Clinical trial NCT04435600
Conditions: Psoriasis
Keywords: Plaque Psoriasis Risankizumab Ustekinumab Psoriasis Biologic ABBV-066 SKYRIZI
Sponsor: AbbVie
Start date: 2020-07-14; Completion date: 2024-10-15
Enrollment: 139 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Psoriasis is a chronic, systemic, inflammatory disease in which skin cells build up and develop thick, red and white scaly patches on the skin. There is an unmet medical need for effective treatment in pediatric patients and this study is being done to evaluate risankizumab in pediatric participants with moderate to severe plaque psoriasis. This study will assess the change in disease symptoms.

Risankizumab is a drug being studied for the treatment for plaque psoriasis in pediatric participants. This study has 4 parts.

Part 1: Participants aged 12 \< 18 will receive a fixed dose of risankizumab. Part 2: Participants aged 12 \< 18 will receive;

* Period A: Risankizumab or ustekinumab based on body weight followed by;
* Period B: Risankizumab or no treatment.
* Period C: Re-treatment with risankizumab (if needed).

Part 3: Participants aged 6 \< 12 will receive risankizumab based on body weight.

Part 4: Participants aged 6 \< 12 will receive risankizumab based on body weight (Japan only: Participants aged 12 \> 18 will receive risankizumab based on body weight).

Around 132 participants will be enrolled in approximately 50 sites worldwide.

Risankizumab and ustekinumab are given as a subcutaneous (under the skin) injection.

Parts 1, 3, and 4: Risankizumab for 40 weeks with a follow-up call 20 weeks later for a study duration of approximately 65 weeks.

Part 2:

* Period A: Risankizumab or ustekinumab for 16 weeks.
* Period B: Risankizumab or no treatment for 36 weeks.
* Period C: Re-treatment with risankizumab for 16 weeks. Follow-up call 20 weeks later for a study duration of approximately 81 weeks. Participants from each Part who meet eligibility criteria for an open-label extension (OLE) study may continue on risankizumab for 216 additional weeks.

There may be a higher burden for study participants compared to standard treatment. Participants will attend monthly visits and medical assessments will check the effect of treatment through blood tests, questionnaires, and checking for side effects.

Detailed description:

Arms: arm 1: Participants age 12 to less than 18 receive fixed dose of risankizumab Dose A for 40 weeks. arm 2: Participants age 12 to less than 18 will receive:

Period A: Ustekinumab Dose A, Dose B, or Dose C based on body weight for 16 weeks (at Week 0 and Week 4).

Period B: Risankizumab Dose A or B based on body weight for 24 weeks. arm 3: Participants age 12 to less than 18 will receive:

Period A: Risankizumab Dose A or B based on body weight for 16 weeks (at Week 0 and Week 4).

Period B: Participants who respond to Risankizumab in Period A are re-randomized to continue Risankizumab Dose A or B based on body weight for up to 24 weeks or withdraw from treatment until flare.

Period C: Participants withdrawn from treatment in Period B and experience a flare in symptoms at Week 28 or beyond are eligible for re-treatment with Risankizumab Dose A or B based on body weight for 16 weeks (at Week 0 and Week 4). arm 4: Participants age 6 to less than 12 will receive Risankizumab Dose A or B based on body weight for 40 weeks. arm 5: Participants age 6 to less than 12 will receive Risankizumab Dose A or B based on body weight for 40 weeks (Japan only: participants age 12 to less than 18 years will be included).
Interventions: intervention 1: Risankizumab intervention 2: Ustekinumab
Intervention descriptions: intervention 1: Subcutaneous Injection intervention 2: Subcutaneous Injection

Protocol documents:
Prot_000.pdf: 


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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
7
2.1
BACKGROUND AND RATIONALE
7
2.2
BENEFITS AND RISKS TO SUBJECTS
7
3
OBJECTIVES AND ENDPOINTS
8
3.1
OBJECTIVES, HYPOTHESES, AND ESTIMANDS
8
3.2
CO-PRIMARY ENDPOINTS
10
3.3
RANKED SECONDARY ENDPOINTS
10
3.4
NON-RANKED SECONDARY EFFICACY ENDPOINTS
10
3.5
OTHER ENDPOINTS
11
3.6
SAFETY ENDPOINTS
11
3.7
PHARMACOKINETIC AND IMMUNOGENICITY ENDPOINTS
12
4
INVESTIGATIONAL PLAN
12
4.1
OVERALL STUDY DESIGN AND PLAN
12
4.2
DISCUSSION OF STUDY DESIGN
18
5
STUDY ACTIVITIES
19
5.1
ELIGIBILITY CRITERIA
19
5.2
CONTRACEPTION RECOMMENDATIONS
23
5.3
PROHIBITED MEDICATIONS AND THERAPY
24
5.4
PRIOR AND CONCOMITANT THERAPY
25
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
26
5.6
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR FROM STUDY
27
5.7
STUDY DRUG
28
5.8
RANDOMIZATION/DRUG ASSIGNMENT
29
5.9
PROTOCOL DEVIATIONS
29
5.10
EU CTR PUBLICATION POLICY
29
6
SAFETY CONSIDERATIONS
30
6.1
COMPLAINTS AND ADVERSE EVENTS
30
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6.2
INDEPENDENT DATA MONITORING COMMITTEE
34
6.3
ANAPHYLAXIS ADJUDICATION COMMITTEE
34
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
35
7.1
STATISTICAL AND ANALYTICAL PLANS
35
7.2
DEFINITION FOR ANALYSIS POPULATIONS
35
7.3
HANDLING POTENTIAL INTERCURRENT EVENTS FOR THE PRIMARY AND SECONDARY ENDPOINTS
35
7.4
STATISTICAL ANALYSES FOR EFFICACY
35
7.5
STATISTICAL ANALYSES FOR SAFETY
36
7.6
INTERIM ANALYSIS
36
7.7
MULTIPLICITY ADJUSTMENT AND OVERALL TYPE I ERROR CONTROL
37
7.8
SAMPLE SIZE DETERMINATION
37
8
ETHICS
38
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD
38
8.2
ETHICAL CONDUCT OF THE STUDY
38
8.3
SUBJECT CONFIDENTIALITY
39
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
39
10 DATA QUALITY ASSURANCE
39
11 COMPLETION OF THE STUDY
40
12 REFERENCES
40
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCT
28
TABLE 2.
SUPPLEMENTAL ADVERSE EVENTS ECRFS
33
LIST OF FIGURES
FIGURE 1.
PART 1 SCHEMATIC
13
FIGURE 2.
PART 2 SCHEMATIC
15
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FIGURE 3.
PART 3 SCHEMATIC
16
FIGURE 4.
PART 4 SCHEMATIC
17
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
41
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
44
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
45
APPENDIX D.
ACTIVITY SCHEDULE
46
APPENDIX E.
SUMMARY OF CHANGES
52
APPENDIX F.
OPERATIONS MANUAL
54
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2 INTRODUCTION
2.1 Background and Rationale
Risankizumab is a humanized monoclonal Antibody (Ab) of the immunoglobin G1 subclass directed 
towards interleukin (IL)-23p19.  The Ab has been engineered to reduce Fcγ receptor and complement 
binding and potential charge heterogeneity.  Risankizumab binds with high affinity to human IL-23.
Positive results were observed from 4 pivotal Phase 3 clinical trials that evaluated risankizumab 
compared with ustekinumab, placebo, and adalimumab for the treatment of adult patients with 
moderate to severe plaque psoriasis (Ps).  Results from these pivotal studies demonstrated that 
risankizumab is highly effective for the treatment of Ps, meeting co-primary endpoints of achieving at 
least a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) and static Physician's Global 
Assessment (sPGA) score of clear or almost clear (0 or 1) versus comparator or placebo at Week 16 
across all 4 studies.1
Why Is This Study Being Conducted?
There is an unmet medical need for effective treatments in pediatric patients with chronic plaque Ps 
who are candidates for systemic therapy.  This study will evaluate the pharmacokinetics (PK), safety, and 
efficacy of risankizumab in subjects with moderate to severe plaque Ps from 6 to less than 18 years of 
age.
2.2 Benefits and Risks to Subjects
In Phase 3 studies of risankizumab in patients with Ps, the majority of subjects receiving risankizumab 
achieved 90% improvement of their disease, and risankizumab was well tolerated.  As with many 
immune modulating agents, risankizumab may impair immune function, resulting in a risk of infection.  
This will be monitored by collection of all adverse events (AEs) during the treatment and observation 
periods.  In addition, subjects with active systemic infection or clinically important infection will not be 
included in the study.
Subjects with a positive QuantiFERON®-tuberculosis (TB) (or interferon gamma release assay [IGRA] 
equivalent)/TB skin test result for TB must fulfill entry criteria as specified in Section 5.1 of this protocol.  
Interleukin-23 inhibition is not known to increase the risk of TB infection or impair the response to TB 
infection in animal models.
Published literature indicates that inhibition of IL-23 is unlikely to increase the risk for cancer.  
Expression of IL-23 is increased in human tumors.4-6  Moreover, preclinical data have demonstrated a 
beneficial effect of IL-23 p19 inhibition in animal models, both for pre-existing and tumor-induction 
models.7  While there is not enough clinical information at this time to rule out a risk of cancer with 
risankizumab, this risk is considered small.
Although rare, a potential for hepatic AEs is under constant surveillance by sponsors and regulators.  
Therefore, this study requires timely detection, evaluation, and follow-up of laboratory alterations in 
selected liver laboratory parameters to ensure subjects' safety.
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Potential Increases in major adverse cardiovascular (major adverse cardiac event) events, including 
myocardial infarction (MI), cerebrovascular accident, and cardiovascular death, reported initially with 
anti-IL-12/23 agents have not been observed in longer term studies with risankizumab.
Local reactions to subcutaneously administered biologic therapies are usually limited to redness, 
swelling, or induration at the injection site.  Manifestations of systemic hypersensitivity reactions 
include anaphylaxis, pruritus, hypotension, and respiratory distress.  Both local and systemic 
hypersensitivity reactions are readily detectable, transient in nature, and manageable with standard 
medical treatment.  Subjects will be closely monitored during study drug administration.  An 
independent Anaphylaxis Adjudication Committee (AAC) will adjudicate observed systemic 
hypersensitivity and anaphylactic events.  The AAC will remain blinded to treatment allocation 
(Section 6.3).
In conclusion, the benefit-risk profile of risankizumab is considered appropriate for this stage of clinical 
development.8  Based on data from the integrated safety analyses, risankizumab is safe and 
well -tolerated and demonstrates a favorable benefit-risk profile.
As this is the first study to use risankizumab in patients under the age of 18, specific risks for this 
population have yet to be identified; however, no significant risks are expected as planned dosing will be 
equivalent to the adult efficacious dose that is considered safe and well-tolerated.  Due to potential 
immunological issues in very young children, it was determined that children under the age of 6 should 
not be included in this study.
For further details on the safety profile of risankizumab, please see findings from completed studies 
including safety data in the current Investigator's Brochure (IB).1
In view of the coronavirus disease of 2019 (COVID-19) pandemic, the benefit-risk profile of various 
immunomodulatory therapies on COVID-19 is being evaluated based on real world and clinical trial data.  
At this time, the effects of risankizumab on the course of COVID-19 are not well defined.
3 OBJECTIVES AND ENDPOINTS
3.1 Objectives, Hypotheses, and Estimands
The objective of this study is to evaluate the PK, safety, and efficacy of risankizumab in subjects from 
6 to less than 18 years of age with moderate to severe plaque Ps.
Primary Efficacy
The primary efficacy objective is to assess the rate of subjects who achieve a) PASI 75 (defined as at least 
75% improvement from baseline in PASI) and b) sPGA clear or almost clear (0 or 1) (US only: and 
≥2 grade improvement from baseline) at Week 16 of initial treatment with study drug based on the 
Intent-to-Treat (ITT) population (as defined in Section 7.2).
There are no statistical hypotheses corresponding to the co-primary efficacy objectives as efficacy will 
be assessed descriptively, providing estimates with confidence intervals without performing statistical 
testing.
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The estimands corresponding to the co-primary efficacy objectives are defined as follows for Part 1, 
Part 3, and Part 4:

Percentage of subjects achieving at least 75% reduction in PASI (PASI 75) from Baseline at 
Week 16 of initial treatment with risankizumab without the use of rescue medication and 
regardless of premature discontinuation of study drug in the ITT population

Percentage of subjects achieving sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at Week 16 of initial treatment with risankizumab without the use 
of rescue medication and regardless of premature discontinuation of study drug in the ITT 
population
The estimands corresponding to the co-primary efficacy objectives are defined as follows for Part 2:

Difference in the percentage of subjects achieving at least 75% reduction in PASI (PASI 75) from 
Baseline at Week 16 of initial treatment with risankizumab compared to ustekinumab without 
the use of rescue medication and regardless of premature discontinuation of study drug in the 
ITT population

Difference in the percentage of subjects achieving sPGA clear or almost clear (0 or 1) (US only: 
and ≥2 grade improvement from baseline) at Week 16 of initial treatment with risankizumab 
compared to ustekinumab without the use of rescue medication and regardless of premature 
discontinuation of study drug in the ITT population
Secondary Efficacy
The secondary efficacy objectives are to assess the rate of subjects who achieve the ranked secondary 
endpoints specified in Section 3.3 below in the ITT population.
There are no statistical hypotheses corresponding to the secondary efficacy objectives as efficacy will be 
assessed descriptively, providing estimates with confidence intervals without performing statistical 
testing.
The estimands corresponding to the secondary efficacy objectives are defined as follows for Part 1, 
Part 3, and Part 4:

Percentage of subjects achieving at least 90% reduction in PASI (PASI 90) from Baseline at 
Week 16 of initial treatment with risankizumab without the use of rescue medication and 
regardless of premature discontinuation of study drug in the ITT population

Percentage of subjects achieving 100% reduction in PASI (PASI 100) from Baseline at Week 16 of 
initial treatment with risankizumab without the use of rescue medication and regardless of 
premature discontinuation of study drug in the ITT population
The estimands corresponding to the secondary efficacy objectives are defined as follows for Part 2:

Difference in the percentage of subjects achieving at least 90% reduction in PASI (PASI 90) from 
Baseline at Week 16 of initial treatment with risankizumab compared to ustekinumab without 
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the use of rescue medication and regardless of premature discontinuation of study drug in the 
ITT population

Difference in the percentage of subjects achieving 100% reduction in PASI (PASI 100) from 
Baseline at Week 16 of initial treatment with risankizumab compared to ustekinumab without 
the use of rescue medication and regardless of premature discontinuation of study drug in the 
ITT population

Percentage of subjects achieving sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at Week 0 and Week 16 of the re-treatment phase in Part 2 with 
risankizumab without the use of rescue medication and regardless of premature discontinuation 
of study drug in the ITT population
Rescue medication for the purposes of this analysis will be considered any systemic (oral or parenteral) 
medication used specifically for the treatment of psoriasis.
3.2 Co-primary Endpoints

Achievement of PASI 75 (defined as at least 75% improvement from baseline in PASI) at 
Week 16 of initial treatment

Achievement of sPGA clear or almost clear (0 or 1) at Week 16 of initial treatment (US only: and 
≥2 grade improvement from baseline)
3.3 Ranked Secondary Endpoints

Achievement of PASI 90 (defined as at least 90% improvement from baseline in PASI) at 
Week 16 of initial treatment

Achievement of PASI 100 (defined as 100% improvement from baseline in PASI) at Week 16 of 
initial treatment

Achievement of sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade improvement from 
baseline) at Week 0 and Week 16 of the re-treatment phase in Part 2
3.4 Non-ranked Secondary Efficacy Endpoints

Achievement of PASI 50 (defined as at least 50% improvement from baseline in PASI) at 
Week 16 of initial treatment

Achievement of PASI 50 (defined as at least 50% improvement from baseline in PASI) at Week 0 
and Week 16 of the re-treatment phase in Part 2

Achievement of PASI 90 (defined as at least 90% improvement from baseline in PASI) at Week 0 
and Week 16 of the re-treatment phase in Part 2

Achievement of PASI 100 (defined as 100% improvement from baseline in PASI) at Week 0 and 
Week 16 of the re-treatment phase in Part 2
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
Achievement of a PASI 75 (defined as at least 75% improvement from baseline in PASI) at 
Week 0 and Week 16 of the re-treatment phase in Part 2

Change in Children's Dermatology Life Quality Index (CDLQI) from Week 0 to Week 16 of initial 
treatment in Part 2

Change in CDLQI from Week 0 to Week 16 of re-treatment phase of Part 2

Change in Family Dermatology Life Quality Index (FDLQI) from Week 0 to Week 16 of initial 
treatment in Part 2

Change in FDLQI from Week 0 to Week 16 of re-treatment phase of Part 2

Change in Itch Numerical Rating Scale (Itch NRS) from Week 0 to Week 16 of initial treatment in 
Part 2

Change in Itch NRS from Week 0 to Week 16 of re-treatment phase in Part 2

Achievement of ≥4-point improvement from baseline in the Itch Numerical Rating Scale (in 
patients with Baseline score ≥4) at Week 16 of initial treatment in Part 2.
3.5 Other Endpoints

Achievement of PASI 75 at Week 12 during the treatment or withdrawal period of Part 2

Achievement of sPGA clear or almost clear (0 or 1) at Week 12 during the treatment or 
withdrawal period of Part 2

Achievement of PASI 50/75/90/100 at all other visits collected

Achievement of sPGA clear (0) at all other visits collected

Achievement of sPGA clear or almost clear (0 or 1) at all other visits collected

Change in Itch Numerical Rating Scale (Itch NRS) at each study visit from Week 0

Achievement of ≥ 4-point improvement from baseline in the Itch Numerical Rating Scale (in 
patients with baseline score ≥ 4) at each study visit in Part 2

Change in CDLQI at each study visit from Week 0

Change in FDLQI at each study visit from Week 0
3.6 Safety Endpoints

Treatment emergent adverse events (TEAEs)

Serious adverse events (SAEs)

Areas of safety interest (ASI)

TEAEs leading to discontinuation

Vital signs and laboratory tests (hematology, chemistry, and urinalysis)
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3.7 Pharmacokinetic and Immunogenicity Endpoints
Serum risankizumab concentrations, antidrug antibody (ADA), and neutralizing antibody (nAb) will be 
determined at the visits indicated in the Study Activities Table (Appendix D).
Serum risankizumab concentrations will be summarized at each timepoint by cohort using descriptive 
statistics.  Population PK analyses combining the data from this study and other studies may be 
performed.  Relationships between risankizumab exposure and efficacy or safety variables of interest 
may be explored.
The number and percentage of subjects (i.e., incidence) with positive ADA and nAb will be summarized 
by cohorts and study visits.  Anti-drug Abs titers will be tabulated for each subject by regimen at the 
respective study visits.  The effect of immunogenicity on risankizumab exposure, efficacy, and/or safety 
variables may be explored.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
The study consists of 4 parts, each with distinct patient populations.  Further details regarding study 
procedures are in the Operations Manual.  See Section 5 for information regarding eligibility criteria.
Subjects who initially do not meet all eligibility criteria for the study may be permitted to repeat the 
Screening Visit one time following re-consent.  There is no minimum period of time that a subject must 
wait prior to the repeat Screening Visit.  The subject must meet all eligibility criteria on the repeat 
Screening Visit in order to qualify for the study.  A repeat of all screening procedures is needed at this 
repeat Screening Visit with these exceptions:

If the repeat Screening Visit is within 30 days of the initial Screening Visit, clinical laboratory 
parameters assessed as normal at the initial Screening Visit do not need to be repeated at the 
repeat Screening Visit

If the subject had a complete initial screening evaluation, including the assessment of an 
Interferon-Gamma Release Assay (IGRA; QuantiFERON TB Gold In Tube test) or a purified 
protein derivative (tuberculin) (PPD) test (or equivalent), and electrocardiogram (ECG), these 
tests do not need to be repeated at the repeat Screening Visit if they were completed within 
90 days since the initial Screening Visit.
Part 1
Part 1 will be a sentinel (open-label) cohort of 12 adolescents (age 12 to less than 18 years) with severe 
disease.  At least 1 subject with a body weight less than 50 kg at baseline will be enrolled in Part 1 to 
ensure good representation of the lower body weight range.  Subjects will undergo PK sampling for 
16 weeks and continue treatment until Week 40 (subjects will receive 
mg risankizumab 
subcutaneously [SC] at Weeks 0, 4, 16, 28, and 40).  A follow-up call will take place 20 weeks after the 
last dose of study drug (Week 40) if the subject does not enroll into Study M19-973, the open-label 
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non-responders (sPGA ≥ 2) and subjects initially randomized to ustekinumab will enter Period B and will 
receive risankizumab every 12 weeks until Week 40 in order to collect additional safety information for 
risankizumab.  Risankizumab responders (sPGA = 0 or 1) will enter Period B and will be re-randomized 
(1:1) to receive no medication until a disease flare or risankizumab every 12 weeks until Week 40.  
Subjects randomized to the withdrawal arm in Period B who experience a disease flare on or after 
Week 28 will enter Re-Treatment Period C to receive risankizumab at Weeks 0 and 4 of the 16-week 
re-treatment period.  Randomization and re-randomization will not be stratified due to the small sample 
size.
For subjects initially randomized to risankizumab in Period A, study duration will be up to approximately 
81 weeks:

Screening period of up to 35 days

Period A:  16-week treatment period (dosing at Weeks 0 and 4)

Period B:  maximum of 36-week treatment or withdrawal period

Risankizumab non-responders:  risankizumab dosed at Weeks 16, 28, and 40

Risankizumab responders:  either no treatment or risankizumab dosed at Weeks 16, 28, 
and 40

Period C:  16-week re-treatment period if a disease flare occurs in subjects randomized to the no 
treatment group

The follow-up call with take place 20 weeks after the last dose of study drug unless the subject 
enrolls into Study M19-973, the OLE study.
For subjects initially randomized to ustekinumab, study duration will be up to approximately 65 weeks:

Screening period of up to 35 days

52-week treatment period (16 weeks on ustekinumab followed by risankizumab with the last 
dose at Week 40)

The follow-up call will take place 20 weeks after the last dose of study drug unless the subject 
enrolls into Study M19-973, the OLE study.
Subjects who complete either the Week 52 visit for those in Period B or 16 weeks of the re-treatment 
Period C have the option to enroll into Study M19-973, the OLE study.
A schematic of Part 2 is shown in Figure 2.
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4.2 Discussion of Study Design
Choice of Control Group
In study Part 2, an active control group is used to assess efficacy and safety of risankizumab compared 
with an approved product for the same indication.  Ustekinumab (Stelara®) is a human IL-12 and 
-23 antagonist indicated for the treatment of moderate to severe plaque Ps.9
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy 
measurements in this study are standard for assessing disease activity in subjects with plaque Ps.  All 
clinical and laboratory procedures in this study are standard and generally accepted.
Suitability of Subject Population
Pediatric subjects 6 through < 18 years of age with plaque Ps who meet all inclusion criteria and who do 
not meet any of the exclusion criteria are eligible for this study.  The specific subject population chosen 
was based on knowledge that IL-23 is involved in the pathogenesis of Ps in the adult population.  Data 
from adult studies have shown that risankizumab is effective and well tolerated in the adult Ps 
population.  This study is intended to confirm safety and efficacy in pediatric subjects as well as to 
identify the most appropriate dose based on subject weight.
Selection of Doses in the Study
Due to the similarity between children and adults in disease pathophysiology and the mechanism of 
action of risankizumab, the objective of dose selection in this study is to approximate a dose based on 
body weight in pediatric patients with plaque Ps to be equivalent to the adult exposure at the approved 
efficacious therapeutic dose of 
 mg SC at Week 0, 4, and every 12 weeks thereafter.  A population PK 
model of risankizumab identified body weight as the primary covariate and therefore body weight 
range-based dosing has been selected for this study.10  The population PK model was also used to 
identify a balance between maximizing the best approximate with adult exposure and minimizing 
complexity of dosing schemes.  Further rationale by study part is provided below.
Selection of doses for Part 2 and Part 3 is based on PK modeling from Part 1.  Subjects who weigh 
≥40 kg will receive 
mg risankizumab, while subjects who weigh < 40 kg will receive
mg 
risankizumab.
During the conduct of the study, if any subject initially assigned to the lower dose of risankizumab has a 
recorded weight ≥40 kg at a dosing visit, they will receive the standard risankizumab dose (
mg).
Part 1
The main objective of Part 1 is to evaluate the PK and safety of the proposed risankizumab pediatric 
dose based on extrapolation from adult data.  According to an adalimumab study in pediatric patients 
with Ps (Study M04-717),11 the median body weight of adolescent patients (age 12 to less than 18 years) 
was 59 kg with a minimum to maximum range of 38 kg to 108 kg.  This largely overlaps with the body 
weight range observed in the risankizumab adult Phase 3 studies in Ps (38.5 kg to 193 kg) and supports 
the use of the same adult therapeutic dose of 
 mg risankizumab in Part 1 of this study without a 
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specific body weight cutoff.  Data collected up to Week 16 from subjects in Part 1 will be useful for PK 
assessments and to guide dose selection for Parts 2 and 3.
Part 2
The risankizumab doses to be administered in Part 2 have been determined by the first 16 weeks of data 
from Part 1 and are 
mg for subjects who weigh ≥40 kg and
mg for subjects who weigh < 40 kg.
Part 3
Similar to Part 1, the main objective of Part 3 is to evaluate PK and safety of the selected risankizumab 
pediatric doses in the 6 to < 12 -year-old patients based on extrapolation from adult data as well as the 
available data from Part 1 of the study.  Due to the lower body weight in many of the younger patients 
compared with adult patients, body weight ranges will be used to determine the dose.  The doses to be 
administered in Part 3 have been determined by the first 16 weeks of data from Part 1 and are 
mg 
for subjects who weigh ≥40 kg and 
mg for subjects who weigh < 40 kg.
Part 4
The doses to be administered in Part 4 have been determined by an updated population PK data analysis 
from Parts 1-3 and are
mg for subjects who weigh ≥40 kg and 
mg for subjects who weigh 
< 40 kg.
During Parts 2, 3, and 4 of the study, the body weight measured prior to each dose administration will 
be used to determine the dose for each subject, with the exception of the doses administered at or prior 
to Week 4 in Part 3, when the baseline body weight will be used to determine the dose.
The target exposures at these doses will be within the range of the risankizumab exposures evaluated as 
safe and well-tolerated in adult programs across multiple indications.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the questions below will result in exclusion from study participation.
Consent
1. Subject's parent or legal guardian must voluntarily sign and date an informed consent, 
approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to 
the initiation of any screening or study-specific procedures.  Subject will be included in all 
discussions to obtain verbal or written assent.
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Demographic and Laboratory Assessments
2. Subject is judged to be in good general health, as determined by the investigator based upon 
the results of a medical history, physical examination, laboratory profile, and a 12-lead ECG 
performed during the Screening period.
3. Subject is male or female, 6 to < 18 years old:

Parts 1 and 2:  ages include 12 to < 18 years at the time of enrollment; 

Parts 3 and 4:  ages include 6 to < 12 years at the time of enrollment.
4. Laboratory values meeting the following criteria within the screening period prior to the 
first dose of study drug:

Serum aspartate transaminase and serum alanine transaminase ≤ 2 × upper limit of normal;

Serum total bilirubin ≤ 2.0 mg/dL; except for subjects with isolated elevation of indirect 
bilirubin related to Gilbert syndrome;

Total white blood cell count ≥3,000/µL;

Absolute neutrophil count ≥1,500/µL;

Platelet count ≥100,000/µL;

Hemoglobin ≥10 g/dL.
5. Subject is willing and able to comply with procedures required in this protocol and is not an 
employee of the sponsor and/or study site or a family member of an employee.
Disease/Condition Activity
6. Diagnosis of chronic plaque Ps for at least 6 months before the Baseline Visit.
7. Subject must be a candidate for systemic therapy as assessed by the investigator and meet 
the following disease activity criteria at both the Screening and Baseline Visits:

Part 1:  Subject has severe disease defined as ≥ 20% body surface area (BSA) Ps involvement 
with sPGA score of 4; OR ≥ 10% BSA Ps involvement that includes facial or genital areas with 
sPGA score of 4; OR PASI ≥ 20;

Part 2:  Subject has moderate to severe disease defined as ≥ 10% BSA Ps involvement with 
sPGA score of ≥ 3 or PASI ≥ 12;

Part 3:  Subject has severe disease defined as ≥ 20% BSA Ps involvement with sPGA score of 
4; OR ≥ 10% BSA Ps involvement that includes facial or genital areas with sPGA score of 4; 
OR PASI ≥ 20;

Part 4:  Subject has moderate to severe disease defined as ≥ 10% BSA Ps involvement with 
sPGA score of ≥ 3 or PASI ≥ 12;
8. Subject must be a candidate for the treatment with ustekinumab according to local label. For 
Japan, this includes subjects ≥ 15 years old.

Subjects in Part 2 age < 15 years should meet the safety requirements of the local label.
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Subject History
9. Subject must not have a history of clinically significant (per investigator's judgment) drug or 
alcohol abuse within the last 6 months.
10. Subject must not have a history of an allergic reaction or significant sensitivity to 
constituents of the study drug (and its excipients) and/or other products in the same class.
11. No history of:

Erythrodermic Ps, generalized or localized pustular Ps, medication-induced or medication-
exacerbated Ps, or new onset guttate Ps;

Active skin disease other than Ps that could interfere with the assessment of Ps;

Clinically significant (per investigator's judgment) drug or alcohol abuse within the last 
6 months;

An allergic reaction or hypersensitivity to a biologic agent or its excipients;

A latex allergy;

An organ transplant that requires continued immunosuppression;

Any malignancy except for successfully treated non-melanoma skin cancer or localized 
carcinoma in situ of the cervix
12. No evidence of the following medical diseases or disorders:

Hepatitis B (HB) (hepatitis B virus [HBV]) or hepatitis C (hepatitis C virus [HCV]) infection, 
defined as

HBV:  Hepatitis B surface antigen (HBs antigen) positive (+) test or detected sensitivity 
on the HBV DNA polymerase chain reaction qualitative test for subjects who are HB core 
Ab (HB core Ab) positive (+) (and for HB surface Ab [HBs Ab] positive [+] subjects where 
mandated by local requirements);

HCV:  hepatitis C virus RNA detectable in any subject with anti-hepatitis C virus 
antibody;

Human immunodeficiency virus (HIV), defined as confirmed positive anti-HIV antibody (HIV 
Ab) test.  Note:  In case a screened subject has a confirmed positive HIV Ab test, eligibility 
criterion 2 regarding good general health criteria should be selected in the electronic case 
report form (eCRF) as the reason for screening failure;

COVID-19: In subjects who test positive for COVID-19, at least 5 days have passed since a 
positive test result in asymptomatic patients. Subjects with mild/ moderate COVID-19 
symptoms can be enrolled if fever-free without use of antipyretics for 24 hours and 
improvement of other symptoms or 5 days have passed since the positive test result 
(whichever comes last). Subjects may be rescreened if judged to be in good general health, 
as determined by the investigator based on medical history and physical examination. 

Active TB:  For subjects with latent TB, please see the Operations Manual for details;

Active systemic infection/clinically important infection during the last 2 weeks prior to 
Baseline Visit as assessed by the investigator.
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
Genetic deficiency in IL-12/IL-23;

Active or suspected malignancy;

Recent (within past 6 months) cerebrovascular accident or MI;

Major surgery performed within 12 weeks prior to randomization or planned during the 
conduct of the study.
13. Subject does not have concurrent clinically significant medical conditions other than the 
indication being studied or any other reason that the investigator determines would interfere 
with the subject's participation in this study, would make the subject an unsuitable candidate to 
receive study drug, or would put the subject at risk by participating in the study.
14. Subject has an updated immunization schedule according to local immunization guidelines
Contraception
15. For all females of child-bearing potential; a negative serum pregnancy test at the Screening 
Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug.
16. Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is effective from Study Day 1 through at least 140 days (20 weeks or as 
guided by the local drug label, whichever is longer) after the last dose of study drug (local 
practices may require 2 methods of birth control).  Female subjects of non-childbearing 
potential do not need to use birth control.
17. Female subjects may not be pregnant, breastfeeding, or considering becoming pregnant 
during the study or for approximately 140 days (20 weeks or as guided by the local drug label, 
whichever is longer) after the last dose of study drug.
Concomitant Medications
18. Subject must not have received any live viral or bacterial vaccine except non-replicating live 
vaccines (e.g., JYNNEOS monkeypox vaccine) within 4 weeks prior to the first dose of study drug 
or expect the need for live vaccination during study participation including at least 140 days (20 
weeks or as guided by the local drug label, whichever is longer) after the last dose of study drug.
19. Subject has not had any previous exposure to risankizumab (all study parts) or ustekinumab 
(study Part 2).
20. Subject must not have been treated with any investigational drug within 30 days or 
5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently 
enrolled in another interventional clinical study.
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5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:

Females, Non-Childbearing Potential

A female who is considered of non-childbearing potential does not need to use birth control 
during or following study drug treatment.

Premenopausal female with permanent sterility or permanent infertility due to one of the 
following:

Permanent sterility due to a hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy;

Non-surgical permanent infertility due to Mullerian agenesis, androgen insensitivity, or 
gonadal dysgenesis; investigator discretion should be applied to determining study entry 
for these individuals.

Premenarchal female

Females who have not experienced menarche (at least one menstrual period).
(Note:  If the childbearing potential changes after start of the study [e.g., a 
premenarchal female participant experiences menarche], the participant must discuss 
this with the investigator, who should determine if a female participant must begin a 
highly effective method of contraception.  If reproductive status is questionable, 
additional evaluation should be considered.)

Females, of Childbearing Potential

Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 140 days (20 weeks or as guided by the local risankizumab or ustekinumab label (if 
approved), whichever is longer) after the last dose of study drug.

Females must commit to one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at 
least 30 days prior to study Baseline Day 1.

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study Baseline Day 1.

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).

Intrauterine device.

Intrauterine hormone-releasing system.

Vasectomized sexual partner(s) (the vasectomized partner should have received medical 
assessment of the surgical success and is the sole sexual partner of the trial participant).
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
Practice true abstinence, defined as:  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).
If required per local practices, male or female condom with or without spermicide OR cap, diaphragm or 
sponge with spermicide should be used in addition to one of the birth control methods listed above 
(excluding true abstinence).
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
5.3 Prohibited Medications and Therapy
Prohibited medications and therapy are defined as using the following prohibited concomitant Ps
treatments within the specified timeframe prior to Baseline Visit and throughout the study.
1.
Any systemic biologic therapy (other than the study drug);
2.
Systemic non-biologic therapy for Ps, including but not limited to cyclosporine, corticosteroids, 
methotrexate, oral retinoids, apremilast, and fumaric acid derivatives within 4 weeks;
3.
Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could 
affect disease severity or interfere with disease assessments within 4 weeks;
4.
Topical Ps treatments, including but not limited to corticosteroids, anthralin, calcipotriene, 
topical vitamin D derivatives, retinoids, urea, alpha- or beta-hydroxyl acids, and medicated 
shampoos (for example those that contain > 3% salicylic acid, corticosteroids, coal tar or vitamin 
D3 analogues) within 2 weeks;

Exception:  Subjects are allowed to use bland (containing no Ps treatment) emollients and 
shampoos and/or low potency topical corticosteroids (US Class 6 - 7) on the palms, soles, 
face, inframammary area, and groin only.  In areas where available topical corticosteroids 
are not easily identified by United States (US) Class, a list of acceptable low potency topical 
corticosteroids will be provided to sites.
5.
Treatment with an experimental non-biologic for Ps within 4 weeks or five half-lives of the drug 
(whichever is longer);
6.
Treatment with an experimental biologic for Ps within 12 weeks or five half-lives of the drug 
(whichever is longer);
7.
Live attenuated vaccines (except non-replicating live vaccines (e.g., JYNNEOS monkeypox 
vaccine) are NOT allowed during the study and including up to 140 days (20 weeks or as guided 
by local drug label (if approved), whichever is longer) after the last dose of study drug.  
Examples of live attenuated vaccines include but are not limited to the following:

Bacille Calmette-Guérin;

Zoster vaccine live (Zostavax);
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
Measles-mumps-rubella or measles mumps rubella varicella;

Monovalent live attenuated influenza A (intranasal);

Oral polio vaccine;

Rotavirus;

Seasonal trivalent live attenuated influenza (intranasal);

Smallpox;

Oral typhoid vaccine;

Varicella (chicken pox);

Yellow fever;

Dengue (Dengvaxia®).
5.4 Prior and Concomitant Therapy
Stable doses of concomitant therapies for chronic conditions, for which neither the condition nor the 
treatment are judged to exclude the patient from participation, are permissible.  Concomitant therapies 
should not be administered with the intent to treat Ps or have demonstrated efficacy for the treatment 
of Ps (except for permitted low-potency topical corticosteroids).  All concomitant medications should be 
carefully evaluated by the investigator, and the clinical monitor should be contacted when there are 
questions regarding concomitant medications.
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject has received from 4 weeks prior to screening or receives during 
the study must be recorded along with the reason for use; date(s) of administration, including start and 
end dates; and dosage information including dose, route, and frequency on the appropriate electronic 
case report form (eCRF).
A detailed history of all prior biologic use needs to be documented in the source notes and captured in 
the EDC.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact.  Information regarding potential drug interactions with risankizumab can be located in the 
risankizumab IB.
Subjects must be able to safely discontinue any prohibited medications (including biologics) 5 half-lives 
or 4 weeks prior to initial study drug administration.  Subjects must be consented for the study prior to 
discontinuing any prohibited medications for the purpose of meeting study eligibility.
Non-live vaccines may be administered during screening or treatment period, if not contraindicated or 
medically inappropriate.
When possible, first dose of study drug should be given at least ± 7 days from non-live SARS-CoV-2 
vaccine administration.  The potential impact of risankizumab on SARS-CoV-2 vaccination is unknown.  
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The decision to receive a locally available non-live vaccine should be based on local guidance and an 
individual discussion between the treating physician and the subject and/or guardian.
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following:

The subject or the subject's parent or legal guardian requests withdrawal from the study.

The investigator believes it is in the best interest of the subject.

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the AbbVie Therapeutic Area Medical Director 
(TA MD).

Subject is non-compliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.

Malignancy, except for localized NMSC or carcinoma in-situ of the cervix, where discontinuation 
is at the discretion of the Investigator.

The subject becomes pregnant while on study drug.

Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk.

Introduction of prohibited medications or dosages and continuation of the study drug would 
place the subject at risk.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the trial.

Post-Baseline occurrence of one or more of the following hepatic test abnormalities (confirmed 
on a second separate sample at least 48 hours apart):

ALT (alanine aminotransferase) or AST (alanine aminotransferase) > 8 × ULN (upper limit of 
normal);

ALT or AST > 5 × ULN for more than 2 weeks;

ALT or AST > 3 × ULN and Total Bilirubin > 2 × ULN or international normalized ratio [INR] 
> 1.5;

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (> 5%).

Subjects who meet any of the above criteria should be evaluated for an alternative etiology of 
the ALT or AST elevation and managed as medically appropriate.  If applicable, the alternative 
etiology should be documented (in the eCRF if reported as an AE).  If ALT or AST values return to 
the normal reference range or its Baseline value, study drug may be restarted.  If restarting 
study drug, documentation should include reason that rechallenge is expected to be safe.  If 
after clinically appropriate evaluation, no alternative etiology for ALT or AST elevation is found 
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or the ALT or AST elevation has not resolved or is not trending down toward normal, the subject 
should be discontinued from study drug.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
COVID-19 Pandemic-Related Acceptable Protocol Modification
During the COVID-19 pandemic, it has been necessary to employ mitigation strategies to enable the 
investigator to ensure subject safety and continuity of care.  Acceptable mitigation strategies are 
identified and included in the Operations Manual in Appendix F.
The investigator should contact the sponsor medical contact before discontinuing a subject from the 
study for a reason other than described in protocol to ensure all acceptable mitigation steps have been 
explored.
Refer to the Operations Manual in Appendix F for details on how to handle study activities/procedures.
Interruption/Discontinuation of Study Drug Due to COVID-19 Infection
During the study drug dosing period, for a subject with confirmed (viral test positive) or suspected 
COVID-19 infection, the timing of next administration of study drug or possibility of premature 
discontinuation would be at the discretion of the investigator. Follow subsequent protocol Section 5.6
for subjects who discontinued study drug.
5.6 Follow-Up After Subject Discontinuation of Study Drug or from 
Study
Discontinuation of Study Drug and Continuation of Study Participation
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
study drug treatment should continue to be followed for all regularly scheduled visits, unless the subject 
has decided to discontinue the study participation entirely (withdrawal of informed consent).  Subjects 
should be advised on the continued scientific importance of their data even if they discontinue 
treatment with study drug early.
Premature Discontinuation of Study (Withdrawal of Informed Consent)
If a subject prematurely discontinues study participation (withdrawal of informed consent), the 
procedures outlined for the Premature Discontinuation visit (PD visit) should be completed as soon as 
possible, preferably within 2 weeks.
In addition, if subject is willing, a follow-up phone call 140 days (20 weeks) after the last dose of study 
drug may be completed to ensure all treatment-emergent AEs/serious adverse events (SAEs) have been 
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resolved.  The 140-day (20 week) follow-up phone call following the last dose of risankizumab study 
drug during the trial will not be required for any subject who initiates commercially available 
risankizumab after completion of the study Completion Visit or PD visit or enters Study M19-973, the 
OLE study.
If a subject withdraws from study follow up or withdraws permission for the collection of their personal 
data, the study staff may still use available public records to obtain information about survival status
only, as appropriate per local regulations.
5.7 Study Drug
Information about the study drug used in this study is presented in Table 1.
Table 1.
Identity of Investigational Product
Study Drug
Dosage Form
Strength
Route of 
Administration
Manufacturer
Risankizumab 
(ABBV-066)
Solution for 
injection in pre-
filled syringe
 mg/
mL
Subcutaneous 
injection
AbbVie
Risankizumab 
(ABBV-066)
Solution for 
injection in pre-
filled syringe
mg/
mL
Subcutaneous 
injection
AbbVie
Ustekinumab
Solution for 
injection in pre-
filled syringe
45 mg/0.5 mL
Subcutaneous 
injection
Janssen
Ustekinumab
Solution for 
injection in vial
45 mg/0.5 mL
Subcutaneous 
injection
Janssen
AbbVie will not supply drug other than risankizumab and ustekinumab.
Open-label risankizumab and ustekinumab will be packaged in quantities sufficient to accommodate 
study design.  Each kit will be labeled per local requirements and this label must remain affixed to the 
kit.  Upon receipt, study drug should be kept in the original packaging and stored as specified on the 
label in a secure, limited-access storage area.  Each kit will contain a unique kit number.
This kit number is assigned to a subject via interactive response technology (IRT) and encodes the 
appropriate study drug to be dispensed at the subject's corresponding study visit.  All blank spaces on 
the label will be completed by the site staff prior to dispensing to subjects.  Study drug will only be used 
for the conduct of this study.
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5.8 Randomization/Drug Assignment
All subjects will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who rescreen, the screening number assigned by the IRT at the initial screening visit should be 
used.
Study Parts 1, 3, and 4 are open-label single arm and all subjects will receive the same dose exposure 
equivalent based on body weight (Parts 3 and 4) and the same frequency of study drug.
For Part 2 only, the IRT will assign a randomization number that will encode the subject's treatment 
group assignment in Period A according to the randomization schedule generated by the statistics 
department at AbbVie.  For subjects re-randomized in Period B of Part 2, the IRT will assign a separate 
randomization number that will encode the subject's treatment group assignment in Period B according 
to a separate randomization schedule generated by the statistics department at AbbVie.  Randomization 
for Period A will be done in a 2:1 ratio of risankizumab vs. ustekinumab.  The re-randomization ratio of 
continued treatment with risankizumab vs. no treatment for Period B will be 1:1. Randomization and 
re-randomization will not be stratified due to the small number of subjects.
The blinded efficacy assessor must be independent from all other study activities.  The efficacy assessor 
will remain blinded to each subject's treatment, clinical laboratory results, and all subject safety data 
during the course of the study.
5.9 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all 
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified, including those that may be due to the COVID-19 pandemic), 
the investigator is responsible for notifying IEC/IRB, regulatory authorities (as applicable), and AbbVie.
5.10 EU CTR Publication Policy
AbbVie as the sponsor has proprietary interest in this study. Authorship and manuscript composition will 
reflect joint cooperation between multiple investigators and sites and sponsor personnel. Authorship 
will be established prior to the writing of the manuscript. As this study involves multiple centers, no 
individual publications will be allowed prior to completion of the final clinical study report of the 
multicenter study except as agreed with the sponsor.
The sponsor will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the sponsor will generally support publication of multicenter 
studies only in their entirety and not as individual site data.
Investigators are NOT employed by the organization sponsoring the study. There is an agreement 
between investigators and the sponsor (or its agents) that restricts the investigator's rights to discuss or 
publish study results after the study is completed.
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AbbVie requests that any investigator or institution that plans on presenting/publishing results, provide 
written notification of their request 60 days prior to their presentation/publication. AbbVie requests 
that no presentation/publication will be instituted until 12 months after a study is completed or after 
the first presentation/publication, whichever occurs first. A delay may be proposed for a 
presentation/publication if AbbVie needs to secure patent or proprietary protection.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
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.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint 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 (e.g., printing illegible), missing components/product, device damage or not 
working properly, or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.  Product complaints occurring during the 
study will be followed up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events
An 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 AE 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 
"special situations" as accidental or intentional overdose, medication error, occupational or accidental 
exposure, off-label use, drug abuse, drug misuse, or drug withdrawal, all which must be reported 
whether associated with an AE or not.  Any worsening of a pre-existing condition or illness is considered 
an AE.  Worsening in severity of a reported AE should be reported as a new AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in discontinuation 
from the study, necessitate therapeutic medical intervention, and/or if the investigator considers them 
to be AEs.
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The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and/or 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 AE.
If an AE, whether associated with study drug or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance or contract research organization (as appropriate) as an 
SAE within 24 hours of the site being made aware of the SAE (refer to Section 4.3 of the Operations 
Manual for reporting details and contact information):
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).
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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 along with any suspected transmission of an 
infectious agent via a medicinal product if no other serious criterion 
is applicable.  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.
All AEs reported from the time of study drug administration until 140 days (20 weeks) after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, study procedure-related serious and non-serious AEs will be 
collected from the time the subject signs the study-specific informed consent.
The following definitions will be used for Serious Adverse Reactions (SAR) and Suspected Unexpected 
Serious Adverse Reaction (SUSAR):
SAR
Defined as all noxious and unintended responses to an Investigational Medicinal 
Product (IMP) related to any dose administered that result in an SAE as defined 
above.
SUSAR
Refers to individual SAE case reports from clinical trials where a causal 
relationship between the SAE and the IMP was suspected by either the sponsor 
or the investigator, is unexpected (not listed in the applicable Reference Safety 
Information [RSI]) and meets one of the above serious criteria.
AbbVie will be responsible for SUSAR reporting for the IMP in accordance with global and local 
requirements, including reporting to Eudravigilance database in accordance with EU Clinical Trial 
Regulation 536/2014.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Areas of Safety Interest/Safety Topics of Interest
Subjects will be screened and monitored throughout the study for Areas of Safety interest (ASI)/Safety 
Topics of Interest.  Screening procedures are outlined in the Activity Schedule (Appendix D).  In 
consideration of the ASI, the following supplemental eCRF(s) must be completed if AEs in any of the 
following areas are reported during the study (Table 2).
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Reasonable 
Possibility
After consideration of factors including timing of the event, biologic plausibility, 
clinical judgment, and potential alternative causes, there is sufficient evidence 
(information) to suggest a causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, biologic plausibility, 
clinical judgment, and potential alternative causes, there is insufficient evidence 
(information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 24 hours after the site 
becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).  If a pregnancy occurs in a study subject, information regarding the 
pregnancy and the outcome will be collected. The pregnancy outcome of an elective or spontaneous 
abortion, stillbirth or congenital anomaly is considered an SAE and must be reported to AbbVie within 
24 hours after the site becomes aware of the event.
6.2 Independent Data Monitoring Committee
An external DMC will review safety data throughout the course of the study.
A separate DMC charter will be prepared outside of the protocol and will describe the roles and 
responsibilities of the DMC members, frequency and triggers of data reviews, and relevant safety data 
to be assessed.  Unblinded ASI events will be presented to the DMC for review on a periodic basis.
6.3 Anaphylaxis Adjudication Committee
While no concerns with anaphylaxis/systemic hypersensitivity have been identified with the use of 
risankizumab, the sponsor has established an independent, blinded, expert committee to adjudicate 
events of anaphylaxis based on pre-specified definitions.  This independent external AAC will adjudicate 
suspected anaphylactic reactions and will remain blinded to treatment allocation.  The event terms to 
be adjudicated and the adjudication process are detailed in the AAC Charter.  A supplemental 
Hypersensitivity Reactions Signs and Symptoms eCRF will be used to collect information pertinent to the 
events.  In addition, the site may be contacted for additional source documentation.
If a suspected systemic hypersensitivity reaction occurs at the investigative site, in addition to testing 
tryptase and histamine levels, pharmacokinetic and ADA/nAb samples should also be collected.  If a 
systemic hypersensitivity reaction such as anaphylaxis is observed or reported while the subject is not at 
the investigative site, every effort should be made to obtain tryptase and histamine levels from the 
treating facility to help better characterize the diagnosis.
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7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol will be focused on primary and secondary analyses.  
Complete and specific details of the statistical analysis will be described and fully documented in the 
Statistical Analysis Plan (SAP).
7.2 Definition for Analysis Populations
The Intent to Treat (ITT) Population in each study part includes all enrolled subjects from Parts 1, 3, and 
4, and all randomized subjects from Part 2.  The ITT Set will be used for all efficacy and baseline 
analyses.  For analyses by study period in Part 2, only subjects enrolled into the respective study period 
will be included for that period.
The Safety Analysis Population in each study part consists of all subjects who received at least 1 dose of 
study drug and will be used for all safety analyses.
7.3 Handling Potential Intercurrent Events for the Primary and 
Secondary Endpoints
The efficacy endpoints (defined in Section 3.2, Section 3.3, Section 3.4, and Section 3.5) will be analyzed 
on the ITT population to address the following potential intercurrent events:
1.
Binary Endpoints

For subjects with the use of rescue medication, values after the start of rescue medication 
will be excluded from analysis and subjects will be considered non-responders at all time 
points after the start of rescue medication.

Data collected will be used regardless of premature discontinuation of study drug.
2.
Continuous endpoints

Values after the use of rescue medication will be excluded.

Data collected will be used regardless of premature discontinuation of study drug.
7.4 Statistical Analyses for Efficacy
Descriptive statistics will include counts and proportions for categorical data, and median, mean, 
standard deviation, first and third quartiles, and minimum/maximum for continuous data.  In addition, 
two-sided 95% confidence intervals (CI) will be reported.  For continuous endpoints, CIs for means and 
differences between means, respectively, will be based on the normal distribution.  For dichotomous 
endpoints, exact CIs will be provided based on the Clopper-Pearson method for proportions and by the 
Miettinen-Nurminen method for differences in proportions.12
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No statistical testing will be performed in this study.
The efficacy analyses in the ITT population for the different study parts will be performed separately, as 
described in Section 7.6.
Primary Efficacy Analysis
The primary efficacy analyses will be conducted by providing descriptive statistics and 95% CI as 
described above.
Secondary Efficacy Analysis
Secondary efficacy analyses will be conducted by providing descriptive statistics and 95% CI as described 
above.
Other Efficacy Analyses
Other efficacy analyses will be conducted providing descriptive statistics and 95% CI as described above.
Subgroup Analysis for Efficacy
Details regarding subgroup analyses will be specified in the SAP.
7.5 Statistical Analyses for Safety
The safety analyses will be carried out using the Safety Analysis Population and will be based on 
treatments the subjects actually received.  Safety will be assessed by AEs, physical examination, 
laboratory assessments, and vital signs.  The safety analyses in the safety population for the different 
study parts will be performed separately as described in Section 7.6.  Analysis details will be specified in 
the SAP.
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA).  Treatment-
emergent adverse events are defined as those that began or worsened in severity after the first dose of 
study drug and within 140 days/20 weeks after the last dose of study drug.  The number and percentage 
of subjects experiencing TEAEs will be tabulated using the MedDRA system organ class and preferred 
term, by severity, and by relationship to the study drug as assessed by the investigator.  Summaries 
(including percentages and events per 100 patient-years) of SAEs, deaths, AEs leading to discontinuation 
and ASI will be provided as well.  Pre-treatment AEs will be summarized separately.
For selected laboratory and vital signs, mean change from baseline and percentage of subjects with 
evaluations meeting criteria for pre-defined Potentially Clinically Significant values will be summarized.
7.6 Interim Analysis
No statistical test will be performed, therefore no formal interim analysis that would require type 1 
error control will be done.  Analyses will be performed at the following timepoints:
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Part 1 data up to Week 16 will be cleaned and analyzed after all subjects have reached Week 16 or have 
prematurely discontinued the study.  Week 16 data will inform the dose(s) and the initiation for Part 2 
and Part 3.  A final analysis of Part 1 will be performed when all subjects have completed Part 2.
Part 2 data, Part 1 data, and all available Part 3 or Part 4 data will be analyzed separately when all 
subjects have completed Part 2 and will be submitted for regulatory purposes.
Part 3 data up to Week 16 have been cleaned and analyzed after all subjects have reached Week 16 or 
have prematurely discontinued the study.  Week 16 data informed the dose(s) and the initiation for Part 
4.  A final analysis of Parts 3 and 4 will be performed together when all subjects have completed Part 4 
or have prematurely discontinued from the study.
An external DMC composed of persons independent of AbbVie and with relevant expertise in their field 
will review unblinded safety data from the ongoing study.  The primary responsibility of the DMC will be 
to protect the safety of the subjects participating in this study.
A separate DMC charter was prepared outside of the protocol and describes the roles and 
responsibilities of the DMC members, frequency of data reviews and relevant safety data to be 
assessed.
7.7 Multiplicity Adjustment and Overall Type I Error Control
Not applicable for this study.
7.8 Sample Size Determination
The sample sizes for the 4 study parts are per the risankizumab Ps pediatric investigational plan (PIP), in 
which it has also been agreed the study does not need to be powered to demonstrate superiority. The 
current study design meets the PIP commitment of at least 120 subjects evaluable for the primary 
endpoint of which at least 40 subjects are age 6 to less than 12 years and at least 80 subjects are age 
12 to less than 18 years.13
All enrolled (for Part 2, all randomized) subjects will be considered evaluable for the primary endpoint.  
Subjects discontinued from the study prior to Week 16 will be included in the analysis as non-
responders.
Part 1 (age 12 to less than 18 years with severe Ps) and Part 3 (age 6 to less than 12 years with severe 
Ps) are being conducted primarily for PK purposes and will each enroll 12 subjects.  Enrollment of 
12 subjects, a sample size typical of Phase 1 PK and safety/tolerability studies, will be sufficient to 
evaluate and confirm if the dosing is able to provide exposures in pediatric subjects consistent with 
exposures at the therapeutic dose in adult subjects, and to provide sentinel efficacy and safety data 
before exposing additional subjects with moderate to severe disease.
Assuming observed response rates for each of the co-primary endpoints of 66.7% (8 of 12), 75% (9 of 12) 
or 83.3% (10 of 12), the 95% exact CI will have a width of 34.9 to 90.1, 42.8 to 94.5, or 51.6 to 97.9, 
respectively.
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Part 2 will enroll 80 subjects ages 12 to less than 18 years in a 2:1 ratio (i.e., 53 subjects will be 
randomized to risankizumab, 27 subjects to ustekinumab).  The assumptions for response rates are 
based on the results for the 2 ustekinumab-controlled risankizumab studies in adult subjects with 
moderate to severe plaque Ps and apply to both co-primary endpoints, PASI 75 and sPGA clear or almost 
clear (0 or 1).  Assuming an observed response rate of 59% (16 of 27) or 70% (19 of 27) for the 
ustekinumab group and a response rate of 79% (42 of 53) for the risankizumab group, the 95% exact CI 
for the difference between treatment groups will have a width of –2.7 to 42.4 or –13.9 to 31.9, 
respectively.
Part 4 will enroll 28 subjects (age 6 to less than 12 years). (Japan only: Approximately 2 adolescents aged 
12 to <18 years will be included.) As the design of Parts 3 and 4 only differs by the intensity of the PK 
sampling, the 40 subjects (aged 6 to <12 years) enrolled into Parts 3 and 4 can be analyzed together if it 
is confirmed in Part 3 that the same dosing regimen is used for both Parts 3 and 4.  Assuming observed 
response rates for each of the co-primary endpoints of 65% (26 of 40), 75% (30 of 40) or 85% (34 of 40), 
the 95% exact CI will have a width of 48.3 to 79.4, 58.8 to 87.3, or 70.2 to 94.3, respectively. Results 
from the approximately 2 Japanese adolescents (ages 12 to < 18 years) will be assessed separately, as 
applicable.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (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 investigator are specified in Appendix B.
In the event a significant disaster/crisis (e.g., epidemic/pandemic, natural disaster, conflict/combat) 
occurs leading to difficulties in performing protocol-specified procedures, AbbVie may engage with 
study site personnel in efforts to ensure the safety of subjects, maintain protocol compliance, and 
minimize risks to the integrity of the study while trying to best manage subject continuity of care.  This 
may include alternative methods for assessments (e.g., phone contacts or virtual site visits), alternative 
locations for data collection (e.g., use of a local lab instead of a central lab) and shipping investigational 
product and/or supplies to ensure continuity of treatment where allowed.  In all cases, these alternative 
measures must be allowed by local regulations and permitted by IRB/IEC.  Investigators should notify 
AbbVie if any urgent safety measures are taken to protect the subjects against any immediate hazard.
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8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
For the personal data that AbbVie Deutschland GmbH & Co acting as sponsor of the submitted study 
("AbbVie") controls and maintains, AbbVie has developed a robust security program focused on due 
diligence in design, managed change, and information security governance. Information Security policies 
govern the Information Security functions including identity and access management, operations, 
infrastructure, application, and third-party security requirements. The risk-based AbbVie Data 
Classification Tool dictates the level of scrutiny and control required for the relevant activities per 
AbbVie's Information Security policies taking into account the sensitivity of the data.
Before patient data is shared with AbbVie, the study doctor and staff will replace any information that 
could directly identify a patient (such as name, address, and contact information) with a generic code 
which AbbVie cannot link to that patient's identity to protect the confidentiality of the data.
AbbVie has a data protection impact assessment (DPIA) program to ensure and document the 
appropriate controls and safeguards stated above are in place for clinical trial data that it controls and 
maintains and these processing activities respect privacy of clinical trial subjects. AbbVie also maintains 
robust security incident response policies and procedures, including requirements for the containment 
of any data related incidents, the mitigation measures where needed, and notification to authorities or 
affected individuals where required.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported. All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data. Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial follows the currently approved 
protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory requirement(s) including EU 
Clinical Trial Regulation 536/2014. During the COVID-19 pandemic, remote data review and verification 
may be employed if allowed by the local regulatory authority, IRB/IEC, and the study site.
Supplemental study case report forms should be completed in the event of COVID-19 related 
missed/virtual visits, study drug interruptions or discontinuations, or adverse events (including capture 
of specific signs/symptoms of infection and testing results).
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
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will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements, including EU Clinical Trial Regulation 536/2014.
11
COMPLETION OF THE STUDY
The end-of-study is defined as the date of the last subject's last visit or the actual date of follow-up 
contact, whichever is later.
12
REFERENCES
1.
AbbVie. Risankizumab Investigator's Brochure Edition 6. 11 May 2020.
2.
Khader SA, Pearl JE, Sakamoto K, et al. IL-23 compensates for the absence of IL-12p70 and is 
essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-
specific IFN-gamma responses if IL-12p70 is available. J Immunol. 2005;175(2):788-95.
3.
O'Garra A, Redford PS, McNab FW, et al. The immune response in tuberculosis. Annu Rev Immunol. 
2013;31:475-527.
4.
Qian X, Gu L, Ning H, et al. Increased Th17 cells in the tumor microenvironment is mediated by IL-23 
via tumor-secreted prostaglandin E2. J Immunol. 2013;190(11):5894-902.
5.
Baird AM, Leonard J, Naicker KM, et al. IL-23 is pro-proliferative, epigenetically regulated and 
modulated by chemotherapy in non-small cell lung cancer. Lung Cancer. 2013;79(1):83-90.
6.
Hu WH, Chen HH, Yen SL, et al. Increased expression of interleukin-23 associated with progression of 
colorectal cancer. J Surg Oncol. 2017;115(2):208-12.
7.
Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature. 
2006;442(7101):461-5.
8.
AbbVie. Data on File, RRT165055.
9.
Stelara (ustekinumab) injection [prescribing information]. Horsham, PA; Janssen Biotech, Inc, 2019.
10. Suleiman AA, Minocha M, Khatri A, et al. Population pharmacokinetics of risankizumab in healthy 
volunteers and subjects with moderate to severe plaque psoriasis: integrated analyses of phase I-III 
clinical trials. Clin Pharmacokinet. 2019;58(10):1309-21.
11. AbbVie. R&D/14/1263. A Multicenter, Randomized, Double-Dummy, Double-Blind Study Evaluating 
Two Doses of Adalimumab versus Methotrexate (MTX) in Pediatric Subjects with Chronic Plaque 
Psoriasis (Ps) (Study M04-717). 2015.
12. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4(2):213-26.
13. Agency EM. P/0205/2016. Opinion of the Paediatric Committee on the agreement of a Paediatric 
Investigation Plan and a deferral and a waiver. 2016.
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APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AAC
Anaphylaxis Adjudication Committee
Ab
Antibody
ADA
antidrug antibody
AE
adverse event
Ag
antigen
ASI
areas of safety interest
BP
blood pressure
BSA
Body surface area
CDLQI
Children's Dermatology Life Quality Index
CI
confidence interval
COVID
Coronavirus disease of 2019
CTCAE
Common Terminology Criteria for Adverse Events
DNA
deoxyribonucleic acid
DMC
Data monitoring committee
EC
Ethics Committee
ECG
electrocardiogram
eCRF
electronic case report form
FDLQI
Family Dermatology Life Quality Index
GCP
Good clinical practice
HB
hepatitis B
HBc
Hepatitis B core
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCT
hematopoietic stem cell transplantation
HCV
hepatitis C virus
HCV Ab
hepatitis C virus antibody
HIV
Human immunodeficiency virus
HIV Ab
HIV antibody
IB
Investigator's Brochure
ICH
International Council for Harmonisation
IEC/IRB
Independent Ethics Committee/Institutional Review Board
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IgA
Immunoglobulin A
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IGRA
interferon gamma release assay
IL
interleukin
IMP
Investigational Medicinal Product
INR
international normalized ratio
IRB
Institutional review board
IRT
Interactive response technology
ITT
intent-to-treat
MedDRA
Medical Dictionary for Regulatory Activities
MI
myocardial infarction
nAb
neutralizing antibody
NRS
Numerical Rating Scale
OLE
open-label extension
PASI
Psoriasis Area Severity Index
PCR
polymerase chain reaction
PD visit
Premature Discontinuation visit
PE
physical examination
PFS
pre-filled syringe
PIP
pediatric investigational plan
PK
Pharmacokinetic(s)
PPD
purified protein derivative (tuberculin)
PRO
patient-reported outcome
Ps
psoriasis
PT
preferred term
q12w
every 12 weeks
QOL
quality of life
RBC
red blood cell
RNA 
ribonucleic acid
RSI
Reference Safety Information
SAE
serious adverse event
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
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SC
subcutaneous
SOC
system organ class
sPGA
Static Physician's Global Assessment
SUSAR
Suspected Unexpected Serious Adverse Reaction
TB
tuberculosis
TBM
T cells, B cells, and monocytes
TEAE
Treatment emergent adverse event
WBC
white blood cell
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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M19-977:  OptIMMize-1:  A Randomized, Active-controlled, Efficacy Assessor-blinded Study to 
Evaluate Pharmacokinetics, Safety, and Efficacy of Risankizumab in Patients From 6 to Less Than 
18 Years of Age With Moderate to Severe Plaque Psoriasis.
Protocol Date:  16 October 2023
Clinical research studies sponsored by AbbVie are subject to the ICH GCP and local regulations and 
guidelines governing the study at the site location.  In signing the Investigator Agreement, the 
investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate IRB/IEC, except when necessary to protect the subject from 
immediate harm.
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., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the IB/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 protocol and all of its amendments.
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. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
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APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Clinical Program Development
Clinical Development, Immunology
Clinical Development, Immunology
Data and Statistical Sciences
Data and Statistical Sciences
Clinical Pharmacology
Page 45 of 107
 














STUDY M19-977  |  Version 5.0 |  EU CT 2023-504156-10-00 
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E. SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
18 March 2020
Version 2.0
06 January 2021
Version 3.0 
27 May 2021
Administrative Change 1
24 June 2021
Version 3.1 (Japan Only)
25 June 2021
Version 4.0
02 February 2023
Administrative Change 2
23 February 2023
The purpose of this version is to correct minor typographical errors and to update the following 
sections:
Protocol

Updated the Sponsor Emergency Medical Contact information on protocol title page.
Rationale: To reflect personnel changes for this study.

The EU CT number was updated on the title page and footer throughout the protocol and 
operations manual.
Rationale: To provide the EU CT number.

Added "For European Union countries: the sponsor is AbbVie Deutschland GmbH & Co. KG" to 
title page.
Rationale: To clarify the MAH in the European Union.

Added Section 5.10 EU CTR Publication Policy.
Rationale:  To provide a binding sponsor statement that the clinical trial will be conducted in 
compliance with EU Clinical Trial Regulation 536/2014 .

In Section 6.1 added that SUSAR reporting for the IMP will be done to the Eudravigilance 
database in accordance with EU Clinical Trial Regulation 536/2014 as part of the global and local 
requirements that AbbVie is applying to.
Rationale: To describe the procedure for reporting of suspected unexpected adverse reactions 
(SUSAR) by the sponsor to the Eudravigilance database as per EU Clinical Trial Regulation 
536/2014.

Updated to include new program lead, therapeutic area MD, and clinical pharmacology contacts 
Appendix C (List of Protocol Signatories).
Rationale: To reflect personnel changes for this study.
Page 52 of 107
 


STUDY M19-977  |  Version 5.0 |  EU CT 2023-504156-10-00 
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Operations Manual

Updated the Sponsor Emergency Medical Contact in Section 1 and Section 4.3.
Rationale: To reflect personnel changes for this study.

Removed the address and phone number for the Safety team from Section 1.
Rationale: To remove unnecessary information from contacts.

In Section 3.14, under Table 1 - Clinical Laboratory Testing changed "gamma glutamyl 
transferase/γ-genotype" to "GGT."
Rationale: To address a typographical error.

In Section 4.3 and Section 5.1, added that SUSAR reporting for the IMP will be done to the 
Eudravigilance database in accordance with EU Clinical Trial Regulation 536/2014.
Rationale:  To describe the procedure for reporting of suspected unexpected adverse reactions 
(SUSAR) by the sponsor to the Eudravigilance database as per EU Clinical Trial Regulation 
536/2014.
Page 53 of 107
 

SAP_001.pdf: 
Risankizumab
M19-977 – Statistical Analysis Plan
Version 4.0 – 16 October 2023
1
Statistical Analysis Plan for Study M19-977
OptIMMize-1: A Randomized, Active-controlled, 
Efficacy Assessor-blinded Study to Evaluate 
Pharmacokinetics, Safety, and Efficacy of 
Risankizumab in Patients From 6 to Less Than 
18 Years of Age With Moderate to Severe 
Plaque Psoriasis
Date: 16 October 2023
Version 4.0
 
NCT04435600


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M19-977 – Statistical Analysis Plan
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Table of Contents
1.0
Introduction...........................................................................5
2.0
Study Design and Objectives ................................................6
2.1
Objectives, Hypotheses and Estimands................................................... 6
2.2
Study Design Overview.......................................................................... 8
2.3
Treatment Assignment and Blinding..................................................... 14
2.4
Sample Size Determination .................................................................. 14
3.0
Endpoints.............................................................................16
3.1
Primary Endpoint(s) ............................................................................. 16
3.2
Secondary Endpoint(s) ......................................................................... 16
3.3
Other Efficacy Endpoint(s)................................................................... 17
3.4
Safety Endpoint(s)................................................................................ 18
3.5
Additional Endpoint(s) ......................................................................... 18
4.0
Analysis Populations ...........................................................18
5.0
Subject Disposition..............................................................19
6.0
Study Drug Duration and Compliance ..............................21
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ...................22
7.1
Demographics and Baseline Characteristics.......................................... 23
7.2
Medical History.................................................................................... 23
7.3
Prior and Concomitant Medications...................................................... 24
8.0
Handling of Potential Intercurrent Events for the 
Primary and Secondary Endpoints ....................................24
9.0
Efficacy Analyses.................................................................25
9.1
General Considerations......................................................................... 25
9.2
Handling of Missing Data..................................................................... 26
9.3
Primary Efficacy Endpoint(s) and Analyses.......................................... 26
9.3.1
Primary Efficacy Endpoint(s) ............................................................... 26
9.3.2
Main Analysis Primary Efficacy Endpoint(s)........................................ 27
9.3.3
Sensitivity and Supplementary Analyses of the Primary Efficacy 
Endpoint(s)........................................................................................... 29
9.4
Secondary Efficacy Endpoints and Analyses ........................................ 29
 


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9.4.1
Key Secondary Efficacy Endpoints....................................................... 29
9.4.2
Main Analyses of Key Secondary Efficacy Analyses............................ 29
9.4.3
Sensitivity and Supplementary Analyses for Key Secondary 
Efficacy Endpoint(s)............................................................................. 32
9.4.4
Supportive Secondary Efficacy Endpoints and Analyses....................... 32
9.5
Additional Efficacy Analyses ............................................................... 32
9.6
Efficacy Subgroup Analyses................................................................. 32
10.0
Safety Analyses....................................................................33
10.1
General Considerations......................................................................... 33
10.2
Adverse Events..................................................................................... 34
10.2.1
Treatment-Emergent Adverse Events.................................................... 34
10.2.2
Adverse Event Overview...................................................................... 34
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT...................... 36
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Risankizumab Exposure ....................................................................... 36
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 37
10.2.6
Areas of Safety Interest ........................................................................ 37
10.2.7
Combined Analyses for Adolescents/Children...................................... 38
10.3
Analysis of Laboratory Data................................................................. 38
10.4
Analysis of Vital Signs......................................................................... 40
10.5
Safety Subgroup Analyses.................................................................... 41
10.6
Other Safety Analyses .......................................................................... 41
11.0
Other Analyses ....................................................................41
12.0
Interim Analyses..................................................................41
12.1
Data Monitoring Committee................................................................. 42
13.0
Overall Type-I Error Control.............................................43
14.0
Version History ...................................................................43
15.0
References............................................................................45
 


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List of Tables
Table 1.
Summary of the Estimand Attributes of the Co-Primary Efficacy 
Endpoints ............................................................................................. 27
Table 2.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints ............................................................................... 30
Table 3.
SAP Version History Summary ............................................................ 43
List of Figures
Figure 1.
Part 1 Schematic..................................................................................... 9
Figure 2.
Part 2 Schematic................................................................................... 11
Figure 3.
Part 3 Schematic................................................................................... 12
Figure 4.
Part 4 Schematic................................................................................... 13
List of Appendices
Appendix A.
Protocol Deviations .............................................................................. 46
Appendix B.
Definition of Area of Safety Interest..................................................... 47
Appendix C.
Potentially Clinically Significant Criteria for Safety Endpoints............. 48
Appendix D.
Criteria for Potentially Clinically Significant Vital Sign Values............ 50
 


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1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for risankizumab 
Study M19-977 "OptIMMize-1: A Randomized, Active-controlled, Efficacy Assessor-
blinded Study to Evaluate Pharmacokinetics, Safety and Efficacy of Risankizumab in 
Patients From 6 to Less Than 18 Years of Age With Moderate to Severe Plaque 
Psoriasis."
Study M19-977 examines the efficacy and safety of risankizumab in subjects from 6 to 
less than 18 years of age with moderate to severe plaque psoriasis.
The study consists of four parts with distinct subject populations (see Section 2.0).  The 
analyses described here will be conducted for each of the parts separately as specified in 
Section 12.0.
The analyses of biomarker research endpoints, pharmacokinetic and immunogenicity 
endpoints will not be covered in this SAP.
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analyses.
Unless noted otherwise, all analyses will be performed using SAS Version 9.4 (SAS 
Institute Inc., Cary, NC  27513) or later under the UNIX operating system.
This SAP includes no changes to analyses described in the protocol with following 
exception:
●
For the other efficacy endpoints "Achievement of sPGA clear or almost clear 
(0 or 1)" at Week 12 during the treatment or withdrawal period of Part 2 and at 
all other visits collected "(US only: and ≥ 2 grade improvement from 
baseline)" was added.
 


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2.0
Study Design and Objectives
2.1
Objectives, Hypotheses and Estimands
The objective of this study is to evaluate the pharmacokinetics (PK), safety, and efficacy 
of risankizumab in subjects from 6 to less than 18 years of age with moderate to severe 
plaque psoriasis (Ps).
Primary Efficacy
The primary efficacy objective is to assess the rate of subjects who achieve a) PASI 75 
(defined as at least 75% improvement from baseline in PASI) and b) sPGA clear or almost 
clear (0 or 1) (US only: and ≥2 grade improvement from baseline) at Week 16 of initial 
treatment with study drug based on the Intent-to-Treat (ITT) population (as defined in 
Section 4.0).
There are no statistical hypotheses corresponding to the co-primary efficacy objectives as 
efficacy will be assessed descriptively, providing estimates with confidence intervals 
without performing statistical testing.
The estimands corresponding to the co-primary efficacy objectives are defined as follows 
for Part 1, Part 3, and Part 4:
●
Percentage of subjects achieving at least 75% reduction in PASI (PASI75) 
from Baseline at Week 16 of initial treatment with risankizumab without the 
use of rescue medication and regardless of premature discontinuation of study 
drug in the ITT population
●
Percentage of subjects achieving sPGA clear or almost clear (0 or 1) (US only: 
and ≥2 grade improvement from baseline) at Week 16 of initial treatment with 
risankizumab without the use of rescue medication and regardless of premature 
discontinuation of study drug in the ITT population
 


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The estimands corresponding to the co-primary efficacy objectives are defined as follows 
for Part 2:
●
Difference in the percentage of subjects achieving at least 75% reduction in 
PASI (PASI75) from Baseline at Week 16 of initial treatment with 
risankizumab compared to ustekinumab without the use of rescue medication 
and regardless of premature discontinuation of study drug in the ITT 
population
●
Difference in the percentage of subjects achieving sPGA clear or almost clear 
(0 or 1) (US only: and ≥2 grade improvement from baseline) at Week 16 of 
initial treatment with risankizumab compared to ustekinumab without the use 
of rescue medication and regardless of premature discontinuation of study drug 
in the ITT population
Secondary Efficacy
The secondary efficacy objectives are to assess the rate of subjects who achieve the 
ranked secondary endpoints specified in Section 3.2 below in the ITT population.
There are no statistical hypotheses corresponding to the secondary efficacy objectives as 
efficacy will be assessed descriptively, providing estimates with confidence intervals 
without performing statistical testing.
The estimands corresponding to the secondary efficacy objectives are defined as follows 
for Part 1, Part 3, and Part 4:
●
Percentage of subjects achieving at least 90% reduction in PASI (PASI90) 
from Baseline at Week 16 of initial treatment with risankizumab without the 
use of rescue medication and regardless of premature discontinuation of study 
drug in the ITT population
●
Percentage of subjects achieving 100% reduction in PASI (PASI100) from 
Baseline at Week 16 of initial treatment with risankizumab without the use of 
rescue medication and regardless of premature discontinuation of study drug in 
the ITT population
 


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The estimands corresponding to the secondary efficacy objectives are defined as follows 
for Part 2:
●
Difference in the percentage of subjects achieving at least 90% reduction in 
PASI (PASI90) from Baseline at Week 16 of initial treatment with 
risankizumab compared to ustekinumab without the use of rescue medication 
and regardless of premature discontinuation of study drug in the ITT 
population
●
Difference in the percentage of subjects achieving 100% reduction in PASI 
(PASI100) from Baseline at Week 16 of initial treatment with risankizumab 
compared to ustekinumab without the use of rescue medication and regardless 
of premature discontinuation of study drug in the ITT population
●
Percentage of subjects achieving sPGA clear or almost clear (0 or 1) (US only: 
and ≥2 grade improvement from baseline) at Week 0 and Week 16 of the 
re-treatment phase in Part 2 with risankizumab without the use of rescue 
medication and regardless of premature discontinuation of study drug in the 
ITT population
Rescue medication for the purposes of this analysis will be considered any systemic (oral 
or parenteral) medication used specifically for the treatment of psoriasis.
Of note: the reference to the US in "sPGA clear or almost clear (0 or 1) (US only: and 
≥2 grade improvement from baseline)" does not refer to the individual subjects' location 
of residence but implies that this is an additional endpoint relevant for US regulatory 
purposes, while the endpoint relevant ex-US does not require a minimum improvement 
from baseline.
2.2
Study Design Overview
The study consists of 4 parts, each with distinct patient populations.
 




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Part 2
Part 2 will be a randomized, evaluator-blinded assessment of efficacy, comparing 
risankizumab with ustekinumab in at least 80 adolescents (age 12 to less than 18 years) 
with moderate to severe disease.  A 16-week initial treatment period (Period A) will be 
followed by an up to 36-week randomized treatment or withdrawal period (Period B) for 
risankizumab responders, and then a 16-week re-treatment period (Period C) for subjects 
who experience a disease flare (defined as sPGA ≥ 3 on or after Week 28).  Risankizumab 
non-responders and subjects who received ustekinumab in Period A will receive 
risankizumab (Period B) until Week 40.
In Period A, subjects will be randomized (2:1) to receive risankizumab SC based on 
weight (subjects who weigh ≥40 kg will receive 
mg risankizumab, while subjects 
who weigh < 40 kg will receive 
mg risankizumab) or ustekinumab SC based on weight 
(0.75 mg/kg for subjects < 60 kg; 45 mg for Subjects 60 to < 100 kg; 90 mg for subjects 
≥100 kg) at Weeks 0 and 4.  At Week 16, risankizumab non-responders (sPGA ≥ 2) and 
subjects initially randomized to ustekinumab will enter Period B and will receive 
risankizumab every 12 weeks until Week 40.  Risankizumab responders (sPGA = 0 or 1) 
will enter Period B and will be re-randomized (1:1) to receive no medication until a 
disease flare (sPGA ≥ 3 on or after Week 28) or risankizumab every 12 weeks until 
Week 40.  Subjects randomized to the withdrawal arm in Period B who experience a 
disease flare on or after Week 28 will enter Re-Treatment Period C to receive 
risankizumab at Weeks 0 and 4 of the 16-week re-treatment period.  Randomization and 
re-randomization will not be stratified due to the small sample size.
Subjects who complete either the Week 52 visit for those in Period B or 16 weeks of the 
re-treatment Period C have the option to enroll into Study M19-973, the OLE study.
A schematic of Part 2 is shown in Figure 2.
 








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2.3
Treatment Assignment and Blinding
All subjects will be assigned a unique identification number by the IRT at the screening 
visit.  For subjects who rescreen, the screening number assigned by the IRT at the initial 
screening visit should be used.
Study Parts 1, 3, and 4 are open-label single arm and all subjects will receive the same 
dose exposure equivalent based on body weight (for Parts 3 and 4) and the same 
frequency of study drug.
For Part 2 only, the IRT will assign a randomization number that will encode the subject's 
treatment group assignment in Period A according to the randomization schedule 
generated by the statistics department at AbbVie.  For subjects re-randomized in Period B 
of Part 2, the IRT will assign a separate randomization number that will encode the 
subject's treatment group assignment in Period B according to a separate randomization 
schedule generated by the statistics department at AbbVie.  Randomization for Period A 
will be done in a 2:1 ratio of risankizumab vs. ustekinumab.  The re-randomization ratio 
of continued treatment with risankizumab vs. no treatment for Period B will be 1:1.  
Randomization and re-randomization will not be stratified due to the small number of 
subjects.
The blinded efficacy assessor must be independent from all other study activities.  The 
efficacy assessor will remain blinded to each subject's treatment, clinical laboratory 
results, and all subject safety data during the course of the study.
2.4
Sample Size Determination
The sample sizes for the 4 study parts are per the risankizumab psoriasis pediatric 
investigational plan (PIP), in which it has also been agreed the study does not need to be 
powered to demonstrate superiority.  The current study design meets the PIP commitment 
of at least 120 subjects evaluable for the primary endpoint of which at least 40 subjects 
are age 6 to less than 12 years and at least 80 subjects are age 12 to less than 18 years.1
 


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All enrolled (for Part 2 all randomized) subjects will be considered evaluable for the 
primary endpoint.  Subjects discontinued from the study prior to Week 16 will be 
included in the analysis as non-responders.  Thus, the PIP commitment of at least 
120 subjects evaluable for the primary endpoint of which at least 40 subjects are age 6 to 
less than 12 years and at least 80 subjects are age 12 to less than 18 years will be fulfilled 
with the current study.
Part 1 (age 12 to less than 18 years with severe psoriasis) and Part 3 (age 6 to less than 
12 years with severe psoriasis) are being conducted primarily for PK purposes and will 
each enroll 12 subjects.  Enrollment of 12 subjects, a sample size typical of Phase 1 PK 
and safety/tolerability studies, will be sufficient to evaluate and confirm if the dosing is 
able to provide exposures in pediatric subjects consistent with exposures at the therapeutic 
dose in adult subjects, and to provide sentinel efficacy and safety data before exposing 
additional subjects with moderate to severe disease.
Assuming observed response rates for each of the co-primary endpoints of 66.7% (8 of 
12), 75% (9 of 12) or 83.3% (10 of 12), the 95% exact CI will have a width of 34.9 to 
90.1, 42.8 to 94.5, or 51.6 to 97.9, respectively.
Part 2 will enroll 80 subjects age 12 to less than 18 years in a 2:1 ratio (i.e., 53 subjects 
will be randomized to risankizumab, 27 subjects to ustekinumab).  The assumptions for 
response rates are based on the results for the 2 ustekinumab-controlled risankizumab 
studies in adult subjects with moderate to severe plaque psoriasis and apply to both 
co-primary endpoints, PASI75 and sPGA clear or almost clear (0 or 1).  Assuming an 
observed response rate of 59% (16 of 27) or 70% (19 of 27) for the ustekinumab group 
and a response rate of 79% (42 of 53) for the risankizumab group, the 95% exact CI for 
the difference between treatment groups will have a width of –2.7 to 42.4 or –13.9 to 31.9, 
respectively.
Part 4 will enroll 28 subjects (age 6 to less than 12 years).  As the design of Parts 3 and 4 
only differs by the intensity of the PK sampling, the 40 subjects enrolled into Parts 3 
and 4 can be analyzed together if it is confirmed in Part 3 that the same dosing regimen is 
 


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used for both Parts 3 and 4.  Assuming observed response rates for each of the co-primary 
endpoints of 65% (26 of 40), 75% (30 of 40) or 85% (34 of 40), the 95% exact CI will 
have a width of 48.3 to 79.4, 58.8 to 87.3, or 70.2 to 94.3, respectively.
3.0
Endpoints
3.1
Primary Endpoint(s)
The co-primary endpoints of this study are:
●
Achievement of PASI 75 (defined as at least 75% improvement from baseline 
in PASI) at Week 16 of initial treatment
●
Achievement of sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at Week 16 of initial treatment.
3.2
Secondary Endpoint(s)
The ranked secondary endpoints of this study are:
●
Achievement of PASI 90 (defined as at least 90% improvement from baseline 
in PASI) at Week 16 of initial treatment
●
Achievement of PASI 100 (defined as 100% improvement from baseline in 
PASI) at Week 16 of initial treatment
●
Achievement of sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at Week 0 and Week 16 of the re-treatment phase 
in Part 2
The non-ranked secondary endpoints are:
●
Achievement of PASI 50 (defined as at least 50% improvement from baseline 
in PASI) at Week 16 of initial treatment
●
Achievement of PASI 50 (defined as at least 50% improvement from baseline 
in PASI) at Week 0 and Week 16 of the re-treatment phase in Part 2
 


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●
Achievement of PASI 90 (defined as at least 90% improvement from baseline 
in PASI) at Week 0 and Week 16 of the re-treatment phase in Part 2
●
Achievement of PASI 100 (defined as 100% improvement from baseline in 
PASI) at Week 0 and Week 16 of the re-treatment phase in Part 2
●
Achievement of PASI 75 (defined as at least 75% improvement from baseline 
in PASI) at Week 0 and Week 16 of the re-treatment phase in Part 2
●
Change in Children's Dermatology Life Quality Index (CDLQI) from Week 0 
to Week 16 of initial treatment in Part 2
●
Change in CDLQI from Week 0 to Week 16 of re-treatment phase of Part 2
●
Change in Family Dermatology Life Quality Index (FDLQI) from Week 0 to 
Week 16 of initial treatment in Part 2
●
Change in FDLQI from Week 0 to Week 16 of re-treatment phase of Part 2
●
Change in Itch Numeric Rating Scale (Itch NRS) from Week 0 to Week 16 of 
initial treatment in Part 2
●
Change in Itch NRS from Week 0 to Week 16 of re-treatment phase of Part 2
●
Achievement of ≥ 4-point improvement from baseline in the Itch Numeric 
Rating Scale (in patients with Baseline score ≥ 4) at Week 16 of initial 
treatment in Part 2
3.3
Other Efficacy Endpoint(s)
The other efficacy endpoints of this study are:
●
Achievement of PASI 75 at Week 12 during the treatment or withdrawal 
period of Part 2
●
Achievement of sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at Week 12 during the treatment or withdrawal 
period of Part 2
●
Achievement of PASI 50/75/90/100 at all other visits collected
●
Achievement of sPGA clear (0) at all other visits collected
●
Achievement of sPGA clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at all other visits collected
 


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●
Change in Itch Numeric Rating Scale (Itch NRS) at each study visit from 
Week 0
●
Achievement of ≥ 4-point improvement from baseline in the Itch Numeric 
Rating Scale (in patients with Baseline score ≥ 4) at each study visit in Part 2
●
Change in CDLQI at each study visit from Week 0
●
Change in FDLQI at each study visit from Week 0
3.4
Safety Endpoint(s)
The following endpoints will be included in the safety analyses:
●
Treatment emergent adverse events (TEAEs);
●
Serious adverse events (SAEs);
●
Areas of safety interest (ASI);
●
TEAEs leading to discontinuation;
●
Vital signs and laboratory tests (hematology, chemistry).
3.5
Additional Endpoint(s)
Not applicable.
4.0
Analysis Populations
The following population sets will be used for the analyses.
Part 1, Part 3, Part 4:
The Intent to Treat (ITT) Population in each study part includes all enrolled subjects.  
The ITT Population will be used for all efficacy and baseline analyses.
The Safety Analysis Population consists of all subjects who received at least 1 dose of 
study drug.
 


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For Part 4, the two Japanese adolescents aged 12 to <18 years, if enrolled, will not be 
included in the Intent to Treat (ITT) and the Safety Analysis Population. Their results will 
be listed separately.
Part 2:
The Intent to Treat (ITT) Population includes all randomized subjects.  The ITT 
Population will be used for all efficacy and baseline analyses.  Subjects will be analyzed 
according to treatment as randomized.
The Safety Analysis Population in each study part consists of all subjects who received 
at least 1 dose of study drug.  Subjects will be included in the analysis according to the 
study drug that they actually received.  For Period A, a subject's actual treatment will be 
determined by the first dose of study drug.  For subjects re-randomized in Period B, only 
subjects who received no drug are included in the withdrawal arm, subjects who received 
at least one dose of study drug are included in the treatment continuation arm.
For analyses by study period in Part 2, only subjects enrolled into the respective study 
period will be included for that period.
For displays by treatment group for Part 2, treatment groups will be based on 
randomization and re-randomization assignments.
5.0
Subject Disposition
Part 1, Part 3, Part 4:
A summary of subject accountability will be provided where the number of subjects in 
each of the following categories will be summarized:
●
Subjects screened
●
Subjects enrolled
●
Subjects who took at least one dose of study drug
 


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●
Only for analyses conducted prior to the completion of the respective study 
part, see Section 12.0: Subjects who completed Week 16
●
Only for analyses conducted prior to the completion of the respective study 
part, see Section 12.0: subjects ongoing at the time of analysis
●
Subjects who completed the study
●
Subjects who prematurely discontinued the study (all reasons and primary 
reason)
●
Subjects who prematurely discontinued study drug (all reasons and primary 
reason)
Part 2:
A summary of subject accountability will be provided where the number of subjects in 
each of the following categories will be summarized overall and by treatment group:
●
Subjects screened
●
Subjects randomized
●
Subjects who completed Period A
●
Subjects enrolled (re-randomized) into Period B (note: subjects randomized to 
ustekinumab and subjects randomized to risankizumab who are non-
responders at Week 16 in Period A are enrolled for OL risankizumab 
treatment, subjects randomized to risankizumab who are responders at 
Week 16 in Period A are re-randomized between withdrawal/no treatment and 
OL risankizumab treatment continuation)
●
Subjects who completed Period B
●
Only for subjects re-randomized to treatment withdrawal: Subjects completed 
36 weeks in withdrawal Period B without disease flare
●
Only for subjects re-randomized to treatment withdrawal: Subjects completed 
withdrawal Period B with disease flare
●
Subjects enrolled into re-treatment Period C
●
Subjects who completed re-treatment Period C
 


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●
Subjects who prematurely discontinued the study by period and overall (all 
reasons and primary reason)
●
Subjects who prematurely discontinued study drug by period and overall (all 
reasons and primary reason)
6.0
Study Drug Duration and Compliance
Part 1, Part 3, Part 4:
For the ITT population, duration of treatment will be summarized using the number of 
subjects treated, mean, standard deviation, median, minimum and maximum.  Duration of 
treatment is defined for each subject as last dose date minus first dose date + 84 days.
Treatment compliance will be summarized for the ITT population as follows:
There will be a summary of the number of subjects receiving study drug and dose at each 
study drug administration visit.  This will be repeated on the cumulative number of doses.
When computing compliance at each study drug administration visit, the denominator will 
include all subjects who have not prematurely discontinued the study drug prior to the 
scheduled study drug injection.
Part 2:
For the ITT population, duration of treatment will be summarized by treatment group 
using the number of subjects treated, mean, standard deviation, median, minimum and 
maximum.  Duration of treatment is defined for each subject as last dose date minus 
first dose date + 84 days.  For subjects re-randomized to treatment withdrawal in 
Period B, treatment duration will be counted until last dose date in Period A + 84 days and 
then restarted at the first re-treatment dose after the treatment withdrawal, if applicable.  
Duration of risankizumab treatment is defined for each subject as last risankizumab 
dose date minus first risankizumab dose date + 84 days.  For subjects re-randomized to 
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last risankizumab dose date in Period A + 84 days and then restarted at the 
first risankizumab re-treatment dose after the treatment withdrawal, if applicable.
Treatment compliance will be summarized for the ITT population by treatment group as 
follows:
There will be a summary of the number of subjects receiving study drug and dose at each 
study drug administration visit.  This will be repeated on the cumulative number of doses.
When computing compliance at each study drug administration visit, the denominator will 
include all subjects in a specific study period who have not prematurely discontinued the 
study drug prior to the scheduled study drug injection.
In addition to the analyses by study part, analyses of duration of risankizumab treatment 
will be created that combine subjects enrolled into Part 1 and Part 2 (adolescents) and 
subjects enrolled into Part 3 and Part 4 (children), respectively. 
The two Japanese adolescents aged 12 to < 18 years enrolled into Part 4 are not included 
in the Safety Analysis Population (see Section 4.0) and listed separately throughout. They 
are therefore not included in the above.
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications
Demographics, baseline or disease characteristics and patient reported outcomes, medical 
history, and prior and concomitant medications will be summarized for the ITT population 
overall and by treatment group (for Part 2).
Categorical variables will be summarized with the number and percentage of subjects; 
percentages will be calculated based on the number of non-missing observations.  
Continuous variables will be summarized with descriptive statistics (number of 
non-missing observations, mean and standard deviation, median, minimum and 
maximum).
 


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7.1
Demographics and Baseline Characteristics
Continuous demographic variables include age (years), weight (kg), height (cm), and 
body mass index (BMI) (kg/m2).  Categorical demographic variables include sex, 
ethnicity, race, age (12 to < 15, 15 to < 18 years for Part 1 and 2; 6 to < 9, 9 to < 12 years 
for Part 3 and 4), weight (< 40 kg or ≥ 40 kg), region (Europe, North America, or rest of 
world).
Disease characteristics include prior systemic biologic for psoriasis (0 vs. ≥ 1), PASI 
(Psoriasis Area and Severity Index), BSA (Body Surface Area), sPGA categories, history 
of psoriatic arthritis (yes, no), duration of plaque psoriasis (in years).
In addition to the analyses by study part, analyses of demographics will be created that 
combine subjects enrolled into Part 1 and Part 2 (adolescents) and subjects enrolled into 
Part 3 and Part 4 (children), respectively.
The two Japanese adolescents aged 12 to < 18 years enrolled into Part 4 are not included 
in the Safety Analysis Population (see Section 4.0) and listed separately throughout. They 
are therefore not included in the above.
Patient Reported Outcomes (PROs) analyzed at baseline include CDLQI (Children's 
Dermatology Life Quality Index), FDLQI (Family's Dermatology Life Quality Index) and 
Itch Numeric Rating Scale (Itch NRS).  In addition to the analysis of Itch Numeric Rating 
Scale (Itch NRS) as a continuous variable, Itch NRS ≥ 4 will be analyzed as a categorical 
baseline variable.
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The actual version of the MedDRA coding dictionary will be noted in the 
statistical tables and clinical study report.  The number and percentage of subjects in each 
medical history category (by MedDRA system organ class and preferred term) will be 
summarized overall and by treatment group.  The system organ class (SOC) will be 
 


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presented in alphabetical order, and the preferred terms will be presented in alphabetical 
order within each SOC.  Subjects reporting more than one condition/diagnosis will be 
counted only once in each row (SOC or preferred term).
7.3
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by generic name.  A prior 
medication is defined as any medication taken prior to the date of the first dose of study 
drug.  A concomitant medication is defined as any medication that started prior to the date 
of the first dose of study drug and continued to be taken on or after the first dose of study 
drug or any medication that started on or after the date of the first dose of study drug, but 
not after the date of the last dose of study drug plus 140 days.  The number and percentage 
of subjects taking medications will be summarized by generic drug name based on the 
World Health Organization (WHO) Drug Dictionary for both prior and concomitant 
medications.
In addition, a table will be generated that displays the number of subjects by visit who 
started rescue medication on or prior to the respective visit.  Rescue medication for the 
purposes of this analysis will be considered any systemic (oral or parenteral) medication 
used specifically for the treatment of psoriasis.
8.0
Handling of Potential Intercurrent Events for the 
Primary and Secondary Endpoints
The efficacy endpoints (defined in Section 3.1, Section 3.2, and Section 3.3) will be 
analyzed on the ITT population to address the following potential intercurrent events:
1.
Binary Endpoints
●
For subjects with the use of rescue medication, values after the start of rescue 
medication will be excluded from analysis and subjects will be considered 
non-responders at all time points after the start of rescue medication.
●
Data collected will be used regardless of premature discontinuation of study 
drug.
 


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2.
Continuous endpoints
●
Values after the use of rescue medication will be excluded.
●
Data collected will be used regardless of premature discontinuation of study 
drug.
9.0
Efficacy Analyses
9.1
General Considerations
All efficacy analyses will be conducted in the ITT Population separately for each study 
part, as described in Section 12.0.  For analyses by study period in Part 2, only subjects 
enrolled into the respective study period will be included.
No statistical testing will be performed.  All confidence intervals will be two-sided with 
95% confidence probability.
Descriptive statistics will include counts and proportions for categorical data, and median, 
mean, standard deviation, first and third quartiles, and minimum/maximum for continuous 
data.  In addition, two-sided 95% confidence intervals (CI) will be reported.  For 
continuous endpoints, CIs for means and differences between means, respectively, will be 
based on the normal distribution.  For dichotomous endpoints, exact CIs will be provided 
based on the Clopper-Pearson method for proportions and by the Miettinen-Nurminen 
method for differences in proportions.2
The primary analysis for each study part will be performed at the time points described in 
Section 12.0.  This will be the only and final analysis for the co-primary efficacy 
endpoints for each part.
"Baseline" refers to the last non-missing observation before the first administration of 
study drug or the date of enrollment (Part 1, 3, 4) or randomization (Part 2) if no study 
drug is given.
 


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9.2
Handling of Missing Data
Missing data will be imputed using the following methods for the efficacy analyses:
●
Non-Responder Imputation (NRI):  the NRI analysis will categorize any 
subject who does not have evaluation during a specific visit window as a 
non-responder for that visit.  NRI will be the primary approach in the analyses 
of categorical variables.
●
Last Observation Carried Forward (LOCF): the LOCF analysis will impute a 
missing value with the last value observed previously. Baseline observations 
are not carried forward. LOCF will be the primary approach in the analyses of 
continuous variables.
●
As Observed (AO): The AO 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 AO analysis for that visit. AO will include all 
values collected in the study.  AO will exclude all values collected in the study 
after the first dose of rescue medication (see also Section 8.0).  AO will be 
used as sensitivity analysis in the analyses of categorical and continuous 
variables.
9.3
Primary Efficacy Endpoint(s) and Analyses
9.3.1
Primary Efficacy Endpoint(s)
The co-primary endpoints to assess the efficacy of risankizumab for the treatment of 
moderate to severe plaque psoriasis are:
●
Achievement of ≥ 75% improvement from baseline in PASI (PASI 75) at 
Week 16 of initial treatment
●
Achievement of sPGA of clear or almost clear (0 or 1) (US only: and ≥2 grade 
improvement from baseline) at Week 16 of initial treatment
 


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9.3.2
Main Analysis Primary Efficacy Endpoint(s)
The attributes of the estimands corresponding to the co-primary efficacy endpoints are 
summarized in Table 1.
Table 1.
Summary of the Estimand Attributes of the Co-Primary Efficacy 
Endpoints
Estimand 
Label
Attributes of the Estimands
Treatment
Endpoint
Population
Handling of 
Intercurrent 
Events
Statistical 
Summary
PASI75 at 
Week 16 of 
initial 
treatment
Risankizumab 
and 
Ustekinumab*
PASI75 at 
Week 16 of 
initial 
treatment
ITT

Subjects with 
the use of 
rescue 
medication on 
or prior to 
Week 16 will be 
considered as 
non-responders

For subjects 
who 
prematurely 
discontinue 
study drug on or 
prior to 
Week 16, data 
will be used 
regardless
Part 1, 3 and 4:
Percentage of 
subjects 
achieving 
PASI75 at 
Week 16 in the 
Risankizumab 
group
Part 2:
Difference in the 
percentage of 
subjects 
achieving 
PASI75 at 
Week 16 in the 
Risankizumab 
group in 
comparison with 
the Ustekinumab 
group
 


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Estimand 
Label
Attributes of the Estimands
Treatment
Endpoint
Population
Handling of 
Intercurrent 
Events
Statistical 
Summary
sPGA clear 
or almost 
clear (0 or 1) 
(US only: 
and 
≥2 grade 
improvement 
from 
baseline) at 
Week 16 of 
initial 
treatment
sPGA clear 
or almost 
clear (0 or 1) 
(US only: 
and 
≥2 grade 
improvement 
from 
baseline) at 
Week 16 of 
initial 
treatment
Part 1, 3 and 4:
Percentage of 
subjects 
achieving sPGA 
0/1 (US only: 
and ≥2 grade 
improvement 
from baseline) at 
Week 16 in the 
Risankizumab 
group
Part 2:
Difference in the 
percentage of 
subjects 
achieving sPGA 
0/1 (US only: 
and ≥2 grade 
improvement 
from baseline) at 
Week 16 in the 
Risankizumab 
group in 
comparison with 
the Ustekinumab 
group
*
Ustekinumab is only applicable for Part 2.
For analysis of the co-primary endpoints, exact CIs will be provided based on the 
Clopper-Pearson method for proportions (Part 1, 3 and 4) and by the Miettinen-Nurminen 
method for differences in proportions2 (Part 2).
NRI will be used as the primary approach for the analyses of the co-primary endpoints.
 


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9.3.3
Sensitivity and Supplementary Analyses of the Primary 
Efficacy Endpoint(s)
For dealing with missing data, AO will be used as sensitivity analysis for the analyses of 
the co-primary endpoints.
9.4
Secondary Efficacy Endpoints and Analyses
9.4.1
Key Secondary Efficacy Endpoints
The key (ranked) secondary efficacy endpoints are specified in Section 3.2.
9.4.2
Main Analyses of Key Secondary Efficacy Analyses
The attributes of the estimands corresponding to the key secondary efficacy endpoints are 
summarized in Table 2.
 


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Table 2.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints
Estimand 
Label
Attributes of the Estimands
Treatment
Endpoint
Population
Handling of 
Intercurrent Events
Statistical 
Summary
PASI90 at 
Week 16 
of initial 
treatment
Risankizumab 
and 
Ustekinumab*
PASI90 
at 
Week 16 
of initial 
treatment
ITT

Subjects with the 
use of rescue 
medication on or 
prior to Week 16 
will be 
considered as 
non-responders

For subjects who 
prematurely 
discontinue study 
drug on or prior 
to Week 16, data
will be used 
regardless
Part 1, 3 and 4:
Percentage of 
subjects achieving 
PASI90 at 
Week 16 in the 
Risankizumab 
group
Part 2:
Difference in the 
percentage of 
subjects achieving 
PASI90 at 
Week 16 in the 
Risankizumab 
group in 
comparison with 
the Ustekinumab
group
PASI100 
at 
Week 16 
of initial 
treatment
PASI100 
at 
Week 16 
of initial 
treatment
Part 1, 3 and 4:
Percentage of 
subjects achieving 
PASI100 at 
Week 16 in the 
Risankizumab 
group
Part 2:
Difference in the 
percentage of 
subjects achieving 
PASI100 at 
Week 16 in the 
Risankizumab 
group in 
comparison with 
the Ustekinumab 
group
 


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Table 2.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints (Continued)
Estimand 
Label
Attributes of the Estimands
Treatment
Endpoint
Population
Handling of 
Intercurrent Events
Statistical 
Summary
sPGA 
clear or 
almost 
clear (0 or 
1) (US 
only: and 
≥2 grade 
improve-
ment from 
baseline)
at Week 0 
of the re-
treatment 
phase in 
Part 2
Risankizumab
sPGA 
clear or 
almost 
clear (0 
or 1) (US 
only: and 
≥2 grade 
improve-
ment 
from 
baseline)
at Week 0 
of the re-
treatment 
phase in 
Part 2
ITT

Subjects with the 
use of rescue 
medication on or 
prior to Week 0 
of the re-
treatment period 
will be 
considered as 
non-responders

For subjects who 
prematurely 
discontinue study 
drug on or prior 
to Week 0 of the 
re-treatment 
period, data will 
be used 
regardless
Percentage of 
subjects achieving 
sPGA 0/1 (US 
only: and ≥2 grade 
improvement from 
baseline) at 
Week 0 of the re-
treatment period in 
the Risankizumab 
group
sPGA 
clear or 
almost 
clear (0 or 
1) (US 
only: and 
≥2 grade 
improve-
ment from 
baseline)
at 
Week 16 
of the re-
treatment 
phase in 
Part 2
sPGA 
clear or 
almost 
clear (0 
or 1) (US 
only: and 
≥2 grade 
improve-
ment 
from 
baseline)
at Week 
16 of the 
re-
treatment 
phase in 
Part 2

Subjects with the
use of rescue 
medication on or 
prior to Week 16 
of the re-
treatment period 
will be 
considered as 
non-responders

For subjects who 
prematurely 
discontinue study 
drug on or prior 
to Week 16 of the 
re-treatment 
period, data will 
be used 
regardless
Percentage of 
subjects achieving 
sPGA 0/1 (US 
only: and ≥2 grade 
improvement from 
baseline) at 
Week 16 of the re-
treatment period in 
the Risankizumab 
group
*
Ustekinumab is only applicable for Part 2
 


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For analysis of the ranked secondary endpoints, exact CIs will be provided based on the 
Clopper-Pearson method for proportions (Part 1, 3 and 4) and by the Miettinen-Nurminen 
method for differences in proportions2 (Part 2).
9.4.3
Sensitivity and Supplementary Analyses for Key Secondary
Efficacy Endpoint(s)
For dealing with missing data, AO will be used as sensitivity analysis for secondary 
endpoints.
9.4.4
Supportive Secondary Efficacy Endpoints and Analyses
The non-ranked secondary efficacy endpoints are specified in Section 3.2.
Analyses of non-ranked secondary efficacy endpoints will be conducted by providing 
descriptive statistics and 95% CI as described above.
9.5
Additional Efficacy Analyses
The other efficacy endpoints are specified in Section 3.3.
Analyses of other efficacy endpoints will be conducted by providing descriptive statistics 
and 95% CI as described above.
9.6
Efficacy Subgroup Analyses
Due to the small sample sizes and the uncontrolled design of Part 1, Part 3, and Part 4, no 
efficacy subgroup analyses will be performed.
For Part 2, the co-primary endpoints will be analyzed for the following subgroups, using 
NRI for imputation of missing data:
●
age group (12 to < 15, 15 to < 18 years)
●
sex (male, female),
●
race (white, non-white)
●
weight group (< 40 kg, ≥ 40 kg),
 


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●
region (Europe, North America, rest of world),
●
baseline PASI (< 20, ≥ 20)
●
baseline sPGA (≤ 3, 4)
●
baseline BSA (< 20, ≥ 20)
●
prior biologic Psoriasis therapy (yes, no)
●
prior systemic Psoriasis therapy (yes, no)
●
anti-drug antibodies (ADA) (positive, negative)
●
neutralizing antibodies (nAb) (positive, negative)
Analyses within subgroups will be conducted providing descriptive statistics and 95% CI 
as described above.
10.0
Safety Analyses
10.1
General Considerations
Safety data will be summarized for the Safety Analysis Population.  Safety summaries 
will be presented overall and by treatment group (Part 2).  For the safety analysis in 
Part 2, subjects are assigned to a treatment group based on the treatment actually received, 
regardless of the treatment randomized.  Safety analyses will include adverse events, 
laboratory, and vital sign measurements.  For Part 2, safety analyses will be presented by 
study period as well as overall, unless otherwise specified.
For Part 2 Period A, a subject's actual treatment will be determined by the first dose of 
study drug.  For subjects re-randomized in Part 2 Period B, only subjects who received no 
drug are included in the withdrawal arm, subjects who received at least one dose of study 
drug are included in the treatment continuation arm.
Missing safety data will not be imputed.
 


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10.2
Adverse Events
Adverse events (AEs) will be summarized and presented using primary MedDRA System 
Organ Classes (SOCs) and preferred terms (PTs) according to the version of the MedDRA 
coding dictionary used for the study at the time of database lock.  The actual version of 
the MedDRA coding dictionary used will be noted in the AE tables and in the clinical 
study report.  Specific adverse events will be counted once for each subject for calculating 
percentages, unless stated otherwise.  In addition, if the same adverse event occurs 
multiple times within a subject, the highest severity and level of relationship to 
investigational product will be reported.
10.2.1
Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any event with an onset that 
is after the first dose of study drug and with an onset date within 20 weeks (140 days) 
after the last dose of study drug.  Events where the onset date is the same as the study 
drug start date and no start times are available are assumed to be treatment-emergent.  For 
subjects re-randomized to treatment withdrawal in Part 2 Period B, AEs are only 
considered treatment emergent until last dose date in Period A + 140 days and then from 
the first re-treatment dose after the treatment withdrawal onwards, if applicable.
For the analysis of TEAEs as exposure-adjusted AEs per 100 patient-years of 
risankizumab exposure, all TEAS prior to the first risankizumab dose will be excluded 
(i.e., the TEAEs observed in the ustekinumab group in Part 2 Period A).
Pre-treatment AEs will be summarized separately in a listing.
10.2.2
Adverse Event Overview
An overview of TEAEs will be presented consisting of the number and percentage of 
subjects experiencing at least one event for each of the following AE categories:
●
Any treatment-emergent AE
●
Any treatment-emergent AE related to study drug according to the investigator
 


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●
Any severe treatment-emergent AE
●
Any serious treatment-emergent AE
●
Any treatment-emergent AE leading to discontinuation of study drug
●
Any serious infection
●
Opportunistic infection excluding tuberculosis and herpes zoster
●
Active tuberculosis
●
Herpes Zoster
●
Any malignant tumor
●
Any malignant tumor excluding NMSC
●
Any NMSC
●
Any hepatic event
●
Any serious hypersensitivity
●
Any injection site reaction
●
Any adjudicated Anaphylactic Reaction
●
Any Suicidal Ideation Behavior (SIB)
●
Any treatment-emergent AE leading to death
●
All deaths
●
Deaths occurring ≤ 140 days after last dose of study drug
●
Deaths occurring > 140 days after last dose of study drug
An overview of TEAEs will also be presented as exposure-adjusted AEs per 100 patient-
years of risankizumab exposure, where AEs per 100 patient-years of exposure are defined 
as the number of AEs divided by the total exposure in 100 patient-years.  This analysis 
will not be broken down by period in Part 2.
Note that one event per preferred term per day per subject will be counted in the 
calculation of the number of AEs (i.e., a preferred term will not be counted twice on the 
same day for the same subject).  See the calculation method below.
Years
Patient 
Total
TEAEs
of
Number 
100 
 


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where total patient years is defined as the sum of the risankizumab exposure (defined as 
date of last risankizumab dose – date of first risankizumab dose + 140 days (5 half-lives)) 
of all subjects normalized by 365.25, and rounded to one decimal place.  For subjects 
re-randomized to treatment withdrawal in Period B, risankizumab exposure will be 
counted until last risankizumab dose date in Period A + 140 days and then restarted at the 
first risankizumab re-treatment dose after the treatment withdrawal, if applicable.  For 
subjects initially randomized to ustekinumab, only TEAEs from the date of 
first risankizumab dose onwards will be included for this analysis which is exposure 
adjusted for risankizumab exposure.
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
Treatment-emergent adverse events will be summarized by SOC and PT; by maximum 
relationship to study drug as assessed by the investigator (e.g., reasonable possibility or no 
reasonable possibility) and SOC and PT; by maximum severity and SOC and PT; and by 
subject number and SOC and PT.  Specific adverse events will be counted once for each 
subject for calculating percentages, unless stated otherwise.  In addition, if the same 
adverse event occurs multiple times within a subject, the highest severity and level of 
relationship to investigational product will be reported.
In addition, treatment-emergent adverse events will be summarized by PT and sorted by 
decreasing frequency.
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Risankizumab Exposure
In addition to the exposure-adjusted Overview of TEAS described in Section 10.2.2, 
exposure-adjusted AEs per 100 patient-years of risankizumab exposure will also be 
provided by SOC and PT, where AEs per 100 patient-years of exposure are defined as the 
number of TEAEs divided by the total risankizumab exposure in 100 patient-years.
 


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Note that one event per preferred term per day per subject will be counted in the 
calculation of the number of AEs (i.e., a preferred term will not be counted twice on the 
same day for the same subject).  See the calculation method below.
where total patient years is defined as the sum of the risankizumab exposure (defined as 
date of last risankizumab dose – date of first risankizumab dose + 140 days (5 half-lives)) 
of all subjects normalized by 365.25, and rounded to one decimal place.  For subjects re-
randomized to treatment withdrawal in Period B, risankizumab exposure will be counted 
until last risankizumab dose date in Period A + 140 days and then restarted at the 
first risankizumab re-treatment dose after the treatment withdrawal, if applicable.
This analysis will not be broken down by period in Part 2.
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
SAEs (including deaths) and AEs leading to study drug discontinuation will be 
summarized by SOC and PT and in listing format.  Exposure-adjusted SAEs per 
100 patient-years of risankizumab exposure will also be provided by SOC and PT.
10.2.6
Areas of Safety Interest
Detailed information about the search criteria for areas of safety interest (ASIs) are 
provided in Appendix B.
The final list will be based on the most updated final version of risankizumab Product 
Safety Statistical Analysis Plan.
Tabular listings of selected area of safety interest will be provided.
Years
Patient 
Total
TEAEs
of
Number 
100 
 


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10.2.7
Combined Analyses for Adolescents/Children
In addition to the analyses by study part, the following tables of exposure-adjusted AEs 
per 100 patient-years of risankizumab exposure will be created that combine subjects 
enrolled into Part 1 and Part 2 (adolescents) and subjects enrolled into Part 3 and Part 4 
(children), respectively:
●
Overview of TEAEs,
●
TEAEs summarized by SOC and PT,
●
TEAEs summarized by SOC and PT by decreasing frequency.
The two Japanese adolescents aged 12 to < 18 years enrolled into Part 4 are not included 
in the Safety Analysis Population (see Section 4.0) and listed separately throughout. They 
are therefore not included in the above.
10.3
Analysis of Laboratory Data
Data collected from central and local laboratories, including additional laboratory testing 
due to an SAE, will be used in all analyses, except for Baseline where SAE-related 
laboratory assessments on or before the first dose of study drug will be excluded.  The
clinical laboratory tests defined in the protocol operations manual (e.g., hematology and 
clinical chemistry) will be summarized.
Mean change from baseline to each applicable post-baseline visit will be summarized for 
selected laboratory variables, with the number of observations, baseline mean, and visit 
mean.  The change from baseline mean, standard error, and 95% confidence interval will 
be presented for the mean change from baseline within each treatment group and 
difference between treatment groups (differences only applicable for Part 2 Period A).
Changes in laboratory parameters will be tabulated using shift tables categorized as low, 
normal, or high based on the normal ranges of the laboratory used for each sample.  A 
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maximum value (based on normal range), will be created.  A similar shift table will be 
provided to summarize shifts from baseline to the final post-baseline value.
Laboratory abnormalities meeting CTC v4.03 criteria grade 3 and 4 will be summarized.
The following analyses will be done combining subjects enrolled into Part 1 and Part 2 
(adolescents) and subjects enrolled into Part 3 and Part 4 (children), respectively:
The two Japanese adolescents aged 12 to < 18 years enrolled into Part 4 are not included 
in the Safety Analysis Population (see Section 4.0) and listed separately throughout. They 
are therefore not included in the above.
Laboratory abnormalities will be evaluated based on Potentially Clinically Significant 
(PCS) criteria (Appendix C).  For each laboratory PCS criterion, the number and 
percentage of subjects who have a laboratory value meeting the criteria will be 
summarized.  Listings will be provided to summarize subject-level laboratory data for 
subjects meeting PCS criteria.
In addition, the number and percentage of subjects meeting criteria for potential 
hepatotoxicity will be provided.
●
ALT > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN
●
AST > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN
●
TBL > 1.5 × ULN, > 2 × ULN
●
ALT and/or AST > 3 × ULN and TBL > 1.5 × ULN
●
ALT and/or AST > 3 × ULN and TBL > 2 × ULN
●
ALT > 3 × ULN and TBL > 1.5 × ULN
●
ALT > 3 × ULN and TBL > 2 × ULN
●
Alkaline phosphatase > 1.5 × ULN
For criteria involving multiple parameters, the values do not need to be concurrent to meet 
the defined criteria.
 


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A listing of potentially clinically important liver function laboratory values will include 
all subjects who met any of the following four criteria:
●
ALT > 3 × ULN, or
●
AST > 3 × ULN, or
●
ALP > 1.5 × ULN, or 
●
Total bilirubin > 1.5 × ULN.
A listing of potential biochemical Hy's Law cases, defined as those who meet all of the 
following conditions at any post-baseline visit, not necessarily concurrent, will be 
provided.
●
ALT of > 3 × ULN or AST of > 3 × ULN
●
Total bilirubin > 2 × ULN
10.4
Analysis of Vital Signs
Vital sign measurements of systolic and diastolic blood pressure as well as height will be 
summarized.
Mean change from baseline to each applicable post-baseline visit will be summarized for 
the above mentioned vital sign variables, with the number of observations, baseline mean, 
and visit mean.  The change from baseline mean, standard error, and 95% confidence 
interval will be presented for the mean change from baseline within each treatment group 
and difference between treatment groups (Period A, Part 2).
The following analyses will be done combining subjects enrolled into Part 1 and Part 2 
(adolescents) and subjects enrolled into Part 3 and Part 4 (children), respectively:
The two Japanese adolescents aged 12 to < 18 years enrolled into Part 4 are not included 
in the Safety Analysis Population (see Section 4.0) and listed separately throughout. They 
are therefore not included in the above.
 


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Vital sign variables will be evaluated based on potentially clinically significant (PCS) 
criteria (Appendix D).  For each vital sign PCS criterion, the number and percentage of 
subjects who have a vital sign value meeting the criteria will be summarized.  Listings 
will be provided to summarize subject-level vital sign data for subjects meeting PCS 
criteria.
10.5
Safety Subgroup Analyses
Counts and percentages of hypersensitivity reactions and injection site reactions will be 
presented for the following subgroups:
●
Anti-drug antibodies (ADA) (positive, negative)
●
Neutralizing antibodies (nAb) (positive, negative)
10.6
Other Safety Analyses
Not applicable.
11.0
Other Analyses
Not applicable.
12.0
Interim Analyses
No statistical test will be performed, therefore no formal interim analysis that would 
require type 1 error control will be done.  Analyses will be performed at the following 
timepoints:
Part 1 data up to Week 16 will be cleaned and analyzed after all subjects have reached 
Week 16 or have prematurely discontinued the study.  Week 16 data will inform the 
dose(s) and the initiation for Part 2 and Part 3.  A final analysis of Part 1 and Part 2 will 
be performed when all subjects have completed Part 2.
 


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Part 2 data, Part 1 data, and all available Part 3 or Part 4 data will be analyzed separately 
when all subjects have completed Part 2 and will be submitted for regulatory purposes.
Part 3 data up to Week 16 will be cleaned and analyzed after all subjects have reached 
Week 16 or have prematurely discontinued the study.  Week 16 data will inform the 
dose(s) and the initiation for Part 4.  A final analysis of Parts 3 and 4 will be performed 
together when all subjects have completed Part 4 or have prematurely discontinued from 
the study.
An external data monitoring committee (DMC) composed of persons independent of 
AbbVie and with relevant expertise in their field will review unblinded safety data from 
the ongoing study.  The primary responsibility of the DMC will be to protect the safety of 
the subjects participating in this study.
A separate DMC charter will be prepared outside of the protocol and will describe the 
roles and responsibilities of the DMC members, frequency of data reviews, relevant safety 
data to be assessed, and expectations for blinded communications.
12.1
Data Monitoring Committee
An external data monitoring committee (DMC) composed of persons independent of 
AbbVie and with relevant expertise in their field will review safety data from the ongoing 
study.  The primary responsibility of the DMC will be to protect the safety of the subjects 
participating in this study.
A separate DMC charter will be prepared outside of the protocol and will describe the 
roles and responsibilities of the IDMC members, frequency and triggers of data reviews, 
and relevant safety data to be assessed.  Unblinded ASI events will be presented to the 
IDMC for review on a periodic basis.
Since there are no efficacy analyses for early stopping, no alpha adjustment is needed.
 


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13.0
Overall Type-I Error Control
Not applicable for this study as no statistical testing will be performed.
14.0
Version History
Table 3.
SAP Version History Summary
Version
Date
Summary
1.0
12 August 2020
Original version
2.0
18 August 2021
Updated SAP to align with edits in protocol version 3.0; 
addition of Itch NRS endpoints; addition of estimands 
language; updated Itch endpoint; updated safety (ASIs and 
hepatotoxicity criteria) wording to align with most current 
version of PSSAP (v4.1)
3.0
01 May 2023
Updated SAP to align with edits in protocol version 4.0; 
added ≥ 2-grade improvement from baseline of sPGA (US 
only), update list of ASIs, summary for height added 
 


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4.0
16 October 2023
Section 6.0: 
added analyses of duration of risankizumab treatment that 
combine subjects enrolled into Part 1 and Part 2 
(adolescents) and subjects enrolled into Part 3 and Part 4 
(children)
rationale: to provide integrated exposure information for 
adolescents and children, respectively
Section 7.1: 
added analyses of demographics that combine subjects 
enrolled into Part 1 and Part 2 (adolescents) and subjects 
enrolled into Part 3 and Part 4 (children)
rationale: to provide integrated demographics information 
for adolescents and children, respectively
Section 10.2.2:
removed assessment of treatment-emergent COVID-19 
related events and COVID-19 related deaths from Adverse 
Event Overview
rationale:  to align with general company approach
Section 10.2.7: 
added analyses of exposure-adjusted AEs per 100 patient-
years of risankizumab exposure that combine subjects 
enrolled into Part 1 and Part 2 (adolescents) and subjects 
enrolled into Part 3 and Part 4 (children)
rationale: to provide integrated safety information for 
adolescents and children, respectively
Section 10.3: 
Replaced analyses of PCS hematology, chemistry, 
hepatoxicity by Part with analyses by age cohort 
(adolescents, children)
rationale: to provide integrated safety information for 
adolescents and children, respectively
Section 10.4: 
Replaced analyses of PCS for vital signs by Part with 
analyses by age cohort (adolescents, children)
rationale: to provide integrated safety information for 
adolescents and children, respectively
Section 10.5: 
Removed subgroup analyses by gender
rationale: small number of subjects
Appendix D
Updated criteria for potentially clinically significant vital 
sign values
rationale: to align with general company approach
 


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15.0
References
1.
European Medicines Agency.  P/0205/2016.  Opinion of the Paediatric Committee 
on the agreement of a Paediatric Investigation Plan and a deferral and a waiver.  
2016.
2.
Miettinen O, Nurminen M.  Comparative analysis of two rates.  Stat Med.  
1985;4(2):213-26.
 


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Appendix A.
Protocol Deviations
The number and percentage of subjects who reported at least one of the following 
protocol deviation categories will be provided.
●
Subject entered into the study even though s/he did not satisfy entry criteria.
●
Subject developed withdrawal criteria during the study and was not 
withdrawn.
●
Subject received wrong treatment or incorrect dose of study.
●
Subject took prohibited concomitant medication.
 


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Appendix B.
Definition of Area of Safety Interest
Area of safety interest (ASI) will be identified using the following search criteria:
Area of Safety Interest
Search Criteria
Include in AE 
Overview (Y/N)
Serious Infections
Serious AEs in the Infections and Infestations SOC 
Y
Tuberculosis
Active TB CMQ (code 10000002)
Y
Opportunistic Infections
Opportunistic Infection Excluding Tuberculosis and 
Herpes Zoster CMQ (code 10000105)
Y
Herpes Zoster
Herpes Zoster CMQ (code 10000079)
Y
Malignant Tumours
Narrow
Malignant tumours (SMQ 20000194)
Y
Non-melanoma Skin 
Cancer (NMSC)
Broad
Skin malignant tumours (SMQ 20000204) 
excluding terms identified by the Melanoma 
CMQ (code 10000100)
Y
Malignant Tumours 
excluding NMSC
'Malignant Tumours excluding NMSC' is identified by 
the 'Malignant Tumours' search excluding terms 
identified by the 'Non-melanoma skin cancer (NMSC)' 
search.
Y
Hypersensitivity 
Narrow
Hypersensitivity (SMQ 20000214)
Y – serious events 
only
Adjudicated 
Anaphylactic Reaction*
Adjudicated terms will be identified using SDTM data 
(e.g., CE and PR domains).
Y
Hepatic Events 
Broad
Hepatic failure, fibrosis and cirrhosis and 
other liver damage-related conditions 
(SMQ 20000013)
Y
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)
Injection Site Reaction
Injection site reaction CMQ (code 10000091)
Y
Suicidal Ideation and 
Behavior (SIB) 
Narrow
Suicide/self-injury (SMQ 20000037)
Y
*
Events will be identified for adjudication by Anaphylactic Reaction SMQ Broad search as specified in the RISA 
AAC Charter.
 


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Appendix C.
Potentially Clinically Significant Criteria for Safety Endpoints
The criteria for Potentially Clinically Significant (PCS) laboratory findings are described 
in Table C-1 and Table C-2.
Table C-1.
Potentially Clinically Significant Chemistry Values
Chemistry Variables
Units
Definition of Potentially Clinically Significant 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
(> 3.0 × BL)
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
Note:
A post-baseline value must be more extreme than the baseline value to be considered a potentially clinically 
significant finding.
 


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Table C-2.
Potentially Clinically Significant Hematology Values
Hematology Variables
Units
Definition of Potentially Clinically Significant 
Current (Version 4) CTCAE Grade 3 or Greater
Very Low
Hemoglobin
g/L
< 80.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
Note:
A post-baseline value must be more extreme than the baseline value to be considered a potentially clinically 
significant finding.
 


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Appendix D.
Criteria for Potentially Clinically Significant Vital Sign Values
Vital signs values will be categorized as follows:
Systolic Blood Pressure (mmHg)
Age Group
Category
Criteria for Potentially Clinically Significant Vital Signs
12 to 
< 18 years
Low
High
Value ≤ 90 mmHg and decrease ≥20 mmHg from baseline
Value ≥ 160 mmHg and increase ≥20 mmHg from baseline
10 and 11 
years
Low
High
Value ≤ 80 mmHg and decrease ≥20 mmHg from baseline
Value ≥ 140 mmHg and increase ≥20 mmHg from baseline
Less than 10 
years
Low
High
Value ≤ 80 mmHg and decrease ≥20 mmHg from baseline
Value ≥ 130 mmHg and increase ≥20 mmHg from baseline
Diastolic Blood Pressure (mmHg)
Age Group
Category
Criteria for Potentially Clinically Significant Vital Signs
12 to 
< 18 years
Low
High
Value ≤ 50 mmHg and decrease ≥10 mmHg from baseline
Value ≥ 100 mmHg and increase ≥10 mmHg from baseline
10 and 
11 years
Low
High
Value ≤ 50 mmHg and decrease ≥10 mmHg from baseline
Value ≥ 90 mmHg and increase ≥10 mmHg from baseline
Less than 
10 years
Low
High
Value ≤ 50mmHg and decrease ≥10 mmHg from baseline
Value ≥ 85 mmHg and increase ≥10 mmHg from baseline
For categorization purposes in case of age specific ranges, age at enrollment will be used.