A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Risankizumab in Adult and Adolescent Subjects With Moderate to Severe Atopic Dermatitis
Phase: PHASE2
Conditions: Dermatitis
Sponsor: AbbVie

NCT03706040

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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
8
2.1
BACKGROUND AND RATIONALE
8
2.2
BENEFITS AND RISKS TO SUBJECTS
9
3
STUDY OBJECTIVES AND ENDPOINTS
11
3.1
OBJECTIVES
11
3.2
PRIMARY ENDPOINT
11
3.3
SECONDARY ENDPOINTS
11
3.4
SAFETY ENDPOINTS
13
3.5
PHARMACOKINETIC AND IMMUNOGENICITY ENDPOINTS
13
3.6
BIOMARKER RESEARCH
13
4
INVESTIGATIONAL PLAN
14
4.1
OVERALL STUDY DESIGN AND PLAN
14
4.2
DISCUSSION OF STUDY DESIGN
15
5
STUDY ACTIVITIES
16
5.1
ELIGIBILITY CRITERIA
16
5.2
CONTRACEPTION RECOMMENDATIONS
19
5.3
PROHIBITED MEDICATIONS AND THERAPY
20
5.4
PRIOR AND CONCOMITANT THERAPY
21
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
22
5.6
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
24
5.7
STUDY DRUG
24
5.8
RANDOMIZATION/DRUG ASSIGNMENT
25
5.9
PROTOCOL DEVIATIONS
26
6
SAFETY CONSIDERATIONS
26
6.1
COMPLAINTS AND ADVERSE EVENTS
26
6.2
INDEPENDENT DATA MONITORING COMMITTEE
30
6.3
CARDIOVASCULAR ADJUDICATION COMMITTEE
30
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6.4
ANAPHYLAXIS ADJUDICATION COMMITTEE
31
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
31
7.1
STATISTICAL AND ANALYTICAL PLANS
31
7.2
DEFINITION FOR ANALYSIS POPULATIONS
31
7.3
STATISTICAL ANALYSES FOR EFFICACY
32
7.4
STATISTICAL ANALYSES FOR SAFETY
32
7.5
ANALYSES OF PHARMACOKINETICS AND IMMUNOGENICITY
33
8
ETHICS
33
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD
33
8.2
ETHICAL CONDUCT OF THE STUDY
33
8.3
SUBJECT CONFIDENTIALITY
33
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
34
10
DATA QUALITY ASSURANCE
34
11
COMPLETION OF THE STUDY
34
12
REFERENCES
35
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCT
24
TABLE 2.
AREAS OF SAFETY INTEREST
29
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMATIC
15
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
38
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
42
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APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
43
APPENDIX D.
ACTIVITY SCHEDULE
44
APPENDIX E.
PROTOCOL AMENDMENT SUMMARY OF CHANGES
49
APPENDIX F.
OPERATIONS MANUAL
50
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted
This study will provide data comparing risankizumab versus placebo for the treatment of adult and 
adolescent subjects with moderate to severe atopic dermatitis (AD).
AD, also known as atopic eczema, is one of the most common chronic skin diseases, affecting 1 - 3% of 
adults worldwide.1  Data from the National Health Interview Survey, a United States (US) population-
based household survey, indicate that the prevalence of childhood AD steadily increased from 
approximately 8% in 1997 to more than 12% in 2010 and 2011.2  AD is often characterized by pruritus, 
erythema, edema, xerosis, erosions/excoriations, oozing, crusting, and lichenification.  In addition, sleep 
disturbance commonly occurs with AD, due in large part to the significant itching associated with the 
disease.3,4  AD is also associated with multiple other comorbid conditions, including a higher prevalence 
of other atopic diseases such as rhinitis, food allergies, and asthma, with the severity of AD directly 
related to the severity of the comorbidities.5
The pathophysiology of AD is influenced by a complex interplay between inflammation, environmental 
factors, genetics, and skin barrier dysfunction.  AD is driven by multiple immune pathways that create 
different disease features.6-11  Two T-cell subsets, Th2 and Th22, are commonly present and activated 
across major subtypes of AD.  Specific subtypes of AD, including Asian-origin, pediatric, and intrinsic AD, 
have a prominent interleukin (IL)-17 component, as well as tissue patterning that overlaps with 
distinctive psoriasis histopathology.12  There is also evidence that the Th17/IL-23 axis is up-regulated in 
patients with AD and that it might have a role in AD development.13,14  Further, it has been shown that 
IL-23 is released in human skin after scratching, which polarizes human skin dendritic cells to drive an 
IL-22 response of epidermal thickening, supporting the utility of IL-23 and IL-22 blockade in AD.15  Hence, 
AD might best be considered a multi-axis immune disease with involvement of the Th2, Th22, and 
potentially Th17 pathways.
The goal of AD treatment is to reduce skin inflammation, and the treatment options depend on the 
extent and severity of disease.  Topical agents, such as corticosteroids, calcineurin inhibitors, and 
moisturizers, are commonly used alone for mild to moderate cases.  When topical therapies are 
insufficient for treating the signs and symptoms of AD, systemic therapy or phototherapy are generally 
added.16  Oral immunosuppressants17 like methotrexate or cyclosporin and glucocorticoids can be 
effective, but are frequently associated with severe toxicity and side effects, thus limiting their use to 
short courses and/or intermittent therapy.
Several biological agents, such as anti-tumor necrosis factor (TNF)-α (e.g., infliximab, etanercept), anti-
immunoglobin (Ig)E (omalizumab), anti-IL-5 (mepolizumab), and anti-CD11a (efalizumab), have not 
shown efficacy in AD clinical studies.  In a small Phase 2 study, ustekinumab, an IL-12/IL-23 blocking 
agent, showed a numerical improvement in clinical AD endpoints when compared to the placebo arm.  
Nonetheless, the study failed to achieve its primary endpoint as the difference was not statistically 
significant.  The study used the same dosing regimen approved by the US Food and Drug Administration 
(FDA) for psoriasis.18  On the other hand, dupilumab, an antibody directed to block both IL-4 and IL-13 
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signal transduction and therefore inhibiting the Th2 inflammatory pathway, was approved by the US 
FDA in March 2017 and the European Commission in September 2017.  In two Phase 3 studies, 
dupilumab significantly improved the signs and symptoms of AD compared with placebo,19 with injection 
site reactions, conjunctivitis, blepharitis, and oral herpes reported as the most common adverse 
reactions in the studies.20  Although dupilumab addresses the needs of some patients with moderate to 
severe AD, a large unmet need for short- and long-term efficacious treatments still exists in this 
population.
Despite the availability of various topical AD therapies, many patients still do not respond adequately to 
these treatments, and there are limited systemic treatment options available.  Since the IL-23/Th17 axis 
is overexpressed in AD, this target may have therapeutic potential.  Among AD patients, IL-23/Th17 
expression has been shown to be higher in various AD subpopulations (i.e., Asian population, pediatric 
population, intrinsic/non-allergic subtype [normal levels of IgE]).8
Risankizumab is a fully humanized monoclonal antibody (mAb) of the IgG1 subclass directed towards 
IL-23 p19.  The antibody has been engineered to reduce Fcγ receptor and complement binding and 
potential charge heterogeneity.  Risankizumab binds with high affinity to human IL-23.  Risankizumab is 
currently being developed for the treatment of psoriasis (Phase 3 studies concluded) and Crohn's 
disease (currently in Phase 3 studies), as well as the treatment of ulcerative colitis, and psoriatic arthritis 
(in Phase 2 studies), and may address the current needs for subjects with AD.
The current study compares the safety and efficacy of risankizumab versus placebo for the treatment of 
moderate to severe AD in adult and adolescent subjects.  For a more detailed description of the 
risankizumab drug profile, refer to the latest version of the Investigator's Brochure (IB).21
Clinical Hypothesis
Risankizumab will provide superior efficacy compared to placebo and will be well tolerated in subjects 
with moderate to severe AD.
2.2 Benefits and Risks to Subjects
This proof-of-concept (POC) study is required to learn more about the potential treatment effect of 
risankizumab in AD.  While IL-23/Th17 has been identified as a potential target in AD, the pathway is 
predominantly overexpressed in subsets of AD patients and has not been definitively confirmed as a 
viable target in clinical studies.  With minimal clinical data on IL-23 in AD, a robust POC study is needed 
to learn about the safety and efficacy of risankizumab in the general AD patient population and at 
different doses.
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 infection will not be included in the study.
Subjects with a positive QuantiFERON®-TB (or interferon gamma release assay [IGRA] 
equivalent)/tuberculosis (TB) skin test result for TB must fulfill entry criteria as specified in Section 5.1 of 
this protocol.  IL-23 inhibition is not known to increase the risk of TB infection or impair the response to 
TB infection in animal models.22,23  No cases of active TB have been reported across all risankizumab 
studies to date.  Across the Phase 3 psoriasis clinical studies, of the 72 subjects with latent TB who were 
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concurrently treated with risankizumab and appropriate TB prophylaxis during the study, none 
developed active TB during a mean follow-up period of 61 weeks.  Of the 31 subjects from 
Study M15-992 (IMMhance) with latent TB who did not receive prophylaxis during the study, none 
developed active TB during the mean follow-up of 55 weeks on risankizumab.  Thus, low-risk subjects 
with positive QuantiFERON-TB testing (or IGRA equivalent)/TB skin test do not need to be treated with 
anti-TB therapy prior to receiving risankizumab, but should be carefully monitored for any sign of TB 
reactivation.  
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.24-26  Moreover, preclinical data have demonstrated a 
beneficial effect of IL-23 p19 inhibition in animal models, both for pre-existing and tumor-induction 
models.  However, 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.
Increases in major adverse cardiovascular events (MACE), including myocardial infarction, 
cerebrovascular accident, and cardiovascular death, reported initially with anti-IL-12/23 agents, such as 
ustekinumab, have not been observed in longer term studies. While the likelihood of increased MACE is 
small, all suspected cardiovascular events (serious or nonserious) observed in this study will be 
adjudicated by an independent committee.  An independent Cardiovascular Adjudication Committee 
(CAC) will adjudicate all observed cardio- and cerebro-vascular events and will remain blinded to 
treatment allocation (Section 6.3).
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 6.4).
In conclusion, the benefit-risk profile of risankizumab is considered appropriate for this stage of clinical 
development.27  Based on data from the integrated safety analyses, risankizumab is safe and well-
tolerated and demonstrates a favorable benefit-risk profile.
For further details, please see findings from completed studies, including safety data, in the 
risankizumab IB.21
In view of the Coronavirus Disease – 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.
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3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objectives
The primary objective of this study is to assess the safety and efficacy of risankizumab for the treatment 
of moderate to severe AD in adult and adolescent subjects.
3.2 Primary Endpoint
The primary endpoint is the proportion of subjects achieving at least a 75% reduction from Baseline in 
Eczema Area and Severity Index (EASI 75) at Week 16.
3.3 Secondary Endpoints
Key Secondary Endpoints
The key secondary endpoints for this study are:
1.
The proportion of subjects achieving validated Investigator Global Assessment Scale for Atopic
Dermatitis (vIGA-AD) of "0" or "1" (on a 5-point scale) with a reduction from Baseline of 
≥2 points at Week 16.
2.
The proportion of subjects achieving a reduction of ≥ 4 points in worst pruritus numerical rating 
scale (NRS) from Baseline to Week 16.
Other Secondary Endpoints
Other secondary endpoints for each of the specified time points include:
!
Percent change in EASI from Baseline to Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving EASI 75 at Week 28 and Week 52.
!
Proportion of subjects achieving EASI 50 at Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving EASI 90 at Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving vIGA-AD of "0" or "1" with a reduction from Baseline of 
≥2 points to Week 28 and Week 52.
!
Change in body surface area (BSA) from Baseline to Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving 50% improvement in SCORing Atopic Dermatitis (SCORAD 50) at 
Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving SCORAD 75 at Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving SCORAD 90 at Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving Dermatology Life Quality index (DLQI) of "0" or "1" at Week 16, 
Week 28, and Week 52.
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!
Proportion of subjects achieving Children's Dermatology Life Quality index (CDLQI) of "0" or "1"
at Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving a DLQI improvement of ≥ 4 points at Week 16, Week 28, and 
Week 52 among subjects with a DLQI ≥ 4 at Baseline.
!
Change in DLQI from Baseline to Week 16, Week 28, and Week 52.
!
Change in CDLQI from Baseline to Week 16, Week 28, and Week 52.
!
Change in worst pruritus NRS from Baseline to Week 16, Week 28, and Week 52.
!
Proportion of subjects achieving a reduction of ≥ 4 points in worst pruritus NRS from Baseline to 
Week 28 and Week 52.
Additional Endpoints
All variables listed as primary or secondary endpoints will be analyzed at all visits in addition to those 
listed above.  In addition, the following additional endpoints will be evaluated at applicable visits:
!
Proportion of subjects achieving EASI 100.
!
Proportion of subjects achieving vIGA-AD of "0" with a reduction from Baseline of ≥2 points.
!
Percent change in SCORAD from Baseline.
!
Change from Baseline in Patient Oriented Eczema Measure (POEM).
!
Proportion of subjects achieving an improvement (reduction) in POEM of ≥ 4 from Baseline 
among subjects with a POEM ≥ 4 at Baseline.
!
Change from Baseline in Patient Global Impression of Severity (PGIS).
!
Proportion of subjects who report symptoms to be "Minimal" or "Absent" for PGIS.
!
Proportion of subjects who have "Very much improved" or "Much improved" for Patient Global 
Impression of Change (PGIC).
!
Change from Baseline in Atopic Dermatitis Symptom Scale (ADerm-SS) total score.
!
Change from Baseline in ADerm-SS skin pain score.
!
Change from Baseline in Atopic Dermatitis Impact Scale (ADerm-IS) total score.
!
Change from Baseline in ADerm-IS sleep domain score.
!
Proportion of subjects achieving an improvement (reduction) in ADerm-SS total score ≥ minimal 
clinically important difference (MCID) from Baseline for subjects with ADerm-SS total score 
≥MCID at Baseline.
!
Proportion of subjects achieving an improvement (reduction) in ADerm-SS skin pain score 
≥MCID from Baseline for subjects with ADerm-SS skin pain score ≥ MCID at Baseline.
!
Proportion of subjects achieving an improvement (reduction) in ADerm-IS total score ≥ MCID 
from Baseline for subjects with ADerm-IS total score ≥ MCID at Baseline.
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!
Proportion of subjects achieving an improvement (reduction) in ADerm-IS sleep disturbance 
score ≥ MCID from Baseline for subjects with ADerm-IS sleep disturbance score ≥ MCID at 
Baseline.
!
Change from Baseline in EuroQoL-5D-5L (EQ-5D-5L).
3.4 Safety Endpoints
Safety evaluations include adverse event (AE) monitoring, vital sign measurements, electrocardiogram 
(ECG) variables, and clinical laboratory testing (hematology, chemistry, and urinalysis) as measures of 
safety and tolerability for the entire study duration.
3.5 Pharmacokinetic and Immunogenicity Endpoints
Serum risankizumab concentrations, anti-drug antibodies (ADA), and neutralizing antibodies (nAb) will 
be determined from blood collected by venipuncture at the visits indicated in the Activity Schedule 
(Appendix D).
3.6 Biomarker Research
Optional blood, skin biopsy, and skin tape samples for biomarker research will be collected as described 
in the Activity Schedule (Appendix D).  Prognostic and predictive biomarker signatures may be 
evaluated.  Biomarker assessments may include, but are not limited to, nucleic acids, proteins, 
metabolites, or lipids.  The objective of biomarker research is to analyze samples that will help to 
understand AD, related conditions, and the subject's response to risankizumab.  Genes of interest may 
include (but are not limited to) those associated with pharmacokinetics (PK), genes within the target 
pathway (IL-23, Janus kinase [JAK]/signal transduction activators of transcription [STAT], tyrosine kinase 
[TYK]2), or other genes believed to be related to AD and other inflammatory diseases (caspase 
recruitment domain [CARD]-containing),11 filaggrin, human leukocyte antigen [HLA], IL).  Blood and skin 
samples may be used to investigate genetic, epigenetic, transcriptomic, proteomic, metabolomic, 
metagenomic, phenotypic, functional, and targeted investigations related to AD, related conditions, and 
response to risankizumab.
AbbVie (or people or companies working with AbbVie) will store the biomarker exploratory 
research/validation studies samples in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained while research on risankizumab (or drugs of this class) or 
this disease and related conditions continues, but for no longer than 20 years after study completion.
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4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 2, randomized, double-blind, placebo-controlled multicenter study to evaluate the safety 
and efficacy of risankizumab for the treatment of moderate to severe AD in adult and adolescent 
subjects with a confirmed diagnosis and onset of symptoms at least 2 years before the Baseline Visit.
The duration of the study will be up to 65 weeks and will include a screening period of up to 35 days, a 
16-week double-blind treatment period (Period A), and a 36-week double-blind treatment period 
(Period B).  In addition, subjects will have a telephone follow-up call 20 weeks after their last dose of 
risankizumab to determine the status of any ongoing AEs/serious adverse events (SAEs) or the 
occurrence of any new AEs/SAEs.
This study plans to enroll approximately 155 subjects from up to 75 sites in the US, Canada, Japan, and 
Australia, although the number, allocation, and location of sites may vary depending on operational 
aspects of the study.  Approximately 20% of subjects will come from sites in Japan.  Subjects who meet 
eligibility criteria (see Section 5.1) will be randomized at Baseline in a 2:2:1 ratio to one of 3 treatment 
groups:  (1) risankizumab 150 mg (62 subjects), (2) risankizumab 300 mg (62 subjects), or (3) matching 
placebo (31 subjects).  In Period A, subjects will receive their randomized treatment as subcutaneous 
(SC) injections at Week 0 and Week 4.
Once a sufficient number of subjects to fulfill the enrollment target have entered the screening process, 
no further subjects will be screened.  Once 155 subjects have been randomized, subjects who have 
started screening but have not yet been randomized will be allowed to enroll in the study if eligible.  
The primary analysis will be performed when all subjects complete Week 16.  The Week 16 evaluation is 
the final analysis for the primary endpoint of EASI 75 and key secondary endpoints of vIGA-AD response 
and pruritus NRS reduction.  At the Week 16 analysis, the sponsor will be unblinded, although study 
sites and subjects will remain blinded for the duration of the study.
In Period B, subjects in the placebo group will be re-randomized at Week 16 in a 1:1 ratio to receive 
either risankizumab 150 mg or 300 mg for the remainder of the study.  Subjects originally randomized to 
the risankizumab 150 mg or 300 mg arms will stay on their previously-assigned treatment through the 
end of the study.  Subjects will receive their randomized treatment as SC injections at Week 16, 
Week 28, and Week 40.  During Period B, subjects with < EASI 50 response, as compared to Baseline, at 
the most recent prior and current scheduled visits will be allowed to begin approved concomitant rescue 
treatment after the assessments at the Week 24 visit and at any visit thereafter (see Section 5.4).
Subjects who prematurely discontinue study drug should complete a Premature Discontinuation (PD) 
Visit as soon as possible, preferably within 2 weeks of discontinuation.  Subjects who prematurely 
discontinue study drug should continue to be followed for safety and efficacy assessments at all 
regularly scheduled visits unless they have decided to discontinue study participation entirely 
(withdrawal of informed consent).  See Section 5.6 for information regarding early discontinuation.
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in the Operations Manual.
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Figure 1.
Study Schematic
EASI = Eczema Area and Severity Index; PBO = placebo; RZB = risankizumab; W = week
4.2 Discussion of Study Design
Choice of Control Group
A placebo control has been selected as the appropriate control group for this study to establish an 
unbiased efficacy and safety profile of risankizumab in subjects with AD.
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 AD.  All clinical 
and laboratory procedures in this study are standard and generally accepted.
Suitability of Subject Population
Adult and adolescent subjects who have moderate to severe AD (defined as an EASI ≥ 16, BSA ≥ 10%, 
and vIGA-AD score ≥ 3 at the Baseline Visit), with onset of symptoms at least 2 years prior to Baseline, 
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are eligible for this study.  The criteria relating to safety have been selected to allow subjects to be safely 
enrolled and treated with risankizumab based on the current knowledge of this drug.
Selection of Doses in the Study
Two dose levels of risankizumab have been selected for evaluation in this study.  The risankizumab 
150 mg SC dose has demonstrated efficacy in Phase 3 clinical trials for psoriasis and could be efficacious 
in subjects with AD.  The additional higher dose of risankizumab 300 mg SC was selected since AD is a 
disease with a high inflammatory burden.  The risankizumab 300 mg dose, along with the 150 mg dose, 
is expected to provide dose/exposure-response data to allow for evaluation of the efficacy plateau.  
Both doses are within the range of doses safely administered in previous risankizumab clinical studies.
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. Subjects or their legally authorized representative must voluntarily sign and date an informed 
consent prior to the initiation of any screening or study-related procedures.  Where locally 
permitted and approved, subjects ≥ 12 and < 18 years of age (hereafter referred to as 
"adolescent subjects") must sign an assent approved by an independent ethics committee 
(IEC)/institutional review board (IRB).  For adolescent subjects, the investigator or his/her 
representative will explain the nature of the study to both the subject and the subject's 
parent/legal guardian, and answer all their questions regarding this study.  Additionally, the 
informed consent statement will be reviewed and signed and dated by the subject's parent/legal 
guardian, the person who administered the informed consent, and any other signatories 
according to local requirements prior to any study-related screening procedures being 
performed on the subject.  If a subject becomes of legal age during the course of the study, that 
subject will need to voluntarily sign and date the current version of the informed consent at 
their next study visit.
Demographic and Laboratory Assessments
2. Adult male or female, at least 18 years old and functionally able to read and understand 
study questionnaires.  Where locally permissible and approved, male or female adolescent 
subjects (at least 12 years old) may participate.    
3. Body weight ≥ 40 kg at the Baseline Visit for subjects between ≥ 12 and < 18 years of age.
4. Laboratory values meeting the following criteria within the screening period prior to the 
first dose of study drug:
!
Serum aspartate transaminase (AST) < 2 × upper limit of normal (ULN);
!
Serum alanine transaminase (ALT) < 2 × ULN;
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!
Serum total bilirubin ≤ 2.0 mg/dL, except for subjects with isolated elevation of indirect 
bilirubin relating to Gilbert syndrome;
!
Total white blood cell (WBC) count > 3,000/μL;
!
Absolute neutrophil count (ANC) > 1,500/μL;
!
Platelet count > 100,000/μL;
!
Hemoglobin > 8.0 g/dL.
5. Willing and/or able to comply with procedures required in this protocol.
AD Disease Activity
6. Diagnosis of AD with onset of symptoms at least 2 years prior to Baseline and subject meets 
Hanifin and Rajka criteria.28
7. Inadequate response to treatment with topical corticosteroids (TCS) and/or topical 
calcineurin inhibitors (TCI), or subject for whom topical treatments are otherwise medically 
inadvisable (e.g., because of side effects or safety risks).  Subjects are potentially eligible after 
appropriate washout (10 days prior to Baseline visit).
8. Moderate to severe AD, defined by EASI ≥ 16, BSA ≥ 10%, and a vIGA-AD score ≥ 3 at the 
Baseline Visit.
9. Twice-daily use of an additive-free, bland emollient for at least 7 days prior to Baseline and 
throughout duration of the study is required.
10. Baseline weekly average of daily worst pruritus NRS ≥ 4.  (Note:  The baseline weekly 
average of daily worst pruritus NRS will be calculated from the 7 consecutive days immediately 
preceding the Baseline Visit.  A minimum of 4 daily scores out of the 7 days is needed.)
Subject History
11. No evidence of hepatitis B (HBV) or hepatitis C (HCV) infection, defined as:
!
HBV:  Hepatitis B surface antigen (HBs Ag) positive (+) test or detected sensitivity on the HBV 
DNA polymerase chain reaction (PCR) qualitative test for subjects who are hepatitis B core 
antibody (HBc Ab) positive (+) (and for hepatitis B surface antibody [HBs Ab] positive [+] 
subjects where mandated by local requirements).
!
HCV:  HCV RNA detectable in any subject with anti-HCV antibody (HCV Ab).
12. No evidence of human immunodeficiency virus (HIV), defined as confirmed positive anti-HIV 
antibody (HIV Ab) test.
13. No case of active TB.  Subjects with a positive QuantiFERON-TB gold test (or IGRA 
equivalent) or TB skin test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that the subject has no evidence of active TB.  If 
presence of latent TB is established, subjects are not required to be treated with prophylactic 
anti-TB therapy prior to or during the study, if the subject is considered low risk for reactivation 
per investigator judgment.
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14. No active systemic infection during the last 2 weeks prior to Baseline Visit (exception:  
common cold), as assessed by the investigator.
15. No documented active or suspected malignancy or history of any malignancy within the last 
5 years except for successfully treated non-melanoma skin cancer (NMSC) or localized 
carcinoma in situ of the cervix.
16. No history of organ transplantation.
17. No major surgery performed within 12 weeks prior to randomization or planned during the 
conduct of the study (e.g., hip replacement, aneurysm removal, stomach ligation).
18. No historical or concurrent clinically significant medical conditions or any other reason,
including any physical, psychological, or psychiatric condition, that the investigator determines 
would compromise the safety or 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 protocol; as well as being permanently wheelchair-bound or bedridden or 
having very poor functional status, preventing the ability to perform self-care.
19. No presence of skin comorbidities that could interfere with study assessment of AD.
20. No skin infections (bacterial, fungal, or viral) requiring intravenous (IV) systemic treatment 
within 4 weeks of the Baseline Visit.
21. No history of clinically significant (per investigator's judgment) drug or alcohol abuse within 
the last 6 months, including medicinal or recreational cannabis or cannabinoids.
22. No 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.
23. Subject is judged to be in good general health, as determined by the principal investigator 
based upon the results of a medical history, physical examination, laboratory profile, and a 
12-lead ECG performed during the Screening period.
Contraception
24. 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.
25. If female, subject must be of non-childbearing potential OR a female of childbearing 
potential practicing at least 1 protocol-specified method of birth control, that is effective from 
Study Day 0 through at least 140 days (20 weeks or as guided by the local risankizumab label (if 
approved), whichever is longer) after the last dose of study drug (local practices may require 
2 methods of birth control).
26. Female who is not pregnant, breastfeeding, or considering becoming pregnant during the 
study or for at least 140 days (20 weeks or as guided by the local risankizumab label (if 
approved), whichever is longer) after the last dose of study drug.
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Prior/Concomitant Medications
27. No prior exposure to any biologic immunomodulatory agent, including but not limited to 
anti-IL-23 (e.g., risankizumab, guselkumab), anti-IL-4R (e.g., dupilumab), anti-IL12/23 
(e.g., ustekinumab), anti-IL-17 (e.g., secukinumab), or anti-IgE (e.g., omalizumab).
28. No prior exposure to any systemic or topical JAK inhibitor (including but not limited to 
tofacitinib, baricitinib, upadacitinib, ruxolitinib, and filgotinib).
29. No exposure to systemic therapy that can also be used for the treatment of AD, including 
but not limited to corticosteroids, methotrexate (MTX), cyclosporine, azathioprine (AZA), 
phosphodiesterase type 4 (PDE4)-inhibitors, and mycophenolate mofetil, within 4 weeks prior to 
the Baseline Visit.
30. No use of TCS, TCI, prescription moisturizers, or moisturizers containing additives such as, 
but not limited to, ceramide, hyaluronic acid, urea, heparin, or filaggrin within 10 days prior to 
the Baseline Visit.
31. No use of traditional Chinese medicines within 4 weeks prior to the Baseline Visit and during 
the study.
32. No phototherapy treatment, tanning booth, or extended sun exposure that could affect 
disease severity or interfere with disease assessments within 4 weeks prior to the Baseline Visit 
and throughout the duration of the study.
33. Subject must not have received any live vaccine within 6 weeks prior to the first dose of 
study drug (Baseline), or expects need of live vaccination during study participation, including at 
least 140 days (20 weeks or as guided by the local risankizumab label (if approved), whichever is 
longer) after the last dose of study drug.
34. Subject must not have been treated with any other investigational drug within 4 weeks or 
5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or be currently 
enrolled in another clinical study.
5.2 Contraception Recommendations
Subjects must follow the following contraceptive guidelines as specified:
!
Females, Non-Childbearing Potential
Females do not need to use birth control during or following study drug treatment if considered 
of non-childbearing potential due to meeting any of the following criteria:
!
Postmenopausal, age > 55 years with no menses for 12 or more months without an 
alternative medical cause.
!
Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause AND a follicle-stimulating hormone (FSH) level > 40 international 
unit (IU)/L.
!
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).
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Females who have not experienced menarche (at least one menstrual period).
!
Females, of Childbearing Potential
Females of childbearing potential must avoid pregnancy while taking study drug(s) and for at 
least 20 weeks (140 days or as guided by the local risankizumab 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 1 month 
prior to study Baseline (Study Day 0).
!
Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 1 month prior to study Baseline (Study Day 0).
!
Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a hysterosalpingogram 
confirms success of the procedure).
!
Intrauterine device (IUD).
!
Intrauterine hormone-releasing system (IUS).
!
Vasectomized sexual partner(s) (the vasectomized partner[s] has received medical 
assessment of the surgical success and is the sole sexual partner of the study subject).
!
True abstinence:  Refraining from heterosexual intercourse when this is in line with the 
preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, 
symptothermal, post-ovulation methods] and withdrawal are not acceptable).
If required per local guidelines, 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 per 
standard of care should be based on the local label.
5.3 Prohibited Medications and Therapy
Use of the following treatments is prohibited throughout the study:
1.
Any immunomodulatory systemic biologic.  Examples of biologic therapies include but are not 
limited to the following:
!
Zolair® (omalizumab);
!
Dupixent® (dupilumab);
!
Rituximab or biosimilar version.
2.
Systemic non-biologic therapy for AD, including but not limited to JAK inhibitors (including but 
not limited to ruxolitinib, tofacitinib, baricitinib, upadacitinib, and filgotinib), MTX, cyclosporine, 
AZA, PDE4-inhibitors, and mycophenolate mofetil.
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3.
Oral, parenteral, intramuscular, and intralesional corticosteroids.  However, use of inhaled, 
topical ophthalmic, or intranasal corticosteroids is permitted during the study.
4.
Phototherapy treatment (ultraviolet B [UVB] or ultraviolet A [UVA] phototherapy, including 
psoralen and UVA [PUVA]), laser therapy, tanning booth, or extended sun exposure.
5.
Topical treatments for AD, including but not limited to topical JAK inhibitors, calcineurin 
inhibitors, corticosteroids, prescription moisturizers, or moisturizers containing additives such 
as, but not limited to, ceramide, hyaluronic acid, urea, heparin, or filaggrin.  Exceptions:  rescue 
treatment (i.e., TCS) started after Week 24 assessment (Section 5.4) and the required additive-
free, bland emollient treatment (Section 5.4).
6.
Wet wrap therapy, regardless of the topical agent used.
7.
Live attenuated vaccines are not permitted during study participation and including up to 
140 days (20 weeks or as guided by the local risankizumab 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 (BCG)
!
Zoster vaccine live (Zostavax)
!
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
8.
Medicinal or recreational cannabis or cannabinoid use.
9.
Traditional Chinese medicines.
10. Investigational drugs are prohibited during the study.
5.4 Prior and Concomitant Therapy
Required Concomitant Therapy
All subjects are required to use an additive-free, bland emollient twice daily for at least 7 days prior to 
Baseline (Study Day 0) and throughout the course of the study.  To allow adequate assessment of skin 
dryness, moisturizers should not be applied on the area(s) of non-lesional skin designated for such 
assessments for at least 8 hours before each clinic visit.  
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Allowed Concomitant Therapy
Stable doses of other concomitant therapies for chronic conditions, for which neither the condition nor 
the treatment are judged to exclude the subject from participation, are permissible.  All concomitant 
medications should be carefully evaluated by the investigator, and the 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).
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 as specified in the eligibility 
criteria; where not specified, discontinuation must occur 5 half-lives or 4 weeks, whichever is longer, 
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.
Rescue Therapy
Topical rescue treatment is allowed only after the assessments at the Week 24 visit and at any visit 
thereafter in subjects with < EASI 50 response, as compared to Baseline, at the most recent prior and 
current scheduled visits (e.g., < EASI 50 at Week 20 and Week 24 OR at Week 24 and Week 28, etc.).  
Rescue treatment is limited to up to twice-daily application of topical corticosteroids (TCS).  (Note:  
Topical calcineurin inhibitors (TCIs) may be applied as rescue treatment to sensitive areas [e.g., facial, 
genital, and intertriginous areas]).  Use of TCS and/or TCI as rescue treatment should be recorded on the 
appropriate concomitant medication eCRF.
Subjects who receive prohibited topical treatment prior to Week 24 assessment will be considered 
treatment failures; however, they will remain on the study treatment assigned at randomization.
Subjects who receive other systemic therapy for AD will be discontinued from study drug.
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
study drug should continue to be followed for all regularly scheduled visits, unless subjects have decided 
to discontinue the study participation entirely (withdrawal of informed consent).
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject will be discontinued from study drug at any time for reasons including but not limited to the 
following:
!
Clinically significant abnormal laboratory result(s) or AEs that preclude continuation of the study 
medication, as determined by the investigator and the AbbVie Therapeutic Area Medical 
Director (TA MD) (as applicable).
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The investigator believes withdrawal from the study is in the best interest of the subject.
!
The subject requests withdrawal from the study.
!
Eligibility criteria violation(s) are noted after the subject started study drug, if continuation of 
the study drug would place the subject at risk as determined by the AbbVie TA MD, after 
consultation with the investigator.
!
Subject needs to initiate prohibited medication(s) or dosages, and continuation of the study 
drug would place the subject at risk as determined by the AbbVie TA MD.
!
Subject is noncompliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.
!
Subject becomes pregnant while participating in the study.
!
Subject is diagnosed with a malignancy.  (Exception:  localized NMSC or carcinoma in-situ of the 
cervix, where discontinuation is at the discretion of the investigator.)
!
Subject is significantly noncompliant with study procedures.
!
Occurrence of one or more of the following hepatic test abnormalities (confirmed on a second 
separate sample):
!
ALT or AST > 8 × ULN;
!
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%).
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 "planned per 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.
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5.6 Follow-Up for Subject Withdrawal from Study
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 subjects 
have decided to discontinue 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.
Subjects who prematurely discontinue study drug should complete a PD Visit as soon as possible, 
preferably within 2 weeks of discontinuation.  Samples for PK and immunogenicity will be collected 
during the PD Visit.  Afterwards, subjects should follow the regular visit schedule as outlined in the 
Activity Schedule (Appendix D) and adhere to all study procedures except for dispensing study drug, PK 
sample collection and blood sample collection for optional exploratory research.  Once the subject has 
discontinued study drug, all rescue- and efficacy-driven discontinuation criteria no longer apply.  If at 
any point a subject no longer wants to provide assessments (withdrawal of informed consent) following 
discontinuation of study drug, a second PD visit is not required.
In addition, if subject is willing and has not withdrawn consent, a follow-up phone call 20 weeks after 
the last dose of study drug may be completed to ensure all treatment-emergent AEs/SAEs have been 
resolved.
All attempts must be made to determine the primary reason for discontinuation of study drug or study 
participation.  The information will be recorded on the appropriate eCRF page.  However, these 
procedures should not interfere with the initiation of any new treatments or therapeutic modalities that 
the investigator feels are necessary to treat the subject's condition.  Following discontinuation of study 
drug, the subject will be treated in accordance with the investigator's best clinical judgment, irrespective 
of whether or not the subject decides to continue participation in the study.
5.7 Study Drug
Information about the study drug and placebo 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 (PFS)
75 mg/0.83 mL 
(90 mg/mL)
SC injection
Boehringer-
Ingelheim Pharma 
GmbH & Co. KG
Placebo for risankizumab 
(ABBV-066)
Solution for injection in 
PFS
N/A
SC injection
Boehringer-
Ingelheim Pharma 
GmbH & Co. KG
PFS = pre-filled syringe; SC = subcutaneous
During Period A, study site staff will administer study drug subcutaneously as follows:
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Risankizumab 150 mg (2 × 75 mg PFS and 2 × placebo PFS)
!
Risankizumab 300 mg (4 × 75 mg PFS), or
!
Matching placebo (4 × placebo PFS).
During Period B, study site staff will administer either risankizumab 150 mg or risankizumab 300 mg 
subcutaneously as described above.
AbbVie will not supply drug other than risankizumab and matching placebo.  If a subject is unable to 
come to the study site for a study visit due to the COVID-19 pandemic, study drug can be taken to the 
subject's house and administered by trained site personnel under appropriate conditions.
Risankizumab and matching placebo 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 must be kept in the original packaging in a secured limited access storage area.  
Study drug must be kept refrigerated between 2°to 8°C (36°to 46°F), and a temperature log must be 
maintained for documentation.
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.  Site staff will complete all blank spaces on the label before dispensing to 
subjects.  Study drug will only be used for the conduct of this study.
Interruption/Discontinuation of Study Drug Due to COVID-19
Delays in study drug dosing due to a subject with COVID-19 must be discussed with the AbbVie medical 
contact, along with the possibility of premature discontinuation from the study drug dosing period.  
Follow protocol Section 5.6 for subjects who discontinued study drug.
5.8 Randomization/Drug Assignment
Each subject will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who rescreen, the identification number assigned by the IRT at the initial screening visit should 
be used.  In addition, the IRT will assign a unique randomization number that will encode the subject's 
treatment group assignment according to the randomization schedule generated by the statistics 
department at AbbVie.  At Baseline (Study Day 0), subjects who meet eligibility criteria will be 
randomized in a 2:2:1 ratio to risankizumab 150 mg (N = 62), risankizumab 300 mg (N = 62), or matching 
placebo (N = 31).  Randomization will be stratified by baseline disease severity (moderate [vIGA-AD 3] 
versus severe [vIGA-AD 4]) and geographic region (Japan versus rest of world).
At Week 16, subjects in the placebo group will be re-randomized in a 1:1 ratio to receive either 
risankizumab 150 mg or 300 mg for the remainder of the study.  Subjects originally randomized to the 
risankizumab 150 mg or 300 mg arms will stay on their previously-assigned treatment through the end 
of the study.
While the sponsor will be unblinded as part of the Week 16 analysis, the investigator, study site 
personnel, and the subject will remain blinded to each subject's treatment for the duration of the study.  
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To maintain the blind, the risankizumab PFS and placebo PFS provided for the study will be identical in 
appearance and number of syringes.
In the event of a medical emergency in which the investigator believes that knowledge of study drug 
treatment is required, reasonable efforts must be made to contact the AbbVie Emergency Contact prior 
to breaking the blind, as long as it does not compromise subject safety. However, if an urgent 
therapeutic intervention is necessary that warrants breaking the blind prior to contacting the AbbVie 
Emergency Contact, the investigator can directly access the IRT system to break the blind without 
AbbVie agreement.
The date and reason that the blind was broken must be recorded in the source documentation and 
eCRF, as applicable.
5.9 Protocol Deviations
The investigator is responsible for complying with all protocol requirements, written instructions, and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when 
necessary to eliminate an immediate hazard to study subjects.  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 the IEC/IRB, regulatory authorities (as applicable), and AbbVie.
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 not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 1 business day of the study site's knowledge of the event.  Product complaints occurring during 
the study will be followed up to a satisfactory conclusion.
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Medical Complaints/AEs and SAEs
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.
An AE can result from use of the drug as stipulated in the protocol or labeling, as well as from accidental 
or intentional overdose, drug abuse, or drug withdrawal.  Any worsening of a pre-existing condition or 
illness is considered an 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 an AE only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, meet protocol-specific 
criteria, and/or the investigator considers it to be an AE.
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 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 as a 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.  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 after discontinuation of study 
drug administration will be collected, whether solicited or spontaneously reported by the subject.  In 
addition, SAEs and protocol-related nonserious AEs will be collected from the time the subject signs the 
study-specific informed consent.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local requirements.
AEs will be monitored throughout the study to identify any of special interest that may indicate a trend 
or risk to subjects.
In the event that an enrolled subject experiences an AE related to asthma, additional information will be 
collected utilizing a supplemental asthma CRF.  
Areas of Safety Interest
Infections, especially opportunistic infections, are a potential risk with immunomodulators.  Subjects will 
be screened and monitored throughout the study for infections and other areas of safety interest (ASI) 
(Table 2).  Screening procedures are outlined in the Activity Schedule (Appendix D).
If any of the following AEs are reported, then the following supplemental report must be completed.
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Grade 5 (Severe); Death related to AE.
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
Reasonable Possibility – After consideration of factors including timing of the event, biologic plausibility, 
clinical judgment, and potential alternative causes, there is sufficient evidence (information) to suggest 
a causal relationship.
No Reasonable Possibility – After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is insufficient evidence 
(information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 1 working day after 
the site becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).
Information regarding a pregnancy occurrence in a study subject and the outcome of the pregnancy will 
be collected.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth, or congenital anomaly is 
considered a 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 independent data monitoring committee (IDMC) will review unblinded safety data on a 
cohort level throughout the course of the study.
!
A separate IDMC 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 adjudicated cardio-cerebrovascular events per the CAC 
charter and anaphylaxis events per the AAC charter will be presented to the IDMC for review on 
a periodic basis.
!
Communications from the IDMC to the Study Teams will not contain information that could 
potentially unblind the team to subject treatment assignments.
6.3 Cardiovascular Adjudication Committee
An independent adjudication committee will be adjudicating all observed cardio- and cerebro-vascular 
events and will remain blinded to treatment allocation.  The events that are adjudicated and the 
adjudication process will be detailed in the CAC Adjudication Committee Charter.  Dedicated eCRFs will 
be used as outlined in Table 2.
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In addition, the site may be contacted for additional source documentation for relevant events.
6.4 Anaphylaxis Adjudication Committee
While no concerns with 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 a pre-specified definition.  This independent external AAC will adjudicate observed suspected 
anaphylactic reactions and will remain blinded to treatment allocation.  The events that are adjudicated 
and the adjudication process will be detailed in the AAC Charter.  A supplemental Hypersensitivity 
Reactions eCRF will be used to collect information pertinent to the events.  In addition, the site may be 
contacted for additional source documentation for relevant events.
If a systemic hypersensitivity reaction such as anaphylaxis is suspected while the subject is not on site, 
every effort should be made to obtain tryptase and histamine levels from the treating facility to help 
better understand and characterize the diagnosis.  If a suspected systemic hypersensitivity reaction 
occurs on site, in addition to testing tryptase and histamine levels, PK and ADA/nAb samples will also be 
collected.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The objective of the statistical analysis is to evaluate the safety and efficacy of risankizumab in 
comparison with the placebo group for the treatment of moderate to severe AD in adult and adolescent 
subjects.  The primary analysis will be performed when all subjects complete Week 16.  This analysis is 
the final and only analysis for the primary and key secondary endpoints.
The statistical analysis will be described and fully documented in the SAP.  The SAP will be finalized prior 
to the blind break and database lock for the primary analysis.  The statistical analyses will be performed 
using Statistical Analysis System (SAS) (SAS Institute Inc., Cary, North Carolina, US).
7.2 Definition for Analysis Populations
The Intention-to-Treat (ITT) Population includes all randomized subjects and will be used for efficacy 
analyses.  Subjects will be analyzed according to treatment as randomized.
Subjects who are randomized to placebo in Period A and do not continue into Period B will be excluded 
from the analysis in Period B.
The Safety Population consists of all randomized subjects who receive at least 1 dose of study drug.  The 
safety analyses for each treatment period include subjects who receive at least 1 dose of study drug 
during that treatment period.  Subjects will be analyzed based on the treatment they actually receive, 
regardless of the treatment to which they are randomized.  
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An "All Risankizumab" Treated Population (ALL_RISA) will consist of all subjects who received at least 
1 dose of risankizumab in the study.  This population will be used to provide a comprehensive summary 
of safety.
7.3 Statistical Analyses for Efficacy
Pairwise comparison of the primary endpoint and the key secondary endpoints will be conducted 
between each risankizumab group (risankizumab 150 mg and 300 mg, respectively) versus the placebo 
group using the Cochran-Mantel-Haenszel (CMH) test, stratified by baseline disease severity (moderate 
[vIGA-AD 3] versus severe [vIGA-AD 4]).  For the analysis of the primary endpoint and key secondary 
endpoints, non-responder imputation (NRI) with multiple imputation (MI) to handle missing data due to 
COVID-19 (NRI-C) will be used as the primary approach. The non-responder imputation with no special 
data handling for missing data due to COVID-19 (NRI-NC) approach, observed cases (OC) approach, and 
MI may be conducted as appropriate sensitivity analyses to handle missing values.
Efficacy data for subjects who switch to rescue medications will be imputed from the point of rescue 
using an NRI approach for the primary endpoint and key secondary endpoints.
Sample Size Estimation
Approximately 155 subjects will be randomized to risankizumab 150 mg, risankizumab 300 mg, or 
placebo in a ratio of 2:2:1 at Baseline (62 subjects each for the risankizumab 150 mg and 300 mg groups 
and 31 subjects for the placebo group).  Assuming a maximum EASI 75 response rate of 15% in the 
placebo group, this sample size will provide at least 90% power to detect the treatment difference of at 
least 36% between each risankizumab group and placebo group using a two-sided test at a 
0.025 significance level.  The graphic approach for controlling multiplicity will be outlined in the SAP.
7.4 Statistical Analyses for Safety
All safety analyses will be performed on the Safety Population for both treatment periods, respectively, 
based on the treatment subjects actually receive.  Safety will be assessed by AEs, laboratory tests, vital 
signs, and ECG variables.  Missing safety data will not be imputed for safety analysis.  Analysis details will 
be specified in the SAP.  AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA).  
A treatment-emergent adverse event (TEAE) is defined as an AE with onset or worsening on or after the 
first dose of study drug and within 140 days (20 weeks) after the last dose of study treatment injection.  
The number and percentage of subjects experiencing TEAEs will be tabulated using MedDRA system 
organ class (SOC) and preferred term (PT), as well as by severity and by relationship to the study drug as 
assessed by the investigator.  Summaries (i.e., number, percentages, and events per 100 patient-years) 
of TEAEs, SAEs, deaths, AEs leading to discontinuation, and ASI will be provided.  Pre-treatment AEs will 
be summarized separately.
For laboratory test and vital signs variables, mean change from baseline and percentage of subjects with 
evaluations meeting criteria for pre-defined Potentially Clinically Significant (PCS) values will be 
summarized.
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7.5 Analyses of Pharmacokinetics and Immunogenicity
Serum risankizumab concentrations will be summarized at each sampling time point for each dose group 
using descriptive statistics.  Population PK analyses combining data from this study and other studies of 
risankizumab may be performed and reported separately.  The relationship between risankizumab 
concentrations and certain efficacy and/or safety variables of interest may be explored.
ADA titers will be tabulated for each subject at the respective study visits.  The number and percentage 
of subjects with ADA and nAb will be calculated by dose group.  As appropriate, the effect of ADAs on 
risankizumab PK, efficacy, and/or safety variable(s), and/or any additional analyses may be explored.
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 of Technical Requirements for Pharmaceuticals for Human Use (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 of a state of emergency due to the COVID-19 pandemic leading to difficulties in performing 
protocol-specified procedures, AbbVie will 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 of assessments 
(e.g., phone contacts or virtual site visits), alternative locations for data collection (e.g., use of a local 
laboratory instead of a central laboratory), study visit schedule modification, and home IP 
administration by trained site personnel to ensure continuity of treatment, where allowed.  Refer to the 
Operations Manual in Appendix F for additional details.  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.
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.
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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 is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).
During the COVID-19 pandemic, remote monitoring of data may be employed if allowed by the local 
regulatory authority, IRB/IEC, and the study site.
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 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
11
COMPLETION OF THE STUDY
The investigator will conduct the study in compliance with the protocol and complete the study within 
the timeframe specified in the contract between the investigator and AbbVie.  Continuation of this study 
beyond this date must be mutually agreed upon in writing by both the investigator and AbbVie.  The 
investigator will provide a final report to the IEC/IRB following conclusion of the study and will forward a 
copy of this report to AbbVie or their representative.
The investigator must submit, maintain, and archive any records related to the study according to ICH 
GCP and all other applicable regulatory requirements.  If the investigator is not able to retain the 
records, he/she must notify AbbVie to arrange alternative archiving options.
AbbVie will select the signatory investigator from the investigators who participate in the study.  
Selection criteria for this investigator will include level of participation as well as significant knowledge 
of the clinical research, investigational drug, and study protocol.  The signatory investigator for the study 
will review and sign the final study report in accordance with the European Medicines Agency (EMA) 
Guidance on Investigator's Signature for Study Reports.
The end of study is defined as the date of the last subject's last contact, which will be a follow-up phone 
call 20 weeks after the last dose.
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12
REFERENCES
1. Williams HC. Atopic Dermatitis.  The Epidemiology, Causes and Prevention of Atopic 
Eczema. Cambridge, UK: Cambridge University Press; 2000.
2. Silverberg JI. Public health burden and epidemiology of atopic dermatitis. Dermatol Clin. 
2017;35(3):283-9.
3. Chamlin SL, Mattson CL, Frieden IJ, et al. The price of pruritus: sleep disturbance and 
cosleeping in atopic dermatitis. Arch Pediatr Adolesc Med. 2005;159(8):745-50.
4. Hanifin JM, Reed ML. A population-based survey of eczema prevalence in the United States. 
Dermatitis. 2007;18(2):82-91.
5. Silverberg JI, Simpson EL. Association between severe eczema in children and multiple 
comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol. 
2013;24(5):476-86.
6. Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting 
paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769-79.
7. Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its 
reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 
2017;139(4s):S65-s76.
8. Mansouri Y, Guttman-Yassky E. Immune pathways in atopic dermatitis, and definition of 
biomarkers through broad and targeted therapeutics. J Clin Med. 2015;4(5):858-73.
9. Malajian D, Guttman-Yassky E. New pathogenic and therapeutic paradigms in atopic 
dermatitis. Cytokine. 2015;73(2):311-8.
10. Oliva M, Renert-Yuval Y, Guttman-Yassky E. The 'omics' revolution: redefining the 
understanding and treatment of allergic skin diseases. Curr Opin Allergy Clin Immunol. 
2016;16(5):469-76.
11. Werfel T, Allam J, Biedermann T, et al. Cellular and molecular immunologic mechanisms in 
patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(2):336-49.
12. Guttman-Yassky E, Krueger JG. Atopic dermatitis and psoriasis: two different immune 
diseases or one spectrum? Curr Opin Immunol. 2017;48:68-73.
13. Nakajima S, Kitoh A, Egawa G, et al. IL-17A as an inducer for Th2 immune responses in 
murine atopic dermatitis models. J Invest Dermatol. 2014;134(8):2122-30.
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14. Esaki H, Brunner PM, Renert-Yuval Y, et al. Early-onset pediatric atopic dermatitis is Th2 by 
also Th17 polarized in skin. J Allergy Clin Immunol. 2016;138(6):1639-51.
15. Yoon J, Leyva-Castillo JM, Wang G, et al. IL-23 induced in keratinocytes by endogenous TLR4 
ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med. 
2016;213(10):2147-66.
16. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic 
dermatitis: section 2. Management and treatment of atopic dermatitis with topical 
therapies. J Am Acad Dermatol. 2014;71(1):116-32.
17. Schmitt J, Schmitt N, Meurer M. Cyclosporin in the treatment of patients with atopic 
eczema - a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 
2007;21(5):606-19.
18. Khattri S, Brunner PM, Garcet S, et al. Efficacy and safety of ustekinumab treatment in 
adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26(1):28-35.
19. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus 
placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-48.
20. European Medicines Agency. Dupixent (dupilumab) SmPC London, England 2018 [Available 
from: 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/0043
90/human_med_002158.jsp&mid=WC0b01ac058001d124.
21. AbbVie. Risankizumab Investigator's Brochure Edition 2. 25 October 2017.
22. 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.
23. O'Garra A, Redford PS, McNab FW, et al. The immune response in tuberculosis. Annu Rev 
Immunol. 2013;31:475-527.
24. 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.
25. 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.
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26. 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.
27. AbbVie. Data on File, RRT165055.
28. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980;92 
(suppl):44-7.
29. US Department of Health and Human Services. Common Terminology Criteria for Adverse
Events (CTCAE) Version 5.0 27 November 2017 [Available from: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Qui
ck_Reference_8.5x11.pdf.
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APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AAC
Anaphylaxis Adjudication Committee
ACQ-5
Asthma Control Questionnaire-5
AD
Atopic dermatitis
ADA
Anti-drug antibodies
ADerm-IS
Atopic Dermatitis Impact Scale
ADerm-SS
Atopic Dermatitis Symptom Scale
AE
Adverse event
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
ASI
Area of safety interest
AST
Aspartate aminotransferase
AZA
Azathioprine
BCG
Bacille Calmette-Guérin
BSA
Body surface area
CAC
Cardiovascular Adjudication Committee
CARD
Caspase recruitment domain
CDLQI
Children's Dermatology Life Quality Index
CMH
Cochran-Mantel-Haenzsel
COVID-19
Coronavirus Disease - 2019
CRO
Contract research organization
CV
Cardiovascular
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
EASI
Eczema Area and Severity Index
ECG
Electrocardiogram
eCRF
Electronic case report form
EMA
European Medicines Agency
EQ-5D-5L
EuroQoL 5D-5L
FDA
Food and Drug Administration
FSH
Follicle-stimulating hormone
GCP
Good clinical practice
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HBc Ab
Hepatitis B core antibody
HBs Ab
Hepatitis B surface antibody
HBs Ag
Hepatitis B surface antigen
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HCV Ab
Hepatitis C virus antibody
HDL-C
High-density lipoprotein cholesterol
HLA
Human leukocyte antigen
HIV
Human immunodeficiency virus
HIV Ab
Human immunodeficiency virus antibody
IB
Investigator's brochure
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IDMC
Independent data monitoring committee
IEC
Independent ethics committee
Ig
Immunoglobulin
IGRA
Interferon gamma release assay
IL
Interleukin
IMP
Investigational medicinal product
INR
International normalized ratio
IRB
Institutional review board
IRT
Interactive response technology
ITT
Intention-to-treat
IU
International unit
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous
JAK
Janus kinase
LDL-C
Low-density lipoprotein cholesterol
mAb
Monoclonal antibody
MACE
Major adverse cardiovascular event
MCID
Minimal clinically important difference
MedDRA
Medical Dictionary for Regulatory Activities
MI
Multiple imputation
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MTX
Methotrexate
nAb
Neutralizing antibody
NMSC
Non-melanoma skin cancer
NRI
Non-responder imputation
NRI-C
Non-responder imputation with multiple imputation to handle missing data due to 
COVID-19
NRI-NC
Non-responder imputation with no special data handling for missing data due to 
COVID-19
NRS
Numerical rating scale
OC
Observed cases
PCR
Polymerase chain reaction
PCS
Potentially clinically significant
PD
Premature discontinuation
PDE4
Phosphodiesterase Type 4
PFS
Pre-filled syringe
PG
Pharmacogenetic
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
Pharmacokinetic(s)
POC
Proof-of-concept
POEM
Patient-Oriented Eczema Measure
PPD
Purified protein derivative
PT
Preferred Term
PUVA
Psoralen and ultraviolet A
RNA
Ribonucleic acid
SAE
Serious adverse event
SAP
Statistical analysis plan
SAP-S
Statistical analysis plan supplement
SAS
Statistical Analysis System
SC
Subcutaneous
SCORAD
SCORing Atopic Dermatitis
SOC
System Organ Class
STAT
signal transduction activators of transcription
SUSAR
Suspected unexpected serious adverse reactions
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TA MD
Therapeutic Area Medical Director
TB
Tuberculosis
TCI
Topical calcineurin inhibitor
TCS
Topical corticosteroids
TEAE
Treatment-emergent adverse event
TNF
Tumor necrosis factor
TYK
Tyrosine kinase
ULN
Upper limit of normal
US
United States
UVA
Ultraviolet A
UVB
Ultraviolet B
vIGA-AD
Validated Investigator Global Assessment scale for Atopic Dermatitis
WBC
White blood count
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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M16-813:  A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to 
Evaluate Risankizumab in Adult and Adolescent Subjects with Moderate to Severe Atopic Dermatitis
Protocol Date:  13 October 2020
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation 
(ICH) Good Clinical Practices (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 Institutional Review Board (IRB)/Independent Ethics Committee 
(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 Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical 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 Strategy Team, Immunology
Therapeutic Area MD, Immunology
Data and Statistical Sciences
Clinical Pharmacology and Pharmacometrics
Clinical Program Development, Immunology
Medical Writing
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APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities across the Screening and subsequent study visits.  The 
individual activities and allowed modifications due to COVID 19 are described in detail in the Operations 
Manual (Appendix F).
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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF 
CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
01 May 2018
Version 2.0
04 June 2018
Version 3.0
13 February 2019
Administrative Change 1
23 May 2019
Version 4.0
29 July 2019
The purpose of this version is to incorporate necessary protocol modifications due to the COVID-19 
pandemic as follows:
!
Section 2.2 – included information on the re-evaluation of the benefit and risk to subjects 
participating in the study.  There is no anticipated additional risk to subjects.
!
Section 5.5 – added instructions to refer to Operations Manual for necessary changes to 
activities or procedures.
!
Section 5.7 – provided instructions in the event of temporary study drug interruption/halt due 
to COVID-19 and that in the event the subject cannot complete an onsite visit, administration of 
study drug at the subject's house is to be performed by study staff if feasible and permitted by 
local regulations.
!
Section 5.9 – clarified that protocol deviations may include modifications due to COVID-19.
!
Section 7.3 – added NRI-C to incorporate handling of missing data due to COVID-19 as the 
primary approach and NRI-NC as sensitivity analysis.
!
Section 8.2 – noted that AbbVie will modify the study protocol as necessary due to the 
pandemic, referring to the Operations Manual in Appendix F for additional details.  Investigators 
must also notify AbbVie if any urgent safety measures are taken.
!
Section 9 – noted that remote monitoring may be employed as needed.
!
Appendix D – added reference to Operations Manual for allowed modification.
!
Appendix F – Operations Manual updated to include details on how to perform specific 
activities/procedures that may be impacted by changes in global/local regulations due to the 
pandemic.
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APPENDIX F. OPERATIONS MANUAL
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OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL M16-813 Version 5.0
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1 CONTACTS
Sponsor/
Emergency 
Medical Contact
AbbVie Inc.
Immunology Clinical Development 
1 North Waukegan Road
North Chicago, IL 60064
USA
EMERGENCY 24 hour Number:  
+1 (973) 784-6402
Phone:
Mobile:
Email:
Safety Concerns
Immunology Safety Team
AbbVie Inc.
Dept. R48S, Bldg. AP31-2
1 North Waukegan Road
North Chicago, IL 60064
Phone:
+1 (847) 938-8737
Email:
GPRD_SafetyManagement_Immunology@abbvie.com
SAE Reporting 
outside of RAVE
Email:
PPDINDPharmacovigilance@abbvie.com
Fax:
+1 (847) 938-0660
Protocol 
Deviations
AbbVie Inc.
1 North Waukegan Road
North Chicago, IL 60064
Phone:
Email:
Certified Clinical 
Lab
Covance Central Laboratory Services SA
8211 Scicor Drive
Indianapolis, IN 46214
Phone:
+001 866-762-6209  (Toll free)
+001 317-271-1200  (Local calls)
Fax:
+001 317-616-2362
For country-specific toll free numbers, please refer to 
Covance Lab Manual.
Pharmacokinetic 
Lab
AbbVie Deutschland GmbH & Co. KG
Bioanalysis Large Molecules
Knollstrasse
67061 Ludwigshafen
Germany
Phone:
+49 621-589-4847
Fax:
+49 621-589-3184
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TABLE OF CONTENTS
1
CONTACTS
2
2
PROTOCOL ACTIVITIES BY VISIT
6
2.1
INDIVIDUAL TREATMENT PERIOD VISIT ACTIVITIES
6
2.2
INDIVIDUAL POST-TREATMENT PERIOD VISIT ACTIVITIES
11
2.3
COVID-19 PANDEMIC-RELATED ACCEPTABLE PROTOCOL MODIFICATIONS
12
3
STUDY PROCEDURES
14
3.1
SUBJECT INFORMATION AND INFORMED CONSENT
14
3.2
MEDICAL HISTORY
15
3.3
ADVERSE EVENT ASSESSMENT
15
3.4
PATIENT-REPORTED OUTCOMES
15
3.5
INVESTIGATOR ASSESSMENTS
19
3.6
12-LEAD ELECTROCARDIOGRAM
20
3.7
HEIGHT, WEIGHT, AND WAIST CIRCUMFERENCE
20
3.8
VITAL SIGNS
21
3.9
PHYSICAL EXAMINATION
21
3.10
HANDHELD EPRO DEVICE
21
3.11
STUDY DRUG ADMINISTRATION
21
3.12
CLINICAL LABORATORY TESTS
23
3.13
DRUG CONCENTRATION AND ANTI-DRUG ANTIBODY MEASUREMENTS
29
3.14
BIOMARKER AND/OR EXPLORATORY RESEARCH SAMPLING
29
3.15
SUBJECT WITHDRAWAL FROM STUDY
30
3.16
UNSCHEDULED VISITS
30
3.17
OUT OF WINDOW VISITS DUE TO COVID-19 PANDEMIC
31
4
SAFETY MANUAL
31
4.1
METHODS AND TIMING OF SAFETY ASSESSMENT
31
4.2
RECORDING DATA AND ANALYSES OF SAFETY FINDINGS
32
4.3
REPORTING ADVERSE EVENTS AND INTERCURRENT ILLNESSES
32
4.4
REPORTING PRODUCT COMPLAINTS
34
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5
COUNTRY-SPECIFIC REQUIREMENTS
34
5.1
SUSAR REPORTING
34
5.2
ADDITIONAL COUNTRY-SPECIFIC REQUIREMENTS – JAPAN
34
6
STUDY DRUG
35
6.1
TREATMENTS ADMINISTERED
35
6.2
PACKAGING AND LABELING
35
6.3
METHOD OF ASSIGNING SUBJECTS TO TREATMENT GROUPS
36
6.4
SELECTION AND TIMING OF DOSE FOR EACH SUBJECT
36
7
REFERENCES
37
LIST OF TABLES
TABLE 1.
MODIFICATIONS TO STUDY VISITS DUE TO COVID-19 PANDEMIC
13
LIST OF FIGURES
FIGURE 1.
INTERPRETATION AND MANAGEMENT OF HBV SEROLOGIC TEST RESULTS
26
FIGURE 2.
SAFETY ASSESSMENT
31
LIST OF APPENDICES
APPENDIX A.
STUDY-SPECIFIC ABBREVIATIONS AND TERMS
38
APPENDIX B.
ACQ-5 EXAMPLE
41
APPENDIX C.
WORST PRURITUS NRS EXAMPLE
42
APPENDIX D.
ADERM-SS QUESTIONNAIRE EXAMPLE
43
APPENDIX E.
ADERM-IS QUESTIONNAIRE EXAMPLE
46
APPENDIX F.
SCORAD EXAMPLE
48
APPENDIX G.
DLQI QUESTIONNAIRE EXAMPLE
50
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APPENDIX H.
CDLQI QUESTIONNAIRE EXAMPLE
52
APPENDIX I.
POEM QUESTIONNAIRE EXAMPLE
54
APPENDIX J.
PGIS QUESTIONNAIRE EXAMPLE
56
APPENDIX K.
PGIC QUESTIONNAIRE EXAMPLE
57
APPENDIX L.
EQ-5D-5L EXAMPLE
58
APPENDIX M.
EASI SCORING EXAMPLE
61
APPENDIX N.
VIGA-AD QUESTIONNAIRE EXAMPLE
63
APPENDIX O.
CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS
64
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Optional blood and/or skin biomarker research samples will only be collected if the subject or their 
legally authorized representative has voluntarily signed and dated a written consent form and assent, as 
applicable, describing the research.  The written consent may be part of the main consent form.  If the 
subject or their legally authorized representative does not consent to providing optional samples, the 
subject will still be allowed to participate in the study.  A subject may withdraw consent for optional 
biomarker research at any time and remain in the clinical study.  Data generated before subject 
withdrawal of consent will remain part of the study results.
Due to the COVID-19 pandemic, it is possible that additional protocol modifications not outlined in this 
protocol may become necessary.  If this situation arises, in addition to the study informed consent, 
additional verbal consent may be obtained prior to these adaptations or substantial changes in study 
conduct in accordance with local regulations.
3.2 Medical History
A complete medical history including demographics; history of AD; previous Hepatitis B vaccination; and 
history of tobacco (including e-cigarettes), alcohol, and drug use will be taken at Screening.  The 
subject's medical history will be updated at the Baseline/Study Day 0 visit, including asthma symptoms 
(if applicable, using the ACQ-5, see Appendix B), prior to administration of the first dose of study drug.  
This updated medical history will serve as the baseline for clinical assessment.
3.3 Adverse Event Assessment
Please refer to Section 4.2.
In the event that an enrolled subject experiences an AE related to asthma, additional information will be 
collected utilizing a supplemental asthma CRF.  
3.4 Patient-Reported Outcomes
Data Collection
Subjects will complete self-administered patient-reported outcome (PRO) instruments.  Subjects should 
be instructed to follow the instructions provided with the instrument(s) and to provide the best possible 
response to each item.  Site personnel shall not provide interpretation or assistance to subjects other 
than encouragement to complete the tasks.  Site personnel will encourage completion of the 
instrument(s) at all specified visits and will ensure that a response is entered for all items.
PRO instruments that are administered at the site should be completed prior to drug administration and 
prior to any discussion of adverse events or any review of laboratory findings.  The subject should 
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complete questionnaires before site personnel perform any clinical assessments and before any 
interaction with site personnel has occurred to avoid biasing the subject's response.
Daily Worst Pruritus NRS, daily and weekly ADerm-SS, and daily and weekly ADerm-IS ePROs will be 
collected from subjects electronically every evening using a handheld device provided to the subject at 
Screening (see Section 3.10).  The handheld electronic device will be programmed to allow data entry 
only once per day.  All data entered on the device will be immediately stored to the device itself, as well 
as automatically uploaded to a central server.  Data from the DLQI, CDLQI, POEM, PGIS, PGIC, SCORAD 
(subject-reported items), and EQ-5D-5L assessments will be collected electronically at the visits specified 
in Section 2.1.  Subjects will use a tablet device at the site to enter the required pieces of information.  
Starting at the Week 16 visit, Daily Worst Pruritus NRS, ADerm-SS, and ADerm-IS ePROs will also be 
collected electronically at the prescribed visits.  The electronic tablet device will be programmed to 
allow data entry for only the visits specified in the protocol and will not allow subjects to complete more 
than one of the same assessment at any one visit.  All data entered on the handheld and electronic 
tablet devices will be immediately stored to the devices themselves and automatically uploaded to a 
central server.
Data stored on the central server will be considered source.  The investigator and delegated staff will be 
able to access uploaded subject-entered data via a password protected website until the generation, 
receipt, and confirmation of the study archive.  Data from the ePRO system will be archived and 
provided to the investigator at that time as a durable record of the site's ePRO data.
Worst Pruritus Numerical Rating Scale
The Worst Pruritus NRS (Appendix C) is an assessment tool used by subjects to report the intensity of 
pruritus during a 24-hour recall period.  Subjects are asked to rate their pruritus at its worst during the 
past 24 hours on a scale of 0 to 10, with 0 being no itch and 10 being the worst imaginable itch.
Atopic Dermatitis Symptoms Scale
The ADerm-SS (Appendix D) is an 11-item questionnaire that assesses signs and symptoms subjects may 
experience due to AD.  The ADerm-SS includes 3 items that subjects complete daily and 8 items that 
subjects complete each week, both using a 24-hour recall period.  The 3 daily items include worst itch 
during sleep hours, worst itch during waking hours, and worst skin pain.  The 8 weekly items include 
worst skin cracking, worst pain caused by skin cracking, worst dry skin, worst skin flaking, worst rash 
(i.e., redness, blisters, bumpy skin), worst skin thickening, worst bleeding, and worst skin oozing.  All 
items of the ADerm-SS are scored on an 11-point NRS ranging from 0 (no [sign/symptom concept]) to 10 
(worst possible [sign/symptom concept]).  The psychometric properties of the ADerm-SS are being 
evaluated to establish its validity in assessing AD symptoms.
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Atopic Dermatitis Impact Scale
The ADerm-IS (Appendix E) is a 10-item questionnaire that assesses a variety of impacts that subjects 
experience due to AD across both a 24-hour recall period (daily items 1-3) and 7-day recall period 
(weekly items 4-10).  Items assessed daily include difficulty falling asleep, impact on sleep, and waking at 
night.  Weekly items include household activities (e.g., washing dishes, sweeping, doing laundry), 
physical activities (e.g., walking, exercising), social activities, concentration, self-consciousness, 
embarrassment, and sadness.  All items of the ADerm-IS are scored on an 11-point NRS from 0 (no 
impact) to 10 (extreme impact).  The psychometric properties of the ADerm-IS are being evaluated to 
assess its validity in assessing the impact of AD to subjects.
SCORing Atopic Dermatitis – Subject-Reported Items
The SCORAD© (Appendix F) is a validated tool used in clinical research and clinical practice that was 
developed to standardize the evaluation of the extent and severity of AD.  The assessment consists of 
3 components:  A = extent or affected body surface area, B = severity, and C = subjective symptoms.  
Component C will be completed by subjects in this study.  Subjective assessment of itch and 
sleeplessness is recorded for each symptom by the subject or relative on a Visual Analog Scale (VAS) on 
the electronic tablet, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or 
sleeplessness), with a maximum possible score of 20.
Dermatology Life Quality Index
The DLQI (Appendix G) is a 10-item validated questionnaire used to assess the impact of AD disease 
symptoms and treatment on quality of life (QoL).  It consists of 10 questions evaluating impact of skin 
diseases on different aspects of a subject's QoL over the prior week, including symptoms and feelings, 
daily activities, leisure, work or school, personal relationships, and the side effects of treatment.  Each 
item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much).  
Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating 
greater impairment of QoL.  For general inflammatory skin conditions, a change in DLQI score of at least 
4 points is considered the minimum clinically important difference (MCID).  In this study, the DLQI will 
be administered to subjects who are ≥ 16 years old at the Baseline visit.
Children's Dermatology Life Quality Index
The CDLQI (Appendix H) is a 10-item, validated questionnaire used in clinical practice and clinical trials to 
assess the impact of AD disease symptoms and treatment on QoL.  The CDLQI has been validated for use 
in subjects 4-16 years old.  It consists of 10 questions assessing impact of skin diseases on different 
aspects of a patient's QoL over the prior week.  The CDLQI items include symptoms and feelings, daily 
activities, leisure, school, relationships, sleep, and treatment.  Each item is scored on a 4-point scale 
(0 = not at all; 1 = only a little; 2 = quite a lot; and 3 = very much).  Item scores (0 to 3) are added to 
provide a total score range of 0 to 30; higher scores indicate greater impairment of QoL.  In this study, 
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the CDLQI will be administered to subjects who are < 16 years old at the Baseline visit and will continue 
to be administered to these subjects for the duration of this study.
Patient Oriented Eczema Measure
The POEM (Appendix I) is a 7-item validated questionnaire used to assess disease symptoms in both 
children and adults.  Subjects respond to 7 items, including dryness, itching, flaking, cracking, sleep loss, 
bleeding, and weeping, with each item scored on a 5-point scale based on frequency (0 = no days; 
1 = 1 to 2 days; 2 = 3 to 4 days; 3 = 5 to 6 days; and 4 = all days).  Item scores (0 to 4) are added to 
provide a total score, ranging from 0 to 28, with the total score reflecting disease-related morbidity.  A 
change in POEM score of 3.4 points is considered the MCID.
Patient Global Impression of Severity
The PGIS (Appendix J) is a single-question assessment in which subjects describe the severity of their AD 
symptoms at the present moment.  Subjects rate their AD symptoms on a 7-point scale, ranging from 0 
(Absent, no symptoms) to 6 (Very Severe, cannot be ignored and markedly limits daily activities).
Patient Global Impression of Change
The PGIC (Appendix K) is a single-question assessment in which subjects rate the overall change in their 
AD symptoms by comparing the severity of their symptoms at the present moment with the severity of 
their symptoms before they began study treatment.  Subjects are asked to rate the overall change in 
their AD symptoms, with responses ranging from 1 ("Very much improved") to 7 ("Very much worse").
EuroQoL EQ-5D-5L
The EQ-5D-5L (Appendix L) is a health state utility instrument that evaluates preference for health status 
(utility).  The 5 items in the EQ-5D-5L comprise 5 dimensions (mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression) each of which are rated on 5 levels of severity.  Responses to 
the 5 items encode a discrete health state which is mapped to a preference (utility) specific for different 
societies.  Subjects also rate their perception of their overall health on a separate VAS.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
If electronic PRO instruments (ePROs) cannot be completed on the tablet, they are permitted to be 
completed via phone or video interview.
Site staff will record the subject's responses on the screen shot of the PRO in the subject's language.  
The date, time, and interviewer name should be recorded in the source document.  The investigator or 
study coordinator must transcribe the PRO responses into the TrialManager website.  No other site roles 
will receive access to enter data into TrialManager.  Training will be required for investigator data entry 
into TrialManager and will be provided upon request of the sponsor.
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If appropriate site personnel can travel to the subject's home, the ePRO tablet can be taken to the 
subject's home for ePRO completion.  All ePROs should be completed for the assigned visit.
3.5 Investigator Assessments
Investigator assessments will be recorded on source documents and then entered into the eCRF and
conducted at the study visits specified in Section 2.  Assessments should be performed by the 
investigator or qualified site personnel.  To minimize variability, the same assessor should evaluate the 
subject at each visit for the duration of the study.  Any assessor must be competent in performing such 
assessments.  It is the responsibility of the site primary investigator to ensure that all assessors are 
qualified and trained to perform assessments and that all training is documented.  If the same assessor 
is not available, the pre-identified back-up assessor should perform such assessments.
Eczema Area and Severity Index
The EASI (Appendix M) is a tool used to measure the extent (area) and severity of atopic eczema in 
4 regions of the body (head and neck; trunk, including lower extremities; upper limbs; and lower limbs).  
An area score and a severity score are determined for each of the 4 regions.  Each region's area score 
and severity score are multiplied together and then by a multiplier.  The total scores from each region 
are added together to determine the final EASI score.  Grades for dryness or scaling are not assessed by 
the EASI score.
Body Surface Area
A clinical estimation is made of the total BSA affected by AD.  The surface area of the subject's right or 
left hand is designated as the measuring device, with the total surface of the palm and 5 digits assumed 
to be approximately equivalent to 1% of the subject's total BSA.
Validated Investigator Global Assessment Scale for Atopic Dermatitis
The vIGA-AD (Appendix N) is a validated assessment instrument used in clinical studies to rate the 
severity of AD globally, based on a 5-point scale ranging from 0 (clear) to 4 (severe).
SCORing Atopic Dermatitis
Study investigators will complete Components A and B of the SCORAD assessment (Appendix F) 
previously described.  The extent of AD (Component A) is assessed as a percentage of each defined body 
area and reported as the sum of all areas, with a maximum score of 100%.  Component B is the 
assessment of the severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, 
skin thickening/lichenification, dryness) using the following scale:  none (0), mild (1), moderate (2), or 
severe (3) (for a maximum of 18 total points).  The SCORAD is calculated using the formula A/5 + 7B/2 + 
C (from the subject assessment), and the maximum score is 103.  SCORAD Components A and B will not 
be on the electronic tablet; instead, they will be performed on paper worksheets and manually entered 
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into the eCRF.  The rule of 9's method should be used to assess the percentage of each defined body 
area on the paper worksheets for Component A.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
Collection of investigator assessment data is not permitted by remote or virtual visits.
3.6 12-Lead Electrocardiogram
A 12-lead ECG will be performed at designated study visits specified in Section 2.  The ECG should be 
performed prior to blood collection.
For subjects with a normal ECG taken within 90 days of Screening, a repeat ECG at Screening will not be 
required, provided all protocol-required documentation is available and nothing has changed in the 
subject's health status since the time of the test that warrants a repeat test.
The ECGs will be evaluated by an appropriately trained physician at the site ("local reader").  The local 
reader from the site will sign and date all ECG tracings and will provide his/her global interpretation as a 
written comment on the tracing using the following categories:
!
Normal ECG
!
Abnormal ECG – not clinically significant
!
Abnormal ECG – clinically significant
Only the local reader's evaluation of the ECG will be collected and documented in the subject's source 
folder.  The automatic machine reading (i.e., machine-generated measurements and interpretation that 
are automatically printed on the ECG tracing) will not be collected.
3.7 Height, Weight, and Waist Circumference
For the adult population, height will be measured at Screening only with shoes off.  Body weight will be 
measured at scheduled visits specified in Section 2.  The subject should wear lightweight clothing and no 
shoes during weighing.  Waist circumference should be measured at Screening and Week 52; however, if 
missed at Screening it can be recorded at the Baseline (Study Day 0) visit.
For the adolescent population (as defined at Baseline), height, body weight, and waist circumference 
will be measured at Screening (however, if missed at Screening it can be recorded at the Baseline [Study 
Day 0]), Week 10, Week 28, and Week 52 with shoes off.  The subject should wear lightweight clothing 
and no shoes during weighing.
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3.8 Vital Signs
Vital sign determinations of systolic and diastolic blood pressure (BP), pulse rate, respiratory rate, and 
body temperature will be obtained at visits specified in Section 2.  BP and pulse rate should be 
measured after the subject has been sitting for at least 3 minutes and before blood draws are 
performed.
3.9 Physical Examination
A complete physical examination will be performed at the designated study visits specified in Section 2.  
The physical examination performed on Study Day 0 will serve as the baseline physical examination for 
the entire study.  If appropriate, a targeted physical exam should be performed at any other visit 
(e.g., to evaluate a reported adverse event).  Any significant physical examination findings after the 
first dose will be recorded as AEs, while any findings prior to the first dose will be recorded as medical 
history.  All findings, whether related to an AE or part of each subject's medical history, will be captured 
on the appropriate eCRF page.
3.10 Handheld ePRO Device
During the Screening Visit, subjects will be dispensed a handheld ePRO device to collect daily Worst 
Pruritus NRS, daily and weekly ADerm-SS, and daily and weekly ADerm-IS information.  At each visit, site 
representatives should check to see that subjects have performed the required assessments between 
study visits.  Data will be collected from the day of the Screening visit through the Week 16 visit.
3.11 Study Drug Administration
Study drug will be administered to subjects beginning at Baseline (Study Day 0) and as specified in 
Section 2.1.  All subcutaneous (SC) doses of risankizumab and placebo will be administered by study site 
personnel under the direction of the investigator.  The date and time (to the nearest minute) of onset of 
study drug administration will be recorded in the subject's medical record.  The first dose of study drug 
will be administered after all other Baseline (Study Day 0) procedures are completed.
Study drug administration instructions for risankizumab pre-filled syringes will be provided for use by 
site staff. 
COVID-19 Pandemic-Related Acceptable Protocol Modifications
If a subject cannot travel to the site for a visit when study drug administration is planned, site personnel 
may travel to the subject's home to conduct an at-home visit.  Study drug may be transported under 
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appropriate storage conditions and administered by trained site personnel.  The site must contact the 
sponsor to obtain instructions on how to dispense drug in the IRT system for at-home visits.
If an at-home visit is scheduled, site staff should also bring the ePRO tablet to the home for the subject 
to complete those assessments, see Section 3.4 for more details.
Monitoring for Hypersensitivity Reactions
Therapeutic protein products, such as biologics, may elicit a range of acute effects, from symptomatic 
discomfort to sudden, fatal reactions that have often been grouped as "infusion or injection reactions"
in the past.  Although the term implies a certain temporal relationship, infusion or injection reactions 
are otherwise not well defined and may encompass a wide range of clinical events, including anaphylaxis 
and other events that may not be directly related to antibody responses, such as cytokine release 
syndrome.
In the event of a suspected systemic hypersensitivity/anaphylactic reaction, in addition to the standard 
AE eCRF, a supplemental Hypersensitivity Reactions eCRF should also be completed by the site.  The 
clinical criterion for diagnosing anaphylaxis is provided in Appendix O for reference; symptoms of 
anaphylactic reaction usually occur within 24 hours after exposure to an allergen.  These are guidelines 
that are used to help diagnose anaphylaxis.  The investigator is encouraged to report any suspected 
reactions.
Subjects should be closely monitored for signs and symptoms of hypersensitivity reactions, including 
allergic reactions and anaphylaxis, for approximately 2 hours after study drug administration at the 
Baseline/Study Day 0 and Week 16 visits, and 1 hour after all other doses of study drug (dosing visits 
other than the Study Day 0 and Week 16 visits).  A medical person qualified in the treatment of acute 
hypersensitivity reactions must be present during the injections.
All appropriate medical support measures (e.g., diphenhydramine, steroids, epinephrine, oxygen) for the 
treatment of suspected hypersensitivity reactions should be available for immediate use in the event 
that a suspected hypersensitivity reaction occurs.  Subjects who manifest any new signs or symptoms 
during the injection should be monitored for appropriate resolution prior to leaving the site.  Subjects 
are encouraged to report any symptoms related to a possible injection-related reactions or local 
injection site reaction or late phase reactions to the site any time during the study.  A patient 
information card listing the symptoms of these reactions will be provided to the participants.
In the event of a suspected anaphylactic reaction, blood and serum samples should also be collected as 
described in Section 3.12.
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3.12 Clinical Laboratory Tests
A certified laboratory will be utilized to process and provide results for the clinical laboratory tests.  
Laboratory reference ranges will be obtained prior to the initiation of the study.  The baseline laboratory 
test results for clinical assessment for a particular test will be defined as the last measurement prior to 
the initial dose of study drug.
Instructions regarding the collection, processing, and shipping of these samples will be provided by the 
central laboratory.
If a laboratory test value is outside the reference range and the investigator considers the laboratory 
result to be clinically significant, the investigator will:
!
repeat the test to verify the out-of-range value;
!
follow the out-of-range value to a satisfactory clinical resolution; or
!
discontinue the subject from the study or require the subject to receive treatment; in this case, 
the laboratory result will be recorded as an adverse event.
Clinical Laboratory Tests
HEMATOLOGY
CLINICAL CHEMISTRY 
URINALYSIS
Hematocrit
Hemoglobin
Red Blood Cell (RBC) count/
  Erythrocytes
Mean Corpuscular Volume (MCV)
White Blood Cell (WBC) count/
  Leukocytes
Platelet count/Thrombocytes
Diff. Automatic (absolute count):
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
Manual Differential (ONLY IF 
  Automated Differential is 
  abnormal):
Neutrophils, bands (Stabs)
Neutrophils, polymorphonuclear
Eosinophils
Basophils
Monocytes
Lymphocytes
Electrolytes
Calcium
Sodium
Potassium
Chloride
Bicarbonate
Substrates
Glucose
Blood urea nitrogen (BUN)
Creatinine
Estimated glomerular filtration rate 
  (eGFR)
Bilirubin Total
Bilirubin Direct (if total is elevated)
Bilirubin Indirect (if total is elevated)
Albumin
High-sensitivity C-Reactive Protein 
(hsCRP)
Cholesterol, totala
LDL Cholesterola
HDL Cholesterola
Triglyceridesa
FSHb
Dipstick Urinalysis
Urine Nitrite
Urine Protein
Urine Glucose
Urine Ketone
Urobilinogen
Urine Bilirubin
Urine RBC/Erythrocytes
Urine WBC/Leukocytes
Urine pH
Urine creatinine
Urine Sediment (microscopic 
examination, only if urine analysis 
abnormal)
Urine Sediment Bacteria
Urine Cast in Sediment
Urine Squamous Epithelial Cells 
Urine Sediment Crystals,
  Unspecified 
Urine Sediment RBC/Erythrocytes 
Urine Sediment WBC/Leukocytes
Urine
Urine Albumin-to-Creatinine Ratio
  (UACR)
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Clinical Laboratory Tests
Coagulation:
International Normalized Ratio (INR)c
Enzymes
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Alkaline Phosphatase (AP)
Gamma-glutamyl transferase
  (GGT/γ-GT)
Creatine Kinase (CK)
Only if CK is elevated:
  Troponin (point-of-care) OR
  Troponin (central lab) + CK-MB
INFECTION SCREENING
PREGNANCY TESTINGe
Hepatitis B surface antigen (HBs
  Ag) (qualitative)d
Hepatitis B surface antibody (HBs
  Ab) (qualitative)d
Anti-Hepatitis B core (HBc) total
  (qualitative)d
Hepatitis B Virus (HBV) DNA
  (quantitative)d
Anti-Hepatitis C Virus (HCV) 
  (qualitative)d
HCV RNA (quantitative)d
HIV 1 and HIV-2 Ab (qualitative)d
QuantiFERON®-TB (or Interferon
  gamma release assay [IGRA]
  equivalent) and/or purified
  protein derivative (PPD)
Urine Pregnancy test (local)f
Serum Pregnancy testg
PK/IMMUNOGENICITY
ADDITIONAL TESTING
Serum risankizumab 
concentration
Serum ADA
Serum nAb
IgE
ANAPHYLAXIS TESTINGh
Serum risankizumab
concentrationi
ADAi
nAbi
Tryptasej
Histamine
a.
Performed only at Baseline visit (following a minimum 8-hour fast).
b.
FSH testing is to be done at Screening in all women aged ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause.
c.
INR test only performed if ALT or AST > 3 × ULN (upper limit of normal).
d.
Performed only at Screening.
e.
Pregnancy testing is not required for female subjects of non-childbearing potential (defined in protocol).
f.
Urine pregnancy test will be performed at every dosing visit and the Week 52/PD Visit and must be conducted prior to 
study drug dosing.  Negative urine pregnancy test results must be confirmed prior to study drug dosing.
g.
Serum pregnancy test is conducted at Screening and at other visits only if urine pregnancy test is positive.  Negative serum 
pregnancy test results must be confirmed prior to study drug dosing.
h.
Only performed in case of a suspected anaphylactic reaction. 
i.
PK and ADA/nAb samples drawn in context of a suspected anaphylactic reaction are collected in addition to those 
collected at scheduled time points for PK/immunogenicity and are only collected if a suspected anaphylactic reaction 
occurs while at the study site.
j.
A follow-up tryptase level should be collected a minimum of 2 weeks after any suspected anaphylaxis event.
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Pregnancy Tests (Serum and Urine)
A pregnant or breastfeeding female will not be eligible for participation or continuation in this study.
Pregnancy testing should not be performed for postmenopausal women.
A serum pregnancy test will be performed at Screening and a urine pregnancy test will be performed at 
Baseline for all female subjects.  The serum pregnancy test will be sent to and performed by the central 
laboratory.  If the serum pregnancy test is positive, the subject is considered a screen failure.  If the 
serum pregnancy test is borderline, it should be repeated to determine eligibility.
If the repeat serum pregnancy test is:
!
Positive, the subject is considered a screen failure;
!
Negative, the subject can be enrolled into the study;
!
Still borderline ≥ 3 days later, this will be considered documentation of continued lack of a 
positive result and the subject can be enrolled into the study in the absence of clinical suspicion 
of pregnancy and other pathological causes of borderline results.
Additional urine pregnancy tests for female subjects of childbearing potential will be performed at visits 
indicated in Section 2.  More frequent pregnancy tests can be performed throughout the study at the 
investigator's discretion or if required per local/country requirements.
If the urine pregnancy test (which is performed at the site) is negative, begin or continue dosing.  If the 
urine pregnancy test is positive, withhold dosing and perform a serum pregnancy test.  Pregnant 
subjects must discontinue from the study.
Follicle-Stimulating Hormone (FSH)
Follicle-stimulating hormone (FSH) should be tested at Screening if the female subject is ≤55 years of 
age AND has had no menses for ≥ 12 months AND has no history of permanent surgical sterilization.
Clinical Chemistry
Blood samples will be collected following a minimum 8-hour fast for the Baseline visit (i.e., for lipid 
testing).  If a subject is not able to fast at this visit, due to unforeseen circumstances, the non-fasting 
status will be recorded in study source documentation and lab requisition.  Blood samples at other visits 
can be drawn without prior fast.
Urinalysis
Dipstick urinalysis will be completed by the central laboratory at the Screening visit.  Specified abnormal 
macroscopic urinalyses, defined as leukocytes, nitrite, protein, ketones, blood greater than negative, or 
glucose greater than normal, will be followed-up with a microscopic analysis at the central laboratory.
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Hepatitis B and C Testing
All subjects will be tested for the presence of the Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) at 
Screening.  Subjects with Hepatitis B (HBs Ag positive [+] or detected sensitivity on the HBV DNA PCR 
qualitative test) or Hepatitis C (HCV RNA detectable in any subject with anti-HCV Ab) will be excluded.  
Subjects who have been vaccinated against Hepatitis B and are HBs Ab positive may be enrolled.  If HBs 
Ag is negative but Hepatitis B core antibodies total is positive, Hepatitis B virus DNA will be quantified.  If 
Hepatitis B virus DNA level is undetectable at Screening, the subject can participate in this study.  If 
Hepatitis C virus antibodies level is positive, Hepatitis C virus RNA will be quantified.  If Hepatitis C RNA 
level is undetectable at Screening, the subject can participate in this study.
Where mandated by local requirements; subjects with HBs Ab+ and/or HBc Ab+ and negative HBV DNA 
at screening should have HBV DNA PCR testing performed every 12 weeks (q12w).  HBV DNA PCR testing 
q12w is not necessary when the subject has a history of HBV vaccine and is HBs Ab+ and HBc Ab–.
Figure 1.
Interpretation and Management of HBV Serologic Test Results
DNA = deoxyribonucleic acid; HBs Ag = hepatitis B surface antigen; HBs Ag = hepatitis B surface antigen; HBV = hepatitis C virus; 
PCR = polymerase chain reaction
*
A positive test result for HBs Ab is expected for subjects who have had a HBV vaccination.  For subjects without a history of
HBV vaccination (and where mandated by local requirements), a positive result for HBs Ab requires HBV DNA PCR testing.
HIV Testing
HIV testing will be performed at Screening.  The investigator must discuss any local reporting 
requirements to local health agencies with the subject.  The site will report confirmed positive results to 
their health agency per local regulations, if necessary.  If a subject has a confirmed positive result, the 
investigator must discuss with the subject the potential implications to the subject's health and subject 
should receive or be referred for clinical care promptly.  A subject will not be eligible for study 
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participation if test results indicate a positive HIV infection.  AbbVie will not receive results from the 
testing and will not be made aware of any positive result.
TB Screening
Subjects will be tested for TB by either the QuantiFERON-TB Gold Test (or IGRA equivalent) or a TB Skin 
Test (PPD) at the Screening visit and at Week 52, as specified in the study activity table.
At Screening, all subjects will be assessed for evidence of TB, and if positive, additional risk factors will 
be evaluated.  If a subject had a negative PPD test or QuantiFERON-TB Gold Test (or IGRA equivalent) 
within 90 days prior to Screening and all protocol-required documentation is available, the test does not 
need to be repeated, provided nothing has changed in the subject's medical history to warrant a repeat 
test.  Subjects who have tested positive will not have another test performed.
At Week 52, subjects with no prior positive TB test will be tested for TB by either the QuantiFERON-TB 
Gold Test (or IGRA equivalent) or a TB Skin Test (PPD).
The QuantiFERON®-TB Gold assay test will be supplied and analyzed by the central laboratory.  
(QuantiFERON-TB test is preferred over TB Skin Test.)  Details on the collection, shipment of samples 
and reporting of results by the central laboratory are provided to investigators in the laboratory manual.
!
If the QuantiFERON-TB Gold Test (or IGRA equivalent) is NOT possible (or if both the 
QuantiFERON-TB Gold Test [or IGRA equivalent] and the PPD Skin Test are required per local 
guidelines), the PPD Skin Test will be performed according to standard clinical practice.
!
The PPD Skin Test should be read by a licensed healthcare professional between 48 and 
72 hours after administration.  A subject who does not return within 72 hours will need to 
be rescheduled for another skin test.
!
The reaction will be measured in millimeters (mm) of induration and induration ≥ 5 mm is 
considered a positive reaction.  The absence of induration will be recorded as "0 mm," not 
"negative."
!
If subject had a positive QuantiFERON-TB Gold (or IGRA equivalent) or PPD test at Screening, the 
test should not be repeated.  Subjects who have had an ulcerating reaction to the TB Skin Test in 
the past should not be re-exposed and should not be tested by a PPD skin test.
!
If the TB screening test (either PPD or the QuantiFERON-TB Gold test [or IGRA equivalent]) is 
positive, or if there is a repeat indeterminate QuantiFERON-TB Gold test (or IGRA equivalent) 
upon retesting, subjects may participate in the study if further work-up (according to local 
practice/guidelines) establishes conclusively that the patient has no evidence of active TB.
!
If the subject is diagnosed with active TB, the subject should not be randomized in the study and 
should not receive study drug.  Subject will be considered as a screening failure.
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!
If presence of latent TB is established, subjects are not required to be treated with prophylactic 
anti-TB therapy prior to or during the study, if considered low risk for reactivation per 
investigator judgment.
!
If the subject is diagnosed with active TB after being randomized, the subject should not receive 
any further study drug and follow the PD Visit procedure (Section 2.2).
!
If TB (latent or active) is diagnosed during the study, it is also necessary to report it as an AE in 
the source documents and eCRFs.  In the case of a TB-related AE, a TB supplemental form that 
provides additional information will be completed by the investigator or designee.
Hypersensitivity/Anaphylaxis Testing
Anaphylaxis testing is only performed in case of a suspected anaphylactic reaction.  Samples should be 
collected as follows:
Plasma tryptase:  Optimally, measurement needs to be obtained from 15 minutes to 3 hours of 
symptom onset, but no later than 6 hours after (tryptase may remain elevated for 6 or more hours after
the onset and therefore may still be informative if obtained after 3 hours); a follow-up tryptase level 
should be collected a minimum of 2 weeks after any suspected anaphylaxis event.
Plasma histamine:  Blood samples for measurement of histamine levels are optimally obtained 
5 - 15 minutes after symptom onset and no later than 1 hour.
If a suspected systemic hypersensitivity reaction occurs on site, in addition to tryptase and histamine 
levels, PK and ADA/nAb samples will also be collected.
In the event that a serious systemic hypersensitivity reaction such as anaphylaxis occurs while the 
subject is not on site at the study clinic, please advise the treating facility to obtain tryptase and 
histamine levels to help better understand and characterize the diagnosis.
COVID-19 Pandemic-Related Acceptable Protocol Modifications
If travel restrictions or other changes in local regulations in light of the COVID-19 pandemic prevent the 
subject from having blood drawn for laboratory testing at the study site, if possible, arrange for subjects 
to have laboratory work done at a local lab, hospital, or other facility.  Local lab results should be 
obtained along with reference ranges.  Local lab results and reference ranges need to be entered into 
the EDC system and also kept with the subjects' source documentation.  Local lab results should be 
reviewed by the investigator as soon as possible.
If laboratory samples cannot be obtained, study drug administration may be continued provided the 
investigator has reviewed all prior laboratory results and confirms and discusses with the subject that 
there is no safety concern for the subject to continue use of the study drug in the absence of current 
labs.  The subject should be scheduled for laboratory draws as soon as feasible.
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3.13 Drug Concentration and Anti-Drug Antibody Measurements
Blood samples for PK, ADA, and nAb assays should be collected within 60 minutes prior to dose 
administration at dosing visits.  For subjects who prematurely discontinue from study drug treatment, 
PK and ADA samples will be collected at any time during the PD Visit.
Collection of Blood Samples for Risankizumab Analysis, ADA Assay, and nAb Assay
Blood samples for analysis of risankizumab serum concentrations, ADA assay, and nAB assay will be 
collected throughout the treatment period on the study days specified in the protocol.  Samples will be 
collected by venipuncture into appropriately-labeled, evacuated serum collection tubes.  The time that 
each blood sample (PK and ADA/nAb) is collected will be recorded to the nearest minute in the source 
document.
Measurement Methods
Serum concentrations of risankizumab and ADA and nAb assessments will be done using validated 
methods at or under the supervision of the Bioanalysis Department at AbbVie.  The presence of ADA to 
risankizumab will be assessed via a tiered approach with an electrochemiluminescence assay using 
screening, confirmatory, and titration analyses. Samples that are confirmed positive may be further 
characterized in a validated nAb assay.  Any additional analytes may be analyzed using nonvalidated 
methods.  Serum samples collected for risankizumab PK and ADA analysis may be used for future assay 
development or validation activities.
Disposition of Samples
The frozen serum samples for risankizumab analysis and ADA and nAb assays will be packed in dry ice 
sufficient to last during transportation and shipped from the study site to the central lab according to 
instructions from AbbVie.
3.14 Biomarker and/or Exploratory Research Sampling
Optional whole blood, biopsy, and skin tape samples will be collected for biomarker research at study 
visits outlined in Section 2 above.  All biomarker samples should be collected, labeled, and shipped as 
outlined in the study-specific laboratory manual.  AbbVie (or people or companies working with AbbVie) 
will store the samples and data in a secure storage space with adequate measures to protect 
confidentiality.  The samples may be retained while research on risankizumab (or drugs of this class) or 
AD and related conditions continues, but for no longer than 20 years after study completion, or per local 
requirement.
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Skin Punch Biopsy and Tape Harvest Samples
Skin punch biopsy and skin tape harvest samples will be obtained for investigations including, but not 
limited to epigenetics, transcriptomics, proteomics, IHC and targeted investigations.
For subjects who consent, both lesional and non-lesional skin punch biopsies and tape strip samples will 
be collected during the study.  Lesional skin punch biopsies and tape strip samples should be collected at 
the Baseline, Week 4, Week 16, and Week 52/PD visits.  In addition, non-lesional skin punch biopsies 
and tape strip samples should also be collected at the Baseline and Week 16 visits.  Suitable sites for skin 
biopsy will include any cutaneous surface except the head and neck, genitals, hands, feet, elbows, lower 
leg, or knees.  The lesional biopsy should be taken from a target lesion initially and always taken from 
the same lesion or comparable lesion thereafter.  The non-lesional sample should be collected from the 
most normal appearing skin in a relative proximity to the lesional skin biopsy site (i.e., same anatomical 
area), at least 5 cm away from the lesion.  It is recommended to photograph the location from which the 
biopsies will be collected and document it on a diagram.  These photographs are to be used only by the 
sites to identify biopsy location for subsequent visits.
Skin tape harvest samples will be taken prior to the punch biopsy and from a site adjacent to the site 
used for skin punch biopsies.  Sites should not biopsy over the taping site.  Patches will be applied to the 
skin briefly and then removed.  Each sample will consist of 20 discs applied to the same exact area in 
succession.  Skin tape harvest samples should be taken from the same lesional and non-lesional areas 
for each visit.
3.15 Subject Withdrawal from Study
All attempts must be made to determine the date of the last study drug dose and the primary reason for 
discontinuation of study drug or study participation.  The information will be recorded on the 
appropriate eCRF page.  However, these procedures should not interfere with the initiation of any new 
treatments or therapeutic modalities that the investigator feels are necessary to treat the subject's 
condition.  Following discontinuation of study drug, the subject will be treated in accordance with the 
investigator's best clinical judgment, irrespective of whether or not the subject decides to continue 
participation in the study.
3.16 Unscheduled Visits
An unscheduled visit should be performed when the subjects comes in for a medical visit for safety 
evaluation and assessment.  During Unscheduled Visits, blood and urine samples may be obtained for 
the laboratory tests listed in Section 3.12, or for other tests, at the investigator's discretion.  No efficacy 
assessments and no drug administration should be performed at this visit.
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Visits for dispensing new study drug in case of temperature excursion, loss, or damage are not 
considered Unscheduled Visits.  In addition, visits to only retest a lab will not be considered an 
Unscheduled Visit.
3.17 Out of Window Visits Due to COVID-19 Pandemic
If a visit can be performed onsite by OOW, consult with the sponsor to determine if the OOW visit is 
permitted.
Regardless of whether an onsite OOW visit can occur, a phone call from the site to the enrolled subject 
should be conducted as close to the date of the study visit as possible to query for any AEs and to review 
concomitant medications.
4 SAFETY MANUAL
4.1 Methods and Timing of Safety Assessment
All serious adverse events (SAEs), as well as protocol-related non-serious AEs (e.g., bruising related to 
blood draw), will be collected from the time the subject signs the study-specific informed consent until 
study drug administration.  From the time of study drug administration until 140 days following 
discontinuation of study treatment has elapsed, all AEs and SAEs will be collected, whether solicited or 
spontaneously reported by the subject.
Figure 2.
Safety Assessment
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4.4 Reporting Product Complaints
Product complaints occurring during the study will be followed-up to a satisfactory conclusion.  All 
follow-up information is to be reported to the sponsor (or an authorized representative) and 
documented in source as required by the sponsor.  Product complaints associated with adverse events 
will be reported in the study summary.  All other complaints will be monitored on an ongoing basis.
Product complaints may require return of the product with the alleged complaint condition.  In 
instances where a return is requested, every effort should be made by the investigator to return the 
product within 30 days.  If returns cannot be accommodated within 30 days, the site will need to 
provide justification and an estimated date of return.
5 COUNTRY-SPECIFIC REQUIREMENTS
5.1 SUSAR Reporting
AbbVie will be responsible for SUSAR reporting for the IMP in accordance with global and local 
guidelines, and Appendix A of the Investigator's Brochure will serve as the Reference Safety Information 
(RSI).  The RSI in effect at the start of a Development Safety Update Report (DSUR) reporting period 
serves as the RSI during the reporting period.  For follow-up reports, the RSI in place at the time of 
occurrence of the 'suspected' Serious Adverse Reaction will be used to assess expectedness.
5.2 Additional Country-Specific Requirements – Japan
For Japanese sites, the following country-specific requirements are applicable:
!
Protocol Section 5.1, Eligibility Criterion 2:  Subjects under 20 years of age must voluntarily sign 
and date an informed consent, in addition to their parent or legal guardian.
!
Protocol Section 5.9:  In addition to the other responsibilities listed, investigators are also 
responsible for recording protocol deviations in the appropriate source records.
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6 STUDY DRUG
6.1 Treatments Administered
Study drug will be administered by a healthcare professional in the form of a SC injection at the visits 
listed in Section 2.1.  For additional details on dispensing study drug in the event of home administration 
due to the COVID-19 pandemic, see Section 3.11.
Risankizumab and matching placebo will be provided by AbbVie as a solution for injection in a pre-filled 
syringe (PFS).
Study site staff will administer study drug as follows:
!
Risankizumab 150 mg:  Two SC injections of 75 mg and 2 SC injections of placebo at Baseline 
(Study Day 0), Week 4, Week 16, Week 28, and Week 40.
!
Risankizumab 300 mg:  Four SC injections of 75 mg at Baseline (Study Day 0), Week 4, Week 16, 
Week 28, and Week 40.
!
Placebo:  Four SC injections at Baseline (Study Day 0) and at Week 4.  At Week 16, subjects are 
re-randomized to receive either risankizumab 150 mg or 300 mg for the remainder of the study 
at Week 16, Week 28, and Week 40.  Study drug will be administered as described above.
Study drug must not be dispensed without contacting the interactive response technology (IRT) system.  
Study drug may only be dispensed to subjects enrolled in the study through the IRT system.  Visit date 
information and study drug return information for each kit will be available through the IRT system.
6.2 Packaging and Labeling
Study drug packaged in 75 mg PFS will be provided in a blinded fashion and packaged in cartons 
containing 1 syringe per carton.  Each kit will be labeled as required per local requirements.  Each kit 
label will contain a unique kit number.  This kit number is assigned to a subject via the IRT and encodes 
the appropriate study drug to be administered at the subjects corresponding study visit.
All labels must remain affixed to the study drug at all times and should never be removed for any 
reason.  All blank spaces should be completed by site staff prior to dispensing to subject.
Storage and Disposition of Study Drug
Risankizumab and matching placebo kits must be kept protected from light in the original packaging, in a 
refrigerator between 2°C to 8°C (36°F to 46°F).  The investigational products are for investigational use 
only and are to be used only within the context of this study.  The study drug supplied for this study 
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must be maintained under adequate security and stored under the conditions specified on the label 
until dispensed for subject use or destroyed on site as appropriate.
The refrigerator temperature must be recorded each business day.  Malfunctions or temperature 
excursions must be reported to the sponsor immediately upon notice.  Study drug should be 
quarantined and not dispensed until AbbVie (or the AbbVie Temperature Excursion Management 
System) deems the drug as acceptable.
All clinical supplies must be stored and locked in a secure place until they are dispensed for subject use 
or are returned to AbbVie.  Investigational products are for investigational use only and are to be used 
only within the context of this study.
6.3 Method of Assigning Subjects to Treatment Groups
This is a Phase 2, randomized, double-blind, placebo-controlled multicenter study to evaluate the safety 
and efficacy of risankizumab in adult and adolescent subjects with a confirmed diagnosis of moderate to 
severe AD and onset of symptoms at least 2 years before the Baseline Visit.  Subjects who meet 
eligibility criteria will be randomized in a 2:2:1 ratio to one of 3 treatment groups:  (1) risankizumab 
150 mg (62 subjects), (2) risankizumab 300 mg (62 subjects), or (3) matching placebo (31 subjects).  
Subjects in the placebo group will be re-randomized in a 1:1 ratio to receive either risankizumab 150 mg 
or 300 mg at Week 16.
At the Screening visit, all subjects will be assigned a unique subject number through the use of the IRT.  
For subjects who do not meet the study selection criteria, the site personnel must contact the IRT 
system and identify the subject as a screen failure.
Subjects who are enrolled will retain their subject number assigned at the Screening visit throughout the 
study.  Upon receipt of study drug, the site will acknowledge receipt in the IRT system.
Contact information and user guidelines for IRT use will be provided to each site.
6.4 Selection and Timing of Dose for Each Subject
During Period A, study site staff will administer study drug (risankizumab 150 mg, risankizumab 300 mg, 
or matching placebo) subcutaneously at the Baseline (Study Day 0) and Week 4 visits.
During Period B, study site staff will administer either risankizumab 150 mg or risankizumab 300 mg at 
the Week 16, Week 28, and Week 40 visits.
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7 REFERENCES
1. Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European 
Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31.
2. Hanifin JM, Thurston M, Omoto M, et al. The eczema area and severity index (EASI): 
assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 
2001;10(1):11-8.
3. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis: summary report - Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin 
Immunol. 2006;117(2):391-7.
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APPENDIX A. STUDY-SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
ACQ-5
Asthma Control Questionnaire-5
AD
Atopic dermatitis
ADA
Anti-drug antibody
ADerm-IS
Atopic Dermatitis Impact Scale
ADerm-SS
Atopic Dermatitis Symptom Scale
AE
Adverse event
ALT
Alanine aminotransferase
AP
Alkaline phosphatase
AST
Aspartate aminotransferase
BP
Blood pressure
BSA
Body surface area
BUN
Blood urea nitrogen
CDLQI
Children's Dermatology Life Quality Index
CK
Creatine kinase
COVID-19
Coronavirus Disease - 2019
CRF
Case report form
DNA
Deoxyribonucleic acid
DLQI
Dermatology Life Quality Index
EASI
Eczema Area and Severity Index
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
ePRO
Electronic patient-reported outcome
EQ-5D-5L
EuroQoL-5D-5L
FSH
Follicle-stimulating hormone
HBc
Hepatitis B core
HBs Ab
Hepatitis B surface antibody
HBs Ag
Hepatitis B surface antigen
HBV
Hepatitis B virus
HCV
Hepatitis C virus
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HIV
Human immunodeficiency virus
hsCRP
High-sensitivity C-reactive protein
Ig
Immunoglobulin
IGRA
Interferon-gamma release assay
IMP
Investigational medical product
IRT
Interactive response technology
MCID
Minimum clinically important difference
MedDRA
Medical Dictionary for Regulatory Activities
nAb
Neutralizing antibody
NRS
Numerical rating scale
OOW
Out of window
PCR
Polymerase chain reaction
PD
Premature discontinuation
PEF
Peak expiratory flow
PFS
Pre-filled syringe
PG
Pharmacogenetic
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
Pharmacokinetic
POEM
Patient Oriented Eczema Measure
PPD
Purified protein derivative
PRO
Patient-reported outcome
PT
Preferred term
QoL
Quality of life
RBC
Red blood cell
RSI
Reference Safety Information
SAE
Serious adverse event
SC
Subcutaneous(ly)
SCORAD
SCORing Atopic Dermatitis
SOC
System organ class
SUSAR
Suspected unexpected serious adverse reaction
TA MD
Therapeutic Area Medical Director
TB
Tuberculosis
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UACR
Urine albumin-to-creatinine ratio
VAS
Visual analog scale
vIGA-AD
Validated Investigator Global Assessment scale for Atopic Dermatitis
WBC
White blood cell
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APPENDIX B. ACQ-5 EXAMPLE
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APPENDIX C. WORST PRURITUS NRS EXAMPLE
Worst Pruritus Numeric Rating Scale
On a scale 0 to 10, with 0 being "no itch" and 10 being "worst imaginable itch," how would you rate your 
itch at its worst during the past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
         No Itch
  Worst Imaginable Itch
Worst Pruritus NRS V1    © AbbVie 12-7-2017
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APPENDIX F. SCORAD EXAMPLE
The SCORAD1 is a tool used in clinical research and clinical practice that was developed to standardize 
the evaluation of the extent and severity of AD.
Body Area Affected:
The extent of AD is assessed as a percentage of each defined body area.  To help in determining this 
extent, the sites affected by eczema are shaded on a drawing of a body.  The rule of 9 is used to 
calculate the affected area as a percentage of the whole body:
!
Head and neck 9%
!
Upper limbs 9% each
!
Lower limbs 18% each
!
Anterior trunk 18%
!
Back 18%
!
Genitals 1%
The score for each area is added up.  The total area is 'A,' which has a possible maximum of 100%.
Symptom Severity:
A representative area of eczema is selected.  In this area, the intensity of each of the following 6 specific 
symptoms is assessed as none (0), mild (1), moderate (2) or severe (3).
!
Redness
!
Swelling
!
Oozing/crusting
!
Scratch marks
!
Skin thickening (lichenification)
!
Dryness (this is assessed in an area where there is no inflammation)
The scores for these 6 specific symptoms should be added, for a maximum of 18 total points, assigned as 
"B" in the overall SCORAD calculation.
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Subjective Symptoms:
Subjective assessment of itch and sleeplessness is recorded for each symptom by the subject on a VAS, 
where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a 
maximum possible score of 20.  This parameter is assigned as "C" in the overall SCORAD calculation.
(10 cm in length)
SCORAD Calculation:
The SCORAD is calculated as:  A/5 + 7B/2 + C.
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APPENDIX G. DLQI QUESTIONNAIRE EXAMPLE
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APPENDIX H. CDLQI QUESTIONNAIRE EXAMPLE
CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX
Hospital No
Name:
Diagnosis:
CDLQI
Age:
SCORE:
Address:
Date:
The aim of this questionnaire is to measure how much your skin problem has affected you OVER THE LAST 
WEEK.  Please tick  one box for each question.
1.
Over the last week, how itchy, "scratchy",
             Very much
□
sore or painful has your skin been?
             Quite a lot
□
Only a little
□
Not at all
□
2.
Over the last week, how embarrassed
            Very much
□
or self conscious, upset or sad have you 
            Quite a lot
□
been because of your skin?
Only a little
□
Not at all
□
3.
Over the last week, how much has your 
            Very much
□
skin affected your friendships?
            Quite a lot
□
Only a little
□
Not at all
□
4.
Over the last week, how much have you changed
             Very much
□
or worn different or special clothes/shoes
             Quite a lot
□
because of your skin?
             Only a little
□
Not at all
□
5.
Over the last week, how much has your 
           
Very much
□
skin trouble affected going out, playing,
            Quite a lot
□
or doing hobbies?
Only a little
□
Not at all
□
6.
Over the last week, how much have you
         
Very much
□
avoided swimming or other sports because
                          Quite a lot
□
of your skin trouble?
Only a little
□
Not at all
□
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7.
Last week,
If school time: Over the
            Prevented school
                □
last week, how much did
             Very much
□
school time?  
your skin problem affect your         Quite a lot
□
school work?
Only a little
□
   
Not at all
□
   OR
was it
  
If holiday time: How much
Very much
□
holiday time?
              over the last week, has your
Quite a lot
□
skin problem interfered with
Only a little
□
your enjoyment of the holiday?       Not at all
□
8.
Over the last week, how much trouble 
            Very much
□
have you had because of your skin with
            Quite a lot
□
other people calling you names, teasing,
           
Only a little
□
bullying, asking questions or avoiding you?
            Not at all
□
9.
Over the last week, how much has your sleep
            Very much
□
been affected by your skin problem?
             Quite a lot
□
Only a little
□
Not at all
□
10.
Over the last week, how much of a 
             Very much
□
problem has the treatment for your 
             Quite a lot
□
skin been?
Only a little
□
Not at all
□
Please check that you have answered EVERY question.  Thank you.
©M.S. Lewis-Jones, A.Y. Finlay, May 1993. This must not be copied without the permission of the authors.
was it
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APPENDIX I.
POEM QUESTIONNAIRE EXAMPLE
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APPENDIX J.
PGIS QUESTIONNAIRE EXAMPLE
Seven point response scale
Please mark an "X" in the box (☒) that best describes the severity of your atopic dermatitis (AD) 
symptoms right now.
1.
Right now, my atopic dermatitis (AD) symptoms are:
☐0
Absent:  No symptoms
☐1
Minimal:  Can be easily ignored without effort
☐2
Mild:  Can be ignored with effort
☐3
Moderate:  Cannot be ignored but does not influence my daily activities
☐4
Moderately severe:  Cannot be ignored and occasionally limits my daily activities
☐5
Severe:  Cannot be ignored and often limits my concentration on daily activities
☐6
Very severe:  Cannot be ignored and markedly limits my daily activities.
© AbbVie Inc., 19October2016 V1
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APPENDIX K. PGIC QUESTIONNAIRE EXAMPLE
Seven-point response scale
Please mark an "X" in the box (☒) that best describes the severity of your atopic dermatitis (AD) 
symptoms right now.
1.
Compared to before your study treatment began, how would you rate the overall change in 
your atopic dermatitis symptoms?:
☐1
Very much improved
☐2
Much improved
☐3
Minimally improved
☐4
No change
☐5
Minimally worse
☐6
Much worse
☐7
Very much worse
© AbbVie Inc., 19October2017 V1
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APPENDIX L.
EQ-5D-5L EXAMPLE
Under each heading, please check the ONE box that best describes your health TODAY:
Mobility
I have no problems walking
☐
I have slight problems walking
☐
I have moderate problems walking
☐
I have severe problems walking
☐
I am unable to walk
☐
Self-Care
I have no problems washing or dressing myself
☐
I have slight problems washing or dressing myself
☐
I have moderate problems washing or dressing myself
☐
I have severe problems washing or dressing myself
☐
I am unable to wash or dress myself
☐
Usual Activities (e.g., work, study, housework, family, or leisure activities)
I have no problems with doing my usual activities
☐
I have slight problems with doing my usual activities
☐
I have moderate problems with doing my usual activities
☐
I have severe problems with doing my usual activities
☐
I am unable to do my usual activities
☐
Pain/Discomfort
I have no pain or discomfort
☐
I have slight pain or discomfort
☐
I have moderate pain or discomfort
☐
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I have severe pain or discomfort
☐
I have extreme pain or discomfort
☐
Anxiety/Depression
I am not anxious or depressed
☐
I am slightly anxious or depressed
☐
I am moderately anxious or depressed
☐
I am severely anxious or depressed
☐
I am extremely anxious or depressed
☐
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APPENDIX M. EASI SCORING EXAMPLE
An EASI2 score is a tool used to measure the extent (area) and severity of atopic eczema (Eczema Area 
and Severity Index).  EASI score does not include a grade for dryness or scaling.
Assignments for the following body regions are as follows: 
!
Head and Neck
!
Trunk:  include with the lower extremities
!
Upper limbs
!
Lower limbs
Area Score
Area score is recorded for each of the four regions of the body.  The area score is the percentage of skin 
affected by eczema.
Area score Percentage of skin affected by eczema in each region:
!
0 = no eczema in this region
!
1 = 1% – 9%
!
2 = 10% – 29% 
!
3 = 30% – 49% 
!
4 = 50% – 69% 
!
5 = 70% – 89% 
!
6 = 90% – 100%:  the entire region is affected by eczema
Severity Score
Severity score is recorded for each of the four regions of the body.  The severity score is the sum of the 
intensity scores for four signs.
The four signs are: 
1.
Redness (erythema, inflammation)
2.
Thickness (induration, papulation, swelling – acute eczema)
3.
Scratching (excoriation) 
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4.
Lichenification (lined skin, prurigo nodules – chronic eczema)
The average intensity of each sign in each body region is assessed as:  none (0), mild (1), moderate (2) 
and severe (3).
Score Intensity of redness, thickness/swelling, scratching, lichenification:
0 = None, absent 
1 = Mild 
2 = Moderate 
3 = Severe
For each region, record the intensity for each of four signs and calculate the severity score.
Severity score = redness intensity + thickness intensity + scratching intensity + lichenification intensity
For each region, multiply the severity score by the area score and by a multiplier.
!
Head and neck:  severity score × area score × 0.1
!
Trunk:  severity score × area score × 0.3
!
Upper limbs:  severity score × area score × 0.2
!
Lower limbs:  severity score × area score × 0.4
Add up the total scores for each region to determine the final EASI score.  The minimum EASI score is 0 
and the maximum EASI score is 72.
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APPENDIX N. VIGA-AD QUESTIONNAIRE EXAMPLE
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APPENDIX O. CLINICAL CRITERIA FOR DIAGNOSING 
ANAPHYLAXIS
Anaphylaxis3 is highly likely when any one of the following 3 criteria is fulfilled:
1)
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or 
both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a)
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow [PEF], hypoxemia)
b)
Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], 
syncope, incontinence)
2)
Two or more of the following that occur rapidly after exposure to a likely allergen for that subject 
(minutes to several hours):
a)
Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-
uvula)
b)
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)
c)
Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence)
d)
Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
3)
Reduced BP after exposure to known allergen for that subject (minutes to several hours):
a)
Infants and children:  low systolic BP (age specific) or greater than 30% decrease in systolic BP*
b)
Adults:  systolic BP of less than 90 mm Hg or greater than 30% decrease from that person's 
baseline.
*
Low systolic BP for children is defined as less than 70 mm Hg from 1 month to 1 year, less than (70 mm Hg + [2 × 
age]) from 1 to 10 years, and less than 90 mg Hg from 11 to 17 years.
Serious Systemic Hypersensitivity Reaction:  A hypersensitivity reaction is a clinical sign or symptom, or 
constellation of signs or symptoms, caused by an inappropriate and excessive immunologic reaction to 
study drug administration.  A systemic hypersensitivity reaction is a hypersensitivity reaction that does 
not occur at the local site of study drug administration (e.g., not an injection site reaction).  A serious 
systemic hypersensitivity reaction is a systemic hypersensitivity reaction that fulfills criteria for a SAE.
In the event of an anaphylactic reaction, blood samples will be drawn per Section 3.12 after the onset of 
the reaction.  Separate instructions for the collection, handling, storage, and shipping of these labs will 
be provided outside of the study protocol.
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