A Phase 4 Multicenter, Randomized, Open-label, Efficacy Assessor-blinded Study of Risankizumab Compared to Apremilast for the Treatment of Adult Subjects With Moderate Plaque Psoriasis Who Are Candidates for Systemic Therapy
Phase: PHASE4
Conditions: Psoriasis
Sponsor: AbbVie



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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
8
3
OBJECTIVES AND ENDPOINTS
10
3.1
OBJECTIVES, HYPOTHESES, AND ESTIMANDS
10
3.2
PRIMARY ENDPOINTS
11
3.3
SECONDARY ENDPOINTS
12
3.4
ADDITIONAL EFFICACY ENDPOINTS
12
3.5
SAFETY ENDPOINTS
13
3.6
PHARMACOKINETIC EVALUATION
13
4
INVESTIGATIONAL PLAN
13
4.1
OVERALL STUDY DESIGN AND PLAN
13
4.2
DISCUSSION OF STUDY DESIGN
15
5
STUDY ACTIVITIES
17
5.1
ELIGIBILITY CRITERIA
17
5.2
CONTRACEPTION RECOMMENDATIONS
21
5.3
PROHIBITED MEDICATIONS AND THERAPY
23
5.4
PRIOR AND CONCOMITANT THERAPY
24
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
24
5.6
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR FROM STUDY
26
5.7
STUDY DRUG
27
5.8
RANDOMIZATION/DRUG ASSIGNMENT
27
5.9
PROTOCOL DEVIATIONS
28
6
SAFETY CONSIDERATIONS
28
6.1
COMPLAINTS AND ADVERSE EVENTS
28
6.2
CARDIOVASCULAR ADJUDICATION COMMITTEE
34
6.3
ANAPHYLAXIS ADJUDICATION COMMITTEE
34
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7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
34
7.1
STATISTICAL AND ANALYTICAL PLANS
34
7.2
DEFINITION FOR ANALYSIS POPULATIONS
35
7.3
HANDLING POTENTIAL INTERCURRENT EVENTS FOR THE PRIMARY AND KEY SECONDARY ENDPOINTS
36
7.4
STATISTICAL ANALYSES FOR EFFICACY
36
7.5
STATISTICAL ANALYSES FOR SAFETY
38
7.6
INTERIM ANALYSIS
39
7.7
OVERALL TYPE I ERROR CONTROL
39
7.8
SAMPLE SIZE DETERMINATION
39
8
ETHICS
40
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
40
8.2
ETHICAL CONDUCT OF THE STUDY
40
8.3
SUBJECT CONFIDENTIALITY
40
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
40
10 DATA QUALITY ASSURANCE
41
11 START AND COMPLETION OF THE STUDY
41
12 REFERENCES
41
LIST OF TABLES
TABLE 1.
TASKS OF THE EFFICACY ASSESSOR AND INVESTIGATORS
17
TABLE 2.
IDENTITY OF INVESTIGATIONAL PRODUCT
27
TABLE 3.
SUPPLEMENTAL ADVERSE EVENTS ECRFS
32
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMATIC
15
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LIST OF APPENDICES
APPENDIX A.
STUDY-SPECIFIC ABBREVIATIONS AND TERMS
43
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
46
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
47
APPENDIX D.
ACTIVITY SCHEDULE
48
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
53
APPENDIX F.
OPERATIONS MANUAL
54
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted?
Psoriasis (PsO) is a chronic debilitating immunologic disease characterized by marked inflammation and 
thickening of the epidermis that result in thick, scaly skin plaques.  In most developed countries, the 
prevalence in adults is between approximately 1.5 and 5%.1  About 20% of patients have moderate to 
severe disease with a considerable negative impact on psychosocial and economic status.2,3  It is 
increasingly recognized that PsO is more than a superficial disease, with 30% of patients having joint 
involvement and a high correlation between PsO and obesity, diabetes, depression, metabolic 
syndrome, and cardiovascular risk exists.4,5
This study seeks to demonstrate that a significantly higher proportion of patients with moderate PsO 
treated with risankizumab can achieve a high level of skin clearance (≥Psoriasis Area and Severity Index 
[PASI] 90) compared to patients treated with apremilast providing a significant improvement in patient 
outcomes.
Evidence generated to date has demonstrated the benefits of risankizumab compared to other 
advanced therapies for PsO, such as adalimumab, ustekinumab, and secukinumab in moderate to severe 
PsO.6-9  However, no head-to-head data currently exist between risankizumab and apremilast.
Risankizumab (Skyrizi™) has been approved for the treatment of moderate to severe PsO and is 
currently being developed for Crohn's disease, ulcerative colitis, and psoriatic arthritis (PsA) (Phase 3 
studies).  Risankizumab is a humanized monoclonal antibody of the immunoglobin (Ig) G1 subclass 
directed towards the p19 subunit of interleukin-23 (IL-23).  The antibody (Ab) has been engineered to 
reduce Fcγ receptor and complement binding and potential charge heterogeneity.  Risankizumab binds 
with high affinity to human IL-23.
This study is designed to evaluate the efficacy and safety of risankizumab versus apremilast for the 
treatment of adult subjects with moderate plaque PsO who are candidates for systemic therapy.  In 
addition, the study aims to evaluate the efficacy and safety of switching to risankizumab versus 
continuing on apremilast for subjects with moderate plaque PsO who do not achieve ≥75% reduction 
from Baseline in Psoriasis Area Severity Index (PASI 75) after 16 weeks of treatment with apremilast.
For a more detailed description of the risankizumab drug profile, refer to the latest version of the 
Investigator's Brochure (IB).8
2.2 Benefits and Risks to Subjects
In risankizumab studies in patients with PsO, the majority of subjects receiving risankizumab achieved 
90% improvement of their disease and risankizumab was well-tolerated.  As with many 
immune-modulating agents, risankizumab may impair immune function, resulting in a risk of infection.  
This will be monitored by collection of all adverse events (AEs) during the treatment and observation 
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periods.  In addition, subjects with active systemic infection or clinically important infection will not be 
included in the study.
This study is designed to learn more about the treatment effect of risankizumab compared with 
apremilast in adult subjects with moderate plaque PsO who are candidates for systemic therapy as well 
as to learn more about the potential treatment effect of switching to risankizumab in a subset of 
apremilast-treated subjects considered as non-responders after 16 weeks of treatment as compared 
with continuing with apremilast.
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.10,11  Subjects with positive QuantiFERON-TB testing (or IGRA 
equivalent)/TB skin test who have latent TB (defined by local guidelines) are not required to be treated 
(unless recommended by local guidelines or by investigator judgement) with TB prophylaxis 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.12-14  Moreover, preclinical data have demonstrated a 
beneficial effect of IL-23 p19 inhibition in animal models, both for pre-existing and tumor-induction 
models.15  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 (MACE) events, including myocardial infarction, cerebrovascular 
accident, and cardiovascular death, reported initially with anti-IL-12/23 agents, such as ustekinumab, have 
not been observed in longer term studies with risankizumab.  While the likelihood of increased MACE is 
small, all suspected cardiovascular or cerebrovascular events (serious or nonserious) observed in this study 
will be adjudicated by an independent Cardiovascular Adjudication Committee (CAC).  The committee will 
remain blinded to treatment allocation (Section 6.2).
Local reactions to subcutaneously administered biologic therapies are usually limited to redness, swelling, 
or induration at the injection site.  Manifestations of systemic hypersensitivity reactions may include 
anaphylaxis, generalized urticaria, hypotension, and respiratory distress.  Both local and systemic 
hypersensitivity reactions are readily detectable, transient in nature, and manageable with standard 
medical treatment.  Subjects will be closely monitored during study drug administration.  An independent 
Anaphylaxis Adjudication Committee (AAC) will adjudicate observed systemic hypersensitivity and 
anaphylactic events.  The AAC will remain blinded to treatment allocation (Section 6.3).
In conclusion, the benefit-risk profile of risankizumab is considered appropriate for this stage of clinical 
development.16  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 current 
risankizumab IB.8
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Apremilast (Otezla®) was first approved as a safe and efficacious product for the treatment of plaque 
PsO by the United States Food and Drug Administration in 2014 and by the European Medicines Agency 
in 2015; since then, it has been approved in a number of additional countries.  Please refer to the local 
label available to you for information regarding the efficacy and safety of this product.17,18
In view of the coronavirus disease of 2019 (COVID-19) pandemic, the benefit-risk profile of various 
immunomodulatory therapies on COVID-19 is being evaluated based on real world and clinical trial data.  
At this time, the effects of risankizumab or apremilast on the course of COVID-19 are not well defined.
3 OBJECTIVES AND ENDPOINTS
3.1 Objectives, Hypotheses, and Estimands
The objective of the study is to evaluate the efficacy and safety of risankizumab versus apremilast for 
the treatment of adult subjects with moderate plaque PsO who are candidates for systemic therapy.
In addition, the study aims to evaluate the efficacy and safety of switching to risankizumab versus 
continuing on apremilast for subjects with moderate plaque PsO who do not achieve PASI 75 after 
16 weeks of treatment with apremilast.
Primary Efficacy Objective
The primary efficacy objective in Period A is to demonstrate a higher rate of a) PASI 90 (defined as ≥90% 
reduction from Baseline in PASI) and b) sPGA 0 or 1 with at least 2-grade improvement from Baseline 
after 16 weeks of treatment with risankizumab when compared to apremilast based on Intent to Treat 
(ITT) Population in Period A (ITT_A), which consists of all randomized subjects.
The hypotheses corresponding to the co-primary endpoints in Period A are:

The proportion of subjects achieving PASI 90 in the risankizumab (RZB) group is greater than 
that in the APR group at Week 16, among the ITT_A Population.

The proportion of subjects achieving sPGA 0 or 1 with at least 2-grade improvement from 
Baseline in the RZB group is greater than that in the apremilast (APR) group at Week 16, among 
the ITT_A Population.
The primary efficacy objective in Period B is to demonstrate a higher rate of PASI 90 after switching the 
treatment at Week 16 from APR to RZB for 36 weeks (APR/RZB) when compared to continuing with APR 
(APR/APR) based on the Intent to Treat Population in Period B for Week 16 APR-PASI75NRs (ITT_B_NR), 
which consists of subjects who are randomized to APR at Baseline, fail to achieve PASI 75 at Week 16, 
and are re-randomized.
The hypothesis corresponding to the primary endpoint in Period B is:

The proportion of APR-PASI75NR subjects achieving PASI 90 in the APR/RZB group is greater 
than that in the APR/APR group at Week 52, among the ITT_B_NR Population.
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Key Secondary Efficacy Objectives
The key secondary efficacy objective in Period A is to demonstrate higher efficacy of treatment with RZB 
when compared to APR with respect to the ranked and only secondary endpoint in Period A, as specified 
in Section 3.3 below.
The hypothesis corresponding to the ranked and only secondary endpoint in Period A is:

The proportion of subjects achieving PASI 75 in the RZB group is greater than that in the APR 
group at Week 16, among the ITT_A Population.
The key secondary efficacy objectives in Period B are to demonstrate higher efficacy of treatment with 
APR/RZB when compared to APR/APR among APR-PASI75NRs, with respect to the key secondary 
endpoints in a ranked order in Period B, as specified in Section 3.3 below.
The hypotheses corresponding to the ranked secondary endpoints in Period B are:

The proportion of APR-PASI75NR subjects achieving PASI 75 in the APR/RZB group is greater 
than that in the APR/APR group at Week 52, among the ITT_B_NR Population.

The proportion of APR-PASI75NR subjects achieving sPGA 0 or 1 with at least 2-grade 
improvement from Baseline in the APR/RZB group is greater than that in the APR/APR group at 
Week 52, among the ITT_B_NR Population.
Estimands Corresponding to the Primary and Ranked Secondary Endpoints
The estimand corresponding to each of the primary and ranked secondary endpoints in Period A is 
defined using composite variable strategy as follows:

Difference in the proportion of subjects achieving the corresponding endpoint at Week 16, 
without receiving alternative PsO treatment, regardless of premature discontinuation of study 
drug, in the RZB group in comparison with the APR group among the ITT_A population.
The estimand corresponding to each of the primary and ranked secondary endpoints in Period B is 
defined using composite variable strategy:

Difference in the proportion of subjects achieving the corresponding endpoint at Week 52 
without satisfying the rescue criteria or receiving the rescue medication, and without receiving 
alternative PsO treatment, regardless of premature discontinuation of study drug in the 
APR/RZB group in comparison with the APR/APR group among the ITT_B_NR population.
3.2 Primary Endpoints
Co-Primary Endpoints in Period A:

Achievement of PASI 90 at Week 16, among subjects in the ITT_A Population.
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
Achievement of sPGA 0 or 1 with at least 2-grade improvement from Baseline at Week 16, 
among subjects in the ITT_A Population.
Primary Endpoint in Period B:

Achievement of PASI 90 at Week 52, among subjects in the ITT_B_NR Population.
3.3 Secondary Endpoints
Ranked Secondary Endpoint in Period A:

Achievement of PASI 75 at Week 16, among subjects in the ITT_A Population.
Ranked Secondary Endpoints in Period B:

Achievement of PASI 75 at Week 52, among subjects in the ITT_B_NR Population.

Achievement of sPGA 0 or 1 with at least 2-grade improvement from Baseline at Week 52, 
among subjects in the ITT_B_NR Population.
3.4 Additional Efficacy Endpoints
All variables listed above as primary or ranked secondary endpoints will also be analyzed at all other 
visits collected.  Additionally, the following endpoints will be evaluated at all visits collected:

Achievement of 100% reduction from Baseline in PASI (PASI 100)

Achievement of sPGA 0

Change from Baseline in PASI

Percent change from Baseline in PASI

Change from Baseline in body surface area (BSA)

Achievement of Palmoplantar Investigator's Global Assessment (ppIGA) 0 or 1, among subjects 
with Baseline ppIGA of at least 3

Change from Baseline in Psoriasis Scalp Severity Index (PSSI), among subjects with Baseline 
scores > 0

Change from Baseline in Nail Psoriasis Severity Index (NAPSI), among subjects with Baseline 
scores > 0

Change from Baseline in Dermatology Life Quality Index (DLQI)

Achievement of DLQI 0 or 1

Achievement of DLQI improvement (reduction) of ≥ 4 points, among subjects with Baseline 
DLQI ≥4
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
Change from Baseline in Work Productivity and Activity Impairment (WPAI) scores

Treatment Satisfaction Questionnaire for Medication version 9 (TSQM-9) scores (at each 
post-Baseline visit in Period A)

Change from Entry of Period B in TSQM-9 scores, among subjects who are re-randomized at 
Week 16

Change from Baseline in Psoriasis Symptoms Scale (PSS) scores

Percentage change from Baseline in PSS, among subjects with Baseline scores > 0

Achievement of PSS 0

Achievement of PSS 0 or 1
3.5 Safety Endpoints
The following safety evaluations will be performed throughout the study as measures of safety and 
tolerability:

Adverse event (AE) monitoring

Vital sign measurements

Physical examinations

Clinical laboratory testing (hematology and chemistry)
3.6 Pharmacokinetic Evaluation
The pharmacokinetics (PK) and immunogenicity of risankizumab have been well characterized in 
subjects with plaque PsO.  No samples will be collected for the purpose of PK and immunogenicity in this 
study, except in cases of hypersensitivity reactions.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 4, global, multicenter, randomized, open-label, efficacy assessor-blinded, active 
comparator study examining the effect of risankizumab compared to apremilast in adult subjects with 
moderate plaque PsO who are candidates for systemic therapy.
The study is designed to enroll 330 subjects.  See Section 5.1 for information regarding enrollment 
criteria.
The study duration for subjects administered risankizumab or provided apremilast will be up to 
approximately 69 weeks or 61 weeks, respectively.  The study is comprised of a Screening period of up 
to 35 days, a 52week treatment period, and a follow-up phone call for safety.  Depending on the 
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treatment at the end of the study, the follow-up phone call for safety will be conducted approximately 
20 weeks (140 days) after administration of the last dose of risankizumab (i.e., Week 40 for subjects 
originally randomized to risankizumab and Week 44 for subjects switched from apremilast to 
risankizumab) or approximately 4 weeks (28 days) after the last dose of apremilast (for subjects who 
remain on the APR arm after re-randomization).
The 52-week treatment duration includes Period A and Period B:

Period A (Baseline to Week 16):  Eligible subjects will be centrally randomized at the Baseline 
(Day 1) visit in a 1:2 ratio to receive either risankizumab 150 mg as a single subcutaneous (SC) 
injection (Arm 1) or apremilast 30 mg orally twice daily (BID) (Arm 2).  The randomization will be 
stratified by Baseline body weight (≤100 kg, > 100 kg) and prior exposure to any systemic 
and/or biologic treatment for PsO (0, ≥1).  Study drug administration for apremilast will occur 
beginning at Baseline (Day 1) based on the dose titration schedule from Day 1 to Day 5 and will 
continue with 30 mg BID until the day prior to the Week 16 visit where re-randomization will 
occur.  Study drug administration for risankizumab will occur at Baseline (Day 1) and Week 4.  
The final efficacy evaluation for Period A will take place at Week 16.

Period B (Week 16 to Week 52):  Subjects initially randomized to risankizumab (Arm 1) will 
continue to receive risankizumab 150 mg as a single SC injection at Weeks 16, 28, and 40.  
Subjects initially randomized to apremilast (Arm 2) will be re-randomized at the Week 16 visit in 
a 1:1 ratio to receive either risankizumab 150 mg as a single SC injection at Weeks 16, 20, 32, 
and 44 (Arm 2a) or apremilast 30 mg orally BID up to Week 52 (Arm 2b).  Rerandomization will 
be stratified by PASI 75 response (responder, non-responder) at Week 16.  Rescue risankizumab 
will be offered to subjects who are re-randomized to apremilast (Arm 2b) and are PASI 50 non-
responders at Week 28 (Arm 3a; rescue risankizumab will be administered at Weeks 28, 32, and 
44) or Week 40 (Arm 3b; rescue risankizumab will be administered at Weeks 40 and 44).  The 
final efficacy evaluation will take place at Week 52.
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in the Operations Manual (Appendix F).
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Figure 1.
Study Schematic
BID = twice daily; PASI = Psoriasis Area Severity Index; SC = subcutaneous
4.2 Discussion of Study Design
Choice of Control Group
An active comparator group randomized to receive apremilast will be used in this study to examine the 
effect of 150 mg risankizumab every 12 weeks versus 30 mg apremilast BID in subjects with moderate 
plaque PsO who are candidates for systemic therapy.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy and 
safety-related measurements in this study are standard for assessing disease activity in subjects with 
moderate plaque PsO.  All clinical and laboratory procedures in this study are standard and generally 
accepted.  All patient-reported outcomes (PRO) measures in this study were adequately developed and 
validated to measure specific concepts of interest relevant to this study.
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Suitability of Subject Population
Male or female subjects with a diagnosis of moderate chronic plaque PsO (with or without PsA) for at 
least 6 months prior to Baseline and who are candidates for systemic therapy are eligible for this study.  
Eligible subjects must also have moderate chronic plaque PsO as defined by BSA ≥ 10% and ≤ 15%, PASI 
≥12, and sPGA = 3 (moderate) based on a 5-point scale (0 to 4) at Screening and the Baseline Visit.  The 
selection criteria relating to safety guarantee that subjects enrolled can safely be treated with 
risankizumab or apremilast based on the current knowledge of these drugs.
Selection of Doses in the Study
The selected dose of 150 mg SC for risankizumab is the same as the approved labeled dose in the 
treatment of moderate to severe plaque PsO tested in Phase 3 global studies in subjects with moderate 
to severe plaque PsO.  The risankizumab 150 mg SC dose has been shown to be efficacious with an 
acceptable safety profile and considered appropriate for the treatment of patients with moderate 
plaque PsO.  For apremilast, the selected dose is as recommended in the approved product labeling for 
the treatment of plaque PsO.
Blinded Efficacy Assessor
A qualified physician (may be a non-dermatologist) or designee (may be a non-physician) from the site 
will be responsible for performing the efficacy assessments, including PASI, BSA, and sPGA at all 
appropriate study visits (Table 1).  The site will make every attempt to have the same qualified physician 
or designee perform these assessments throughout the study for each subject.  The efficacy assessor 
must remain blinded to patient's treatment, clinical laboratory results, and all subject safety data during 
the course of the study.  The efficacy assessor will not view or discuss any subject specific safety data 
with the investigators or any other site personnel, with the exception of the dermatologic safety findings 
requiring urgent medical attention.  The efficacy assessor therefore cannot be the Principal Investigator.  
The efficacy assessor will not access patient's electronic case report form (eCRF) and will document the 
dermatologic assessments and potential dermatologic safety findings on paper worksheets that will be 
filed as source in the patient's record.  It is recommended that each study site has a designated back-up 
for the efficacy assessor.
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Table 1.
Tasks of the Efficacy Assessor and Investigators
Activities
Responsible Party
Assesses PASI, sPGA, BSA, ppIGA, NAPSI, and PSSI
Efficacy Assessora
Looks for any potential dermatologic safety finding
Efficacy Assessor
Documents the efficacy assessments and any potential 
dermatologic safety findings on worksheets
Efficacy Assessor
Assesses safety
Investigator
Knows treatment allocation
Investigator
Reviews laboratory data
Investigator
Conduct the complete and any targeted physical 
examinationsb
Investigator
Completes the CRF
Investigator, unblinded study team
Documents findings in the eCRF
Investigator, unblinded study team
Reports information about safety findingsc
Investigator
BSA = body surface area; CRF = case report form; eCRF = electronic case report form; NAPSI = Nail Psoriasis Severity Index; 
PASI = Psoriasis Area and Severity Index; ppIGA = Palmoplantar Investigator's Global Assessment; PSSI = Psoriasis Scalp Severity 
Index; sPGA = Static Physician Global Assessment
a.
The efficacy assessor is a physician or a designee that is blinded to all aspects of the study other than the efficacy 
assessments.
b.
The investigator will also look for potential dermatologic safety findings.
c.
If the efficacy assessor identifies a safety issue this will be transmitted to the investigator over the worksheet via paper 
collection.  Dermatologic safety findings requiring urgent medical attention will be the only safety issues that the efficacy 
assessor may discuss with the investigator.
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, approved by an independent ethics committee (IEC)/institutional review board (IRB), 
prior to the initiation of any screening or study-specific procedures.
2. Employees of the Sponsor and/or study sites and their family members may not be enrolled in 
this study.
3. Subjects must be willing and able to comply with procedures required in this protocol.
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Demographic and Laboratory Assessments
4. Adult male or female, at least 18 years old (subjects must also meet the legal age of majority 
per local law).
5. 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;

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 ≥ 1,500/µL;

Platelet count ≥ 100,000/µL;

Hemoglobin ≥ 10 g/dL (100 g/L);

Estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology 
Collaboration equation (eGFR [CKD-EPI]) ≥30 mL/min/1.73 m2.
Disease/Condition Activity
6. Male or female subject with a diagnosis of chronic plaque PsO with or without PsA, for at 
least 6 months prior to Baseline.
7. Stable moderate chronic plaque PsO at both Screening and Baseline as defined as:

BSA ≥10% and ≤ 15%,

PASI ≥12, and

sPGA = 3 (moderate) based on a 5-point scale (0 to 4).
8. PsO inadequately controlled disease by topicals, phototherapy and/or systemic treatments.
9. Subject must be a candidate for systemic therapy as assessed by the investigator.
Subject History
10. Subject is judged to be in good general health, as determined by the investigator based upon 
the results of a medical history, physical examination, laboratory profile, and a 12-lead 
electrocardiogram (ECG) performed during the Screening period.
11. Subject must not have any form of PsO other than chronic plaque PsO (e.g., pustular PsO, 
palmoplantar pustulosis, acrodermatitis of Hallopeau, erythrodermic, or guttate PsO).
12. Subject must not have a history of current drug-induced PsO or a drug-induced exacerbation 
of pre-existing PsO.
13. Subject must not have a history of active ongoing inflammatory skin diseases other than PsO 
and PsA that could interfere with the assessment of PsO (e.g., hyperkeratotic eczema).
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14. Subject must not have a history of severe renal insufficiency defined as creatinine clearance
< 30 mL/min and/or requiring hemodialysis or peritoneal dialysis.
15. Subject must not have a history of clinically significant (per investigator's judgment) drug or 
alcohol abuse within the last 6 months.
16. Subject must not have a history of an allergic reaction or significant sensitivity to 
constituents of the study drugs (and its excipients) and/or other products in the same class.
17. Subject must not have had 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 known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.  If 
a subject has signs/symptoms suggestive of SARS-CoV-2 infection, they should undergo 
molecular (e.g., polymerase chain reaction [PCR]) testing to rule out SARS-CoV-2 infection.  In 
addition, if based on the answers to the SARS-CoV-2 Infection Risk Assessment Tool the site 
considers the subject currently at risk for developing SARS-CoV-2 infection, then the subject 
should either be tested or advised to come back for study screening after 14 days.
Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may 
only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:

At least 14 days since first PCR test result have passed in asymptomatic patients or 14 days 
since recovery, defined as resolution of fever without use of antipyretics and improvement 
in symptoms.
19. Subjects must not have evidence of:
Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as:

HBV:  Hepatitis B surface antigen (HBs Ag) positive (+) test or detected sensitivity on the 
HBV DNA 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).
Human immunodeficiency virus (HIV), defined as confirmed positive anti-HIV Ab test.  Note:  
In case a screened subject has a confirmed positive HIV Ab test, Eligibility Criterion 10 
(Subject is judged to be in good general health criteria…) should be selected in electronic 
case report form (eCRF) for documentation of screening failure.
Active TB.  For subjects with latent TB, please see Section 3.13 of the Operations Manual.
Active systemic infection/Clinically important infection during the last 2 weeks prior to 
Baseline visit as assessed by the investigator.
20. Subjects must not have any of the following medical diseases or disorders:

Recent (within past 6 months) cerebrovascular accident or myocardial infarction;

History of an organ transplant which requires continued immunosuppression;
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
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.

Prior history of suicide attempt at any time in the subject's lifetime prior to signing the 
informed consent and randomization, or major depression or suicidal ideation or attempt 
requiring hospitalization within the last 3 years prior to signing the informed consent.

Hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose 
malabsorption.
21. Subject must not have concurrent clinically significant medical conditions other than the 
indication being studied or any other reason that the investigator determines would interfere 
with the subject's participation in this study, would make the subject an unsuitable candidate 
to receive study drug, or would put the subject at risk by participating in the study.
Contraception
22. 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 is 
required.
23. Risankizumab:

Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is effective from Study Day 1 through at least 140 days (20 weeks or as 
guided by the local risankizumab label [if approved], whichever is longer) after the last dose
of study drug (local practices may require 2 methods of birth control).  Female subjects of 
non-childbearing potential do not need to use birth control.

Female subjects may not be pregnant, breastfeeding, or considering becoming pregnant or 
donating eggs during the study or for approximately 140 days (20 weeks or as guided by the 
local risankizumab label [if approved], whichever is longer) after the last dose of study drug.
Apremilast:

Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is effective from Study Day 1 through at least 28 days (or as guided by 
the local apremilast label, whichever is longer) after the last dose of study drug (local 
practices may require 2 methods of birth control).  Female subjects of non-childbearing 
potential do not need to use birth control.

Female subjects may not be pregnant, breastfeeding, or considering becoming pregnant or 
donating eggs during the study or for approximately 28 days (or as guided by the local 
apremilast label, whichever is longer) after the last dose of study drug.
Concomitant Medications (Prior Medication Restrictions)
24. Subject must not have had any prior exposure to risankizumab or apremilast.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
25. Subject must not have received any live viral or bacterial vaccine within 4 weeks prior to the 
first dose of study drug, or expect the need for live vaccination during study participation 
including at least 140 days (20 weeks or as guided by the local risankizumab label [if approved], 
whichever is longer) after the last dose of risankizumab or at least 28 days after the last dose of 
apremilast.
26. Subject did not receive any systemic biologics to treat PsO for the following timeframes prior 
to the Baseline visit:

Etanercept (Enbrel®) and biosimilar versions within 3 weeks;

Certolizumab (Cimzia®), adalimumab (Humira®), ixekizumab (Taltz®), brodalumab 
(Siliq®/Kyntheum®), infliximab (Remicade®), and biosimilar versions within 10 weeks;

Ustekinumab (Stelara®) and guselkumab (Tremfya®) within 15 weeks;

Tildrakizumab (Ilumya™) and secukinumab (Cosentyx®) within 20 weeks.
27. Subject did not receive for at least 30 days prior to Baseline any: 

Other systemic immunomodulating treatments (including, but not limited to:  e.g., 
methotrexate, cyclosporine A, corticosteroids, cyclophosphamide, tofacitinib [Xeljanz®]);

Other systemic PsO treatments (e.g., retinoids, fumarates, any other drug known to possibly 
benefit PsO);

Photochemotherapy (e.g., psoralen and ultraviolet A radiation [PUVA]), phototherapy (e.g., 
ultraviolet B rays [UVB]) or prolonged exposure or use of tanning booths or ultraviolet light 
sources.
28. Subject must not have been treated with any investigational drug within 30 days or 5 half-
lives of the drug (whichever is longer) prior to the first dose of study drug or be currently 
enrolled in another interventional clinical study.
29. Subject did not receive for at least 14 days prior to Baseline any topical treatment for PsO or 
any other skin condition (including, but not limited to:  e.g., corticosteroids, vitamin D 
analogues, vitamin A analogues, pimecrolimus, retinoids, salicyl vaseline, salicylic acid, lactic 
acid, tacrolimus, tar, urea, or anthralin).
30. Subject must not be treated with any strong cytochrome P450 enzyme inducers (e.g., 
rifampin, phenobarbital, carbamazepine, phenytoin, St. John's Wort) within 30 days or 5 half-
lives of start of treatment with apremilast.
5.2 Contraception Recommendations
Contraception Requirements for Females
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:
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1.
Premenopausal female with permanent sterility or permanent infertility due to one of the 
following:

Permanent sterility due to a hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy;

Non-surgical permanent infertility due to Mullerian agenesis, androgen insensitivity, or 
gonadal dysgenesis; investigator discretion should be applied to determining study entry 
for these individuals.
2.
Postmenopausal, female:

Age > 55 years with no menses for 12 or more months without an alternative medical 
cause.

Age ≤ 55 years with no menses for 12 or more months without an alternative medical 
cause AND a follicle-stimulating hormone (FSH) level > 30 IU/L.

Females, of Childbearing Potential
Females of childbearing potential must avoid pregnancy while taking study drug and 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 risankizumab or 28 days (or as guided by the local 
apremilast label, whichever is longer) after the last dose of apremilast.  Females must 
commit to one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation-initiated at 
least 30 days prior to study Baseline Day 1.

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study Baseline Day 1.

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).

Intrauterine device.

Intrauterine hormone-releasing system.

Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the trial subject).

Practice true abstinence, defined as:  Refraining from heterosexual intercourse when 
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are 
not acceptable).
For those subjects who are re-randomized to risankizumab or are rescued with risankizumab, 
contraception guidelines for risankizumab apply.
If required per local practices, male or female condom with or without spermicide OR cap, diaphragm or 
sponge with spermicide should be used in addition to one of the birth control methods listed above 
(excluding true abstinence).
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
5.3 Prohibited Medications and Therapy
1.
During the study, no biologic treatment (including any biosimilar thereof) to treat moderate 
plaque PsO is allowed.  Exception:  Treatment with commercially available risankizumab after 
the Week 52/Premature Discontinuation (PD) assessments if this has been determined as an 
appropriate subsequent treatment by the investigator in discussion with the subject.
2.
Systemic (including oral or injectable administrations) non-biologic therapy that can be used to 
treat PsO, including but not limited to cyclosporine, corticosteroids, methotrexate, retinoids, 
and fumaric acid derivatives.  Exception:  Treatment with commercially available apremilast 
after the Week 52/PD assessments if this has been determined as an appropriate subsequent 
treatment by the investigator in discussion with the subject.
3.
Phototherapy treatment (UVB or ultraviolet A [UVA] phototherapy, including PUVA), laser 
therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere 
with disease assessments.
4.
Topical PsO treatments, including but not limited to corticosteroids, anthralin, calcipotriene, 
topical vitamin D derivatives, retinoids, urea, α- or β-hydroxyl acids, and medicated shampoos 
(for example those that contain corticosteroids, coal tar, or vitamin D3 analogues).
5.
All other investigational drugs and enrollment in another clinical study are prohibited.
6.
For subjects on apremilast:  strong cytochrome P450 enzyme inducers (e.g., rifampin, 
phenobarbital, carbamazepine, phenytoin, and St. John's Wort).
7.
Live attenuated vaccines (except non-replicating live vaccines, e.g., JYNNEOS monkeypox 
vaccine) 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 risankizumab or up to 28 days after the last dose of apremilast.
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)
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
Yellow fever

Dengue (Dengvaxia®)
5.4 Prior and 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.
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject has received from 4 weeks prior to Screening or receives during 
the study must be recorded along with the reason for use; date(s) of administration, including start and 
end dates; and dosage information including dose, route, and frequency on the appropriate electronic 
case report form (eCRF).
A detailed history of all prior biologic use will be obtained in the electronic data capture (EDC).
Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact.  Information regarding potential drug interactions with risankizumab and/or apremilast can be 
located in the risankizumab Investigator's Brochure8 or apremilast label.17,18
Subjects must be able to safely discontinue any prohibited medications (including biologics) 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.
Allowed Concomitant Medications/Therapy
Allowed concomitant medications and therapies include the following:

Moisturizers:  Provided that moisturizers (without active ingredients) have been used for at least 
2 weeks prior to Baseline (Day 1) and are anticipated to be continuously used at least until the 
Week 16 visit.  Subjects should not apply emollients within 8 hours prior to study assessments.

Only inhaled, ophthalmic, otic, or intranasal corticosteroids are permitted during the study.
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including 
but not limited to, the following:

The subject requests withdrawal from the study.

The investigator believes it is in the best interest of the subject.

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the Sponsor.
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
Subject is non-compliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.

Malignancy, except for localized NMSC or carcinoma in-situ of the cervix where discontinuation 
is at the discretion of the Investigator.

The subject becomes pregnant while on study drug.

Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk.

Introduction of prohibited medications or dosages when continuation of the study drug would 
place the subject at risk.

The investigator determines the subject is significantly noncompliant with study procedures.

Post-Baseline occurrence of new or worsening psychiatric symptoms, including suicidal ideation 
or a suicidal attempt.

Post-Baseline occurrence of one or more of the following hepatic abnormalities (confirmed on a 
second separate sample as least 48 hours apart):

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%).

Subjects who meet any of the above criteria should be evaluated for an alternative etiology 
of the ALT or AST elevation and managed as medically appropriate.  If applicable, the 
alternative etiology should be documented in the source documents. If after clinically 
appropriate evaluation, no alternative etiology for ALT or AST elevation is found or the ALT 
or AST elevation has not resolved or is not trending down toward normal, the subject should 
be discontinued from study drug.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at their site if they have 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.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The investigator should contact the sponsor medical contact before discontinuing a subject from the 
study for a reason other than described in the protocol, to ensure all acceptable mitigation steps have 
been explored.
Refer to the Operations Manual in Appendix F for details on how to handle study activities/procedures.
Interruption/Discontinuation of Study Drug Due to COVID-19 Infection
During the study drug dosing period, a subject with confirmed (viral test positive) or suspected COVID-
19 infection can only be dosed with study drug if the following COVID-19 viral clearance criteria are met:

At least 14 days since first positive test result have passed in asymptomatic patients or at least 
14 days since recovery, defined as resolution of fever without use of antipyretics and 
improvement in symptoms.
Delays in study drug dosing due to the above COVID-19 testing guidance for subjects must be discussed 
with the AbbVie medical contact, along with the possibility of premature discontinuation from the study 
drug dosing period.  Follow subsequent protocol Section 5.6 for subjects who discontinued study drug.
5.6 Follow-Up After Subject Discontinuation of Study Drug or from 
Study
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 the study participation entirely (withdrawal of informed consent).  Subjects 
should be advised on the continued scientific importance of their data even if they discontinue 
treatment with study drug early.
If, during the course of study drug administration, the subject prematurely discontinues study drug use, 
the subject has the option to continue in the study and complete the remaining visits as scheduled.  If 
remaining visits will be completed, a PD visit is not required.  If the subject does not continue in the 
study, the procedures outlined for the PD visit must be completed, ideally within 2 weeks of the decision 
and preferably prior to the initiation of another therapy.  However, these procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the Investigator feels 
are necessary to treat the subject's condition.
Following discontinuation of the study drug, the subject will be treated in accordance with the 
Investigator's best clinical judgment.
If a subject prematurely discontinues study participation (withdrawal of informed consent), the 
procedures outlined for the Premature Discontinuation visit (PD visit) should be completed as soon as 
possible, preferably within 2 weeks.  In addition, if subject is willing, a follow-up phone call 
approximately 140 days (20 weeks) after the last dose of risankizumab or approximately 28 days after 
the last dose of apremilast may be completed to ensure all treatment-emergent AEs/serious adverse 
events (SAEs) have been resolved.  The 140-day (20-week) or 28-day follow-up phone calls following the 
last dose of risankizumab or apremilast, respectively, during the trial will not be required for any subject 
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
who initiates commercially available risankizumab or apremilast upon or after the study Completion 
Visit (i.e., Week 52 or during the follow-up period) or PD visit.
If a subject withdraws from study follow up or withdraws permission for the collection of their personal 
data, the study staff may still use available public records to obtain information about survival status 
only, as appropriate per local regulations.
5.7 Study Drug
Study site staff will administer risankizumab (150 mg [1 × 1 mL 150 mg/mL pre-filled syringe]) 
subcutaneously or study staff will provide apremilast (30 mg [10 mg, 20 mg, 30 mg, film-coated tablets]) 
beginning at Baseline (Day 1) (Table 2).
Apremilast subject dosing (orally) will be recorded on a subject dosing diary.  The subject will be 
instructed to return all apremilast packaging (even if empty) to the study site personnel at each study 
visit.  The study site personnel will document compliance.
Table 2.
Identity of Investigational Product
Study Drug
Dosage Form
Strength
Route of 
Administration
Manufacturer
Risankizumab 
(ABBV-066)
Solution for 
injection in pre-
filled syringe (PFS)
150 mg (1x 1 mL 
150 mg/mL PFS)
Subcutaneous 
injection
AbbVie
Apremilast
Tablets
10 mg, 20 mg, 30 mg 
film-coated tablets
Oral
Amgen
AbbVie will not supply drug other than risankizumab and apremilast.  AbbVie provided study drugs 
should not be substituted or alternately sourced unless otherwise directed by AbbVie.
Open-label risankizumab and apremilast will be packaged in quantities sufficient to accommodate study 
design.  Each risankizumab kit or apremilast package will be labeled per local requirements and this label 
must remain affixed to the respective packaging.  Upon receipt, study drug should be stored as specified 
on the label in their original packaging and kept in a secure location.  A temperature log must be 
maintained for documentation.  Each kit or package will contain a unique kit or package number.  This 
number is assigned to a subject via interactive response technology (IRT) and encodes the appropriate 
study drug to be dispensed at the subject's corresponding study visit.  All blank spaces on the label will 
be completed by the site staff prior to dispensing to subjects.  Study drugs will only be used for the 
conduct of this study.
5.8 Randomization/Drug Assignment
All subjects will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who rescreen, the screening number assigned by the IRT at the initial screening visit should be 
used.  The IRT will assign a randomization number that will encode the subject's treatment group 
assignment according to the randomization schedule.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Study treatment duration includes Period A and Period B:

Period A (Baseline to Week 16):  Eligible subjects will be centrally randomized at the Baseline 
(Day 1) visit in a 1:2 ratio to receive either risankizumab 150 mg as a single SC injection (Arm 1) 
or apremilast orally with a dose titration from Day 1 to Day 5 and continuing with 30 mg BID 
until the day prior to Week 16 (Arm 2).  The randomization will be stratified by Baseline body 
weight (≤100 kg, > 100 kg) and prior exposure to any systemic and/or biologic treatment for 
PsO (0, ≥ 1).

Period B (Week 16 to Week 52):  Subjects initially randomized to apremilast (Arm 2) will be 
rerandomized at the Week 16 visit in a 1:1 ratio to receive either risankizumab 150 mg as a 
single SC injection (Arm 2a) or apremilast 30 mg orally BID (Arm 2b).  Rerandomization will be 
stratified by PASI 75 response (responder, non-responder) at Week 16.  Rescue risankizumab 
will be offered for subjects who are re-randomized to the apremilast arm and are PASI 50 non-
responders at Week 28 (Arm 3a) or Week 40 (Arm 3b).
This is an open-label study; however, the efficacy assessor will remain blinded to each subject's 
treatment, clinical laboratory results, and all subject safety data during the course of the study.
In the event of a medical emergency in which the Investigator believes that knowledge of study drug 
treatment is required for the efficacy assessor, reasonable efforts must be made to contact the AbbVie 
Emergency Contact.
The date and reason that the efficacy assessor's blind was broken must be recorded in the source 
documentation and eCRF, as applicable.
5.9 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all 
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified, including those that may be due to the COVID-19 pandemic), 
the investigator is responsible for notifying IEC/IRB, regulatory authorities (as applicable), and AbbVie.
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 the investigational 
products must be reported to AbbVie.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device damage or not 
working properly, or packaging issues.
Product complaints concerning the investigational products and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.
Reporting will be done via electronic data capture (EDC).  The date the product complaint details are 
entered into EDC and the form is saved represents the date reported to AbbVie.  A back-up paper form 
will be provided for reporting complaints related to unassigned product or in the event of an EDC system 
issue.  If a back-up paper form is used, the date the form is emailed to RD_PQC_QA@abbvie.com 
represents the date reported to AbbVie.
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. Product complaints occurring during the study will be followed 
up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events:  Study Drug
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
"special situations" such as accidental or intentional overdose, medication error, occupational or 
accidental exposure, off-label use, drug abuse, drug misuse, or drug withdrawal, all which must be 
reported whether associated with an AE or not.  Any worsening of a pre-existing condition or illness is 
considered an AE.  Worsening in severity of a reported AE should be reported as a new AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in discontinuation 
from the study, necessitate therapeutic medical intervention, and/or if the investigator considers them 
to be AEs.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and/or the surgery/procedure has 
been pre-planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
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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 an SAE within 24 hours of the site being made aware of 
the SAE (refer to Section 4.3 of the Operations Manual for reporting details and contact information):
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not been 
taken.  This does not include an event that would have been fatal if it 
had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length 
of time or prolongs the subject's hospital stay.  This does not include 
an emergency room visit or admission to an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with 
the activities of daily living of a study subject.  Disability is not 
intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle).
Important Medical Event 
Requiring Medical or Surgical 
Intervention to Prevent 
Serious Outcome
An important medical event that may not be immediately life-
threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life-threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent or 
significant disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event along with any suspected transmission of an 
infectious agent via a medicinal product if no other serious criterion 
is applicable.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or 
drug abuse.
All AEs reported from the time of risankizumab or apremilast administration until 140 days (20 weeks) 
after discontinuation of risankizumab administration or 28 days after discontinuation of apremilast 
administration will be collected, whether solicited or spontaneously reported by the subject.  After 
140 days (20 weeks) following the last dose of study drug or completion of study treatment only 
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spontaneously reported SAEs will be collected (nonserious AEs will not be collected.)  In addition, study 
procedure-related serious and nonserious AEs will be collected from the time the subject signs the 
study-specific informed consent.  If a subject prematurely discontinues study participation and begins 
commercially available risankizumab (Skyrizi) or apremilast (Otezla) all adverse events reported by 
healthcare professionals or the patient, will be captured as postmarketing reports.  The follow-up phone
call following the last dose of risankizumab during the study will not occur for subjects who begin 
commercially available risankizumab or apremilast.
The following definitions will be used for Serious Adverse Reactions (SAR) and Suspected Unexpected 
Serious Adverse Reaction (SUSAR):
SAR
Defined as all noxious and unintended responses to an Investigational Medicinal 
Product (IMP) related to any dose administered that result in an SAE as defined 
above.
SUSAR
Refers to individual SAE case reports from clinical trials where a causal 
relationship between the SAE and the IMP was suspected by either the sponsor 
or the investigator, is unexpected (not listed in the applicable Reference Safety 
Information [RSI]), and meets one of the above serious criteria.
AbbVie will be responsible for SUSAR reporting for the IMP in accordance with global and local 
requirements.
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk to subjects.
Areas of Safety Interest/Safety Topics of Interest
Infections, especially opportunistic infections, are a potential risk with immunomodulators.  Subjects will 
be screened and monitored throughout the study for Areas of Safety interest (ASI)/Safety Topics of 
Interest.  Screening procedures are outlined in the Activity Schedule (Appendix D).  In consideration of 
the ASI, the following supplemental eCRF(s) must be completed if AEs in any of the following areas are 
reported during the study (Table 3).
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Additionally, apremilast administration should be evaluated at any time during the study in the following 
circumstances:

Psychiatric disorders:  If subjects suffered from new or worsening psychiatric symptoms, or 
suicidal ideation or suicidal attempt is identified, it is recommended to discontinue treatment 
with apremilast.

Diarrhea, nausea, and vomiting: If patients develop severe diarrhea, nausea, or vomiting, 
discontinuation of treatment with apremilast may be considered.

Weight decrease: If unexplained or clinically significant weight loss occurs, evaluate weight loss 
and according to outcomes of the assessment, consider discontinuation of apremilast.
Adverse Event Severity and Relationship to Study Drug
Adverse events must be graded to the 5 criteria described in the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.19
Grades:  Grade refers to the severity of the AE.  The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this guideline:

Grade 1 (Mild); asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.

Grade 2 (Moderate); minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living.

Grade 3 (Severe); medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living.

Grade 4 (Severe); Life-threatening consequences; urgent intervention indicated.

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 24 hours after the site 
becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
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discontinued (Section 5.5).  If a pregnancy occurs in a study subject, information regarding the 
pregnancy and the outcome will be collected.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered an SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
6.2 Cardiovascular Adjudication Committee
An independent adjudication committee will adjudicate 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 Charter.  Dedicated eCRFs will be used as outlined in Table 3.
In addition, the site may be contacted for additional source documentation for relevant events.
6.3 Anaphylaxis Adjudication Committee
While no concerns with anaphylaxis/systemic hypersensitivity have been identified with the use of 
risankizumab, the sponsor has established an independent, blinded, expert committee to adjudicate 
events of anaphylaxis based on pre-specified definitions.  This independent external Anaphylaxis 
Adjudication Committee (AAC) will adjudicate suspected anaphylactic reactions and will remain blinded 
to treatment allocation.  The event terms to be adjudicated and the adjudication process are detailed in 
the AAC Charter.  A supplemental Hypersensitivity Reactions Signs and Symptoms eCRF will be used to 
collect information pertinent to the events.  In addition, the site may be contacted for additional source 
documentation.
If a suspected systemic hypersensitivity reaction occurs at the investigative site, in addition to testing 
tryptase and histamine levels, PK, and antidrug antibody (ADA)/neutralizing antibody (nAb) samples 
should also be collected.  If a systemic hypersensitivity reaction such as anaphylaxis is observed or 
reported while the subject is not at the investigative site, every effort should be made to obtain tryptase 
and histamine levels from the treating facility to help better characterize the diagnosis.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol will be focused on primary and ranked secondary 
analyses.  Complete and specific details of the statistical analysis will be described in the Statistical 
Analysis Plan (SAP).
The Primary Analysis for Period A will be conducted after all continuing subjects have completed 
Week 16 visit and the database is locked.  This will be the only and final analysis for the primary and 
secondary efficacy endpoints for Period A.
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The Primary Analysis for Period B will be conducted after all continuing subjects have completed 
Week 52 visit and the database is locked.  This will be the only and final analysis for the primary and 
secondary efficacy endpoints for Period B.
The final analysis will be conducted upon study completion.  The statistical analysis will be described and 
fully documented in the SAP.  All statistical tests will be performed at a two-sided alpha level of 0.05.  
The statistical analyses will be performed using SAS (SAS Institute Inc., Cary, North Carolina, USA).
7.2 Definition for Analysis Populations
The Intent to Treat Population in Period A (ITT_A) includes all randomized subjects.  The ITT_A 
Population will be used for all efficacy analyses in Period A.
The Intent to Treat Population for APRPASI75NRs in Period B (ITT_B_NR) includes subjects who are 
randomized at Baseline (Day 1), fail to achieve PASI 75 at Week 16, and are re-randomized.  The 
ITT_B_NR Population will be used for the analysis comparing switch-to-RZB (APR/RZB) versus continue-
with-APR (APR/APR) among APR-PASINRs in Period B.
The Intent to Treat Population for APR-PASI75 responders in Period B (ITT_B_R) includes subjects who 
are randomized to APR at Baseline, achieve PASI 75 at Week 16, and are re-randomized (APR-PASI75Rs).  
The ITT_B_R Population will be used for the summary of efficacy for APR/RZB and APR/APR among 
APR-PASI75Rs in Period B.
The Intent to Treat Population for Period B combined Population (ITT_B_Combined) includes subjects 
who are randomized to APR at Baseline and are re-randomized at Week 16.  The ITT_B_Combined 
Population will be used for combined analysis (APR-PASI75NRs and APR-PASI75Rs) between subjects 
re-randomized to APR/RZB and APR/APR in Period B.
The Intent to Treat Population for Long Term Efficacy (ITT_LT) includes subjects who are randomized to 
receive continuous RZB (i.e., all subjects randomized to RZB at Baseline) and subjects who are 
randomized and re-randomized to receive continuous APR, including half of the subjects randomized to 
APR at Baseline and prematurely discontinued from study before entering Period B.  The ITT_LT 
Population will be used for the analysis comparing long term efficacy between continuous treatment of 
RZB/RZB and APR/APR in Period B.
The Intent to Treat Population for Rescued Population (ITT_Res) includes subjects who are 
re-randomized to APR at Week 16, fail to achieve PASI 50 at Week 28 and Week 40, and receive RZB as 
the rescue medication.  The ITT_Res Population will be used for the summary of efficacy after being 
rescued with RZB.
Each ITT Population will have a corresponding Safety Population.  In addition, an all risankizumab 
treated (ALL_RZB) Population will be utilized for a comprehensive safety summary of RZB.  The ALL_RZB 
Population is defined as all subjects who receive at least one dose of RZB as the study drug.
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7.3 Handling Potential Intercurrent Events for the Primary and Key 
Secondary Endpoints
The co-primary endpoints (Section 3.2) and the ranked secondary endpoint (Section 3.3) in Period A will 
be analyzed in the ITT_A Population and subjects with the following intercurrent event will be 
considered as non-responders:

Subjects who receive alternative PsO treatment regardless of premature discontinuation of 
study drug before Week 16.
The primary endpoints (Section 3.2) and the ranked secondary endpoints (Section 3.3) in Period B will be 
analyzed in the ITT_B_NR Population and subjects with the following intercurrent event will be 
considered as non-responders:

Subjects who receive alternative PsO treatment regardless of premature discontinuation of 
study drug before Week 52.

Subjects who satisfy rescue criteria or receive the rescue medication at Week 28 or Week 40.
7.4 Statistical Analyses for Efficacy
Summary and Analysis of the Primary Endpoints
All statistical tests will be performed at a 2-sided alpha level of 0.05.
Analysis of the co-primary endpoints in Period A will be conducted among the ITT_A Population based 
on treatment as randomized.  The number and proportion (n, %) of subjects achieving the endpoints will 
be summarized within each treatment group.  Comparison of the proportion of responders for each 
co-primary endpoint will be made between the RZB and APR groups (i.e., adjusted difference, 95% CI, 
p-value) using the Cochran-Mantel-Haenszel (CMH) test adjusting for the actual values of stratification 
factors in the initial randomization at Baseline.
Analysis of the primary endpoint in Period B will be conducted among the ITT_B_NR Population based 
on treatment as re-randomized.  The number and proportion (n, %) of subjects achieving the endpoint 
will be summarized within each treatment group.  Comparison of the proportion of responders will be 
made between the APR/RZB and APR/APR groups (i.e., difference, 95% CI, p-value) using the Chi-square 
test.  Subjects who satisfy the rescue criteria at Week 28 or Week 40 or receive rescue medication in 
Period B will be counted as non-responders for the primary endpoint in Period B.
Non-Responder Imputation incorporating multiple imputation to handle missing data due to COVID-19 
(NRI-MI) will be used to handle missing data.
Summary and Analysis of Ranked Secondary Endpoints
Analysis of the ranked secondary endpoint in Period A will be conducted among the ITT_A Population 
based on treatment as randomized.  The number and proportion (n, %) of subjects achieving the 
endpoint will be summarized within each treatment group.  Comparison of the proportion of responders 
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will be made between RZB and APR groups (i.e., adjusted difference, 95% CI, p-value) using the CMH test 
adjusting for the actual values of stratification factors in the initial randomization at Baseline.
Analysis of the ranked secondary endpoints in Period B will be conducted among the ITT_B_NR 
Population based on treatment as rerandomized.  The number and proportion (n, %) of subjects 
achieving the endpoint will be summarized within each treatment group.  Comparison of the proportion 
of responders will be made between APR/RZB and APR/APR groups (i.e., difference, 95% CI, p-value) 
using the Chi-square test.  Subjects who satisfy the rescue criteria at Week 28 or Week 40 or receive 
rescue medication will be counted as non-responders for the ranked secondary endpoints in Period B.
NRI-MI will be used to handle missing data.
Summary and Analysis of Additional Efficacy Endpoints
Additional binary endpoints will be analyzed among each Population as follows:

Comparison of additional endpoints among the ITT_A and ITT_LT Populations will be made using 
CMH test adjusting for the actual values of stratification factors in the initial randomization at 
Baseline.  NRI-MI will be used to handle missing data.

Comparison of additional endpoints among the ITT_B_NR Population will be made using 
Chi-square test.  NRI-MI will be used to handle missing data.

Comparison of additional endpoints among the ITT_B_Combined Population will be made using 
CMH test adjusting for the actual value of the stratification factor in the re-randomization at 
Week 16.  NRI-MI will be used to handle missing data.

Summary statistics will be provided for additional endpoints among the ITT_B_R Population.  
NRI-MI will be used to handle missing data.

Summary statistics will be provided for additional endpoints among the ITT_Res Population, 
based on Observed Cases (OC).
Additional continuous endpoints will be analyzed among each Population as follows:

Comparison of additional endpoints on ITT_A and ITT_LT Population will be made based on the 
fixed term of treatment from a Mixed-effect Model Repeat Measurement (MMRM), adjusting 
for treatment, actual values of stratification factors and Baseline value if applicable (if not 
duplicating the stratification factors).

Comparison of additional endpoints on ITT_B_NR Population will be made based on the fixed 
term of treatment from a MMRM, adjusting for treatment and Baseline value.

Comparison of additional endpoints among the ITT_B_Combined Population will be made based 
on the fixed term of treatment from a MMRM, adjusting for treatment, actual values of 
stratification factors in the re-randomization at Week 16 and Baseline value.

Summary statistics will be provided for additional endpoints among the ITT_B_R Population, 
based on the fixed term of treatment from a MMRM, adjusting for treatment and Baseline 
value.
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
Summary statistics will be provided for additional endpoints among the ITT_Res Population, 
based on OCs.
Subgroup Analysis for Efficacy
Subgroup analysis will be performed on co-primary endpoints in Period A using the following subgroups:

Age group:  < 40, ≥40 to < 65, ≥65

Sex (male, female)

Race (white, non-white)

Smoking (current, ex or never)

Body mass index (BMI) (normal:  < 25, overweight:  ≥25 to < 30, obese:  ≥30)

Baseline PASI score (by median)

Psoriatic arthritis (yes, no)

Prior systemic treatment (0, ≥1)
Age ≥65 years or BMI ≥30 subgroups will be combined with their adjacent subgroup when having fewer 
than 10% subjects.
7.5 Statistical Analyses for Safety
All safety analyses will be performed among the Safety Populations.  Subjects will be analyzed based on 
the first dose of treatment received after randomization or re-randomization.  A treatment-emergent 
adverse event (TEAE) in each analysis period is defined as follows:
A TEAE in Period A is defined as any AE with an onset date on or after the first dose of study drug in 
Period A and 
1.
within the minimum of 140 days after the last dose of RZB in Period A and first dose of study 
drug in Period B for subjects who receive RZB at Baseline and
2.
within the minimum of 28 days after the last dose of APR in Period A and first dose of study drug 
in Period B for subjects who receive APR at Baseline.
A TEAE in Period B is defined as any AE with an onset date on or after the first dose of study drug in 
Period B and 
1.
within 140 days after the last dose of RZB in Period B for subjects who receive RZB in Period B 
and
2.
within the minimum of 28 days after the last dose of APR in Period B, first dose of rescue 
risankizumab (if any) for subjects who receive APR in Period B.
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A TEAE during the administration of rescue risankizumab is defined as any AE with an onset date on or 
after the first dose of rescue risankizumab and within 140 days after the last dose of rescue 
risankizumab.
A TEAE during the administration of risankizumab (i.e., among the ALL_RZB Population) is defined as any 
AE with an onset date on or after the first dose of RZB and within 140 days after the last dose of RZB.
The number and percentage of subjects experiencing TEAEs will be tabulated using the Medical 
Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term, by severity, and 
by relationship to the study drug as assessed by the investigator.  Summaries (including percentages and 
events per 100 PYs) of SAEs, deaths, and AEs leading to discontinuation of study drug will be provided as 
well. Pre-treatment SAEs will be summarized separately.
For selected lab parameters, a listing of all subjects with any laboratory value that is above Grade 3 of 
Common Toxicity Criteria will be provided. Mean change in laboratory and vital signs variables will be
summarized. Additional details for the safety analysis are provided in the SAP.
7.6 Interim Analysis
No interim analysis is planned for this study.
7.7 Overall Type I Error Control
Overall type-I error for Period A will be controlled by testing the co-primary endpoints, followed by the 
ranked and only secondary endpoint, in a hierarchical order as described in Section 3.2 and Section 3.3.
Overall type-I error for Period B will be controlled by testing the primary endpoint, followed by the 
ranked secondary endpoints, in a hierarchical order as described in Section 3.2 and Section 3.3.
7.8 Sample Size Determination
This study plans to enroll a total of N = 330 subjects, to be sufficiently powered to detect the treatment 
difference between RZB and APR with respect to the co-primary endpoints in Period A, as well as 
between APR/RZB and APR/APR with respect to the primary endpoint in Period B:

Assuming that 50% of APR-PASI75NR subjects in the APR/RZB group and 20% of APR-PASI75NR 
subjects in the APR/APR group will achieve PASI 90 at Week 52 in Period B, the sample size of 
120 re-randomized APR-PASI75NR subjects (60 subjects per group) will have more than 90%
power to detect the treatment difference between APR/RZB and APR/APR, using a Chi-square 
test with a 2-sided significance level of 0.05.

Assuming 55% of subjects initially randomized to APR will be re-randomized at Week 16 under 
the APR-PASI75NR (as defined by the PASI 75 response at Week 16) stratum, the total sample 
size for the initial APR group is 120/55% = 220.  Assuming the treatment difference is at least 
40% with respect to the co-primary endpoints of PASI 90 and sPGA of 0 or 1 at Week 16 in 
Period A, the total sample size of N = 330 subjects (RZB:  110, APR:  220) will also provide more 
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than 90% power to detect the treatment difference between RZB and APR, using a Chi-square 
test with a 2-sided significance level of 0.05.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study 
conduct and the ethical principles that have their origin in the Declaration of Helsinki.  Responsibilities of 
the investigator are specified in Appendix B.
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.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
Supplemental study case report forms should be completed in the event of COVID-19 related 
missed/virtual visits, study drug interruptions or discontinuations, or AEs (including capture of specific 
signs/symptoms of infection and testing results).
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 and geo-political conflict in Ukraine and surrounding 
impacted regions, remote monitoring of data may be employed if allowed by the local regulatory 
authority, IRB/IEC, and the study site.
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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
START AND COMPLETION OF THE STUDY
The start-of-study is defined as the date of the first site activated.
The end-of-study is defined as the date of end of study participation by the last subject in the last 
country where the study was conducted.
12
REFERENCES
1.
World Health Organization. Global report on psoriasis. Geneva, Switzerland: WHO; 2016 [cited 2017 
Sep 17]. Available from: http://apps.who.int/iris/handle/10665/204417.
2.
Menter A, Griffiths CE. Current and future management of psoriasis. Lancet. 2007;370(9583):272-84.
3.
Helmick CG, Lee-Han H, Hirsch SC, et al. Prevalence of psoriasis among adults in the U.S.: 2003-2006 
and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47(1):37-
45.
4.
Mease PJ, Gladman DD, Papp KA, et al. Prevalence of rheumatologist-diagnosed psoriatic arthritis in 
patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol. 
2013;69(5):729-35.
5.
Davidovici BB, Sattar N, Prinz J, et al. Psoriasis and systemic inflammatory diseases: potential 
mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol. 
2010;130(7):1785-96.
6.
Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe 
plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-
controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-61.
7.
Reich K, Gooderham M, Thaci D, et al. Risankizumab compared with adalimumab in patients with 
moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-
controlled phase 3 trial. Lancet. 2019;394(10198):576-86.
8.
AbbVie. Risankizumab Investigator's Brochure Edition 6. 11 May 2020.
9.
Warren RB, Blauvelt A, Poulin Y, et al. Efficacy and safety of risankizumab vs. secukinumab in 
patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, 
open-label, efficacy-assessor-blinded clinical trial. Br J Dermatol. 2021;184(1):50-9.
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10. 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.
11. O'Garra A, Redford PS, McNab FW, et al. The immune response in tuberculosis. Annu Rev Immunol. 
2013;31:475-527.
12. 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.
13. 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.
14. 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.
15. Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature. 
2006;442(7101):461-5.
16. AbbVie. Data on File, RRT165055.
17. Otezla (apremilast) [US Prescribing Information]. Thousand Oaks, CA: Amgen Inc.; 2020.
18. Agency EM. Otezla (apremilast) [SmPC]. Thousand Oaks, CA: Amgen Inc.; 2020.
19. US Department of Health and Human Services NIoH, National Cancer Institute. Common 
Terminology Criteria for Adverse Events (CTCAE) Version 5.0 2017 [cited 10 Feb 2020]. Available 
from: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer
ence_8.5x11.pdf.
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APPENDIX A. STUDY-SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AAC
Anaphylaxis Adjudication Committee
Ab
Antibody
ADA
Antidrug antibody
AE
Adverse event
ALL_RZB
All risankizumab treated population
ALT
Alanine aminotransferase/transaminase
APR
Apremilast
APR-PASI75NR
Apremilast PASI75 non-responders
APR-PASI75R
Apremilast PASI75 responders
ASI
Areas of safety interest/adverse events of safety interest
AST
Aspartate aminotransferase/transaminase
BCG
Bacille Calmette-Guérin
BID
Twice daily
BMI
Body mass index
BSA
Body surface area
CAC
Cardiovascular Adjudication Committee
CBC
Complete blood count
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CMH
Cochran-Mantel-Haenszel
COVID-19
Coronavirus disease of 2019
CTCAE
Common Terminology Criteria for Adverse Events
DLQI
Dermatology Life Quality Index
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
eGFR
Estimated glomerular filtration rate
FSH
Follicle-stimulating hormone
GCP
Good clinical practice
HB
Hepatitis B
HBV
Hepatitis B virus
HCV
Hepatitis C virus
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HIV
Human immunodeficiency virus
IB
Investigator's Brochure
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IEC
Independent ethics committee
Ig
Immunoglobin
IGRA
Interferon gamma release assay
IL-23
Interleukin-23
IMP
Investigational Medicinal Product
INR
International normalized ratio
IRB
Institutional review board
IRT
Interactive response technology
ITT
Intent to treat
ITT_A
Intent to Treat Population in Period A
ITT_B_Combined
Intent to Treat Population for Period B combined Population
ITT_LT
Intent to Treat Population for Long-term Efficacy
ITT_Res
Intent to Treat Population for Rescued Population
MACE
Major adverse cardiovascular events
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed-effect Model Repeat Measurement
nAb
Neutralizing antibody
NAPSI
Nail Psoriasis Severity Index
NCI
National Cancer Institute
NMSC
Non-melanoma skin cancer
NRI-MI
Non-Responder Imputation incorporating multiple imputation
OC
Observed case
PASI
Psoriasis Area and Severity Index
PCR
Polymerase chain reaction
PD
Premature Discontinuation
PFS
Pre-filled syringe
PK
Pharmacokinetic(s)
PPD
Purified protein derivative (tuberculin)
ppIGA
Palmoplantar Investigator's Global Assessment
PRO
Patient-reported outcome
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PsA
Psoriatic arthritis
PsO
Psoriasis
PSS
Psoriasis Symptoms Scale
PSSI
Psoriasis Scalp Severity Index
PT
Preferred term
PY
Patient year
q12w
Every 12 weeks
QTcF
QT interval corrected for heart rate using Fridericia's formula
RSI
Reference Safety Information
RZB
Risankizumab
SAE
Serious adverse event
SAP
Statistical analysis plan
SAR
Serious adverse reaction
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SC
Subcutaneous
SOC
System organ class
sPGA
Static Physician Global Assessment
SUSAR
Suspected unexpected serious adverse reactions
TA MD
Therapeutic Area Medical Director
TB
Tuberculosis
TEAE
Treatment emergent adverse event
TSQM-9
Treatment Satisfaction Questionnaire for Medication version 9
ULN
Upper limit of normal
US
United States
WPAI
Work Productivity and Activity Impairment
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STUDY M20-326  |  Version 2.0  |  EudraCT 2020-005512-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M20-326:  A Phase 4 Multicenter, Randomized, Open-label, Efficacy Assessor-blinded Study of 
Risankizumab Compared to Apremilast for the Treatment of Adult Subjects with Moderate Plaque Psoriasis who 
are Candidates for Systemic Therapy
Protocol Date:  10 November 2022
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practices (GCP) and local laws and 
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, (within 1 calendar day) to AbbVie, the ethics committees/institutional review boards 
(as required) and other appropriate individuals (e.g., coordinating investigator, institution director): 

All changes in the research activity and all unanticipated problems involving risks to human subjects 
or others

Rights, safety, physical or mental integrity of the subjects in the clinical trial

Scientific value of the clinical trial, reliability or robustness of data generated
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
Therapeutic Area Medical Director
Medical Affairs, Immunology
Director, Statistics
Data and Statistical Sciences
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STUDY M20-326  |  Version 2.0  |  EudraCT 2020-005512-21
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APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities across the subject encounters.  The individual activities 
are described in detail in the Operations Manual.  Allowed modifications due to COVID-19 and/or the 
geo-political conflict in Ukraine and surrounding impacted regions are detailed within the Operations 
Manual.
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STUDY M20-326  |  Version 2.0  |  EudraCT 2020-005512-21
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
BSA = body surface area; CBC= complete blood count; ECG = electrocardiogram; FSH = follicle-stimulating hormone; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; IGRA = interferon gamma release assay; IRT = interactive response technology; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity 
Index; PPD = purified protein derivative (tuberculin); ppIGA = Palmoplantar Investigator's Global Assessment; PSSI = Psoriasis Scalp Severity Index; SARS-CoV-2 = Severe acute 
respiratory syndrome coronavirus 2; sPGA = static Physician Global Assessment; TB = tuberculosis; US = United States
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STUDY M20-326  |  Version 2.0  |  EudraCT 2020-005512-21
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
29 March 2021
Administrative Change 1
15 April 2021
Administrative Change 2
17 February 2022
The purpose of Protocol Version 2.0 is to capture Administrative Changes 1 and 2, and update text for 
Primary Analysis for Period B. Administrative Change 1, which changed the study phase from Phase 4 to 
Phase 3b, was not incorporated into Protocol Version 2.0. The study drug, risankizumab 150 mg/ml, has 
now been approved in all study countries, and the study phase is re-confirmed as Phase 4.
Protocol Version 2.0 also incorporates necessary protocol modifications in the protocol template and 
new safety information as follows:
Protocol

Text was updated throughout the Protocol to align with revisions in the protocol template and 
changes due to new safety information available.

Protocol sections include:  Section 2.2, Section 4.1, Section 5.1, Section 5.4, Section 5.5, 
Section 5.6, Section 6.1, Section 9, Section 11, Appendix B, Appendix C, Appendix D, and
Appendix E.

Protocol Section 7.1: added the interim lock for primary analysis for Period B.

Administrative Change 2: Update the Sponsor/Emergency Medical Contact information to 
 as Sponsor/Emergency Medical Contact.

Rationale:  Reflects a change in the Sponsor/Emergency Medical Contact for the study.
Operations Manual

Text was updated throughout the Operations Manual to align with revisions in the Operations 
Manual template and changes due to new safety information available.

Operations Manual sections include:  Section 1, Section 2.1, Section 3.1, Section 3.12, 
Section 3.13, Section 4.1, Section 4.3, Section 6.3, and Section 8.7.

Administrative Change 2: Update the Sponsor/Emergency Medical Contact information to 
 as Sponsor/Emergency Medical Contact.

Rationale:  Reflects a change in the Sponsor/Emergency Medical Contact for the study.
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