Conditions: Psoriasis
Keywords: Generalized Pustular Psoriasis Erythrodermic Psoriasis risankizumab Japanese
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 18
Healthy volunteers: no

Brief summary:
The purpose of this study is to investigate the safety and efficacy of two different dose regimens of risankizumab for Japanese subjects with generalized pustular psoriasis (GPP) or erythrodermic psoriasis (EP).

Detailed description:
Safety and efficacy data through 14 December 2017 are included in the interim analysis, which was conducted after all participants completed the Week 28 visit or discontinued from the study.

Arms:
arm 1: Participants randomized to receive risankizumab 75 mg at Week 0, Week 4, and every 12 weeks up to Week 172. arm 2: Participants randomized to receive risankizumab 150 mg at Week 0, Week 4, and every 12 weeks up to Week 172.

Interventions: intervention 1: risankizumab
Intervention descriptions: intervention 1: risankizumab administered by subcutaneous injection

Protocol document:
Prot_001.pdf: 


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1.1
Protocol Amendment:  Summary of Changes
Protocol 
Date
Original
21 October 2016
The purpose of this amendment is to:
●
Update emergency contact information on Title Page.
Rationale:  Reflect correct AbbVie personnel information.
●
Revise verbiage in Section 3.2, Benefits and Risks, Section 5.1, Overall Study 
Design and Plan, Section 5.2.2, Exclusion Criteria, Section 5.3.1.1, Study 
Procedures and Appendix C, Study Activities, to add an optional PPD skin 
test.
Rationale:  To provide an alternative test if QuantiFERON-TB test is not 
available.
●
Revise verbiage in Section 5.1, Overall Study Design and Plan to add a more 
detailed description to the rescreening process.
Rationale:  To provide more details regarding the time frame and the 
assessments to allow for a patient to rescreen.
●
Revise verbiage in Section 5.2.4, Contraception Recommendations and 
Pregnancy Testing, to match Standard Safety Risk language.
Rationale:  To ensure that the elements match.
●
To clarify the time frame for follow-up TB testing in Section 5.3.1.1, Study 
Procedures and Appendix C, Study Activities.
Rationale:  To have the TB assessments annually and at EOT visit rather than 
Week 188 visit.
●
Revise the pre-dose time frame for PK and ADA blood sample collection from 
30 minutes prior to dosing to 60 minutes prior to dosing in Section 5.3.2.1, 
Collection of Samples for Analysis and Appendix C, Study Activities.
Rationale:  To provide a larger window of time for the assessment to be 
performed.
●
Add the source documents required for adjudication in Section 5.3.4, Safety
Variables.


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Rationale:  For Japan sites, the process and the list of source documents to be 
reported to CCVT adjudication committee should be mentioned in the 
protocol.
●
Revise and check the assessments in Appendix C, Study Activities, to correlate 
with the text in the body of the protocol.
Rationale:  To ensure that all the assessment time points accurately reflect the 
text in the protocol.
●
Revise the pregnancy testing language in Section 5.3.1.1, Study Procedures, 
Table 2, Laboratory Tests, and Appendix C, Study Activities.
Rationale:  To ensure consistency in pregnancy testing language for all 
females subjects and for female subjects of child-bearing potential.
●
Revise the text throughout the protocol to correct clerical errors and provide 
clarification.
An itemized list of all changes made to this protocol under this amendment can be found 
in Appendix J.


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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M15-988
Name of Study Drug:  ABBV-066
Phase of Development:  3
Name of Active Ingredient:  Risankizumab 
Date of Protocol Synopsis:  18 January 2017
Protocol Title:  A Phase 3, Randomized, Open-Label Study to Assess Efficacy and Safety of Two 
Different Dose Regimens of Risankizumab Administered Subcutaneously in Japanese Subjects with 
Generalized Pustular Psoriasis or Erythrodermic Psoriasis
Objective:  The objective of this trial is to assess the long-term safety and efficacy of two different dose 
regimens of risankizumab in Japanese subjects with generalized pustular psoriasis (GPP) or 
erythrodermic psoriasis (EP).
Investigator:  Multicenter
Study Sites:  Multi-centre trial in Japan
Study Population:  Adult male or female subjects with a diagnosis of generalized pustular psoriasis or 
erythrodermic psoriasis.
Number of Subjects to be Enrolled:  Approximately 16 subjects will be randomized, 8 with 
generalized pustular psoriasis and 8 with erythrodermic psoriasis.
Methodology:
This is a 172 week randomized, open-label, parallel design study with two substudies, Substudy GPP 
and Substudy EP for subjects with generalized pustular psoriasis and subjects with erythrodermic 
psoriasis, respectively.  In each Substudy, subjects will be randomized in 1:1 ratio to one of the two dose 
regimens of risankizumab.  Subjects in each group will receive either 150 mg or 75 mg of risankizumab 
at Week 0, 4 and every 12 weeks after.  From Week 16, subjects in the 75 mg group with no clinical 
response will be uptitrated to 150 mg.  The primary efficacy evaluation will be performed at Week 16 
and an assessment of long-term maintenance of response will be performed over 52 weeks.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:  
1.
Male or female subjects, age ≥ 20 years at screening.
2.
Signed and dated written informed consent prior to admission to the study in accordance with Good 
Clinical Practice (GCP) and local legislation.
For generalized pustular psoriasis
!
Have a diagnosis of generalized pustular psoriasis for at least 60 days prior to informed consent 
based on the diagnostic criteria of the Japanese Dermatological Association (JDA).  Subjects 
not fulfilling one of the diagnostic criteria i.e., "accompanying systemic symptoms including 
fever or malaise" at the time of screening can be entered.
!
Subjects with an erythema area with pustules accounting for ≥ 10% of the body surface area 
(BSA), and with a severity assessment criteria score (JDA total score) specified by the JDA of 
less than 14.
!
Must be candidates for systemic therapy or phototherapy for generalized pustular psoriasis, as 
assessed by the investigator. 


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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
For erythrodermic psoriasis
!
Have a diagnosis of erythrodermic psoriasis prior to informed consent.
!
Subjects with an inflammatory erythema area accounting for ≥ 80% of the BSA at screening 
and at the time of the first administration of the study drug.
!
Must be candidates for systemic therapy or phototherapy for erythrodermic psoriasis, as 
assessed by the investigator. 
Main Exclusion:
1.
Previous exposure to risankizumab.
2.
Currently enrolled in another investigational study or less than 30 days (from screening) since 
completing another investigational study (participation in observational studies is permitted).
For generalized pustular psoriasis
!
Subjects with active ongoing inflammatory diseases other than generalized pustular psoriasis 
that might confound trial evaluations according to investigator's judgment.
For erythrodermic psoriasis
!
Subjects with active ongoing inflammatory diseases other than erythrodermic psoriasis that 
might confound trial evaluations according to investigator's judgment.
!
Subject diagnosed with medication-induced or medication-exacerbated EP.
Investigational Product:
Risankizumab (ABBV-066):  75 mg pre-filled syringe, 90 mg/mL, 
0.83 mL dispensed volume, 0.87 mL fill volume
Doses:
Risankizumab (ABBV-066):  150 mg (2 syringes, 75 mg each) or 
75 mg (1 syringe) administered at Week 0, 4 and every 12 weeks
Mode of Administration:
Subcutaneous injection
Duration of Treatment:  172 weeks
Criteria for Evaluation:
Efficacy:
The primary endpoint for Substudy GPP is the proportion of subjects achieving a GPP Clinical 
Response, defined as at least "Slightly Improved" in the overall improvement rating from baseline, at 
Week 16, according to JDA total score for GPP.
The primary endpoint for Substudy EP is the proportion of subjects achieving an EP Clinical Response, 
defined as at least "Minimally Improved" in Clinical Global Impression-Global Improvement (CGI-GI) 
for EP at Week 16.
In addition, JDA total score and components as well as, Physician Global Assessment-Generalized 
pustular psoriasis (PGA-GPP), Clinical Global Impression-Global Improvement (CGI-GI), Psoriasis 
Area and Severity Index (PASI), BSA and Dermatology Life Quality Index (DLQI) will be assessed.
Pharmacokinetics and Immunogenicity:
Blood samples will be collected for measurement of risankizumab concentration and anti-drug antibody 
(ADA) during the treatment period and also at the follow up visit.


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Criteria for Evaluation (Continued):
Safety:
!
Adverse events (AE)
!
Serious adverse events (SAE)
!
Physical examination
!
Vital signs
!
Clinical laboratory values (hematology, clinical chemistry and urinalysis)
!
Local tolerability
Statistical Methods:
Descriptive statistics will be provided for all efficacy endpoints by treatment group for Substudy GPP 
and Substudy EP separately.
Efficacy:
The efficacy analyses will be performed on the Intent-to-treat and Safety populations, defined as all 
randomized subjects with at least one dose of study drug.  No formal hypothesis testing will be 
conducted.  Summary statistics will be provided.
Primary Endpoint
The primary endpoint for Substudy GPP is the proportion of subjects achieving a GPP Clinical 
Response, defined as at least "Slightly Improved" in the overall improvement rating from baseline, at 
Week 16, according to JDA total score for GPP.
The primary endpoint for Substudy EP is the proportion of subjects achieving an EP Clinical Response, 
defined as at least "Minimally Improved" in CGI-GI for EP at Week 16.
Secondary Endpoint(s)
For generalized pustular psoriasis:
!
Proportion of subjects achieving a GPP Clinical Response, defined at least "Slightly Improved" 
in the overall improvement rating from baseline, at Week 52, according to JDA total score for 
GPP at Week 52
!
Proportion of subjects achieving ≥ 90% reduction from baseline Psoriasis Area Severity Index 
(PASI) score (PASI 90) at Week 16
!
Proportion of subjects achieving PASI 90 at Week 52
For erythrodermic psoriasis:
!
Proportion of subjects achieving an EP Clinical Response, defined at least "Minimally 
Improved" in CGI-GI for EP at Week 52 
!
Proportion of subjects achieving PASI 90 at Week 16
!
Proportion of subjects achieving PASI 90 at Week 52


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Statistical Methods (Continued):
Pharmacokinetics (PK) and Immunogenicity:
Risankizumab plasma concentrations will be determined.  Descriptive statistics will be calculated for 
each sampling time.  PK and ADA data may be combined with data from other studies and analyzed 
using a mixed-effects modeling approach.  This analysis will estimate the population central value and 
the empirical Bayesian estimates of the individual values for risankizumab apparent clearance (CL/F) 
and volume of distribution (Vss/F).  Additional parameters may be estimated if useful in the 
interpretation of the data.  Relationships between exposure and clinical observations (efficacy or safety 
variables of interest) may be explored.
The number and percentage of subjects with ADA will be calculated.
Safety:
All AEs, SAEs, AEs leading to discontinuation, and pre-specified AEs of special interest will be 
collected during the study.  A treatment-emergent AE (TEAE) is defined as an event with onset or 
worsening after the first study dose of risankizumab and within 15 weeks after the last risankizumab 
injection.  The number and percentages of subjects experiencing TEAE will be tabulated using the 
Medical Dictionary for Drug Regulatory Activities (MedDRA®) system organ class and preferred term.  
Summaries (including percentages and event per 100 subject-years) of SAEs, deaths, AEs leading to 
discontinuation from the study, and pre-specified AEs of special interest will be provided as well.  Mean 
change in laboratory variables, and vital signs variables will be summarized.  For selected parameters, a 
listing of all subjects with clinically significant laboratory values, or vital sign determinations will be 
provided.  Shift tables for changes from baseline according to the normal range will also be provided.
The sample size of this study is not estimated based on powering for any hypothesis testing.  There are 
only approximately 1600 and 40000 Japanese subjects with generalized pustular psoriasis and 
erythrodermic psoriasis respectively, thus finding subjects to participate in the trial will be difficult.  
Therefore, the sample size is determined based on feasibility.  In total, at least 16 subjects will be 
enrolled:  at least 8 subjects for GPP and EP separately.


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1.3
List of Abbreviations and Definition of Terms
Abbreviations
ADA
Anti-drug antibody
AE
Adverse event
AESI
Adverse event of special interest
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
BI
Boehringer Ingelheim
BSA
Body surface area
CASPAr
ClASsification of Psoriatic Arthritis
CCVT
Cardiac, Cerebrovascular and Thrombotic Events
CGI-GI
Clinical Global Impression-Global Improvement
CL/F
Apparent total clearance
CRF
Case report form
CRP
C-reactive protein
DILI
Drug induced liver injury
DNA
Deoxyribonucleic acid
DLQI
Dermatology Life Quality Index
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
EOT
End of treatment
EP
Erythrodermic Psoriasis
EudraCT
European Union Drug Regulatory Authority Clinical Trials
GCP
Good Clinical Practice
GPP
Generalized Pustular Psoriasis
GMP
Good Manufacturing Practice
HIV
Human Immunodeficiency Virus
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IL
Interleukin
IRB
Institutional Review Board
IRT
Interactive response system


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ISF
Investigator site file
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
JDA
Japanese Dermatological Association
mAb
Monoclonal antibody
MACE
Major Adverse Cardiac Events
MedDRA
Medical Dictionary for Drug Regulatory Activities
PASI
Psoriasis Area and Severity Index
PD
Premature discontinuation
PGA-GPP
Physician's Global Assessment of Generalized Pustular Psoriasis
PK
Pharmacokinetics
PMDA
Pharmaceutical and Medical Devices Agency
PRO
Patient reported outcome
RNA
Ribonucleic acid
SAE
Serious Adverse Event
SUSAR
Suspected Unexpected Serious Adverse Reactions 
TA MD
Therapeutic Area Medical Director
TB
Tuberculosis
TEAE
Treatment –emergent adverse events
TNF
Tumor necrosis factor
ULN
Upper limit of normal
WBC
White blood cell count
VSS/F
Volume of distribution


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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 ................................................................ 10
3.0
Introduction......................................................................... 14
3.1
Differences Statement .......................................................................... 15
3.2
Benefits and Risks................................................................................ 15
4.0
Study Objective ................................................................... 17
5.0
Investigational Plan.............................................................17
5.1
Overall Study Design and Plan:  Description ........................................ 17
5.2
Selection of Study Population............................................................... 22
5.2.1
Inclusion Criteria.................................................................................. 22
5.2.2
Exclusion Criteria................................................................................. 24
5.2.3
Prior and Concomitant Therapy............................................................ 25
5.2.3.1
Prohibited Therapy............................................................................... 26
5.2.3.2
Rescue Therapy.................................................................................... 28
5.2.4
Contraception Recommendations and Pregnancy Testing ..................... 28
5.3
Efficacy, Pharmacokinetic and Safety Assessments/Variables .............. 29
5.3.1
Efficacy and Safety Measurements Assessed ........................................ 29
5.3.1.1
Study Procedures.................................................................................. 29
5.3.2
Drug Concentration Measurements....................................................... 35
5.3.2.1
Collection of Samples for Analysis....................................................... 35
5.3.2.2
Handling/Processing of Samples........................................................... 36
5.3.2.3
Disposition of Samples......................................................................... 36
5.3.2.4
Measurement Methods ......................................................................... 37
5.3.3
Efficacy Variables................................................................................ 37
5.3.4
Safety Variables ................................................................................... 39
5.3.5
Pharmacokinetic Variables ................................................................... 40
5.4
Removal of Subjects from Therapy or Assessment ............................... 41
5.4.1
Discontinuation of Individual Subjects ................................................. 41


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5.4.2
Discontinuation of Entire Study............................................................ 42
5.5
Treatments ........................................................................................... 42
5.5.1
Treatments Administered...................................................................... 42
5.5.2
Identity of Investigational Products ...................................................... 42
5.5.2.1
Packaging and Labeling........................................................................ 43
5.5.2.2
Storage and Disposition of Study Drug................................................. 43
5.5.3
Method of Assigning Subjects to Treatment Groups ............................. 44
5.5.4
Selection and Timing of Dose for Each Subject .................................... 44
5.5.5
Blinding ............................................................................................... 45
5.5.5.1
Blinding of Investigational Product ...................................................... 45
5.5.6
Treatment Compliance ......................................................................... 45
5.5.7
Drug Accountability ............................................................................. 45
5.6
Discussion and Justification of Study Design........................................ 46
5.6.1
Discussion of Study Design and Choice of Control Groups .................. 46
5.6.2
Appropriateness of Measurements........................................................ 46
5.6.3
Suitability of Subject Population .......................................................... 47
5.6.4
Selection of Doses in the Study ............................................................ 47
6.0
Complaints........................................................................... 48
6.1
Medical Complaints ............................................................................. 48
6.1.1
Definitions ........................................................................................... 49
6.1.1.1
Adverse Event...................................................................................... 49
6.1.1.2
Serious Adverse Events........................................................................ 50
6.1.1.3
Adverse Events of Special Interest........................................................ 51
6.1.2
Adverse Event Severity ........................................................................ 52
6.1.3
Relationship to Study Drug................................................................... 52
6.1.4
Adverse Event Collection Period.......................................................... 53
6.1.5
Adverse Event Reporting...................................................................... 53
6.1.6
Pregnancy............................................................................................. 55
6.1.7
Supplemental Safety CRFs ................................................................... 56
6.2
Product Complaint................................................................................ 56
6.2.1
Definition............................................................................................. 56
6.2.2
Reporting ............................................................................................. 57
7.0
Protocol Deviations ............................................................. 57


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8.0
Statistical Methods and Determination of Sample 
Size ....................................................................................... 58
8.1
Statistical and Analytical Plans............................................................. 58
8.1.1
Analysis Population.............................................................................. 59
8.1.2
Null and Alternative Hypotheses .......................................................... 59
8.1.3
Planned Analyses ................................................................................. 59
8.1.3.1
Demographics and Baseline Characteristics.......................................... 60
8.1.4
Primary Endpoint Analyses .................................................................. 60
8.1.5
Secondary Endpoint Analyses .............................................................. 60
8.1.6
Safety Analyses.................................................................................... 60
8.1.7
Pharmacokinetic and Exposure-Response Analysis .............................. 61
8.1.8
Interim Analyses .................................................................................. 62
8.1.9
Handling of Missing Data..................................................................... 62
8.2
Determination of Sample Size .............................................................. 63
8.3
Randomization Methods....................................................................... 63
9.0
Ethics.................................................................................... 63
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ......................................................................................... 63
9.2
Ethical Conduct of the Study................................................................ 64
9.3
Subject Information and Consent.......................................................... 64
9.3.1
Informed Consent Form and Explanatory Material ............................... 65
9.3.2
Revision of the Consent Form and Explanatory Material ...................... 65
10.0
Source Documents and Case Report Form 
Completion ..........................................................................65
10.1
Source Documents................................................................................ 65
10.2
Case Report Forms............................................................................... 66
11.0
Data Quality Assurance ...................................................... 67
12.0
Use of Information ..............................................................67
13.0
Completion of the Study ..................................................... 67
14.0
Investigator's Agreement....................................................69
15.0
Reference List......................................................................70


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List of Tables
Table 1.
Restricted Medications ......................................................................... 27
Table 2.
Laboratory Tests................................................................................... 33
Table 3.
Description of Test Product Risankizumab ........................................... 43
List of Figures
Figure 1.
Trial Design ......................................................................................... 18
Figure 2.
Adverse Event Collection..................................................................... 53
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.......................................... 71
Appendix B.
List of Protocol Signatories .................................................................. 73
Appendix C.
Study Activities.................................................................................... 74
Appendix D.
Severity Assessment Criteria Score ...................................................... 78
Appendix E.
Psoriasis Area and Severity Index (PASI)............................................. 80
Appendix F.
Diagnosis and Assessments for Subjects with Psoriatic Arthritis........... 83
Appendix G.
Clinical Global Impression-Global Improvement (CGI-GI) .................. 84
Appendix H.
Patient Reported Outcomes .................................................................. 85
Appendix I.
PGA Scale for Generalized Pustular Psoriasis....................................... 87
Appendix J.
Protocol Amendment:  List of Changes ................................................ 88


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3.0
Introduction
Generalized pustular psoriasis (GPP) is a rare and severe skin disorder that presents with 
flares of widespread sterile pustules on a background of red and tender skin.  It may in 
some cases require subject's hospitalization in intensive burn units and in rare cases be 
fatal.
There is no cure-all treatment for GPP, and as such, the mortality rate is high.
Erythrodermic psoriasis (EP) is a generalised erythema.  It is also a very severe skin 
condition that can be fatal and difficult to treat.  It is marked by widespread involvement 
(> ¾ of the body surface area) with redness and scaling and can be accompanied by 
systemic manifestations such as fever, chills, or malaise.  It can be the first presentation of 
a subject's psoriasis or can result after many years of psoriasis, sometimes as the result of 
a poor control of subject's existing psoriasis.  Erythrodermic psoriasis should be 
distinguished as much as possible from cutaneous manifestation of abrupt systemic 
medication withdrawal or response to malignancy.
Drug Profile
For a more detailed description of the risankizumab profile please refer to the current 
Investigator's Brochure.
Rationale for Performing the Trial
This study will randomize from two subtypes of subjects:  Generalized pustular psoriasis 
(GPP) and erythrodermic psoriasis (EP).
Interleukin (IL)-23 plays a key role in the pathophysiology of psoriasis through induction 
and maintenance of Th-17 type cells that secrete inflammatory cytokines.  Risankizumab 
is a humanized monoclonal antibody (mAB) that specifically neutralizes the IL-23 axis.  
About 10% of subjects with GPP have a preceding history of psoriasis, in which there are 


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persistent, circumscribed, red and scaly plaques.  In considering with action of mechanism 
of risankizumab, this medicine might be effective for GPP and EP.
 
  
 
 
  
 
therefore the aim of this trial is to obtain the efficacy, pharmacokinetic, safety, and 
tolerability data during a 52-week treatment period with two different dose regimens of 
risankizumab in Japanese subjects with GPP or EP.
The current trial is being performed to assess the safety and efficacy of risankizumab to 
support registration in Japan of subjects with GPP or EP.
3.1
Differences Statement
This study is specifically conducted to fulfill a requirement from the Pharmaceuticals and 
Medical Devices Agency (PMDA) in Japan and is focused on the most severe forms of 
psoriasis, for which the medical need is particularly high.
3.2
Benefits and Risks
Participation in this study may help to generate future benefit for larger groups of subjects 
with psoriasis if risankizumab proves to be successful in treating this disease.  In Phase 1 
and Phase 2 studies, risankizumab has been studied in approximately 200 subjects with 
moderate to severe plaque psoriasis.  In these studies, the majority of subjects receiving 
risankizumab achieved 90% improvement of their disease.  The most common adverse 
events (AE) reported in these trials were mild symptoms of the upper respiratory tract, 
including nasal stuffiness, sore throat, and influenza, and headache, that showed no dose 
dependency.  These events were not considered to be related to drug treatment.  Local 


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reactions following subcutaneous administration of risankizumab were uncommon, and 
limited to redness, swelling or induration at the injection site.
As with any immune modulating agent, 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 clinically important active infection will 
not be included in the study.  Subjects with positive QuantiFERON® tuberculosis (TB) 
test or a positive PPD (purified protein derivative) skin test must fulfill entry criteria as 
specified in Section 5.2.2, item 5, prior to receiving risankizumab.  There is not enough 
information at this time to rule out a risk of cancer with risankizumab, but this risk is 
considered small with this type of compound as experience with the anti-IL-12/23 mAb 
ustekinumab has not suggested significant risk for cancer/serious infection.  Subjects will 
be monitored for signs and symptoms of malignancy at each visit.
Increases in major adverse cardiovascular events (MACE) including myocardial 
infarction, cerebrovascular accident, and cardiovascular death, reported initially with 
anti-IL-12/23 agents, such as ustekinumab, have not been observed in longer term studies.  
While the likelihood of increased MACE is small, all suspected cardiovascular events 
(serious or non-serious) observed in this study will be adjudicated by an independent 
Cardiac, Cerebrovascular and Thrombotic Events (CCVT) Adjudication Committee.
The subjects will be administrated either 150 mg or 75 mg dose of risankizumab treatment 
during the clinical trial.  From Week 16, subjects will be uptitrated to 150 mg if they have 
not achieved a clinical response.
Although rare, a potential for drug-induced liver injury (DILI) is under constant 
surveillance by sponsors and regulators.  Therefore, this trial requires timely detection, 
evaluation, and follow-up of laboratory alterations in selected liver laboratory parameters 
to ensure subjects' safety.
In conclusion, the benefit-risk profile is considered appropriate for this stage of clinical 
development.


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4.0
Study Objective
The primary objectives of this study are to investigate the safety and efficacy of
two different dose regimens of risankizumab for Japanese subjects with GPP or EP.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This trial is a randomized, open-label study of two different dose regimens of 
risankizumab, 150 mg (2 syringes, 75 mg each) or 75 mg (1 syringe) at Week 0, 4 and 
every 12 weeks in two populations (subjects with GPP and with EP).  Starting after the 
Week 16 visit, subjects on 75 mg may increase dosage to 150 mg.  In total, at least 
16 subjects, 8 with generalized pustular psoriasis and 8 with erythrodermic psoriasis will 
be randomized in this trial.
Subjects are included in the trial once they have signed the informed consent.  Subjects 
suitable after screening will be eligible to participate.


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Figure 1.
Trial Design
Visit Schedule
All subjects are to adhere to the visit schedule as specified in the Appendix C.  Each visit 
date (with its window) is to be counted from Day 1.  If any visit has to be rescheduled, 
subsequent visits should follow the original visit date schedule.  Additional visits for the 
purpose of re-testing of laboratory parameters or AE monitoring may be included as 
deemed necessary by the investigator.
Details of Trial Procedures at Selected Visits
Study procedures to be performed at each visit are listed in Appendix C and the respective 
protocol sections.  Refer to Section 5.3.1.1 for explanations of procedures.  Additional 
details on procedures at selected visits are provided below.


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Measurement of vital signs should precede blood sampling and be assessed pre-dose at all 
dosing visits.
Patient reported outcomes (PRO)s should be completed by the subject on his/her own 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.  At Visit 2 these 
questionnaires should be obtained before having the subject randomized.
Screening and Run-In Period(s)
No trial procedures should be done until the subject has consented to taking part in the 
trial.
Once consented, the subject is considered to be enrolled in the trial and has started 
screening.  The subject number should be recorded on the enrollment log and registered in 
the Interactive Response System (IRT) as a screened subject.
The Screening Period (Visit 1) is from Day –42 to Day –1.  Visit 1 procedures may be 
extended to two physical visits, if needed.  Re-screening will be permitted.
Subjects that initially screen-fail for the study may be permitted to re-screen one time 
following re-consent and:
●
a repeat of all screening procedures is needed with the possible exceptions 
noted below.  
●
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 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 5.2.2 and 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-


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screening within the 42 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.
Infection Screening
Refer to exclusion criteria Section 5.2.2 with study participation directive for subjects 
with a positive result for PPD or QuantiFERON® for TB, Hepatitis B, Hepatitis C, and 
Human Immunodeficiency Virus (HIV).
Medical History:
Cardiovascular and risk factors will be collected and reported in the Medical History 
electronic case report form (eCRF) page.
Baseline Conditions
Chronic diseases, current observable conditions, any new clinically relevant findings 
discovered from the physical examination, electrocardiogram (ECG), safety laboratory 
tests, and any condition requiring therapy (excluding psoriasis) will be reported on the 
Baseline Condition eCRF Page.
History of Psoriatic Arthritis
At Visit 1, all subjects at all sites will be evaluated via CASPAr (ClASsification of 
Psoriatic Arthritis) criteria for history of psoriatic arthritis.
Interactive Response System (IRT)
All subjects who are screened must be registered with IRT.  If the subject must be 
designated as a screen failure, IRT should be notified as soon as possible and within the 
Screening Period.  Details of IRT procedures can be found in the IRT manual located in 
the Investigator Site File (ISF).


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For the comprehensive list of the trial procedures required at the Screening Visit (Visit 1) 
please refer to Appendix C.
Treatment Period(s)
The treatment period is from Visit 2 to EOT (End of Treatment) Visit.
Visits 2, 4, 6, 8, 10, 12, 16, 20, end of treatment (EOT), Week 184 follow-up visit and 
Week 188 follow-up visit will be performed in fasted state (8 hours no food and only 
water).  If a subject comes in non-fasted where a fasting condition is required, the visit 
should be performed, the non-fasted condition documented on the laboratory requisition, 
and the subject reminded about the expected conditions.  At Visits 3, 5, 7, 9, 11, 13, 14, 
15, 17, 18, 19, 21, only white blood cell count (WBC), serum C-reactive protein (CRP) 
and serum albumin ("targeted" lab) will be collected and fasting is not required for these 
labs.
Urine pregnancy testing for all woman of child-bearing potential will be conducted on-site 
prior to every dosing and must be negative to further treat the subject.  A positive urine 
test must be confirmed with a serum pregnancy test.
Randomization via IRT and administration of study medication should be the last activity 
at Visit 2.
Venipuncture (i.e., safety laboratories, PK, anti-drug antibody [ADA]), should be the last 
procedure prior to study drug administration.
Follow Up Period and Trial Completion
For all randomized subjects termination of trial medication and trial completion must be 
recorded on the corresponding eCRFs.
Early Treatment and Trial Termination 
Subjects who prematurely discontinue (PD) treatment prior to the planned Appendix C
visit schedule will complete EOT visit procedures instead of the planned treatment period 


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visit.  If study medication is discontinued, every effort should be made to have the subject 
continue in the trial and complete all of the follow remaining trial and follow up visits.  If 
a subject cannot or will not continue in the trial, these subjects should be registered as 
withdrawn/discontinued in IRT.  These subjects should be registered as withdrawn in IRT 
and return to the clinic for Week 188 Follow-Up visit 16 weeks after last dose of study 
medication.
Trial Completion
Subjects who finish the randomized treatment period will return to the clinic for 
Week 184 Follow-Up Visit and Week 188 Follow-Up Visit.  Completion is defined as a 
subject having completed the Week 188 Follow-Up visit.
5.2
Selection of Study Population
5.2.1
Inclusion Criteria
Subjects must have generalized pustular psoriasis or erythrodermic psoriasis.
General Inclusion Criteria
1.
Male or female subjects, age ≥ 20 years at screening.
2.
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)
OR
●
Women of Childbearing Potential (WOCBP) should be practicing at least 
one protocol specified method of birth control (Section 5.2.4) starting on Study 
Day 1 (or earlier) through at least 16 weeks after the last dose of study drug.


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3.
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-child bearing potential (either postmenopausal or permanently 
surgically sterile as defined above) at screening do not require pregnancy testing at 
study Day 1.
4.
Signed and dated written informed consent prior to admission to the study in 
accordance with Good Clinical Practice and local legislation.
Disease Specific Inclusion Criteria 
For Generalized Pustular Psoriasis
5.
Have a diagnosis of generalized pustular psoriasis for at least 60 days prior to 
informed consent based on the diagnostic criteria of the Japanese Dermatological 
Association (JDA).  Subjects not fulfilling one of the diagnostic criteria 
i.e., "accompanying systemic symptoms including fever or malaise" at the time of
screening can be entered.
6.
Subjects with an erythema area with pustules accounting for ≥ 10% of the body 
surface area (BSA), and with a severity assessment criteria score (JDA total score) 
specified by the  JDA of less than 14 (Appendix D).
7.
Must be candidates for systemic therapy or phototherapy for generalized pustular 
psoriasis, as assessed by the investigator.
For Erythrodermic Psoriasis
8.
Have a diagnosis of erythrodermic psoriasis prior to informed consent.
9.
Subjects with an inflammatory erythema area accounting for ≥ 80% of the BSA at 
screening and at the time of the first administration of the study drug.
10.
Must be candidates for systemic therapy or phototherapy for erythrodermic 
psoriasis, as assessed by the investigator.


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5.2.2
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following 
criteria:
General Exclusion Criteria
1.
Previous exposure to risankizumab.
2.
Currently enrolled in another investigational study or less than 30 days (from 
screening) since completing another investigational study (participation in 
observational studies is permitted),
3.
Use of any restricted medication as specified in Table 1 or any drug considered 
likely to interfere with the safe conduct of the study.
4.
Major surgery performed within 12 weeks prior to assignment or planned within 
12 months after baseline (e.g., hip replacement, aneurysm removal, stomach 
ligation).
5.
Known chronic or relevant acute infections including HIV, viral hepatitis and/or 
tuberculosis as defined by either a positive QuantiFERON® TB test or a positive 
PPD (purified protein derivative) skin test.  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.
6.
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.
7.
Evidence of a current or previous disease, medical condition (including chronic 
alcohol or drug abuse) other than psoriasis, surgical procedure (i.e., organ 
transplant), medical examination finding (including vital signs and ECG), or 
laboratory value at the Screening Visit outside the reference range that, in the 
opinion of the investigator, is clinically significant and would make the study 


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participant unreliable to adhere to the protocol or to complete the trial, compromise 
the safety of the subject, or compromise the quality of the data.
8.
History of allergy/hypersensitivity to a systemically administered biologic agent or 
its excipients.
9.
Female subject who is pregnant, breastfeeding or is considering becoming pregnant 
during the study or for approximately 16 weeks after the last dose of study drug.
10.
Previous enrollment in this trial.
Disease Specific Exclusion Criteria
For Generalized Pustular Psoriasis
11.
Subjects with active ongoing inflammatory diseases other than generalized pustular 
psoriasis that might confound trial evaluations according to investigator's 
judgment.
For Erythrodermic Psoriasis
12.
Subjects with active ongoing inflammatory diseases other than erythrodermic 
psoriasis that might confound trial evaluations according to investigator's 
judgment.
13.
Subject diagnosed with medication-induced or medication-exacerbated EP.
5.2.3
Prior and Concomitant Therapy
Any biologic or systemic medication or vaccine for psoriasis (including over-the-counter 
or prescription medicines, vitamins and/or herbal supplements) that the subject has or is 
receiving at the time of enrollment, 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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Complete systemic psoriasis medication history, whether biologic or not, and including 
phototherapy will be captured as well as topical psoriasis medicine use should be captured 
for the past 5 years.
Stable doses of concomitant therapies for chronic conditions, for which neither the 
condition nor the treatment are judged to exclude the subject from participation are 
permissible.  All concomitant medications should be carefully evaluated by the 
investigator and the AbbVie TA MD should be contacted if there are any questions 
regarding concomitant or prior therapy(ies).
5.2.3.1
Prohibited Therapy
Uses of the following therapies are prohibited from administration in the time periods 
specified.


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Table 1.
Restricted Medications
Medication or Class of Medications
Restriction Duration
(Through Week 188 Follow-Up Visit)
secukinumab (Cosentyx®), biologics targeting IL-12 
except ustekinumab), IL-17 (except ixekizumab and 
brodalumab), and/or IL-23 directly
26 weeks prior to randomization
ustekinumab (Stelara®), Tumor Necrosis Factor 
(TNF)-α inhibitors except infliximab, adalimumab and 
etanercept
12 weeks prior to randomization
granulocyte and monocyte adsorptive apheresis (GMA)
12 weeks prior to randomization
brodalumab, ixekizumab 
4 months prior to randomization
infliximab (Remicade®)
8 weeks prior to randomization
adalimumab (Humira®)
2 weeks prior to randomization
etanercept (Enbrel®) live virus vaccinations
6 weeks prior to randomization
Tofacitinib, apremilast
30 days prior to randomization
any investigational device or product (excludes 
psoriasis products)
30 days prior to randomization
investigational drug for psoriasis (biologics and non-
biologics) 
12 weeks prior to randomization, or five half-
life if longer
other systemic immunomodulating treatments 
(e.g., methotrexate, cyclosporine A, corticosteroids,a
cyclophosphamide)
other systemic psoriasis treatments (e.g., retinoids, 
fumarates, any other drug known to possibly benefit 
psoriasis)
These therapies have to be unchanged for at 
least 4 weeks prior to randomization, and any 
change in the dose should be avoided.
After Week 16, only dose decreasing will be 
permitted.  Cyclosporine A and systemic 
corticosteroid will be tapered off after 
confirmation of a clinical improvement in the 
opinion of the investigator.
phototherapy (e.g., PUVA)
4 weeks prior to assignment
phototherapy (e.g., UVA, UVB)
2 weeks prior to assignment
topical treatment for psoriasis or any other skin 
condition (e.g., corticosteroids,b vitamin D analogues, 
vitamin A analogues, retinoids, salicylvaseline, salicylic 
acid, lactic acid, tacrolimus, tar, urea,α-hydroxy acid 
[fruit acids])
2 weeks prior to randomization
a.
No restriction on corticosteroids with only a topical effect (e.g., inhalative corticosteroids to treat asthma or 
corticosteroid drops used in the eye or ear).
b.
Exception:  Topical steroids of mild potency such as locoid or weak potency such as prednisolone for use on the 
face, axilla, and/or genitalia with a restriction of use within 24 hours prior to trial visit in which PASI is assessed.


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5.2.3.2
Rescue Therapy
There are no special emergency procedures to be followed.
In the event that a subject experiences an intolerable worsening of GPP or EP, as deemed 
by the investigator, during the course of the trial the subject will be discontinued from the 
trial to receive rescue treatment.
In case of adverse events in need of treatment, symptomatic therapy according to 
investigator judgment will be permitted.  All concomitant and/or rescue therapies will be 
recorded on the appropriate pages of the eCRF.
5.2.4
Contraception Recommendations and Pregnancy Testing
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 16 weeks after the last dose of 
study drug.
Combined (estrogen and progestogen containing) hormonal contraception (oral) 
associated with the inhibition of ovulation, initiated at least 1 month prior to Study Day 1.
Progestogen-only hormonal contraception (oral) associated with inhibition of ovulation, 
initiated at least 1 month prior to Study Day 1.
Bilateral tubal occlusion/ligation.
Vasectomized partner(s), provided the vasectomized partner has received medical 
assessment of the surgical success and is the sole sexual partner of the WOCBP trial 
participant.
Intrauterine device (IUD).
Intrauterine hormone-releasing system (IUS).


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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, Pharmacokinetic 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.
5.3.1.1
Study Procedures
Informed Consent
The subject will sign and date a study specific, Independent Ethics Committee 
(IEC)/Independent 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 both the Screening and the Week 0 visit.
Demographics
The subject's demographic data, including date of birth, gender, race, ethnicity, and 
disease status will be collected at the Screening Visit.
Physical Examination
Complete and targeted physical examinations will be performed at visits as described in 
Appendix C.  Complete physical examination will include general appearance as well as 


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evaluation of all relevant organ systems.  Targeted physical examination will include vital 
signs assessment and evaluation of organ systems associated with AE(s) symptoms or 
laboratory abnormalities.
Physical examination findings that are related to subject's medical history will be captured 
on the appropriate medical history eCRF.
Vital Signs
Vital sign assessment includes temperature, pulse rate, sitting blood pressure, and 
respiratory rate, after subjects have been seated comfortably for at least 5 minutes.
Measurement of vital signs should precede blood sampling and be assessed pre-dose at all 
dosing visits.  At Visit 2 and Visit 3 additional vital signs will be taken at 5 minutes 
post-dose and 60 minutes post-dose.
Subjects should be closely monitored for signs and symptoms of hypersensitivity 
reactions for approximately 2 hours after the first dose administered and 1 hour following 
all other doses of study drug.  Hypersensitivity reactions should be treated according to 
medical standards.  Pre-medications for further injections might be considered and will be 
agreed on between investigator and AbbVie TA MD.
Body Weight and Waist Circumference
Waist circumference measurements should be made around a subject's bare midriff, after 
the subject exhales while standing without shoes and with both feet touching and arms 
hanging freely.  The tape should be placed perpendicular to the long axis of the body and 
horizontal to the floor and applied with sufficient tension to conform to the measurement 
surface.  Waist circumference should be determined by measuring the midpoint between 
the lowest rib and the iliac crest.
Body weight measurements should be done on the same scale for each subject.  In order to 
get comparable body weight values, it should be performed in the following way:


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●
fasting (except for the Screening Visit)
●
after the urine sampling (body weight after bladder voiding)
●
shoes and coat/jackets should be taken off
●
pockets should be emptied of heavy objects (i.e., keys, coins, etc.)
Electrocardiogram
The 12-lead ECGs will be performed as scheduled in Appendix C.
The ECG 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.
The ECG may be repeated for quality reasons and the repeat used for analysis.  Additional 
ECGs may be collected for safety reasons.  Clinically relevant, abnormal findings will be 
reported as AEs.
Information about the details of ECG collection and the parameters assessed will be 
provided in the ISF.
The electronic version of the ECG is regarded as source data.
Pregnancy Testing
A serum pregnancy test will be performed for all female subjects at the Screening Visit.  
A urine pregnancy testing will be done on all women of child-bearing potential prior to 
administration of study drug at all dosing visits and at each Follow-Up Visit.  Additional 
serum pregnancy testing will occur in case of a positive urine test result at any of the visits 
and must be negative to further treat the subject.
Females of non-childbearing potential (either postmenopausal or permanently surgically 
sterile as defined in Section 5.2.4) do not require pregnancy testing after screening.


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Safety Laboratory Parameters
The laboratory tests listed in Table 2 will be performed by the central laboratory service 
provider at Visits 1, 2, 4, 6, 8, 10, 12, 16, 20, EOT and at Week 188 follow-up visit 
("complete" lab).  At Visits 3, 5, 7, 9, 11, 13, 14, 15, 17, 18, 19, 21, only WBC, serum 
CRP and serum albumin will be collected ("targeted" lab).  A local laboratory may be 
used for selected tests in exceptional cases.  Subjects should be fasting for at least 8 hours 
prior to the blood sample being taken at the "complete" visits, except for screening (see 
Appendix C).
Instructions regarding sample collection, sample handling/processing and sample shipping 
are provided in the Laboratory Manual in the ISF.  For time points of laboratory sampling, 
see Appendix C.
Laboratory results (i.e., all safety laboratory and clinical laboratory data relevant for 
current clinical practice) of the subjects will be available in real time to the respective 
investigator (via laboratory reports) and to the sponsor (via the central laboratory website) 
and selected abnormal laboratory alerts will be flagged to the site and sent to sponsor in 
real time.
A clinically relevant value may be either in or outside the reference range.  Clinically 
relevant abnormal laboratory test results must be confirmed using an unscheduled visit 
laboratory kit and should be repeated until normalization or stabilization or until an 
alternative explanation has been found.  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 adverse events.


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Table 2.
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 (relative count)
Eosinophils (relative count)
Basophils (relative count)
Monocytes (relative count)
Lymphocytes (relative 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 Transferase (GGT/γ-GT)
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate


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Table 2.
Laboratory Tests (Continued)
Category
Test Name
Substrates
Glucose
BUN
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Albumin
C-Reactive Protein (CRP) (high sensitivity)
Cholesterol, total
Triglycerides
LDL-Cholesterol
HDL-Cholesterol
Urine Pregnancy test (only for female subjects of 
childbearing potential)d
Human Chorionic Gonadotropin in the urine
Serum Pregnancy test (in all female subjects at 
screening or if urine pregnancy test is positive)
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
Albumin (quantitative)


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Table 2.
Laboratory Tests (Continued)
Category
Test Name
Infection screening 
Hepatitis B Surface Antigen (qualitative)a
Hepatitis B Surface Antibody (qualitative)a
Hepatitis B Core Antibodies total (qualitative)a
Hepatitis B Virus DNA (quantitative)a,b
Hepatitis C Antibodies (qualitative)a
Hepatitis C Virus RNA (quantitative)a
HIV-1, and HIV-2 Antibody (qualitative)a
PPD or QuantiFERON®-TBc
a.
Hepatitis B, Hepatitis C and HIV testing will be performed at screening.
b.
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 trial.  In these cases, HBV DNA level will be 
monitored at least every 6 months.  If positive, the subject's treatment will be discontinued.  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 trial.  In these cases, HCV RNA level will be monitored at least every 
6 months.  If positive, the subject's treatment will be discontinued.
c.
TB testing will be performed at screening, Visit 12, 16, 20 and Week 184. 
d.
Urine pregnancy test will be performed at all dosing visits.
Other Safety Parameters
Local Tolerability
Local tolerability at the administration site of the subcutaneous injection will be assessed 
by the investigator according to "swelling," "induration," "heat," "redness," "pain," or 
"other findings" at the specified visits as noted in Appendix C.  This assessment should be 
done pre-dose.
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 at the study 
visits at the time points specified in Appendix C by venipuncture into appropriately 
labeled collection tubes.  The timing of blood collection will take priority over all other 


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scheduled study activities except for ECG, vital signs, and dosing.  Blood samples for the 
PK assay should be collected as closely as possible relative to the time of dosing and 
within 60 minutes prior to dosing.  Date and exact time (to the nearest minute) of drug 
administration will be recorded on eCRFs.
Eleven samples will be collected per subject for pharmacokinetic analysis during the 
treatment and follow-up periods.
Blood Samples for Risankizumab Anti-Drug Antibody (ADA) Assay:
Blood samples, approximately 3 mL, for risankizumab ADA assay will be collected at the 
study visits 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 
60 minutes prior to dosing.  Date and exact time (to the nearest minute) of drug 
administration will be recorded on eCRFs.
Eleven samples will be collected per subject for ADA analysis during the treatment and 
follow-up periods.
After completion of the study, PK and ADA plasma samples may be used for further 
methodological investigations, e.g., stability testing.
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 plasma samples for risankizumab 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.


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5.3.2.4
Measurement Methods
Plasma 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.  
Plasma 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 
as appropriate).  Samples that are confirmed positive may be further characterized in a 
validated neutralizing antibody (NAb) assay.
5.3.3
Efficacy Variables
Primary Endpoint(s)
For generalized pustular psoriasis:
The primary endpoint for Substudy GPP is the proportion of subjects achieving a GPP 
Clinical Response, defined as at least "Slightly Improved" in the overall improvement 
rating from baseline, at Week 16, according to JDA total score (Appendix D) for GPP.
For erythrodermic psoriasis:
The primary endpoint for Substudy EP is the proportion of subjects achieving an EP 
Clinical Response, defined as at least "Minimally Improved" in Clinical Global 
Impression-Global Improvement (CGI-GI) (Appendix G) for EP at Week 16.
Secondary Efficacy Endpoint(s) in Substudy GPP
●
Proportion of subjects achieving a GPP Clinical Response at Week 52
●
Proportion of subjects achieving ≥ 90% reduction from baseline Psoriasis Area 
Severity Index (PASI) score (PASI 90) at Week 16
●
Proportion of subjects achieving PASI 90 at Week 52


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Secondary Efficacy Endpoint(s) in Substudy EP
●
Proportion of subjects achieving an EP Clinical Response at Week 52 
●
Proportion of subjects achieving PASI 90 at Week 16
●
Proportion of subjects achieving PASI 90 at Week 52
Other Efficacy Endpoint(s) in Substudy GPP
The following endpoints will be summarized at each scheduled visit that the respective 
variable is collected:
●
Proportion of subjects achieving a GPP Clinical Response, defined at least 
"Slightly Improved" in the overall improvement rating from baseline according 
to JDA total score for GPP.
●
Change from baseline in each of the JDA component scores
●
Change and Percent change from baseline in JDA score
●
Change and Percent change from baseline in PASI
●
Change from baseline in BSA
●
Proportion of subjects achieving PASI 50/75/90/100 response
●
Proportion of subjects achieving Dermatology Life Quality Index (DLQI) of 
0/0 or 1
●
Change from baseline in DLQI
●
Proportion of subjects achieving at least two grades of improvement in 
Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP).
Other Efficacy Endpoint(s) in Substudy EP
The following endpoints will be summarized at each scheduled visit that the respective 
variable is collected:
●
Proportion of subjects achieving an EP Clinical Response, defined at least 
"Minimally Improved" in CGI-GI for EP
●
Proportion of subjects achieving at least "Much Improved" in CGI-GI for EP


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●
Percent change from baseline in PASI
●
Change from baseline in PASI
●
Proportion of subjects achieving PASI 50/75/90/100 response
●
Change from baseline in BSA
●
Proportion of subjects achieving DLQI of 0/0 or 1
●
Change from baseline in DLQI
5.3.4
Safety Variables
Safety will be assessed descriptively based on:
●
Adverse events (AE)
●
Serious adverse events (SAE)
●
Clinical laboratory values (hematology, clinical chemistry and urinalysis)
●
Vital signs
●
Local tolerability
Major Cardiac, Cerebrovascular and Thrombotic Events Adjudication Committee
An independent adjudication committee will be used to adjudicate all observed cardio-
and cerebro-vascular events reported during the conduct of the study to assure consistent 
assessment of major cardiac, cerebrovascular and thrombotic events.  The events that are 
adjudicated and the adjudication process will be detailed in the CCVT Adjudication 
Committee Charter.  Site personnel will collect source documentation for the identified 
events and submit to the CCVT Adjudication Committee.  Source documentation should 
be obscured before submission by site personnel. 
Source documentation:  (below types of source may be included with the case and will 
vary depending on type of event and available source):
●
SAE form or narrative
●
Hospital Discharge Summary


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●
Death Summary/Details of death note
●
Local Lab Values (e.g., normal ranges; cardiac biomarkers)
●
Imaging reports (e.g., X-Ray, CT, MRI, MRA, Angiography, 
Ultrasonography)
●
Consultation Notes (e.g., Cardiology, Neurology)
●
Procedure Reports (e.g., cardiac catheterization, PCI, CABG)
●
Echocardiography
●
Admission History/Emergency Room report
●
Autopsy result
●
Death Certificate
●
Clinical Course (e.g., progress notes, doctor visit notes)
●
Narrative Form
●
ECG
●
Other Source (specified)
Details to perform the assessments and complete the necessary documentation will be 
available in the adjudication charter and investigator training material.
5.3.5
Pharmacokinetic Variables
Risankizumab plasma concentrations will be determined.  Descriptive statistics will be 
calculated for each sampling time.  PK and ADA data may be combined with data from 
other studies and analyzed using a mixed-effects modeling approach.  This analysis will 
estimate the population central value and the empirical Bayesian estimates of the 
individual values for risankizumab apparent clearance (CL/F) and volume of distribution 
(Vss/F).  Additional parameters may be estimated if useful in the interpretation of the 
data.  Relationships between exposure and clinical observations (efficacy or safety 
variables of interest) may be explored.
The number and percentage of subjects with ADA will be calculated.  As appropriate, the 
effect of ADA on risankizumab pharmacokinetics and efficacy may be explored.


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5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
All subjects have the right to withdraw from the study at any time without the need to 
justify their decision.  The investigator has the right to remove subjects from the study for 
noncompliance, administrative or other reasons.  It should be clearly understood that an 
excessive rate of withdrawals can render the study results uninterpretable.  The sponsor 
reserves the right to remove any study subject from the trial for non-compliance.
An individual subject is to be withdrawn from trial treatment if:
●
The subject withdraws consent for trial treatment or trial participation, without 
the need to justify the decision.
●
The subject can no longer be treated with trial medication for other medical 
reasons (such as surgery, adverse events, other diseases, or pregnancy)
●
Development of a toxicity or adverse event which warrants risankizumab 
discontinuation including but not limited to SAEs or Suspected Unexpected 
Serious Adverse Reactions (SUSAR)s.
●
If prohibited treatment is used during the study for any indication, the subject 
must discontinue use of the prohibited treatment if he/she wishes to continue in 
the study.  In case of undue safety risk for the subject, the subject should 
discontinue study treatment at the discretion of the investigator.  If the subject 
received a live virus vaccination during the study, the subject must discontinue 
study treatment
●
If a subject experiences an intolerable increase of psoriasis during the course 
of the trial the subject will be discontinued from the trial to receive rescue 
treatment as deemed appropriate by the investigator
●
The subject has repeatedly shown to be non-compliant with important trial 
procedures and, in the opinion of the investigator, is not willing or able to stick 
to the trial requirements in the future.
Discontinuation of study medication should not lead to withdrawal from the study.  If 
possible the subject should complete all study visits and procedures as initially planned.


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Given the subject's agreement, the subject will undergo the procedures for premature 
discontinuation and follow up as outlined in Appendix C.  If a subject becomes pregnant, 
refer to Section 6.1.6 for instructions on treatment termination.
For all subjects the reason for withdrawal (e.g., AE) must be recorded in the eCRF.  These 
data will be included in the trial database and reported.
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.
5.5
Treatments
5.5.1
Treatments Administered
Subjects in each group will receive either 150 mg or 75 mg of risankizumab at Week 0, 4 
and every 12 weeks after.  All products will be supplied by BI.
5.5.2
Identity of Investigational Products
Information about the risankizumab formulation to be used in this study is presented in 
Table 3.


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Table 3.
Description of Test Product Risankizumab
Substance:
Risankizumab
Pharmaceutical form:
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG
Chemical form:
Anti-human IL-23p19 mAb
Molecular weight
Approximately 148 kDa
Unit Strength:
75 mg risankizumab in a pre-filled syringe, concentration 90 mg/mL
Route of administration:
Subcutaneous injection
Posology:
Week 0, Week 4, then every 12 weeks
Duration of use:
172 weeks 
5.5.2.1
Packaging and Labeling
The investigational products will be provided by BI.  They will be packaged and labelled 
in accordance with the principles of Good Manufacturing Practice (GMP).  Re-supply to 
the sites will be managed via an IRT system, which will also monitor expiry dates of 
supplies available at the sites.
For details of packaging and the description of the label, refer to the ISF.
5.5.2.2
Storage and Disposition of Study Drug
Drug supplies will be kept in their original packaging and in a secure limited access 
storage area according to the recommended storage conditions on the medication label.  A 
temperature log must be maintained for documentation.
If the storage conditions are found to be outside the specified range, the sponsor must be 
contacted immediately. 
Trial medication must be securely stored, e.g., in a locked refrigerator or at a pharmacy.  
The medication may only be dispensed to trial subjects by authorized personnel as 
documented in the trial staff list.


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5.5.3
Method of Assigning Subjects to Treatment Groups
Within each substudy, subjects will be randomized to receive risankizumab 75 mg or 
risankizumab 150 mg in a ratio of 1:1.
After the eligibility criteria are confirmed, the investigator or designee will randomize the 
subject on Day 1 (Visit 2) through IRT call or website entry.  At visits where study 
medication is to be administered, study sites will be required to complete the medication 
resupply module in the IRT.
5.5.4
Selection and Timing of Dose for Each Subject
An IRT will be used to allocate medication to subjects through medication numbers.  At 
visits where study medication is to be administered, study sites will be required to 
complete the medication resupply module in the IRT.  These visits are specified in 
Appendix C.
At randomization as well as subsequent medication administration visits, IRT will assign 
medication numbers.  At visits after Week 16, subjects in the 75 mg arm who do not 
achieve GPP or EP Clinical Response may be uptitrated to receive 150 mg; this process 
will be managed through IRT.  Site personnel will enter the kit numbers in the eCRF.
Study drugs will be administered subcutaneously.  Injections will be given with each 
subject receiving 1 or 2 injections of risankizumab at each dosing visit.  Syringes will be 
administered per Appendix C schedule as assigned by IRT.
Risankizumab will be administered as a subcutaneous injection in the abdomen, thighs, 
gluteal regions, or upper arms (contra-lateral to that used for PK/ADA samples).  
Injections should be at least 2 cm apart and should not be close to a vein.  The injection 
sites should avoid sites of psoriasis involvement as well as sites where the skin is tender, 
bruised, erythematous, or indurated, and should be alternated to other areas for subsequent 
doses.


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5.5.5
Blinding
5.5.5.1
Blinding of Investigational Product
In this open-label trial, treatment allocation will not be concealed throughout the trial.  
The eCRF will contain information on randomized treatment.
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.
5.5.7
Drug Accountability
The Investigator/Pharmacist/investigational drug storage manager will receive the 
investigational drugs delivered by the sponsor when the following requirements are 
fulfilled:
●
Approval of the trial protocol by the IRB
●
Availability of a signed and dated clinical trial contract between the sponsor 
and the head of the investigational site,
●
Notification of the regulatory authority, e.g., competent authority,
●
Availability of the curriculum vitae of the principal Investigator,
●
Availability of a signed and dated clinical trial protocol
●
Availability of the proof of a medical license for the principal Investigator 
The investigator/pharmacist who is documented in the trial staff list/investigational drug 
storage manager must maintain records of the product's delivery to the trial site, the 
inventory at the site, the use by each subject, and the return to the sponsor or 
warehouse/drug distribution centre or alternative disposal of unused products.  If 
applicable, the sponsor or warehouse/drug distribution centre will maintain records of the 
disposal.


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These records will include dates, quantities, batch/serial numbers, expiry ('use-by') dates, 
and the unique code numbers assigned to the investigational product and trial subjects.  
The investigator/pharmacist who is documented in the trial staff list/investigational drug 
storage manager will maintain records that document adequately that the subjects were 
provided the doses specified by the protocol and reconcile all investigational products 
received from the sponsor.  At the time of return to the sponsor the 
investigator/pharmacist who is documented in the trial staff list/investigational drug 
storage manager must verify that all unused or partially used drug supplies are in the 
Investigator's possession.
All unused medication must be returned to the Sponsor.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
This is a randomized, open-label, parallel design trial.  The trial design is appropriate for 
assessing the safety and efficacy of two different doses risankizumab for Japanese 
subjects with generalized pustular psoriasis or erythrodermic psoriasis.  Since the 
population of subjects, especially GPP subjects, is very small, it is not feasible to have a 
control group.  In addition to 150 mg, a 75 mg dose was also selected for this study to 
provide dose response information as well as evaluation of efficacy at a lower dose in 
Japanese subjects.
5.6.2
Appropriateness of Measurements
All measurements performed during this trial are standard measurements in GPP and/or 
EP treatment trials and will be performed in order to monitor safety aspects or assess 
treatment response in an appropriate way.  Therefore, the appropriateness of all 
measurements applied in this trial is given.


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5.6.3
Suitability of Subject Population
The subjects enrolled in the present study are subjects with GPP or EP, in agreement with 
the indication that is being pursued.
The inclusion and exclusion criteria, for most of them limit the factors of variability that 
could confuse efficacy and safety outcomes and/or have the purpose of protecting 
subject's safety.
Any active ongoing inflammatory disease other than GPP or EP that might confound 
efficacy evaluation according to investigator's judgment is exclusionary, as well as the 
intake of psoriasis medications that may interfere with risankizumab in the evaluation of 
the psoriatic disease.
GPP is a potentially severe disease and EP may lead to dehydration.  Both diseases may 
be fatal.  In order to protect subject's safety and control, medical conditions that could, in 
the opinion of the investigator, compromise the safety of the subjects are exclusionary.  
This is also the case for the exclusion criteria relating to GPP and EP. 
Moreover, the restriction of the subject population will facilitate the interpretation of 
safety results.
5.6.4
Selection of Doses in the Study
A dose of 150 mg has been selected for global Phase 3 trials of risankizumab for psoriasis.  
The dose selection strategy for global Phase 3 involved analyses of data from the 
completed Phase 1 study (Trial 1311.1, c02434648), the Phase 2 study (Trial 1311.2, 
c03272682) and PK-Pharmacodynamic analysis of all available data from the Phase 1 and 
2 studies.  In Study 1311.16, following single dose administration of risankizumab 18 mg 
to 300 mg SC doses,
 
 
 
 in the 


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Phase 2 study (Trial 1311.2).  Therefore, the dose of 150 mg was selected in this trial, 
which is the same dose as being evaluated in other global Phase 3 trials of risankizumab 
for psoriasis.
In the Phase 2 study (Trial 1311.2), risankizumab 90 mg dose showed about 10% lower 
PASI90 response rate compared to the 180 mg dose.  In addition to 150 mg, a 75 mg dose 
was also selected for this study to provide dose response information as well as evaluation 
of efficacy at a lower dose in Japanese subjects.  The 75 mg dose in Japanese subjects is 
expected to provide risankizumab exposures comparable to the 90 mg dose evaluated in 
the Phase 2 study (Trial 1311.2) in Western subjects.
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).
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
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 


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adverse event to study drug, and any action(s) taken.  For SAEs considered as having "no 
reasonable possibility" of being associated with study drug, the investigator will provide 
an Other 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.
6.1.1
Definitions
6.1.1.1
Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a subject 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.


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6.1.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as a 
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.
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.


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For SAEs with the outcome of death, the date and cause of death will be recorded on the 
appropriate case report form.
6.1.1.3
Adverse Events of Special Interest
The term adverse events of special interest (AESI) relates to any specific AE that has been 
identified at the compound level as being of particular concern for prospective safety 
monitoring and safety assessment within this trial, e.g., the potential for AEs based on 
knowledge from other compounds in the same class.  Ongoing evaluation of adverse 
events may identify future AESI.
The following are considered as AESI:
Hepatic Injury
A hepatic injury is defined by the following alterations of hepatic laboratory parameters:
●
an elevation of aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) > 3-fold upper limit of normal (ULN combined with 
an elevation of total bilirubin > 2-fold ULN measured in the same blood draw 
sample, and/or
●
marked peak aminotransferase (ALT, and/or AST) elevations ≥ 10-fold ULN.
These lab findings constitute a hepatic injury alert and the subjects showing these lab 
abnormalities need to be followed up according to instructions from the sponsor including 
completion of the hepatic adverse events form.
In case of clinical symptoms of hepatic injury (icterus, unexplained encephalopathy, 
unexplained coagulopathy, right upper quadrant abdominal pain, etc.) without lab results 
(ALT, AST, total bilirubin) available, the investigator should make sure these parameters 
are analysed, if necessary with an unscheduled blood test.  Should the results meet the 
criteria of hepatic injury alert, investigators are advised to provide a hepatic workup as 
directed by the Sponsor.


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6.1.2
Adverse Event Severity
Intensity of AEs
The intensity grading of AEs will be performed according to Rheumatology Common 
Toxicity Criteria (RCTC) Version 2.0 developed by OMERACT.  Refer to the ISF for 
intensity/severity classification.
Intensity options are:
Grade 1
mild
Grade 2
moderate
Grade 3
severe
Grade 4
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
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
No Reasonable 
Possibility
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event.
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.


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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 AEs reported from the time of study drug administration until 16 weeks following 
discontinuation of study drug administration have elapsed will be collected, whether 
solicited or spontaneously reported by the subject.  In addition, SAEs and protocol-related 
non-serious adverse events will be collected from the time the subject signed the study-
specific informed consent.
Figure 2.
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.  SAEs 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-
Case Report Forms (CRF) and emailed (preferred route) or faxed to Clinical 
Pharmacovigilance within 24 hours of the site being made aware of the serious adverse 
event.
SAEs and
Protocol-Related 
Nonserious AEs
Consent
Signed
Study Drug 
Start
Study Drug 
Stopped
16 weeks After 
Study Drug 
Stopped (Week 188)
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported


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For safety concerns, contact the Medical Science Group at:
For any subject safety concerns, please contact the physician listed below:


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In emergency situations involving study subjects when the primary 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:
Phone:  
The sponsor will be responsible for 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.
In Japan, the principal investigator will provide documentation of all SAEs to the Director 
of the investigative site and the Sponsor.
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.


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Pregnancy in a study subject is not considered an adverse event.  However, the medical 
outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a serious adverse event and must be reported to AbbVie within 24 hours of the 
site becoming aware of the event.
6.1.7
Supplemental Safety CRFs
Supplemental CRFs have been developed to facilitate the routine and consistent collection 
of information for events including hepatic injury (see also Section 6.1.1.3) and MACE 
(to facilitate the work of the CCVT adjudication committee, see Section 5.3.4), systemic 
hypersensitivity/anaphylactic reactions, and tuberculosis.
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.
For medical devices, a product complaint also includes all deaths of a subject 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.


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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) 
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):


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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.
In Japan, the Investigator will record all protocol deviations in the appropriate medical 
records at site.
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
The objective of this study is to assess the long term safety and efficacy of two different 
dose regimens of risankizumab for Japanese subjects with generalized pustular psoriasis 
or erythrodermic psoriasis. 
There are two substudies.  Substudy GPP will include subjects with GPP, and Substudy 
EP will include subjects with EP.


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The primary endpoint for Substudy GPP is the proportion of subjects achieving a GPP 
Clinical Response, defined as at least "Slightly Improved" in the overall improvement 
rating from baseline, at Week 16, according to JDA total score for GPP.
The primary endpoint for Substudy EP is the proportion of subjects achieving an EP 
Clinical Response, defined as at least "Minimally Improved" in CGI-GI for EP at 
Week 16.
The summary tables will be presented separately for each Substudy and each 
risankizumab dose regimen.  Integration across two doses for efficacy and safety within 
each study, and integration across the two Substudies for safety will be provided when 
appropriate.
Complete, specific details of the statistical analysis will be described and fully 
documented in the Statistical Analysis Plan (SAP).  The SAP will be finalized prior to the 
database lock.
8.1.1
Analysis Population
The Intent-to-Treat (ITT) subject population in each Substudy is defined as all 
randomized subjects with at least one dose of study drug.  The Safety population is the 
same as the ITT population.
8.1.2
Null and Alternative Hypotheses
Not applicable.
8.1.3
Planned Analyses
No formal hypothesis testing is planned for this trial.
The analysis will be performed using SAS® (SAS Institute Inc., Cary, NC, USA).


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8.1.3.1
Demographics and Baseline Characteristics
Demographics and Baseline characteristics of the study subjects will be summarized for 
each arm of each Substudy and overall using descriptive statistics.
8.1.4
Primary Endpoint Analyses
For each Substudy and dose, the primary efficacy endpoint per Section 5.3.3 will be 
summarized descriptively, with count and proportion.
8.1.5
Secondary Endpoint Analyses
For each Substudy, descriptive statistics for secondary endpoints will be provided.  These 
include the number of observations, min/max, range, median, 25th percentile, 
75th percentile, median, mean, and standard deviation for continuous variables and counts 
and percentages for discrete variables.
8.1.6
Safety Analyses
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®) coding dictionary.  Standard AbbVie summary tables and listings will be 
produced.
All AEs, SAEs, AEs leading to discontinuation, and pre-specified AEs of special interest 
will be collected during the study.  A treatment-emergent AE (TEAE) is defined as an 
event with onset or worsening after the first study dose of risankizumab and within 
15 weeks (105 days) after the last risankizumab injection.  The number and percentages of 
subjects experiencing TEAE will be tabulated using the MedDRA system organ class and 
preferred term.  Summaries (including percentages and event per 100 subject-years) of 
SAEs, deaths, AEs leading to discontinuation from the study, and pre-specified AEs of 
special interest will be provided as well.  Mean change in laboratory variables, and vital 
signs determinations will be summarized.  For selected parameters, a listing of all subjects 
with clinically significant laboratory values and vital sign determinations will be 


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provided.  Shift tables for changes from baseline according to the normal range will also 
be provided.
8.1.7
Pharmacokinetic and Exposure-Response Analysis
Individual risankizumab plasma 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.
Data from this study may be combined with data from other risankizumab studies for the 
population pharmacokinetic and exposure-response analyses or for external evaluation of 
pharmacokinetic or exposure-response models developed from other studies.  Population 
pharmacokinetic and exposure-response analyses of only data from this study may not be 
conducted.  The following general methodology will be used for the population 
pharmacokinetic analysis.  Population pharmacokinetic analyses of risankizumab will be 
performed using 
.  Pharmacokinetic models will 
be built using a non-linear mixed-effects modeling approach with NONMEM software 
(Version 7, or a higher version).  The structure of the starting pharmacokinetic model will 
be based on the pharmacokinetic analysis data from previous studies.  Apparent CL/F and 
apparent Vss/F of risankizumab will be the pharmacokinetic parameters of major interest 
in the NONMEM analyses.  If necessary, other parameters, including the parameters 
describing absorption characteristics, may be estimated if useful in the analysis.
Once an appropriate base pharmacokinetic model 
 
 is developed, 
 
  The 
relationship between 
 
 
 
will be explored using 
 or another suitable 
regression/smoothing method at a significance
  After identification of all 


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relevant covariates, a 
 
 
As appropriate, the effect of 
 on 
 as well 
as the relationships between exposure and clinical observations
 
may be explored.  Results of the PK and exposure-response analyses 
may be summarized in a separate report rather than in the clinical study report.
8.1.8
Interim Analyses
An interim analysis will be conducted when the last subject completes the Week 28 visit 
and all data pertaining to Week 28 and earlier are cleaned.  For this analysis all Week 16 
efficacy endpoints will be analysed, and all safety as well as pharmacokinetic and anti-
immunogenicity data received by cut-off date will be analysed.  Another interim analysis 
will be conducted when the last subject completes the Week 52 visit.  The analyses will be 
performed for the efficacy endpoints until Week 52, as well as all safety and 
pharmacokinetic and immunogenicity data received by cut-off date.
Additional interim analysis may be performed if deemed necessary for regulatory 
purpose.
8.1.9
Handling of Missing Data
Every effort should be made to collect complete data at all visits.
In addition to the as-observed analysis, the following rules will be used to impute for 
missing data:
●
For continuous endpoints, LOCF (Last Observation Carried Forward) will be 
used to impute missing values
●
For all binary endpoints (i.e., endpoints that are either 1 (subject responded) or 
0 (subject did not respond):


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○
If no assessment after that visit*, then impute as failure (NRI [No 
Response Imputation])
○
If there are assessments at visits* before and after, only impute as success 
if both visits are successes; else impute as failure
*
Subjects that take prohibited medications to treat Psoriasis will be treated the same as those that discontinued from 
the trial – i.e., subsequent visits following start of prohibited medication will be considered as failure for binary 
endpoints.
8.2
Determination of Sample Size
The sample size is not estimated based on powering for any hypothesis testing.  There are 
only approximately 1600 and 40000 Japanese subjects with generalized pustular psoriasis 
and erythrodermic psoriasis respectively, thus finding subjects to participate in the trial 
will be difficult.  Therefore, the sample size is determined based on feasibility.  In total, at 
least 16 subjects will be enrolled:  at least 8 subjects for GPP and EP separately.
8.3
Randomization Methods
An IRT will be used to determine the randomization of subjects.  Detailed instructions for 
using the IRT will be provided to the site personnel.  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 fashion in each group to either 150 mg (2 syringes, 75 mg 
each) or 75 mg (1 syringe) at Week 0, 4 and every 12 weeks.  The randomization schedule 
will be prepared by the Statistics Department of AbbVie and provided to drug supply for 
adequate packaging.  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 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 IEC/IRB.  The IEC/IRB will review the ethical, scientific 


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and medical appropriateness of the study before it is conducted.  IEC/IRB approval of the 
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.
Any SAEs 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.
9.3.1
Informed Consent Form and Explanatory Material
In Japan, the principal investigator will prepare the consent form and explanatory material 
required to obtain subject's consent to participate in the study with the cooperation of the 
sponsor and will revise these documents as required.  The prepared or revised consent 
forms and explanatory material will be submitted to the sponsor.  Approval of the IRB 
will be obtained prior to use in the study.
9.3.2
Revision of the Consent Form and Explanatory Material
In Japan, when important new information related to the subject's consent becomes 
available, the principal investigator will revise the consent form and explanatory material 
based on the information without delay and will obtain the approval of the IRB prior to 
use in the study.  The investigator will provide the information, without delay, to each 
subject already participating in the study, and will confirm the intention of each subject to 
continue the study or not.  The investigator shall also provide a further explanation using 
the revised form and explanatory material and shall obtain written consent from each 
subject of their own free will to continue participating in the study.
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 


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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(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 
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 


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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.
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.
12.0
Use of Information
Any research that may be done using optional exploratory research samples from this
study will be experimental in nature and the results will not be suitable for clinical 
decision making or subject management.  Hence, the subject will not be informed of 
individual results, should analyses be performed, nor will anyone not directly involved in 
this research.  Correspondingly, researchers will have no access to subject identifiers.  
Individual results will not be reported to anyone not directly involved in this research 
other than for regulatory purposes.  Aggregate data from optional exploratory research 
may be provided to investigators and used in scientific publications or presented at 
medical conventions.  Optional exploratory research information will be published or 
presented only in a way that does not identify any individual subject.
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 Director of the Site in 
Japan and AbbVie.  Continuation of this study beyond this date must be mutually agreed 


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upon in writing by both the Director of the Site in Japan and AbbVie.  The investigator 
will provide a 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 Director of the Site in Japan must retain any records related to the study according to 
local requirements.  If the Director of the Site in Japan 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.


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14.0
Investigator's Agreement
1.
I have received and reviewed the Investigator's Brochure for ABBV-066.
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 Phase 3, Randomized, Open-Label Study to Assess Efficacy and 
Safety of Two Different Dose Regimens of Risankizumab 
Administered Subcutaneously in Japanese Subjects with Generalized 
Pustular Psoriasis or Erythrodermic Psoriasis
Protocol Date:
18 January 2017
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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15.0
Reference List
Published References
Treatment of erythrodermic psoriasis:  from the medical board of the 
National Psoriasis Foundation.  Rosenbach M, Hsu S, Korman NJ, et al; 
National Psoriasis Foundation Medical Board.  J Am Acad Dermatol.  
2010;62(4):655-62.
R05-2548
Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI)--a 
simple practical measure for routine clinical use.  Clin Exp Dermatol.  
1994;19:210-6.
R13-3515
Woodworth T, Furst DE, Alten, R, et al.  Standardizing assessment and 
reporting of adverse effects in rheumatology clinical trials II:  the 
Rheumatology Common Toxicity Criteria v.2.0.  J Rheumatol.  
2007;34(6):1401-14.
R15-3845
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.
R96-3541
Fredriksson T, Pettersson U.  Severe psoriasis--oral therapy with a new 
retinoid.  Dermatologica.  1978;157(4):238-44.
Unpublished References
c01569420
Investigator's Brochure Risankizumab, Psoriasis, Crohn's Disease, 
Ankylosing Spondylitis, Asthma, Psoriatic Arthritis 
1311.P1/1311.P2/1311.P3/1311.P4/ 1311.P5, Current Version.
c02434648
Summary report of analysis, Trial 1311.1.  26 March 2015.
c03272682
Summary report of interim analysis at Week 48, Trial 1311.2.  
05 May 2015.


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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.


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


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Appendix C.
Study Activities
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448 532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Informed consent
X
Demographics
X
Medical history
X
Smoking/alcohol 
history
X
Prior and ongoing 
medication
X
Psoriatic arthritis 
history1
X
In-/exclusion criteria
X
X
Height
X
Weight/waist 
circumference2
X
X
X
Physical 
examination3
Xc
Xt
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xc
Vital signs4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448 532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Infection screening5
X
X
X
X
X
Chest X-ray
X
X
X
X
Pregnancy testing6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory 
tests7
Xc
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xc
Xc
Xc
12 lead-ECG
X
PK sampling8
X
X
X
X
X
X
X
X
X
X
X
X
ADA sampling8
X
X
X
X
X
X
X
X
X
X
X
X
Local tolerability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
JDA score and 
responder rating
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PGA-GPP9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CGI-GI10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Contact IRT
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Administration of 
trial drugs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448 532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Last injection of trial 
medication11
X
Trial completion
X
Vital status12
X
1.
At Visit 1, all subjects at all sites will be evaluated via CASPAr for history of psoriatic arthritis as detailed in Appendix F.
2.
Refer to Section 5.3.1.1 for weight procedures.
3.
Physical examination:  C = complete, T = targeted.  Refer to Section 5.3.1.
4.
Vital signs should precede blood sampling and be assessed pre-dose at all dosing visits.  At Visit 2 and Visit 3, additional vital sign assessments should be taken at 5 minutes 
post-dose and 60 minutes post-dose.  Subjects should be closely monitored for signs and symptoms of hypersensitivity reactions for approximately 2 hours after the first dose 
administered and 1 hour following all other doses of study drug.
5.
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 or QuantiFERON-TB.  Hepatitis B, Hepatitis C and HIV testing will be performed at screening.  TB testing will be performed at screening, Visit 12, 16, 20 and 
Week 184.
6.
Serum pregnancy testing in all female subjects at screening and if urine pregnancy test is positive.  Urine pregnancy testing will be done in women of child-bearing potential 
prior to administration of study drug at all dosing visits and at each Follow-Up Visit.  
7.
C = complete, T = targeted.  Targeted lab samples should be limited to WBC, serum CRP and serum albumin for the measurement of JDA.  Subjects should be fasting for at 
least 8 hours prior to the blood sample being taken at the "complete" visits, except for screening.  If not fasted mark on laboratory requisition form.
8.
On dosing visits, PK and ADA sampling should be taken approximately within 1 hour prior to administration of study drug.
9.
Collected for Substudy GPP.
10. Collected for Substudy EP.


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11. Subjects that terminate trial medication early will complete EOT Visit procedures instead of the planned treatment period visit and return for Week 188 Follow-up Visit, 
16 weeks after last dose of study medication.
12. Vital Status should be collected for subjects leaving the study before the planned Week 188 Follow-up visit.


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Appendix D.
Severity Assessment Criteria Score
Severity assessment criteria score (JDA total score) specified by the Japanese 
Dermatological Association
A
Assessment of skin symptoms:  erythema, pustules, Edema (0 – 9)
B
Systemic symptoms/assessment of test findings:  fever, WBC count, serum CRP, serum albumin 
(0 – 8)
o
Severity:  
Mild 
Moderate
Severe
(Total score)
(0 – 6) 
(7 – 10)
(11 – 17)
A Assessment of skin symptoms (0 – 9)
Severe
Moderate
Mild
None
Erythema area (total)*
Erythema area with pustules **
Edema area **
3
3
3
2
2
2
1
1
1
0
0
0
*
% vs. BSA (severe:  ≥ 75%, moderate:  ≥ 25% and < 75%, mild:  < 25%
**
% vs. BSA (severe:  ≥ 50%, moderate:  ≥ 10% and < 50%, mild:  < 1 0%)
B
Systemic symptoms/assessment of test findings (0 – 8)
Score
2
1
0
Fever (°C)
WBC count (/μL)
Serum CRP (mg/dL)
Serum albumin (g/dL)
≥38.5
≥15,000
≥7.0
< 3.0
≥37 and < 38.5
≥ 10,000 and < 15,000
≥0.3 and < 7.0
≥3.0 and < 3.8
< 37
< 10,000
< 0.3
≥3.8


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Overall Improvement Rating Defined According to JDA Total Score
JDA Total Score Change
Other Criteria 
Markedly 
improved
Decreased by ≥ 3 points
or
No or little symptom of generalized pustular 
psoriasis
Moderately 
improved
Decreased by 1 or 2 points
or
≥ 30% reduction of erythema area with pustules 
compared to baseline, without reaching "no or little 
symptoms of generalized psoriasis" or,
Clinically meaningful improvement in at least 2 of 
the other parameters of the severity assessment 
criteria (erythema area, oedema area, WBC count, 
CRP, fever, serum albumin)
AND the sum of the changes in individual JDA 
components is < 3
Slightly 
improved
0 points (no change)
and
≥ 20% and < 30% reduction of erythema area with 
pustules compared to baseline, or,
Clinically meaningful improvement in at least 1 of 
the other parameters of the severity assessment 
criteria (erythema area, oedema area, WBC count, 
CRP, fever, serum albumin)
Unchanged
0 points (no change)
and
Does not fulfil the other criteria of "slight 
improvement"
Worsened
Increased by ≥ 1 point
-
-


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Appendix E.
Psoriasis Area and Severity Index (PASI)
The PASI score is an established measure of clinical efficacy for psoriasis medications 
(Study R96-3541).
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 < 30%
●
3 = 30% to < 50%
●
4 = 50% to < 70%
●
5 = 70% to < 90%
●
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
The table below outlines the characteristics of each category.
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


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●
The inguinal canal separates the trunk and legs anteriorly
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.


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Appendix F.
Diagnosis and Assessments for Subjects with Psoriatic Arthritis
At Visit 1, subjects with a positive history of PsA or suspected to have PsA will be further 
evaluated for PsA diagnosis based on CASPAr (ClASsification of Psoriatic Arthritis) 
criteria (Study R15-1001).  To be classified has having PsA, a subject must have 
inflammatory articular disease (joint, spine, or entheseal) with at least 3 points total from 
the 5 categories below.  All trial participants will have 2 points assigned due to evidence 
of current psoriasis per trial entry criteria and require at least one additional point for 
diagnosis of PsA.
CASPAr Criteria
Category
Point Assignment
Evidence of current psoriasis, a personal history of psoriasis, or a family history of 
psoriasis
2 points
Typical psoriatic nail dystrophy, including onycholysis, pitting, or hyperkaratosis 
observed on current physical examination
1 point
A negative test result for rheumatoid factor by any method except latex
1 point
Either current dactylitis, defined as swelling of an entire digit, or a history of 
dactylitis recorded by a rheumatologist
1 point
Radiographic evidence of juxta-articular new bone formation appearing as 
ill-defined ossification near joint margins (but excluding osteophyte formation) on 
plain radiographs of the hand or foot
1 point


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Appendix G.
Clinical Global Impression-Global Improvement (CGI-GI)
Clinical Global Impression (CGI)
2. Global improvement:  Rate total improvement whether or not, in your judgement, it is due entirely to drug 
treatment.
Compared to his condition at admission to the project, how much has he changed?
0 = Not assessed
4 = No change
1 = Very much improved
5 = Minimally worse
2 = Much improved
6 = Much worse
3 = Minimally improved
7 = Very much worse
Reproduced from Guy W, editor.  ECDEU Assessment Manual for Psychopharmacology.  1976.  Rockville, MD, U.S. 
Department of Health, Education, and Welfare


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




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Appendix I.
PGA Scale for Generalized Pustular Psoriasis
The Physician's Global Assessment of Generalized Pustular Psoriasis is a 6-point scale 
used to measure the severity of skin disease at the time of the qualified investigator's 
evaluation of the subject.  The degree of overall severity will be evaluated using the 
following categories:  erythema, pustulation, and edema.
Scoring Instructions:
If a subject has signs of erythema, pustulation, or edema intermediate between two grades, 
then the subject's erythema, pustulation, or edema grade should be assigned the higher of 
the two grades.  For example, if a subject's erythema is considered to be worse than 'mild' 
but less than 'moderate,' the subject's erythema grade should be considered 'moderate.'
The subject's score is an arithmetic average (mean) of the grades for erythema, 
pustulation, and edema, rounded to the nearest whole integer.  For example, if a subject's 
erythema is moderate (3), pustulation is mild (2), and edema is moderate (3), the average 
grade is 2.67, which is rounded to the nearest whole integer of 3, giving the subject a 
score of 'moderate.'
Grade
Erythema
Pustulation
Edema
Score
0
No evidence of 
erythema
No evidence of pustulation 
No evidence of 
edema
Cleared, except for 
residual discoloration
1
Faint erythema
Scattered isolated pustules
Minimal edema
Minimal
2
Light red 
coloration
A cluster of non-confluent 
pustules involving 1 skin 
location
Mild edema
Mild
3
Moderate red 
coloration
Clusters of non-confluent 
pustules involving more 
than 1 skin location
Moderate edema
Moderate
4
Bright-red 
coloration
A confluent 'lake of pus' in 
1 skin location
Marked edema
Severe
5
Dusky to deep-
red coloration
Confluent 'lakes of pus' in 
more than 1 skin location
Severe edema
Very severe


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Appendix J.
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:" 
Contact previously read:
Has been changed to read:
Section 3.2  Benefits and Risks
Second paragraph, fourth sentence previously read:
Subjects with positive QuantiFERON® tuberculosis (TB) test must fulfill entry criteria as 
specified in Section 5.2.2, item 5, prior to receiving risankizumab.
Has been changed to read:
Subjects with positive QuantiFERON® tuberculosis (TB) test or a positive PPD (purified 
protein derivative) skin test must fulfill entry criteria as specified in Section 5.2.2, item 5, 
prior to receiving risankizumab.


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Figure 1.  Trial Design
Previously read:


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Has been changed to read:
Section 5.1  Overall Study Design and Plan:  Description
Subsection Screening and Run-In Period(s)
Add:  new fourth paragraph 
Subjects that initially screen-fail for the study may be permitted to re-screen one time 
following re-consent and:
●
a repeat of all screening procedures is needed with the possible exceptions 
noted below.  
●
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 PPD test (or equivalent), and 
electrocardiogram (ECG), these tests will not be required to be repeated for re-


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screening provided the conditions noted in Section 5.2.2 and 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 42 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.
Section 5.1  Overall Study Design and Plan:  Description
Subsection Screening and Run-In Period(s)
Heading "Infection Screening"
Previously read:
Refer to exclusion criteria Section 5.2.2 with study participation directive for subjects 
with a positive result for QuantiFERON® for TB, Hepatitis B, Hepatitis C, and Human 
Immunodeficiency Virus (HIV).
Has been changed to read:
Refer to exclusion criteria Section 5.2.2 with study participation directive for subjects 
with a positive result for PPD or QuantiFERON® for TB, Hepatitis B, Hepatitis C, and 
Human Immunodeficiency Virus (HIV)
Section 5.1  Overall Study Design and Plan:  Description
Subsection Treatment Period(s)
Second paragraph, first sentence previously read:
Visits 2, 4, 6, 8, 10, 12, 16, 20, end of treatment (EOT) and Week 188 follow-up visit  
will be performed in fasted state (8 hours no food and only water).  
Has been changed to read:
Visits 2, 4, 6, 8, 10, 12, 16, 20, end of treatment (EOT), Week 184 follow-up visit and 
Week 188 follow-up visit will be performed in fasted state (8 hours no food and only 
water).


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Section 5.2.3  Prior and Concomitant Therapy
Last paragraph, last sentence previously read:
All concomitant medications should be carefully evaluated by the investigator and the 
AbbVie Therapeutic Area Medical Director (TA MD) should be contacted if there are any 
questions regarding concomitant or prior therapy(ies).
Has been changed to read:
All concomitant medications should be carefully evaluated by the investigator and the 
AbbVie TA MD should be contacted if there are any questions regarding concomitant or 
prior therapy(ies).
Table 1.  Restricted Medications
Medication "brodalumab, ixekizumab" previously read:
Medication or Class of Medications
Restriction Duration
(Through Week 188 Follow-Up Visit)
brodalumab, ixekizumab 
4 months prior to assignment
Has been changed to read:
Medication or Class of Medications
Restriction Duration
(Through Week 188 Follow-Up Visit)
brodalumab, ixekizumab 
4 months prior to randomization
Section 5.2.4  Contraception Recommendations and Pregnancy Testing
Delete:  eighth, ninth, tenth and eleventh paragraph
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.
Male or female condom with or without spermicide.
Cap, diaphragm or sponge with spermicide.


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A combination of male condom with either cap, diaphragm or sponge with spermicide 
(double barrier method).
Section 5.3.1.1  Study Procedures
Subsection Vital Signs
Second paragraph, last sentence previously read:
At Visit 2 and Visit 3 additional evaluations will be taken at 5 minutes post-dose and 
60 minutes post-dose.
Has been changed to read:
At Visit 2 and Visit 3 additional vital signs will be taken at 5 minutes post-dose and 
60 minutes post-dose.
Section 5.3.1.1  Study Procedures
Subsection Pregnancy Testing
Previously read: 
A serum pregnancy test will be performed for all female subjects at the Screening Visit.  
A urine pregnancy test will occur at every other study visit for all women of child-bearing 
potential, prior to every dosing, and at the Week 188 follow-up visit.  Additional serum 
pregnancy testing will occur in case of a positive urine test result at any of the visits and 
must be negative to further treat the subject.
Females of non-childbearing potential (either postmenopausal or permanently surgically 
sterile as defined in Section 5.2.4) do not require pregnancy testing.
Has been changed to read:
A serum pregnancy test will be performed for all female subjects at the Screening Visit.  
A urine pregnancy testing will be done on all women of child-bearing potential prior to 
administration of study drug at all dosing visits and at each Follow-Up Visit.  Additional 
serum pregnancy testing will occur in case of a positive urine test result at any of the visits 
and must be negative to further treat the subject.


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Females of non-childbearing potential (either postmenopausal or permanently surgically 
sterile as defined in Section 5.2.4) do not require pregnancy testing after screening.
Table 2.  Laboratory Tests
Category "Urine Pregnancy test (only for female subjects of childbearing 
potential)c" and " Serum Pregnancy test (only for female subjects of childbearing 
potential at screening or if urine pregnancy test is positive)" previously read:
Category
Test Name
Urine Pregnancy test (only for female subjects of 
childbearing potential)c
Human Chorionic Gonadotropin in the urine
Serum Pregnancy test (only for female subjects of 
childbearing potential at screening or if urine 
pregnancy test is positive)
Human Serum Chorionic Gonadotropin 
Has been changed to read:
Category
Test Name
Urine Pregnancy test (only for female subjects of 
childbearing potential)d
Human Chorionic Gonadotropin in the urine
Serum Pregnancy test (in all female subjects at 
screening or if urine pregnancy test is positive)
Human Serum Chorionic Gonadotropin 
Table 2.  Laboratory Tests
Category "Urine Pregnancy test (only for female subjects of childbearing 
potential)c" previously read:
Category
Test Name
Infection screening 
Hepatitis B Surface Antigen (qualitative)a
Hepatitis B Surface Antibody (qualitative)a
Hepatitis B Core Antibodies total (qualitative)a
Hepatitis B Virus DNA (quantitative)a,b
Hepatitis C Antibodies (qualitative)a
Hepatitis C Virus RNA (quantitative)a
HIV-1, and HIV-2 Antibody (qualitative)a
QuantiFERON®-TBc (if applicable)b


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Has been changed to read:
Category
Test Name
Infection screening 
Hepatitis B Surface Antigen (qualitative)a
Hepatitis B Surface Antibody (qualitative)a
Hepatitis B Core Antibodies total (qualitative)a
Hepatitis B Virus DNA (quantitative)a,b
Hepatitis C Antibodies (qualitative)a
Hepatitis C Virus RNA (quantitative)a
HIV-1, and HIV-2 Antibody (qualitative)a
PPD or QuantiFERON®-TBc
Table 2.  Laboratory Tests
Table note "b." and "c." previously read:
b.
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 trial.  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 trial.  
TB testing will be performed at screening Visit 12, 16, and Week 188 Follow-up Visit.
c.
Urine pregnancy test performed at every visit.
Has been changed to read:
b.
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 trial.  In these cases, HBV DNA level will be 
monitored at least every 6 months.  If positive, the subject's treatment will be discontinued.  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 trial.  In these cases, HCV RNA level will be monitored at least every 
6 months.  If positive, the subject's treatment will be discontinued.
c.
TB testing will be performed at screening, Visit 12, 16, 20 and Week 184.
d.
Urine pregnancy test will be performed at all dosing visits.
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Blood Samples for Risankizumab Assay
First paragraph, third and fourth sentence previously read:
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 and PK and ADA sampling will be recorded on eCRFs.


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Has been changed to read:
Blood samples for the PK assay should be collected as closely as possible relative to the 
time of dosing and within 60 minutes prior to dosing.  Date and exact time (to the nearest 
minute) of drug administration will be recorded on eCRFs.
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Blood Samples for Risankizumab Anti-Drug Antibody (ADA) Assay:
First paragraph, second and third sentence previously read:
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 and PK and ADA sampling will be recorded on eCRFs.
Has been changed to read:
Blood samples for the ADA assay should be collected as closely as possible relative to the 
time of dosing and within 60 minutes prior to dosing.  Date and exact time (to the nearest 
minute) of drug administration will be recorded on eCRFs.
Section 5.3.4  Safety Variables
Subsection Major Cardiac, Cerebrovascular and Thrombotic Events Adjudication 
Committee
First paragraph previously read:
An independent adjudication committee will be used to adjudicate all observed cardio-
and cerebro-vascular events reported during the conduct of the study to assure consistent 
assessment of major cardiac, cerebrovascular and thrombotic events.  The events that are 
adjudicated and the adjudication process will be detailed in the CCVT Adjudication 
Committee Charter.
Has been changed to read:
An independent adjudication committee will be used to adjudicate all observed cardio-
and cerebro-vascular events reported during the conduct of the study to assure consistent 
assessment of major cardiac, cerebrovascular and thrombotic events.  The events that are 


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adjudicated and the adjudication process will be detailed in the CCVT Adjudication 
Committee Charter.  Site personnel will collect source documentation for the identified 
events and submit to the CCVT Adjudication Committee.  Source documentation should 
be obscured before submission by site personnel. 
Source documentation:  (below types of source may be included with the case and will 
vary depending on type of event and available source):
●
SAE form or narrative
●
Hospital Discharge Summary
●
Death Summary/Details of death note
●
Local Lab Values (e.g., normal ranges; cardiac biomarkers)
●
Imaging reports (e.g., X-Ray, CT, MRI, MRA, Angiography, 
Ultrasonography)
●
Consultation Notes (e.g., Cardiology, Neurology)
●
Procedure Reports (e.g., cardiac catheterization, PCI, CABG)
●
Echocardiography
●
Admission History/Emergency Room report
●
Autopsy result
●
Death Certificate
●
Clinical Course (e.g., progress notes, doctor visit notes)
●
Narrative Form
●
ECG
●
Other Source (specified)
Section 5.5.4  Selection and Timing of Dose for Each Subject
Second paragraph, last sentence previously read:
Site personnel will enter the medication numbers in the eCRF.


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Has been changed to read:
Site personnel will enter the kit numbers in the eCRF.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics
Pharmacokinetics
Clinical
Clinical
Has been changed to read:
Name
Title
Functional Area
Clinical
Clinical
Clinical
Statistics
Pharmacokinetics
Clinical
Clinical


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Appendix C.  Study Activities
Previously read:
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448
532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Informed consent
X
Demographics
X
Medical history
X
Smoking/alcohol 
history
X
Prior and ongoing 
medication
X
Psoriatic arthritis 
history1
X
In-/exclusion criteria
X
X
Height
X
Weight/waist 
circumference2
X
X
X
Physical examination3
Xc
Xt
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xc
Vital signs4
X
X
X
X
X
X
X
X4
X
X
X
X
X
X
X
X
X
X4
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


Risankizumab
M15-988 Protocol Amendment 1
100
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448
532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Infection screening5
X
X
X
X
Chest X-ray
X
X
X
Pregnancy testing6
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory tests7
Xc
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xc
Xc
12 lead-ECG
X
PK sampling8
X
X
X
X
X
X
X
X
X
X
X
ADA sampling8
X
X
X
X
X
X
X
X
X
X
X
Local tolerability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
JDA score and 
responder rating
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PGA-GPP9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CGI-GI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Contact IRT
X
X
X
X
X
X
X
X
X
X
X
X
Administration of trial 
drugs
X
X
X
X
X
X
X
X
X
X
X


Risankizumab
M15-988 Protocol Amendment 1
101
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448
532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Last injection of trial 
medication10
X
Trial completion
X
Vital status11
X
1.
At Visit 1, all subjects at all sites will be evaluated via CASPAr for history of psoriatic arthritis as detailed in Appendix F.
2.
Refer to Section 5.3.1.1 for weight procedures.
3.
Physical examination:  C = complete, T = targeted.  Refer to Section 5.3.1.
4.
Vital signs should precede blood sampling and be assessed pre-dose at all dosing visits.  Additional vital signs assessments at 5 minutes post-dose and 60 minutes post-dose at 
Visit 2 and Visit 3.  Monitor for signs and symptoms of hypersensitivity reactions for approximately 2 hours after the first dose administered at Visit 2 and 1 hour following 
all other doses of study drug.
5.
Infection screening consists in 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), 
QuantiFERON-TB.  Refer to Appendix D.
6.
Serum pregnancy testing at screening and if urine pregnancy test is positive.  Urine pregnancy testing will be done prior to administration of study drug at all dosing visits and 
at each Follow-Up (FU) Visit.  
7.
C = complete, T = targeted.  Targeted lab samples should be limited to WBC, serum CRP and serum albumin for the measurement of JDA.  Subjects should be fasting for at 
least 8 hours prior to the blood sample being taken at the "complete" visits, except for screening.  If not fasted mark on laboratory requisition form.
8.
On dosing visits, PK and ADA sampling should be taken approximately within 1 hour prior to administration of study drug.
9.
Collected for Substudy GPP.
10. Subjects that terminate trial medication early will complete EOT Visit procedures instead of the planned treatment period visit and return for Week 188 Follow-up Visit, 
16 weeks after last dose of study medication.


Risankizumab
M15-988 Protocol Amendment 1
102
11. Vital Status should be collected for subjects leaving the study before the planned Week 188 Follow-up visit.


Risankizumab
M15-988 Protocol Amendment 1
103
Has been changed to read:
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448 532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Informed consent
X
Demographics
X
Medical history
X
Smoking/alcohol 
history
X
Prior and ongoing 
medication
X
Psoriatic arthritis 
history1
X
In-/exclusion criteria
X
X
Height
X
Weight/waist 
circumference2
X
X
X
Physical 
examination3
Xc
Xt
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xt
Xc
Vital signs4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


Risankizumab
M15-988 Protocol Amendment 1
104
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448 532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Infection screening5
X
X
X
X
X
Chest X-ray
X
X
X
X
Pregnancy testing6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory 
tests7
Xc
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xt
Xt
Xc
Xt
Xc
Xc
Xc
12 lead-ECG
X
PK sampling8
X
X
X
X
X
X
X
X
X
X
X
X
ADA sampling8
X
X
X
X
X
X
X
X
X
X
X
X
Local tolerability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
JDA score and 
responder rating
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PGA-GPP9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CGI-GI10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Contact IRT
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Administration of 
trial drugs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


Risankizumab
M15-988 Protocol Amendment 1
105
Trial Periods
Screening
Treatment
Follow-Up
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
17
V
18
V
19
V
20
V
21
EOT/ 
PD
Week
0
4
8
12
16
22
28
34
40
46
52
64
76
88
100
112
124
136
148
160
172
184
188
Day 
–42 to –1
1
28
56
84
112
154 196
238
280 322 364 448 532
616
700
784
868
952 1036 1120 1162 1246 1274
Visit window (days)
± 3
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
± 7
Last injection of trial 
medication11
X
Trial completion
X
Vital status12
X
1.
At Visit 1, all subjects at all sites will be evaluated via CASPAr for history of psoriatic arthritis as detailed in Appendix F.
2.
Refer to Section 5.3.1.1 for weight procedures.
3.
Physical examination:  C = complete, T = targeted.  Refer to Section 5.3.1.
4.
Vital signs should precede blood sampling and be assessed pre-dose at all dosing visits.  At Visit 2 and Visit 3, additional vital sign assessments should be taken at 5 minutes 
post-dose and 60 minutes post-dose.  Subjects should be closely monitored for signs and symptoms of hypersensitivity reactions for approximately 2 hours after the first dose 
administered and 1 hour following all other doses of study drug.
5.
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 or QuantiFERON-TB.  Hepatitis B, Hepatitis C and HIV testing will be performed at screening.  TB testing will be performed at screening, Visit 12, 16, 20 and 
Week 184.
6.
Serum pregnancy testing in all female subjects at screening and if urine pregnancy test is positive.  Urine pregnancy testing will be done in women of child-bearing potential 
prior to administration of study drug at all dosing visits and at each Follow-Up Visit.  
7.
C = complete, T = targeted.  Targeted lab samples should be limited to WBC, serum CRP and serum albumin for the measurement of JDA.  Subjects should be fasting for at 
least 8 hours prior to the blood sample being taken at the "complete" visits, except for screening.  If not fasted mark on laboratory requisition form.
8.
On dosing visits, PK and ADA sampling should be taken approximately within 1 hour prior to administration of study drug.
9.
Collected for Substudy GPP.
10. Collected for Substudy EP.


Risankizumab
M15-988 Protocol Amendment 1
106
11. Subjects that terminate trial medication early will complete EOT Visit procedures instead of the planned treatment period visit and return for Week 188 Follow-up Visit, 
16 weeks after last dose of study medication.
12. Vital Status should be collected for subjects leaving the study before the planned Week 188 Follow-up visit.


Risankizumab
M15-988 Protocol Amendment 1
107
Appendix D.  Severity Assessment Criteria Score
Third paragraph, in-text table
Last row previously read:
Score
2
1
0
Serum albumin (mg/dL)
< 3.0
≥3.0 and < 3.8
≥3.8
Has been changed to read:
Score
2
1
0
Serum albumin (g/dL)
< 3.0
≥3.0 and < 3.8
≥3.8



SAP_000.pdf: 
Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
1
1.0
Title Page
Statistical Analysis Plan
Study M15-988
A Phase 3, Randomized, Open-Label Study to Assess 
Efficacy and Safety of Two Different Dose Regimens 
of Risankizumab Administered Subcutaneously in 
Japanese Subjects with Generalized Pustular 
Psoriasis or Erythrodermic Psoriasis
Date:  05 Jan 2018
Version 2.0


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
2
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
Primary Study Objective......................................................................... 5
4.2
Design Diagram ..................................................................................... 5
4.3
Sample Size............................................................................................ 6
4.4
Interim Analysis..................................................................................... 7
5.0
Analysis Populations .............................................................7
5.1
Variables Used for Stratification of Randomization ................................ 7
6.0
Analysis Conventions ............................................................7
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications..............14
7.1
Demographic and Baseline Characteristics ........................................... 14
7.2
Medical History.................................................................................... 16
7.3
Previous Treatment and Concomitant Medications ............................... 16
7.4
Protocol Deviation................................................................................ 17
8.0
Patient Disposition............................................................... 17
9.0
Study Drug Exposure and Compliance.............................. 18
10.0
Efficacy Analysis .................................................................18
10.1
General Considerations......................................................................... 18
10.2
Primary Efficacy Endpoints.................................................................. 19
10.3
Secondary Efficacy Endpoints.............................................................. 20
10.4
Other Efficacy Endpoint(s)................................................................... 20
11.0
Safety Analysis.....................................................................21
11.1
General Considerations......................................................................... 21
11.2
Analysis of Adverse Events.................................................................. 22
11.2.1
Treatment-Emergent Adverse Events.................................................... 22
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 28
11.3
Analysis of Laboratory Data................................................................. 28


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
3
11.3.1
Variables and Criteria Defining Abnormality........................................ 28
11.3.2
Statistical Methods ............................................................................... 30
11.4
Analysis of Vital Signs and Weight ...................................................... 33
11.4.1
Variables and Criteria Defining Abnormality........................................ 33
11.4.2
Statistical Methods ............................................................................... 33
12.0
Pharmacokinetic Analysis...................................................34
13.0
Biomarkers Analysis ...........................................................34
14.0
Summary of Changes .......................................................... 34
14.1
Summary of Changes between the Latest Version of Protocol and 
the Current SAP ................................................................................... 34
14.2
Summary of Changes between the Previous Version and the 
Current Version of the SAP .................................................................. 34
15.0
Appendix.............................................................................. 34
16.0
References............................................................................34
17.0
List of Tables, Figures and Data Listings that Are to 
be Programmed ...................................................................34
List of Tables
Table 1.
Visit Windows for Analysis of Clinical Laboratory Tests (WBC, 
CRP and ALB), Vital Signs, Local Tolerability, and Efficacy 
Variables (PASI/JDA Score and Responder Rating/PGA-
GPP/CGI-GI/BSA)............................................................................... 10
Table 2.
Visit Windows for Analysis of Clinical Laboratory Tests
(excluding WBC, CRP and ALB)......................................................1010
Table 3.
Visit Windows for Analysis of Efficacy Variable (DLQI)..................... 12
Table 4.
Areas of Safety Interest ........................................................................ 26
Table 5.
Clinical Laboratory Tests ..................................................................... 29
Table 6.
Criteria for Potentially Clinically Important Chemistry Values ............. 31
Table 7.
Criteria for Potentially Clinically Important Hematology Values .......... 31
Table 8.
Criteria for Potentially Clinically Significant Vital Sign Findings ......... 33


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
4
List of Figures
Figure 1.
Trial Design ........................................................................................... 6


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
5
3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Clinical Statistics Department for study Protocol M15-988 Amendment 1 
dated 18 January 2017. 
This SAP will provide details to further elaborate statistical methods as outlined in the 
Protocol M15-988 and will describe analysis conventions to guide the statistical 
programming work.  The SAP will be signed off before the study database is locked. 
Analyses will be performed using SAS® version 9.4 (SAS Institute, Inc., Cary, NC  
27513) or higher using the UNIX operating system.
4.0
Study Objectives, Design and Procedures
4.1
Primary Study Objective
The primary objectives of this study are to investigate the safety and efficacy of 
two different dose regimens of risankizumab for Japanese subjects with GPP or EP.
4.2
Design Diagram
This trial is a randomized, open-label study of two different dose regimens of 
risankizumab, 150 mg (2 syringes, 75 mg each) or 75 mg (1 syringe) at Week 0, 4 and 
every 12 weeks in two populations (subjects with GPP and with EP).  Starting after the 
Week 16 visit, subjects on 75 mg may increase dosage to 150 mg.  In total, at least 
16 subjects, 8 with generalized pustular psoriasis and 8 with erythrodermic psoriasis will 
be randomized in this trial.  From Week 16, subjects will be uptitrated to 150 mg if they 
have not achieved a clinical response (for subjects with GPP:at least "Slightly Improved" 
in the overall improvement rating from baseline according to JDA total score; for subjects 
EP:  at least "Minimally Improved" in Clinical Global Impression-Global Improvement).


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
6
Figure 1.
Trial Design
All subjects are to adhere to the visit schedule as specified in the Protocol Appendix C 
Each visit date (with its window) is to be counted from Day 1.  If any visit has to be 
rescheduled, subsequent visits should follow the original visit date schedule.  Additional 
visits for the purpose of re-testing of laboratory parameters or AE monitoring may be 
included as deemed necessary by the investigator.
4.3
Sample Size
The sample size is not estimated based on powering for any hypothesis testing.  There are 
only approximately 1600 and 40000 Japanese subjects with generalized pustular psoriasis 
and erythrodermic psoriasis respectively, thus finding subjects to participate in the trial 
will be difficult.  Therefore, the sample size is determined based on feasibility.  In total, at 
least 16 subjects will be enrolled:  at least 8 subjects for GPP and EP separately.


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
7
4.4
Interim Analysis 
An interim analysis will be conducted when the last subject completes the Week 28 visit 
and all data pertaining to Week 28 and earlier are cleaned.  For this analysis all Week 16 
efficacy endpoints will be analysed, and all safety as well as pharmacokinetic and 
antiimmunogenicity data received by cut-off date will be analysed.  Another interim 
analysis will be conducted when the last subject completes the Week 52 visit.  The 
analyses will be performed for the efficacy endpoints until Week 52, as well as all safety 
and pharmacokinetic and immunogenicity data received by cut-off date.
Additional interim analysis may be performed if deemed necessary for regulatory purpose.
5.0
Analysis Populations
The Intent-to-Treat (ITT) subject population in each Substudy is defined as all 
randomized subjects with at least one dose of study drug.  The Safety population is the 
same as the ITT population.
5.1
Variables Used for Stratification of Randomization
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 fashion in each group to 
either 150 mg (2 syringes, 75 mg each) or 75 mg (1 syringe) at Week 0, 4 and every 
12 weeks.  Randomization will be done using an adequate block size. 
6.0
Analysis Conventions
Since this is an open-label continuation study, no statistical test will be conducted.  
Summary statistics will be provided.  Data from preceding studies will be integrated with 
data from this study in the summaries.


Risankizumab
M15-988 – Statistical Analysis Plan
Version 2.0 – 05 Jan 2018
8
Definition of Baseline
For this study, baseline values are defined as the last non-missing values prior to the 
first dose of study drug in this study.  These baseline values will be referred to as "BL" in 
this document.  Unless otherwise specified, this will be the "baseline" for analysis.
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 this study.  
They are defined as the number of days between the day of the first dose of risankizumab 
and the specific time point.  Rx days are negative values when the time point of interest is 
prior to the first risankizumab dose day.  Rx days are positive values when the time point 
of interest is on or after the first risankizumab dose day.  The day of the first dose of 
risankizumab is defined as Rx Day 1, while the day prior to the first risankizumab 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.
For efficacy analyses, local tolerability, laboratory parameters, and vital sign variables, 
analysis windows are constructed using the following algorithm:
●
Determine the nominal Rx day for each visit (e.g., Week 4 [4 weeks after 
Baseline visit] equals Rx Day 28).
●
In order to include all post baseline data, the first post-baseline interval starts 
on the first day and the time after the first dose of risankizumab (Rx Day 1).
●
Determine the window around a specific nominal Rx day, are presented in the 
Protocol Appendix C.
●
If more than one assessment is included in a time window the assessment 
closest to the nominal day will be used.  If there are two observations 
equidistant to the nominal day, the one after the nominal day will be used in 
analyses.  If more than one post baseline assessment is included on the same 


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day, then the worst assessment on that day will be used in analyses, except 
those specified in Section 11.0.
The protocol specified visits and corresponding time windows used in the efficacy 
analyses, local tolerability, laboratory parameters, and vital sign variables, are presented 
in the following Table 1 – Table 32. 


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Table 1.
Visit Windows for Analysis of Clinical Laboratory Tests, Vital 
Signs, Local Tolerability (WBC, CRP and ALB), and Efficacy 
Variables (PASI/JDA Score and Responder Rating/PGA-GPP/CGI-
GI/BSA)
Window Label
Target Day
Interval
Screening
–
[–42, –1]
Baselinea
1
≤ 1b
Week 4
29
[2, 43]
Week 8
57
[44, 71]
Week 12
85
[72, 99]
Week 16
113
[100, 134]
Week 22
155
[135, 176]
Week 28
197
[177, 218]
Week 34
239
[219, 260]
Week 40
281
[261, 302]
Week 46
323
[303, 344]
Week 52
365
[345, 407]
Week 64
449
[408, 491]
Week 76
533
[492, 575]
Week 88
617
[576, 659]
Week 100
701
[660, 743]
Week 112
785
[744, 827]
Week 124
869
[828, 911]
Week 136
953
[912, 995]
Week 148
1037
[996, 1079]
Week 160
1121
[1080, 1142]
Week 172
1163
[1143, 1205]
Week 184
1247
[1206, 1261]
Week 188
1275
[1262, 1282]
Rx Day calculated relative to first dose of risankizumab.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
There is no baseline for local tolerability measurements and CGI-GI.
b.
If time is collected, restrict to records prior to the first dose of study drug.


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Table 2.
Visit Windows for Analysis of Clinical Laboratory Tests (excluding 
WBC, CRP and ALB)
Window Label
Target Day
Interval
Screening
–
[–42, –1]
Baselinea
1
≤ 1a
Week 8
57
[2, 85]
Week 16
113
[86, 155]
Week 28
197
[156, 239]
Week 40
281
[240, 323]
Week 52
365
[324, 533]
Week 100
701
[534, 869]
Week 148
1037
[870, 1100]
Week 172
1163
[1101, 1205]
Week 184
1247
[1206, 1261]
Week 188
1275
[1262, 1282]
Rx Day calculated relative to first dose of risankizumab.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
If time is collected, restrict to records prior to the first dose of study drug.


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Table 32.
Visit Windows for Analysis of Efficacy Variable (DLQI) 
Window Label
Target Day
Interval
Baseline
1
≤ 1a
Week 12
85
[2, 99]
Week 16
113
[100, 239]
Week 52
365
[240, 407]
Week 64
449
[408, 491]
Week 76
533
[492, 575]
Week 88
617
[576, 659]
Week 100
701
[660, 743]
Week 112
785
[744, 827]
Week 124
869
[828, 911]
Week 136
953
[912, 995]
Week 148
1037
[996, 1079]
Week 160
1121
[1080, 1142]
Week 172
1163
[1143, 1205]
Week 184
1247
[1206, 1261]
Week 188
1275
[1262, 1282]
Rx Day calculated relative to first dose of risakizumab.  For subjects randomized but not dosed, Rx Day calculated 
relative to Randomization.
a.
If time is collected, restrict to records prior to the first dose of study drug.
Definition of Missing Data Imputation
The following rules will be used to impute for missing data.  Data imputation will be used 
for missing values in the efficacy analysis, but not the safety analyses.
●
For continuous endpoints, LOCF (Last Observation Carried Forward) will be 
used to impute missing values.  The LOCF will use the last observed non-
missing evaluation (last completed non-missing evaluation, from composite 
endpoint) from the previous visit within the particular period for efficacy 
measures assessed to impute missing data at later visits in the same period.  
Baseline efficacy evaluations will not be carried forward.
●
For all binary endpoints (i.e., endpoints that are either 1 (subject responded) or 
0 (subject did not respond):


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1.
If no assessment after that visit*, then impute as failure (NRI [No 
Response Imputation])
2.
If there are assessments at visits* before and after, only impute as 
success if both visits are successes; else impute as failure
Subjects that take prohibited medications to treat Psoriasis will be treated the same as 
those that discontinued from the trial – i.e., subsequent visits following start of prohibited 
medication will be considered as failure for binary endpoints.
Rounding of Numeric Results
Rounding will be performed for presentation of results.  No rounding will be performed 
before or during analyses.  The ROUND function of SAS will be used to round results. 
When dichotomizing continuous variables, associated continuous variables will be 
rounded to 9 decimal points before applying the cutoff point to determine the response 
status (for example, percent change from baseline in PASI score will be rounded to 
9 decimal places before comparing to 90%).
The mean and median will be rounded for presentation to 1 decimal more than the data 
entered into the database.  The standard deviation will be rounded to 2 decimal places 
more than the data entered into the database.  The minimum and maximum values will be 
presented as entered into the database.
Probabilities will be rounded to 3 decimal places before assignment of statistical 
significance and will be presented in rounded format.  Probabilities that round to zero or 
are reported by SAS as zero will be presented as "< 0.001."  Probabilities that round to 1 
or are reported by SAS as 1 will be presented as "> 0.999."


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7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
Demographics and Baseline characteristics will be summarized for ITT population, 
two different treatment arms (150 mg or 75 mg) and two diseases (GPP or EP).  
Continuous variables will be summarized with the number of non-missing observations 
by mean, standard deviation, median, minimum and maximum values.  Categorical data 
will be summarized using frequencies and percentages.  No Statistical tests will be 
performed for this study. 
The following demographic and baseline parameters will be summarized. 
Subject Demographics
●
Sex (male, female)
●
Age (years), defined as the number of years from date of birth to date of 
first drug
●
Age categories (< 40 years, ≥ 40 – < 65 years, ≥ 65 years.)
●
Race (American Indian or Alaska Native, Asian, Black or African American, 
Native Hawaiian or Other Pacific Islander, White, Multi Race)
●
Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
●
Body weight (kg)
●
Body weight category (≤ MEDIAN kg, > MEDIAN kg)
●
Height (cm)
●
BMI (kg/m2)
●
BMI category (< 25, ≥ 25 – < 30, ≥ 30)
General Baseline Characteristics
●
PASI (Psoriasis Area and Severity Index)
●
JDA (Japanese Dermatological Association) component scores (Mild, 
Moderate, Severe)


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●
PGA-GPP (Physician's Global Assessment of Generalized Pustular Psoriasis) 
(Cleared, except for residual, Minimal, Mild, Moderate, Severe, Very severe)
●
DLQI (Dermatology Life Quality Index)
●
BSA (Body surface area)
●
C-Reactive Protein
Psoriatic Arthritis and Cardiovascular History
●
Psoriatic arthritis (yes, no)
●
Cardiovascular Diseases (myocardial infarction, angina pectoris, transient 
ischemic attack, stroke, deep vein thrombosis)
●
Cardiovascular Risk Factors (hypertension, hyperlipidemia, diabetes mellitus, 
obesity)
General Use 
●
Smoking status (Current, Former, Never, Unknown)
●
Alcohol status (Current, Former, Never, Unknown)
Prior Treatment
●
Prior Biological Medication History (yes, no)
●
Prior non-Biological Medication History (yes, no)
●
Prior Psoriasis Therapy (yes, no)
Vital Signs at Baseline
●
Systolic blood pressure (mmHg)
●
Diastolic blood pressure (mmHg)
●
Pulse (beats per minute)
●
Respiratory rate (breaths per minute) 
●
Temperature (°C)


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Clinical Tests at Screening
●
Chest x-ray
●
Tuberculin PPD skin test, QuantiFERON TB Gold test
●
Hepatitis Testing
●
Serum pregnancy test
●
ECG
Immunization History
●
BCG immunization
●
Hepatitis B immunization
Also, Physical Exam and Pregnancy Test will be presented in listing format.
7.2
Medical History
Medical or surgical history other than psoriatic arthritis or cardiovascular diseases will be 
summarized using body systems and condition/diagnosis as captured on the eCRF for ITT 
population, two different treatment arms (150 mg or 75 mg) and two diseases (GPP or EP).  
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 and disease.  Subjects reporting more than one condition/diagnosis within a 
body system will be counted only once for that body system.  Tuberculosis history will be 
also summarized.
7.3
Previous Treatment and Concomitant Medications
Prior and concomitant medications will be summarized for ITT population, 
two different treatment arms (150 mg or 75 mg) and two diseases (GPP or EP) by generic 
name.  A prior medication is defined as any medication taken at the time of entry into the 
study and prior to the first dose of risankizumab.  A concomitant medication is defined as 
any medication that started prior to the first dose of risankizumab and continued to be 


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taken after the first dose of risankizumab or any medication that started after the first dose 
of risankizumab, 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.
7.4
Protocol Deviation
Number and percentage of subjects who reported at least one of the following protocol 
deviation categories will be provided in the ITT population, two different treatment arms 
(150 mg or 75 mg) and two diseases (GPP or EP).
●
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 
8.0
Patient Disposition 
The number of subjects will be tabulated by investigator site and overall.  The number of 
subjects for each of the following categories will be summarized, for overall, 
two different treatment arms (150 mg or 75 mg) and two diseases (GPP or EP) in the ITT 
population.
●
Number of subjects randomized
●
Number of subjects that took at least one dose of study drug
●
Number of subjects who completed at Week 28
●
Number of subjects who prematurely discontinued from the study before 
Week 28
In addition, the number and percentage of subject who discontinued the study drug will be 
summarized by following categorized reason (primary and all) with frequencies and 


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percentages for overall, two different treatment arms (150 mg or 75 mg) and two diseases 
(GPP or EP) in the ITT population.  Subjects with multiple reasons for premature 
discontinuation will be counted once in the calculation of the number and percentage of 
total discontinuations ("Premature Discontinuation").
●
Adverse event
●
Withdrew consent
●
Lost to follow-up
●
Others.
9.0
Study Drug Exposure and Compliance
Study drug exposure (days) will be summarized using the sample size, mean, standard 
deviation, minimum, median and maximum.  Study drug exposure will be summarized for 
overall, two different treatment arms (150 mg or 75 mg) and two diseases (GPP or EP) in 
the ITT population as follows:
Risankizumab Exposure (in Days):
The Risankizumab Exposure (total duration) will be defined as follows:
The Risankizumab Exposure = Last risankizumab dose date – First risankizumab dose 
date + 1
10.0
Efficacy Analysis
10.1
General Considerations
The efficacy analysis will be performed for two different treatment arms (150 mg or 
75 mg) and two diseases (GPP or EP) in the ITT population.  The efficacy analysis will 
use the data from the study after subjects started to take Risankizumab.  The BL values 
(baseline values) will be used to determine responses and changes in the efficacy variables. 


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Continuous variables will be summarized by the number of observations, mean, standard 
deviation, median, minimum, maximum as well as the 95% confidence intervals (CIs) of 
the mean values.  Categorical variables will be summarized by counts and percentages, as 
well as the 95% CIs of the percentages.  No statistical tests will be performed in this study.
Missing data will be imputed using NRI and LOCF methods (see Section 6.0) for the 
efficacy analyses.  And As-Observed Cases (OC) method also will be used for efficacy 
analyses.
●
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.
10.2
Primary Efficacy Endpoints
The following key efficacy variables will be summarized at all visits it the ITT population 
for each disease:
For GPP:
●
Proportion of subjects achieving a GPP Clinical Response according to JDA 
total score, defined as at least "Slightly Improved" in the overall improvement 
rating from baseline, at Week 16.
For EP:
●
Proportion of subjects achieving an EP Clinical Response, defined as at least 
"Minimally Improved" in Clinical Global Impression-Global Improvement 
(CGI-GI) at Week 16.


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10.3
Secondary Efficacy Endpoints
The following additional efficacy variables will be summarized at all visits in the ITT 
population:
For GPP:
●
Proportion of subjects achieving a GPP Clinical Response at Week 52
●
Proportion of subjects achieving ≥ 90% reduction from baseline Psoriasis Area
●
Severity Index (PASI) score (PASI 90) at Week 16
●
Proportion of subjects achieving PASI 90 at Week 52
For EP
●
Proportion of subjects achieving an EP Clinical Response at Week 52
●
Proportion of subjects achieving PASI 90 at Week 16
●
Proportion of subjects achieving PASI 90 at Week 52
10.4
Other Efficacy Endpoint(s)
The following endpoints will be summarized at each scheduled visit that the respective 
variable is collected:
For GPP
●
Proportion of subjects achieving a GPP Clinical Response, defined at least 
"Slightly Improved" according to JDA total score in the overall improvement 
rating from baseline.
●
Change from baseline in each of the JDA component scores
●
Change and Percent change from baseline in JDA score
●
Change and Percent change from baseline in PASI
●
Change from baseline in BSA
●
Proportion of subjects achieving PASI 50/75/90/100 response


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●
Proportion of subjects achieving Dermatology Life Quality Index (DLQI) of 
0/0 or 1
●
Change from baseline in DLQI
●
Proportion of subjects achieving at least two grades of improvement in 
Physician's Global Assessment of Generalized Pustular Psoriasis (PGA-GPP).
For EP
●
Proportion of subjects achieving an EP Clinical Response, defined at least 
"Minimally Improved" in CGI-GI for EP
●
Proportion of subjects achieving at least "Much Improved" in CGI-GI for EP
●
Percent change from baseline in PASI
●
Change from baseline in PASI
●
Proportion of subjects achieving PASI 50/75/90/100 response
●
Change from baseline in BSA
●
Proportion of subjects achieving DLQI of 0/0 or 1
●
Change from baseline in DLQI
11.0
Safety Analysis
11.1
General Considerations
Safety analyses will include adverse events, laboratory, local tolerability, ECG, and vital 
sign measurements. 
For the safety analyses, a baseline value (BL) is defined as the last non-missing 
observation on or prior to the date of the first dose of Risankizumab in this study.  Safety 
summaries will be performed for two different treatment arms (150 mg or 75 mg) total 
arms, two diseases (GPP or EP) and overall in the safety population.  The safety 
population is same as the ITT population.


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11.2
Analysis of Adverse Events
11.2.1
Treatment-Emergent Adverse Events
Treatment emergent adverse events (TEAEs) are defined as any event with an onset that is 
after the first dose of risankizumab and with an onset date within 105 days after the last 
dose of study drug in the analysis period.
●
TEAE of Retreatment:  TEAE are defined as any event with an onset that is 
after the first dose of retreatment and no more than 105 days after the last dose 
of study drug.
Events where the onset date is the same as the study drug start date are assumed to be 
treatment emergent, unless the adverse event start time is prior to the study drug start time.  
If an incomplete onset date is collected for an adverse event, the event will be assumed to 
be treatment-emergent unless there is other evidence that confirms that the event is not 
treatment-emergent (e.g., the event end date is prior to the study drug start date).
The number and percent of subjects experiencing treatment-emergent TEAEs will be 
tabulated using the Medical Dictionary for Drug Regulatory Activities (MedDRA®) 
system organ class and preferred term.
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
●
Any serious AE that was assessed as related to study drug by the investigator
●
Any AE leading to discontinuation of study drug


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●
Any AE leading to death
●
Any deaths
●
Areas of Safety Interest
2.
Adverse Events by System Organ Class and Preferred Term
TEAEs will also be summarized and presented using primary Medical Dictionary 
for Regulatory Activities (MedDRA) 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.
In addition, the number and percentage of adverse events events with causal 
relationship between the events and the study drug will be summarized using the 
same conventions described above.
3.
Adverse Events by Maximum Severity
The severity grading of AEs follows Rheumatology Common Toxicity Criteria 
(RCTC).  
●
Grade 1 – mild
●
Grade 2 – moderate
●
Grade 3 – severe
●
Grade 4 – life threatening
Adverse events will also be summarized by maximum severity.  If a subject has an 
adverse event with unknown severity, then the subject will be counted in the 
severity category of "unknown," even if the subject has another occurrence of the 
same event with a severity present.  The only exception is if the subject has another 


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occurrence of the same adverse event with the most extreme severity – ("Life-
threatening").  In this case, the subject will be counted under the "Life-threatening" 
category.  
4.
Adverse Events by Maximum Relationship
Adverse events will be summarized by maximum relationship to study drug, as 
assessed by the investigator.  Relationship of an AE to study drug is assessed by 
the investigator and collected in the CRF as 'Yes' or 'No.'  If a subject has an 
adverse event with unknown relationship, the subject will be counted in the 
relationship category of "unknown," even if the subject has another occurrence of 
the same event with a relationship of "No."  If the subject has another occurrence of 
the same adverse event with a relationship assessment of "Yes," the subject will be 
counted under the "yes" category. 
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 System Organ Class and Preferred Term
●
Grouped by System Organ Class, Preferred Term and Relationship to Study 
Drug
●
Grouped by System Organ Class, Preferred Term and Severity
Treatment-emergent serious adverse events will be summarized as follows:
●
Grouped by System Organ Class and Preferred Term
●
A by-subject listing will be provided
Pre-treatment serious adverse events will be summarized as follows:
●
A by-subject listing will be provided


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Treatment-emergent adverse events leading to death or premature discontinuation 
of study drug will be summarized as follows:
●
Grouped by System Organ Class and Preferred Term
●
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 System Organ Class and Preferred Term
●
A listing by subject will be provided.
Areas of Safety Interest:
Areas of Safety Interest groupings are listed in Table 43.  These events are of interest due 
to a higher rate in the moderate to severe psoriasis population, or of interest for all Ig 
products or products in general (DILI).
The final list will be based on the most updated final version of risankizumab Product 
Safety Statistical Analysis Plan, which is consistent to the most updated risankizumab 
Risk Management Plan.
Grouped Terms
Grouped terms will be summarized by grouped term or SMQ, including sub-SMQs and 
preferred term for any adverse event, adverse events leading to discontinuation, serious 
adverse events, moderate or severe adverse events and related adverse events.


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Table 43.
Areas of Safety Interest
ASI 
Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Adjudicated 
CV Events
Major adverse 
cardiovascular 
events 
(MACE)
Adjudicated 
events
Display underlined terms defined by 
the following adjudicated terms:
!
CV Death which includes 
CETERM values:  Fatal CV, 
Fatal PE, Fatal Non-
Cardiac/Non-Neuro Arterial 
Thrombosis/Thromboembolism, 
Undetermined Death, Not 
assessable death 
(cardiac/neuro/thrombotic), Fatal 
Stroke
!
Myocardial infarction
!
Stroke
Y
Extended 
MACE
Adjudicated 
events
Display underlined terms from MACE 
and underlined terms below:
!
Hospitalization for Unstable 
Angina
!
Coronary Revascularization 
Procedures
N
Other CV 
events
Adjudicated 
events
Display underlined terms defined by 
the following adjudicated terms:  
!
Thrombotic events which 
includes CETERM values:  Deep 
Vein Thrombosis, TIA,  
Pulmonary Embolism, Non-fatal 
Non-Cardiac/Non-Neurological 
Arterial Thrombosis/ 
Thromboembolism, Other 
Venous Thrombosis, specified 
(non-fatal)
!
Cardiac arrhythmia which 
includes CETERM of:  Clinically 
Significant Arrhythmia
!
Congestive heart failure which 
includes CETERM of Heart 
Failure
!
Hypertensive emergency
N


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Table 43.
Areas of Safety Interest (Continued)
ASI 
Grouping
Categories 
(ASI)
Search Criteria
Terms to Display
Include 
in AE 
Overview 
(Y/N)
Possible 
Drug 
induced 
liver injury 
(DILI)
Possible Drug 
induced liver 
injury (DILI)
Broad – Hepatic 
failure, fibrosis 
and cirrhosis and 
other liver 
damage-related 
conditions 
(SMQ 20000013)
Broad – Hepatitis, 
non-infectious 
(SMQ 20000010)
Broad –
Cholestasis and 
jaundice of 
hepatic origin 
(SMQ 20000009)
Broad – Liver 
related 
investigations, 
signs and 
symptoms 
(SMQ 20000008)
Narrow – Liver-
related 
coagulation and 
bleeding 
disturbances 
(SMQ 20000015)
PTs
Y
Adverse Event per 100 Patient-Years of Exposure
Adverse events occurring during the entire study will be presented by event rate per 
100 patient-year.  These will be presented for any TEAEs, serious adverse events, Areas 
of Special 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 


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subject will be counted in the calculation of the number of AEs (i.e., a preferred term will 
not be counted twice on the same day for the same subject).  See the calculation method 
below.
where total patient years is defined as the sum of the study drug exposure (defined as date 
of last dose – date of first dose + 105 days (5 half-lives)) of all subjects normalized by 
365.25, and rounded to one decimal place.
11.2.2
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Deaths and all SAEs will be presented in listing format.  In addition, SAEs and AE 
leading to study drug discontinuation will be summarized by System Organ Class and 
MedDRA Preferred Term.
11.3
Analysis of Laboratory Data
Listing and descriptive statistics of laboratory values over time, changes from baseline, 
and extreme abnormal value on treatment will be provided.  Baseline is understood as the 
last available measurement before study drug administration.  Extreme abnormal value on 
treatment is understood as the on treatment laboratory 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 are listed in Table 54.
Years
Patient 
Total
TEAEs
of
Number 
100 ∀


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Table 54.
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 (relative count)
Eosinophils (relative count)
Basophils (relative count)
Monocytes (relative count)
Lymphocytes (relative count) 
Enzymes
AST (GOT)
ALT (GPT)
Alkaline Phosphatase (AP)
Creatine Kinase (CK)
Gamma-Glutamyl Transferase (GGT/γ-GT) 
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate
Substrates
Glucose
BUN (blood urea nitrogen)
Creatinine
eGFR (estimated by CKD-EPI formula)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Albumin
C-Reactive Protein (CRP) (high sensitivity)
Cholesterol, total
Triglycerides
LDL-Cholesterol
HDL-Cholesterol
Urinalysis (dipstick)
Urine pH


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11.3.2
Statistical Methods
Analysis of Quantitative Laboratory Parameters (Hematology, Chemistry and
Urinalysis)
Though the protocol indicates utilizing the Rheumatology Common Toxicity Criteria 
(RCTC) scale for grading laboratory values, given that the National Cancer Institute 
Common Toxicity Criteria for Adverse Events (NCI CTCAE) scale includes a more 
comprehensive list of laboratory values, the lab analyses based on the NCI CTCAE scale 
will be presented.  Changes from Baseline to each scheduled visit and to the final value in 
continuous laboratory parameters will be summarized with the mean, standard deviation 
and median.
If there are multiple post-baseline measurements on the same day, average value will be 
used.
Shift Tables
Shift tables for changes from Baseline according to the normal range will be provided for 
each hematology, clinical chemistry and urinalysis (pH only) parameter.  Shifts from 
Baseline to the following endpoints will be considered:  minimum value, maximum value 
and final value.  Categories of "low or normal" and "high or normal" will be included at 
Baseline in addition to the categories of "low," "normal," "high" and "missing."  If there 
are multiple post-baseline measurements on the same day, last value will be used.
Potentially Clinically Significant Laboratory Values
Frequencies and percentages of subjects with post Baseline lab values met the following 
criteria in Table 65 and Table 76 will be summarized. 


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Table 65.
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
ALP
U/L
> 5.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
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
Table 76.
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.


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If there are multiple 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
●
≥ 20.0 × ULN
Shift tables of Baseline to the maximum (relative to the normal range, i.e., the largest 
multiple relative to the upper limit of normal) values, and from Baseline to final value will 
be presented using these five categories.  A listing of potentially clinically significant liver 
function laboratory values will be provided.  The listing will include all subjects who met 
any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or
●
Alkaline phosphatase ≥ 1.5 × ULN, or
●
Total bilirubin ≥ 2 × ULN.
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


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●
Alkaline phosphatase < 2 × ULN
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 87 presents the Criteria for 
Potentially Clinically Significant Vital Sign Findings.
Table 87.
Criteria for Potentially Clinically Significant Vital Sign Findings
Vital Sign
Category
Criteria for Potential Clinically Significant Vital Signs
Systolic Blood Pressure
Low Value
≤ 90 mmHg or decrease ≥ 20 mmHg from Baseline
High Value
≥ 180 mmHg or increase ≥ 20mmHg from Baseline
Diastolic Blood Pressure
Low Value
≤ 50 mmHg or decrease ≥ 15 mmHg from Baseline
High Value
≥ 105 mmHg or increase ≥ 15 mmHg from Baseline
Pulse
Low Value
≤ 50 bpm or decrease ≥ 15 bpm from Baseline
High Value
≥ 120 bpm or increase ≥ 15 bpm from Baseline
11.4.2
Statistical Methods
Changes from Baseline to each visit and to the final value in vital sign parameters will be 
summarized with the mean, standard deviation and median.  The Baseline and final value 
means will also be presented for subjects who have both the Baseline and final values.
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 
listed.  The number and percentage of subjects who have at least one value meeting 


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criteria for potentially clinically important values will be provided for each selected vital 
sign parameter.
12.0
Pharmacokinetic Analysis
Pharmacokinetic analysis will not be covered in this SAP.
13.0
Biomarkers Analysis
Biomarker Analysis is not covered in this SAP.
14.0
Summary of Changes
Not applicable.
14.1
Summary of Changes between the Latest Version of 
Protocol and the Current SAP
14.2
Summary of Changes between the Previous Version and the 
Current Version of the SAP
15.0
Appendix
Not applicable.
16.0
References
Not applicable.
17.0
List of Tables, Figures and Data Listings that Are to 
be Programmed
To be provided in a separate document.