Conditions: Psoriasis
Keywords: ABBV-0066 BI 655066 risankizumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 120
Healthy volunteers: no

Brief summary:
The purpose of this study is to compare the efficacy and safety of subcutaneous (SC) risankizumab and oral FUMADERM provided as study medication in participants with moderate to severe plaque psoriasis who are naïve to and candidates for systemic therapy.

Detailed description:
The efficacy analysis was performed in the Intent to Treat (ITT) set which included all participants who were randomized. The safety analysis was performed in the safety set which included all participants who received at least one dose of study drug. No participants were excluded from the efficacy analysis. Three participants in the FUMADERM® group discontinued after randomization prior to receiving any study drug and were thus not included in the safety set.

Arms:
arm 1: Participants randomized to receive open-label risankizumab 150 mg by subcutaneous injection at Weeks 0, 4, and 16. arm 2: Participants randomized to receive open-label Fumaderm 30 mg administered as a tablet orally once daily from Week 0 to Week 2 and then up to 240 mg, 3 times daily from Week 3 to Week 24 if 90% Improvement in Psoriasis Area and Severity Index (PASI90) is not achieved and if tolerability allows.

Interventions: intervention 1: Fumaderm intervention 2: risankizumab
Intervention descriptions: intervention 1: Fumaderm tablet administered orally intervention 2: Risankizumab administered by subcutaneous (SC) injection

Protocol document:
Prot_000.pdf: 
Risankizumab
M16-178 Protocol Amendment 3
EudraCT 2016-003718-28
1
1.0
Title Page
Clinical Study Protocol M16-178
A Randomized, Controlled, Multicenter, Open Label 
Study with Blinded Assessment of the Efficacy of 
the Humanized Anti-IL-23p19 Risankizumab 
Compared to FUMADERM® in Subjects with Moderate 
to Severe Plaque Psoriasis Who are Naïve to and 
Candidates for Systemic Therapy
Incorporating Amendments 1, 2 and 3
AbbVie Investigational
  Product:
Risankizumab
Date:
28 November 2017
Development Phase:
3
Study Design:
A Randomized, Controlled, Multicenter, Open Label Study with Blinded 
Assessment of the Efficacy of the Humanized Anti-IL-23p19 Risankizumab 
Compared to FUMADERM® in Subjects with Moderate to Severe Plaque 
Psoriasis Who are Naïve to and Candidates for Systemic Therapy
EudraCT Number:
2016-003718-28
Investigator(s):
Multicenter Trial (Investigator information is on file at AbbVie)
Sponsor:
AbbVie Deutschland GmbH & Co KG
Knollstrasse 50
67061 Ludwigshafen
Germany
Sponsor/Emergency 
  Contact:
Phone:
Fax:
* The specific contact details of the AbbVie legal/regulatory entity (person) within the relevant country are provided 
within the clinical trial agreement with the Investigator/Institution and in the Clinical Trial Application with the 
Competent Authority.
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other applicable regulatory 
requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NCT03255382


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M16-178 Protocol Amendment 3
EudraCT 2016-003718-28
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1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol
Date
Original
05 January 2017
Amendment 1
13 March 2017
Amendment 2
05 July 2017
The purpose of this amendment is to implement the following changes:
●
Section 1.0, Title Page:  to change the Emergency Contact, Therapeutic Area 
Medical Director´s fax number.
Rationale:  New fax number.
●
Section 5.2.1, Inclusion Criteria:  removal of the following redundancy: 
"Females of non-childbearing potential (either postmenopausal or permanently 
surgically sterile as defined above) at Screening do not require pregnancy 
testing at Study Day 1."
Rationale:  Editorial change.
●
Section 5.2.3.3, Prohibited Therapy:  moving the time point from which 
phototherapy (e.g., UVA, UVB, any other UV-therapy or balneotherapy) not-
associated with systemic UV-sensitizing agents, topical treatment for psoriasis 
or any other skin condition (e.g., corticosteroids,c vitamin D analogues, 
vitamin A analogues, pimecrolimus, retinoids, salicylvaseline, salicylic acid, 
lactic acid, tacrolimus, tar, urea, andanthralin, α-hydroxy acid, fruit acids) are 
prohibited from 14 days prior to Screening  to 14 days prior to Baseline.
Rationale:  The half-life of those therapies is short and no interaction with 
study medication is to be expected if they are discontinued 14 weeks before 
1st dose of study medication, i.e., 14 days before Baseline (Day 1, Week 0).  
●
Section 5.3.1.1, Study Procedures, and Appendix C, Study Activities:  
FUMADERM® INITIAL and FUMADERM® Subject Diary:  Clarification 
that the subject diary will be dispensed to the subject at every visit, starting at 
the Week 0/Baseline Visit rather than at the Screening Visit, and that the 


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M16-178 Protocol Amendment 3
EudraCT 2016-003718-28
3
subject will be trained on how to complete the diary at the Week 0/Baseline 
Visit.
Rationale:  Clarification.
●
Section 5.4.1.1, Discontinuation of Subjects on FUMADERM®:  Point 8:  
Restriction of the discontinuation of the subjects on FUMADERM® for 
rash/flush to those with severe rash/flush.
Rationale:  In clinical practice only severe persistent rash/flush leads to 
discontinuation of the patients from FUMADERM®.
The FUMADERM® label language does not request discontinuation of 
FUMADERM® treatment for all adverse events of rash/flush, but says: "… 
severe forms (of rash/flush) may lead to (FUMADERM®) treatment 
discontinuation." 
●
Section 5.5.1, Treatments Administered:  the sentence "Additional dosing 
instructions will be provided separately from this protocol" has been removed.
Rationale:  Risankizumab will be administered by site personnel only, 
therefore no additional instructions on how to administer an SC injection is 
required.
●
Appendix J, NAPPA-CLIN®:  Extension of the prohibition of artificial nail 
and/or nail polish to all subjects instead of subjects with nail psoriasis only.
Rationale:  Consistency within the protocol.  The analysis of the efficacy on 
nail psoriasis is planned on all subjects regardless of a concomitant nail 
psoriasis.
An itemized list of all changes made to this protocol under this amendment can be found 
in Appendix K.


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M16-178 Protocol Amendment 3
EudraCT 2016-003718-28
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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M16-178
Name of Study Drug:  Risankizumab 
Phase of Development:  3
Name of Active Ingredient:  Risankizumab 
Date of Protocol Synopsis:  28 November 2017
Protocol Title:  A Randomized, Controlled, Multicenter, Open Label Study with Blinded Assessment of 
the Efficacy of the Humanized Anti-IL-23p19 Risankizumab Compared to FUMADERM® in Subjects 
with Moderate to Severe Plaque Psoriasis who are Naïve to and Candidates for Systemic Therapy
Objective:  
The objective of this study is to compare the efficacy and safety of subcutaneous (SC) risankizumab and 
oral FUMADERM® provided as study medication in subjects with moderate to severe plaque psoriasis 
who are naïve to and candidates for systemic therapy.
Investigator:  Investigator information on file at AbbVie.
Study Site:  Approximately 25 sites in Europe
Study Population:  
Adults with moderate to severe plaque psoriasis [Psoriasis Area and Severity Index (PASI > 10), 
affected body surface area (BSA) > 10% and Dermatology Life Quality Index (DLQI) > 10] who are 
naïve to and candidates for systemic therapy.
Number of Subjects to be Enrolled:  Approximately 110 [2 × 55]
Methodology:  
This study is a randomized, controlled, multicenter, open-label study with blinded assessment of efficacy 
to demonstrate the efficacy and safety of SC risankizumab in adult subjects with moderate to severe 
plaque psoriasis who are naïve to and candidates for systemic therapy compared with oral 
FUMADERM® provided as study medication.  This study will be conducted in approximately 
110 subjects.
Subjects will be randomized in a 1:1 ratio (stratified by prior phototherapy, with a maximum of 20% of 
subjects with prior phototherapy) to one of two arms of either risankizumab or oral FUMADERM®
provided as study medication.  The following are the dosing arms:
!
Risankizumab 150 mg SC at Week 0/Day 1, Week 4 and Week 16 or,
!
Oral FUMADERM® provided as study medication daily starting at Week 0/Day 1 and until 
Week 24 (last intake in the morning on the day of Week 24 visit):
FUMADERM® INITIAL provided as study medication starting at Week 0/Day 1 until Week 2 
and FUMADERM® provided as study medication starting at Week 3, both at starting dose of 
1 tablet per day, followed by an increase in the daily dose of 1 tablet per week, with the 
intention of achieving PASI 90.  The maximum daily dose of FUMADERM® provided as study 
medication may not exceed 6 tablets per day.  After the targeted efficacy on the psoriasis 
cutaneous lesions has been reached, an attempt should be made to reduce the dose of 
FUMADERM® provided as study medication to the individual maintenance dose.
Efficacy outcomes will be measured at each visit until Week 24 and safety data will be collected 
throughout the study.


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Methodology (Continued):
At the Week 24 visit, subjects who completed the study will be offered the opportunity to participate in a 
separate extension study.  For subjects that do not elect to enroll into the extension study, a follow-up 
phone call will be performed at Week 31.
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion:  
1. Male or female subject ≥ 18 and < 80 years of age at the time of screening.
2. Have a diagnosis of chronic plaque psoriasis for at least 6 months before the first administration of 
study drug. Duration since diagnosis may be reported by the patient.
3. Subject has stable moderate to severe plaque psoriasis with or without psoriatic arthritis at Baseline
!
Has an involved BSA > 10% and
!
Has a PASI score > 10 and
!
Has a DLQI > 10.
4. Must be naïve to and candidate for systemic therapy, as assessed by the investigator.
5. Subject has an inadequate response, intolerance or contraindication to topical psoriasis treatment as 
documented in the patient's medical history or reported by the patient or determined by the 
investigator at screening.
Main Exclusion:  
1. Subjects with
!
Non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)
!
Drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium 
channel blockers, or lithium)
!
Active ongoing inflammatory diseases other than psoriasis that might confound study 
evaluations according to investigator's judgment
2. Subject has previously received systemic therapy for psoriasis, whether biologic or non-biologic, or 
photochemotherapy (e.g., PUVA therapy, any UV-therapy or balneotherapy associated with 
UV-sensitizing agent).
3. Active systemic infection during the last 2 weeks (exception:  common cold) prior to screening.
4. 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.
5. Subject has any condition or contraindication to FUMADERM® that would preclude the patient's 
participation in the present study, including, but not limited to:
!
A known hypersensitivity to fumaric acid derivatives or other components of FUMADERM®
Initial or FUMADERM®,
!
Any parameter of the complete blood count (CBC), at Screening Visit, outside of normal range 
according to the central laboratory
!
Severe liver disease (ALT or AST > 2 × ULN according to central laboratory normal range, or 
total bilirubin > 1.5 × ULN according to central laboratory normal range at Screening visit),
!
Severe kidney disease (serum creatinine above normal value according to central laboratory 
normal range at Screening visit),


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EudraCT 2016-003718-28
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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
!
Severe gastro-intestinal disease, such as a known active gastro-duodenal ulcer,
!
Inability to understand the complexity of FUMADERM® dosing regimen,
!
Any other exclusionary condition provided in Fumaderm® local label,
!
Any of the following risk factors for renal toxicity:
o
peripheral vascular disease
o
diabetes mellitus with microalbuminuria (UACR > 30 mg/g), at Screening Visit,
o
systolic blood pressure measurement of > 140 mmHg or a diastolic blood pressure 
measurement of > 90 mmHg at the Screening visit,  unless there is confirmation from 
an internist or a cardiologist that no renal or cardiovascular risk is associated with the 
elevated blood pressure.  
o
history of congestive heart failure (NYHA Class III or IV*)
Investigational Product:
Risankizumab
Doses:
150 mg at Weeks 0 and 4, and 16.
Mode of Administration:
Subcutaneous Injection (SC) (pre-filled syringe)
Investigational Product:
FUMADERM® INITIAL and FUMADERM® provided as study 
medication
Doses:
QD to TID
Mode of Administration:
Oral 
Duration of Treatment:  The treatment duration will be 16 weeks for risankizumab and 24 weeks for 
FUMADERM®.
Criteria for Evaluation:
Efficacy:
The primary efficacy endpoint is the proportion of subjects with a ≥ 90% improvement in Psoriasis Area 
and Severity Index (PASI90) at Week 24.
Secondary efficacy variables are:
PASI, Body Surface Area (BSA), static Physician Global Assessment (sPGA), Palmoplantar psoriasis 
Severity Index (PPASI), Psoriasis Scalp Severity Index (PSSI), Nail Assessment in Psoriasis and 
Psoriatic Arthritis (NAPPA-CLIN), Total Score Psoriasis Symptom Scale (PSS), Dermatology Life 
Quality Index (DLQI), Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental 
Component Summary (MCS) Scores, Patient Benefit Index (PBI), Hospital Anxiety and Depression 
Scale (HADS) Patient Global Assessment (PtGA), European quality of life – 5 dimensions 5 Level (EQ-
5D-5L)
Pharmacokinetics and Immunogenicity:
Blood samples will be collected for measurement of risankizumab concentration and anti-drug antibody 
(ADA) between Day 1/Week 0 and Week 24/early termination (ET) visits.
Safety: 
Safety and tolerability evaluations include adverse event monitoring, physical examinations, vital sign 
measurements, and clinical laboratory testing (hematology, chemistry, and urinalysis).  Toxicity 
management guidelines are provided within the study protocol.


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EudraCT 2016-003718-28
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Statistical Methods:
Efficacy:
The efficacy analysis will be performed in the Intent to Treat (ITT) set which includes all subjects who 
are randomized.
The primary efficacy endpoint (PASI90 at Week 24) will be analyzed using a two-sided Cochran-Mantel 
Haenszel test stratified by prior phototherapy at level of significance 5%.  Missing data will be imputed 
using non-responder imputation, i.e., a subject with missing PASI90 at Week 24 will be considered a 
non-responder in the primary analysis.
For categorical secondary endpoints, the same statistical test as for the primary endpoint will be used, 
missing data will be imputed using non-responder imputation.  For continuous secondary endpoints, 
two-sided two-way ANOVA will be used with treatment and prior phototherapy as factors and missing 
data will be imputed using last observation carried forward (LOCF). 
Secondary endpoints will not be used for confirmatory interpretation, thus no adjustment for multiplicity 
will be done.
Pharmacokinetics (PK) and Immunogenicity:
Risankizumab serum concentrations will be determined.  Descriptive statistics will be calculated for each 
sampling time (study visit).  The number and percentage of subjects with ADA will be calculated.
Additional analyses combining pharmacokinetic and ADA data from this study and other studies may be 
conducted if appropriate.  
Safety:
The safety analysis will be performed in the safety set which includes all subjects who received at least 
one dose of study drug.
Treatment-emergent adverse events will be tabulated by system organ class and preferred term, whereby 
the most current implemented MedDRA dictionary will be used.  Also, summaries by severity and 
relationship to study drug will be done.  Certain adverse events, like serious or severe, leading to 
discontinuation, will be listed and described in detail.  Adverse events of interest for treatment with 
biologics will be defined in the statistical analysis plan and analyzed separately.
Adverse events will be summarized by frequency and percentage and presented by treatment group, 
statistical comparisons will be performed using Fisher's exact test.
Other safety variables like laboratory data and vital signs will also be described by descriptive statistics 
for each treatment group.  Treatment comparisons will be performed by one way ANOVA.  In addition, 
shift tables and listings will be provided for abnormal values, whereby the normal range of the analyzing 
laboratory will be used.
*
Criteria Committee, New York Heart Association, Inc.  Diseases of the heart and blood vessels.  Nomenclature and 
criteria for diagnosis, 6th edition Boston, Little, Brown and Co. 1964, p 114.


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1.3
List of Abbreviations and Definition of Terms
Abbreviations
ADA
Anti-Drug Antibody
AE
Adverse event
AP
Alkaline phosphatase
ALT
Alanine aminotransferase
ANOVA
Analysis of variance
AST
Aspartate aminotransferase
ATEMS
AbbVie Temperature Excursion Management System
AUC
Area under the curve
BI
Boehringer Ingelheim
BSA
Body surface area
CA
Competent authority
CASPAR
ClASsification criteria for Psoriatic Arthritis
CBC
Complete blood count
CCVT
Cardiovascular, cerebro Vascular and Thrombosis
CDSM
Clinical Drug Supply Management
CK
Creatine kinase
CK-MB
Creatine kinase MB isozyme
Cmax
Maximal concentration
CRA
Clinical research associate
CRP
C-reactive protein
CYP3A
Cytochrome P450 3A
DILI
Drug induced liver injury
DLQI
Dermatology Life Quality Index
DMC
Data monitoring committee
DMF
Dimethyl fumarate
DNA
Deoxyribonucleic acid
DSM-IV
Diagnostic and Statistical Manual of Mental Disorders, 4th edition
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
EDTA
Edetic acid (ethylenediaminetetraacetic acid)


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EMA
European Medicines Agency
EQ-5D-5L
European Quality of Life – 5 Dimensions 5 Level
EP
European Pharmacopoeia
ET
Early termination
EudraCT
European Clinical Trials Database
FDA
US Food and Drug Administration
FSH
Follicle stimulating hormone
G-BA
Gemeinsamen Bundesausschusses 
GGT
Gamma-glutamyl transferase
GCP
Good Clinical Practice
GOT
glutamic oxaloacetic transaminase
GPT
glutamate-pyruvate transaminase
gCV
Geometric mean of coefficient vatiation
HADS
Hospital Anxiety & Depression Scale
HAV-IgM
Hepatitis A virus immunoglobulin M
Hb
Hemoglobin
HBsAg
Hepatitis B surface antigen
Hct
Hematocrit
HCV Ab
Hepatitis C virus antibody
HIV
Human immunodeficiency virus
IB
Investigator's brochure
IC
Inhibitor concentration
ICH
International Conference on Harmonization
IEC
Independent ethics committee
IGRA
Interferon-gamma release assay
IL
Interleukin
IMP
Investigational medicinal product
IRB
Institutional Review Board
ITT
Intent to treat
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IVRS/IWRS
Interactive voice response system/Interactive web response system
LOCF
Last observation carried forward
mAB
Monoclonal antibodies


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10
MACE
Major adverse cardiovascular events
MCS
Mental Component Summary
MHF
Methyl hydrogen fumarate
MedDRA
Medical Dictionary for Regulatory Activities
NAb
Neutralizing antibody
NAPPA-CLIN
Nail Assessment in Psoriasis and Psoriatic Arthritis
NDC
National Drug Code
NYHA
New York Heart Association
PASI
Psoriasis Area and Severity Index
PBI
Patient Benefit Index
PCS
Physical Component Summary
PD
Pharmacodynamic
PEE
Primary Efficacy Endpoint
PGA
Physician's Global Assessment
PK
Pharmacokinetic
PMN
Polymorphonuclear
PoCC
Proof of clinical concept
PPASI
Palmoplantar Posoriasis Severity Index
PPD
Purified Protein Derivative
POR
Proof of Receipt
PRO
Patient Reported Outcome
PSSI
Psoriasis scalp severity index
PSS
Psoriasis Symptom Severity
PtGA
Patient Global Assessment
PUVA
Psoralen plus ultraviolet light
QD
One a day
QTc
QT interval corrected for heart rate
RNA
Ribonucleic acid
SAE
Serious adverse event
SC
Subcutaneous
SF-36
Short Form 36
sPGA
Static Physician Global Assessment
SUSAR
Suspected unexpected serious adverse reactions
TA MD
Therapeutic Area Medical Director


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TB
Tuberculosis
TEAE
Treatment-emergent adverse event
TID
Three times a day
TNF
Tumor necrosis factor
UACR
Urinary Albumin-to-Creatinine Ratio
ULN
Upper limit of normal
US
Ultrasound
USP
United States Pharmacopoeia
UV
Ultra Violet
VAS
Visual Analog Scale
VCAM-1
Vascular cell adhesion molecule 1
WOCBP
Women of childbearing potential
Definition of Terms
Moderate to severe psoriasis defined as:1  BSA > 10 and PASI > 10 and DLQI > 10


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12
2.0
Table of Contents
1.0
Title Page ...............................................................................1
1.1
Protocol Amendment:  Summary of Changes ......................................... 2
1.2
Synopsis................................................................................................. 4
1.3
List of Abbreviations and Definition of Terms........................................ 8
2.0
Table of Contents ................................................................ 12
3.0
Introduction......................................................................... 16
3.1
Differences Statement .......................................................................... 20
3.2
Benefits and Risks................................................................................ 20
4.0
Study Objective ................................................................... 22
5.0
Investigational Plan.............................................................22
5.1
Overall Study Design and Plan:  Description ........................................ 22
5.2
Selection of Study Population............................................................... 25
5.2.1
Inclusion Criteria.................................................................................. 26
5.2.2
Exclusion Criteria................................................................................. 27
5.2.3
Prior and Concomitant Therapy............................................................ 30
5.2.3.1
Prior Therapy ....................................................................................... 30
5.2.3.2
Concomitant Therapy........................................................................... 30
5.2.3.3
Prohibited Therapy............................................................................... 31
5.2.4
Contraception Recommendations and Pregnancy Testing ..................... 32
5.3
Efficacy and Safety Assessments/Variables.......................................... 33
5.3.1
Efficacy and Safety Measurements Assessed ........................................ 33
5.3.1.1
Study Procedures.................................................................................. 34
5.3.2
Drug Concentration Measurements....................................................... 48
5.3.2.1
Collection of Samples for Analysis....................................................... 48
5.3.2.2
Handling/Processing of Samples........................................................... 49
5.3.2.3
Disposition of Samples......................................................................... 49
5.3.2.4
Measurement Methods ......................................................................... 49
5.3.3
Efficacy Variables................................................................................ 50
5.3.3.1
Primary Variable .................................................................................. 50
5.3.3.2
Secondary Variables............................................................................. 50
5.3.4
Safety Variables ................................................................................... 51


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5.3.5
Pharmacokinetic Variables ................................................................... 51
5.4
Removal of Subjects from Therapy or Assessment ............................... 51
5.4.1
Discontinuation of Individual Subjects for Either Risankizumab or 
FUMADERM®..................................................................................... 51
5.4.1.1
Discontinuation of Subjects on FUMADERM® .................................... 53
5.4.2
Discontinuation of Entire Study............................................................ 54
5.5
Treatments ........................................................................................... 55
5.5.1
Treatments Administered...................................................................... 55
5.5.2
Identity of Investigational Product(s).................................................... 56
5.5.2.1
Identity of Risankizumab Investigational Product................................. 56
5.5.2.2
Identity of FUMADERM® INITIAL and FUMADERM® 
Investigational Product......................................................................... 57
5.5.2.3
Packaging and Labeling........................................................................ 57
5.5.2.4
Storage and Disposition of Study Drug(s)............................................. 58
5.5.3
Method of Assigning Subjects to Treatment Groups ............................. 59
5.5.4
Selection and Timing of Dose for Each Subject .................................... 59
5.5.5
Blinding ............................................................................................... 60
5.5.6
Treatment Compliance ......................................................................... 60
5.5.7
Drug Accountability ............................................................................. 61
5.6
Discussion and Justification of Study Design........................................ 62
5.6.1
Discussion of Study Design and Choice of Control Groups .................. 62
5.6.2
Appropriateness of Measurements........................................................ 62
5.6.3
Suitability of Subject Population .......................................................... 63
5.6.4
Selection of Doses in the Study ............................................................ 63
6.0
Complaints........................................................................... 64
6.1
Medical Complaints ............................................................................. 64
6.1.1
Definitions ........................................................................................... 65
6.1.1.1
Adverse Event...................................................................................... 65
6.1.1.2
Serious Adverse Events........................................................................ 65
6.1.1.3
Area of Safety Interest.......................................................................... 66
6.1.1.4
CCVT Adjudication Committee ........................................................... 68
6.1.2
Adverse Event Severity ........................................................................ 68
6.1.3
Relationship to Study Drug................................................................... 69


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6.1.4
Adverse Event Collection Period.......................................................... 69
6.1.5
Adverse Event Reporting...................................................................... 70
6.1.6
Pregnancy............................................................................................. 72
6.2
Product Complaint................................................................................ 72
6.2.1
Definition............................................................................................. 72
6.2.2
Reporting ............................................................................................. 73
7.0
Protocol Deviations ............................................................. 73
8.0
Statistical Methods and Determination of Sample 
Size ....................................................................................... 74
8.1
Statistical and Analytical Plans............................................................. 75
8.1.1
Analysis Populations ............................................................................ 75
8.1.2
Planned Methods of Statistical Analysis ............................................... 75
8.1.3
Demographic and Baseline Characteristics ........................................... 75
8.1.4
Analysis of Efficacy ............................................................................. 75
8.1.5
Analysis of Safety ................................................................................ 76
8.1.6
Interim Analysis................................................................................... 77
8.1.7
Pharmacokinetic and Exposure-Response Analysis .............................. 77
8.2
Determination of Sample Size .............................................................. 78
8.3
Randomization Methods....................................................................... 78
9.0
Ethics.................................................................................... 78
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ......................................................................................... 78
9.2
Ethical Conduct of the Study................................................................ 79
9.3
Subject Information and Consent.......................................................... 79
10.0
Source Documents and Case Report Form 
Completion ..........................................................................80
10.1
Source Documents................................................................................ 80
10.2
Case Report Forms............................................................................... 80
11.0
Data Quality Assurance ...................................................... 82
12.0
Use of Information ..............................................................83
13.0
Completion of the Study ..................................................... 84
14.0
Investigator's Agreement....................................................85
15.0
Reference List......................................................................86


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List of Tables
Table 1.
Prohibited Psoriasis Medications .......................................................... 31
Table 2.
Tasks of the Efficacy Assessora and Investigator .................................. 40
Table 3.
Clinical Laboratory Tests ..................................................................... 42
Table 4.
Identity of Risankizumab Investigational Product................................. 56
Table 5.
FUMADERM® INITIAL and FUMADERM® Pre-Specifed 
Dosing Schedule (in the Absence of an Adjustment to the 
Efficacy and/or Safety Response): ........................................................ 57
List of Figures
Figure 1.
PASI 90 Over Time (Observed) – Full Analysis Set ............................. 18
Figure 2.
Study Schematic................................................................................... 25
Figure 3.
Adverse Event Collection..................................................................... 70
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.......................................... 91
Appendix B.
List of Protocol Signatories .................................................................. 93
Appendix C.
Study Activities.................................................................................... 94
Appendix D.
Recommendations on the Technique of Blood Pressure 
Measurement........................................................................................ 97
Appendix E.
CASPAR Classification Criteria..........................................................100
Appendix F.
PASI SCORE Definitions and Use Psoriasis Area and Severity 
Index (PASI) .......................................................................................101
Appendix G.
Static Physician Global Assessment (sPGA)........................................104
Appendix H.
Palmoplantar Psoriasis Severity Index (PPASI) ...................................107
Appendix I.
Psoriasis Scalp Severity Index (PSSI)..................................................109
Appendix J.
NAPPA-CLIN.....................................................................................110
Appendix K.
Protocol Amendment:  List of Changes ...............................................113


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3.0
Introduction
Psoriasis is a chronic inflammatory disease with raised, well-demarcated erythematous 
plaques with adherent silvery scales.2  It is the most prevalent immune mediated skin 
disease, affecting 2% of the world population.3  Twenty-five percent of patients have 
moderate to severe disease with considerable negative impact on psychosocial and 
economic status.4  It is increasingly recognized that psoriasis is more than a superficial 
disease, with 30% of patients having joint involvement and a high correlation between 
psoriasis and obesity, diabetes, depression, metabolic syndrome and cardiovascular risk.5
While the majority of psoriasis patients are managed initially with topical therapies, those 
with severe and/or refractory disease may require phototherapy and/or systemic therapy.  
Oral systemic agents provide modest efficacy, but increasingly patients are treated with 
biological agents such as tumor necrosis factor (TNF)-alpha inhibitors (etanercept, 
adalimumab) and the interleukin (IL)-12/23 inhibitor (ustekinumab).6  While the clinical 
efficacy of ustekinumab indicates a role for both IL-12 and IL-23 in the pathogenesis of 
psoriasis,7 more recent data suggest that IL-23 is disproportionately involved in the 
maintenance of chronic psoriasis.7  IL-23 is thought to be involved in the pathophysiology 
of psoriasis via induction and maintenance of Th17 type cells, and other IL-23 responsive 
cells.  This is supported by recent clinical data indicating that monoclonal antibodies 
(mAb) that block IL-17, the cytokine produced by Th17 cells, have high efficacy in 
psoriasis.8
There is still clinical need for increased efficacy as the most effective anti-TNF and 
IL12/23 agents provide approximately 75% improvement in psoriasis in about 60 – 70% 
of patients and these responses tend to be lost over time.  While the anti-IL-17 agents 
(i.e., secukinumab) may provide better efficacy, they require monthly injections, thus their 
long term utility is still undetermined.8
Risankizumab is a fully humanized mAb of the IgG1 subclass directed towards IL-23p19.  
The antibody has been engineered to reduce Fcγ receptor and complement binding and 
potential charge heterogeneity.  Risankizumab binds with high affinity to human IL-23 


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and inhibits IL-23 stimulated IL-17 production at inhibitory concentration (IC) 50 
concentrations below 10 pM, as compared with 167 nM for ustekinumab in the same 
system.  Risankizumab does not affect IL-12 at a maximum tested concentration (33 nM) 
and it does not inhibit IL-12 stimulated IFN-γ production.
The toxicology data suggest that risankizumab can be safely administered to humans, as 
supported by chronic administration to monkeys for up to 26 weeks.  The monkey was 
identified as the most relevant toxicology species with no observed adverse effect level 
(NOAEL) of 50 mg/kg/dose, corresponding to an exposure (combined sex) of 677 μg/mL 
for the maximal concentration (Cmax) and 86,250 μg•h/mL for area under the curve (AUC) 
0 – 168, respectively.
In Phase 1 and Phase 2 risankizumab has been studied in approximately 200 subjects with 
psoriasis without any unexpected adverse events (AEs) or safety signals.  Based on the 
efficacy and safety findings in the completed and ongoing studies, the risk benefit profile 
of risankizumab is appropriate for further conduct of Phase 3 studies.  In the Boehringer 
Ingelheim (BI) Study 1311.1,9 a Phase 1 single rising dose study in 39 subjects with 
chronic plaque psoriasis, both intravenous (i.v.) and subcutaneous (s.c.) administration of 
risankizumab was well tolerated.  Over the 24 weeks following a single i.v. or s.c. 
administration of risankizumab, 65% (20/31) of subjects experienced an adverse event 
(AE) compared with 88% (7/8) of subjects receiving placebo.  There was no relationship 
between the overall frequency of AEs and treatment groups, or between the occurrence of 
AEs in specific system organ classes, or individual AEs, and treatment groups.  
Four serious adverse events (SAE) were reported in subjects receiving risankizumab.  All 
resolved without sequelae and were considered unrelated to study treatment.
After a single i.v. administration, risankizumab geometric mean AUCAUC0-inf ranged 
from 2.93 – 1650 day•μg/mL and Cmax from 0.311 – 110 μg/mL, with exposure increasing 
in a dose-proportional manner.  Group mean clearance and terminal phase volume of 
distribution were 0.33 L/day and 10.8 L, respectively.  Based on all dose groups, the 
absolute bioavailability of risankizumab after SC administration was estimated to be 73%.


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In a 48 week Phase 2 dose ranging study of risankizumab vs. ustekinumab in 
166 subjects, approximately 73% of subjects reported an AE; the most common were 
nasopharyngitis (32% of 126 subjects in risankizumab arms), headache (9%), back pain 
(6%) and arthralgia (5%).  Overall, there was no difference in the AEs across treatment 
groups and no evidence of a dose effect for any AE.  During the 48-week study, 
11 subjects (8.7%) on risankizumab reported at least 1 serious adverse event. One subject 
administered risankizumab (90 mg) experienced an SAE that was considered related to 
study treatment (basal cell carcinoma).  All other SAEs were considered unrelated to 
study treatment.  
Treatment with 90 or 180 mg risankizumab resulted in a higher percentage of subjects 
satisfying and maintaining Psoriasis Area and Severity Index (PASI) 90 through Week 48 
as compared with ustekinumab and risankizumab 18 mg.10
Figure 1.
PASI 90 Over Time (Observed) – Full Analysis Set


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The 12 week data indicate a 37% greater improvement for risankizumab (90 mg and 
180 mg, pooled data) compared to ustekinumab in the proportion of subjects achieving 
PASI 90.10
The current study compares the safety and efficacy of risankizumab versus Fumaderm®
provided as study medication in subjects with moderate to severe psoriasis.
For a more detailed description of the drug profile, refer to the latest version of the 
investigator's brochure (IB).9
Fumaric acid esters was approved in Germany as systemic therapy for the treatment of 
psoriasis in 1995.  The commercial product, Fumaderm® contains a mixture of dimethyl 
fumarate (DMF) and three salts of ethyl hydrogen fumarate.  DMF is considered to be the 
actual active ingredient.1
Most of the reports on the clinical effects of Fumaderm® on psoriasis are from open label 
studies that consistently showed that a significant improvement in the condition of the 
skin is reached over a period of about 3 months of treatment.1-16
Preliminary results of a recent adequate and well controlled clinical study including a 
Fumaderm® arm indicate that PASI 75 and PGA 0 or 1 responses were achieved at 
Week 16 in 40.3% and 37.4% of the subjects treated with Fumaderm®, whereas 22.3% of 
the subjects achieved PASI 90 at Week 16.17
Serious adverse events were reported in 2.8% of the subjects and discontinuation due to 
adverse events occurred in 24% of the subjects receiving FUMADERM®.  The most 
frequently reported treatment-emergent adverse events (TEAEs) were gastrointestinal 
disorders, including diarrhea (39.9%), upper abdominal pain (22.6%), abdominal pain 
(15.9%) and nausea (8.5%).  Flushing was also commonly reported (16.3%) as well as 
pruritus (9.9%).  Lymphopenia was observed in 10.6% of the subjects and was considered 
severe in two subjects (0.07%).  Erythema, headache and nasopharyngitis were also 
reported (8.1% each).  Proteinuria was reported in 2.1% of the subjects.


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3.1
Differences Statement
The present study will only include subjects with moderate to severe plaque psoriasis who 
are naïve to systemic therapy, whereas the subjects included in the worldwide 
risankizumab psoriasis development program may have previously been exposed to 
biologic or non-biologic systemic treatment for psoriasis.
The comparator will be fumaric acid esters, commercialized as FUMADERM® in 
Germany whereas the ongoing studies of risankizumab use placebo, ustekinumab or 
adalimumab as comparators.
One further difference between other studies of risankizumab in psoriasis and this study 
relates to the definition of moderate to severe psoriasis, which, for this study, is defined as 
PASI > 10, body surface area (BSA) > 10% and dermatology life quality index (DLQI) 
> 10, this later definition being based on a European consensus decision.1,18  In other 
studies of risankizumab, moderate to severe psoriasis is defined as PASI ≥ 12, BSA 
≥10% and static physician global assessment (sPGA) ≥ 3.
3.2
Benefits and Risks
In Phase 1 and Phase 2 studies of risankizumab in patients with psoriasis, the majority of 
subjects receiving risankizumab achieved 90% improvement of their disease and 
risankizumab was well tolerated.  
As with many immune modulating agents, risankizumab may impair immune function 
resulting in a risk of infection.  This will be monitored by collection of all AEs during the 
treatment and observation periods.
Subjects with active infection will not be included in the study.
Subjects with a positive QuantiFERON®-test or a positive Purified Protein Derivative 
(PPD) skin test for tuberculosis (TB) must fulfill entry criteria as specified in 
Section 5.2.1 of this protocol.  Interleukin-23 inhibition is not known to increase the risk 
of TB infection or impair the response to TB infection in animal models.19,20  Thus, low 


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risk subjects with positive Quantiferon testing do not need to be treated with anti-
tuberculosis therapy prior to receiving risankizumab, but should be carefully monitored 
for any sign of TB reactivation.  Absence of TB reactivation, despite not receiving 
anti-tuberculosis prophylaxis will provide important information in humans as to whether 
TB testing is required prior to treatment with risankizumab.21
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 or 
serious infection.
Increases in major adverse cardiovascular (MACE) events including myocardial 
infarction, cerebrovascular accident, and cardiovascular death, reported initially with 
anti-IL-12/23 agents, such as ustekinumab, have not been observed in longer term studies.  
Although rare, a potential for drug-induced liver injury (DILI) is under constant 
surveillance by sponsors and regulators.  Therefore, this study requires timely detection, 
evaluation, and follow-up of laboratory alterations in selected liver laboratory parameters 
to ensure subjects' safety.
In conclusion, the benefit-risk profile of risankizumab is considered appropriate for this 
stage of clinical development.
Fumaderm® is a widely prescribed systemic therapy for moderate to severe psoriasis, 
although registered for this indication in Germany only, a high proportion of patients 
treated with FUMADERM® experience a significant improvement in their psoriatic skin 
disease over a period of about 3 months of treatment.1
The safety profile of FUMADERM® is well characterized.  Gastrointestinal complaints 
(in up to 60% of subjects especially in the initial weeks of therapy) and flush are the most 
common side effects of fumaric acid esters.  Gastrointestinal tract symptoms include 
diarrhea, increased frequency of stools, nausea, and abdominal cramps.  The symptoms of 
flush are highly variable and range from a brief feeling of warmth to reddening of the face 


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lasting for several hours.  Leukocytopenia, lymphocytopenia, and eosinophilia are 
common side effects of fumaric acid esters.  The other adverse events reported in 
association with FUMADERM® remain uncommon to very rare:  acute lymphocytic 
leukemia, increase in liver function tests, Fanconi syndrome, opportunistic infection 
increases including isolated cases of progressive multifocal encephalopathy. 
There is no known association of FUMADERM® with malignancy.1,22
There are no studies on the use of fumaric acid esters during pregnancy or in nursing 
women.  Toxicology studies have shown that fumaric acid esters have neither teratogenic 
nor mutagenic potential.
The well codified dosing schedule for FUMADERM®, based on individual efficacy and 
safety response and the long experience in clinical practice since its commercialization 
guarantees an acceptable risk-benefit balance.  Pregnancy and breastfeeding as well as 
severe liver, kidney and gastrointestinal diseases are contraindication to Fumaderm®.
4.0
Study Objective
The objective of this study is to compare the efficacy and safety of SC risankizumab and 
oral FUMADERM® provided as study medication in subjects with moderate to severe 
plaque psoriasis who are naïve to and candidates for systemic therapy.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This is a randomized, controlled, multicenter, open-label study with blinded assessment of 
efficacy to demonstrate the efficacy and safety of SC risankizumab in adult subjects with 
moderate to severe plaque psoriasis who are naïve to and candidates for systemic therapy 
as compared with oral FUMADERM® provided as study medication.  Eligible male and 
female subjects with moderate to severe plaque psoriasis will be selected to participate in 
the study according to the selection criteria.


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The study will include a 30-day screening period and a 24 week active-controlled 
treatment period followed by a follow-up phone call at Week 31 for subjects that do not 
elect to enroll into the extension study.  The maximum study duration is approximately 
35 weeks for subjects that do not elect to enroll into the extension study and 
approximately 28 weeks for subjects that do participate in the extension study.  This study 
was designed to enroll 110 subjects to meet scientific and regulatory objectives without 
enrolling an undue number of subjects in alignment with ethical considerations.  
Therefore, if the target number of subjects has been enrolled, there is a possibility that 
additional subjects in screening will not be enrolled.
After meeting the selection criteria, enrolled subjects will be randomly assigned in a 
1:1 ratio to one of two arms as shown below:
●
Risankizumab 150 mg SC at Week 0/Day 1, Week 4 and Week 16 or,
●
Oral FUMADERM® INITIAL provided as study medication starting at 
Week 0/Day 1 until Week 2 and FUMADERM® provided as study medication 
starting at Week 3 until Week 24 (last intake in the morning on the day of 
Week 24 visit):
Screening Period 
Within 30 days prior to the Week 0/Day 1 visit, subjects will receive a full explanation of 
the study design and study procedures, provide a written informed consent, and undergo 
the screening procedures outlined in Appendix C.
Paper diaries for FUMADERM® INITIAL and FUMADERM® (provided as study 
medication) dosing will be provided to the subjects at the visits outlined in Appendix C.
Subjects that initially screen-fail for the study may be permitted to re-screen one time 
following re-consent.
●
A repeat of all screening procedures is needed with the possible exceptions 
noted below.


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○
If the subject had a complete initial screening evaluation including the 
assessment of an Interferon-Gamma Release Assay (IGRA; QuantiFERON 
Tuberculosis [TB] Gold In Tube test) or a purified protein derivative 
(PPD) test (or equivalent), and electrocardiogram (ECG), these tests will 
not be required to be repeated for re-screening provided the conditions 
noted in Section 5.3.1.1 are met.  
●
There is no minimum period of time a subject must wait to re-screen for the 
study.  If there is an exclusionary laboratory result during screening or 
re-screening within the 30 day screening window, one re-test of that particular 
value is allowed without repeating all other laboratory tests.  
●
The subject must meet all inclusion and none of the exclusion criteria at the 
time of re-screening in order to qualify for the study.  
Treatment Period
This period will begin at the Week 0/Day 1 (Baseline) Visit and will end at the 
Week 24/Early Termination (ET) Visit.  At the Baseline Visit, subjects who meet all the 
inclusion criteria and none of the exclusion criteria described in Section 5.2 will be 
enrolled into the study and randomized to open-label treatment.  During this period of the 
study, subjects will visit the site at Week 0 (Day 1/Baseline), Week 4, Week 8, Week 12, 
Week 16, Week 20 and Week 24/ET.  A ± 4 day window is permitted around scheduled 
study visits.  If any visit has to be rescheduled, subsequent visits should follow the 
original visit date schedule.  Visits should take place on the same day of the week as much 
as possible.  At the Week 24 visit, subjects who have completed the study will be offered 
the opportunity to participate in a separate extension study.  For subjects that do not elect 
to enroll into the extension study, a follow-up phone call will be performed at Week 31.
Safety data will be collected throughout the treatment period and up to 15 weeks after the 
last dose of risankizumab and/or 7 weeks after the last dose of FUMADERM® provided 
as study medication in this study.  Subjects may discontinue study drug treatment at any 
time during study participation.  Subjects that discontinue the study prior to Week 24 will 
have an ET visit and complete the procedures outlined in Appendix C within 2 weeks 


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after the decision to discontinue and preferably prior to the administration of any new 
therapies.
Follow-Up Period
Subjects will have a follow-up phone call at approximately Week 31 (approximately 
15 weeks after the last dose of risankizumab and 7 weeks after the last dose of 
FUMADERM® provided as study medication) with the exception of those subjects that 
elect to enroll into the extension study.  All follow-up phone call procedures are noted in 
Appendix C.
A schematic of the study design is shown below in Figure 2.
Figure 2.
Study Schematic
5.2
Selection of Study Population
It is anticipated that approximately 110 subjects with stable moderate to severe Plaque 
Psoriasis will be enrolled at approximately 25 sites in Europe.  The subject population 


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will include adults with moderate to severe plaque psoriasis (PASI score of > 10, affected 
BSA > 10% and DLQI > 10) who are naïve to and candidates for systemic therapy.
A subject may be enrolled in this study provided that he/she has met all of the inclusion 
criteria and none of the exclusion criteria specified in this protocol.
5.2.1
Inclusion Criteria
1.
Male or female subject ≥ 18 and < 80 years of age at the time of screening.
2.
Have a diagnosis of chronic plaque psoriasis for at least 6 months before the 
first administration of study drug.  Duration since diagnosis may be reported by the 
patient.
3.
Subject has stable moderate to severe plaque psoriasis with or without psoriatic 
arthritis at Baseline
●
Has an involved BSA > 10% and
●
Has a PASI score > 10 and
●
Has a DLQI > 10
4.
Must be naïve to and candidate for systemic therapy, as assessed by the 
investigator.
5.
Subject has an inadequate response, intolerance or contraindication to topical 
psoriasis treatment as documented in the patient's medical history or reported by 
the patient or determined by the investigator at screening.
6.
Patient who is a candidate for Fumaderm®, Ciclospirin, Methotrexate or 
phototherapy as per investigator's discretion.
7.
If female, subject must be either postmenopausal OR Women of Childbearing 
Potential (WOCBP) and practicing at least one protocol specified method of birth 
control (detailed in Section 5.2.4), starting at Study Day 1 (or earlier) through at 
least 15 weeks after the last dose of risankizumab or FUMADERM® provided as 
study medication.


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8.
Females of childbearing potential must have a negative serum pregnancy test result 
at Screening, and a negative urine pregnancy test at Study Day 1.  Females of 
non-childbearing potential (either postmenopausal or permanently surgically sterile 
as defined above) at Screening do not require pregnancy testing at Study Day 1.
9.
Signed and dated written informed consent in accordance with GCP and local 
legislation prior to admission to the study and prior to any study related procedure.
Rationale for the Inclusion Criteria:
1 – 6
To select the adequate subject population
7 – 8
The impact of risankizumab on pregnancy and reproduction is unknown
9
In accordance with harmonized Good Clinical Practice (GCP)
5.2.2
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following 
criteria:
1.
Female subject who is pregnant, breastfeeding or is considering becoming pregnant 
during the study or for at least 15 weeks (i.e., 105 days) after the last dose of study 
drug.
2.
Subjects with:
●
Non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)
●
Drug-induced psoriasis (including an exacerbation of psoriasis from beta 
blockers, calcium channel blockers, or lithium)
●
Active ongoing inflammatory diseases other than psoriasis that might 
confound study evaluations according to investigator's judgment
3.
Subject has previously received systemic therapy for psoriasis, whether biologic or 
non-biologic or photochemotherapy (e.g., PUVA therapy, any UV-therapy or 
balneotherapy associated with UV-sensitizing agent).


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4.
Subject cannot avoid excessive sun exposure (e.g., occupational exposure for a 
gardener or a roofer) or use of tanning booth for at least 4 weeks before baseline 
and during the study.
5.
Participation in another study with an investigational drug or device within 4 weeks 
or 5 half-lives (whichever is greater) prior to screening.
6.
Subjects who must or wish to continue the intake of restricted medications or any 
drug considered likely to interfere with the safe conduct of the study, as assessed 
by the investigator, (see Section 5.2.3).
7.
Plans for administration of live vaccines during the study period or within 6 weeks 
prior to screening.
8.
Major surgery performed within 12 weeks prior to screening or planned within the 
duration of the study (e.g., hip replacement, aneurysma removal, stomach ligation).
9.
Active systemic infection during the last 2 weeks (exception:  common cold) prior 
to screening.
10.
Known chronic or relevant acute infections including HIV, viral hepatitis and/ or 
tuberculosis.  Subjects with a positive QuantiFERON® TB/PPD test result may 
participate in the study if further work up (according to local practice/guidelines) 
establishes conclusively that the subject has no evidence of active tuberculosis.
11.
Subjects with a documented history of active TB may not enter the study unless 
they have completed a full course of anti-TB therapy and have been discussed with 
the AbbVie Therapeutic Area Medical Director (TA MD).
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.
Evidence of a current or previous disease, medical condition other than psoriasis, 
surgical procedure (i.e., organ transplant), medical examination finding (including 
vital signs and ECG), or laboratory value at the screening visit outside the 
reference range that in the opinion of the investigator is clinically significant and 


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would make the study participant unreliable to adhere to the protocol or to 
complete the study, compromise the safety of the patient, or compromise the 
quality of the data.
14.
Subject has any condition or contraindication to FUMADERM® that would 
preclude the patient's participation in the present study, including, but not limited 
to:
●
A known hypersensitivity to fumaric acid derivatives or other components of 
FUMADERM® Initial or FUMADERM®
●
Any parameter of the CBC outside of normal range according to the central 
laboratory at Screening visit,
●
Severe liver disease (ALT or AST > 2 × ULN according to central lab normal 
range, or total bilirubin > 1.5 × ULN according to central laboratory normal 
range at Screening visit),
●
Severe kidney disease (serum creatinine above normal value according to 
central laboratory normal range at Screening visit),
●
Severe gastro-intestinal disease, such as a known active gastro-duodenal ulcer, 
●
Inability to understand the complexity of FUMADERM® dosing regimen,
●
Any other exclusionary condition provided in FUMADERM® local label,
●
Any of the following risk factors for renal toxicity:
○
peripheral vascular disease
○
diabetes mellitus with microalbuminuria (UACR > 30 mg/g) at Screening 
visit
○
Systolic blood pressure measurement of > 140 mmHg or a diastolic blood 
pressure measurement of > 90 mmHg at the Screening visit unless there is 
confirmation from an internist or a cardiologist that no renal or 
cardiovascular risk is associated with the elevated blood pressure.  
○
History of congestive heart failure (NYHA Class III or IV23)
15.
History of allergy/hypersensitivity to any of the excipients in the risankizumab 
formulation.


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Rationale for Exclusion Criteria: 
1
The impact of risankizumab on pregnancy and reproduction is 
unknown
2 – 6
To select the adequate subject population
7 – 15
To ensure the safety of the subjects throughout the study
5.2.3
Prior and Concomitant Therapy
The AbbVie TA MD should be contacted if there are any questions regarding concomitant 
or prior therapy(ies).
5.2.3.1
Prior Therapy
Any prior use of systemic treatment for psoriasis is prohibited.
Complete history of phototherapy will be captured as well as topical psoriasis medicine 
use for the past 5 years.
5.2.3.2
Concomitant Therapy
Any medication or vaccines (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject is receiving 4 weeks prior to 
screening or receives during the study, must be recorded along with the reason for use, 
date(s) of administration including start and end dates, and dosage information including 
dose, route and frequency on the appropriate eCRF.


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5.2.3.3
Prohibited Therapy
Table 1.
Prohibited Psoriasis Medications
Medication or Class of Medications
Restriction Duration
(Through 15 Weeks After 
the Last Dose of 
Risankizumab and Through 
1 Week after Last Dose of 
FUMADERM®a Provided as 
Study Medication)
All systemic biologics (including investigational products) to treat 
psoriasis, including guselkumab, tildrakizumab, briakinumab, 
efalizumab (Raptiva®), secukinumab (Cosentyx®), ustekinumab 
(Stelara®), brodalumab, ixekizumab, adalimumab (Humira®), 
infliximab (Remicade®), etanercept (Enbrel®), alefacept (Amevive®)
Not allowed before or during 
study participation
All systemic non biologic to treat psoriasis (including investigational 
products), including Fumaderm®, except if provided as study 
medication, methotrexate, cyclosporine A, cyclophosphamide, 
mycophenolate mofetyl, retinoids, corticosteroids,b tofacitinib, 
apremilast, and any other drug known to possibly benefit psoriasis
Not allowed before or during 
study participation
Any investigational device or product (excludes psoriasis products)  
30 days prior to screening or 
during study participation
Photochemotherapy (e.g., PUVA therapy, UV-therapy or 
balneotherapy associated with UV-sensitizing agent).
Not allowed before or during 
study participation
Phototherapy (e.g., UVA, UVB, any other UV-therapy or 
balneotherpy) not- associated with UV-sensitizing agents, topical 
treatment for psoriasis or any other skin condition 
(e.g., corticosteroids,c vitamin D analogues, vitamin A analogues, 
pimecrolimus, retinoids, salicylvaseline, salicylic acid, lactic acid, 
tacrolimus, tar, urea, andanthralin, α-hydroxy acid, fruit acids)
14 days prior to Baseline 
(Week 0/Day 1) or during 
study participation
a.
Except if a psoriasis flare requires urgent therapy.
b.
No restriction on corticosteroids with only a non-dermatological topical effect (e.g., inhalative corticosteroids to 
treat asthma or corticosteroid drops used in the eye or ear).
c.
Exception:  Topical corticosteroids of US class 7 (mild, such as desonide) or German class 1 (least potent, such as 
hydrocortisone 0.5 to 2.5%) for use on the face, axilla, and/or genitalia with a restriction of use within 24 hours 
prior to study visit in which PASI is assessed.


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The following therapies are prohibited in both groups.
●
Live virus vaccines, from 6 weeks prior to Screening through 15 weeks after 
the last dose of risankizumab and 1 week after the last dose of FUMADERM®
provided as study medication.
●
Nephrotoxic drugs, from 2 weeks prior to Screening through 15 weeks after 
the last dose of risankizumab and 1 week after the last dose of FUMADERM®
provided as study medication.  Namely:
○
retinoids, psoralens, methotrexate, cyclosporine, immunosuppressants, 
cytostatics 
○
aminoglycosides, amphotericin B, foscarnet, indinavir, tacrolimus, 
cisplatin, gold therapy, lithium, radiocontrast dyes
Rationale for the prohibited therapies:
Psoriasis medications (Table 1):  prevent an interaction with efficacy outcome and protect 
patient's safety.
Live vaccine and nephrotoxic drugs:  protect patient's safety.  The investigator should 
review the FUMADERM® label for a current list of excluded or cautionary medications.
5.2.4
Contraception Recommendations and Pregnancy Testing
If female, subject must be either postmenopausal defined as:
●
Age > 55 years with no menses for 12 or more months without an alternative 
medical cause.
●
Age ≤ 55 years with no menses for 12 or more months without an alternative 
medical cause AND an FSH level > 40 IU/L OR
●
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy 
or hysterectomy).


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Women of child bearing potential should practice at least one of the following methods of 
birth control, on Study Day 1 (or earlier) through at least 15 weeks after the last dose of 
study drug.
●
Combined (estrogen and progestogen containing) hormonal contraception 
(oral, intravaginal, transdermal) associated with the inhibition of ovulation, 
initiated at least 1 month prior to Study Day 1.
●
Progestogen-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation, initiated at least 1 month prior to Study 
Day 1.
●
Progestogen-only oral hormonal contraception, where inhibition of ovulation 
is not the primary mode of action, initiated at least 1 month prior to Study 
Day 1.
●
Bilateral tubal occlusion/ligation.
●
Bilateral tubal occlusion via hysteroscopy (i.e., Essure), provided a 
hysterosalpingogram confirms success of the procedure.
●
Vasectomized partner(s), provided the vasectomized partner verbally confirms 
receipt of medical assessment of the surgical success, and is the sole sexual 
partner of the WOCBP study participant.
●
Intrauterine device (IUD).
●
Intrauterine hormone-releasing system (IUS).
●
True abstinence:  Refraining from heterosexual intercourse when this is in line 
with the preferred and usual lifestyle of the subject [periodic abstinence 
(e.g., calendar, ovulation, symptothermal, post-ovulation methods) and 
withdrawal are not acceptable].
5.3
Efficacy and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed 
Study procedures described are listed in the following section of this protocol and are 
summarized in tabular format in Appendix C.


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5.3.1.1
Study Procedures
Study procedures will be performed at the study visits as specified in Appendix C.  Study 
visits are scheduled at Week 0/Day 1, Weeks 4, 8, 12, 16, 20 and 24/ET.  Study 
procedures are discussed in detail in this section, with the exception of drug concentration 
measurements and antibody measurements (discussed in Section 5.3.2), study drug 
administration (discussed in Section 5.5.1), and the collection of AE information 
(discussed in Section 6.1.1.1).  All study data will be recorded in source documents and 
on the appropriate eCRFs.
Informed Consent
The subject will sign and date a study specific, Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) approved, informed consent form before any 
study specific procedures are performed in order to participate in this study.  Details 
regarding how informed consent will be obtained and documented are provided in 
Section 9.3.
Inclusion/Exclusion Criteria
Subjects will be evaluated to ensure they meet all inclusion criteria and have none of the 
exclusion criteria at the Week 0/Day 1 visit.
Medical and Surgical History
A complete medical history, including history of tobacco, nicotine-containing products 
and alcohol use and ClASsification criteria for Psoriatic Arthritis (CASPAR)24
classification will be taken from each subject during the Screening Visit.  An updated 
medical history will be obtained prior to study drug administration and updated as 
necessary.  Phototherapy and topical psoriasis medication history prior to Baseline visit, 
other medication (prescription or over-the-counter, including vitamins and/or herbal 
supplements) use at the time of enrollment and through the end of the study will also be 
recorded.


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Demographics
The subject's demographic data, including year of birth, gender, race, and ethnicity will be 
collected.
Physical Examination
A complete or targeted physical examination will be performed at the designated study 
visits as specified in Appendix C.  A 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.
All physical examination findings whether related to an AE or part of a subject's medical 
history will be recorded on the appropriate eCRF page.
Vital Signs
Vital signs evaluations will be performed at visits as shown in Appendix C.
This includes temperature, pulse rate, systolic/diastolic blood pressure and respiratory 
rate.  Respiratory rate, pulse rate, and blood pressure will be measured after subjects have 
been sitting comfortably for at least 5 minutes.  In the case of an elevated blood pressure 
(systolic blood pressure > 140 mmHg or a diastolic blood pressure > 90 mmHg) at initial 
measurement, the recommendations in Appendix D40 should be followed in order to 
screen the subjects that will require further explorations.  Measurement of vital signs 
should precede blood sampling to avoid the impact of blood sampling on the vital 
measurements.
12-Lead Electrocardiogram (ECG)
The 12-lead ECGs will be performed as scheduled in Appendix C.


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ECGs will be recorded after the subjects 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 at the Investigator's discretion.  Clinically 
relevant, abnormal findings will be reported as AEs.
The electronic version of the ECG is regarded as source data.  Dated and signed printouts 
will be stored in the subject's medical file. 
Pregnancy Testing
A serum pregnancy test will be performed for all female subjects at the Screening Visit 
and at any other visit if the urine pregnancy test is positive.  The serum pregnancy test 
will be sent to and performed by the central laboratory.  If the serum pregnancy test at 
screening is positive in a female of child bearing potential, the subject is considered a 
screen failure.  If the serum pregnancy test at screening is borderline, it should be repeated 
to determine eligibility.  If the repeat test is not negative, the subject must be 
excluded/discontinued.
A urine pregnancy test will be performed for all female subjects of child-bearing 
potential, by the site at the Baseline Visit prior to the first dose of study drug and at all 
subsequent visits.  More frequent pregnancy tests will be performed throughout the study 
if required per local/country requirements.
●
If the urine pregnancy test performed at the site is negative, then dosing with 
study drug may begin/continue.  
●
If the urine pregnancy test performed at the site is positive, dosing must not be 
started/must be withheld and a serum pregnancy test is required.  For the 
serum pregnancy test, follow the steps above.


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A pregnant or breastfeeding female will not be eligible for participation or continuation in 
this study.
HIV Testing
Subjects with a known history of HIV infection are excluded from study participation.  
HIV testing will be conducted as part of the infection screening at the screening visit.  A 
subject will not be eligible for study participation if test results indicate a positive HIV 
infection.  AbbVie will not receive results from the testing and will not be made aware of 
any positive result.
Tuberculosis Screening
All subjects will be tested for TB by either the QuantiFERON-TB Gold Test (or 
equivalent) or a TB Skin Test (Purified Protein Derivative, PPD) at Screening visit as 
specified in Appendix C.  If the TB screening test [either, PPD or, the 
QuantiFERON®-TB Gold test (or Interferon gamma release assay (IGRA) equivalent)] is 
positive, or if there is a repeat indeterminate QuantiFERON®-TB Gold test (or IGRA 
equivalent) upon retesting, subjects 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 prophylaxis should be pursued according to clinical judgment of investigator 
and local country guidelines.
●
QuantiFERON®-TB Gold Test will be analyzed by the central laboratory 
(QuantiFERON test is preferred over TB Skin Test).
●
If the QuantiFERON®-TB Gold Test is NOT possible (or if both the 
QuantiFERON®-TB Gold Test and the PPD Skin Test are required per local 
guidelines) the PPD Skin Test will be performed according to standard clinical 
practice.
●
The PPD Skin Test should be read by a licensed healthcare professional 
between 48 and 72 hours after administration.  A subject who does not return 
within 72 hours will need to be rescheduled for another skin test.


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●
The reaction will be measured in millimeters (mm) of induration and 
induration ≥ 5 mm is considered a positive reaction.  The absence of induration 
will be recorded as "0 mm" not "negative."
●
If PPD and/or the QuantiFERON®-TB Gold test (or IGRA equivalent) is 
positive, or if there is a repeat indeterminate QuantiFERON®-TB Gold test (or 
IGRA equivalent) upon retesting, subjects may continue in the study if further 
work up (according to local practice/guidelines) establishes conclusively that 
the subject has no evidence of active tuberculosis.
●
If the subject is diagnosed with active tuberculosis, the subject should not 
receive any further study drug and follow the premature treatment 
discontinuation procedure (Early EOT visit) in Section 5.4.1.
●
If presence of latent tuberculosis is established treatment should be initiated 
and maintained according to local country guidelines.  If latent tuberculosis 
occurs during the study, it is also necessary to report it as an adverse event in 
the source documents and eCRFs.
●
If subject had a positive QuantiFERON®-TB Gold or PPD test at Screening, 
the test should not be repeated
●
Subjects who have had an ulcerating reaction to the TB Skin Test in the past 
should not be re-exposed and should not be tested by a PPD skin test.
●
In the case of a tuberculosis-related adverse event, a TB supplemental form 
that provides additional information will be completed by the investigator or 
designee.
Blinded Efficacy Assessor
At all treatment visits, the subjects will be assessed for efficacy by a blinded efficacy 
assessor.  
Prior to all examinations by the efficacy assessor, a bandage of the previous risankizumab 
injection site(s) in the subjects randomized to risankizumab will be applied.


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To maintain the efficacy assessor's blind to treatment, site personnel (except the blinded 
efficacy assessor) will put a bandage over a viable injection site location in those subjects 
who are receiving FUMADERM®.
A qualified physician (may be a non-dermatologist) or designee (may be a non-physician) 
from the site will be responsible for performing the efficacy assessments, including PASI, 
BSA, static physician global assessment (sPGA), palmoplantar psoriasis severity index 
(PPASI), psoriasis scalp severity index (PSSI) and nail assessment in psoriasis and 
psoriatic arthritis (NAPPA-CLIN), at all appropriate study visits.  The site will make 
every attempt to have the same qualified physician or designee perform these assessments 
throughout the study for each subject.  The efficacy assessor must remain blinded to 
patient's treatment, clinical laboratory results and all subject safety data during the course 
of the study.  The efficacy assessor will not view or discuss any subject specific safety 
data with the investigators or any other site personnel, with the exception of the 
dermatologic safety findings requiring urgent medical attention.  The efficacy assessor 
therefore cannot be the Principal Investigator. 
The efficacy assessor will not access patient's eCRF and will document the dermatologic 
assessments and potential dermatologic safety findings on paper worksheets that will be 
filed as source in the patient's record.
It is recommended that each study site has a designated back-up for the efficacy assessor.
The tasks of the blinded efficacy assessor are described in Table 2.


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Table 2.
Tasks of the Efficacy Assessora and Investigator
Activities
Responsible Party
Assesses PASI, BSA, sPGA, PPASI, PSSI and NAPPA-CLIN
Efficacy Assessor
Looks for any potential dermatologic safety finding
Efficacy Assessorb
Documents the efficacy assessments and any potential safety findings on 
worksheets
Efficacy Assessor
Assesses safety
Investigator
Knows treatment allocation 
Investigator
Inquires about treatment compliance, whether relating to psoriasis or not
Investigator
Reviews laboratory data
Investigator
Conduct the complete and targeted physical examinationsb
Investigator
Completes the CRF and PROs
Investigator
Adjust FUMADERM® dosage according to protocol
Investigator
Documents findings in the e-CRF
Investigator
Reports information about safety findingsc
Investigator
a.
The efficacy assessor is a physician or a designee that is blinded to all aspects of the study other than the efficacy 
assessments.
b.
The investigator will also look for potential dermatologic safety findings.
c.
If the efficacy assessor identifies a safety issue this will be transmitted to the investigator over the worksheet.  
Dermatologic safety findings requiring urgent medical attention will be the only safety issues that the efficacy 
assessor may discuss with the investigator.
Clinical Laboratory Tests
Blood samples will be obtained for the laboratory tests listed ("complete lab") in Table 3
at Screening, Week 0, 8, 16 and 24 visits.  At Week 4, 12, 20 visits only "targeted lab," 
i.e., CBC with differential count (hematology), ALT, AST, gamma-GT, alkaline 
phosphatase (AP) and serum creatinine, will be obtained.  Blood draws should be 
performed after all clinical assessments and patient reported outcomes, ECGs, and vital 
sign determinations are obtained before study drug administration during a visit.
Urine samples will be obtained for urinalysis testing at all visits as listed in Table 3.  The 
central laboratory will be responsible for performing a macroscopic urinalysis (urine 


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dipstick) on the collected urine specimens.  Specified abnormal macroscopic urinalyses 
will be followed up with a microscopic analysis at the central laboratory.
A certified central laboratory will be utilized to process and provide results for the clinical 
laboratory tests.  All abnormal laboratory tests that are considered clinically significant by 
the investigator will be followed to a satisfactory resolution.  Laboratory abnormalities are 
considered to be adverse events only if they result in discontinuation from the study, 
necessitate therapeutic medical intervention, and/or if the Investigator considers them to 
be an adverse event.
Instructions regarding the collection, processing and shipping of these samples will be 
provided by the central laboratory chosen for this study.


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Table 3.
Clinical Laboratory Tests
Category
Test Name
Hematology
Hematocrit (Hct)
Hemoglobin (Hb)
Red Blood Cell Count/Erythrocytes
White Blood Cells/Leukocytes
Platelet Count/Thrombocytes
Diff. Automatic
Neutrophils (absolute count)
Eosinophils (absolute count)
Basophils (absolute count)
Monocytes (absolute count)
Lymphocytes (absolute count)
Diff. Manual (if Diff Automatic is abnormal)
Neutrophils, bands (Stabs)
Neutrophils, polymorphonuclear (PMN)
Eosinophils
Basophils
Monocytes
Lymphocytes
Enzymes
AST(GOT)
ALT(GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
CK-MB, only if CK is elevated
Gamma-glutamyl gransferase (GGT/γ-GT)
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate
Substrates
Glucose
BUN
Creatinine
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Albumin
C-Reactive Protein (CRP) (high sensitivity)
Cholesterol, totala
Triglyceridesa
LDL-Cholesterola
HDL-Cholesterola
FSHb


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Table 3.
Clinical Laboratory Tests (Continued)
Category
Test Name
Urine Pregnancy test (only for female subjects of 
childbearing potential)c
Human Chorionic Gonadotropin in the urine
Serum Pregnancy test (in all female subjects at 
screening or if urine pregnancy test is positive in 
female subjects of child bearing potential)
Human Serum Chorionic Gonadotropin 
Autoantibodies (only at screening)
Rheumatoid Factor
Urinalysis (dipstick)
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/Erythrocytes
Urine WBC/Leukocytes
Urine pH
Urine creatinine
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
UACR
Infection screening
Hepatitis B Surface Antigen (qualitative)d,e
Hepatitis B Surface Antibody (qualitative)d,e
Hepatitis B Core Antibodies total (qualitative)d,e
Hepatitis B Virus DNA (quantitative)d,e
Hepatitis C Antibodies (qualitative)d,e
Hepatitis C Virus RNA (quantitative)d,e
HIV-1, and HIV-2 Antibody (qualitative)d,e
QuantiFERON®-TB (if applicable)
a.
To be done at screening only.
b.
(FSH) To be done at Screening in all women aged ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause.
c.
Urine pregnancy test performed at every visit except Screening. 
d.
Hepatitis B, Hepatitis C and HIV testing will be performed at screening.
e.
If Hepatitis B Surface Antigen is negative but Hepatitis B Core Antibodies total is positive and/or Hepatitis B 
Surface Antibody is positive, Hepatitis B Virus DNA will be quantified.  If Hepatitis B Virus DNA level is 
undetectable at screening, the subject can participate in this study.  If Hepatitis C Virus Antibodies is positive, 
Hepatitis C Virus RNA will be quantified.  If Hepatitis C RNA level is undetectable at screening, the subject can 
participate in this study.


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Clinically relevant abnormal findings will be reported as baseline conditions or AEs.  A 
clinically relevant value may be either in- or outside the reference range.  Clinically 
relevant abnormal laboratory test results must be confirmed and should be repeated until 
normalization or stabilization or until an alternative explanation has been found.  
Clinical Assessments and Patient Reported Outcomes
Clinical and patient reported efficacy endpoints will be assessed over the course of the 
study at the time points defined in Appendix C.  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.  Details of the following clinical 
and efficacy assessments are listed in the appendices.  Details of the patient reported 
outcomes are listed below.
Clinical Assessments
●
PASI 
●
BSA
●
sPGA  
●
PPASI
●
PSSI
●
NAPPA-CLIN
Patient Reported Outcomes
The order of completion should be as follows, applicable for each PRO as specified in 
Appendix C.
●
PSS
●
DLQI
●
SF36 
●
PBI


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●
HADS
●
PtGA
●
EQ-5D-5L
Psoriasis Symptom Scale (PSS)
The PSS is a four-item PRO instrument that assesses the severity of psoriasis symptoms in 
patients with moderate to severe psoriasis.  The symptoms included are:  pain, redness, 
itching and burning from psoriasis.  Current symptom severity is assessed as a daily diary, 
using a 5-point Likert-type scale ranging from 0 (none) to 4 (very severe).  
Dermatology Life Quality Index (DLQI)26,27
The DLQI has been extensively used in clinical studies and has a large evidence base 
supporting reliability and validity.  The DLQI is a self-administered, ten-question 
questionnaire used to assess the effect of different skin diseases on a subject's quality of 
life, overall health, and disability status.  The questionnaire covers six domains including 
symptoms and feelings, daily activities, leisure, work and school, personal relationships 
and treatment and has a one week recall period.26,27  Each item is scored on a 4 point scale 
where a 0 score indicates "not relevant/not at all," and scores from 1 to 3 range from "a 
little," to "very much."  Question 7 is a "yes"/"no" question where "yes" is scored as 3.  If 
Question 7 is answered "no," scores range from 0 ("not at all") to 2 ("a lot").  
Medical Outcome Short Form Health Survey (SF-36) Version 2 (Acute Form)28,29
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.  Two overall summary scores, the Physical Component Summary (PCS) 
and the Mental Component Summary (MCS) also can be computed.  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 


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treatments, and in screening individual subjects.  The purpose of the SF-36 in this study is 
to assess the Health Related Quality of Life (HRQoL) of subjects.  Given the acute nature 
of this disease, version 2, with a 1-week recall period, will be used in this study.
Patient Benefit Index (PBI)30,31
The PBI is a 25 item PRO instrument that assesses the benefit of psoriasis treatment.  
Patient relevant treatment needs and benefits are assessed through these 5 subscales:  
Reducing social impairment, reducing psychosocial impairments, reducing impairments 
due to therapy, reducing physical impairments, having confidence in healing.  Treatment 
benefit is assessed using the PBI score ranging from 0 ("no benefit") to 4 ("maximal 
benefit").  
Hospital Anxiety & Depression Scale (HADS)32,33,34
The HADS is a self-assessment scale which detects the presence and severity of anxiety 
and depression in the general population.  It contains 14 items and is comprised of anxiety 
(7 items) and depression (7 items) subscales, which are scored separately and summed to 
give a total score.  Item scores range from 0 (best) to 3 (worst) and total scores are 
categorized as normal (0 – 7), borderline abnormal (8 – 10) and abnormal (11 – 21).  The 
HADS has been widely used in clinical trials in a variety of disease areas and has 
extensive evidence to support its acceptability, reliability and validity.
Patient's Global Assessment (PtGA)35,36
The PtGA is a PRO instrument to assess the patient's assessment of disease severity.  This 
self-reported measure is used to assess disease activity using a 4-point scale where a 
higher score indicates higher level of disease activity.  Disease activity is assessed from 0 
("complete disease control") to 3 ("uncontrolled disease").  
European Quality of Life 5 Dimensions (EQ-5D)37
The EQ-5D is a standardized non-disease specific instrument for describing and valuing 
health-related quality of life.1  The EQ-5D consists of 5 dimensions:  mobility, self-care, 


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usual activity, pain/discomfort, and anxiety/depression.  Each dimension has 5 levels:  no 
problem, slight problem, moderate problem, severe problem or unable to perform 
activity/extreme problem.  It also contains a Visual Analogue Scale (VAS).  Subjects are 
asked to indicate the level that describes their current level of function or experience for 
each dimension.  As a measure of health status, it provides a descriptive profile and can be 
used to generate a single index value for health status, where full health is equal to 1 and 
death is equal to 0.  The VAS records the subject's assessment of his/her own health along 
a vertical 20 cm line, which has health state scores between 0 and 100.  
FUMADERM® INITIAL and FUMADERM® Subject Diary
Subjects will be dispensed a paper diary at every visit, starting at the Week 0/Baseline 
visit and will be trained on how to complete the diary for FUMADERM® INITIAL and 
FUMADERM® (provided as study medication) dosing by site staff during the 
Week 0/Baseline visit.  All subjects should complete their subject diary on a daily basis 
throughout the entire study.  The diary will be reviewed by site personnel with the subject 
at each visit and collected at the Week 24/ET Visit.
The dosing records will be reviewed and verified for compliance at each visit by the site 
personnel at the study center and reinforced if necessary.  All relevant dosing information 
will be captured into the eCRF by site personnel.
Study Drug Administration
Refer to Section 5.5.1.
Monitoring for Hypersensitivity Reactions
A hypersensitivity reaction is a clinical sign or symptom, or constellation of signs or 
symptoms, caused by an inappropriate and excessive immunologic reaction to study drug 
administration.  A systemic hypersensitivity reaction is a hypersensitivity reaction that 
does not occur at the local site of study drug administration (e.g., not an injection site 
reaction).  A serious systemic hypersensitivity reaction is a systemic hypersensitivity 
reaction that fulfills criteria for a serious adverse event.


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Subjects should be closely monitored for signs and symptoms of hypersensitivity 
reactions for approximately 2 hours after the first dose administration (Week 0/Day 1) and 
1 hour after all other doses of study drug (visits after Week 0/Day 1) in the patients 
randomized to risankizumab.  Hypersensitivity reactions should be treated according to 
medical standards.
In the event of a suspected hypersensitivity reaction or other systemic post-dose reaction, 
a (PK/ADA) blood and urine sample will be collected once within 24 hours of the 
reaction.
In the event of a suspected systemic hypersensitivity reaction, a supplemental form that 
provides additional information is be completed by the investigator or designee.
5.3.2
Drug Concentration Measurements
5.3.2.1
Collection of Samples for Analysis
Blood Samples for Risankizumab Assay
Blood samples, approximately 3 mL, for risankizumab assay will be collected by 
venipuncture into appropriately labeled collection tubes at the time points specified in 
Appendix C.  The timing of blood collection will take priority over all other scheduled 
study activities except for PROs, ECG and vital signs.  Blood samples for the PK assay 
should be collected as closely as possible relative to the time of dosing and within 
30 minutes prior to dosing.  Date and exact time (to the nearest minute) of drug 
administration will be recorded on eCRFs.  The time that each blood sample is collected 
will be recorded to the nearest minute in the source document.
A total of three samples will be collected per subject for pharmacokinetic analysis during 
the treatment and follow-up periods.


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Blood Samples for Risankizumab Anti-Drug Antibody (ADA) Assay:
Blood samples, approximately 3 mL, for risankizumab ADA assay will be collected at the 
time points specified in Appendix C.  Blood samples for the ADA assay should be 
collected as closely as possible relative to the time of dosing and within 30 minutes prior 
to dosing.  Date and exact time (to the nearest minute) of drug administration will be 
recorded on eCRFs.  The time that each blood sample is collected will be recorded to the 
nearest minute in the source document.
A total of four samples will be collected per subject for ADA analysis during the 
treatment and follow-up periods.
5.3.2.2
Handling/Processing of Samples
Details for the handling and processing of the samples will be provided outside this 
protocol in the laboratory manual.
5.3.2.3
Disposition of Samples
The frozen serum samples for risankizumab concentration and risankizumab ADA assays 
will be packed and shipped from the study site to the Central Laboratory according to 
instructions in the central laboratory Lab Manual.  An inventory of the samples included 
will accompany the package.
5.3.2.4
Measurement Methods
Serum concentrations of risankizumab and relative titers of risankizumab ADA will be 
determined using validated methods under the supervision of the Bioanalysis department 
at AbbVie.  Any additional analytes may be analyzed using non-validated methods.  
Serum samples collected for risankizumab and risankizumab ADA analysis may be used 
for future assay development or validation activities.
The presence of ADA to risankizumab will be assessed via a tiered approach using a 
validated electrochemiluminescence assay (screening, confirmatory, and titration analysis 


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as appropriate).  Samples that are confirmed positive may be further characterized in a 
validated neutralizing antibody (NAb) assay.
5.3.3
Efficacy Variables
5.3.3.1
Primary Variable
The primary efficacy endpoint is the proportion of subjects with a ≥ 90% improvement in 
Psoriasis Area and Severity Index (PASI 90)30 at Week 24.
5.3.3.2
Secondary Variables
1.
Proportion of subjects with a PASI 50/75/90/100 response at Weeks 4, 8, 12, 16, 20 
and 24.
2.
Change from baseline in PASI at Weeks 4, 8, 12, 16, 20 and 24.
3.
Change from baseline in BSA affected by psoriasis at Weeks 4, 8, 12, 16, 20 and 
24.
4.
Proportion of subjects with a sPGA24 of 0 or 1 at Weeks 4, 8, 12, 16, 20 and 24.
5.
Proportion of subjects with sPGA of 0 at Weeks 4, 8, 12, 16, 20 and 24.
6.
Change from Baseline in PPASI Total Score at Weeks 16 and 24.
7.
Change from Baseline in PSSI Total Score at Weeks 16 and 24.
8.
Change from Baseline on the NAPPA-CLIN Total Score at Weeks 16 and 24.
9.
Change from Baseline in Psoriasis Symptom Scale (PSS) total score at Weeks 16 
and 24.
10.
Proportion of subjects achieving PSS (0) at Weeks 16 and 24.
11.
Change from Baseline in DLQI total score at Weeks 16 and 24.
12.
Proportion of subject achieving DLQI (0, 1) at Weeks 16 and 24.
13.
Change from Baseline in SF-36 PCS and MCS Scores at Weeks 16 and 24.
14.
Change from Baseline in PBI at Weeks 16 and 24.


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15.
Change from Baseline on HADS at Weeks 16 and 24.
16.
Change from Baseline on PtGA at Weeks 16 and 24.
17.
Change from Baseline in EQ-5D-5L Index, EQ-5D Utility Index and VAS at 
Weeks 16 and 24.
The order of the secondary endpoints does not reflect a ranking.
5.3.4
Safety Variables
Safety evaluations include AE monitoring, physical examinations, vital sign 
measurements, and clinical laboratory testing (hematology, chemistry, and urinalysis) as a 
measure of safety and tolerability for the entire study duration.
5.3.5
Pharmacokinetic Variables
Risankizumab serum concentrations will be determined.  Descriptive statistics will be 
calculated for each sampling time (study visit).  The number and percentage of subjects 
with ADA will be calculated.  Additional analyses combining pharmacokinetic and ADA 
data from this study and other studies may be conducted if appropriate.  
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects for Either 
Risankizumab or FUMADERM®
A subject may withdraw from the study at any time.  The Investigator may discontinue 
any subject's participation for any reason, including an adverse event, safety concerns or 
failure to comply with the protocol.
Whether randomized to risankizumab or to FUMADERM®, subjects will be withdrawn 
from the study immediately if any of the following occur:


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1.
Clinically significant abnormal laboratory results or adverse events, which rule out 
continuation of study drug, as determined by the Investigator and the AbbVie TA 
MD.
2.
The Investigator believes it is in the best interest of the subject.
3.
The subject requests withdrawal from the study.
4.
Deviation from inclusion and exclusion criteria was noted after the subject started 
study drug, when continuation of the study drug would place the subject at risk as 
determined by the AbbVie TA MD.
5.
Introduction of prohibited medications or dosages when continuation of the study 
drug would place the subject at risk as determined by the AbbVie TA MD.
6.
Subject is non-compliant with TB prophylaxis (if applicable) or develops active TB 
at any time during the study.
7.
The subject becomes pregnant while on study drug.
8.
Subject has known malignancy, except for localized non-melanoma skin cancer.  
Discontinuation for carcinoma in-situ of the cervix is at the discretion of the 
Investigator.
9.
Subject is significantly non-compliant with study procedures which would put the 
subject at risk for continued participation in the study in consultation with the 
AbbVie TA MD.
10.
Occurrence of following hepatic test abnormalities considered by the investigator 
to be related to study drug:
●
Confirmed ALT or AST > 8 × Upper Limit of Normal (ULN)
●
Confirmed ALT or AST > 5 × ULN for more than 2 weeks 
●
Confirmed ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN)
●
Confirmed ALT or AST > 3 × ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%)


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If, during the course of study drug administration, the subject prematurely discontinues 
study drug use, the procedures outlined for the Early Termination Visit must be completed 
within 2 weeks after the decision to discontinue, and preferably prior to the initiation of 
another therapy.  However, these procedures should not interfere with the initiation of any 
new treatments or therapeutic modalities that the Investigator feels are necessary to treat 
the subject's condition.  Following discontinuation of the study drug, the subject will be 
treated in accordance with the Investigator's best clinical judgment.
A final telephone call will occur for all subjects who do not roll over into the extension 
study, approximately 15 weeks after the last dose of risankizumab and 7 weeks after the 
last dose of FUMADERM®, provided as study medication, to determine the status of any 
ongoing AEs/SAEs or the occurrence of any new AEs/SAEs.
All attempts must be made to determine the date of the last study drug dose and the 
primary reason for early termination.  The information will be recorded on the appropriate 
eCRF page.
For subjects that are considered lost to follow-up, reasonable attempts must be made to 
obtain information on the final status of the subject.  At a minimum, two phone calls must 
be made and one certified letter must be sent and documented in the subject's source 
documentation.
Subjects who discontinue the study prematurely will not be replaced.
Subjects are considered study completers if they have completed the Week 24 visit.
5.4.1.1
Discontinuation of Subjects on FUMADERM®
Subjects that are randomized to FUMADERM® INITIAL or FUMADERM® should be 
discontinued if any of the following occur:
1.
A pronounced decrease in WBC count of > 50% between 2 visits or an absolute 
WBC count below 3,000/μl.


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2.
A lymphocyte count below 500/μl.
3.
A lymphocyte count below 700/μl that persists 4 weeks after having reduced the 
dose of FUMADERM® INITIAL or FUMADERM® by half.
4.
A Platelet count < 100 000/μl.
5.
A diagnosis of progressive multifocal leukoencephalopathy.
6.
An opportunistic infection, including but not limited to visceral herpes simplex, 
disseminated candidiasis, aspergillus colonization, acute pneumocystis carinii 
pneumonia or visceral CMV infection.
7.
An increase in creatinine level above normal according to central laboratory normal 
range.
8.
Severe rash/flush that does not resolve with continued treatment.
9.
Major gastro-intestinal complaints that do not resolve with continued treatment in 
spite of dose reduction.
5.4.2
Discontinuation of Entire Study
AbbVie may terminate this study prematurely, either in its entirety or at any study site, for 
reasonable cause provided that written notice is submitted in advance of the intended 
termination.  The investigator may also terminate the study at his/her site for reasonable 
cause, after providing written notice to AbbVie in advance of the intended termination.  
Advance notice is not required by either party if the study is stopped due to safety 
concerns.  If AbbVie terminates the study for safety reasons, AbbVie will immediately 
notify the investigator by telephone and subsequently provide written instructions for 
study termination.


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5.5
Treatments
5.5.1
Treatments Administered
Subjects randomized to risankizumab will receive SC injections of risankizumab in the 
form of 
 mg (150 mg total) pre-filled syringes at Weeks 0, 4 and 16.
Risankizumab will be administered as a SC injection in the abdomen, thighs, gluteal 
regions, or upper arms (contra-lateral to that used for pharmacokinetic 
(PK)/pharmacodynamics (PD) samples).  The two injections done subsequently 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.  
Subjects randomized to FUMADERM® will receive doses as noted in Table 5.
FUMADERM® dose is increased with the intention of achieving PASI 90, if tolerability 
allows.  The decision of a slow increase in FUMADERM® INITIAL or FUMADERM®
dose or of a return to FUMADERM® INITIAL after initiation of FUMADERM® will be 
made by the investigator and the justifications for all deviations from the pre-specified 
dosing schedule of FUMADERM® will be documented in the eCRF.  The maximum daily 
dose of FUMADERM® may not exceed 6 tablets per day.  After the targeted efficacy on 
the psoriasis cutaneous lesions has been reached, an attempt should be made to reduce the 
dose of FUMADERM® to the individual maintenance dose.  FUMADERM® INITIAL 
and FUMADERM® tablets must be swallowed without chewing with plenty of liquid 
during and immediately after meals.  In general, care must be taken to ensure subjects 
drink sufficient liquids (i.e., 1½ to 2 liters) daily.
The dose of FUMADERM® INITIAL or FUMADERM® should be reduced if any of the 
following occur:
1.
A drop in lymphocyte count below 700/μl.
2.
A platelet count < 150 000/μl and ≥ 100 000/μl.


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3.
WBC count < 3 500/μl and ≥ 3 000/μl.
4.
Gastrointestinal disorders, nausea, abdominal cramps, diarrhea.
5.
Nervous system disorders (i.e., tiredness, dizziness or headache).
After dose reduction of FUMADERM®, the blood count should be monitored until it 
returns to normal.
5.5.2
Identity of Investigational Product(s)
5.5.2.1
Identity of Risankizumab Investigational Product
Information about the risankizumab formulation to be used in this study is presented in 
Table 4.
Risankizumab supplies will be provided by Boehringer Ingelheim Pharma GmbH & Co 
KG, Biberach, Germany.
●
Risankizumab (ABBV-066) 
mg/
mL Solution for Injection Pre-filled 
Syringe
Risankizumab is presented in a 1 mL pre-filled syringe with 
 mL of solution for 
injection.  Dispensed volume is 
 mL.  The solution in the risankizumab syringes has a 
concentration of 90 mg/mL, to deliver 
 mg per syringe.  
 syringes will be used 
to achieve the 150 mg dose.
Table 4.
Identity of Risankizumab Investigational Product
Study Drug
Dosage Form
Strength
Route of 
Administration
Manufacturer
Risankizumab 
(ABBV-066)
Solution for 
injection in pre-
filled syringe
 mg/
 mL
Subcutaneous 
injection
Boehringer 
Ingelheim Pharma 
GmbH & Co. KG


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5.5.2.2
Identity of FUMADERM® INITIAL and FUMADERM® 
Investigational Product
The two formulations of Fumaderm are used in this study are FUMADERM® INITIAL 
and FUMADERM® gastro-resistant tablets, FUMADERM® INITIAL being the low dose 
formulation to be taken in the first weeks of treatment before moving to FUMADERM®.
Table 5.
FUMADERM® INITIAL and FUMADERM® Pre-Specifed Dosing 
Schedule (in the Absence of an Adjustment to the Efficacy and/or 
Safety Response):
Week
Dosage (n of Tablets/Day)
Morning
Noon
Evening
FUMADERM® INITIAL
0
-
-
1
1
1
-
1
2
1
1
1
FUMADERM®
3
-
-
1
4
1
-
1
5
1
1
1
6
1
1
2
7
2
1
2
8 – 24*
2
2
2
*
Last intake of FUMDERM® in the morning on the day of Week 24 visit.
5.5.2.3
Packaging and Labeling
Risankizumab packaged in 
 mg pre-filed syringes will be provided in open-label 
fashion and packaged in cartons containing one (1) syringe per carton.  Each kit will be 
labeled as required per local requirements.  The number of kits dispensed will be managed 
by the Interactive Response System (IRT).
FUMADERM® is packaged as follows:


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●
FUMADERM® INITIAL is packaged as a blister pack of 30 mg tablets.  
●
FUMADERM® is packaged as a blister pack of 120 mg tablets. 
FUMADERM® INITIAL and FUMADERM® will be provided in an open-label fashion 
and packaged in cartons containing blister packs.  Each kit will be labeled as required per 
local requirements.  The number of kits dispensed will be managed by the IRT 
(Interactive Response System).  All labels for risankizumab, FUMADERM® INITIAL 
and FUMADERM® must remain affixed to the study drug at all times, and should never 
be removed for any reason.
5.5.2.4
Storage and Disposition of Study Drug(s)
Risankizumab kits will be kept protected from light in their original packaging, in a 
refrigerator between 2°C to 8°C (36°F to 46°F), and within a secure limited access storage 
area, and in accordance with the recommended storage conditions on the label.  
Risankizumab must not be frozen at any time.
A temperature log must be maintained for documentation of risankizumab storage.
The refrigerator temperature must be recorded each business day.  Malfunctions or any 
temperature excursion must be reported to AbbVie immediately.  Risankizumab should be 
quarantined and not dispensed until AbbVie or the AbbVie Temperature Excursion 
Management System (ATEMS) deems the drug as acceptable.
FUMADERM® INITIAL and FUMADERM® must be stored at 15°C to 25°C (59°F to 
77°F).
A temperature log must be maintained for documentation of FUMADERM® INITIAL and 
FUMADERM®.
Any temperature excursion for FUMADERM® INITIAL and FUMADERM® must be 
reported to AbbVie immediately.  FUMADERM® INITIAL and FUMADERM® should 


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be quarantined and not dispensed until AbbVie or the AbbVie Temperature Excursion 
Management System (ATEMS) deems the drug as acceptable.
All clinical supplies must be stored and locked in a secure place until they are dispensed 
for subject use or are returned to AbbVie.
Investigational products (IP) are for investigational use only and are to be used only 
within the context of this study.
5.5.3
Method of Assigning Subjects to Treatment Groups
All subjects will be centrally randomized using an Interactive Voice Response 
System/Interactive Web Response System (IVRS/IWRS).  Before the study is initiated, 
the telephone number/call-in directions and web based information for the IVRS/IWRS 
will be provided to each site.
All subjects will be assigned a unique identification number by the IVRS/IWRS at the 
Screening Visit.  Subjects who meet the inclusion and exclusion criteria defined in 
Section 5.2.1 and Section 5.2.2 respectively will be centrally randomized in a 1:1 ratio to 
one of two dosing arms at Week 0/Day 1 (Baseline).  The IVRS/IWRS will assign a 
randomization number according to the randomization schedule generated by the 
Statistics Department at AbbVie.
5.5.4
Selection and Timing of Dose for Each Subject
An IRT will be used to allocate study drug to subjects.  At visits where study drug is to be 
administered/dispensed, study sites will be required to complete the study drug resupply 
module in the IRT to receive assigned study drug/kit numbers.
Risankizumab will be administered at the study site by authorized site personnel 
(e.g., study nurse) after all study procedures have been completed. 
For subjects randomized to risankizumab, injections will be given in an open label fashion 
with each subject receiving  injections of risankizumab (
 mg) at each dosing visit.


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In exceptional cases of missed or delayed visits, risankizumab should not be administered 
within 14 days of the prior dose.  There should be at least 14 days between 
two consecutive risankizumab administrations.
For subjects randomized to FUMADERM® INITIAL and FUMADERM®, drug will be 
provided to subjects for dosing at home as specified in Section 5.5.1.
Dose modifications or adjustments are not permitted for risankizumab.  The dose 
modifications or adjustments for FUMADERM® INITIAL and FUMADERM® will be 
according to the investigator's instructions.
If one or several doses of FUMADERM® are missed, the patient should re-initiate the 
treatment with FUMADERM® according to the individualized dosing schedule.  The 
subject should contact the site personnel or the investigator to confirm their dosing 
schedule.  Any further adjustment of FUMADERM® dosing based on patient's individual 
efficacy and safety response is at the discretion of the investigator.
5.5.5
Blinding
This is an open-label study; however, the efficacy assessor will be blinded to the patient's 
study treatment as noted in Section 5.3.1.1.
5.5.6
Treatment Compliance
The investigator or his/her designated and qualified representatives will
administer/dispense study drug only to subjects enrolled in the study in accordance with 
the protocol.  The study drug must not be used for reasons other than that described in the 
protocol.
Subjects randomized to the FUMADERM® INITIAL and FUMADERM® arm will record 
all subject dosing information on a subject dosing diary and will return the dosing diary at 
each visit.  Subjects will be instructed to return all drug cartons (even if empty) to the 
study site personnel at each Study Visit.  The study site personnel will document 
compliance for risankizumab and FUMADERM® INITIAL and FUMADERM®.


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5.5.7
Drug Accountability
The investigator and/or named sub-investigators must agree not to supply study drug to 
any persons not enrolled in the study.
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, (temperature recording devices [e.g., TempTales] are provided in 
the shipments), and in the correct amounts from the drug depot. 
This will be documented by signing and dating the proof of receipt (POR) or similar 
document included with each drug shipment and by registering the arrival of drug through 
the IRT.  The original POR note or similar document and the IRT confirmation sheet will 
be kept in the site files as a record of what was received.
An accurate (running) inventory of study drug will be kept by the site, and will include the 
kit number, lot number, subject number, Proof of Receipt number(s), the number of 
pre-filled syringes or FUMADERM® blisters dispensed, initials of person who 
dispensed/administered the drug, and the date study drug was administered for each 
subject.
All empty/used study drug packaging and used pre-filled syringes will be inventoried by 
the site and verified by the site monitor.  Each site will use their own sharps disposal 
container designated to store used pre-filled syringes for this study.  Empty/used study 
drug packaging and sharps containers will be retained (unless prohibited by local law or 
site policy/procedure) by the site for accountability and compliance purposes.  Study drug 
accountability will be completed via IRT, source documents, subject dosing diaries, and 
by visually inspecting the packaging and syringes in the sharps container whenever 
possible.  Used sharps containers should never be opened.  
An overall accountability of the study drug will be performed by the site and verified by 
an AbbVie monitor throughout the study and at the site close-out visit.  After verification 
of drug accountability, used syringes must be destroyed at the site according to local 
regulations governing biohazardous waste.  Destruction of used study supplies must be 


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documented.  All unused supplies must be inventoried, accounted for and destroyed on 
site according to local procedures or regulation or returned to a destruction facility by the 
CRA.  A copy of the Drug Accountability Form, in accordance with instructions provided 
by the AbbVie monitor, will be included in the return shipments.
5.6
Discussion and Justification of Study Design
This is a parallel group, two arm, open-label study comparing risankizumab with 
Fumaderm® with a blinded assessment of efficacy. 
Although a double-blind study would have been preferable to potentially reduce bias, the 
logistical difficulties associated with blinding Fumaderm® led to a compromise on an 
open label-study with a blinded assessment of efficacy.
5.6.1
Discussion of Study Design and Choice of Control Groups
Fumaderm® is widely used for the treatment of psoriasis and is registered as 1st line 
treatment for moderate to severe psoriasis in Germany where it has a market share > 50%.  
Fumaderm® will be familiar to the participating investigators, particularly in Germany 
where the study will be initiated.  Alignment on the protocol Fumaderm® dosing 
adjustment, which are based on the labelled dosing instructions, is expected to be easy to 
achieve.
In spite of requesting dosing adjustment, Fumaderm® is suitable for a clinical study, since 
the labelled dosing recommendations are straightforward based on the routine assessment 
of efficacy and safety.
5.6.2
Appropriateness of Measurements
The primary efficacy endpoint will be PASI 90 at Week 24, which is in line with the 
Gemeinsamen Bundesausschusses (G-BA) strong requirement for "long-term" data and 
for a stringent endpoint reflecting a PASI response of at least 75% compared to Baseline.  
Although PASI 75 has been the primary efficacy variable recommended by the EMA for 


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clinical trials in psoriasis subjects, the recent breakthroughs in this therapeutic field have 
led to using a more stringent criterion.
The secondary efficacy endpoints will evaluate the impact of study treatment on the 
different facets of the cutaneous disease as well as on multiple aspects of quality of life, 
which will also address a request from the G-BA.
5.6.3
Suitability of Subject Population
The subject enrolled are adults with moderate to severe plaque psoriasis PASI score of 
> 10, affected BSA > 10% and DLQI > 10 who are naïve to and candidates for systemic 
therapy.
Risankizumab will be positioned as first line systemic therapy for moderate to severe 
psoriasis and the study population corresponds to this target population.  The definition of 
moderate to severe psoriasis is derived from the European guideline1 and differs from that 
used in risankizumab pivotal studies [PASI ≥ 12, BSA ≥ 10% and sPGA ≥ 3].
The selection criteria relating to safety guarantee that the subjects enrolled can safely be 
treated with both study drugs, risankizumab and Fumaderm®, based on the current 
knowledge on those drugs.
5.6.4
Selection of Doses in the Study
Risankizumab is currently in Phase 3 development for treatment of subjects with 
moderate to severe chronic plaque psoriasis.  Four Phase 3 studies are currently ongoing, 
which have enrolled approximately 2100 subjects, and evaluating risankizumab dose of 
150 mg administered at Week 0, 4 and thereafter every 12 weeks.  The risankizumab 
dosing regimen selected for the current study is the same as used in the ongoing 
risankizumab Phase 3 studies.
The Fumaderm® dosing recommendations are taken from the Fumaderm® label, with the 
caveat that the dose will be increased until PASI 90 is achieved, if tolerance allows. 


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6.0
Complaints
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
The investigational product in this trial contains both: 
●
Biologic compound(s) and
●
Device component(s) (pre-filled syringe, pen).
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For adverse events, please refer to Sections 6.1.1
through 6.1.6.  For product complaints, please refer to Section 6.2.
6.1
Medical Complaints
The investigator will monitor each subject for clinical and laboratory evidence of adverse 
events on a routine basis throughout the study.  The investigator will assess and record 
any adverse event in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
adverse event to study drug, and any action(s) taken.  For serious adverse events 
considered as having "no reasonable possibility" of being associated with study drug, the 
investigator will provide another cause of the event.  For adverse events to be considered 
intermittent, the events must be of similar nature and severity.  Adverse events, whether in 
response to a query, observed by site personnel, or reported spontaneously by the subject 
will be recorded.
All adverse events will be followed to a satisfactory conclusion.  


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6.1.1
Definitions
6.1.1.1
Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or 
clinical investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An adverse event can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an adverse event.  
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  Laboratory abnormalities and changes in vital signs are considered to be adverse 
events only if they result in discontinuation from the study, necessitate therapeutic 
medical intervention, and/or if the investigator considers them to be adverse events.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event if the surgery/procedure is being performed for a pre-existing condition and 
the surgery/procedure has been pre-planned prior to study entry.  However, if the 
pre-existing condition deteriorates unexpectedly during the study (e.g., surgery performed 
earlier than planned), then the deterioration of the condition for which the elective 
surgery/procedure is being done will be considered an adverse event.
6.1.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie a 
serious adverse event (SAE) within 24 hours of the site being made aware of the serious 
adverse event.
Death of Subject
An event that results in the death of a subject.


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Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have 
been fatal if it had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to an 
outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss.
Persistent or 
Significant 
Disability/Incapacity
An event that results in a condition that substantially 
interferes with the activities of daily living of a study subject.  
Disability is not intended to include experiences of relatively 
minor medical significance such as headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Important Medical 
Event Requiring 
Medical or Surgical 
Intervention to 
Prevent Serious 
Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but 
based on medical judgment may jeopardize the subject and 
may require medical or surgical intervention to prevent any 
of the outcomes listed above (i.e., death of subject, 
life-threatening, hospitalization, prolongation of 
hospitalization, congenital anomaly, or persistent or 
significant disability/incapacity).  Additionally, any elective 
or spontaneous abortion or stillbirth is considered an 
important medical event.  Examples of such events include 
allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.
For serious adverse events with the outcome of death, the date and cause of death will be 
recorded on the appropriate case report form.
6.1.1.3
Area of Safety Interest
Additional information may be collected for the following events:


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Hepatic Adverse Events
In the case of any of the following AEs, a Hepatic Adverse Event eCRF should be 
completed:
●
Discontinuation or interruption of study drug due to a hepatic related AE 
●
A hepatic related SAE 
●
A subject experiencing an ALT/AST > 8 × ULN 
●
A subject experiencing an ALT/AST > 3 × ULN in conjunction with a total 
bilirubin > 2 × ULN.
Systemic Hypersensitivity/Anaphylactic Reactions
●
A Hypersensitivity Reaction Signs and Symptoms Supplemental eCRF should 
be used for the reporting of systemic hypersensitivity/anaphylactic reactions.
Major Adverse Cardiovascular Events [MACE] Events
In the case of any of the following reported events, appropriate supplemental MACE 
eCRF/s should be completed:
●
Cardiovascular (Cardiac) Adverse Event;
●
Myocardial Infarction or Unstable Angina Adverse Event;
●
Heart Failure Adverse Event;
●
Cerebral Vascular Accident and Transient Ischemic Attack Adverse Event;
●
Combination Thrombotic Event
●
Arrhythmias
●
Non serious AE's Supplemental Laboratory
●
Cardiovascular procedures
Tuberculosis [TB]
Infections, especially opportunistic infections, are a theoretical risk with 
immunomodulators.  Subjects will be screened for tuberculosis and those with active 


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tuberculosis will be excluded from participation in the study.  The screening procedures 
are outlined in Appendix C.  A Tuberculosis Supplemental eCRF should be used for the 
reporting of tuberculosis.
6.1.1.4
CCVT Adjudication Committee
An independent adjudication committee will be adjudicating all observed cardiovascular, 
cerebro-vascular and thrombotic events (CCVT) including MACE and will remain 
blinded to treatment allocation.  The events that are adjudicated and the adjudication 
process will be detailed in the CCVT Adjudication Committee Charter.  Dedicated CRFs 
will be used for:
●
Cardiovascular (Cardiac) Adverse Event;
●
Myocardial Infarction or Unstable Angina Adverse Event;
●
Heart Failure Adverse Event;
●
Cerebral Vascular Accident and Transient Ischemic Attack Adverse Event;
●
Combination Thrombotic Event
●
Arrhythmias
●
Non serious AE's Supplemental Laboratory
●
Death
●
Cardiovascular procedures 
In addition, the site may be contacted for additional source documentation for relevant 
events.
6.1.2
Adverse Event Severity
Intensity of AEs
The investigator will use the following definitions to rate the severity of each adverse 
event:
Mild
The adverse event is transient and easily tolerated by the subject.


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Moderate
The adverse event causes the subject discomfort and interrupts the 
subject's usual activities.
Severe
The adverse event causes considerable interference with the subject's 
usual activities and may be incapacitating or life-threatening.
6.1.3
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study drug:
Reasonable 
Possibility
After consideration of factors including timing of the event, 
biologic plausibility, clinical judgment, and potential alternative 
causes, there is sufficient evidence (information) to suggest a 
causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, 
biologic plausibility, clinical judgment, and potential alternative 
causes, there is insufficient evidence (information) to suggest a 
causal relationship.
For causality assessments, events assessed as having a reasonable possibility of being 
related to the study drug will be considered "associated."  Events assessed as having no 
reasonable possibility of being related to study drug will be considered "not associated."  
In addition, when the investigator has not reported a causality or deemed it not assessable, 
AbbVie will consider the event associated.
If an investigator's opinion of no reasonable possibility of being related to study drug is 
given, an Other cause of event must be provided by the investigator for the serious 
adverse event.
6.1.4
Adverse Event Collection Period
All adverse events reported from the time of study drug administration until 15 weeks 
following discontinuation of risankizumab and 7 weeks following discontinuation of 
FUMADERM® (provided as study medication) administration have elapsed will be 


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collected, whether solicited or spontaneously reported by the subject.  In addition, serious 
adverse events and protocol-related non-serious adverse events will be collected from the 
time the subject signed the study-specific informed consent.
Adverse event information will be collected as shown in Figure 3.
Figure 3.
Adverse Event Collection
6.1.5
Adverse Event Reporting
In the event of a serious adverse event, whether associated with study drug or not, the 
Investigator will notify Clinical Pharmacovigilance within 24 hours of the site being made 
aware of the serious adverse event by entering the serious adverse event data into the 
electronic data capture (EDC) system.  Serious adverse events that occur prior to the site 
having access to the RAVE® system, or if RAVE is not operable, should be documented 
on the SAE Non-CRF forms and emailed (preferred route) or faxed to Clinical 
Pharmacovigilance within 24 hours of the site being made aware of the serious adverse
event.
Email:  
FAX to


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For safety concerns, contact the Immunology Safety Team at:
Immunology Safety Team
1 North Waukegan Road
North Chicago, IL 60064
USA
Office:
Email:
For any subject safety concerns, please contact the physician listed below:
Primary AbbVie Therapeutic Area Medical Director:
Telephone Contact Information:
Office:
Mobile:
Email:
In emergency situations involving study subjects when the primary Therapeutic Area 
Medical Director (TA MD) is not available by phone, please contact the 24-hour AbbVie 
Medical Escalation Hotline where your call will be re-directed to a designated backup 
AbbVie TA MD:
24-hour AbbVie Medical Escalation 
Phone Hotline:  


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The sponsor will be responsible for Suspected Unexpected Serious Adverse Reactions 
(SUSAR) reporting for the Investigational Medicinal Product (IMP) in accordance with 
Directive 2001/20/EC.  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the Investigator's Brochure for risankizumab 
and the Summary of Product Characteristics for FUMADERM® INITIAL and 
FUMADERM®.
6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued (Section 5.4.1).
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an adverse event.  The medical outcome for 
either mother or infant, meeting any serious criteria including an elective or spontaneous 
abortion, is considered a serious adverse event and must be reported to AbbVie within 
24 hours of the site becoming aware of the event.
6.2
Product Complaint
6.2.1
Definition
A Product Complaint is any Complaint (see Section 6.0 for the definition) related to the 
biologic or drug component of the product or to the medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device not working properly, or packaging issues.


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For medical devices, a product complaint also includes all deaths of a patient using the 
device, any illness, injury, or adverse event in the proximity of the device, an adverse 
event that could be a result of using the device, any event needing medical or surgical 
intervention including hospitalization while using the device and use errors.
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product and/or device must be reported 
to the Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 
Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.
Product Complaints may require return of the product with the alleged complaint 
condition (syringe).  In instances where a return is requested, every effort should be made 
by the investigator to return the product within 30 days.  If returns cannot be 
accommodated within 30 days, the site will need to provide justification and an estimated 
date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol unless when 
necessary to eliminate an immediate hazard to study subjects.  The principal investigator 
is responsible for complying with all protocol requirements, and applicable global and 
local laws regarding protocol deviations.  If a protocol deviation occurs (or is identified) 


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after a subject has been enrolled, the principal investigator is responsible for notifying 
Independent Ethics Committee (IEC)/Independent Review Board (IRB) regulatory 
authorities (as applicable), and the following AbbVie Clinical Monitor(s):
Primary Contact:
Alternate Contact:
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.
8.0
Statistical Methods and Determination of Sample 
Size
The specification described here is that envisaged at the time of planning the trial.  Should 
new evidence come to light as a result of running other trials before this trial is analyzed, 
or should new methods of analysis become available in the statistical literature, or should 
the trial be affected by unforeseen circumstances, it may be necessary to modify the 
analysis strategy.
The analysis strategy described below will be supplemented by a detailed statistical 
analysis plan (SAP), which will be completed prior to database lock.  


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8.1
Statistical and Analytical Plans
8.1.1
Analysis Populations
The intent-to-treat (ITT) population consists of all subjects who were randomized.  The 
safety population consists of all subjects who were randomized and received at least 
one dose of study drug.
In order to evaluate the impact of major protocol deviations on the results of the trial, 
additional sensitivity analyses may be performed on the per-protocol population, which 
excludes subjects with major protocol deviations from the ITT population.  If it is decided 
that this analysis should be performed, the criteria for exclusion of subjects from the 
protocol analysis will be fully defined and documented in the final SAP and before the 
database lock.
8.1.2
Planned Methods of Statistical Analysis
All statistical tests will be two-tailed.  The statistical tests for the primary endpoint will be 
performed at the significance level 0.05.  All P values will be rounded to 3 decimal 
places.  Descriptive statistics will be provided.  These include the number of observations, 
mean, standard deviation, minimum, median, quartiles and maximum for continuous 
variables, and counts and percentages for discrete variables.  The analyses will be 
performed using SAS® (SAS Institute Inc., Cary, NC, USA).
8.1.3
Demographic and Baseline Characteristics
Demographics and Baseline characteristics of the study subjects will be summarized for 
each treatment arm using descriptive statistics.  Statistical tests will be performed to 
assess the comparability of the treatment arms.  Continuous variables will be analyzed 
using one-way analysis of variance (ANOVA), and discrete variables will be analyzed 
using Chi squared test or Fisher's exact test as appropriate.
8.1.4
Analysis of Efficacy
All efficacy analyses will be performed in the ITT population.


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The primary efficacy endpoint (PASI90 at Week 24) will be analyzed using a two-sided 
Cochran-Mantel Haenszel test stratified by prior phototherapy at level of significance 5%.  
Missing data will be imputed using non-responder imputation, i.e., a subject with missing 
PASI90 at Week 24 will be considered a non-responder in the primary analysis.  Further 
sensitivity analyses for the primary endpoint may be specified in the SAP prior to 
database lock.
For the analysis of categorical secondary endpoints, the same statistical test as for the 
primary endpoint will be performed, missing data will be imputed using non-responder 
imputation.  For the analysis of continuous secondary endpoints, two-sided two-way 
ANOVA with treatment and prior phototherapy as factors will be imputed using last 
observation carried forward (LOCF).
The order of the secondary endpoints does not reflect a ranking and secondary endpoints 
will not be used for confirmatory interpretation, thus no adjustment for multiplicity will 
be done.
Further details regarding the statistical analysis will be specified in the SAP.
8.1.5
Analysis of Safety
All safety analyses will be performed in the safety population.
Treatment-emergent adverse events are defined as events with an onset date on or after 
the first dose of study drug until 15 weeks (105 days) following the last dose of 
risankizumab or 1 week (7 days) after the last dose of FUMADERM® provided as study 
medication or until rollover into the extension study.  In a sensitivity analysis, adverse 
events with an onset date until 7 weeks (49 days) after the last dose of FUMADERM®
provided as study medication or until rollover into the extension study will be included.
SAEs and protocol-related non-serious AEs with onset after informed consent but before
the first study drug administration will be considered as pretreatment events and reported 
separately.


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Adverse events will be tabulated by system organ class and preferred term, whereby the 
most current implemented MedDRA dictionary will be used.  Also, summaries by severity 
and relationship to study drug will be done.  Certain adverse events, like serious or severe, 
leading to discontinuation, will be listed and described in detail.  Adverse events of 
interest for treatment with biologics will be defined in the statistical analysis plan and 
analyzed separately.
Adverse events will be summarized by frequency and percentage and presented by 
treatment group, statistical comparisons will be performed using Fisher's exact test.
Other safety variables like laboratory data and vital signs will also be described by 
descriptive statistics for each treatment group.  Treatment comparisons will be performed 
by one way ANOVA.  In addition, shift tables and listings will be provided for abnormal 
values, whereby the normal range of the analyzing laboratory will be used.
8.1.6
Interim Analysis
No interim analysis will be done for this study.
8.1.7
Pharmacokinetic and Exposure-Response Analysis
Individual risankizumab serum concentrations will be tabulated and summarized with 
appropriate statistical methods.  In addition, ADA titers will be tabulated for each subject 
at the respective study visits.  The number and percentage of subjects with ADA will be 
calculated.
Additional analyses with combining pharmacokinetic and ADA data from this study and 
other studies may be conducted if appropriate; this may include exploratory analyses of 
the effect of ADA on risankizumab pharmacokinetics and efficacy as well as the 
relationships between exposure and clinical observations (efficacy or safety variables of 
interest).  Such analyses, if conducted, may be summarized in a separate report rather than 
in the clinical study report for this study.


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8.2
Determination of Sample Size
Using a two-sided Chi squared test at level of significance 5%, the sample size of 
110 (2 × 55) subjects will provide 94% power assuming response rates of the primary 
endpoint (PASI90 at Week 24) of 70% for risankizumab and 35% for FUMADERM®.
These assumptions are in line with what has been observed in recent studies for 
Risankizumab (63/83 (75.9%) at Week 24)9 and FUMADERM® 61/273 (22.3%) of the 
subjects achieved PASI 90 at Week 16 in the FUMADERM® arm in the BRIDGE trial.15
8.3
Randomization Methods
An IVR/IWR system will be used to determine the randomization of subjects.  Detailed 
instructions for using the IVR/IWR system will be provided to the site personnel.
The randomization schedule will be prepared by the statistics department of AbbVie.  
Subjects who are eligible based on inclusion and exclusion criteria and have had all 
pre-randomization procedures performed will be randomized in a 1:1 ratio to receive 
risankizumab or FUMADERM® stratified by prior phototherapy, with a maximum of 20% 
of subjects with prior phototherapy.  Randomization will not be stratified by center due to 
the limited number of subjects per center.  Randomization will be done using an adequate 
block size.
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB).  The IEC/IRB will review the ethical, scientific 
and medical appropriateness of the study before it is conducted.  IEC/IRB approval of the 


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protocol, informed consent and subject information and/or advertising, as relevant, will be 
obtained prior to the authorization of drug shipment to a study site.
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  The investigator will be required to submit, 
maintain and archive study essential documents according to ICH GCP and all other 
applicable regulatory requirements.
Any serious adverse events that meet the reporting criteria, as dictated by local 
regulations, will be reported to both responsible Ethics Committees and Regulatory 
Agencies, as required by local regulations.  During the conduct of the study, the 
investigator should promptly provide written reports (e.g., ICH Expedited Reports, and 
any additional reports required by local regulations) to the IEC/IRB of any changes that 
affect the conduct of the study and/or increase the risk to subjects.  Written documentation 
of the submission to the IEC/IRB should also be provided to AbbVie.
9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
study conduct and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical investigator are specified in Appendix A.
9.3
Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the 
subject, and answer all questions regarding this study.  Prior to any study-related 
screening procedures being performed on the subject, the informed consent statement will 
be reviewed and signed and dated by the subject, the person who administered the 
informed consent, and any other signatories according to local requirements.  A copy of 
the informed consent form will be given to the subject and the original will be placed in 
the subject's medical record.  An entry must also be made in the subject's dated source 


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documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
Information regarding incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation 
in the study can be found in the informed consent form.
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents.  The Investigator Awareness Date (SAE CRF) may serve 
as the source for this data point.  This adverse event data point required for eCRF 
completion can be entered directly in the eCRF.
The investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
10.2
Case Report Forms
Case report forms (CRF) must be completed for each subject screened/enrolled in this 
study.  These forms will be used to transmit information collected during the study to 
AbbVie and regulatory authorities, as applicable.  The CRF data for this study are being 
collected with an electronic data capture (EDC) system called Rave® provided by the 
technology vendor Medidata Solutions Incorporated, NY, USA.  The EDC system and the
study-specific electronic case report forms (eCRFs) will comply with Title 21 CFR 
Part 11.  The documentation related to the validation of the EDC system is available 


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through the vendor, Medidata, while the validation of the study-specific eCRFs will be 
conducted by AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system.  All data entered into the 
eCRF will be supported by source documentation.
The investigator or an authorized member of the investigator's staff will make any 
necessary corrections to the eCRF.  All change information, including the date and person 
performing the corrections, will be available via the audit trail, which is part of the EDC 
system.  For any correction, a reason for the alteration will be provided.  The eCRFs will 
be reviewed periodically for completeness, legibility, and acceptability by AbbVie 
personnel (or their representatives).  AbbVie (or their representatives) will also be allowed 
access to all source documents pertinent to the study in order to verify eCRF entries.  The 
principal investigator will review the eCRFs for completeness and accuracy and provide 
his or her electronic signature and date to eCRFs as evidence thereof.
Medidata will provide access to the EDC system for the duration of the trial through a 
password-protected method of internet access.  Such access will be removed from 
investigator sites at the end of the site's participation in the study.  Data from the EDC 
system will be archived on appropriate data media (CD-ROM, etc.) and provided to the 
investigator at that time as a durable record of the site's eCRF data.  It will be possible for 
the investigator to make paper printouts from that media.
Patient Reported Outcome (PRO) data must be completed for each subject 
screened/enrolled in this study.  These data are being collected with an Electronic Patient 
Reported Outcome (ePRO) system called Trialmax, provided by the technology vendor 
CRF Health of Plymouth Meeting, PA, USA.  The ePRO system is in compliance with 
Title 21 CFR Part 11.  The documentation related to the system validation of the ePRO 
system is available through the vendor, CRF Health, while the user acceptance testing of 
the study-specific PRO design will be conducted and maintained at AbbVie.


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The subject will be entering the data on an electronic device; these data will be uploaded 
to a server.  The data on the server will be considered source, and maintained and 
managed by CRF Health.
Internet access to the ePRO data will be provided by CRF Health for the duration of the 
study.  This access will be available for the duration of the study to the site investigator, as 
well as delegated personnel.  Such access will be removed from investigator sites 
following the receipt of the study archive.  Data from the ePRO system will be archived 
on appropriate data media (CD-ROM, etc.) and provided to the investigator at that time as 
a durable record of the site's ePRO data.  It will be possible for the investigator to make 
paper print-outs from that media.
The ePRO data will be collected by the following methods:
Tablet Based
●
The instruments/scales will be collected electronically via a Tablet/Laptop 
device into which the patient will directly enter the required pieces of 
information.  The electronic device will be programmed to allow data entry for 
only the visits specified in the protocol and will not allow for subjects to 
complete more than one of the same assessment at any one visit.  All data 
entered on the device will be immediately stored to the device itself and 
automatically uploaded to a central server administrated by CRF Health.  The 
Investigator and delegated staff will be able to access all uploaded patient 
entered data via a password protected website, up until the generation, receipt 
and confirmation of the study archive.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
Prior to the initiation of the study, a meeting will be held with AbbVie personnel, the 
investigators and appropriate site personnel.  This meeting will include a detailed 


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discussion of the protocol, performance of study procedures, eCRF, Subject 
Questionnaires, and Subject Diary completion, and specimen collection methods.  The 
AbbVie monitors will monitor each site throughout the study. 
All data hand entered in the database will be verified at AbbVie.  Any discrepancies will 
be reviewed.  After completion of the entry process, computer logic checks will be run to 
check for such items as inconsistent study dates.  Any necessary corrections will be made 
to the eCRF.
The data from the central laboratory analyses will be electronically transferred from the 
central laboratory to the study database.
12.0
Use of Information
All information concerning specify study drug and AbbVie operations, such as AbbVie 
patent applications, formulas, manufacturing processes, basic scientific data, or 
formulation information, supplied by AbbVie and not previously published is considered 
confidential information.  The information developed during the conduct of this clinical 
study is also considered confidential and will be used by AbbVie in connection with the 
development of specify study drug.  This information may be disclosed as deemed 
necessary by AbbVie to other clinical investigators, other pharmaceutical companies, and 
to governmental agencies.  To allow for the use of the information derived from this 
clinical study and to ensure complete and thorough analysis, the investigator is obligated 
to provide AbbVie with complete test results and all data developed in this study and to 
provide direct access to source data/documents for trial-related monitoring, audits, 
IEC/IRB review and regulatory inspection.  This confidential information shall remain the 
sole property of AbbVie, shall not be disclosed to others without the written consent of 
AbbVie, and shall not be used except in the performance of this study.  The investigator 
will maintain a confidential subject identification code list of all subjects enrolled in the 
study (by name and subject number).  This list will be maintained at the site and will not 
be retrieved by AbbVie.


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13.0
Completion of the Study
The investigator will conduct the study in compliance with the protocol and complete the 
study within the timeframe specified in the contract between the investigator and AbbVie.  
Continuation of this study beyond this date must be mutually agreed upon in writing by 
both the investigator and AbbVie.  The investigator will forward a copy of this final report 
to the IEC/IRB following conclusion of the study and will forward a copy of this report to 
AbbVie or their representative.
The investigator must submit, maintain, and archive any records related to the study 
according to ICH GCP and all other applicable regulatory requirements.  If the 
investigator is not able to retain the records, he/she must notify AbbVie to arrange 
alternative archiving options.
AbbVie will select the signatory investigator from the investigators who participate in the 
study.  Selection criteria for this investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigator's Signature for Study Reports.
The end-of-study is defined as the date of the last subject's last visit, Week 24/Early 
Termination Visit, see Appendix C.


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14.0
Investigator's Agreement
1.
I have received and reviewed the Investigator's Brochure for risankizumab and the 
product labeling for FUMADERM INITIAL® and FUMADERM®.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title:
A Randomized, Controlled, Multicenter, Open Label Study with 
Blinded Assessment of the Efficacy of the Humanized 
Anti-IL-23p19 Risankizumab Compared to FUMADERM® in 
Subjects with Moderate to Severe Plaque Psoriasis Who are Naïve 
to and Candidates for Systemic Therapy
Protocol Date:
28 November 2017
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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15.0
Reference List
1.
Nast A, Boehncke WH, Mrowietz U, et al.  S3 – Guidelines on the treatment of 
psoriasis vulgaris (English version).  Update.  J Dtsch Dermatol Ges.  
2012;10 (Suppl 2):S1-95.
2.
Nestle FO, Kaplan DH, Barker J. Mechanisms of disease: psoriasis.  N Engl J Med.  
2009;361(5):496-509.
3.
Lowes MA, Bowcock AM, Krueger JG.  Pathogenesis and therapy of psoriasis.  
Nature.  2007;445(7130):866-73.
4.
Menter A, Griffiths CEM.  Psoriasis 2:  current and future management of 
psoriasis.  Lancet.  2007;370:272-84.
5.
Davidovici BB, Sattar N, Joerg PC, et al; Psoriasis Education and Learning 
Syllabus (PEARLS).  Psoriasis and systemic inflammatory diseases:  potential 
mechanistic links between skin disease and co-morbid conditions.  J Invest 
Dermatol.  2010;130(7):1785-96.
6.
Reich K, Puig L, Paul C; TRANSIT investigators.  One-year safety and efficacy of 
ustekinumab and results of dose adjustment after switching from inadequate 
methotrexate treatment:  the TRANSIT randomised trial in moderate-to-severe 
plaque psoriasis.  Br J Dermatol.  2014; 170(2):435-44.
7.
Smith RLI, Warren RB, Eyre S, et al.  Polymorphisms in the IL-12beta and IL-23R 
genes are associated with psoriasis of early onset in a UK cohort.  J Invest 
Dermatol.  2008;128:1325-7.
8.
Langley RG, Elewski BE, Lebwohl M, et al; the ERASURE Study Group and 
FIXTURE Study Group.  Secukinumab in plaque psoriasis--results of two phase 3 
trials.  N Engl J Med.  2014;371(4):326-38.
9.
AbbVie.  Risankizumab Investigator's Brochure Edition 1.  22 December 2016.


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10.
Berner B, Scudamore O, Bennett N, et al.  A 48 weeks study of three different dose 
regimens of BI 655066 administered subcutaneously in patients with moderate to 
severe chronic plaque psoriasis (randomized, dose-ranging, active-comparator-
controlled [ustekinumab], double-blind within dose groups of BI 655066).  
2016;1-134.
11.
Altmeyer P, Matthes U, Pawlak F, et al.  Antipsoriatic effect of fumaric acid 
derivatives.  Results of a multicenter double-blind study in 100 patients.  J Am 
Acad Dermatol.  1994;30(6):977-81.
12.
Carboni I, de Felice C, de Simoni R, et al.  Fumaric acid esters in the treatment of 
psoriasis:  an Italian experience.  J Dermatolog Treat.  2004;15(1):23-6.
13.
Gollnick H, Altmeyer P, Kaufmann R, et al.  Topical calcipotriol plus oral fumaric 
acid is more effective and faster acting than oral fumaric acid monotherapy in the 
treatment of severe chronic plaque psoriasis vulgaris.  Dermatology.  
2002;205(1):46-53.
14.
Kolbach D, Nieboer C.  Fumaric acid therapy in psoriasis:  results and side effects 
of 2 years of treatment.  J Am Acad Dermatol.  1992;27 (5 Pt 1):769-71.
15.
Mrowietz U, Chritophers E, Altmeyer P, et al.  Treatment of psoriasis with fumaric 
acid esters:  results of a prospective multicentre study.  Br J Dermatol.  
1998;138(3):456-60.
16.
Litjens NHR, Nibbering PH, Barrois AJ, et al.  Beneficial effects of fumarate 
therapy in psoriasis vulgaris patients coincide with downregulation of type 1 
cytokines.  Br J Dermatol.  2003;148(3):444-51.
17.
Mrowietz U, Szepietowski JC, Van De Kerkhof P, et al.  Efficacy and safety of 
LAS41008 (dimethyl fumarate) in adults with moderate-to-sever chronic plaque 
psoriasis:  results of the BRIDGE trial.  2016.  doi:  10.1111/bjd.14947.
18.
European Medicines Agency Evaluation of Medicines for Human Use.  CHMP.  
Guideline on Clinical Investigational Medicinal Products Indicated for the 
Treatment of Psoriasis.  2004; CHMP/EWP/2454/02 corr.


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19.
Khader SA, Pearl JE, Sakamoto K, et al.  IL-23 compensates for the absence of IL 
12p70 and is essential for the IL-17 response during tuberculosis but is dispensable 
for protection and antigen-specific IFN-y responses if IL-12p70 is available.  
J Immunol.  2005;175(2):788-95.
20.
O'Garra A, Redford PS, McNab FW, et al.  The immune response in tuberculosis.  
Annu Rev Immunol.  2013;31:475-527.
21.
Tsai TF, Blauvelt A, Gong Y, et al.  Secukinumab treatment shows no evidence for 
reactivation of previous or latent TB infection in subjects with psoriasis:  a pooled 
phase 3 safety analysis.  J Am Acad Dermatol.  2015;607.
22.
Fumaderm® initial Fumaderm® Prescribing Information.  Biogen.  2016; 000847 
18647.
23.
Criteria Committee, New York Heart Association, Inc.  Diseases of the heart and 
blood vessels.  Nomenclature and criteria for diagnosis, 6th edition Boston, Little, 
Brown and Co. 1964, p 114.
24.
Taylor W, Gladman D, Helliwell P, et al; CASPAR Study Group.  Classification 
criteria for psoriatic arthritis:  development of new criteria from a large 
international study.  Arthritis Rheum.  2006;54(8):2665-73.
25.
Robinson A, Kardos, Kimball AB.  Physician Global Assessment (PGA) and 
Psoriasis Area and Severity Index (PASI):  why do both?  A systematic analysis of 
randomized controlled trials of biologic agents for moderate to severe plaque 
psoriasis.  J Am Acad Dermatol.  2012;66(3):369-75.
26.
Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI) - a simple practical 
measure for routine clinical use.  Joint Ann Mtg of the British Association of 
Dermatologists and the Canadian Dermatology Association, Oxford, 
6 – 10 Jul 1993.  Clin Exp Dermatol.  1994;19(3):210-6.
27.
Basra MKA, Fenech R, Gatt RM, et al.  The Dermatology Life Quality Index.  
1994 - 2007:  a comprehensive review of validation data and clinical results.  Br J 
Dermatol.  2008;159(5):997-1035.


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28.
Ware JE Jr, Sherbourne CD.  The MOS 36 item short form health survey (SF-36), 
1:  conceptual framework and item selection.  Med Care.  1992;30(6):473-83.
29.
Ware JE Jr.  SF-36 health survey update.  Spine.  2000;25(24):3130-9.
30.
Feuerhahn J, Blome C, Radtke M, et al.  Validation of the patient benefit index for 
the assessment of patient-relevant benefit in the treatment of psoriasis.  Archives 
Dermatol Res.  2012;304(6):433-41.
31.
Augustin M, Radtke MA, Zschocke I, et al.  The patient benefit index:  a novel 
approach in patient-defined outcomes measurement for skin diseases.  Arch 
Dermatol Res.  2009;301(8):561-71.
32.
Zigmond AS, Snaith RP.  The hospital anxiety and depression scale.  
Acta Psychiatr Scand.  1983;67:361-70.
33.
Herrmann C.  International experiences with the Hospital Anxiety and Depression 
Scale – a review of validation data and clinical results.  J Psychosom Res.  
1997;42(1):17-41.
34.
Bjelland I, Dahl AA, Haug TT, et al.  The validity of the Hospital Anxiety and 
Depression Scale:  an updated literature review.  J Psychosom Res.  
2002;52(2):69-77.
35.
Nikiphorou E, Radner H, Chatzidionysiou K, et al.  Patient global assessment in 
measuring disease activity in rheumatoid arthritis:  a review of the literature.  
Arthritis Res Therapy.  2016;18(1):251.
36.
Anderson JK, Zimmerman L, Caplan L, et al.  Measures of rheumatoid arthritis 
disease activity:  patient (PtGA) and provider (PrGA) global assessment of disease 
activity, disease activity score (DAS) and disease activity score with 28   joint 
counts (DAS28), simplified disease activity index (SDAI), clinical disease activity 
index (CDAI), patient activity score (PAS) and patient activity score   II (PASII), 
routine assessment of patient index data (RAPID), rheumatoid arthritis disease 
activity index (RADAI) and rheumatoid arthritis disease activity.  Arthritis Care 
Res.  2011;63(S11):S14-36.


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37.
Cheung K, Oemar M, Oppe M, et al.  EQ-5D user guide.  March 2009.  
Version 2.0.
38.
Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new retinoid.  
Dermatologica.  1978;157(4):238-44.
39.
Langley RGB, Feldman SR, Nyirady J, et al.  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.
40.
Williams JS, Brown SM, Conlin PR.  Videos in clinical medicine.  Blood-pressure 
measurement.  N Engl J Med.  2009;29;360(5):e6.


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Appendix A.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the Good Clinical Practices 
(GCP) and local regulations and guidelines governing the study at the site location.  In 
signing the Investigator Agreement in Section 14.0 of this protocol, the investigator is 
agreeing to the following:
1.
Conducting the study in accordance with the relevant, current protocol, making 
changes in a protocol only after notifying AbbVie, except when necessary to 
protect the safety, rights or welfare of subjects.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed 
consent and ethics committees (e.g., independent ethics committee [IEC] or 
institutional review board [IRB]) review and approval of the protocol and 
amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
5.
Reading the information in the Investigator's Brochure/safety material provided, 
including the instructions for use and the potential risks and side effects of the 
investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making 
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and 
approved the initial clinical investigation and all amendments.


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9.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
10.
Following the protocol and not make any changes in the research without ethics 
committee approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.
11.
Not disclosing the treatment codes or any patient information to the blinded 
efficacy assessor.


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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Clinical
Clinical
Pharmacokinetics
Clinical
Statistics


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Appendix C.
Study Activities
Activity
Screening
–30 to –1
Week 0/ 
Baseline
Week
4
Week
8
Week
12
Week
16
Week
20
Week 
24/ETa
Week 31 
Follow-Up Callb
Day
–30 to –1
Day 1
Day 29
Day 57
Day 85
Day 
113
Day 
141
Day 
169
Day 218
Informed Consent
X
Medical/Surgical History
X
Xc
Alcohol and Nicotine Use
X
X
Pregnancy Testsd
u = urine, s = serum
X(s)
X(u)
X(u)
X(u)
X(u)
X(u)
X(u)
X(u)
Physical Exam
c = complete, t = targeted
X(c)
X(c)
X(t)
X(t)
X(t)
X(c)
X(t)
X(c)
Vital Signse
X
X
X
X
X
X
X
X
Safety Laboratory Testingf
c = complete, t = targeted
X(c)
X(c)
X(t)
X(c)
X(t)
X(c)
X(t)
X(c)
Urinalysis 
X
X
X
X
X
X
X
X
CASPAR Assessment
X
FSHg
X
PASI/% BSA Involvement
X
X
X
X
X
X
X
X
Assess Concomitant Medications
X
X
X
X
X
X
X
X
X
12 Lead ECG
X
X
Infection Screeningh
X
Dispense Subject Diaryi
X
X
X
X
X
X


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Activity
Screening
–30 to –1
Week 0/ 
Baseline
Week
4
Week
8
Week
12
Week
16
Week
20
Week 
24/ETa
Week 31 
Follow-Up Callb
Day
–30 to –1
Day 1
Day 29
Day 57
Day 85
Day 
113
Day 
141
Day 
169
Day 218
DLQIj
X
X
X
X
Randomization
X
Risankizumab Administrationk
X
X
X
FUMADERM® Dispensationl
X
X
X
X
X
X
Blood Sampling for PKm
X
X
X
Blood Sampling for ADA Assaym
X
X
X
X
Subject Diary Review
X
X
X
X
X
X
X
Monitor Adverse Events
X
X
X
X
X
X
X
X
PPASI/PSSI/NAPPA-CLINj
X
X
X
sPGA
X
X
X
X
X
X
X
PSSj
X
X
X
Monitor Compliancei
X
X
X
X
X
X
X
Short Form SF-36j
X
X
X
Patient Benefit Index (PBI)j
X
X
X
HADSj
X
X
X
PtGAj
X
X
X
EQ-5D-5Lj
X
X
X
a.
Subjects that discontinue the study prior to the end of the study will have an Early Termination visit within 2 weeks after the decision to discontinue.


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b.
Subjects that discontinue the study prior to the end of the study will have a follow-up phone call within 15 weeks after the last dose of risankizumab and 7 weeks after the last 
dose of FUMADERM® provided as study medication for collection of safety data.  Subjects that elect to enroll into a separate extension study will not require the Week 31 
Follow-Up phone call as part of this trial.
c.
Update history.
d.
Serum pregnancy test in all women at screening and if the urine pregnancy test is positive at any other visit.  Urine pregnancy tests are to be performed in all women of child 
bearing potential prior to administration of study drug at all dosing visits.
e.
Height and weight will be measured at the Screening Visit only (with shoes off).
f.
Targeted laboratory samples should be limited to CBC with differential count (hematology), serum creatinine (substrates) and ALT, AST, gamma-GT and AP (enzymes).
g.
(FSH) To be done at Screening in all women aged ≤ 55 years with no menses for 12 or more months without an alternative medical cause.
h.
Infection screening consists of Hepatitis B Surface Antigen (qualitative), Hepatitis B Surface Antibody (qualitative), Total Hepatitis B Core Antibodies (qualitative), 
Hepatitis B Virus DNA (quantitative) reflex, Hepatitis C Antibodies (qualitative), Hepatitis C Virus RNA (quantitative) reflex, HIV-1 and HIV-2 Antibody (qualitative), 
PPD/QuantiFERON-TB.
i.
For FUMADERM® INITIAL and FUMADERM® provided as study medication only.
j.
Prior to other procedures.
k.
SC risankizumab 150 mg at Week 0/Day 1, Week 4 and Week 16.  Risankizumab will be administered at the study site by authorized site personnel (e.g., study nurse) after all 
study procedures have been completed.
l.
Oral FUMADERM® daily starting at Week 0/Day 1 and until Week 24 (the last dose will be in the morning of the day of Week 24 visit).  FUMADERM® INITIAL starting at 
Week 0/Day 1 until Week 2 and FUMADERM® starting at Week 3, both at starting dose of 1 tablet per day, followed by a dose increase of one tablet per week, depending on 
efficacy response and tolerability.  The maximum dose of FUMADERM® of 6 tablets per day should not be exceeded.
m.
PK and ADA samples are collected only from the subjects receiving risankizumab.


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Appendix D.
Recommendations on the Technique of Blood Pressure 
Measurement
Proper techniques to measure blood pressure are important to ensure consistent and 
reliable measurements.  The purpose of the recommendations below is to screen in routine 
practice the patients that will require explorations in a specialized department.40
1.
If anatomical conditions, deformity or surgical history interfering with proper 
access or blood flow to the upper arm, use the opposite arm for the blood pressure 
measurement
2.
Use a high quality and well calibrated equipment
3.
Prepare the patient
●
The examination room should be quiet, with a comfortable ambient 
temperature.
●
Ideally, blood pressure should not be measured if the patient has engaged in 
recent physical activity, used tobacco, ingested caffeine, or eaten within the 
past 30 minutes
●
Correct positioning of the patient is essential. 
○
The patient's back and legs should be supported, with the legs uncrossed 
and the feet resting on a firm surface.
○
The arm in which blood pressure will be measured should be bare to the 
shoulder, and the garment sleeve, if raised, should be loose, so that it does 
not interfere with blood flow or with proper positioning of the blood-
pressure cuff.
○
The arm should be supported and level with the heart.  The manometer 
should be positioned at the health care practitioner's eye level.
4.
Make sure that you are using the properly fitted cuff (undersized cuffs will result in 
overestimation of blood pressure)
●
Selection of an appropriately sized cuff requires assessment of the patient's 
arm circumference at the midpoint of the upper arm. 


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5.
Place the cuff on a bare arm, approximately 2 cm above the elbow crease, with the 
midline of the bladder (usually indicated by the manufacturer) directly over the 
brachial artery.  It should fit snugly but should still allow for two fingers to slide 
under the cuff.
6.
Estimate the systolic blood pressure by first measuring pulse-obliteration pressure
7.
For blood pressure measurement, proceed as follows:
●
Place the bell of the stethoscope over the brachial artery, using sufficient 
pressure to provide good sound transmission without over-compressing the 
artery.  To avoid extraneous noise during cuff deflation, ensure that the 
stethoscope is not in contact with the patient's clothing or with the blood-
pressure cuff.
●
Initiate the auscultatory blood pressure measurement by rapidly inflating the 
cuff to a level 20 to 30 mmHg above the pulse-obliteration pressure. 
●
Then deflate the cuff at a rate of 2 mmHg per second while listening for the 
Korotkoff sounds.  As the cuff is deflated, turbulent blood flow through the 
brachial artery generates a series of sounds.  Classically, these have been 
described according to five phases.
○
Phase 1 is characterized by a clear, repetitive tapping sound, coinciding 
with reappearance of a palpable pulse.  The initial appearance of Phase 1 
sounds is equal to the systolic blood pressure. 
○
During Phase 2, audible murmurs in the tapping sounds are heard. 
○
In Phases 3 and 4, muted changes in the tapping sounds occur (usually 
within 10 mmHg of the true diastolic pressure) as the pressure 
measurement approaches the diastolic pressure. 
○
Phase 5 is not really a sound; it indicates the disappearance of sounds and 
equates to the diastolic blood pressure.  To ensure that diastole has been 
reached, continue to deflate the cuff pressure for an additional 10 mmHg 
beyond the fifth Korotkoff sound.


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Obtain a minimum of two blood-pressure measurements at intervals of at least 1 minute 
and record the average of the measurements as the blood pressure.
Cross reference:  Williams JS et al 200940


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Appendix E.
CASPAR Classification Criteria
CASPAR 
Classification 
Criteria
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:
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 healthcare 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 immuosorbent 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.
Taylor W, Gladman D, Helliwell P, et al; CASPAR Study Group.  Classification criteria for psoriatic arthritis.  Arthritis 
Rheum.  2006;54(8):2665-73.


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Appendix F.
PASI SCORE Definitions and Use Psoriasis Area and Severity 
Index (PASI)
The PASI score is an established measure of clinical efficacy for psoriasis medications.24
The PASI is a tool which provides a numeric scoring for subjects overall psoriasis disease 
state, ranging from 0 to 72.  It is a linear combination of percent of surface area of skin 
that is affected and the severity of erythema, infiltration, and desquamation over four body 
regions. 
The endpoints used are based on the percent reduction from baseline, generally 
summarized as a dichotomous outcome based on achieving over an X% reduction (or 
PASI X), where X is 50, 75, 90 and 100.
To calculate the PASI score, the four main body areas are assessed:  head (h), trunk (t), 
upper extremities (u) and lower extremities (l).  These correspond to 10, 30, 20 and 
40% of the total body area respectively.
The area affected by psoriasis within a these four areas site is estimated as a percentage of 
the total area of that anatomic site and assigned a numerical value according to the degree 
of psoriatic involvement as follows:
●
0 = no involvement
●
1 = < 10%
●
2 = 10% to 29%
●
3 = 30% to 49%
●
4 = 50% to 69%
●
5 = 70% to 89%
●
6 = 90% to 100%
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 


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for each of the areas, h, t, u and l and represents a composite score for each area.  The 
signs of severity, erythema (E), induration (I) and desquamation (D) of lesions are 
assessed using a numeric scale 0 – 4:
●
0 = No symptoms
●
1 = Slight
●
2 = Moderate
●
3 = Marked
●
4 = Very marked
Erythemaa
Desquamation
Induration
0 = none
No redness
No scaling
No elevation over normal 
skin
1 = slight
Faint redness
Fine scale partially 
covering lesions
Slight but definite 
elevation, typically edges 
indistinct or sloped
2 = moderate
Red coloration
Fine to coarse scale 
covering most of all of the 
lesions
Moderate elevation with 
rough or sloped edges
3 = marked
Very or bright red 
coloration
Coarse, non-tenacious scale 
predominates covering 
most or all of the lesions
Marked elevation typically 
with hard or sharp edges
4 = very marked
Extreme red 
coloration; dusky to 
deep red coloration
Coarse, thick, tenacious 
scale over most or all 
lesions; rough surface
Very marked elevation 
typically with hard sharp 
edges
a.
Do not include residual hyperpigmentation or hypopigmentation as erythema.
Assignments for the following body regions are as follows:
●
Neck:  include with the head
●
Buttocks:  include with the lower extremities
●
Axillae:  include with the trunk
●
Genitals:  include with the trunk
●
The inguinal canal separates the trunk and legs anteriorly


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The PASI score for each body region is obtained by multiplying the sum of the severity 
scores by the area score, then multiplying the result by the constant weighted value 
assigned to that body region.  Since the head, upper extremities, trunk, and lower 
extremities correspond to approximately 10%, 20%, 30%, and 40% of BSA, respectively, 
the PASI score is calculated using the formula.
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
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 degree.
*
Fredriksson T38


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Appendix G.
Static Physician 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.39
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 efficacy assessor (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)


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Scaling
0
No scaling
1
Minimal focal scaling (surface dryness with some desquamation)
2
Predominately fine scaling (fine scale partially or mostly covering lesions)
3
Moderate scaling (coarser scale covering most or all of the lesions)
4
Severe/coarse scaling covering almost all or all lesions (coarse, non-
tenacious scale predominates)
Scoring
A composite score is generated from the above data and the final sPGA is determined 
from this composite score as follows:
Clear
0 = 0 for all three
Almost clear
1 = mean > 0, < 1.5
Mild
2 = mean ≥ 1.5, < 2.5
Moderate
3 = mean ≥ 2.5, < 3.5
Severe
4 = mean ≥ 3.5


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


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palm) + (sum of scored for E+I+D)*Area *0.3(location:  right sole) + (sum of scores for 
E+I+D)*Area *0.3 (location:  left sole).  The range is 0 to 72.
*
Fredriksson T38


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Appendix I.
Psoriasis Scalp Severity Index (PSSI)
If a subject has scalp psoriasis, the physician will assess the erythema (redness), 
induration (hardness), desquamation (shedding of skin) and percent of scalp covered at 
each protocol defined time point.
Erythema, Induration and Desquamation:
0 = None
1 = Slight
2 = Moderate
3 = Severe
4 = Very Severe
Percent of Scalp Covered:
1 = < 10%
2 = 10 – 29%
3 = 30 – 49%
4 = 50 – 69%
5 = 70 – 89%
6 = 90 – 100%
The PSSI is a composite score derived from the sum of the scores for erythema, 
induration and desquamation multiplied by the score recorded for the extent of scalp area 
involved.  The range is 0 to 72.
*
Fredriksson T38


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Appendix J.
NAPPA-CLIN
Clinical Severity of Nail Psoriasis (Nappa-Clin)
Please indicate how many quadrants (0 – 4) of the nail are affected by a nail matrix 
psoriasis (leukonychia, red spots, dots, nail plate crumbling) and how many quadrants are 
affected by psoriasis of the nail bed (oil drop, splinter haemorrhage, subungual 
hyperkeratosis, onycholysis).  Use of artificial nails and/or nail polish should be avoided 
throughout the study in order to ensure accuracy of assessments.


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Please record the severity of nail psoriasis for all fingers:
left hand
Number of affected 
quadrants:
matrix
bed
little finger
|__|
|__|
ring finger
|__|
|__|
middle finger
|__|
|__|
index finger
|__|
|__|
thumb
|__|
|__|
right hand
Number of affected 
quadrants:
matrix
bed
little finger
|__|
|__|
ring finger
|__|
|__|
middle finger
|__|
|__|
index finger
|__|
|__|
thumb
|__|
|__|


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Please record the severity of nail psoriasis for all toes:
left foot
Number of affected 
quadrants:
matrix
bed
little toe (D. minimus)
|__|
|__|
Digitus IV
|__|
|__|
Digitus III
|__|
|__|
Digitus II
|__|
|__|
big toe (hallux)
|__|
|__|
right foot
Number of affected 
quadrants:
matrix
bed
little toe (D. minimus)
|__|
|__|
Digitus IV
|__|
|__|
Digitus III
|__|
|__|
Digitus II
|__|
|__|
big toe (hallux)
|__|
|__|
*
Fredriksson T38


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Appendix K.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes
Section 1.0  Title Page
"Sponsor/Emergency Contact:," "Fax:" previously read:
Has been changed to read:
Section 5.2.1  Inclusion Criteria
Criterion 8
Delete:  last paragraph
Females of non-childbearing potential (either postmenopausal or permanently surgically 
sterile as defined above) at Screening do not require pregnancy testing at Study Day 1.
Table 1.  Prohibited Psoriasis Medications
Last row previously read:
Medication or Class of Medications
Restriction Duration
(Through 15 Weeks After 
the Last Dose of 
Risankizumab and Through 
1 Week after Last Dose of 
FUMADERM®a Provided as 
Study Medication)
Phototherapy (e.g., UVA, UVB, any other UV-therapy or 
balneotherpy) not- associated with UV-sensitizing agents, topical 
treatment for psoriasis or any other skin condition 
(e.g., corticosteroids,c vitamin D analogues, vitamin A analogues, 
pimecrolimus, retinoids, salicylvaseline, salicylic acid, lactic acid, 
tacrolimus, tar, urea, andanthralin, α-hydroxy acid, fruit acids)
14 days prior to screening or 
during study participation


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Has been changed to read:
Medication or Class of Medications
Restriction Duration
(Through 15 Weeks After 
the Last Dose of 
Risankizumab and Through 
1 Week after Last Dose of 
FUMADERM®a Provided as 
Study Medication)
Phototherapy (e.g., UVA, UVB, any other UV-therapy or 
balneotherpy) not- associated with UV-sensitizing agents, topical 
treatment for psoriasis or any other skin condition 
(e.g., corticosteroids,c vitamin D analogues, vitamin A analogues, 
pimecrolimus, retinoids, salicylvaseline, salicylic acid, lactic acid, 
tacrolimus, tar, urea, andanthralin, α-hydroxy acid, fruit acids)
14 days prior to Baseline 
(Week 0/Day 1) or during 
study participation
Section 5.3.1.1  Study Procedures
Subsection FUMADERM® INITIAL and FUMADERM® Subject Diary
First paragraph, first sentence previously read:
Subjects will be dispensed a paper diary at every visit Screening and will be trained on 
how to complete the diary for FUMADERM® INITIAL and FUMADERM® (provided as 
study medication) dosing by site staff during the Screening Visit.  
Has been changed to read:
Subjects will be dispensed a paper diary at every visit, starting at the Week 0/Baseline 
visit and will be trained on how to complete the diary for FUMADERM® INITIAL and 
FUMADERM® (provided as study medication) dosing by site staff during the 
Week 0/Baseline visit.  
Section 5.4.1.1  Discontinuation of Subjects on FUMADERM®
Item 8 previously read:
Rash/flush that does not resolve with continued treatment.
Has been changed to read:
Severe rash/flush that does not resolve with continued treatment.


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Section 5.5.1  Treatments Administered
Second paragraph
Delete:  last sentence
Additional dosing instructions will be provided separately from this protocol.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Clinical
Clinical
Pharmacokinetics
Clinical
Statistics
Has been changed to read:
Name
Title
Functional Area
Clinical
Clinical
Pharmacokinetics
Clinical
Statistics


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Appendix C.  Study Activities
Activity "Dispense Subject Diaryi" previously read:
Activity
Screening
–30 to –1
Week 0/ 
Baseline
Week
4
Week
8
Week
12
Week
16
Week
20
Week 
24/ETa
Week 31 
Follow-Up Callb
Day
–30 to –1
Day 1
Day 29
Day 57
Day 85
Day 
113
Day 
141
Day 
169
Day 218
Dispense Subject Diaryi
X
X
X
X
X
X
X
Has been changed to read:
Activity
Screening
–30 to –1
Week 0/ 
Baseline
Week
4
Week
8
Week
12
Week
16
Week
20
Week 
24/ETa
Week 31 
Follow-Up Callb
Day
–30 to –1
Day 1
Day 29
Day 57
Day 85
Day 
113
Day 
141
Day 
169
Day 218
Dispense Subject Diaryi
X
X
X
X
X
X


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Appendix J.  NAPPA-CLIN
Subsection Clinical Severity of Nail Psoriasis (Nappa-Clin)
First paragraph, last sentence previously read:
Use of artificial nails and/or nail polish should be avoided for subjects with nail psoriasis 
throughout the study in order to ensure accuracy of assessments.
Has been changed to read:
Use of artificial nails and/or nail polish should be avoided throughout the study in order to 
ensure accuracy of assessments.



SAP_001.pdf: 
Risankizumab
M16-178 – Statistical Analysis Plan
Version 1.0 – 11 Jan 2018
1
1.0
Title Page
Statistical Analysis Plan 
Study M16-178
A Randomized, Controlled, Multicenter, Open Label 
Study with Blinded Assessment of the Efficacy of 
the Humanized Anti-IL-23p19 Risankizumab 
Compared to FUMADERM® in Subjects with Moderate 
to Severe Plaque Psoriasis Who are Naïve to and 
Candidates for Systemic Therapy
Date:  11 Jan 2018
Version 1.0
NCT03255382


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2.0
Table of Contents
1.0
Title Page ...............................................................................1
2.0
Table of Contents ..................................................................2
3.0
Introduction...........................................................................5
4.0
Study Objectives, Design and Procedures............................5
4.1
Objectives .............................................................................................. 5
4.2
Design Diagram ..................................................................................... 5
4.3
Sample Size............................................................................................ 7
4.4
Interim Analysis ..................................................................................... 7
5.0
Analysis Populations and Stratification...............................7
5.1
Analysis Populations .............................................................................. 7
5.2
Variables Used for Stratification of Randomization ................................ 7
6.0
Analysis Conventions ............................................................8
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications..............12
7.1
Demographic and Baseline Characteristics ........................................... 12
7.2
Medical History.................................................................................... 15
7.3
Previous Treatment and Concomitant Medications ............................... 15
7.4
Protocol Deviations .............................................................................. 16
8.0
Patient Disposition............................................................... 16
9.0
Study Drug Exposure and Compliance..............................16
10.0
Efficacy Analysis .................................................................18
10.1
General Considerations......................................................................... 18
10.1.1
Analyses of Categorical Variables ........................................................ 18
10.1.2
Analyses of Continuous Variables ........................................................ 19
10.1.3
Missing Data Imputations..................................................................... 20
10.2
Primary Efficacy Analysis.................................................................... 21
10.3
Secondary Efficacy Analyses ............................................................... 21
10.4
Handling of Multiplicity....................................................................... 23
10.5
Efficacy Subgroup Analysis ................................................................. 23
11.0
Safety Analysis.....................................................................23
11.1
General Considerations......................................................................... 23


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11.2
Analysis of Adverse Events.................................................................. 24
11.2.1
Treatment-Emergent Adverse Events.................................................... 24
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 31
11.2.3
Safety Subgroup Analysis..................................................................... 31
11.3
Analysis of Laboratory Data................................................................. 32
11.3.1
Variables and Criteria Defining Abnormality........................................ 32
11.3.2
Statistical Methods ............................................................................... 33
11.4
Analysis of Vital Signs and Weight ...................................................... 38
11.4.1
Variables and Criteria Defining Abnormality........................................ 38
11.4.2
Statistical Methods ............................................................................... 38
11.5
Analysis of ECG Parameters ................................................................ 39
12.0
Pharmacokinetic Analysis...................................................39
13.0
Biomarkers Analysis ........................................................... 39
14.0
Summary of Changes .......................................................... 39
14.1
Summary of Changes Between the Latest Version of Protocol and 
the Current SAP ................................................................................... 39
15.0
Appendix..............................................................................40
16.0
References............................................................................43
17.0
List of Tables, Figures, and Data Listings to Be 
Programmed........................................................................ 43
List of Tables
Table 1.
Visit Windows for Analysis of Vital Signs, PASI, BSA 
Involvement, sPGA, Urinalysis, Targeted Safety Laboratory 
Testing (ITT/Safety Populations).......................................................... 10
Table 2.
Visit Windows for Analysis of DLQI, PPASI, PSSI, 
NAPPA-CLIN, PSS, SF-36, PBI, HADS, PtGA, EQ-5D-5L 
(ITT Population)................................................................................... 10
Table 3.
Visit Windows for Analysis of Complete Safety Laboratory 
Testing (Safety Population) .................................................................. 11
Table 4.
Visit Windows for Analysis of ECG (Safety Population) ...................... 11


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Table 5.
Visit Windows for Summary of Study Drug Injection of 
Risankizumab....................................................................................... 11
Table 6.
Areas of Safety Interest ........................................................................ 28
Table 7.
Clinical Laboratory Tests ..................................................................... 33
Table 8.
Criteria for Potentially Clinically Important Chemistry Values ............. 35
Table 9.
Criteria for Potentially Clinically Important Hematology Values .......... 35
Table 10.
NCI CTCAE Grading........................................................................... 36
Table 11.
Criteria for Potentially Clinically Important Vital Sign Findings........... 38
List of Figures
Figure 1.
Study Design Schematic......................................................................... 6
List of Appendices
Appendix A.
PASI Calculation.................................................................................. 40
Appendix B.
sPGA Calculation................................................................................. 40
Appendix C.
PPASI Calculation................................................................................ 40
Appendix D.
PSSI Calculation .................................................................................. 41
Appendix E.
NAPPA-CLIN Calculation ................................................................... 41
Appendix F.
NAPSI Calculation............................................................................... 41
Appendix G.
PSS Calculation.................................................................................... 41
Appendix H.
DLQI Calculation................................................................................. 41
Appendix I.
SF-36 Calculation................................................................................. 42
Appendix J.
PBI Calculation .................................................................................... 42
Appendix K.
HADS Calculation................................................................................ 42
Appendix L.
EQ-5D-5L Calculation ......................................................................... 42
Appendix M.
CASPAR Calculation ........................................................................... 43


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3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Clinical Statistics Department for Study Protocol M16-178 dated 
28 November 2017, which incorporates Amendments 1, 2 and 3 (original Protocol:  
05 January 2017, Amendment 1:  13 March 2017, Amendment 2:  05 July 2017). 
This SAP will provide details to further elaborate statistical methods as outlined in the 
Protocol M16-178 and will describe analysis conventions to guide the statistical 
programming work.  The SAP will be signed off before the study database is locked.
Analyses will be performed using SAS® version 9.4 (SAS Institute, Inc., Cary, NC 27513) 
or higher using the UNIX operating system.
4.0
Study Objectives, Design and Procedures
4.1
Objectives
The objective of this study is to compare the efficacy and safety of subcutaneous (SC) 
risankizumab and oral FUMADERM® provided as study medication in subjects with 
moderate to severe plaque psoriasis who are naïve to and candidates for systemic therapy.
4.2
Design Diagram
This is a randomized, controlled, multicenter, open-label study with blinded assessment of 
efficacy to demonstrate the efficacy and safety of SC risankizumab in adult subjects with 
moderate to severe plaque psoriasis who are naïve to and candidates for systemic therapy 
as compared with oral FUMADERM® provided as study medication.  Eligible male and 
female subjects with moderate to severe plaque psoriasis will be selected to participate in 
the study according to the selection criteria.  Approximately 110 subjects will be enrolled 
in this study.


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The study will include a 30-day screening period and a 24 week active-controlled 
treatment period followed by a follow-up phone call at Week 31 for subjects that do not 
elect to enroll into the extension Study M15-997.
After meeting the selection criteria, enrolled subjects will be randomly assigned in a 
1:1 ratio to one of two arms as shown below:
●
Risankizumab 150 mg SC at Week 0/Day 1, Week 4 and Week 16 or,
●
Oral FUMADERM® INITIAL provided as study medication starting at 
Week 0/Day 1 until Week 2 and FUMADERM® provided as study medication 
starting at Week 3 until Week 24 (last intake in the morning on the day of 
Week 24 visit)
A schematic of the study design is shown below in Figure 1.
Figure 1.
Study Design Schematic


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4.3
Sample Size
Using a two-sided Chi squared test at level of significance 5%, the sample size of 
110 (2 × 55) subjects will provide 94% power assuming response rates of the primary 
endpoint (PASI 90 at Week 24) of 70% for risankizumab and 35% for FUMADERM®.
These assumptions are in line with what has been observed in recent studies for 
risankizumab (63/83 (75.9%) at Week 24)1 and FUMADERM® 61/273 (22.3%) of the 
subjects achieved PASI 90 at Week 16 in the FUMADERM® arm in the BRIDGE trial.2
4.4
Interim Analysis
No interim analysis will be done for this study.
5.0
Analysis Populations and Stratification
5.1
Analysis Populations
Efficacy Population:
Intent-to-Treat (ITT) Population:  The ITT Population is defined as all subjects who are 
randomized.  The ITT Population will be used for the efficacy analyses.  The ITT 
Population will be analyzed by treatment group as randomized.
Safety Population:
The Safety Population is defined as all randomized subjects who received at least 
one dose of study drug.  The Safety Population will be used for the safety analyses.  The 
Safety Population will be analyzed based on the actual treatment received.  
5.2
Variables Used for Stratification of Randomization
Subjects will be randomized in 1:1 ratio to receive risankizumab or FUMADERM®
stratified by prior phototherapy, with a maximum of 20% of subjects with prior 
phototherapy.  Randomization will not be stratified by center due to the limited number of 
subjects per center.  Randomization will be done using an adequate block size.


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6.0
Analysis Conventions
Definition of Baseline
The last non-missing observation collected on or before the date of the first dose of study 
drug will be used as Baseline for summary of demographics and disease characteristics, 
safety and efficacy analyses.
Definition of Final Observation (Applicable to Safety Analyses)
Final observation is defined as the last non-missing observation collected within 15 weeks 
(105 days) following the last dose of risankizumab or 1 week (7 days) after the last dose 
of FUMADERM® provided as study medication.  In a sensitivity analysis, adverse events 
with an onset date until 7 weeks (49 days) after the last dose of FUMADERM® provided 
as study medication or until rollover into the extension study will be included.
Definition of Rx Days (Days Relative to the Date of First Dose of Study Drug)
Rx Days are calculated for each time point relative to the date of first dose of study drug.  
They are defined as the number of days between the day of the first dose of study drug 
and the specific time point.  Rx Days are negative values when the time point of interest is 
prior to the first study drug dose day.  Rx Days are positive values when the time point of 
interest is on or after the first study drug dose day.  The day of the first dose of study drug 
is defined as Rx Day 1, while the day prior to the first study drug dose is defined as Rx 
Day –1 (there is no Rx Day 0). 
Definition of Analysis Windows 
All time points and corresponding time windows are defined based on Rx Days.  
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).


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●
In order to include all post baseline data, the first post-baseline interval starts 
on the first day after the first dose of study drug (Rx Day 2).
●
Determine the window around a specific nominal Rx day by adding or 
subtracting half of the interval between adjacent visits (e.g., days between 
Week 4 and Week 8 is 28).  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 4 and Week 8 would be between Rx Days 43 and 
44).
●
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 later one will be used in analyses.  If more 
than one assessment is included on the same day, then the worst assessment on 
that day will be used in analyses, except those specified in Section 11.0.
For subjects who were randomized and not dosed, the date of randomization will be used 
for determining window definitions.
The following analysis windows have been specified:


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Table 1.
Visit Windows for Analysis of Vital Signs, PASI, BSA Involvement, 
sPGA, Urinalysis, Targeted Safety Laboratory Testing (ITT/Safety 
Populations)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 4
29
[2, 43]
Week 8
57
[44, 71]
Week 12
85
[72, 99]
Week 16
113
[100, 127]
Week 20
141
[128, 155]
Week 24
169
[156, 183a]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
Targeted Safety Laboratory Testing includes CBC with differential count (hematology), ALT, AST, gamma-GT, 
alkaline phosphatase (AP) and serum creatinine.
a.
For safety analyses (urinalysis and targeted laboratory testing):  The minimum of upper bound and 105 or 7 days 
after the last dose for risankizumab and FUMADERM®, respectively.
Table 2.
Visit Windows for Analysis of DLQI, PPASI, PSSI, NAPPA-CLIN, 
PSS, SF-36, PBI, HADS, PtGA, EQ-5D-5L (ITT Population)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 16
113
[2, 141]
Week 24
169
[142, 197]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.


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Table 3.
Visit Windows for Analysis of Complete Safety Laboratory Testing 
(Safety Population)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 8
57
[2, 85]
Week 16
113
[86, 141]
Week 24
169
[142, 197a]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
Complete Safety Laboratory Testing includes all laboratory parameters (see Table 8) excluding CBC with differential 
count (hematology), ALT, AST, gamma-GT, alkaline phosphatase (AP) and serum creatinine.
a.
For safety analyses:  The minimum of upper bound and 105 or 7 days after the last dose for risankizumab and 
FUMADERM®, respectively.
Table 4.
Visit Windows for Analysis of ECG (Safety Population)
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 24
169
[2, 337a]
Rx Day calculated relative to first dose date of study drug.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
The minimum of upper bound and 105 or 7 days after the last dose for risankizumab and FUMADERM®, 
respectively.
Table 5.
Visit Windows for Summary of Study Drug Injection of 
Risankizumab
Window Label
Target Day
Interval
Baseline
1
≤ 1
Week 4
29
[2, 43]
Week 16
113
[44, 155]
Rx Day calculated relative to the first dose date of study drug.
No global imputation is taking place at the database level.  Efficacy related imputations 
are outlined in Section 10.1.2.  There is no imputation for missing values in the safety 
analyses.


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Rounding of Numeric Results
Rounding will be performed for presentation of results.  No rounding will be performed 
before or during analyses.  The ROUND function of SAS will be used to round results. 
When dichotomizing continuous variables from single observations, associated 
continuous variables will be rounded to 9 decimal points before applying the cutoff point 
to determine the response status (for example, percent change from baseline in PASI score 
will be rounded to 9 decimal places before comparing to 90%).
The mean, median and quartiles will be rounded for presentation to 1 decimal more than 
the data entered into the database.  The standard deviation will be rounded to 2 decimal 
places more than the data entered into the database.  The minimum and maximum values 
will be presented as entered into the database.
Probabilities will be rounded to 3 decimal places before assignment of statistical 
significance and will be presented in rounded format.  Probabilities that round to zero or 
are reported by SAS as zero will be presented as "< 0.001."  Probabilities that round to 
1 or are reported by SAS as 1 will be presented as "> 0.999."
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
Demographic and baseline characteristics will be summarized for each arm and overall for 
the ITT population.  The number of observations, mean, standard deviation, median, 
first and third quartile, minimum and maximum will be summarized for continuous 
variables; and treatment groups will be compared using a one-way analysis of variance 
(ANOVA) model with treatment as the independent factor.  Categorical or discrete 
variables will be summarized via counts and percentages; and treatment groups will be 
compared using a two-sided Pearson's Chi-Square test (or Fisher's exact test if expected 
cell count < 5).


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The following demographic and baseline parameters will be summarized. 
Subject Demographics
●
Sex (male, female)
●
Age (years), defined as the number of years from date of birth to date of 
first drug
●
Age categories (< 40 years, ≥ 40 – < 65 years, ≥ 65 years)
●
Race (White, Black or African American, Asian, American Indian or Alaska 
Native, Native Hawaiian or Other Pacific Islander, Multi Race)
●
Asian race (Japanese, Chinese, Korean, Taiwanese, Other)
●
Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
●
Body weight (kg)
●
Body weight category (≤ 100 kg, > 100 kg)
●
Height (cm)
●
BMI (kg/cm2)
●
BMI category (< 25, ≥ 25 – < 30, ≥ 30)
General Baseline Characteristics
●
PASI (Psoriasis Area and Severity Index)
●
BSA (Body Surface Area)
●
sPGA categories (Static Physician Global Assessment)
●
NAPPA-CLIN (Nail Assessment in Psoriasis and Psoriatic Arthritis)
●
PSSI (Psoriasis Scalp Severity Index)
●
PPASI (Palmoplantar Psoriasis Area Severity Index)
●
PSS (Psoriasis Symptom Severity)
●
SF-36 (Short Form 36)
●
PBI (Patient Benefit Index)
●
HADS (Hospital Anxiety & Depression Scale)
●
Patient Global Assessment (PtGA)


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●
EQ-5D-5L (European Quality of Life – 5 Dimensions 5 Level)
●
Dermatology Life Quality Index (DLQI)
●
CASPAR:
○
Total score
○
Evidence of current personal psoriasis (yes, no)
○
Evidence of history of psoriasis
●
personal history of psoriasis (yes, no)
●
Evidence of family history of psoriasis (yes, no)
○
Psoriatic nail dystrophy (yes, no)
○
Negative test for presence of rheumatoid factor (yes, no)
○
Current or history of dactylitis (yes, no)
○
Radiographic evidence of juxtaarticular bone formation (yes, no)
Disease History
●
Time since initial diagnosis of Plaque Psoriasis (years)
●
Time since initial symptoms of Plaque Psoriasis (years)
●
Prior phototherapy (yes, no)
●
For subjects with prior phototherapy:  Type of prior phototherapy (UVA, UVB 
Broad Band, UVB Narrow Band, Balneotherapy, Other) including outcome 
(success, failure)
General Use
●
Smoking history (Never-smoked, Former-smoker, Currently smokes)
●
Alcohol History (Non-drinker, Former-drinker, Currently drinks)
Physical Exam and Pregnancy Test will be presented in listing format in the full data 
listings.
TB History/PPD Test/TB Prophylaxis
●
Former BCG vaccination (yes, no)


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●
Induration of Tuberculin PPD skin test (mm)
●
PPD test (positive, negative) – the PPD test is considered positive for an 
induration of 5 mm or greater
●
QuantiFERON-TB Gold or equivalent test (positive, negative, indeterminate)
●
TB test (positive, negative, indeterminate) – in the event that both a PPD test 
and QuantiFERON-TB gold or equivalent test are performed, the result of the 
QuantiFERON-TB gold or equivalent test will supersede the result of the PPD 
test
●
Active TB (yes, no)
●
Latent TB (yes, no)
7.2
Medical History
Medical history will be summarized using body systems and condition/diagnosis as 
captured on the eCRF.  The body systems will be presented in alphabetical order and the 
conditions/diagnoses will be presented in alphabetical order within each body system.  
The number and percentage of subjects with a particular condition/diagnosis will be 
summarized for each treatment arm.  Subjects reporting more than 
one condition/diagnosis within a body system will be counted only once for that body 
system.
7.3
Previous Treatment and Concomitant Medications
Prior and concomitant medications will be summarized by generic name, separately for 
Psoriasis Therapy and other medications, per the category documented on the eCRF.  A 
prior medication is defined as any medication taken prior to the first dose of study drug.  
A concomitant medication is defined as any medication that started prior to the first dose 
of study drug and continued to be taken after the first dose of study drug or any 
medication that started after the first dose of study drug, but not after the last dose of 
study drug.  The number and percentage of subjects who had taken medications will be 
summarized by generic drug name assigned by the World Health Organization (WHO) for 
both prior and concomitant medications.


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7.4
Protocol Deviations
Number and percentage of subjects who reported at least one of the following protocol 
deviation categories will be provided.
●
Subject entered into the study even though she/he did not satisfy entry criteria
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded or prohibited concomitant treatment
8.0
Patient Disposition
The number of subjects for each of the following categories will be summarized, overall 
and for each treatment group in the ITT population, overall and per study site:
●
Number of subjects randomized
●
Number of subjects randomized with prior phototherapy
●
Number of subjects treated
●
Number of subjects who completed the study
●
Number of subjects who discontinued the study drug
●
Number of subjects who prematurely discontinued study
In addition, the reasons for premature discontinuation (all reasons and primary reasons) 
will be summarized with frequencies and percentages.
Beyond patient disposition, number of screening failures and reasons for screening failure 
will also be summarized among all screened subjects in a subject screening status table.
9.0
Study Drug Exposure and Compliance
Summary of study drug treatment duration and compliance will be provided for each 
treatment arm in the ITT Population.


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Study drug treatment duration (days) will be summarized using the sample size, mean, 
standard deviation, minimum, first quartile, median, third quartile and maximum.  Study 
drug treatment duration will be summarized as follows:
Risankizumab Exposure (in Days)
Risankizumab Exposure (days) = Date of last injection – Date of first injection + 84 days.
FUMADERM® Exposure (in Days) [this includes FUMADERM® Initial]
FUMADERM® Exposure (days) = Date of last dose of oral study drug – date of first dose 
of oral study drug + 7 days.
For subjects in the FUMADERM® group, there will also be the following analyses
●
Interruption of FUMADERM® dosing of more than 7 consecutive days 
between first and last dose (yes, no)
●
For subjects with an interruption of more than 7 consecutive days, total 
number of days without FUMADERM® dosing between first and last dose
In addition, the total dose of FUMADERM® (mg) and the average daily dose of 
FUMADERM® (mg) calculated as total dose divided by number of days with doses taken, 
will be presented.  The presentation of average daily dose will be done overall as well as 
for each week separately.
Compliance
For subjects in the Risankizumab group, there will be a summary of the number of 
subjects receiving study drug and dose at each study drug administration visit.  This will 
be repeated on the cumulative number of doses.
For subjects in the Risankizumab group, when computing compliance at each study drug 
administration visit, the denominator will include all subjects in each analysis population 
who have not prematurely discontinued the study drug prior to the scheduled study drug 


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injection.  Subjects who have prematurely discontinued the study drug but have not 
prematurely discontinued the study are not used in the denominator.
For subjects in the FUMADERM® group, for each visit (Week 4, 8, 12, 16, 20, 24), the 
number of subjects deviating from the pre-specified dosing schedule including reasons 
will be provided, including non-compliance.
10.0
Efficacy Analysis
10.1
General Considerations
The treatment effect will be evaluated based on a two-sided significance level of 0.05 
(when rounded to three decimal places).
The ITT population will be used for the analyses of efficacy endpoints.
Subjects' prior phototherapy exposure will be used as the stratum in the stratified analyses.
10.1.1
Analyses of Categorical Variables
For categorical variables, frequencies and percentages will be summarized.  Treatment 
comparison will be conducted using a Cochran-Mantel-Haenszel (CMH) test with the 
above stratification factor as stratum for the analysis.  The CMH test will use weights 
proposed by Greenland & Robins,3 which is calculated as follows:
 =
∑

 ∙


∑

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

 =  ∙
 + 
  denotes the weight of stratum &, & = 1, ⋯, )
 denotes the number of subjects with event in treatmentin stratum i, & = 1, ⋯, )
 denotes the number of subjects with event in treatment/in stratum i, & = 1, ⋯, )


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




)/
where 6 = ( −) 
9 + ( −) 
9
 ∙ ∙( + )/
 , & = 1, ⋯, )
Assuming a normal distribution of , an approximate 95% CI is given as follows, 
where :;.=>? is the 97.5% quantile of the standard normal distribution:
@A =  B  ± :;.=>? ∙D012
3 45E
Also, the approximate p-value can be calculated using the following:
pvalue =  2 ∙Pr
⎣
⎢
⎢
⎡
M > OO

D012
3 45
OO 
⎦
⎥
⎥
⎤
 , where M ~ T(0, 1)
If there is a stratum for a treatment group that has 0 subjects in any cell in the contingency 
table, all cells from the stratum will be added by 0.1 in order to prevent dividing by 0 in 
the above equations, as suggested in Greenland & Robins.
10.1.2
Analyses of Continuous Variables
Change from baseline in PSS will be analyzed by stratified van Elteren test.  For other 
continuous variables, the model based mean and standard error will be presented.  The 
Baseline and visit means will also be presented for each treatment group for subjects who 
have both Baseline and post Baseline visit values.  The treatment groups will be compared 
using ANCOVA with treatment group, Baseline value, and stratification factor in the 
model.


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10.1.3
Missing Data Imputations
Missing data will be imputed using the following methods for the efficacy analyses: 
●
Non-Responder Imputation (NRI):  the NRI analysis will categorize any 
subject who has a missing value at a specific visit as a non-responder for that 
visit.  The only exception is when the subject is a responder both before and 
after a specific visit window, and then the subject will be categorized as a 
responder for the visit.  The NRI will be the primary approach in the analyses 
of categorical variables.  
●
Last Observation Carried Forward (LOCF):  The LOCF analyses will use the 
completed evaluation from the previous visit for efficacy measures assessed to 
impute missing data at later visits.  Baseline values will not be carried forward.  
LOCF will be the primary approach in the analyses of continuous variables, 
and the secondary approach in the analyses of categorical variables.
●
As-Observed Cases (OC):  The as-observed analysis will not impute values for
missing evaluations, and thus a subject who does not have an evaluation on a 
scheduled visit will be excluded from the as-observed analysis for that visit.  
As-observed analysis will be the secondary approach in the analysis of 
continuous variables.
●
Multiple Imputation (MI):  The MI will be used as sensitivity approach to 
impute missing data in the primary endpoint.  The variables to be included in 
the imputation model are listed below.  If MI is not applicable due to the 
nature of our data (e.g., MCMC algorithm does not converge), this analysis 
will not be performed.
The Multiple Imputation analysis will be carried out in three steps.
●
Imputation of missing data.  The imputation will be generated for the primary 
endpoint measurement.  The variables to be included in the imputation model 
are:  Baseline disease severity (PASI), Baseline weight, treatment group, prior 
phototherapy exposure, and PASI measurements at each visit from 
randomization up to the end of the study.  For each endpoint, 
20 'complete' datasets will be generated using SAS PROC MI.  The imputed 


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post-baseline measurements will be rounded to the same precision as the 
observed data before the determination of responder status (PASI 90).
●
Analysis of imputed data sets.  A CMH test, stratified by stratification factor, 
will be used to analyze categorical endpoints in each imputed dataset.  
Synthesis of imputation and analysis results.  SAS PROC MIANALYZE will 
be used to generate the final inferences of the risk difference between 
treatment groups.
Of note, subjects who discontinued due to AE of "worsening of disease under study" will 
be counted as non-responders in all subsequent visits in the NRI and MI analyses, and will 
have their last observation prior to discontinuation carried forward in the LOCF analyses.
10.2
Primary Efficacy Analysis
The primary efficacy endpoint is the proportion of subjects with a ≥ 90% reduction from 
baseline in Psoriasis Area and Severity Index (PASI 90) at Week 24.
The primary null hypothesis is that risankizumab is not different from FUMADERM® in 
achieving ≥ 90% reduction from baseline in the Psoriasis Area and Severity Index score 
(PASI 90) at Week 24.
The primary endpoint will be analyzed in the ITT Population.  The difference in 
proportion of subjects achieving PASI 90 between treatment arms will be estimated and 
tested using the two-sided Cochran-Mantel-Haenszel risk difference estimate stratified by 
prior phototherapy exposure at level of significance 5%.
Non-responder imputation will be used as the primary approach for missing values.  
LOCF and MI will be performed as sensitivity analyses.
10.3
Secondary Efficacy Analyses
The secondary endpoints will be analyzed in the ITT Population.  The following null 
hypotheses will be tested using two-sided tests with a type I error of 0.05.


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The secondary endpoints are as follows:
●
Proportion of subjects with a PASI 50/75/90/100 response at Week 4, 8, 12, 
16, 20 and 24.
●
Change from baseline in PASI at Week 4, 8, 12, 16, 20 and 24.
●
Change from baseline in BSA affected by psoriasis at Week 4, 8, 12, 16, 20 
and 24.
●
Proportion of subjects with a sPGA of 0 or 1 at Week 4, 8, 12, 16, 20 and 24.
●
Proportion of subjects with sPGA of 0 at Week 4, 8, 12, 16, 20 and 24.
●
Change from Baseline in PPASI Total Score at Week 16 and 24.
●
Change from Baseline in PSSI Total Score at Week 16 and 24.
●
Change from Baseline on the NAPPA-CLIN Total Score at Week 16 and 24 
(for all subjects and for subjects with NAPPA-CLIN > 0 at baseline).
●
Change from Baseline on the NAPSI at Week 16 and 24 (for all subjects and 
for subjects with NAPSI > 0 at baseline).
●
Change from Baseline in Psoriasis Symptom Scale (PSS) total score at 
Week 16 and 24.
●
Proportion of subjects achieving PSS (0) at Week 16 and 24.
●
Change from Baseline in DLQI total score at Week 16 and 24.
●
Proportion of subject achieving DLQI (0, 1) at Week 16 and 24.
●
Change from Baseline in SF-36 PCS and MCS Scores at Week 16 and 24.
●
Change from Baseline in PBI at Week 16 and 24
●
Change from Baseline on HADS at Week 16 and 24.
●
Change from Baseline on PtGA at Week 16 and 24.
●
Change from Baseline in EQ-5D-5L Index, EQ-5D Utility Index and VAS at 
Week 16 and 24.
The order of the secondary endpoints does not reflect a ranking.


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10.4
Handling of Multiplicity
The order of the secondary endpoints does not reflect a ranking and secondary endpoints 
will not be used for confirmatory interpretation, thus no adjustment for multiplicity will 
be done.
10.5
Efficacy Subgroup Analysis
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, summaries and analyses will be performed for the following subgroups for 
the primary efficacy endpoint.
●
Age (< 40 years, ≥ 40 – < 65 years, ≥ 65 years)
●
Sex (male, female)
●
Race (white, non-white)
●
Smoking (current, former or never)
●
BMI (normal:  < 25, over weight:  ≥ 25 – < 30, obese:  ≥ 30)
●
Baseline PASI score (by median)
●
Baseline sPGA (≤ 2, 3, 4)
●
Prior Phototherapy (yes/no)
11.0
Safety Analysis
11.1
General Considerations
Safety evaluations include AE monitoring, physical examinations, vital sign 
measurements, and clinical laboratory testing (hematology, chemistry, and urinalysis) as a 
measure of safety and tolerability for the entire study duration.  Safety summaries will be 
provided using the safety population as defined in Section 5.1.  Pairwise comparisons of 
risankizumab vs FUMADERM® will be performed in the Safety Population.  AEs will be 
analyzed using Fisher's exact test, only P values ≤ 0.100, when rounded to three digits, 
will be presented.


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Missing safety evaluations will not be imputed.
11.2
Analysis of Adverse Events
11.2.1
Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAE) are defined as events with an onset date on or 
after the first dose of study drug until 15 weeks (105 days) following the last dose of 
risankizumab or 1 week (7 days) after the last dose of FUMADERM® or until rollover 
into the extension study.  In a sensitivity analysis, adverse events with an onset date until 
7 weeks (49 days) after the last dose of FUMADERM® or until rollover into the extension 
study will be included.  In this sensitivity analysis, the observation period for TEAEs will 
be identical for both treatment arms, i.e., up to the 31 week safety follow-up call.
SAEs and protocol-related non-serious AEs with onset after informed consent but before 
the first study drug administration will be considered as pretreatment events and reported 
separately.  Posttreatment events for FUMADERM® are included in the above sensitivity 
analysis.
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).
Summary tables will be presented as follows:
1.
Adverse Event Overview
The number and percentage of subjects experiencing treatment-emergent adverse 
events will be summarized for the following adverse event categories.  
●
Any AE
●
Any AE that was assessed as related to study drug by the investigator
●
Any severe AE
●
Any serious AE (SAE)
●
Any SAE that was assessed as related to study drug by the investigator


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●
Any AE leading to discontinuation of study drug.
●
Any AE leading to death.
●
Any deaths
●
Areas of Safety Interest
2.
Adverse Events by System Organ Class and Preferred Term
TEAEs will be summarized and presented using primary Medical Dictionary for 
Regulatory Activities (MedDRA) system organ classes (SOCs) and preferred terms 
(PTs).  The SOCs will be presented in alphabetical order, and the PTs will be 
presented in alphabetical order within each SOC.
Subjects reporting more than one adverse event for a given MedDRA preferred 
term will be counted only once for that term (most severe incident for the severity 
tables and most related incident for the relationship tables).  Subjects reporting 
more than one type of adverse event within a SOC will be counted only once for 
that SOC.  Subjects reporting more than one type of adverse event will be counted 
only once in the overall total. 
TEAEs will also be summarized presenting PTs in descending order of frequency 
in the risankizumab arm.
In addition, the number and percentage of adverse events with causal relationship 
as assessed by the investigator, between the events and the study drug will be 
summarized using the same conventions described above.
3.
Adverse Events by Maximum Severity
The investigator will use the following definitions to rate the severity of each 
adverse event:
●
Mild – The adverse event is transient and easily tolerated by the subject.
●
Moderate – The adverse event causes the subject discomfort and interrupts the 
subject's usual activities.
●
Severe – The adverse event causes considerable interference with the subject's 
usual activities and may be incapacitating or life-threatening.


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Adverse events will 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.  In this case, 
the subject will be counted under the "Severe" category.
4.
Adverse Events by Maximum Relationship
Adverse events will be summarized by maximum relationship to study drug, as 
assessed by the investigator.  Relationship of an AE to study drug is assessed by the 
investigator and collected in the CRF as 'Reasonable possibility' or 'No reasonable 
possibility.'  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 
reasonable possibility."  If the subject has another occurrence of the same adverse 
event with a relationship assessment of "Reasonable possibility," the subject will be 
counted under the "Reasonable possibility" category. 
A listing of all pretreatment (i.e., events start prior to the first study drug injection) serious 
adverse events will be provided. 
The following tables are planned.
Treatment-emergent adverse events will be summarized as follows:
●
Grouped by SOC and PT
●
Grouped by SOC, PT and maximum relationship to study drug
●
Grouped by SOC, PT and maximum severity
●
By PT in descending order of frequency in the risankizumab arm.
Treatment-emergent SAEs will be summarized as follows:
●
Grouped by SOC and PT


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●
By PT in descending order of frequency in the risankizumab arm.
●
A by-subject listing will be provided
Pre-treatment SAEs will be summarized as follows:
●
A by-subject listing will be provided
Treatment-emergent adverse events leading to death or premature discontinuation 
of study drug will be summarized as follows:
●
Grouped by SOC and PT
●
Separate listings by subject for deaths and premature terminations of study 
drug due to adverse events will be provided.
Treatment-emergent areas of safety interest will be summarized as follows:
●
Grouped by SOC and PT
●
A listing by subject will be provided.
Areas of Safety Interest
Areas of Safety Interest groupings are listed in Table 6.  These events are of interest due 
to a higher rate in the moderate to severe psoriasis population, or of interest for all 
immunoglobulin products or products in general.


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Table 6.
Areas of Safety Interest
ASI 
Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated 
CV Events
MACE
Adjudicated events
Display underlined terms 
defined by the following 
adjudicated terms:
!
CV Death which includes 
CETERM values:  Fatal 
CV, Fatal PE, Fatal Non-
Cardiac/Non-Neuro Arterial 
Thrombosis/Thromboembol
ism, Undetermined Death, 
Not assessable death 
(cardiac/neuro/thrombotic), 
Fatal Stroke
!
Myocardial infarction
!
Stroke
Y
Extended 
MACE
Adjudicated events
Display underlined terms from 
MACE and underlined terms 
below:
!
Hospitalization for Unstable 
Angina
Coronary Revascularization 
Procedures
N
Serious 
infections, 
TB, fungal 
and 
opportunistic 
infections 
(including 
herpes zoster)
Serious 
infections
SOC Infections and 
Infestations, serious 
events only
PTs
Y
TB
Tuberculosis 
(including 
Investigations) CMQ 
(code 80000033)
PTs
Y
Opportunistic 
infections
Opportunistic 
infections CMQ 
(code 80000073)
PTs
N


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Table 6.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include in 
AE 
Overview 
(Y/N)
Serious 
infections, TB, 
fungal and 
opportunistic 
infections 
(including 
herpes zoster) 
(Continued)
Fungal 
infections
Fungal infections 
CMQ 
(code 80000063)
PTs
N
Herpes Zoster
Herpes zoster 
CMQ 
(code 80000175)
PTs
N
Malignancies
All possible 
malignancies
Narrow –
Malignancies 
(SMQ 20000090) 
PTs
N
Malignant 
Tumours
Narrow –
Malignant 
tumours 
(SMQ 20000194)
PTs
Y
Non-melanoma 
skin cancer 
(NMSC)
Broad – Skin 
malignant 
tumours 
(SMQ 20000204) 
excluding terms 
identified by the 
Melanoma CMQ 
(code 80000119)
PTs
N
Malignant 
Tumours 
excluding 
NMSC
'Malignant 
Tumours 
excluding 
NMSC' is 
identified by the 
'Malignant 
Tumours' search 
excluding terms 
identified by the 
'Non-melanoma 
skin cancer 
(NMSC) search.
PTs
Y


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Table 6.
Areas of Safety Interest (Continued)
ASI Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include in 
AE 
Overview 
(Y/N)
Hypersensitivity 
Reaction
Hypersensitivity
Narrow –
Hypersensitivity 
(SMQ 20000214)
PTs
Y –
serious 
events 
only
Anaphylactic 
Reaction
Narrow –
Anaphylactic 
reaction 
(SMQ 20000021)
PTs
N
Hepatic Events
Hepatic Events
Broad – Hepatic 
failure, fibrosis 
and cirrhosis and 
other liver 
damage-related 
conditions 
(SMQ 20000013)
Broad –
Hepatitis, 
non-infectious 
(SMQ 20000010)
Broad –
Cholestasis and 
jaundice of 
hepatic origin 
(SMQ 20000009)
Broad – Liver 
related 
investigations, 
signs and 
symptoms 
(SMQ 20000008)
Narrow –
Liver-related 
coagulation and 
bleeding 
disturbances 
(SMQ 20000015)
PTs
N


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Adverse Event per 100 Patient-Years of Exposure
AEs occurring during the entire study will be presented by event rate per 
100 patient-years.  These will be presented for any TEAEs, serious adverse events, Areas 
of Safety Interest. 
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 or + 7 / 49 (sensitivity analysis) days for 
risankizumab or FUMADERM®, respectively) of all subjects normalized by 365.25, and 
rounded to one decimal place.
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Deaths and all SAEs will be presented in listing format.  In addition, SAEs will be 
summarized by System Organ Class and MedDRA Preferred Term.
11.2.3
Safety Subgroup Analysis
The AE overview and AE by SOC and preferred term will also be analyzed by 
stratification factor prior phototherapy (yes, no) as well as gender (male, female), age 
(< 65 years; 65 – 74 years; ≥ 75 years) and weight (≤ 100 kg, > 100 kg).
Years
Patient 
Total
TEAEs
of
Number 
100 ∀


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11.3
Analysis of Laboratory Data
For the assessments of laboratory data, values observed more than 105 days after the last 
dose of risankizumab and 7 days after the last dose of FUMADERM will be excluded (see 
Section 6.0, Definition of final observation).
Listing and descriptive statistics of laboratory values over time, change from baseline, and 
extreme abnormal value on treatment will be provided.  Extreme abnormal value is the 
value which is most significantly away from the reference range.  Frequency of subjects 
with transitions relative to reference range and listing of subjects with significant 
abnormal laboratory values will be presented as well.
11.3.1
Variables and Criteria Defining Abnormality
Clinical laboratory tests performed by central laboratory service provider are listed below.


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Table 7.
Clinical Laboratory Tests
Category
Test Name
Hematology
Hematocrit (Hct)
Hemoglobin (Hb)
White Blood Cells/Leukocytes
Platelet Count/Thrombocytes
Diff. Automatic
Neutrophils (absolute count)
Lymphocytes (absolute count)
Enzymes
AST (GOT)
ALT (GPT)
Alkaline Phosphatase (ALP)
Creatine Kinase (CPK)
Gamma-glutamyl gransferase (GGT/γ-GT)
Electrolytes
Calcium
Sodium
Potassium
Substrates
Glucose
Creatinine
Bilirubin Total (TBL)
Bilirubin Direct (if total is elevated)
Albumin
C-Reactive Protein (CRP) (high sensitivity)
Cholesterol, totala
Triglyceridesa
LDL-Cholesterola
HDL-Cholesterola
Urine
UACR
a.
To be done at screening only.
11.3.2
Statistical Methods
Analysis of Continuous Laboratory Parameters
Analyses of laboratory data will presented based on the National Cancer Institute 
Common Toxicity Criteria for Adverse Event (NCI CTCAE) scale.  Change from 
Baseline to each scheduled visit and to the final value in continuous laboratory parameters 
will be summarized with the mean, standard deviation and median.  The Baseline and 
visit/final value means will also be presented for subjects who have both the Baseline and 


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visit/final values (see Section 6.0 for the definition of Baseline and final values).  If there 
are multiple post-baseline measurements on the same day, the average value will be used. 
Shift Tables
Shift tables for changes from Baseline according to the normal range will be provided for 
each hematology and clinical chemistry parameter.  Shifts from Baseline to the following 
endpoints will be considered:  minimum value, maximum value and final value.  
Categories of "low or normal" and "high or normal" will be included at Baseline in 
addition to the categories of "low," "normal," "high" and "missing."  If there are multiple 
measurements on the same day, the last value will be used.
Potentially Clinically Important Laboratory Values
Frequencies and percentages of subjects with post Baseline lab values meeting the 
following criteria will be summarized. 


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Table 8.
Criteria for Potentially Clinically Important Chemistry Values
Chemistry Variables
Units
Definition of Potentially Clinically Important 
Current (Version 4) NCI CTCAE Grade 3 or Greater
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Sodium
mmol/L
< 130
> 155 
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CPK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN
ALP
> 5.0 × ULN
Table 9.
Criteria for Potentially Clinically Important Hematology Values
Hematology Variables
Units
Definition of Potentially Clinically Important 
Current (Version 4) 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
A separate listing will be provided that presents all of the subjects and values that are NCI 
CTCAE toxicity grade 3 or above.  For each of these subjects, the whole course of the 
respective parameter will be listed.  The NCI CTCAE grading is shown in Table 10
below:


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Table 10.
NCI CTCAE Grading
Test
Grade 1
Grade 2
Grade 3
Grade 4
SGPT/ALT 
increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
SGOT/AST 
increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
GGT increased
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
ALP increased
> ULN – 3.0 × ULN
> 3.0 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
TBL increased
> ULN – 1.5 × ULN
> 1.5 – 3.0 × ULN
> 3.0 – 10.0 × ULN
> 10.0 × ULN
Creatinine 
increased
> ULN – 1.5 × ULN
> 1.5 – 3.0 × ULN
> 3.0 – 6.0 × ULN
> 6.0 × ULN
CPK increased
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 10.0 × ULN
> 10.0 × ULN
Hemoglobin 
decreased
< LLN – 100.0 g/L
< 100.0 – 80.0 g/L
< 80.0 – 65.0 g/L
N/A
Neutrophil count 
decreased
< LLN – 1.5 × 109/L
< 1.5 – 1.0 × 109/L
< 1.0 – 0.5 × 109/L
< 0.5 × 109/L
WBC decreased
< LLN – 3.0 × 109/L
< 3.0 – 2.0 × 109/L
< 2.0 – 1.0 × 109/L
< 1.0 × 109/L
Lymphocyte 
count decreased
< LLN – 0.8 × 109/L
< 0.8 – 0.5 × 109/L
< 0.5 – 0.2 × 109/L
< 0.2 × 109/L
If there are multiple post-baseline measurements on the same day, the worst value will be 
used.
Liver Function Tests
Additional summaries will be presented for liver function tests including ALT or serum 
glutamic-pyruvic transaminase (SGPT), AST or serum glutamic-oxaloacetic transaminase 
(SGOT), alkaline phosphatase, and total bilirubin.  Each laboratory value will be 
categorized as follows:
●
< 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


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●
≥ 20.0 × ULN
Shift tables of Baseline to the maximum (relative to the normal range, i.e., the largest 
multiple relative to the upper limit of normal) values, and from Baseline to final value will 
be presented using these categories.  A listing of potentially clinically important liver 
function laboratory values will be provided.  The listing will include all subjects who met 
any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or
●
Alkaline phosphatase ≥ 1.5 × ULN, or
●
Total bilirubin ≥ 2 × ULN.
A listing of possible Hy's Law cases, defined as those who meet all of the following 
conditions will be provided:  
●
ALT > 3 × ULN or AST > 3 × ULN
●
Associated with an increase in bilirubin ≥ 2 × ULN 
●
Alkaline phosphatase < 2 × ULN.
In addition, a graphical summary highlighting potential cases of Hy's Law within each 
treatment group will be presented.  The maximum on-treatment values of total bilirubin 
and ALT will be plotted each on a scale as multiples of the upper limit of normal.  The 
figure will show areas that meet the criteria of cholestasis (total bilirubin > 2 × ULN), 
Temple's corollary (ALT > 3 × ULN) and Hy's Law as the combination of these 
two factors.
All analyses will be conducted in the Safety Population.


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11.4
Analysis of Vital Signs and Weight
11.4.1
Variables and Criteria Defining Abnormality
The following vital sign parameters will be assessed:  Systolic blood pressure [mmHg], 
Diastolic blood pressure [mmHg], Pulse [beats per minute], Respiratory rate [breaths per 
minute], Temperature [°C], Weight [kg].  The following table presents the Criteria for 
Potentially Clinically Important Vital Sign Findings.
Table 11.
Criteria for Potentially Clinically Important Vital Sign Findings
Vital Sign
Category
Criteria for Potential Clinically Important Vital Signs
Systolic Blood Pressure
Low Value
≤ 90 mmHg and decrease ≥ 20 mmHg from Baseline
High Value
≥ 160 mmHg and increase ≥ 20 mmHg from Baseline
Diastolic Blood Pressure
Low Value
≤ 50 mmHg 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
Respiratory rate
High Value
> 3/min increase 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 and median.  The Baseline and final value 
means will also be presented for subjects who have both the Baseline and final values (see 
Section 6.0 for the definition of Baseline and final values).
For baseline, if there are multiple measurements on the same day, the last measurement 
prior to the first dose of study drug will be used as the Baseline vital sign value.  If there 
are multiple post-baseline measurements on the same day, average value will be used.
For systolic blood pressure, diastolic blood pressure and pulse, a listing of all subjects 
with any vital sign value meeting criteria for potentially clinically important values will be 
provided.  For each of these subjects, the whole course of the respective parameter will be 


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listed.  The number and percentage of subjects who have at least one value meeting 
criteria for potentially clinically important values will be provided for each selected vital 
sign parameter.
All analyses will be conducted in the Safety Population.
11.5
Analysis of ECG Parameters
No analyses of ECG will be done.
12.0
Pharmacokinetic Analysis
Pharmacokinetic analysis is not covered in this SAP.
13.0
Biomarkers Analysis
Biomarkers Analysis is not covered in this SAP.
14.0
Summary of Changes
14.1
Summary of Changes Between the Latest Version of 
Protocol and the Current SAP
In Section 10.1.2 of this SAP, the strategy for analysis of continuous endpoints was 
further refined.  The protocol had specified ANOVA with treatment group and 
stratification factor in the model.  The SAP now clarifies that for change from baseline in 
PSS a stratified van Elteren test will be used.  For other continuous variables, treatment 
groups will be compared using ANCOVA with treatment group, Baseline value, and 
stratification factor in the model.  This modification was done to align the study with the 
other studies in the Risankizumab Psoriasis development program.
In Section 10.3, NAPSI was added as a secondary endpoint to make optimal use of the 
data collected for NAPPA-CLIN assessments.


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15.0
Appendix
Appendix A.
PASI Calculation
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
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 degree.
Appendix B.
sPGA Calculation
The sPGA is a 5 point score ranging from 0 to 4, based on the physician's assessment of 
the average thickness, erythema, and scaling of all psoriatic lesions.
Erythema, induration and scaling of all psoriatic lesions are scored from 0 – 4.  The 
composite score is the arithmetic mean of erythema, induration and scaling.  The final 
sPGA is determined from this 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
Appendix C.
PPASI Calculation
The PPASI is a composite score and will be computed for each palm and sole, left and 
right and is derived from the sum of the scores for erythema (E), induration (I) and 
desquamation (D) multiplied by the score recorded for the extent of palm and sole area 
involved.  PPASI is calculated as follows:  (sum of scored for E + I + D)*Area *0.2 


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(location:  right palm) + (sum of scored for E + I + D)*Area *0.2 (location:  left palm) + 
(sum of scored for E+I+D)*Area *0.3(location:  right sole) + (sum of scores for 
E+I+D)*Area *0.3 (location:  left sole).  The range is 0 to 72.
Appendix D.
PSSI Calculation
The PSSI is a composite score derived from the sum of the scores for erythema, 
induration and desquamation multiplied by the score recorded for the extent of scalp area 
involved.  The range is 0 to 72.
Appendix E.
NAPPA-CLIN Calculation
The NAPPA-CLIN is calculated by summing the number of quadrants of the nail affected 
by a nail matrix psoriasis and number of quadrants of the nail affected by a nail bed 
psoriasis for the least and the worst affected nail for both hands and/or both feet.
Appendix F.
NAPSI Calculation
The NAPSI score is calculated by summing the scores of all the nails which for each nail 
are the sum of the nail matrix score and nail bed score.  Each of these is scored as 
0 = none, 1 = present in 1/4 nail, 2 = present in 2/4 nail, 3 = present in 3/4 nail, 4 = present 
in 4/4 nail.  The NAPSI score is calculated only if all questions in the CRF are completed.
Appendix G.
PSS Calculation
The total PSS score is calculated by summing the score of each question.  Each question 
of the PSS is scored as 0 = none to 4 = very severe.  If one or more of the items are 
missing, the total score will be set to missing.
Appendix H.
DLQI Calculation
The DLQI score is calculated by summing the score of each question.  Each question of 
the DLQI is scored as 0 = not at all, 1 = a little, 2 = a lot, 3 = very much, 0 = not relevant.  
For question no. 7, yes is scored as 3.  If one or more of the items are missing, the total 
score will be set to missing.


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Appendix I.
SF-36 Calculation
The SF-36 (version 2.0) PCS and MCS scores will be calculated as described in 'SF-36 
health survey update.  Spine, 2000,' and rounded to 0.1.  If one or more of the items are 
missing, the total score will be set to missing.
Appendix J.
PBI Calculation
PBI is the arithmetic mean of all rated benefits (PBQ items) weighted by the relative 
importance of each corresponding need item (PNQ). Each question of PBQ and PNQ is 
scored as 0 = not at all, 1 = somewhat, 2 = moderately, 3 = quite, 4 = very.
PBI = X
YTZ
∑
YTZ[
\
[
  Y]Z
\

If one or more of the items are missing, the total score will be set to missing.
Appendix K.
HADS Calculation
The HADS considers anxiety and depression.  Each question of HADS anxiety and 
depression is scored as 0 = best to 3 = worst.  The scores are summed up to a total score 
separately for anxiety and depression.  If one or more of the four items are missing, the 
total score will be set to missing.  These total scores are categorized as normal (0 – 7), 
borderline abnormal (8 – 10) and abnormal (11 – 21) for anxiety and depression.  If one or 
more of the items are missing, the total score will be set to missing.
Appendix L.
EQ-5D-5L Calculation
For calculation of a single index value the German EQ-5D-5L Crosswalk Value Set4 is 
used.  If one or more of the items are missing, the total score will be set to missing.


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Appendix M.
CASPAR Calculation
The score is only calculated as total score based on the sum of 6 questions, if the number 
of non-missing questions ≥ 3.  Allocate 2 points if there is an evidence of current personal 
psoriasis and allocate 1 point for the other questions if the response is "Yes."
If there is an evidence of current personal history the total score is calculated as sum of all 
questions other than question 3 (history of Ps).  Otherwise the total score is calculated 
based on the sum of all questions.
16.0
References
1.
AbbVie.  Risankizumab Investigator's Brochure Edition 1.  22 December 2016.
2.
Mrowietz U, Christophers E, Altmeyer P, et al.  Treatment of psoriasis with 
fumaric acid esters:  results of a prospective multicenter study.  Br J Dermatol.  
1998;138(3):456-60.
3.
Greenland S, Robins JM.  Estimation of a common effect parameter from sparse 
follow-up data.  Biometrics.  1985;41(1):55-68.
4.
Van Reenen M, Janssen M.  EQ-5D-5L user guide:  basic information on how to 
use the EQ-5D-5L instrument.  April 2015.  Version 2.1.
17.0
List of Tables, Figures, and Data Listings to Be 
Programmed
To be provided in a separate document.