Clinical trial NCT03875482
Conditions: Psoriasis
Keywords: Risankizumab Psoriasis Plaque Psoriasis
Sponsor: AbbVie
Start date: 2019-05-13; Completion date: 2020-07-15
Enrollment: 157 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study was to evaluate the safety and efficacy of risankizumab (150 mg/mL) administered by prefilled syringe (PFS) for the treatment of adult participants with moderate to severe plaque psoriasis.

Detailed description:
This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of risankizumab 150 mg/mL formulation in PFS in adult participants with moderate to severe plaque psoriasis. The study included a 30-day screening period, a 28-week treatment period with study visits at Weeks 0, 4, 16 and 28, and a subsequent follow-up telephone call at approximately 20 weeks after the last dose of study drug. Study drug dosing consisted of 3 self-administered, subcutaneous (SC) doses on Weeks 0, 4, and 16. Dosing on Week 4 was self-administered at home.

Arms: arm 1: Subcutaneous (SC), self-administered 150 mg doses of risankizumab at Weeks 0, 4, and 16 arm 2: Subcutaneous (SC), self-administered doses of placebo solution at Weeks 0, 4, and 16
Interventions: intervention 1: Risankizumab intervention 2: Placebo solution for risankizumab
Intervention descriptions: intervention 1: Risankizumab 150 mg (150 mg/mL) in prefilled syringes, self-administered subcutaneously intervention 2: Placebo solution in prefilled syringes, self-administered subcutaneously

Protocol documents:
Prot_000.pdf: 
NCT03875482


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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
7
2.1
BACKGROUND AND RATIONALE
7
2.2
BENEFITS AND RISKS TO SUBJECTS
7
3
STUDY OBJECTIVES AND ENDPOINTS
9
3.1
OBJECTIVE
9
3.2
PRIMARY ENDPOINT
9
3.3
SECONDARY ENDPOINTS
9
3.4
ADDITIONAL ENDPOINTS
9
3.5
SAFETY ENDPOINTS
10
3.6
PHARMACOKINETIC ENDPOINTS
10
3.7
BIOMARKER RESEARCH
10
4
INVESTIGATIONAL PLAN
10
4.1
OVERALL STUDY DESIGN AND PLAN
10
4.2
DISCUSSION OF STUDY DESIGN
12
5
STUDY ACTIVITIES
13
5.1
ELIGIBILITY CRITERIA
13
5.2
CONTRACEPTION RECOMMENDATIONS
15
5.3
PROHIBITED MEDICATIONS AND THERAPY
16
5.4
PRIOR AND CONCOMITANT THERAPY
18
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
18
5.6
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
19
5.7
STUDY DRUG
19
5.8
RANDOMIZATION/DRUG ASSIGNMENT
20
5.9
PROTOCOL DEVIATIONS
20
6
SAFETY CONSIDERATIONS
20
6.1
COMPLAINTS AND ADVERSE EVENTS
20
6.2
CARDIOVASCULAR ADJUDICATION COMMITTEE
24


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6.3
ANAPHYLAXIS ADJUDICATION COMMITTEE
24
6.4
PRODUCT COMPLAINT
25
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
25
7.1
STATISTICAL AND ANALYTICAL PLANS
25
7.2
DEFINITION FOR ANALYSIS POPULATIONS
25
7.3
STATISTICAL ANALYSES FOR EFFICACY
25
7.4
STATISTICAL ANALYSES FOR SAFETY
26
7.5
ANALYSES OF PK AND IMMUNOGENICITY
26
8
ETHICS
27
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
27
8.2
ETHICAL CONDUCT OF THE STUDY
27
8.3
SUBJECT CONFIDENTIALITY
27
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
27
10 DATA QUALITY ASSURANCE
27
11 COMPLETION OF THE STUDY
28
12 REFERENCES
28
LIST OF TABLES
TABLE 1.
DESCRIPTION OF STUDY DRUG AND PLACEBO
19
TABLE 2.
ADVERSE EVENTS THAT REQUIRE SUPPLEMENTAL REPORTS
23
TABLE 3.
STUDY ACTIVITY SCHEDULE
34
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMATIC FOR PROTOCOL M15-999
11
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
29


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APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
31
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
32
APPENDIX D.
ACTIVITY SCHEDULE
33
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
37
APPENDIX F.
OPERATIONS MANUAL
38






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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted
Risankizumab is a fully humanized mAb of the immunoglobin G1 subclass directed towards interleukin 
(IL)-23p19.  The antibody has been engineered to reduce Fcγ receptor and complement binding and 
potential charge heterogeneity.  Risankizumab binds with high affinity to human IL-23.
Positive results were observed from 4 pivotal Phase 3 clinical trials that evaluated risankizumab 
compared with ustekinumab, placebo, and adalimumab for the treatment of patients with moderate to 
severe plaque psoriasis.  Results from these pivotal studies demonstrated that risankizumab is highly 
effective for the treatment of psoriasis, meeting co-primary endpoints of achieving at least a 90% 
improvement in the Psoriasis Area and Severity Index (PASI 90) and static physician global assessment 
(sPGA) score of clear or almost clear (0 or 1) versus comparator or placebo at Week 16 across all 
4 studies.1
In the pivotal Phase 3 clinical trials, the risankizumab 150-mg dose was administered with a 90-mg/mL 
formulation via 2 subcutaneous (SC) 75-mg injections delivered with a pre-filled syringe (PFS).  To deliver 
a more patient-friendly experience, a new formulation was developed at 150 mg/mL that will enable 
delivery of the 150 mg dose with one SC injection.  This study will evaluate the new 150-mg single 
injection formulation of risankizumab versus placebo using the same dosing regimen and delivery 
method (PFS) of risankizumab and same co-primary endpoints used in the Phase 3 pivotal trials.
Clinical Hypothesis
The primary null hypothesis of this study is that risankizumab is not different from placebo with respect 
to either achieving PASI 90 or achieving sPGA of clear or almost clear at Week 16.
2.2 Benefits and Risks to Subjects
In Phase 1 and Phase 2 studies of risankizumab in patients with psoriasis, the majority of subjects 
receiving risankizumab achieved 90% improvement of their disease, and risankizumab was well 
tolerated.  As with many immune modulating agents, risankizumab may impair immune function 
resulting in a risk of infection.  This will be monitored by collection of all adverse events (AEs) during the 
treatment and observation periods.  In addition, subjects with active infection will not be included in the 
study.
Subjects with a positive QuantiFERON®-test or a positive Purified Protein Derivative (PPD) skin test for 
tuberculosis (TB) must fulfill entry criteria as specified in Section 5.1 of this protocol.  Interleukin-23 
inhibition is not known to increase the risk of TB infection or impair the response to TB infection in 
animal models.2,3  There have been no cases of active tuberculosis, including no reactivation of 
tuberculosis in subjects diagnosed with latent TB, across the entire risankizumab development program.  
Across the Phase 3 psoriasis clinical studies, of the 72 subjects with latent TB who were concurrently 
treated with risankizumab and appropriate TB prophylaxis during the study, none developed active TB 
during a mean follow-up of 61 weeks on risankizumab.  Of the 33 subjects in Study M15-992 with a 


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positive test for latent TB and who did not receive prophylaxis during the study, none developed active 
TB during the mean follow-up of 77 weeks on risankizumab. 
Thus, low risk subjects with positive QuantiFERON testing do not need to be treated with 
anti-tuberculosis therapy prior to receiving risankizumab, but should be carefully monitored for any sign 
of TB reactivation.  Absence of TB reactivation, despite not receiving anti-tuberculosis prophylaxis, will 
provide important information in humans as to whether TB testing is required prior to treatment with 
risankizumab.4
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.  Preclinical data have moreover demonstrated 
beneficial effect of IL-23 p19 inhibition in animal models, both for pre-existing and tumor-induction 
models.  However, there is not enough clinical information at this time to rule out a risk of cancer with 
risankizumab, but this risk is considered small.
Although rare, a potential for hepatic adverse events is under constant surveillance by sponsors and 
regulators.  Therefore, this study requires timely detection, evaluation, and follow-up of laboratory 
alterations in selected liver laboratory parameters to ensure subjects' safety.
Increases in major adverse cardiovascular events (MACE) including myocardial infarction, 
cerebrovascular accident, and cardiovascular death, reported initially with anti-IL-12/23 agents, such as 
ustekinumab, have not been observed in longer term studies.  While the likelihood of increased MACE is 
small, all suspected cardiovascular events (serious or nonserious) observed in this study will be 
adjudicated by an independent adjudication committee.  An independent Cardiovascular Adjudication 
Committee will adjudicate all observed cardio- and cerebro-vascular events and will remain blinded to 
treatment allocation (Section 6.2).
Injection-site reactions to biologic therapies may be characterized by redness, swelling, or induration at 
the injection site.  Manifestations of anaphylaxis may include pruritus, hypotension, swollen lips and 
tongue, abdominal pain, and respiratory distress.  Both local and systemic hypersensitivity reactions and 
anaphylaxis are readily detectable, transient in nature, and manageable with standard medical 
treatment.  Subjects will be closely monitored on site during study drug administration at Weeks 0 and 
16.  The duration of the post-drug-administration safety surveillance is 2 hours post-first dose and 
1 hour postdose at Week 16.  Subjects will be given instructions regarding management of signs and 
symptoms of anaphylaxis to be followed during home dosing at Week 4.  An independent Anaphylaxis 
Adjudication Committee (AAC) will adjudicate suspected anaphylactic reactions.  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.  Based on data from the integrated safety analyses, risankizumab is safe and 
well-tolerated and demonstrates a favorable benefit-risk profile.  For further details, please see findings 
from completed studies, including safety data in the risankizumab Investigator Brochure.1


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3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objective
The objective of this study is to evaluate the efficacy and safety of the 150 mg/mL formulation of 
risankizumab in a PFS compared with placebo for the treatment of adult subjects with moderate to 
severe plaque psoriasis.
3.2 Primary Endpoint
The co-primary endpoints of this study are: 
1.
Proportion of subjects achieving PASI 90 (defined as at least 90% improvement from baseline in 
PASI) at Week 16
2.
Proportion of subjects achieving sPGA of clear or almost clear at Week 16.
3.3 Secondary Endpoints
Key Secondary Endpoints: 
The following ranked secondary endpoints will be tested between risankizumab and placebo in a 
hierarchical order only if the null hypotheses for the primary endpoints have been rejected:
1.
Proportion of subjects achieving PASI 100 (defined as 100% improvement from baseline in PASI) 
at Week 16
2.
Proportion of subjects achieving sPGA of clear at Week 16.
3.4 Additional Endpoints
All primary and key secondary endpoints will be analyzed at all other visits collected. In addition, the 
following endpoints will be analyzed in all visits collected.
!
Proportion of subjects achieving PASI 50/75
!
Change and percent change from baseline in PASI
The following usability endpoints will also be summarized, for each treatment arm, at all visits collected.
!
Proportion of subjects with an observer rating of successful subject self-administration, defined 
as any subjects who successfully completed the sequence of 3 critical steps in the Instructions 
for Use (IFU) without errors to administer study drug 
!
Proportion of subjects who experienced no potential hazards as measured by an observer 
!
Subject rating of acceptability using the Self-Injection Assessment Questionnaire (SIAQ) 


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3.5 Safety Endpoints
Safety evaluations include AE monitoring, physical examinations, vital sign measurements, and clinical 
laboratory testing (hematology and chemistry) as measures of safety and tolerability.
3.6 Pharmacokinetic Endpoints
Serum risankizumab concentrations and anti-drug antibodies (ADA), and neutralizing antibodies (nAb) 
will be determined at the visits indicated in the Study Activities Table (Appendix D).  Serum risankizumab 
concentrations will be summarized at Week 16, using descriptive statistics.  ADA titers will be tabulated 
for each subject by regimen at the respective study visits.  The number and percentage of subjects with 
ADA and NAb by regimen will be calculated.
3.7 Biomarker Research
Optional blood samples for exploratory biomarker research will be collected as described in the Study 
Activities Table (Appendix D).  The objective of biomarker research is to analyze samples that will help 
understand psoriasis or related conditions and the subject's response to risankizumab.  Prognostic, 
surrogate, predictive and pharmacodynamics biomarkers signatures may be investigated.  Samples for 
different applications, potentially including but not limited to pharmacogenetic, epigenetic, 
transcriptomic, proteomic, metabolomic, metagenomic, phenotypic, functional and targeted 
investigations will be collected at various time points.  Assessments may include but may not be limited 
to nucleic acids, proteins, metabolites, lipids, or peripheral blood mononuclear cells (PBMC).  AbbVie (or 
people or companies working with AbbVie) will store the biomarker exploratory biomarker samples in a 
secure storage space with adequate measures to protect confidentiality.  The samples will be retained 
while research on risankizumab (or drugs of this class) or this disease and related conditions continues, 
but for no longer than 20 years after study completion.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study that will 
evaluate the safety and efficacy of risankizumab 150 mg/mL formulation in PFS in patients with 
moderate to severe plaque psoriasis.  The study includes a 30-day screening period, a 28-week 
treatment period with study visits at Weeks 0, 4, 16 and 28, and a subsequent follow up telephone call 
at approximately 20 weeks after the last dose of study drug.  Study drug dosing will consist of 3 self-
administered doses given subcutaneously on Weeks 0, 4, and 16.  Dosing on Week 4 will be self-
administered at home.  Efficacy and safety will be assessed throughout at the Visits described in Study 
Activities Table (Appendix D).
The schematic of the study is shown in Figure 1.


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Figure 1.
Study Schematic for Protocol M15-999
If an exclusionary laboratory result is obtained at the initial Screening Visit, one re-test of that particular 
test is allowed without repeating all other laboratory tests within the 30 day screening window.
Subjects who initially do not meet all eligibility criteria for the study may be permitted to repeat the 
Screening Visit one time following re-consent.  The subject must meet all eligibility criteria on the repeat 
Screening Visit in order to qualify for the study.  The repeat screening procedure is:
!
A repeat of all screening procedures is needed at this repeat Screening Visit with these 
exceptions: 
!
If the subject had a complete initial screening evaluation, including the assessment of an 
Interferon-Gamma Release Assay (IGRA; QuantiFERON Tuberculosis [TB] Gold In Tube test) 
or a PPD test (or equivalent), and electrocardiogram (ECG), these tests will not be required 
to be repeated at the repeat Screening Visit.
!
There is no minimum period of time a subject must wait prior to the repeat Screening Visit. 
Subjects will be instructed at Week 0 (pre-injection) by the site staff on how to self-inject via the PFS.  
Self-injections will be administered into one of the following body regions, changing the injection site if 
possible at each timepoint:  right thigh, left thigh, right abdominal area, left abdominal area. 


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At Week 0 (after training) and Week 16, subjects will be instructed by site staff to refer to the IFU and 
proceed with self-injection.  At the Week 4 Visit, subjects will be sent home with one PFS to be 
self-administered within 24 hours of the Week 4 Visit with instructions from the site staff to use the IFU.  
The Week 0 and Week 16 usability assessments will take place in the context of an observed assessment 
under the supervision of one site staff member.  Each assessment is to be conducted on a 1:1 basis.  The 
observer (site staff member) will measure and evaluate the subject's usability of the PFS using the 
self-injection assessment checklist as they observe the injections at Week 0 and Week 16.  Site staff will 
also assess potential hazards with a predefined potential use hazards checklist for self-injections at 
Week 0 and Week 16.  During the self-injection, if a subject is not acting in a safe or reasonable manner, 
the observing site staff member is required to intervene.  Use errors, which could pose a risk to the 
health or well-being of a subject, require the observing staff member to ask the subject to pause, to 
point out the use error, and to decide whether to terminate the self-injection.  If the observing site staff 
judges the self-injection can continue, they should correct the subject's usage of the product and notify 
the subject to recommence at the same point.  These errors will be documented from the list of 
potential use hazards.  Any risk of a health and safety incident could result in termination of the self-
injection at the discretion of the observing site staff member. 
Subject-derived usability assessment will measure acceptability of the PFS using the SIAQ.  Subjects will 
fill out the SIAQ PRE module immediately before the first self-injection at Week 0 and the POST module 
20 to 40 minutes following self-injections at Week 0, Week 4, and Week 16.  These modules are to be 
completed by subjects while alone in a quiet environment.  The subject's self-rated assessment of each 
item of the SIAQ, will be transformed during analysis to scores ranging from 0 (worst experience) to 10 
(best experience).
4.2 Discussion of Study Design
Choice of Control Group
Placebo control will be used in this study to address potential confounding factors, such as placebo 
effect, potential investigator bias in safety and efficacy assessment, or regression to the mean in 
endpoint scoring.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All efficacy 
measurements in this study are standard for assessing disease activity in subjects with plaque psoriasis.  
All clinical and laboratory procedures in this study are standard and generally accepted.
The SIAQ evaluates patients' experiences with self-injection and enables assessment of their success in 
giving self-injections and the likelihood of them adhering to a self-injection regimen.5  It has been 
validated in patients with rheumatoid arthritis and measured in patients with psoriasis and psoriatic 
arthritis.6-8
Suitability of Subject Population
Subjects who have moderate to severe plaque psoriasis, defined as a PASI score ≥ 12, body surface area 
(BSA) involvement ≥ 10%, and sPGA ≥ 3 who are candidates for systemic therapy are eligible for this 


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study.  Criteria such as laboratory values (minimums and maximums) and subject history (absence of 
chronic infections such as human immunodeficiency virus [HIV], hepatitis B or C, and other exclusions) 
are specified to ensure subject safety and to allow adequate evaluation of the study drug. The study 
population selected reflects a standard population for moderate to severe psoriasis trials with new 
treatment intervention.
Selection of Doses in the Study
The risankizumab dosing regimen selected for the current study (i.e., 150 mg SC at Weeks 0, 4, and 16) is 
the same as used in the risankizumab pivotal Phase 3 studies in subjects with moderate to severe 
chronic plaque psoriasis.  Risankizumab has been found to be safe and well tolerated with no dose 
limiting safety findings following single- or multiple-dose administration at doses up to 360 mg SC or 
1800 mg intravenously in Phase 1 to 3 clinical studies.1
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.
Demographic and Laboratory Assessments
2. Adult male or female, at least 18 years old.
3. Laboratory values meeting the following criteria within the screening period prior to the 
first dose of study drug:  
!
Serum aspartate transaminase < 2 × upper limit of normal (ULN);
!
Serum alanine transaminase < 2 × ULN;
!
Serum direct bilirubin ≤ 2.0 mg/dL; except for subjects with isolated elevation of indirect 
bilirubin relating to a confirmed diagnosis of Gilbert syndrome;
!
Total white blood cell count > 3,000/μL;
!
Absolute neutrophil count > 1,500/μL;
!
Platelet count > 100,000/μL;
!
Hemoglobin > 8 g/dL.
4. Are willing or able to comply with procedures required in this protocol including 
self-administration of study drug.


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Disease Activity
5. Diagnosis of chronic plaque psoriasis for at least 6 months before the baseline visit.
6. Subject meets the following disease activity criteria: 
!
Stable moderate to severe chronic plaque psoriasis, defined as ≥ 10% BSA psoriasis 
involvement, sPGA score of ≥ 3, and PASI ≥ 12 at Screening and baseline visit;
!
Candidate for systemic therapy as assessed by the investigator;
Subject History
7. No history of:
!
Erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or 
medication-exacerbated psoriasis, or new onset guttate psoriasis;
!
Active skin disease other than psoriasis that could interfere with the assessment of 
psoriasis;
!
Chronic infections including human immunodeficiency virus, viral hepatitis (hepatitis B, 
hepatitis C), and/or active TB.  Subjects with a positive QuantiFERON®-TB/purified protein 
derivative (tuberculin) test result may participate in the study if further work up (according 
to local practice/guidelines) establishes conclusively that the subject has no evidence of 
active TB.  If presence of latent TB is established, subjects are not required to be treated 
with prophylactic anti-TB therapy prior to or during the study, if the subject is considered 
low risk for reactivation per investigator judgment. 
!
Active systemic infection during the last 2 weeks prior to baseline visit (exception:  common 
cold), as assessed by the investigator.
8. No history of any documented active or suspected malignancy or history of any malignancy 
within the last 5 years except for successfully treated non-melanoma skin cancer or localized 
carcinoma in situ of the cervix.
9. No history of clinically significant (per investigator's judgment) drug or alcohol abuse within 
the last 6 months.
10. No history of underlying medical diseases or problems including but not limited to the 
following:
!
Subject has been a previous recipient of a solid organ transplant;
!
Evidence of a current or previous disease, medical condition (including chronic alcohol or 
drug abuse) other than psoriasis, surgical procedure (i.e., organ transplant), medical 
examination finding (including vital signs and electrocardiogram), or laboratory value at the 
screening visit outside the given range that, in the opinion of the investigator, is clinically 
significant and would make the study participant unreliable to adhere to the protocol or to 
complete the trial, compromise the safety of the patient, or compromise the quality of the 
data;
11. No history of an allergic reaction or significant sensitivity to constituents of the study drug 
(and its excipients) and/or other products in the same class.


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12. No major surgery performed within 12 weeks prior to randomization or planned to be 
performed during the conduct of the trial (e.g., hip replacement, aneurysm removal, stomach 
ligation) as assessed by the Investigator.
Contraception
13. For all females of child-bearing potential; a negative serum pregnancy test at the Screening 
Visit and a negative urine pregnancy test at baseline and following visits (as outlined in the 
Study Activity Table of this protocol) prior to the first dose of study drug.
14. Female subjects must be postmenopausal OR permanently surgically sterile OR for a woman 
of child bearing potential be practicing at least one protocol-specified method of birth control 
(Section 5.2) that is effective from the baseline visit through at least 140 days (20 weeks) after 
the last dose of study drug
15. Female who is not pregnant, breastfeeding, or considering becoming pregnant during the 
study or for approximately 140 days (20 weeks) after the last dose of study drug.
16. Additional local requirements may apply.
Concomitant Medications
17. No previous exposure to risankizumab.
18. No use of any restricted medication as specified in the prohibited medications/therapy 
section or any drug considered likely to interfere with the safe conduct of the study.
19. Subject must not have been treated with any investigational drug within 30 days or 
5 half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently 
enrolled in another clinical study.
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:
!
Postmenopausal, age > 55 years with no menses for 12 or more months without an 
alternative medical cause.
!
Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause AND a follicle-stimulating hormone level > 40 International Unit/L.
!
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).


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!
Females who have not experienced menarche (at least one menstrual period)
!
Females of Childbearing Potential
!
Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 140 days after the last dose of study drug.
!
Females must commit to one of the following methods of birth control:
!
Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at 
least 30 days prior to study baseline Day 1.
!
Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study baseline Day 1.
!
Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).
!
Intrauterine device.
!
Intrauterine hormone-releasing system.
!
Vasectomized 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).
If required per local guidelines, male or female condom with or without spermicide OR cap, diaphragm 
or sponge with spermicide should be used in addition to one of the birth control methods listed above 
(excluding true abstinence)
Contraception recommendations related to use of concomitant therapies prescribed should be based on 
the local label.
5.3 Prohibited Medications and Therapy
In addition to the medications listed in the eligibility criteria, the following concomitant psoriasis 
treatments are prohibited within the specified timeframe prior to baseline visit and throughout the 
study.
1.
Any systemic biologic to treat psoriasis:
!
Adalimumab, infliximab or biosimilar versions within 12 weeks;
!
Etanercept or biosimilar versions within 6 weeks;
!
Ixekizumab, brodalumab, secukinumab or other IL-17 inhibitors within 16 weeks;
!
Ustekinumab, efalizumab, guselkumab, tildrakizumab, mirikizumab, or other IL-23 inhibitors 
within 24 weeks.


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2.
Systemic non-biologic therapy for psoriasis, including but not limited to cyclosporine, 
corticosteroids, methotrexate, oral retinoids, apremilast, and fumaric acid derivatives within 
4 weeks.
3.
Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could 
affect disease severity or interfere with disease assessments within 4 weeks.
4.
Topical psoriasis treatments, including but not limited to corticosteroids, anthralin, 
calcipotriene, topical vitamin D derivatives, retinoids, urea, alpha- or beta-hydroxyl acids, and 
medicated shampoos (for example those that contain > 3% salicylic acid, corticosteroids, coal tar 
or vitamin D3 analogues) within 2 weeks.
!
Exception:  Subjects are allowed to use bland (containing no psoriasis treatment) emollients 
and shampoos and/or low potency topical corticosteroids (US Class 6 - 7) on the palms, 
soles, face, inframammary area, and groin only.
5.
Treatment with an experimental non-biologic for psoriasis within 4 weeks or 5 half-lives of the 
drug (whichever is longer).
6.
Treatment with an experimental biologic for psoriasis within 12 weeks or 5 half-lives of the drug 
(whichever is longer).
7.
Receipt of any live vaccine within 6 weeks or is expected to need live vaccination during study 
participation, including at least 20 weeks after the last dose of study drug.
Live or attenuated vaccines are NOT allowed during the study and for 140 days after the last dose of 
study drug.  Examples of such vaccines include but are not limited to the following:
!
Live attenuated influenza
!
Herpes zoster (i.e., Zostavax®)
!
Rotavirus
!
Varicella (chicken pox)
!
Measles-mumps-rubella or measles mumps rubella varicella 
!
Oral polio vaccine 
!
Smallpox
!
Yellow fever
!
Bacille Calmette-Guérin 
!
Oral typhoid
Vaccines that are inactivated, toxoid, or biosynthetic may be administered at any time without 
restrictions.  Examples of common vaccines that meet these criteria include but are not limited to:  
injectable influenza vaccine, pneumococcal, pertussis (Tdap), and Shingrix®.


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5.4 Prior and Concomitant Therapy
Stable doses of concomitant therapies for chronic conditions, for which neither the condition nor the 
treatment are judged to exclude the patient from participation are permissible.  All concomitant 
medications should be carefully evaluated by the investigator, and the AbbVie clinical monitor should be 
contacted when there are questions regarding concomitant medications.
Subjects must be able to safely discontinue any prohibited medications 5 half-lives or 4 weeks prior to 
initial study drug administration.  Subjects must be consented for the study prior to discontinuing any 
prohibited medications for the purpose of meeting study eligibility.
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:  
!
Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the AbbVie Therapeutic Area Medical Director 
(TA MD) (as applicable).
!
The investigator believes it is in the best interest of the subject.
!
The subject requests withdrawal from the study.
!
Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk as determined by the AbbVie TA MD, after 
consultation with the Investigator.
!
Introduction of prohibited medications or dosages and continuation of the study drug would 
place the subject at risk as determined by the AbbVie TA MD.
!
Subject develops active TB at any time during the study.
!
The subject becomes pregnant while on study drug.
!
Subject is diagnosed with a malignancy.  Exception:  localized non-melanoma skin cancer or 
carcinoma in-situ of the cervix, where discontinuation is at the discretion of the Investigator.
!
Subject is significantly noncompliant with study procedures, which would put the subject at risk 
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.


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5.6 Follow-Up for Subject Withdrawal from Study
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
study drug treatment should continue to be followed for all regularly scheduled visits, unless subjects 
have decided to discontinue 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 a subject prematurely discontinues study participation (withdrawal of informed consent), the 
procedures outlined for the Premature Discontinuation visit should be completed as soon as possible, 
preferably within 2 weeks.  In addition, a 20-week (140 days) follow-up phone call after the last dose of 
study drug may be completed to ensure all treatment-emergent AEs/serious adverse event (SAE) have 
been resolved.
In the event a subject withdraws consent from the clinical study, biomarker research will continue 
unless the subject explicitly requests analysis to be stopped.  When AbbVie is informed that samples are 
withdrawn from research, samples will not be analyzed, no new biomarker analysis data will be 
collected, and the samples will be destroyed.  A subject may withdraw consent for optional biomarker 
research at any time and remain in the clinical study.  Data generated for biomarker research before 
subject withdrawal of consent will remain part of the study results.
5.7 Study Drug
Information about the study drug and placebo used in this study is presented in Table 1.
Table 1.
Description of Study Drug and Placebo
Study Drug
Dosage Form
Strength
Route of Administration
Risankizumab (ABBV-066)
Solution for injection in PFS
150 mg/1.0 mL
SC injection
Placebo for Risankizumab
Solution for injection in PFS
Not applicable
SC injection
PFS = pre-filled syringe; SC = subcutaneous
Blinded risankizumab or matching placebo will be packaged in quantities sufficient to accommodate 
study design.  Each kit will be labeled per local requirements and this label must remain affixed to the 
kit.  Risankizumab or matching placebo kits will be kept protected from light in their original packaging, 
in a refrigerator between 2°C to 8°C (36°F to 46°F), and within a secure limited access storage area, and 
in accordance with the recommended storage conditions on the label.  Risankizumab or matching 
placebo must not be frozen at any time.  At the Week 4 visit, subjects will be provided with a cooler bag 
and ice pack to maintain adequate storage temperature of the study drug kit.
Upon receipt, study drug should be stored as specified on the label and kept in a secure location.  A 
temperature log must be maintained for documentation.  Each kit will contain a unique kit number.  This 
kit number is assigned to a subject via interactive response technology (IRT) and encodes the 
appropriate study drug to be dispensed at the subject's corresponding study visit. 


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AbbVie will not supply drug other than risankizumab and matching placebo, and study drug will only be 
used for the conduct of this study.  AbbVie provided study drug should not be substituted or alternately 
sourced unless otherwise directed by AbbVie.
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 generated by the statistics department at AbbVie.
Subjects will be randomized in a 2:1 ratio to risankizumab 150 mg or placebo.  Stratification is not 
planned for this study.
The investigator, study site personnel, and the subject will remain blinded to each subject's treatment 
throughout the study.  To maintain the blind, the risankizumab PFS and placebo PFS provided for the 
study will be identical in appearance. 
In the event of a medical emergency in which the investigator believes that knowledge of study drug 
treatment is required, reasonable efforts must be made to contact the AbbVie emergency contact prior 
to breaking the blind, as long as it does not compromise subject safety.  However, if an urgent 
therapeutic intervention is necessary which warrants breaking the blind prior to contacting the AbbVie 
emergency contact, the investigator can directly access the IRT system to break the blind without 
AbbVie agreement.  The date and reason that the blind was broken must be recorded in the source 
documentation and electronic case report form (eCRF), as applicable.
5.9 Protocol Deviations
The investigator is responsible for complying with all protocol requirements, written instructions, and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when
necessary to eliminate an immediate hazard to study subjects.  If a protocol deviation occurs (or is 
identified), the investigator is responsible for notifying independent ethics committee (IEC)/independent 
review board (IRB), regulatory authorities (as applicable), and AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.


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Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 1 business day of the study site's knowledge of the event.  Product complaints occurring during 
the study will be followed up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and the surgery/procedure has been 
pre planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an AE.
If an AE, whether associated with study drug or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance or vendor (as appropriate) as a SAE within 24 hours of the 
site being made aware of the SAE (refer to Section 4.3 of the Operations Manual for reporting details 
and contact information):
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not been 
taken.  This does not include an event that would have been fatal if it 
had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length 
of time or prolongs the subject's hospital stay.  This does not include 
an emergency room visit or admission to an outpatient facility.


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Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with 
the activities of daily living of a study subject.  Disability is not 
intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle).
Important Medical Event 
Requiring Medical or Surgical 
Intervention to Prevent 
Serious Outcome
An important medical event that may not be immediately life-
threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent or 
significant disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or 
drug abuse.
All adverse events reported from the time of study drug administration until 30 days or 5 half-lives after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, serious adverse events and protocol-related nonserious adverse 
events will be collected from the time the subject signs the study-specific informed consent.
AbbVie will be responsible for Suspected unexpected serious adverse reactions (SUSAR) reporting for 
the Investigational Medicinal Product 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.
If AEs in any of the following areas of safety interest are reported during the study, then the 
corresponding supplemental report must be completed (Table 2).




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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 1 working day after 
the site becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
discontinued (Section 5.5).  If a pregnancy occurs in a study subject, information regarding the 
pregnancy and the outcome will be collected.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a 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 Adjudication Committee Charter.  Dedicated eCRFs will be used as 
outlined in Table 2. 
In addition, the site may be contacted for additional source documentation for relevant events.
6.3 Anaphylaxis Adjudication Committee
While no concerns with systemic hypersensitivity have been identified with the use of risankizumab, the 
sponsor has established an independent, blinded, expert committee to adjudicate events of anaphylaxis 
based on pre-specified definitions.  This independent external AAC will adjudicate suspected 
anaphylactic reactions and will remain blinded to treatment allocation.  The event terms to be 
adjudicated and the adjudication process are detailed in the AAC Charter.  A supplemental 
Hypersensitivity Reactions eCRF will be used to collect information pertinent to the events (Table 2).  In 
addition, the site may be contacted for additional source documentation.


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If a suspected systemic hypersensitivity reaction occurs at the investigative site, subjects should be 
tested for tryptase and histamine levels.  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.
6.4 Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 1 business day of the study site's knowledge of the event.  Product complaints occurring during 
the study will be followed up to a satisfactory conclusion.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The primary analysis for all primary and secondary efficacy endpoints will occur after all ongoing 
subjects complete the Week 16 Visit.  This will be the only and final analysis for the primary and 
secondary efficacy endpoints at Week 16.
The statistical analysis will be described and fully documented in the Statistical Analysis Plan (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 (ITT) Population includes all randomized subjects.  The ITT Population will be used for 
all efficacy analyses.  Subjects will be analyzed according to treatment as randomized.
The Safety Analysis Population consists of all subjects who received at least 1 dose of study drug.  For 
the safety analysis, subjects will be analyzed according to the first dose of study drug (risankizumab or 
placebo) that the subject received.
7.3 Statistical Analyses for Efficacy
Analysis of the primary and secondary efficacy endpoints will be conducted on the ITT Population based 
on treatment as randomized.


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Overall type-I error will be controlled by testing the co-primary endpoints, followed by the ranked 
secondary endpoints, in a hierarchical order as described in Section 3.2 and Section 3.3.
Comparison of the primary and secondary efficacy endpoints will be made between the risankizumab 
and the placebo treatment groups using the Chi-square test.
Non-Responder Imputation will be used for categorical endpoints.  Mixed-effect Model Repeat 
Measurements will be used for continuous endpoints.
Usability endpoints will be analyzed by as-observed cases.  
Additional details on the primary and other efficacy analyses are provided in the SAP.
Sample Size Estimation
This study is designed to enroll approximately 150 subjects, randomized in a 2:1 ratio to risankizumab or 
placebo.  Assuming the response rates at Week 16 to be 74% for the risankizumab arm and 3% for the 
placebo arm for PASI 90, and 85% for the risankizumab arm and 7% for the placebo arm for sPGA of 
clear or almost clear, the study will provide more than 95% power for each of the two co-primary 
efficacy endpoints (an overall power of more than 90%).
7.4 Statistical Analyses for Safety
All safety analyses will be performed on the Safety Populations.  Subjects will be analyzed based on the 
first dose of treatment received after randomization.  A treatment-emergent adverse event (TEAE) is 
defined as an event with onset or worsening after the first dose of study drug and within 20 weeks 
(140 days) after the last dose of study drug.  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 will be provided as well.  Pre-treatment AEs 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.
7.5 Analyses of PK and Immunogenicity
Serum risankizumab concentrations will be summarized at Week 16 using descriptive statistics.  For 
immunogenicity assessment, the number and percentage of subjects with ADA and NAb by regimen will 
be calculated.  In addition, ADA titers will be tabulated for each subject by regimen at the respective 
study visits. 


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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
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).
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.


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11
COMPLETION OF THE STUDY
The end-of-study is defined as the date of the last's subject's last visit.
12
REFERENCES
1.
AbbVie.  Risankizumab Investigator's Brochure Edition 3.  10 May 2018.
2.
Khader SA, Pearl JE, Sakamoto K, et al.  IL-23 compensates for the absence of IL 12p70 and is 
essential for the IL-17 response during tuberculosis but is dispensable for protection and 
antigen-specific IFN-y responses if IL-12p70 is available.  J Immunol.  2005;175(2):788-95.
3.
O'Garra A, Redford PS, McNab FW, et al.  The immune response in tuberculosis.  Annu Rev 
Immunol.  2013;31:475-527.
4.
Tsai TF, Blauvelt A, Gong Y, et al.  Secukinumab treatment shows no evidence for reactivation of 
previous or latent TB infection in subjects with psoriasis:  a pooled phase 3 safety analysis.  J Am 
Acad Dermatol.  2015;607.
5.
Keininger D, Coteur G.  Assessment of self-injection experience in patients with rheumatoid 
arthritis:  psychometric validation of the Self-Injection Assessment Questionnaire (SIAQ).  Health 
Qual Life Outcomes.  2011;9:2.
6.
Blauvelt A, Prinz J, Gottlieb A, et al.  Secukinumab administration by pre-filled syringe:  efficacy, 
safety and usability results from a randomized controlled trial in psoriasis (FEATURE).  Br J 
Dermatol.  2015;172(2):484-93. 
7.
Nash P, Mease PJ, McInnes IB, et al.  Efficacy and safety of secukinumab administration by 
autoinjector in patients with psoriatic arthritis:  results from a randomized, placebo-controlled 
trial (FUTURE 3).  Arthritis Res Ther.  2018;20(1):47.
8.
Lacour J, Paul C, Jazayeri S, et al.  Secukinumab administration by autoinjector maintains 
reduction of plaque psoriasis severity over 52 weeks:  results of the randomized controlled 
JUNCTURE trial.  J Eur Acad Dermatol Venereol.  2017;31(5):847-56.
9.
US Dept. of Health and Human Services.  Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0.  27 November 2017.  Available from:  
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R 
eference_8.5x11.pdf.


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APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AAC
anaphylaxis adjudication committee
ADA
antidrug antibody
AE
Adverse event
BSA
body surface area
ECG
electrocardiogram
eCRF
electronic case report form
GCP
good clinical practice
HIV
human immunodeficiency virus
ICH
International Council for Harmonisation
IEC
Independent ethics committee
IFU
Instructions for Use
IL
interleukin
IRB
Institutional review board
IRT
Interactive response technology
ITT
intent-to-treat
mAb
monoclonal antibody
MACE
major adverse cardiovascular events
MedDRA
Medical Dictionary for Regulatory Activities
NAb
neutralizing antibody
PASI
Psoriasis Area Severity Index
PBMC
peripheral blood mononuclear cell
PFS
pre-filled syringe
PK
Pharmacokinetic(s)
PPD
purified protein derivative
SAE
Serious adverse event
SAP
Statistical analysis plan
SC
subcutaneous
SIAQ
Self-Injection Assessment Questionnaire
sPGA
static physician global assessment
SUSAR
Suspected unexpected serious adverse reactions
TA MD
Therapeutic Area Medical Director


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TB
tuberculosis
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
US
United States


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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M15-999:  A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the 
Safety and Efficacy of Risankizumab Using a New Formulation for the Treatment of Adult Subjects with 
Moderate to Severe Plaque Psoriasis
Protocol Date:  08 January 2020
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation 
(ICH) Good Clinical Practices (GCP) and local regulations and guidelines governing the study at the site 
location.  In signing the Investigator Agreement, the investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC), except when necessary to protect the subject from immediate harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed consent and 
ethics committees (e.g., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
9.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Immunology Development
Immunology Development
Clinical Program Development
Data and Statistical Sciences 
Clinical Pharmacology 
Data and Statistical Sciences
Medical Writing (Protocol Author) 


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APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities the subject encounters.  The individual activities are 
described in detail in the Operations Manual (Appendix F).








STUDY M15-999  |  Version 4.0
CONFIDENTIAL INFORMATION
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
27 November 2018
Version 2.0
07 January 2019
Version 3.0
11 March 2019
The purpose of this amendment was to:
!
Update ranking of Secondary Endpoints
!
Add additional detail around controlling for type-I error
!
Update Sponsor/emergency medical contact
!
Update protocol signatories


STUDY M15-999  |  Version 4.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX F. OPERATIONS MANUAL

SAP_001.pdf: 
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Statistical Analysis Plan for Study M15-999
A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled Study to Assess the Safety and 
Efficacy of Risankizumab Using a New Formulation 
for the Treatment of Adult Subjects with Moderate 
to Severe Plaque Psoriasis
Date:  05 March 2020
Version 4.0
NCT03875482


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Table of Contents
1.0
Introduction .............................................................................5
2.0
Study Design and Objectives..................................................5
2.1
Objectives and Hypotheses ........................................................................5
2.2
Study Design Overview .............................................................................6
2.3
Treatment Assignment and Blinding .........................................................7
2.4
Sample Size Determination........................................................................8
3.0
Endpoints..................................................................................8
3.1
Primary Efficacy Endpoints.......................................................................8
3.2
Secondary Efficacy Endpoints...................................................................9
3.3
Additional Endpoints .................................................................................9
3.4
Safety Endpoints ........................................................................................9
3.5
Pharmacokinetic Endpoints .....................................................................10
4.0
Analysis Populations .............................................................10
5.0
Subject Disposition................................................................10
6.0
Study Drug Duration and Compliance................................11
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ....................11
7.1
Demographics and Baseline Characteristics............................................11
7.2
Medical History .......................................................................................12
7.3
Prior and Concomitant Medications ........................................................12
8.0
Efficacy Analyses...................................................................13
8.1
General Considerations............................................................................13
8.2
Handling of Missing Data........................................................................14
8.3
Primary Efficacy Endpoints and Analyses ..............................................15
8.3.1
Primary Efficacy Endpoints.....................................................................15
8.3.2
Handling of Missing Data for the Primary Efficacy Endpoint(s)............15
8.3.3
Primary Efficacy Analysis .......................................................................15
8.3.4
Additional Analyses of the Primary Efficacy Endpoints.........................16
8.4
Secondary Efficacy Analyses...................................................................16
8.4.1
Key Secondary Efficacy Analyses...........................................................16
8.4.2
Supportive Secondary Efficacy Analyses................................................16


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8.5
Other Efficacy Analyses ..........................................................................16
8.6
Efficacy Subgroup Analyses....................................................................16
9.0
Safety Analyses ......................................................................17
9.1
General Considerations............................................................................17
9.2
Adverse Events ........................................................................................17
9.2.1
Treatment-Emergent Adverse Events ......................................................18
9.2.2
Adverse Event Overview .........................................................................18
9.2.3
Treatment-Emergent Adverse Events by SOC and/or PT .......................19
9.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure ..................................................................................................19
9.2.5
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation...............................................................................20
9.2.6
Area of Safety Interest .............................................................................20
9.3
Analysis of Laboratory Data....................................................................20
9.4
Analysis of Vital Signs ............................................................................22
9.5
Safety Subgroup Analyses .......................................................................22
9.6
Other Safety Analyses..............................................................................22
10.0
Other Analyses.......................................................................23
11.0
Interim Analyses....................................................................23
11.1
Data Monitoring Committee....................................................................23
12.0
Overall Type-I Error Control ..............................................23
13.0
Version History......................................................................24
14.0
References...............................................................................24
List of Tables
Table 1.
SAP Version History Summary...............................................................24
List of Figures
Figure 1.
Study Schematic.........................................................................................7


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List of Appendices
Appendix A.
Protocol Deviations..................................................................................25
Appendix B.
Definition of Area of Safety Interest........................................................26
Appendix C.
Potentially Clinically Important Criteria for Safety Endpoints ...............28
Appendix D.
Criteria for Potentially Clinically Important Vital Sign Values ..............30


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1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for risankizumab 
Study M15-999 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to 
Assess the Safety and Efficacy of Risankizumab Using a New Formulation for the 
Treatment of Adult Subjects with Moderate to Severe Plaque Psoriasis.  Study M15-999 
evaluates the safety and efficacy of the 150 mg/mL formulation of risankizumab in a pre-
filled syringe (PFS) compared with placebo for the treatment of adult subjects with 
moderate to severe plaque psoriasis.
This SAP provides summaries of the planned statistical analyses for safety and efficacy 
endpoints, interim analysis, and overall type-I error control strategies.
The analyses of pharmacokinetic endpoints will not be covered in this SAP.
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analysis.
Unless noted otherwise, all analyses will be performed using SAS Version 9.4 (SAS 
Institute Inc., Cary, NC  27513) or later under the UNIX operating system.
This SAP includes changes to analyses described in the protocol.  Details are outlined in 
Section 13.0.
2.0
Study Design and Objectives
2.1
Objectives and Hypotheses
The primary objective of this study is to evaluate the safety and efficacy of the 
150 mg/mL formulation of risankizumab in a pre-filled syringe (PFS) compared with 
placebo for the treatment of adult subjects with moderate to severe plaque psoriasis.
The co-primary endpoints are:


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●
The proportion of subjects achieving ≥ 90% reduction from Baseline in 
Psoriasis Area and Severity Index (PASI 90) response at Week 16.
●
The proportion of subjects achieving a static physician global assessment 
(sPGA) clear or almost clear (0 or 1) at Week 16.
2.2
Study Design Overview
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study 
that will evaluate the safety and efficacy of risankizumab 150 mg/mL formulation in PFS 
in patients with moderate to severe plaque psoriasis.  The study includes a 30-day 
screening period, a 28-week treatment period with study visits at Weeks 0, 4, 16 and 28, 
and a subsequent follow up telephone call at approximately 20 weeks after the last dose of 
study drug.  Study drug dosing will consist of 3 self-administered doses given 
subcutaneously on Weeks 0, 4, and 16.  Dosing on Week 4 will be self-administered at 
home.  Efficacy assessments will be performed at each study visit (Weeks 0, 4, 16, and 
28).
The schematic of the study is shown in Figure 1.


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Figure 1.
Study Schematic
2.3
Treatment Assignment and Blinding
All subjects will be assigned a unique identification number by the IRT at the screening 
visit.  For subjects who rescreen, the screening number assigned by the IRT at the initial 
screening visit should be used.  The IRT will assign a randomization number that will 
encode the subject's treatment group assignment according to the randomization schedule 
generated by the statistics department at AbbVie.
Subjects will be randomized in a 2:1 ratio to risankizumab 150 mg or placebo.  
Stratification is not planned for this study.


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The investigator, study site personnel, and the subject will remain blinded to each 
subject's treatment throughout the study.  To maintain the blind, the risankizumab PFS 
and placebo PFS provided for the study will be identical in appearance.
In the event of a medical emergency in which the investigator believes that knowledge of 
study drug treatment is required, reasonable efforts must be made to contact the AbbVie 
emergency contact prior to breaking the blind, as long as it does not compromise subject 
safety.  However, if an urgent therapeutic intervention is necessary which warrants 
breaking the blind prior to contacting the AbbVie emergency contact, the investigator can 
directly access the IRT system to break the blind without AbbVie agreement.  The date 
and reason that the blind was broken must be recorded in the source documentation and 
electronic case report form (eCRF), as applicable.
2.4
Sample Size Determination
This study is designed to enroll approximately 150 subjects, randomized in a 2:1 ratio to 
risankizumab or placebo.  Assuming the response rates at Week 16 to be 74% for the 
risankizumab arm and 3% for the placebo arm for PASI 90, and 85% for the risankizumab 
arm and 7% for the placebo arm for sPGA of clear or almost clear, the study will provide 
more than 95% power for each of the two co-primary efficacy endpoints (an overall 
power of more than 90%) based on Pearson Chi-square test with 2-sided significance level 
of 0.05.
3.0
Endpoints
3.1
Primary Efficacy Endpoints
The co-primary endpoints of this study are:
1.
Proportion of subjects achieving PASI 90 (defined as at least 90% improvement 
from baseline in PASI) at Week 16.
2.
Proportion of subjects achieving sPGA of clear or almost clear at Week 16.


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3.2
Secondary Efficacy Endpoints
Key Secondary Endpoints:  The following ranked secondary endpoints will be tested 
between risankizumab and placebo in the hierarchical order only if the null hypotheses for 
both co-primary endpoints have been rejected:
1.
Proportion of subjects achieving PASI 100 (defined as 100% improvement from 
baseline in PASI) at Week 16.
2.
Proportion of subjects achieving sPGA of clear at Week 16.
3.3
Additional Endpoints
All primary and key secondary endpoints will be analyzed at all other visits collected.  In 
addition, the following endpoints will be analyzed in all visits collected.
●
Proportion of subjects achieving PASI 50/75
●
Change and percent change from baseline in PASI
The following usability endpoints will also be summarized, for each treatment arm, at all 
visits collected.
●
Proportion of subjects with an observer rating of successful subject self-
administration, defined as any subjects who successfully completed the
sequence of 3 critical steps in the Instructions for Use (IFU) without errors to 
administer study drug
●
Proportion of subjects who experienced no potential hazards as measured by 
an observer
●
Subject rating of acceptability using the Self-Injection Assessment 
Questionnaire (SIAQ)
3.4
Safety Endpoints
The following endpoints will be included in the safety analyses:


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Treatment emergent adverse events (TEAEs);
●
Serious adverse events (SAEs);
●
Areas of safety interest (ASI);
●
Adverse events (AEs) leading to discontinuation;
●
Vital signs and laboratory tests.
3.5
Pharmacokinetic Endpoints
The pharmacokinetic endpoints will be analyzed separately.
4.0
Analysis Populations
The intent-to-treat (ITT) Population includes all randomized subjects.  The ITT 
Population will be used for all efficacy analyses.  Subjects will be analyzed according to 
treatment as randomized.
The Safety Analysis Population consists of all randomized subjects who received at least 
1 dose of study drug.  For the safety analysis, subjects will be analyzed according to the 
first dose of study drug (risankizumab or placebo) that the subject received.
5.0
Subject Disposition
The total number of subjects who were randomized, treated, completed, and discontinued 
will be summarized.
A summary of subject accountability will be provided where the number of subjects in 
each of the following categories will be summarized for each treatment group:
●
Subjects randomized in the study;
●
Subjects who received randomized study drug;
●
Subjects who completed study;
●
Subjects who discontinued study drug (all reasons and primary reason);


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For end of study participation, the number and percentage of subjects who completed this 
study (or did not with associated reasons) will be summarized overall and by treatment 
group.
6.0
Study Drug Duration and Compliance
For the ITT population, duration of treatment will be summarized for each treatment 
group.  Duration of treatment is defined for each subject as last dose date minus first dose 
date + 84 days.  Duration of treatment will be summarized using the number of subjects 
treated, mean, standard deviation, median, minimum and maximum.  
Treatment compliance will be summarized for the entire treatment period by treatment 
group for the ITT population.  
There will be a summary of the number of subjects receiving study drug and dose at each 
study drug administration visit.  This will be repeated on the cumulative number of doses.  
When computing compliance at each study drug administration visit, the denominator will 
include all subjects in each analysis population who have not prematurely discontinued 
the study drug prior to the scheduled study drug injection.  
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications
7.1
Demographics and Baseline Characteristics
Continuous demographic variables include age, weight, height, and body mass index 
(BMI).  Categorical demographic variables include sex, ethnicity, race, age (< 40, 40 – 65, 
≥ 65 years), weight (≤ 100 or > 100 kg), BMI (< 25, ≥ 25 – < 30, ≥ 30 kg/m2), tobacco 
user (current, former, never, unknown), and alcohol user (current, former, never, 
unknown).


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Disease characteristics include prior systemic biologic for psoriasis (0 vs. ≥ 1), PASI 
(Psoriasis Area and Severity Index), BSA (Body Surface Area), sPGA categories, history 
of psoriatic arthritis (yes, no), duration of plaque psoriasis (in years).
Demographics and baseline characteristics will be summarized among the ITT Population, 
overall and by treatment group.  Categorical variables will be summarized with the 
number and percentage of subjects; percentages will be calculated based on the number of 
non-missing observations.  Continuous variables will be summarized with descriptive 
statistics (number of non-missing observations, mean and standard deviation, median, 
minimum and maximum).
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The actual version of the MedDRA coding dictionary will be noted in the 
statistical tables and clinical study report.  The number and percentage of subjects in each 
medical history category (by MedDRA system organ class and preferred term) will be 
summarized overall and by treatment group.  The system organ class (SOC) will be
presented in alphabetical order, and the preferred terms will be presented in alphabetical 
order within each SOC.  Subjects reporting more than one condition/diagnosis will be 
counted only once in each corresponding category (SOC or preferred term).
Medical history will be summarized among the ITT Population.
7.3
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by generic name.  A prior 
medication is defined as any medication taken prior to the date of the first dose of study 
drug.  A concomitant medication is defined as any medication that started prior to the date 
of the first dose of study drug and continued to be taken on or after the first dose of study 
drug or any medication that started on or after the date of the first dose of study drug, but 
not after the date of the last dose of study drug plus 28 days.  The number and percentage 
of subjects taking medications will be summarized by generic drug name based on the 


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World Health Organization (WHO) Drug Dictionary for both prior and concomitant 
medications.
In addition, subjects' prior biologic therapy for psoriasis will also be summarized by the 
reason for discontinuation.
Prior and concomitant medications will be summarized among the ITT Population.
8.0
Efficacy Analyses
8.1
General Considerations
All efficacy analyses will be conducted in the ITT Population.  All tests will be 2-sided at 
an alpha level of 0.05.
The Primary Analysis will be performed after the last subject has completed the Week 16 
visit or has discontinued from the study participation, and the data up to Week 16 have be 
cleaned.  This will be the only and final primary efficacy analyses.  All efficacy endpoints 
will be analyzed up to Week 16 during this analysis.
Categorical variables will be analyzed using Chi-square test.  Continuous variables will be 
analyzed using MMRM with treatment as the fixed effect term, with treatment and 
Baseline values in the model.
Usability endpoints will be summarized by each treatment arm, by numbers and 
proportions for categorical variables; and by mean, standard deviation, median, minimal, 
and maximal values for continuous variables.
"Baseline" refers to the last non-missing observation on or before the date of the 
first administration of study drug or the date of randomization if no study drug is given.  
For variables where assessment time is collected, the baseline measurement must be prior 
to the time of the first administration of study drug.


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8.2
Handling of Missing Data
Missing data will be imputed using the following methods for the efficacy analyses:
●
Non-Responder Imputation (NRI):  The NRI analysis will categorize any 
subject who does not have evaluation during a specific visit window as a non-
responder for that visit.  The only exception is when if the subject is a 
responder both before and after a specific visit window in the particular period, 
then the subject will be categorized as a responder for the visit.  The NRI will 
be the primary approach to handle missing data in the analyses of categorical 
variables.
●
Modified-NRI: Patients who discontinue study drug due to lack of efficacy or 
due to AE of worsening of psoriasis and do not have Week 16 measurements 
will be counted as non-responders. The only exception is when if the subject 
is a responder both before and after a specific visit window in the particular 
period, then the subject will be categorized as a responder for the visit.  Other 
patients will be summarized using as-observed data.  The modified-NRI 
analysis will be the sensitivity approach to handle missing data in the analysis 
of the co-primary and the ranked secondary endpoints.
●
As-observed: The as-observed analysis will not impute values for missing 
assessments, thus subjects who do not have the assessments on a scheduled 
visit will be excluded from the analysis of that visit. The as-observed analysis 
will be the sensitivity approach to handle missing data in the analysis of the 
co-primary and the ranked secondary endpoints.
●
Mixed-effect Model Repeat Measurement (MMRM):  The repeated measures 
analysis will be conducted using a mixed model including baseline value and 
observed measurements at all post-baseline visits, using all available data even 
if a subject has missing data at some post-baseline visits.  The mixed model 
includes the categorical fixed effects of treatment, visit and treatment-by-visit 
interaction as covariates.  An unstructured variance covariance matrix will be 
used.  Parameter estimation is based on the assumption of data being missing 
at random and using the method of restrictive maximum likelihood (REML).  
MMRM will be the primary approach in the analysis of continuous variables.


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Usability endpoints will be analyzed by as-observed cases.
8.3
Primary Efficacy Endpoints and Analyses
8.3.1
Primary Efficacy Endpoints
The co-primary endpoints to assess the efficacy of risankizumab for the treatment of 
moderate to severe plaque psoriasis are:
●
Proportion of subjects achieving ≥ 90% improvement from baseline in PASI 
(PASI 90) at Week 16
●
Proportion of subjects achieving an sPGA of clear or almost clear (0 or 1) at 
Week 16
The corresponding null hypotheses based on the Co-Primary Endpoints will be tested 
simultaneously:
●
No difference in the proportion of subjects achieving PASI 90 at Week 16 
between risankizumab 150 mg and placebo
●
No difference in the proportion of subjects achieving sPGA clear or almost 
clear at Week 16 between risankizumab 150 mg and placebo
8.3.2
Handling of Missing Data for the Primary Efficacy 
Endpoint(s)
The co-primary endpoints will be analyzed using the NRI method to handle missing data.  
Modified-NRI and as-observed approaches will also be performed to handle missing data 
as sensitivity analyses.
8.3.3
Primary Efficacy Analysis
The two categorical variables will be analyzed using Chi-square test among the ITT 
Population.  Both null hypotheses must be rejected simultaneously under a two-sided 
significance level of 0.05.


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8.3.4
Additional Analyses of the Primary Efficacy Endpoints
Not applicable.
8.4
Secondary Efficacy Analyses
8.4.1
Key Secondary Efficacy Analyses
The ranked secondary efficacy endpoints at Week 16 will be tested between the 
risankizumab and placebo treatment groups among the ITT Population in a hierarchical 
order only if the null hypotheses for both primary endpoints have been rejected.
Secondary efficacy endpoints will be analyzed using the NRI method to handle missing 
data.  Modified NRI and as-observed approaches will also be performed to handle missing 
data as sensitivity analyses for these ranked secondary endpoints.
8.4.2
Supportive Secondary Efficacy Analyses
Not applicable.
8.5
Other Efficacy Analyses
Additional efficacy endpoints will be compared between the risankizumab and placebo
treatment groups among the ITT Population.
Non-Responder Imputation (NRI) will be used for categorical efficacy endpoints to 
handle missing data.  Mixed-effect Model Repeat Measurements (MMRM) will be used 
for continuous efficacy endpoints.
Usability endpoints will be analyzed by as-observed cases.
8.6
Efficacy Subgroup Analyses
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, summaries and analyses will be performed for selected subgroups for the 
primary efficacy endpoints.


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●
Age group (< 40 years, ≥ 40 – < 65 years, ≥ 65 years)
●
Sex (male, female)
●
Smoking (current, ex or never)
●
BMI (normal:  < 25, over weight:  ≥ 25 – < 30, obese:  ≥ 30)
●
Baseline Weight (≤ 100 kg, > 100 kg)
●
Baseline PASI (by median)
●
Baseline BSA (by median)
●
Baseline sPGA (3, 4)
●
Psoriatic arthritis (yes, no)
●
Prior systemic biologic for psoriasis (naïve to biologics, experienced to 
biologics, biologic failures)
9.0
Safety Analyses
9.1
General Considerations
Safety data will be summarized for the Safety Analysis Population.  Safety summaries 
will be presented by treatment group.  For the safety analysis, subjects are assigned to a 
treatment group based on the treatment actually received, regardless of the treatment 
randomized.  Safety analyses will include adverse events, laboratory, and vital sign 
measurements.
A subject's actual treatment will be determined by the first dose of study drug that the 
subject received.
Missing safety data will not be imputed.
9.2
Adverse Events
Adverse events (AEs) will be summarized and presented using primary MedDRA System 
Organ Classes (SOCs) and preferred terms (PTs) according to the version of the MedDRA 
coding dictionary used for the study at the time of database lock.  The actual version of 
the MedDRA coding dictionary used will be noted in the AE tables and in the clinical 


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study report.  When summarizing the number and percentages of subjects, subjects with 
multiple occurrences of the same adverse event will be counted once, and only the 
maximum severity level will be presented in the severity summaries, and the 
worst/highest relationship level in the relationship summaries.
9.2.1
Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any event newly developed 
on or after the first dosing of study drug to 20 weeks (140) days after the last dose of 
study drug.
9.2.2
Adverse Event Overview
An overview of TEAEs will be presented consisting of the number and percentage of 
subjects experiencing at least one event for each of the following AE categories:
●
Any treatment-emergent AE
●
Any treatment-emergent AE related to study drug according to the investigator
●
Any severe treatment-emergent AE
●
Any serious treatment-emergent AE
●
Any treatment-emergent AE leading to discontinuation of study drug
●
Any adjudicated MACE
●
Any infection
●
Any serious infection
●
Any tuberculosis
●
Any malignant tumor
●
Any malignant tumor excluding NMSC
●
Any serious hypersensitivity 
●
Any treatment-emergent AE leading to death
All deaths will also be summarized:
●
Deaths occurring ≤ 140 days after last dose of study drug


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●
Deaths occurring > 140 days after last dose of study drug.
9.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
Treatment-emergent adverse events will be summarized by SOC and PT; by maximum 
relationship to study drug as assessed by the investigator (e.g., reasonable possibility or no 
reasonable possibility) and by SOC and PT; by maximum severity and by SOC and PT; 
and by SOC and PT listing associated subject number.  When summarizing the number 
and percentages of subjects, subjects with multiple occurrences of the same adverse event 
will be counted once, and only the maximum severity level will be presented in the 
severity summaries, and the worst/highest relationship level in the relationship
summaries.
In addition, treatment-emergent adverse events will be summarized by PT and sorted by 
decreasing frequency for the active group.
9.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure
Exposure-adjusted AEs per 100 patient-years will be provided, where AEs per 
100 patient-years of exposure are defined as the number of AEs divided by the total 
exposure in 100 patient-years.
Note that one event per preferred term per day per subject will be counted in the 
calculation of the number of AEs (i.e., a preferred term will not be counted twice on the 
same day for the same subject).  See the calculation method below.
,
Where total patient years is defined as the sum of the study drug exposure (defined as date 
of last dose – date of first dose + 140 days (5 half-lives)) of all subjects normalized by 
365.25, and rounded to one decimal place.
Years
Patient 
Total
TEAEs
of
Number 
100 !


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9.2.5
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Treatment-emergent SAEs (including deaths) and AEs leading to study drug 
discontinuation will be summarized by SOC and PT and in listing format.
Pre-treatment AEs with onset dates prior to the first dose of study drug will be 
summarized separately.
9.2.6
Area of Safety Interest
Detailed information about the search criteria for areas of safety interest (ASIs) are 
provided in Appendix B.
The final list will be based on the most updated final version of risankizumab Product 
Safety Statistical Analysis Plan, which is consistent to the most updated risankizumab 
Risk Management Plan.
In addition, any injection site reactions by CMQ (code 80000019) will also be 
summarized by preferred terms in this study.
Tabular listings of selected area of safety interest will be provided.
9.3
Analysis of Laboratory Data
Data collected from central and local laboratories, including additional laboratory testing 
due to an SAE, will be used in all analyses, except for Baseline where SAE-related 
laboratory assessments on or before the first dose of study drug will be excluded.  The 
clinical laboratory tests defined in the protocol operations manual (e.g., hematology and 
clinical chemistry) will be summarized.
Mean change from baseline to each applicable post-baseline visit will be summarized for 
selected laboratory variables, with the number of observations, baseline mean, and visit 
mean.  The change from baseline mean, standard error, and 95% confidence interval will 


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be presented for the mean change from baseline within each treatment group and 
difference between treatment groups.
Changes in laboratory parameters will be tabulated using shift tables categorized as low, 
normal, or high based on the normal ranges of the laboratory used for each sample.  A 
shift table from baseline to minimum and maximum value (based on normal range), will 
be created.  A similar shift table will be provided to summarize shifts from baseline to the 
final post-baseline value.
Laboratory abnormalities meeting CTC criteria grade 3 and 4 will be summarized.
Laboratory abnormalities will be evaluated based on Potentially Clinically Important 
(PCI) criteria (Appendix C).  For each laboratory PCI criterion, the number and 
percentage of subjects who have a laboratory value meeting the criteria will be 
summarized.  Listings will be provided to summarize subject-level laboratory data for 
subjects meeting PCI criteria. 
In addition, ALT/SGPT, AST/SGOT, alkaline phosphatase, and total bilirubin will be 
categorized as follows:
●
< 1.5 × ULN
●
≥ 1.5 × ULN – < 3.0 × ULN
●
≥ 3.0 × ULN – < 5.0 × ULN
●
≥ 5.0 × ULN – < 10.0 × ULN
●
≥ 10.0 × ULN – < 20.0 × ULN
●
≥ 20.0 × ULN
A listing of potentially clinically important liver function laboratory values will include 
all subjects who met any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or


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●
ALP ≥ 1.5 × ULN, or 
●
Total bilirubin ≥ 2 × ULN.
A listing of possible Hy's Law cases, defined as those who meet all of the following 
conditions will be provided.  
●
ALT of > 3 × ULN or AST of > 3 × ULN, 
●
Associated with an increase in total bilirubin ≥ 2 × ULN,
●
ALP < 2 × ULN
9.4
Analysis of Vital Signs
Vital sign measurements of systolic and diastolic blood pressure will be summarized.
Mean change from baseline to each applicable post-baseline visit will be summarized for 
each vital sign variable, with the number of observations, baseline mean, and visit mean.  
The change from baseline mean, standard error, and 95% confidence interval will be 
presented for the mean change from baseline within each treatment group and difference 
between treatment groups.
Vital sign variables will be evaluated based on potentially clinically important (PCI) 
criteria (Appendix D).  For each vital sign PCI criterion, the number and percentage of 
subjects who have a vital sign value meeting the criteria will be summarized.  Listings 
will be provided to summarize subject-level vital sign data for subjects meeting PCI 
criteria.
9.5
Safety Subgroup Analyses
No subgroup for safety analyses.
9.6
Other Safety Analyses
No other safety analyses.


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10.0
Other Analyses
No other analyses.
11.0
Interim Analyses
11.1
Data Monitoring Committee
An external data monitoring committee (DMC) composed of persons independent of 
AbbVie and with relevant expertise in their field will review unblinded safety data from 
the ongoing study.  The primary responsibility of the DMC will be to protect the safety of 
the subjects participating in this study.
A separate DMC charter describes the roles and responsibilities of the DMC members, 
frequency of data reviews, relevant data to be assessed, and general operations.
Since there are no efficacy analyses for early stopping, no alpha adjustment is needed.
12.0
Overall Type-I Error Control
The Primary Analysis will be the only and final analysis for the co-primary efficacy 
endpoints.  Both primary endpoints need to be achieved simultaneously under a two-sided 
significance level of 0.05.
Overall type-I error will be controlled by testing the co-primary endpoints, followed by 
the ranked secondary endpoints, in a hierarchical order as described in Section 8.3 and 
Section 8.4.
Since there are no efficacy analyses for early stopping planned for the DMC review, no 
alpha spending is needed due to the DMC review.


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13.0
Version History
Table 1.
SAP Version History Summary
Version
Date
Summary
1.0
28 Nov 2018
Original version
2.0
20 Dec 2018
Updated study title to be consistent with Protocol Amendment 1
3.0
12 Jul 2019
Added baseline weight by 100 kg to the efficacy subgroup analysis.  
Added more statistical analysis details to the document.
4.0
05 Mar 2020
Clarified weight and BMI categories in demographics.
Clarified items to be summarized for disposition to align with the 
new standard table. 
Removed baseline BSA from MMRM model in efficacy analysis, as 
most BSA information is covered by the corresponding components 
in baseline PASI.
Updated key secondary and other efficacy endpoints and analyses, as 
well as type-I error control, to align with Protocol Amendment 
(protocol version 4)
Updated the definition of concomitant medication to align with the 
most updated risankizumab PSSAP.
Clarified shift tables, PCI, and ASI definitions for safety analysis, to 
align with the most updated risankizumab PSSAP.
Added the AE summary of any injection site reactions, according to 
FDA suggestion.
Clarified that all efficacy endpoints will be analyzed up to Week 16 
during the Primary Analysis.
Added modified-NRI and as-observed sensitivity analyses to handle 
missing data for the co-primary and ranked secondary endpoints.
14.0
References


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


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Appendix B.
Definition of Area of Safety Interest
Area of safety interest (ASI) will be identified using the following search criteria:
Area of Safety 
Interest
Search Criteria
Include in AE 
Overview (Y/N)
MACE
Adjudicated terms will be identified as described in PSSAP 
Table 3 using CECAT and CETERM from the CE SDTM 
dataset.
Y
Extended 
MACE
Adjudicated terms will be identified as described in PSSAP 
Table 3 (for MACE +) using CECAT and CETERM from the CE 
SDTM dataset.
N
Serious 
Infections
Serious AEs in the Infections and Infestations SOC 
Y
Tuberculosis
Active Tuberculosis CMQ (code 80000188 )
Y
Opportunistic 
Infections
Opportunistic infection excluding tuberculosis and herpes zoster 
CMQ (code 80000189 )
N
Fungal 
Infections
Fungal infections CMQ (code 80000063)
N
Malignant 
Tumours
Narrow
Malignant tumours (SMQ 20000194)
Y
Non-melanoma 
Skin Cancer 
(NMSC)
Broad
Skin malignant tumours (SMQ 20000204) excluding 
terms identified by the Melanoma CMQ 
(code 80000119)
N
Malignant 
Tumours 
excluding 
NMSC
'Malignant Tumours excluding NMSC' is identified by the 
'Malignant Tumours' search excluding terms identified by the 
'Non-melanoma skin cancer (NMSC)' search.
Y
Hypersensitivity 
Narrow
Hypersensitivity (SMQ 20000214)
Y – serious 
events only
Adjudicated 
Anaphylactic 
Reaction*
Adjudicated terms will be identified using SDTM data (e.g., CE 
and PR domains).
N
Hepatic Events 
Broad
Hepatic failure, fibrosis and cirrhosis and other liver 
damage-related conditions (SMQ 20000013)
N
Broad
Hepatitis, non-infectious (SMQ 20000010)
N
Broad
Cholestasis and jaundice of hepatic origin 
(SMQ 20000009)
N


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Area of Safety 
Interest
Search Criteria
Include in AE 
Overview (Y/N)
Broad
Liver related investigations, signs and symptoms 
(SMQ 20000008)
N
Narrow
Liver-related coagulation and bleeding disturbances 
(SMQ 20000015)
N
*
Events will be identified for adjudication by Anaphylactic Reaction SMQ Broad search as specified in the RISA 
AAC Charter.


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Appendix C.
Potentially Clinically Important Criteria for Safety Endpoints
The criteria for Potentially Clinically Important (PCI) laboratory findings are described in 
Table C-1 and Table C-2.
Table C-1.
Criteria for Potentially Clinically Important Hematology Values
Hematology Variables
Units
Definition of Potentially Clinically Important:
NCI CTCAE (Version 4) Grade 3 or Greater
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
Note:
A post-baseline grade must be more extreme than the baseline grade to be considered a potentially clinically 
important finding.


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Table C-2.
Criteria for Potentially Clinically Important Chemistry Values
Chemistry Variables
Units
Definition of Potentially Clinically Important: 
NCI CTCAE (Version 4) Grade 3 or Greater
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
ALP
U/L
> 5.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
Sodium
mmol/L
< 130
> 155
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CPK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN
Note:
A post-baseline grade must be more extreme than the baseline grade to be considered a potentially clinically 
important finding.


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Appendix D.
Criteria for Potentially Clinically Important Vital Sign Values 
Vital Signs Variables
Criterion
Definition of Potentially Clinically Important
Systolic Blood 
Pressure (mmHg)
Low
Value ≤ 90 mmHg and decrease ≥ 20 mmHg from Baseline
High
Value ≥ 160 mmHg and increase ≥ 20 mmHg from Baseline
Diastolic Blood 
Pressure (mmHg)
Low
Value ≤ 50 mmHg and decrease ≥ 10 mmHg from Baseline
High
Value ≥ 100 mmHg and increase ≥ 10 mmHg from Baseline