medications
Prior and concomitant medications will be summarized.  A prior medication is defined as 
any medication taken prior to the first dose of study drug.  A concomitant medication is 
defined as any medication that started prior to the first dose of study drug and continued 
to be taken after the first dose of study drug or any medication that started after the 


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first dose of study drug, until 105 days (15 weeks) after the last dose of study drug.  The 
number and percentage of subjects who had taken medications will be summarized by 
generic drug name assigned by the World Health Organization (WHO) Drug Dictionary 
for both prior and concomitant medications.  The following medication will be 
summarized:
●
Prior systemic corticosteroid 
●
Prior MTX
●
Prior csDMARDS other than MTX
●
Prior biologic DMARDS 
●
Prior NSAIDS
●
Concomitant systemic corticosteroid 
●
Concomitant MTX
●
Concomitant csDMARDS other than MTX 
●
Concomitant biologic DMARDS
●
Concomitant NSAIDS
Concomitant biologic DMARDS and csDMARDS other than MTX and on or before 
Week 16 are protocol violations.
7.4
Protocol Deviations
As BI and AbbVie have different criteria of protocol deviation, a list of important protocol 
deviations according to BI and AbbVie is given in Appendix Section 15.A4.  Number and 
percentage of subjects who reported at least one of the following protocol deviation 
categories will be provided.
●
Subject entered into the study even though she/he did not satisfy entry criteria
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded or prohibited concomitant treatment
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn


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8.0
Subject Disposition 
The number of subjects will be tabulated by country, investigator site and overall for the 
following sets:  Full Analysis Set and Safety Analysis Set.  The number of subjects for 
each of the following categories will be summarized, for overall and for each treatment 
group in the FAS population:
●
Number of subjects randomized
●
Number of subjects that took at least one dose of study drug
●
Number of subjects who completed EOT
●
Number of subjects who prematurely discontinued from the study before EOT
●
Number of subjects who elect to participate in the open label extension 
Study M16-244
In addition, the reasons for premature discontinuation (primary reason and all reasons) 
from the trial and/or from the medication collected from CRF by the following categories 
will be summarized with frequencies and percentages.  Subjects with multiple reasons for 
premature discontinuation will be counted once in the calculation of the number and 
percentage of total discontinuations ("Premature Discontinuation").
●
Adverse event
○
Worsening of disease under study
○
Worsening of other preexisting condition
○
Other adverse event
●
Protocol violation
●
Lost to follow-up,
●
Withdrew by subject,
●
Others.


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9.0
Study Drug Duration and Compliance
A summary of study drug duration will be provided for each treatment arm in each 
treatment part in the corresponding Safety populations. 
Study drug duration (days) will be summarized with the number of subjects, mean, 
standard deviation, minimum, median and maximum for each treatment arm.  It will also 
be summarized in 4-week intervals with frequencies and percentages for the number of 
subjects receiving study drug doses in each interval.  In addition cumulative duration of 
risankizumab (including total subject years) will be summarized. 
The study drug duration will be calculated as the follows:
Duration = date of last injection – date of first injection + 28 days
Compliance
Each subject will receive five risankizumab (active or placebo) injections Treatment 
compliance (TC) will be summarized based on Safety Analysis Set for each treatment 
group.  The treatment compliance is defined as the number of visits that the subject 
received injections divided by the number of visits a subject is supposed to receive 
injections during the treatment period (i.e., from the date of the subject's first injection 
through the date of the last injection).  Subjects with missing data for study drug 
administration will be excluded from the summary.  Specifically, TC will be calculated 
using the following formula:
TC = number of visits where injections are received/number of visits where injections are 
supposed to be received * 100%
The number of visits where injections are supposed to be received for a subject = Round 
([Last Study Drug Dose Date – First Study Drug Dose Date – 1]/28 + 1), where round (x) 
rounds x to the nearest integer.
The actual drug and dose delivered to the subject will be listed. 


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10.0
Efficacy Analysis
10.1
General Considerations
Table 11 provides the overview of all efficacy endpoint assessments during the study.
Table 11.
Overview of Efficacy Endpoint Assessments
Trial Periods
Treatment
Follow-Up
Visit
V2
V3
V4
V5
V6
V7
V8
V9
V101
EOS2
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


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Table 11.
Overview of Efficacy Endpoint Assessments (Continued)
Trial Periods
Treatment
Follow-Up
Visit
V2
V3
V4
V5
V6
V7
V8
V9
V101
EOS2
Week
0
2
4
8
12
16
20
24
28
32
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
x
MDA (calculated)
x
x
x
x
x
x
x
x
x
x
mTSS (X-Ray)
x
x
PsAMRIS
x
x
1.
Subjects that enrol in the extension study, at Week 24 or Week 28 visit, do not need to attend any remaining visits 
in Study 1311.5; however, the Trial Completion page and Visit date page at the EOS visit in the eCRF must be 
completed.
2.
End of Study (EOS).
Table 12 provides an overview of the efficacy endpoints to be analyzed and the general 
analysis methods.  The general analysis methods for binary and continuous endpoints will 
be described in detail following the table.  Some endpoints may require additional 
analyses other than the general ones listed in Table 12 – these additional analyses will be 
described in detail in later sections.


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Table 12.
Summary of Efficacy Variables and Corresponding Analyses
Efficacy Variables
Analysis Method
Binary Efficacy Endpoints:
!
Primary and Secondary Endpoints:
o
ACR20/50/70 responses at Week 16
o
PASI90 response at Week 16 in 
subjects with PsO BSA ≥ 3% at 
baseline
!
Point estimate and 90% CI of the response rate for 
each treatment group using exact method
!
Point estimate, 90% CI and p-value of the response 
rate difference between combined Arm 1 and Arm 2 
vs the placebo, as well as the response rate 
difference between combined Arm 2 and Arm 3 
using the stratified Cochran-Mantel-Haenszel test. 
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted using the 
same stratified Cochran-Mantel-Haenszel methods. 
!
Histogram of response rates by treatment group
!
MCP-Mod to evaluate dose-response for ACR 
20/50/70
!
Forest plot 
!
No multiplicity adjustments. 
!
Imputation:  NRI (primary), OC
Further Binary Endpoints:
At all measured time points except Week 16:
!
ACR20/50/70 
At all measured time points:
!
PASI75 in subjects with a ≥ 3% 
baseline PsO BSA
!
PASI100 in subjects with a ≥ 3% 
baseline PsO BSA
!
sPGA Response (0 = clear and 
1 = almost clear) in subjects with a 
≥3% baseline PsO BSA
!
EULAR response 
!
Presence of Dactylitis
!
MDA
!
PsARC
!
Point estimate and 90% CI of the response rate for 
each treatment group using exact method
!
Point estimate, 90% CI and p-value of the response 
rate difference between combined Arm 1 and Arm 2 
vs the placebo, as well as the response rate 
difference between combined Arm 2 and Arm 3 
using the stratified Cochran-Mantel-Haenszel risk 
difference estimate. 
!
Pairwise comparisons of the risankizumab dose 
groups vs placebo will be conducted using the same 
stratified Cochran-Mantel-Haenszel methods. 
!
Plot of ACR20/50/70 response rates overtime by 
treatment group
!
Ordinal Logistic Regression of EULAR response
!
Forest plot
!
Imputation:  NRI (primary), OC


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Table 12.
Summary of Efficacy Variables and Corresponding Analyses 
(Continued)
Efficacy Variables
Analysis Method
Continuous Efficacy Endpoints:
Secondary Endpoints:
Change from baseline at Week 16:
!
TJC68
!
SJC66
!
HAQ-DI
!
SF-36
!
Dactylitis Count in subjects with 
dactylitis at baseline
!
SPARCC in subjects with enthesitis 
at baseline
!
mNAPSI assessed in subjects with 
nail psoriasis at baseline
Further Continuous Endpoints:
Change from baseline at all measured time 
points:
!
Physician's Global (VAS)
!
Patient's Pain (VAS)
!
Patient's Global Activity (VAS)
!
CRP
!
DAS28(CRP)
!
LDI in subjects with dactylitis at 
baseline
!
LEI in subjects with Enthesitis at 
baseline
!
Presence of enthesitis
!
FACIT-F Change from baseline at 
Week 16 and 24:
!
BASDAI in subjects with baseline 
inflammatory spondylitis
!
Point estimate and 90% CI within each treatment 
group using mixed model repeated measures 
(MMRM) model; 
!
Point estimate, 90% CI and p-value for the mean 
change difference  between combined Arm 1 and 
Arm 2 vs placebo, as well as the mean change 
difference between combined Arm 2 and Arm 3 
with mixed model repeated measures (MMRM) 
model
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted MMRM 
model
!
Box plots and change from baseline over time will 
be plotted for key continuous variables
!
For SF-36, spyderdiagram will be provided
!
Imputation:  OC (primary)


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Table 12.
Summary of Efficacy Variables and Corresponding Analyses 
(Continued)
Efficacy Variables
Analysis Method
Continuous Efficacy Endpoints (continued):
mTSS and PsAMRIS:
!
Change from baseline (CFB) at 
Week 24 in mTSS
!
Change from baseline (CFB) at 
Week 16 in PsAMRIS
!
Mean CFB and 90% CI within each treatment 
group; 
!
Mean CFB , 90% CI and p-value for the difference 
between combined Arm 1 and Arm 2 and the 
placebo, as well as the difference between 
combined Arm 2 and Arm 3 using ANCOVA 
model
!
Pairwise comparisons of the each risankizumab 
dose group vs placebo will be conducted with 
ANCOVA model
The treatment effect will be evaluated based on a two-sided significance level of 0.1 
(when rounded to three decimal places).  The efficacy analysis will be conducted in the 
FAS.
For categorical variables, frequencies and percentages will be summarized by treatment 
group.  The treatment groups will be compared using the Cochran-Mantel-Haenszel 
(CMH) risk difference estimate stratified by the randomization factors with weights 
proposed by Greenland & Robins.10  Pairwise comparisons of all doses of treatment 
received versus placebo will be conducted using the same Cochran-Mantel-Haenszel 
methods, 90% confidence intervals as well as nominal p-values of the comparison of 
doses will be provided.  There will be no adjustments for multiplicity in these analyses.
For continuous variables, the model based mean and standard error will be presented.  The 
Baseline, visit means, change from baseline at each visit will also be presented by 
treatment group for subjects who have both Baseline and post Baseline visit values.  For 
continuous variables, the mixed model repeated measurement (MMRM) model with 
treatment regimen, clinical visit and stratification factors (prior TNF and concurrent MTX 
use) as fixed factors, and baseline score as a fixed continuous covariate, will be used.  In 
addition, participants will be included in the model as a random effect.  Furthermore, the 


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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).
At Week 16 analysis, MMRM models will only include visits through Week 16.  At final 
analysis, MMRM models will include all visits through Week 24.  Any observations 
beyond Week 24 will be summarized using descriptive statistics and p-value will be based 
on ANOVA. 
Some endpoints may require additional analyses other than the general ones listed in 
Table 10 – these additional analyses will be described in detail in later sections.
10.2
Primary Efficacy Analysis
The primary endpoint to assess the efficacy of risankizumab is ACR20 response at 
Week 16.
The primary null hypothesis is the proportion of subjects  who achieve ACR 20 at 
Week 16 in the combined Arm 1 and Arm 2 of risankizumab is less than or equal to that 
of the placebo. 
Alternative hypothesis is that 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 that of 
the placebo.
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, stratified based on prior TNFi use and concurrent MTX use.  Pairwise 
comparisons of the risankizumab dose groups versus the placebo, as well as comparison 
of the combined groups of risankizumab (Arm 2 and Arm 3) versus the placebo, will be 


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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 subject 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 subjects 
until the end of study database lock. 
10.3
Sensitivity Analysis of Primary Efficacy Variable
The following sensitivity analyses for the primary endpoint ACR20 at Week 16 will be 
conducted:
●
The primary analysis for point estimate and treatment comparisons will be 
repeated using as observed cases without any imputation.
10.4
Dose Response Modelling
The dose-response relationship among the 4 Risankizumab dose groups (weighted 
cumulative doses between Week 0 and Week 12 are 600 mg (Arm 1), 300 mg (Arm 2), 
200 mg (Arm 3), and 75 mg (Arm 4) and the placebo group will be characterized for the 
primary endpoint ACR20 at Week 16 using the Multiple Comparison Procedure –
Modeling (MCP-Mod)1,2 method.  The response based on the primary analysis approach 
NRI will be used, and ADDPLAN DF software will be used to perform the MCP-Mod 
analyses.
A set of 5 pre-specified standardized candidate dose-response models, as described in 
Table 13, will be utilized to examine the dose-response relationship.  A statistically 
significant dose response relationship will be declared if at least one model is identified 
by the MCP-Mod method to be statistically significant at α = 0.05 one-sided.  The fitted 
dose response curves will be presented graphically for all statistically significant models 
along with confidence bands.  The minimum effective dose (MED) will be identified for 


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each statistically significant model based on the pre-specified clinical meaningful target 
20% target difference from placebo.  The weighted MED across all significant models 
will be calculated, with weight being inverse of model AIC.
Table 13.
Candidate Models
Model
ƒ(d, θ)
d = dose,
θ = Model Parameters
ƒ0(d, θ)
Standardized Model
Initial Value(s) for 
Parameter(s)
Linear
 +  

NA
Logistic
 + 
	

1 +   –


1
1 +   –


 = 150, δ = 95
Emax
 + 
	

 + 

 + 
 = 150
sigEmax
 + 
	

 + 


 + 
 = 150, ℎ = 0.8
Quadratic
 +   + !!
 + !
| | !
 = –0.001
Note:
The candidate model and model parameters provided in the above table are just examples and should be 
adjusted case by case based on input from CPPM.
10.5
Secondary Efficacy Analyses
The secondary endpoints are as follows:
●
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 subjects 
with dactylitis at baseline)


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●
Change in SPARCC Enthesitis Index at Week 16 as compared to baseline (in 
subjects with enthesitis at baseline)
●
Change in mNAPSI at Week 16 as compared to baseline (in subjects with nail 
psoriasis)
●
PASI90 response at Week 16 assessed in subjects with a ≥ 3% baseline PsO 
BSA
Binary endpoints will be analyzed in a similar fashion as the primary endpoint.
For continuous endpoints, the baseline, visit mean, change from baseline within treatment 
group will be presented by treatment group.  The comparison between combined Arm 1 
and Arm 2 vs placebo will be analyzed 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 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 such as prior TNF and MTX use 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. 


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10.6
Further Efficacy Analysis
Further endpoints are as follows:
●
ACR 20/50/70 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 subjects with a ≥ 3% 
baseline PsO BSA:
○
PASI75 response
○
PASI100 response
●
Change in sPGA clear and almost clear 
●
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 subjects 
with dactylitis at baseline)
●
Change in LEI at all measured time points as compared to baseline (in subjects 
with enthesitis at baseline)
●
Change in FACIT-F at all measured time points as compared to baseline


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●
Change in BASDAI at Weeks 16 and 24 (in subject 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
Analyses at all measured time points will be conducted in a similar fashion as for 
Week 16 endpoints except for EULAR response, mTSS, and PSAMRIS.  EULAR 
response will be analysed using ordinal logistic regression with treatment group, prior 
TNFi use, and concurrent MTX use as main factors and baseline DAS value as a 
covariate.  mTSS and PSAMRIS will be analysed using ANCOVA with treatment group, 
prior TNFi use, and concurrent MTX use as main factors and baseline value as a 
covariate.  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.
10.7
Handling of Multiplicity
There will be no adjustments for multiplicity in these analyses. 
10.8
Efficacy Subgroup Analysis
The following subgroup analyses will be performed to evaluate the consistency of 
efficacy in the primary endpoint across demographic data, baseline disease characteristics, 
and drug history for PsA.
Subgroup Factor
Categories
Age
< 65, ≥ 65
Sex
Male or Female
BMI
< 30 or ≥ 30
Race
White or Others
Prior TNFi use
Naïve or experienced
Concurrent MTX use
Yes or no
.


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10.9
Efficacy Variables Definition and Conventions
This section introduces the detailed definition of the efficacy variables.  For detailed 
example and information, please refer to Section 10.0 Appendix of the protocol.
10.9.1
ACR Criteria
ACR criteria is a commonly used standard criteria mentioned in the guidance of American 
College of Rheumatology to evaluate the effectiveness of investigation drug in PsA 
clinical trials.  It is a composite measurement calculated based on the improvement over 
aset of core measurements.
ACR20 is defined as at least 20% improvement (compared to baseline values) in tender 
and swollen joint counts and at least 20% improvement in 3 of the remaining 5 core set 
measures (patient's assessment of pain [VAS], PtGA, PhGA, HAQ-DI and CRP).
ACR50 and ACR70 are similarly defined with at least 50% and 70% improvement, 
respectively. 
Calculation Rules for ACR Criteria
A subject will be classified as an ACR20 (ACR50, ACR70) responder, if the following 
conditions are met:
1.
≥ 20% (50%, 70%) improvement from baseline in tender joint count (TJC)* and
2.
≥ 20% (50%, 70%) improvement from baseline in swollen joint count (SJC)* and
3.
≥ 20% (50%, 70%) improvement from baseline in at least 3 of the following 5:
●
patient's assessment of pain
●
Patient's Global Assessment of Disease Activity for Arthritis (PtGA)
●
Patient's Global Assessment of Disease Activity for Arthritis (PhGA)
●
patient's self-assessment of physical function (i.e., measured by Health 
Assessment Questionnaire  (HAQ-DI score)
●
Acute-phase reactant value CRP


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There are seven components to be evaluated to define an ACR response.  Missing values 
for each component can occur due to a missed visit or due to dropout from the study.  
Depending on the pattern of the missing components, ACR responses may be or may not 
be determined using observed values only.
To maximize the utilization of observed information at certain visits and be scientifically 
as robust as possible, the principle to calculate ACR response is to minimize imputation 
whenever possible.  "As Observed" ACR response will be calculated first based on a 
derived visit window instead of the nominal visit identifier (e.g., Week 6 visit) collected 
from the CRF.
To calculate "as observed" ACR responses:
●
Identify the observed component xx% improvement indicator (0/1/missing), 1 
means achieving ≥ xx% improvement from baseline and 0 means < xx% 
improvement from baseline (e.g., xx% representing 20%/50%/70%).
●
ACRxx = 0 if TJC indicator = 0 OR SJC indicator = 0 OR at least 3 out of 
5 components improvement indicators = 0;
●
ACRxx = 1 if TJC indicator = 1 AND SJC indicator = 1 AND at least 3 out of 
5 components improvement indicators = 1
●
For all other cases, "as observed" ACRxx = missing since ACRxx cannot be 
determined.
The following table illustrates examples for as-observed ACR calculations. 


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Example
TJC 
68
SJC 
66
Component 
1
Component 
2
Component 
3
Component 
4
Component 
5
ACR20-
Response?
A
1
1
1
1
1
.
.
Yes
B
1
0
1
1
1
1
1
No
C
.
0
.
.
.
.
.
No
D
1
.
1
1
1
1
1
.
E
1
1
0
0
0
1
1
No
F
.
.
0
0
0
.
.
No
G
1
1
1
1
0
0
.
.
Legend:  1 = ≥ 20% improved compared to baseline; 0 = < 20% improved compared to baseline; "." missing
Derived Visit Windowing Rule for ACR Response Calculation
To identify the component value in a visit window:
●
ACR component values will first be determined at each date within a visit 
window. 
●
ACR component values at each date will be combined to determine the "as 
observed" ACR composite score at each date in each window.
●
After this calculation, if multiple non-missing ACR composite scores are 
available within a given visit window, the non-missing ACR composite score 
closest to the target day will be used.  If two composite scores have the same 
distance from the target day, the later one will be used.  The corresponding 
date will be used as the "as observed" ACR response date in the derived 
efficacy dataset.
●
If a non-missing ACR composite score is not available for any day within a 
given visit window, the windowed component values for that visit will be used 
to calculate the ACR composite score for that visit window (component value 
windowing follow the same rules as in steps described above).  The date of 
observed ACR composite score will be determined by the first available ACR 
component date, in the order of TJC, SJC, Pain, PGA, PhGA, HAQ-DI, 
CRP/ESR, in the derived efficacy dataset.


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10.9.2
Joint Evaluation
Anatomical joints are evaluated for swelling and tenderness at every study visit.  The 
34 anatomical joints in Table 14 are assessed in this study for both the left and right side 
of the body.
Table 14.
Anatomical Joints Assessed for Calculation of Tender and Swollen 
Joint Counts (TJC68 and SJC66)
Temporomandibular
Sternoclavicular
Acromio-clavicular
Shoulder
Elbow
Wrist
Metacarpophalangeal I
Metacarpophalangeal II
Metacarpophalangeal 
III
Metacarpophalangeal 
IV
Metacarpophalangeal V
Interphalangeal Thumb 
Joint 
Proximal 
Interphalangeal Joint II 
of the Hand
Proximal 
Interphalangeal Joint III 
of the Hand
Proximal 
Interphalangeal Joint IV 
of the Hand
Proximal 
Interphalangeal Joint V 
of the Hand
Distal Interphalangeal 
Joint II of the Hand
Distal Interphalangeal 
Joint III of the Hand
Distal Interphalangeal 
Joint IV of the Hand
Distal Interphalangeal 
Joint V of the Hand
Hipa
Knee
Ankle
Transverse Tarsus
Metatarsophalangeal I
Metatarsophalangeal II
Metatarsophalangeal III
Metatarsophalangeal IV
Metatarsophalangeal V
Interphalangeal Joint I 
of the Foot
Proximal 
Interphalangeal Joint II 
of the Foot
Proximal 
Interphalangeal Joint III 
of the Foot
Proximal 
Interphalangeal Joint IV 
of the Foot
Proximal 
Interphalangeal Joint V 
of the Foot
a.
Hip joints are not assessed for swelling.
At each study visit, a joint evaluator assessed whether a particular joint was "tender or 
painful" where presence of tenderness was scored as "1" and the absence of tenderness 
was scored as "0."  The total tender joint count (TJC68), which is based on 68 joints, will 
be derived as the sum of all "1"s and proportional extrapolation will be used to compute 
joint counts for the joints that are replaced or not assessed.  A similar method will be 
followed for the derivation of total swollen joint count (SJC66), which is based on 
66 joints as the hip joints are excluded.  Thus, the range for TJC68 will be 0 to 68 and 0 to 
66 for SJC66.  Joints with surgery (e.g., joint replacement) will not be assessed.


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10.9.3
Patient's Global Assessment of Disease Activity for Arthritis 
(PtGA)
The patient global assessment VAS will be self-administered by the patient at Baseline, 
Week 2,4,8, 12, 16 (EOT), 20, 24, 28 and 32 (EOS).
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."
10.9.4
Physician's Global Assessment of Disease Activity for 
Arthritis (PhGA)
The physician will assess Patient's disease activity at the time of visit using a Physician's 
Global Assessment of Disease VAS at Baseline, Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 
and 32 (EOS).  The range is 0 to 100 mm with no activity being indicated by 0 and severe 
activity by 100.
10.9.5
Patient's Assessment of Pain (VAS)
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."
The pain-VAS will be self-administered by the patient at baseline, Week 2, 4, 8, 12, 16 
(EOT), 20, 24, 28 and 32 (EOS).
10.9.6
Disease Activity Score Based on DAS28
The Disease Activity Score (DAS) is a combined index used to measure the joint disease 
activity in patients with PsA.  The DAS provides a score between 0 and 10, indicating 
how active the joint disease is in psoriatic arthritis is at the time of measurement.


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DAS28(CRP) score will be determined based on a continuous scale of combined 
measures of TJC28, SJC28, PtGA (in mm), and CRP (in mg/L).
DAS28(CRP) = 0.56 √("TJC28") + 0.28 √("SJC28") + 0.36 ln (CRP + 1) + 0.014
PtGA + 0.96, where √is square root and ln is natural log.
Low Disease Activity (LDA) by DAS28 (CRP) is defined as 2.6 ≤ DAS28 (CRP) < 3.2.  
Clinical Remission (CR) by DAS28 (CRP) is defined as DAS28 (CRP) < 2.6.
Table 15.
Anatomical Joints for DAS28(CRP) Calculation
Shoulder
Elbow
Wrist
Interphalangeal of the 
Thumb
Metacarpophalangeal I
Metacarpophalangeal II
Metacarpophalangeal 
III
Metacarpophalangeal 
IV
Metacarpophalangeal V
Proximal 
Interphalangeal of the 
Hand II
Proximal 
Interphalangeal of the 
Hand III
Proximal 
Interphalangeal of the 
Hand IV
Proximal 
Interphalangeal of the 
Hand V
Knee
Proportional extrapolation will be used to compute joint counts for the joints that are 
replaced or not assessed.
As-Observed DAS28 Scores
To calculate "as observed" DAS28 scores, the "as observed" component value will be 
calculated first.  Then the components will be included in the calculation per the DAS 
formula selected.  If any "as observed" component is missing in a window, then the "as 
observed" DAS28 score will be missing.
The DAS28 will be evaluated at baseline, Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 
(EOS).


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10.9.7
European League Against Rheumatism (EULAR) Response 
Criteria 
EULAR response will be evaluated according to the following table at Week 2, 4, 8, 12, 
16 (EOT), 20, 24, 28 and 32 (EOS).
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
For missing data use Non-Responder Imputation using the score of "None" as non-
response.
10.9.8
Minimal Disease Activity (MDA) in PsA
Table 16.
Minimal Disease Activity (MDA) Criteria in Psoriatic Arthritis
A subject is classified as in MDA when 5 of the following 7 criteria are met:
!
TJC68 ≤ 1
!
SJC66 ≤ 1
!
PASI ≤ 1 or BSA ≤ 3%
!
Patient assessment of pain ≤ 15
!
PtGA ≤ 20
!
HAQ-DI ≤ 0.5
!
Tender entheseal points ≤ 1 (Presence of Enthesitis in the 18 sites examined for the LEI and 
SPARCC evaluation)
Derivation rules for MDA follow the same logic as ACR.  MDA response can be 
determined if at least 5 of the 7 criteria are met (responder), or if at least 3 of the 7 criteria 
are not met (non-responder).  Selection of multiple MDA responses within one visit 
window follows the same rules as ACR.  See Section 6.0 for details on imputation. The 
MDA will be evaluated at baseline, Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 (EOS).


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10.9.9
Psoriatic Arthritis Response Criteria (PsARC) Response
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%)
Derivation rules for PsARC follow the same logic as ACR.  The PsARC will be evaluated 
at Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 (EOS).
10.9.10
Psoriasis Area and Severity Index (PASI) and Body Surface 
Area (BSA)
Four anatomic sites – head, upper extremities, trunk, and lower extremities – are assessed 
for erythema, induration and desquamation using a 5-point scale:
●
0 = no symptoms
●
1 = slight
●
2 = moderate
●
3 = marked
●
4 = very marked
Based on the extent of lesions in a given anatomic site, the area affected is assigned a 
numerical value:
●
1 = < 10%
●
2 = 10% – 29%


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●
3 = 30% – 49%
●
4 = 50% – 69%
●
5 = 70% – 89%
●
6 = 90% – 100%
Since the head, upper extremities, trunk and lower extremities correspond to 
approximately 10, 20, 30 and 40% of body surface area, respectively; the PASI score is 
calculated using the formula:
PASI = 0.1(Eh + Ih + Dh)Ah + 0.2(Eu + Iu + Du)Au + 0.3(Et + It + Dt)At + 0.4(El + Il + 
Dl)Al
where E, I, D, and A denote erythema, induration, desquamation, and area, respectively, 
and h, u, t, and l denote head, upper extremities, trunk, and lower extremities, 
respectively.  PASI scores range from 0.0 to 72.0 with the highest score representing 
complete erythroderma of the severest possible degree.  Typically scores of 3 or less 
represent mild disease, scores over 3 and up and including 15 represent moderate disease 
and scores over 15 are considered to be associated with severe disease.
The frequency and percentage of PASI75/90/100 (defined as at least 75% and 90% 
reduction in PASI score compared to baseline) will be summarized by treatment group in 
subjects with ≥ 3% BSA (Body Surface Area) psoriasis involvement at baseline.
The PASI will be evaluated at baseline, Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 
(EOS) only for subjects with ≥ 3% BSA of psoriatic plaques at baseline and/or at current 
visit.
If any "as observed" component is missing in a window, then the "as observed" PASI 
score will be missing.


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10.9.11
Static Physician's Global Assessment (sPGA)
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 17).
The assessment is considered "static" which refers to the subjects disease state at the time 
of the assessments, without comparison to any of the subject's previous disease states, 
whether at Baseline or at a previous visit.
A lower score indicates less body coverage, with 0 being clear and 1 being almost clear.
The investigator (or qualified site personnel) scores the erythema, induration and scaling 
of all psoriatic lesions from 0 – 4 based on the following descriptors
Scoring
A composite score is generated from the above data and the final sPGA is determined 
from this composite score as follows:
Clear
0 = 0 for all three
Almost clear
1 = mean > 0, < 1.5
Mild
2 = mean ≥ 1.5, < 2.5
Moderate
3 = mean ≥ 2.5, < 3.5
Severe
4 = mean ≥ 3.5


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Table 17.
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
If any "as observed" component is missing in a window, then the "as observed" sPGA 
score will be missing.
sPGA Responder
The sPGA will be dichotomized into Responders, 0 (clear) and 1 (almost clear) in one 
category, and Non-Responders, ≥ 2 in the other.  The sPGA will be evaluated at baseline, 
Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 (EOS) only for subjects with ≥ 3% BSA of 
psoriatic plaques at baseline and/or at current visit. 
10.9.12
Leeds Dactylitis Index (LDI)
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.  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 


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provided in the standard reference tables  The reference tables for standard digit 
circumference are listed in the Appendix A1.  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.  Overall LDI for a patient will be 
calculated as the sum of their individual LDIs from the digits where the assessment was 
done.  The LDI for a single digit will be calculated using the formula (A/B-1)*100*C, 
where A is the circumference of the affected digit, B is the circumference of the 
contralateral digit (or digit from the reference table if it is also affected), and C is the 
binary tenderness score for the digit.
Dactylitis Count:
The dactylitis count is the number of fingers and toes with dactylitis that are both affected 
and tender, with a range of 0 – 20.  If a site is not assessed assign it a value of "0."
Presence of Dactylitis:
If dactylitis is present with any finger or toe, the subject is counted as a subject with 
dactylitis.  The imputation rule for presence of dactylitis is that if all sites are missing then 
presence of dactylitis will be imputed as "present."
The dactylitis will be evaluated at baseline, Week 2, 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 
(EOS) for subjects with dactylitis at baseline.
10.9.13
Leeds Enthesitis Index (LEI)
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.


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Enthesitis Count:
Tenderness on examination is recorded as either present (1) or absent (0) for each of the 
6 sites (If a site is not assessed assign it a value of "0"), for an overall score range of 0 – 6.
Presence of Enthesitis Based on LEI:
If enthesitis is present with any of the 6 sites for LEI, the subject is counted as a subject 
with enthesitis based on LEI.  The imputation rule for presence of enthesitis is that if all 
sites are missing then presence of enthesitis will be imputed as "present."
10.9.14
Research Consortium of Canada (SPARCC) Enthesitis Index 
The SPARCC Enthesitis index is an outcome measure for enthesitis in SpA created by the 
Spondyloarthritis Research Consortium of Canada.3  Sixteen sites are evaluated.  
Tenderness at each site is quantified on a dichotomous basis:  0 means non-tender and 
1 means tender.  The SPARCC Enthesitis index is calculated by taking the sum of the 
scores from the 16 sites.  If a site is not assessed assign it a value of "0."  The SPARCC 
score ranges from 0 to 16.
Table 18.
Enthesial Sites Examined for SPARCC Calculation
Medial epicondyle
Lateral epicondyle
Supraspinatus insertion 
into greater tuberosity of 
humerus
Greater trochanter
Quadriceps insertion 
into superior border 
of patella
Atellar ligament 
insertion into inferior 
pole of patella or tibial 
tubercle
Achilles tendon insertion 
into calcaneum
Plantar fascia 
insertion into 
calcaneum
Presence of Enthesitis Based on LEI and SPARCC:
If enthesitis is present with any of the 18 sites for LEI or SPARCC, the subject is counted 
as a subject with enthesitis based on LEI and SPARCC. Accordingly, "subjects with 
ehthesitis at baseline" will also be defined using presense at any of the 18 LEI and 


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SPARCC sites.  The imputation rule for presence of enthesitis is that if all sites are 
missing then presence of enthesitis will be imputed as "present."
10.9.15
Modified Nail Psoriasis Severity Index (mNAPSI)
mNAPSI is the tool to assess each abnormality for each of a subject's fingernails.  
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.  Four features 
(leukonychia, splinter hemorrhages, hyperkeratosis, and red spots in the lunula) will be 
graded as either present or absent for each fingernail.  After a subject has assessed all of 
their nails consider all aspects of all of the subject's fingernails and place a mark on the 
visual analog scale giving a global assessment of their fingernails.  For detailed 
instruction, please see protocol Section 10.13.  The overall mNAPSI is calculated as the 
sum of all the components for all of a subject's nails.  In the case of missing data for any 
component of mNAPSI sum up all available component values and divide it by the total 
weight (if a score ranges 0 – 1, the weight is 1.  If a score ranges 0 – 3, the weight is 3), 
then multiply by 130 (the upper range of the total score).  If missing more than half of the 
total weight then the total score will be set as missing.
The mNAPSI will be evaluated at Baseline, Week 4, 8, 12, 16 (EOT), 20, 24, 28 and 32 
(EOS) for patients with nail psoriasis at baseline. 
10.9.16
Health Assessment Questionnaire-Disability Index (HAQ-DI)
HAQ-DI is a self-reported patient outcome measurement tool commonly used in RA and 
PsA clinical trials to measure physical functioning in RA and PsA patients.  The HAQ-DI 
composite score is calculated as the mean of the scores from the 8 following categories 
with a range of 0 – 3 (0 = no disability; 3 = worst disability):  Dressing and Grooming, 
Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities.  The higher the score, the 
more likely to be associated with morbidity and mortality for the PsA patient.  Under each 
category there are 2 – 3 items on the amount of difficulty they have in performing specific 
activities with four response options from 0 (no difficulty) to 3 (unable to do).  In addition 
to these eight categories, there is an aids or devices/help from other person section 


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("companion items") that is used to record the type of assistance, if any, a subject uses for 
his/her usual activities in each of the eight categories.
The preferred and traditional scoring method for scoring HAQ-DI is the Standard HAQ-
DI approach which takes into account the use of the aids/devices section.  There are 
three steps to compute the HAQ-DI score and a patient must have a score for at least 
six of the eight categories, otherwise a HAQ-DI score cannot be computed.  The first step 
is to compute each of the category score.  The maximum score for all the questions in 
each category is considered as the score for the category.  The second step is to adjust the 
score of each category based on use or no use of aids/devices and/or help from another 
person when indicated.  If aids or devices and/or assistance from another person are 
checked for a disability category, and the score for the category is 0 (no difficulty) or 1 
(some difficulty), increase it to 2 (much difficulty).  If the score for the category is a 2, it 
remains a 2, and if it is a 3, it remains a 3.  The third step is to sum the adjusted categories 
scores and divide by the number of categories answered (minimum 6) to obtain a HAQ-DI 
score of 0 to 3.
The HAQ-DI will be self-administered by the subject at Baseline, Week 2, 4, 8, 12, 16 
(EOT), 20, 24, 28 and 32 (EOS).
10.9.17
SF-36v2
The 36-Item Short Form, Version 2 (SF-36v2) Questionnaire with 1 week recall will be 
completed by the subject at Baseline, Weeks 4, 16 and 24 or at PD.  The SF-36v2 health 
survey consists of 36 general health questions and this study is using the form for 4 weeks 
recall period (standard form).  It has 2 components:  physical and mental.  For each 
component, a transformed summary score is calculated using 8 subdomains:  physical 
functioning, role-physical, bodily pain, general health, vitality, social functioning, role-
emotional, and mental health.4
The coding and scoring for the SF-36 will use the software provided by Optimum.


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Changes from baseline for each component and each of the 8 subdomains will be 
summarized by visit and treatment group.  Analysis will be based on Observed Case only.
Spydergrams will be plotted for the 8 sub-domains of SF-36v28.  In a spydergram, 
physical function (PF) is at the top, 12 o'clock, followed clockwise by role physical (RP), 
bodily pain (BP) and general health perceptions (GH), and vitality (VT) at the 6 o'clock 
position, followed by social functioning (SF), role emotional (RE) and mental health 
index (MH) clockwise (Figure 2A, B).  Domain scores are plotted from 0 (worst) at the 
center to 100 (best) at the outside; demarcations along axes of the domains present 
changes of 10 points, representing one to two times minimally clinical important 
differences (MCID).  An example of a spydergram is shown below.  The spydergram is a 
radar chart that can be plotted using PROC GRADAR in SAS version 9.4.
For a given time point, the values from the five treatment groups will be plotted in one 
spydergram.  Each time point (baseline, Week 4, 16 and 24) will have its own spydergram 
showing difference between treatment groups.
Figure 2.
An Example of Spydergram of SF-36
Note:
Strand 20096


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10.9.18
Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-F)
The FACIT-Fatigue is a 13-item questionnaire7 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:  I feel fatigued (-), I feel weak all over (-), I feel listless 
(washed out) (-), I feel tired (-), I have trouble starting things because I am tired (-), I have 
trouble finishing things because I am tired (-), I have energy (+), I am able to do my usual 
activities (+), I need to sleep during the day (-), I am too tired to eat (-), I need help doing 
my usual activities (-), I am frustrated by being too tired to do the things I want to do (-), I 
have to limit my social activity because I am tired (-).
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 (4 = not at all fatigued 
to 0 = very much fatigued).  The FACIT Fatigue Scale is ranged from 0 to 52 and the 
higher the score, the better the quality of life.
Score for each item is calculated by either subtracted from 4 or adding 0 depending on 
whether it is a reversal item or not.  FACIT Fatigue Scale is then calculated by adding up 
all item scores, multiplied by 13 and divided by the number of items answered.  It is 
essentially a prorated subscale if there are missing values for some items.  If less than or 
equal to 50% of the items are answered (e.g., 6 out of 13), the proration is not acceptable 
and the scale will not be computed.   
Recall period for items:  7 days.  FACIT-F will be evaluated at Weeks 0, 4, 16, and 24.


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10.9.19
Bath Ankylosing Spondylitis Disease Activity Index 
(BASDAI)
The BASDAI is composed of 6 questions investigating 5 domains (fatigue, spinal pain, 
joint pain/swelling, areas of localized tenderness, morning stiffness), with 1 item for each 
of the first four domains and 2 items for the last domain (morning stiffness).  Each item is 
scored on a 10 cm Visual Analogue Scale.  A lower score indicates less disease activity.
Scoring of the BASDAI is as follows:
1.
Measure each item of the BASDAI in centimeters (out of a total of 10)
2.
BASDAI Score = 0.2*(Question 1 + Question 2 + Question 3 + Question 4 + 0.5* 
Question 5 + 0.5* Question 6)
The BASDAI Score ranges from 0 – 10.  If one or more items are unanswered, take the 
average of the non-missing items.  If there are more than one mark for an item, take the 
average.
Below are the 6 questions.
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?


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The BASDAI will be evaluated at Baseline, 16 and 24.
10.9.20
Modified Total Sharp Score (mTSS)
To obtain the total mTSS score, scores for erosions and joint space narrowing (JSN) in 
both the hands and feet will be added together.  If a joint or bone is scored as not visible 
(e.g., poor film quality, missing imaging, severe misalignment, flexion deformity, 
dislocation) or if radiographs show a joint or bone with surgical fusion, replacement 
(prosthesis), or amputation, the joint will be counted as missing  in the calculation of the 
total mTSS score. 
Erosions
There are in total 52 erosion scoring locations.  The range of the total erosion score for 
both hands and feet for 1 patient per time point is from 0 to 320.  Maximum total erosion 
score of hands is 200 and the maximum total erosion score of the feet is 120.  An erosion 
total score is computed by summing the erosion values at each of the scored locations. 
Gross osteolysis and "pencil in cup" is scored separately.  In the final summary score, 
joints with one of these abnormalities get the maximum score assigned for erosions.
When a joint location has not been scored due to inadequate coverage or poor image 
quality, that location will be designated as NA and the total erosion score will be 
calculated using the following rules:
●
If the scores of more than 50% of erosion scoring locations are available 
(e.g., 27 or more, erosion scoring locations out of 52 total erosion scoring 
locations), the total erosion score will be calculated as Total Erosion Score = 
average of all available scores*52
●
If 50% or less (e.g., 26 or fewer erosion scoring locations out of 52 total 
erosion scoring locations) of the erosion scoring locations are readable, the 
Total Erosion Score will not be calculated


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Erosion will be scored at the following 20 hand/wrist locations in each hand/wrist:  1 IP 
joint of the thumb; 4 DIP joints; 4 PIP joints; 5 MCP joints; the first metacarpal (MC1) 
bone; the radius, ulna, and trapezium/trapezoid (scored as 1 unit; multangular [Mul]); the 
navicular (Nav); and the lunate.
The following 6 locations will be scored in each foot:  5 MTP joints and 1 IP of the great 
toe.  Each side of each foot joint (i.e., proximal and distal) is graded and added together 
for a joint score; therefore, a range of 0 to 10 is the range per foot joint.
Since two independent readers evaluate each film, the mean score will be calculated for 
the two readers from the individual erosion scores.
Joint Space Narrowing (JSN)
There are 52 total JSN scoring locations.  The range of the total JSN Score for both hands 
and feet per patient per time point is from 0 to 208.  The maximum possible score for joint 
space narrowing is 160 for the hands and 48 for the feet.  A total JSN score is computed 
by summing the joint narrowing values at each of the scored locations.
Gross osteolysis and "pencil in cup" are scored separately.  In the final summary score, 
joints with one of these abnormalities get the maximum score assigned for joint space 
narrowing.
When a bone location has not been scored because of inadequate coverage or image 
quality, that location will be scored as NA and the total JSN score will be calculated using 
the following rules:
●
If the scores of more than 50% of JSN scoring locations are available 
(e.g., 27 or more JSN scoring locations out of 52 total JSN scoring locations), 
the total JSN score would be calculated as Total JSN Score = Avg of all 
available scores*52
●
If 50% or less (e.g., 26 or fewer JSN scoring locations out of 52 total JSN 
scoring locations) of the JSN scoring locations are readable, the Total JSN 
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The JSN Score will be determined for the following 20 hand/wrist locations in each 
hand/wrist:  1 IP joint; 4 DIP joints; 4 PIP joints; 5 MCP joints; carpometacarpal (CMC) 
joints 3, 4, and 5; the radiocarpal (RC) joint, the multangular navicular (MAN) joint; and 
the capitonaviculolunate (CNL) joint.
The following 6 locations will be scored in each foot:  5 MTP joints and the IP joint of the 
great toe.
Since two independent readers evaluate each film, the mean score will be calculated for 
the two readers from the individual JSN scores.
Modified Total Sharp Score
The modified Total Sharp Score (mTSS) is the sum of the Erosion Score (i.e., Total 
Erosion Score) combined with the sum of the JSN Score (i.e., Total JSN Score).  The 
range of the mTSS for both hands and feet, per patient per timepoint is 0 to 528.  Each of 
the Total Change Score for Erosion, JSN and mTSS will be calculated by substracting 
respective post-treatment from baseline scores.  Total Change Scores will not be 
calculated for patients with baseline only visit.
The average modified TSS from the two readers will be used in statistical analysis.
Adjudication
Cases for adjudication will be determined based on the difference in Change Score for 
mTSS between Reviewer 1 and 2.
Queries to the assessment database will be performed on an ongoing basis to designate 
cases for adjudication.  For each patient dataset, the query will compare primary 
Reviewers' results to determine if differences necessitate adjudication.  The queries will 
be defined by the thresholds described below:
1.
The difference in mTSS change from Week 0 to Week 24 is greater than ± 6 mTSS 
units between Reviewer 1 and Reviewer 2


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2.
Change in mTSS that represents a difference in direction (one positive, one 
negative) by 3 or more mTSS units between Reviewer 1 and Reviewer 2.
3.
Reviewer 1 scores adequate number of scoring locations resulting in calculation of 
mTSS and the Reviewer 2 scores less than adequate scoring locations resulting in 
no calculation of mTSS in either baseline of post-treatment assessments.
Once the system has determined a case for adjudication the case will be presented to a 
third reader for adjudication.  The average modified TSS from the adjudicator and the 
reader whose result is closest to the adjudicator will be used in the analysis.
The total mTSS will be evaluated at Baseline and Week 24.  Change from baseline in total 
mTSS score at Week 24 will be summarized.
10.9.21
Psoriatic Arthritis Magnetic Resonance Image Scoring 
System (PsAMRIS)
The international "MRI in inflammatory arthritis" group of OMERACT (Outcome 
Measures in Rheumatology) has developed the OMERACT PsAMRIS for evaluation of 
inflammatory and destructive changes in PsA hand6 (or foot, if no swollen joint is 
available in hands at baseline) MRI will be performed as presented in the 
first approximately 90 subjects from the sites selected for MRI sub-study.  Images will be 
read centrally for each subject at two time points (Weeks 0 and 16) in a chronological 
order and without knowledge of subject identity or treatment assignment.  If a subject 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. 
An MRI Reviewer will assess images from baseline and Week 16 to produce MRI data on 
inflammation and damage for each given patient.  The Reviewer will be presented with 
2 time points from a given patient (as well as unscheduled if acquired and submitted).  
The MRI efficacy review assessments will be conducted as a side by side paired review.  
The Reviewer will not know the chronological order of visits belonging to the same 


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subject.  The MRIs will be read in a random manner with the Reviewer being blinded to 
the site-subject number, visit and MRI scan date.
Each feature will be scored by following the criteria listed in Table 19.
The scored regions of the fingers are: D, the distal interphalangeal (DIP) joint region; P, 
the proximal interphalangeal joint (PIP) region; and M, the metacarpophalangeal (MCP) 
joint region.  Each joint region is further delineated into distal (di), proximal (pr), dorsal 
(do) and volar (vo) joint regions.  See the appendix for a diagram of the joints of the 
hands.
The regions of the toes are:  D, the distal interphalangeal (DIP) joint region (DIP joints are 
not scored in the foot); P, the proximal interphalangeal joint (PIP) region; and M, the 
metacarpophalangeal (MCP) joint region.  Each joint region is further delineated into 
distal (di), proximal (pr), dorsal (do) and volar (vo) joint regions.  See the appendix for a 
diagram of the joints of the foot.


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Table 19.
PsAMRIS Scoring Guidance
Feature
Location
Scoring Criteria
Synovitis
M, P, and D
0:  Normal
1:  Mild
2:  Moderate
3:  Severe
NA
Tenosynovitis
M, P, and D
0:  None
1:  < ½ tendon thickness
2:  > ½ and < 1 tendon thickness
3:  > 1 tendon thickness NA
Periarticular
Inflammation
M, P, and D (dorsal and volar)
0:  Present
1:  Absent
NA
Osteitis
M1, M2, P1, P2, D1, and D2 
(distal and proximal)
0:  Normal
1:  Mild
2:  Moderate
3:  Severe
NA
Bone Erosion
M1, M2, P1, P2, D1, and D2 
(distal and proximal)
0 – 10 or NA, based on proportion of eroded 
bone compared to assessed bone volume 
from the articular surface
Bone Proliferation
M, P, and D
0:  Present
1:  Absent
NA
The PsAMRIS will be evaluated at Baseline and Week 16.  Change from baseline in 
PsAMRIS score at Week 16 will be summarized.  PSAMRIS will have six separate scores 
for Synovitis (0 – 72), Tenosynovitis (0 – 72), Periaticular Inflammation (0 – 48), Osteitis 
(0 – 144), Bone Erosion (0 – 480), and Bone Proliferation (0 – 24).


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11.0
Safety Analysis
11.1
General Considerations
Safety analyses will include reporting of adverse events, laboratory, and vital signs.  
Safety summaries will be provided using the Safety Analysis Set as defined in 
Section 5.1.
Mean changes from baseline of continuous laboratory and vital sign variables will be 
summarized for the Safety Analysis Set.  Categorical data will be summarized using 
frequencies and percentages.  Continuous variables will be analyzed using one-way 
ANOVA and categorical variables will be analyzed using Fisher's exact test.  Number of 
non-missing values will be given.  Missing safety data will not be imputed.
11.2
Analysis of Adverse Events
Treatment-Emergent Adverse Events (TEAE)
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 
(105 days) 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.'
Events where the onset date is the same as the study drug start date are assumed to be 
treatment emergent, unless the study drug start time and the adverse event start time are 
collected and the adverse event start time is prior to the study drug start time.  If an 
incomplete onset date is collected for an adverse event, the event will be assumed to be 
treatment-emergent unless there is other evidence that confirms that the event is not 
treatment-emergent (e.g., the event end date is prior to the study drug start date).
The number and percent of subjects experiencing treatment-emergent TEAEs will be 
tabulated using the Medical Dictionary for Drug Regulatory Activities (MedDRA®) 
version 20.0 by system organ class (SOC) and preferred term (PT). 


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Summary tables of TEAEs will be presented as follows:
1.
Overview of Adverse Events
The number and percentage of subjects experiencing TEAEs will be summarized 
for the following adverse event categories:
●
Any TEAEs
●
Any severe TEAEs 
●
Any serious AEs (SAE)
●
Any related TEAEs
●
Any TEAEs leading to discontinuation of study drug
●
Any TEAEs leading to death
●
Any deaths
●
Any TEAEs in areas of safety interest (Refer to Table 20)
2.
Adverse Events by System Organ Class and Preferred Term
The number and percentage of subjects experiencing TEAEs will be tabulated 
according to the primary MedDRA SOC and PT for each treatment group.  Subjects 
reporting more than one adverse event for a given MedDRA PT will be counted 
only once for that term (most severe incident for the severity tables and most 
related incident for the relationship tables).  Subjects reporting more than one type 
of adverse event within a SOC will be counted only once for that SOC.  Subjects 
reporting more than one type of adverse event will be counted only once in the 
overall total. 
The system organ classes will be presented in alphabetical order and the preferred 
terms will be presented in alphabetical order within each system organ class.
3.
Adverse Events by Maximum Severity/Toxicity
The severity grading of AEs follows Rheumatology Common Toxicity Criteria 
(RCTC).  
●
Grade 1 – mild


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●
Grade 2 – moderate
●
Grade 3 – severe
●
Grade 4 – life threatening
Adverse events will also be summarized by maximum severity.  If a subject has an 
adverse event with unknown severity, then the subject will be counted in the 
severity category of "unknown," even if the subject has another occurrence of the 
same event with a severity present.  The only exception is if the subject has another 
occurrence of the same adverse event with the most extreme severity (Life 
threatening).  In this case, the subject will be counted under the "Life-threatening" 
category.
4.
Adverse Events by "Reasonably Possibly Related" Relationship
TEAEs will also be summarized by relationship defined by "reasonably possibly 
related" to drug, as assessed by the investigator.  If a subject has an AE with an 
unknown relationship, then the subject will be counted in as 'related.'
5.
TEAEs by Preferred Term in Descending Frequency
TEAEs, SAEs, and TEAEs leading to discontinuation of study drug will be 
summarized by treatment group in decreasing order of frequency of MedDRA PT 
in the total risankizumab doses as well as the highest dose arm.  The most frequent 
TEAEs, SAEs and TEAEs leading to discontinuation of study drug can be 
identified from this summary. 
6.
Serious Adverse Events (Including Deaths) and TEAEs Leading to Study Drug 
Discontinuation
All serious adverse events (SAEs), deaths, and TEAEs leading to discontinuation of 
study drug will be listed.  The number and percentage of subjects experiencing 
SAEs (including deaths) and TEAEs leading to discontinuation of study drug will 
be tabulated by SOC and PT for each treatment group.
7.
Areas of safety interest


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The list of Areas of safety interest will be based on the most updated version of the 
risankizumab Product Safety Statistical Analysis Plan, which is consistent with the 
most updated risankizumab Product Safety Plan.
Grouped Terms
Areas of safety interest will be summarized by grouped term or SMQ, including 
sub-SMQs and preferred term for any adverse event, adverse events leading to 
discontinuation, serious adverse events, moderate or severe adverse events and 
related adverse events.  The groupings are provided in below Table 20.


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Table 20.
Areas of Safety Interest Listing
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated CV 
Events
MACE
Adjudicated terms will be 
identified as described in 
Table 6 using CECAT 
and CETERM from the 
CE SDTM dataset.
Display underlined terms defined 
by the following adjudicated 
terms:
!
CV Death which includes 
adjudicated results of:  
Sudden Cardiac death, 
Death due to Acute MI, 
Death due to Heart Failure, 
Death due to CV 
Procedures, Death due to 
CV Hemorrhage, Death due 
to Other CV Causes 
(specify), Fatal PE, Fatal 
Non-Cardiac/Non-Neuro 
Arterial 
Thrombosis/Thromboembol
ism, Undetermined Death, 
Not assessable death, fatal 
stroke (ischemic, 
hemorrhagic, undetermined)
!
Myocardial infarction which 
includes adjudicated results 
of Type 1 Myocardial 
Infarction, Type 2 
Myocardial Infarction, 
Type 3 Myocardial 
Infarction, Type 4 
Myocardial Infarction, 
Type 5 Myocardial 
Infarction 
!
Stroke:  Ischemic stroke, 
Hemorrhagic stroke, 
Undetermined stroke
Y
Extended 
MACE
Adjudicated terms will be 
identified as described in 
Table 6 (for MACE +) 
using CECAT and 
CETERM from the CE 
SDTM dataset.
Display underlined terms from 
MACE and underlined terms 
below:
!
Hospitalization for Unstable 
Angina
!
PCI
!
CBG
N


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Table 20.
Areas of Safety Interest Listing (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated CV 
Events 
(continued)
Other CV 
events
Adjudicated terms will be 
identified as described in 
Table 6 using CECAT 
and CETERM from the 
CE SDTM dataset.
Display underlined terms defined 
by the following adjudicated 
terms:
!
Thrombotic events which 
includes adjudicated results 
of:  Stent Thrombosis, 
DVT, TIA, PE, Non-fatal 
Non-Cardiac/Non-
Neurologic Arterial 
Thrombosis/Thromboembol
ism, Other Venous 
Thrombosis, specified (non-
fatal), Carotid 
revascularization
!
Cardiac arrhythmia which 
includes adjudicated results 
of:  Supraventricular 
Arrhythmia, Ventricular 
Arrhythmia, Heart Block, 
Other Clinically Significant 
Arrhythmia (no evidence of 
ischemia)
!
Congestive heart failure
which includes adjudicated 
results of Heart Failure –
Requiring hospitalization, 
Heart Failure – Urgent heart 
failure visit
!
Hypertensive emergency
N


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Table 20.
Areas of Safety Interest Listing (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Serious 
infections, TB, 
fungal and 
opportunistic 
infections 
(including 
herpes zoster)
Serious 
infections
Serious PTs of the CMQ 
(company MedDRA 
query) Infections 
(CMQ 80000018)
PTs
Y
TB
Tuberculosis (including 
Investigations) CMQ 
(code 80000033)
PTs
Y
Opportunistic 
infections
Opportunistic infections 
CMQ (code 80000073)
PTs
Y
Fungal 
infections
Fungal infections CMQ 
(code 80000063)
PTs
N
Herpes Zoster
Herpes zoster CMQ 
(code 80000175)
PTs
N
Malignancies
All possible 
malignancies
Narrow
Malignancies 
(SMQ 20000090)
PTs
N
Malignant 
Tumours
Narrow
Malignant tumours 
(SMQ 20000194)
PTs
Y
Non-melanoma 
skin cancer 
(NMSC)
Broad
Skin malignant tumours 
(SMQ 20000204) 
excluding terms 
identified by the 
Melanoma CMQ (code 
80000119)
PTs
N
Malignancies 
excluding 
NMSC
'Malignancies excluding 
NMSC' is identified by 
the 'Malignant Tumours' 
search excluding terms 
identified by the 'Non-
melanoma skin cancer 
(NMSC) search.
PTs
Y


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Table 20.
Areas of Safety Interest Listing (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Hypersensitivity 
Reaction 
(Hypersensitivity 
Serious Event 
only OR 
Anaphylactic 
Reaction = "Y")
Hypersensitivity
Narrow
Hypersensitivity 
(SMQ 20000214)
PTs
Y
Anaphylactic 
Reaction
Narrow
Anaphylactic reaction 
(SMQ 20000021)
PTs
Y
Depression, 
Suicidal ideation 
and behavior 
(SIB)
Suicidal 
ideation and 
behavior (SIB)
Suicide/self-injury
(SMQ 20000037)
PTs
N
Drug induced 
liver injury 
(DILI)
Drug induced 
liver injury 
(DILI)
Broad
Hepatic failure, fibrosis 
and cirrhosis and other 
liver damage-related 
conditions 
(SMQ 20000013)
Broad
Hepatitis, non-infectious 
(SMQ 20000010)
Broad
Cholestasis and jaundice 
of hepatic origin 
(SMQ 20000009)
Broad
Liver related 
investigations, signs and 
symptoms 
(SMQ 20000008)
Narrow
Liver-related coagulation 
and bleeding disturbances 
(SMQ 20000015)
PTs
N
8.
Adjudicated events including CCVT
Table A5 illustrates the events and sub-events that will be adjudicated along with 
which events will comprise the definition of a MACE event.


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9.
Adverse Event per 100 Patient Years of Exposure
The treatment-emergent adverse events occurring during the entire study will be 
presented by event rate per 100 patient years.  These will be presented for any 
TEAEs, serious adverse events, AE of special interest in addition to MACE events. 
AEs per 100 patient years of exposure is defined as the number of AEs divided by 
the total exposure in 100 patient years.  Note that one event per preferred term per 
day per subject will be counted in the calculation of the number of AEs (i.e., a 
preferred term will not be counted twice on the same day for the same subject).  
See the calculation method below.
where total patient years is defined as the sum of the study drug exposure (defined 
as date of last dose – date of first dose + 105 days (5 half-lives)) of all subjects 
normalized by 365.25, and rounded to one decimal place.
10.
Listing of Adverse Events
The following additional summaries of AEs will be prepared.
●
Listing of Subjects with TEAE of Area of Safety Interests
●
Listing of Subjects with Pretreatment Serious Adverse Events
●
Listing of Subjects with Treatment-Emergent Serious Adverse Events
●
Listing of all adverse events that led to discontinuation of study drug
●
Listing of all deaths
11.3
Analysis of Laboratory Data
Changes from Baseline in continuous laboratory parameters will be summarized by n, 
mean, standard deviation, minimum value, median, and maximum value for each 
treatment group.
Years
Patient 
Total
TEAEs
of
Number 
100 ∀


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Shift tables from Baseline to the final value (the last assessment during each treatment 
period) according to the normal range will be provided for each hematology, clinical 
chemistry parameter and urinalysis parameter.  The laboratory data will be categorized as 
low, normal, or high based on the normal ranges of the laboratory used in this study.  The 
shift tables will tabulate the number and percentage of subjects with Baseline values 
below/within/above the normal range versus final values below/within/above the normal 
range.
Frequencies and percentages of subjects with post Baseline lab values meeting the 
following criteria in Table 21 and Table 22 will be summarized.
Table 21.
Criteria for Potentially Clinically Important Chemistry Values
Definition of Potentially Clinically Important Current 
(Version 3) NCI CTCAE Grade 3
Chemistry Variables
Units
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
ALP
U/L
> 5.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN


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Table 22.
Criteria for Potentially Clinically Important Hematology Values
Definition of Potentially Clinically Important 
Current (Version 3) Grade 3
Hematology Variables
Units
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0
Though the protocol indicates utilizing the Rheumatology Common Toxicity Criteria 
(RCTC) scale for grading laboratory values, given that the National Cancer Institute 
Common Toxicity Criteria for Adverse Events (NCI CTCAE) scale includes a more 
comprehensive list of laboratory values; the lab analyses based on the NCI CTCAE scale 
will be presented.  
For selected laboratory parameter with CTCAE a listing of all subjects with any 
laboratory determinations meeting CTC Version 4.0 (or later) of Grade ≥ 3 will be 
provided.  For each of these subjects, the whole course of the parameter will be listed.  
For subjects with laboratory values with CTC ≥ 3, all of the laboratory parameters for 
those subjects will be listed.
11.3.1
Variables and Criteria Defining Abnormality
Clinical laboratory tests conducted in the study are listed in Table 23.


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Table 23.
Laboratory Tests
Category
Test Name
Hematology
Activated Partial Thromboplastin Time
Basophils/Leukocytes
Eosinophils/Leukocytes
Neutrophils/Leukocytes
Fibrinogen
Hematocrit
Hemoglobin
Hemoglobin A1C
Prothrombin Intl. Normalized Ratio
Lymphocytes/Leukocytes
Monocytes/Leukocytes
Platelets
Erythrocytes
Reticulocytes/Erythrocytes
Leukocytes
Chemistry
Alkaline Phosphatase
Alanine Aminotransferase
Amylase
Aspartate Aminotransferase
Bicarbonate
Direct Bilirubin
Bilirubin
Indirect Bilirubin
Calcium
Cholesterol
Creatine Kinase
Creatine Kinase MB
Chloride
Creatinine
C Reactive Protein
Gamma Glutamyl Transferase
Glucose
Hepatitis B DNA
Hepatitis B Virus Surface Antigen
Hepatitis C Virus Antibody


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Table 23.
Laboratory Tests (Continued)
Category
Test Name
Chemistry 
(continued)
Choriogonadotropin Beta
HDL Cholesterol
HIV-1/2 Antibody
Potassium
Lactate Dehydrogenase
Lipase
M. tuberculosis IFN Gamma Response
Protein
Rheumatoid Factor
Sodium
Triiodothyronine, Free
Thyroxine, Free
Triglycerides
Troponin I
Thyrotropin
Urate
Albumin
Urea Nitrogen
Urinalysis (dipstick)
Albumin/Creatinine
Bacteria
Casts
Creatinine Clearance
Crystals
Squamous Epithelial Cells
Ketones
Neutrophils/Leukocytes
Nitrite
pH
Urobilinogen
11.3.2
Statistical Methods
1.
Analysis of Quantitative Laboratory Parameters (Hematology, Chemistry and 
Urinalysis)


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Changes from Baseline to each scheduled visit and to the final value in continuous 
laboratory parameters will be summarized with mean, standard deviation, median, 
minimum, Q1, Q3 and maximum.  The Baseline and visit/final value means will also be 
presented for subjects who have both the Baseline and visit/final values (see Section 6.0
for the definition of Baseline and final values). 
If there are multiple measurements on the same day, average value will be used.
Additional summaries will be presented for liver function tests including ALT or serum 
glutamic-pyruvic transaminase (SGPT), AST or serum glutamic-oxaloacetic transaminase 
(SGOT), alkaline phosphatase, and total bilirubin.  Each laboratory value will be 
categorized as follows:
●
< 1.5 × ULN
●
≥ 1.5 × ULN – < 3.0 × ULN
●
≥ 3.0 × ULN – < 5.0 × ULN
●
≥ 5.0 × ULN – < 10.0 × ULN
●
≥10.0 × ULN – < 20.0 × ULN
●
≥ 20.0 × ULN
where ULN is the upper normal limit.
Shift tables of Baseline to the maximum (relative to the normal range, i.e., the largest 
multiple relative to the upper limit of normal) values, and from Baseline to final value will 
be presented using these categories.  A listing of potentially clinically significant liver 
function laboratory values will be provided.  The listing will include all subjects who met 
any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or
●
Alkaline phosphatase ≥ 1.5 × ULN, or
●
Total bilirubin ≥ 2 × ULN.


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A listing of possible Hy's Law cases will be provided which includes subjects with any 
elevated ALT of > 3 × ULN or AST of > 3 × ULN, Alkaline phosphatase < 2 × ULN, and 
associated with an increase in bilirubin ≥ 2 × ULN).
In addition, the Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) plot9 will be 
generated to evaluate the liver safety profile of risankizumab.  eDISH plot is a log/log 
display of correlation between peak total bilirubin (TBIL) vs. ALT, both in multiples of 
ULN, with horizontal and vertical lines indicating Hy's law thresholds, i.e., ALT = 
3 × ULN and total bilirubin = 2 × ULN.  The eDISH plot makes immediately evident 
subjects potentially matching Hy's law laboratory criteria, all located in the upper right 
quadrant of the graph.  Data points in the lower right quadrant, i.e., exceeding 3 × ULN 
for ALT, but being below 2 × ULN for total bilirubin, suggest an increased risk for liver 
injury as well, if incidence is differing between active treatment and control groups, 
however, not to the same extent and with less specificity as compared to Hy's law.
Figure 3.
An Example of eDISH Plot
Note:
Merz 20149


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11.4
Analysis of Vital Signs and Weight
All analyses will be conducted in the Safety Analysis Set.  The analyses of vital sign data 
will be descriptive. 
11.4.1
Variables and Criteria Defining Abnormality
Table 24 presents the Criteria for Potentially Clinically Significant Vital Sign Findings.
Table 24.
Criteria for Potentially Clinically Significant Vital Sign Findings
Vital Signs
Category
Criteria for Potential Clinically Significant Vital Signs
Systolic blood pressure
Low
Value ≤ 90 mmHg or decrease ≥ 20 mmHg from Baseline
High
Value ≥ 180 mmHg or increase ≥ 20 mmHg from Baseline
Diastolic blood pressure
Low
Value ≤ 50 mmHg or decrease ≥ 15 mmHg from Baseline
High
Value ≥ 105 mmHg or increase ≥ 15 mmHg from Baseline
Pulse
Low
Value ≤ 50 bpm or decrease ≥ 15 bpm from Baseline
High
Value ≥ 120 bpm or increase ≥ 15 bpm from Baseline
11.4.2
Statistical Methods
Changes from Baseline to each visit and to the final value in vital sign parameters will be 
summarized with the mean, standard deviation, median, minimum, Q1, Q3 and maximum.  
The Baseline and final value means will also be presented for subjects who have both the 
Baseline and final values (see Section 6.0 for the definition of Baseline and final values). 
If there are multiple measurements on the same day, average value will be used.
For systolic blood pressure, diastolic blood pressure and pulse, a listing of all subjects 
with any vital sign value meeting criteria for potentially clinically significant values will 
be provided.  For each of these subjects, the whole course of the respective parameter will 
be listed.  The number and percentage of subjects who have at least one value meeting 
criteria for potentially clinically significant values will be provided for each selected vital 
sign parameter.


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11.4.3
Analysis of ECG Parameters
ECG abnormalities will be captured as AE.  They will not be captured if they are normal.  
Hence no ECG analyses (categorical or outlier will be performed). 
11.5
Local Tolerability 
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 post dosing. 
A frequency table for the local tolerability will be provided at each visit by treatment 
group based on Safety Analysis Set.
12.0
Biomarkers Analysis
Soluble, cellular blood biomarkers and Ribonucleic Acid (RNA) will be collected in this 
study.  Biomarker analysis will be performed by Exploratory Statistics group in a separate 
statistical analysis plan and results will be summarized in a separate report. 
13.0
Pharmacokinetic Analysis
Descriptive statistics of risankizumab trough concentration measurements and 
risankizumab anti-drug antibody titer by treatment group and visit will be provided. 
14.0
Summary of Changes
14.1
Summary of Changes Between the Latest Version of 
Protocol and the Current SAP
●
The SAP includes Arm 2 + 3 vs Placebo in the evaluation and the protocol's 
Section 7.3.1 does not.
●
The protocol Section 7.3 plans to evaluate dose response by comparing Arm 1 
vs 2 and Arm 2 vs 3 at various time points.  The SAP proposes to evaluate 
dose response by MCP-Mod approach which is more comprehensive and takes 
various dose response curves into consideration.


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●
Protocol Section 7.3.2 states an unstructured covariance structure will be used 
in MMRMs in secondary endpoint analysis.  SAP goes on to say that other 
structures will be tested if it fails to converge.
●
In the safety section the SAP mentions MACE, adverse events by decreasing 
frequency, and the use of an eDISH plot for laboratory parameters, whereas 
the protocol does not.  
●
Protocol Section 5.3.3 states that abnormal laboratory values will be also 
graded for intensity by using RCTC Version 2.0 criteria.  In the SAP, the more 
comprehensive CTCAE 4.0 criteria is used instead to evaluate abnormal 
laboratory values.
●
The SAP rephrases the missing-data handling paragraph of Protocol 
Section 7.5 for clarity.  
15.0
References
1.
Pinheiro J, Bornkamp B, Bretz F.  Design and analysis of dose-finding studies 
combining multiple comparisons and modeling procedures.  J Biopharm Stat.  
2006;16(5):639-56.
2.
Bretz F, Pinheiro JC, Branson M.  Combining multiple comparisons and modeling 
techniques in dose-response studies.  Biometrics.  2005;61(3):738-48.
3.
Maksymowych WP, Mallon C, Morrow S, et al.  Development and validation of 
the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index.  
Ann Rheum Dis.  2009;68(6):948-53.
4.
Minnock P, Kirwan J, Veale D, et al.  Fatigue is an independent outcome measure
and is sensitive to change in patients with psoriatic arthritis.  Clin Exp Rheumatol.  
2010;28(3):401-4.
5.
Ware JE.  Measuring patients' views:  the optimum outcome measure.  SF-36:  
valid, reliable assessment of health from the patient's point of view.  BMJ.  
1993;306(6890):1429-30.


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6.
Strand V, Crawford B, Singh J, et al.  Use of "spydergrams" to present and 
interpret SF-36 health-related quality of life data across rheumatic diseases.  Ann 
Rheum Dis.  2009;68(12):1800-4.
7.
Yellen SB, Cella DF, Webster K, et al.  Measuring fatigue and other anemia-related 
symptoms with the Functional Assessment of Cancer Therapy (FACT) 
measurement system.  J Pain Symptom Manage.  1997;13(2):63-74.
8.
Active Psoriatic Arthritis Review Charter version Final_v1.0_08-SEP-2016 for 
1311.5.
9.
Merz M, Lee K, Kullak-Ublick G, et al.  Methodology to assess clinical liver safety 
data.  Drug Saf.  2014;37 (Suppl 1):S33-45.
10.
Greenland S, Robins M.  Estimation of a common effect parameter from sparse 
follow-up data.  Biometrics.  1985;41(1):55-68.
16.0
Appendix
A1.
Standard Digit Reference Tables
Table A1.1.
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


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Table A1.2.
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
A2.
Modified Nail Psoriasis Severity Index (mNAPSI) 
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.


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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.
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.  


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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.


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A3.
PSAMRIS Joints
Figure A3.1
PsAMRIS Scoring Regions – Hand


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Figure A3.2
PsAMRIS Scoring Regions – Foot


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A4.
Important Protocol Violations
Category/
BI Code
Description
Automatic/Manual
AbbVie 
Criterion
A
Entrance Criteria Not Met
A1
Inclusion criterion not met
Automatic
1
A2
Exclusion criterion met
Automatic
1
B
Informed Consent
B1
Informed consent not available/not done
Automatic and manual
1
B2
Informed consent too late
Automatic and manual
1
C
Trial Medication and Randomization
C1
Incorrect trial medication taken
Manual
2
C3
Non-compliance with study medication
Manual
2
D
Concomitant Medication
D1
Prohibited medication use before and 
during the treatment period of the trial
Manual
3
D2
Violation of concomitant medication
Manual
3
E
E
Incorrect study procedure(s) performed.
Manual
4


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Table A5.
Adjudicated Events and Composition of MACE Event Definition
Decision Form 
(CECAT from 
SDTM.CE – Select 
Records Using this 
Variable)
Event (for NON-FATAL Events, 
CETERM from SDTM.CE – to Be 
Produced in Table; for FATAL 
EVENTS, CETERM = 'DEATH' 
and Reason for Death in 
DDORRES (Note that DDORRES 
= Null Indicates 'NOT 
ASSESSABLE')) Take AESTDT 
from CEREFID < AELLTCD:  
AETERM:  AESTDTC >
Charter Event
MACE
MACE+
Other 
CV
NON-FATAL 
CARDIOVASCULAR 
DECISION
MI
MI Type 1
X
X
MI Type 2
X
X
MI Type 4
X
X
MI Type 5
X
X
NON-FATAL 
NEUROLOGICAL 
DECISION
Stroke
Ischemic 
Stroke
X
X
Hemorrhagic 
Stroke
X
X
Undetermined 
Stroke
X
X
FATAL 
CARDIOVASCULAR 
DECISION
Fatal CV
Sudden 
Cardiac Death
X
X
Due to Acute 
MI
X
X
Death due to 
Heart Failure
X
X
Death due to 
CV Procedures
X
X
Death due to 
CV 
Hemorrhage
X
X
Death due to 
Other CV 
Causes
X
X
FATAL 
NEUROLOGICAL 
DECISION
Fatal Stroke
Ischemic 
Stroke
X
X
Hemorrhagic 
Stroke
X
X
Undetermined 
Stroke
X
X


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Table A5.
Adjudicated Events and Composition of MACE Event Definition 
(Continued)
Decision Form 
(CECAT from 
SDTM.CE – Select 
Records Using this 
Variable)
Event (for NON-FATAL Events, 
CETERM from SDTM.CE – to Be 
Produced in Table; for FATAL 
EVENTS, CETERM = 'DEATH' 
and Reason for Death in 
DDORRES (Note that DDORRES 
= Null Indicates 'NOT 
ASSESSABLE')) Take AESTDT 
from CEREFID < AELLTCD:  
AETERM:  AESTDTC >
Charter Event
MACE
MACE+
Other 
CV
FATAL 
THROMBOTIC 
DECISION
Fatal PE
Fatal PE
X
X
FATAL 
THROMBOTIC 
DECISION
Fatal Non-Cardiac/Non-Neuro 
Arterial 
Thrombosis/Thromboembolism
Fatal Non-
Cardiac/Non-
Neuro Arterial 
Thrombosis/Th
romboembolis
m
X
X
FATAL 
CARDIOVASCULAR*
Non-CV Death
Non-cardiac 
Death
FATAL 
CARDIOVASCULAR
Undetermined Death
Undetermined 
Death
X
X
FATAL 
CARDIOVASCULAR/
NEUROLOGICAL/ 
THROMBOTIC 
DECISION
Not assessable deaths 
(cardiac/neuro/thrombotic)
Not assessable 
Death
X
X
NON-FATAL 
CARDIOVASCULAR 
DECISION
Hospitalization for Unstable Angina
Hospitalization 
for Unstable 
Angina
X
NON-FATAL 
CARDIOVASCULAR 
DECISION
Coronary Revascularization 
Procedures
PCI
X
CABG
X
NON-FATAL 
CARDIOVASCULAR 
DECISION
Hypertensive emergency
Hypertensive 
Emergency
X
NON-FATAL 
NEUROLOGICAL 
DECISION
TIA
TIA
X


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Table A5.
Adjudicated Events and Composition of MACE Event Definition 
(Continued)
Decision Form 
(CECAT from 
SDTM.CE – Select 
Records Using this 
Variable)
Event (for NON-FATAL Events, 
CETERM from SDTM.CE – to Be
Produced in Table; for FATAL 
EVENTS, CETERM = 'DEATH' 
and Reason for Death in 
DDORRES (Note that DDORRES 
= Null Indicates 'NOT 
ASSESSABLE')) Take AESTDT 
from CEREFID < AELLTCD:  
AETERM:  AESTDTC >
Charter Event
MACE
MACE+
Other 
CV
NON-FATAL 
THROMBOTIC 
DECISION
Deep Vein Thrombosis
DVT
X
NON-FATAL 
THROMBOTIC 
DECISION
Pulmonary Embolism
PE
X
NON-FATAL 
THROMBOTIC 
DECISION
Non-fatal Non-Cardiac/Non-
Neurological Arterial 
Thrombosis/Thromboembolism
Non-fatal Non-
Cardiac/ 
Non-Neurological 
Arterial 
Thrombosis/ 
Thromboembolism
X
NON-FATAL 
THROMBOTIC 
DECISION
Other Venous Thrombosis, specified 
(non-fatal)
Other Venous 
Thrombosis, 
specified (non-
fatal)
X
NON-FATAL 
CARDIOVASCULAR
Heart Failure
Heart Failure –
Requiring 
hospitalization
X
NON-FATAL 
CARDIOVASCULAR 
DECISION
Heart Failure –
Urgent heart 
failure visit
X
NON-FATAL 
CARDIOVASCULAR 
DECISION
Clinically Significant Arrhythmia 
(no evidence of ischemia)
Supraventricular 
Arrhythmia
X
Ventricular 
Arrhythmia
X
Heart Block
X
Other
X