A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety and Efficacy of Risankizumab in Adult Subjects With Moderate to Severe Hidradenitis Suppurativa
Phase: PHASE2
Conditions: Hidradenitis Suppurativa
Sponsor: AbbVie



STUDY M16-833  |  Version 5.0  |  EudraCT 2019-000122-21
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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
8
2.1
BACKGROUND AND RATIONALE
8
2.2
BENEFITS AND RISKS TO SUBJECTS
9
3
STUDY OBJECTIVES AND ENDPOINTS
10
3.1
OBJECTIVES
10
3.2
PRIMARY ENDPOINT
11
3.3
SECONDARY ENDPOINTS
11
3.4
SAFETY ENDPOINTS
12
3.5
PHARMACOKINETIC AND IMMUNOGENICITY ENDPOINTS
12
3.6
BIOMARKER RESEARCH
12
4
INVESTIGATIONAL PLAN
13
4.1
OVERALL STUDY DESIGN AND PLAN
13
4.2
DISCUSSION OF STUDY DESIGN
15
5
STUDY ACTIVITIES
15
5.1
ELIGIBILITY CRITERIA
15
5.2
CONTRACEPTION RECOMMENDATIONS
19
5.3
PROHIBITED CONCOMITANT MEDICATIONS AND THERAPY
20
5.4
PRIOR AND CONCOMITANT THERAPY
21
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
23
5.6
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
24
5.7
STUDY DRUG
25
5.8
RANDOMIZATION/DRUG ASSIGNMENT
26
5.9
PROTOCOL DEVIATIONS
26
6
SAFETY CONSIDERATIONS
26
6.1
COMPLAINTS AND ADVERSE EVENTS
26
6.2
INDEPENDENT DATA MONITORING COMMITTEE
30
6.3
CARDIOVASCULAR ADJUDICATION COMMITTEE
31
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6.4
ANAPHYLAXIS ADJUDICATION COMMITTEE
31
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
31
7.1
STATISTICAL AND ANALYTICAL PLANS
31
7.2
DEFINITION FOR ANALYSIS POPULATIONS
32
7.3
STATISTICAL ANALYSES FOR EFFICACY
32
7.4
STATISTICAL ANALYSES FOR SAFETY
33
7.5
ANALYSES OF PHARMACOKINETICS AND IMMUNOGENICITY
33
8
ETHICS
34
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
34
8.2
ETHICAL CONDUCT OF THE STUDY
34
8.3
SUBJECT CONFIDENTIALITY
34
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
34
10 DATA QUALITY ASSURANCE
35
11 COMPLETION OF THE STUDY
35
12 REFERENCES
35
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCT......................................................................................25
TABLE 2.
SUPPLEMENTAL ADVERSE EVENTS ECRFS........................................................................................29
TABLE 3.
POWER WITH A 1:1:1 RANDOMIZATION.........................................................................................33
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMATIC..........................................................................................................................14
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
38
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APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
41
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
42
APPENDIX D.
ACTIVITY SCHEDULE
43
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
48
APPENDIX F.
OPERATIONS MANUAL
52
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted
This study will compare risankizumab versus placebo for the treatment of adult subjects with moderate 
to severe hidradenitis suppurativa (HS).
Hidradenitis suppurativa is an inflammatory, debilitating skin disease with a characteristic clinical 
presentation of recurrent or chronic painful or suppurating lesions that most commonly present in the 
axilla, inguinal, and anogenital regions.1,2  The estimated prevalence of HS varies between < 1% and 4%.3-
7  Important differential diagnoses of HS are furuncles, carbuncles, abscesses, cutaneous Crohn's 
disease, and acne.8  It is a difficult to diagnose condition, and therefore, there is a significant delay 
(7.2 years on average) in establishing the diagnosis of HS after its initial presentation.9
Hidradenitis suppurativa lesions (i.e., nodules, abscesses, and sinuses) are characterized by painful 
lesions located in the intertriginous areas, which can be malodorous and have purulent discharge.  This 
constellation results in substantial disability and social stigma of the patients and a profound impact on 
the quality of life.10  Depression, anxiety, and an increased suicide risk may be seen in patients with HS, 
as well as an adverse influence on a patient's sexual health.11-15  Patients may have several 
comorbidities, such as obesity, metabolic syndrome, diabetes, arthritis, Crohn's disease, and polycystic 
ovary disease.2,16  Patients with HS have an increased risk of adverse cardiovascular (CV) outcomes and 
all-cause mortality, and their risk of CV-associated death was shown to be higher than in psoriasis 
patients.17
Available treatment options for patients with HS include medical treatments such as topical non-
antibiotics (e.g., exfoliants and peels), topical antibiotics (e.g., clindamycin), systemic antibiotics 
(e.g., clindamycin, tetracycline, rifampicin), anti-inflammatory therapies (e.g., corticosteroids, dapsone, 
ciclosporin A), hormones (e.g., antiandrogens and estrogens), retinoids (e.g., isotretinoin, acitretin), 
biologics (e.g., adalimumab, infliximab), analgesics (e.g., NSAIDs, opioids), and surgical treatments 
(e.g., deroofing, excision, laser).18  However, most of those treatments have not been adequately 
studied in patients with HS or do not appear to be very effective through the course of the disease.  The 
only approved treatment option for patients with moderate to severe HS is adalimumab (Humira®), a 
TNF-α inhibitor that demonstrated in 2 Phase 3, multicenter, double-blind, placebo controlled studies 
(PIONEER I and PIONEER II) its safe and efficacious use in this patient population.  The primary endpoint 
in these studies was the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as at least a 
50% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess 
count and no increase in draining fistula count relative to Baseline.  At Week 12, HiSCR was achieved by 
41.8% (PIONEER I) and 58.9% (PIONEER II) of subjects treated with adalimumab, respectively, in 
comparison to 26% (PIONEER I) and 27.6% (PIONEER II) of subjects treated with placebo.19  In the 
context of this single HS-approved treatment option, there is still a high unmet need for new safe and 
efficacious HS therapies.
Hidradenitis suppurativa is a disease of unknown etiology characterized by a perifollicular lymphocytic 
infiltrate with subsequent sebaceous gland loss.20  It is hypothesized that this process may be the result 
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of local immune system deregulation.20,21  As HS progresses, increased levels of interleukin (IL)-1, tumor 
necrosis factor (TNF), IL-17, S100A8, S100A9, caspase-1, and IL-10 appear in the tissue accompanied by 
an influx of immune competent cells.21-23  Macrophages are the most numerous inflammatory cells 
found in HS infiltrates and release numerous pro-inflammatory cytokines such as IL-23, IL-1β, and TNF-α, 
exacerbating the inflammation and contributing to the pathogenesis of HS.24  IL-23 and IL-1β help 
differentiate T helper 17 (Th17) cells, which lead to abundant production of IL-17 in HS lesions.  
Macrophages that infiltrate the papillary and reticular dermis of HS lesions showed the expression of 
high amounts of IL-23 compared to skin of patients who do not have HS.25  In accordance with the high 
expression of IL-23 and its important role in the development of Th17 cells, IL-17-producing T helper 
cells were found to distinctly infiltrate lesional dermis, suggesting that the IL-23/Th17 pathway is 
involved in HS.25
In a small uncontrolled, open-label, investigator-initiated study using standard weight-based psoriasis 
dosing of ustekinumab (Stelara®), a monoclonal antibody (mAb) that inhibits the p40 subunit of both the 
IL-12 and IL-23 receptor, 82% of the enrolled patients had moderate to marked improvements of the 
modified Sartorius score (a clinical scoring system for HS) at Week 40.26  In a small, 28-week open-label, 
investigator-initiated pilot study investigating 300mg of secukinumab, a mAb that inhibits IL-17A, 78% of 
patients achieved HiSCR and a 40% decrease in mean Sartorius score at Week 24.27  These results 
suggest that a targeted inhibition of IL-23 mediated inflammation with risankizumab may improve the 
signs and symptoms of the patients with HS.
Risankizumab is a humanized mAb of the IgG1 subclass directed towards IL 23p19.  The antibody (Ab) 
has been engineered to reduce Fcγ receptor and complement binding and potential charge 
heterogeneity.  Risankizumab binds with high affinity to human IL-23 and is currently being developed 
for the treatment of psoriasis (Phase 3 studies concluded and under registration review), Crohn's 
disease (in Phase 3 studies), psoriatic arthritis (in Phase 3 studies), ulcerative colitis (in Phase 2/3 
studies), and atopic dermatitis (in a Phase 2 study).  Risankizumab may also address the current needs 
for subjects with HS.
Clinical Hypothesis
Risankizumab will provide superior efficacy compared to placebo and will be well tolerated in subjects 
with HS.
2.2 Benefits and Risks to Subjects
This study is required to learn more about the potential treatment effect of risankizumab in HS.
As with many immune modulating agents, risankizumab may impair immune function, resulting in a risk 
of infection.  This will be monitored by collection of all adverse events (AEs) during the treatment and 
observation periods.  In addition, subjects with active systemic infection or clinically important infection 
will not be included in the study.
Subjects with a positive QuantiFERON®-TB (or interferon gamma release assay [IGRA] 
equivalent)/tuberculosis (TB) skin test result for TB must fulfill entry criteria as specified in Section 5.1 of 
this protocol.  IL-23 inhibition is not known to increase the risk of TB infection or impair the response to 
TB infection in animal models.28,29  Subjects with positive QuantiFERON-TB testing (or IGRA 
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equivalent)/TB skin test who have latent TB and are considered at low risk for reactivation (defined by 
local guidelines and investigator judgment) are not required to be treated with TB prophylaxis prior to 
receiving risankizumab, but should be carefully monitored for any sign of TB reactivation.
Published literature indicates that inhibition of IL-23 is unlikely to increase the risk for cancer.  
Expression of IL-23 is increased in human tumors.30-32  Moreover, preclinical data have demonstrated a 
beneficial effect of IL-23 p19 inhibition in animal models, both for pre-existing and tumor-induction 
models.  However, while there is not enough clinical information at this time to rule out a risk of cancer 
with risankizumab, this risk is considered small.
Although rare, a potential for hepatic AEs is under constant surveillance by sponsors and regulators.  
Therefore, this study requires timely detection, evaluation, and follow-up of laboratory alterations in 
selected liver laboratory parameters to ensure subjects' safety.
Increases in major adverse cardiovascular (MACE) events, including myocardial infarction (MI), 
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 Cardiovascular Adjudication Committee (CAC), which will adjudicate all observed 
cardio- and cerebro-vascular events and will remain blinded to treatment allocation (Section 6.3).
Local reactions to subcutaneously-administered biologic therapies are usually limited to redness, swelling, 
or induration at the injection site.  Manifestations of systemic hypersensitivity reactions include 
anaphylaxis, pruritus, hypotension, and respiratory distress.  Both local and systemic hypersensitivity 
reactions are readily detectable, transient in nature, and manageable with standard medical treatment.  
Subjects will be closely monitored during study drug administration.  An independent Anaphylaxis 
Adjudication Committee (AAC) will adjudicate observed systemic hypersensitivity and anaphylactic events.  
The AAC will remain blinded to treatment allocation (Section 6.4).
In conclusion, the benefit-risk profile of risankizumab is considered appropriate for this stage of clinical 
development.33  Based on data from the integrated safety analyses, risankizumab is safe and well-
tolerated and demonstrates a favorable benefit-risk profile.
For further details, please see findings from completed studies, including safety data in the current 
risankizumab Investigator's Brochure (IB).
In view of the coronavirus disease of 2019 (COVID-19) pandemic, the benefit-risk profile of various 
immunomodulatory therapies on COVID-19 is being evaluated based on real world and clinical trial data.  
At this time, the effects of risankizumab on the course of COVID-19 are not well defined.
3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objectives
The primary objective of this study is to assess the safety and efficacy of risankizumab 180 mg and 
360 mg versus placebo for the treatment of signs and symptoms of moderate to severe HS in adult 
subjects diagnosed for at least one year before the Baseline visit.
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3.2 Primary Endpoint
The primary endpoint is the proportion of subjects achieving Hidradenitis Suppurativa Clinical Response 
(HiSCR) at Week 16.  HiSCR is defined as at least a 50% reduction in the total AN count with no increase 
in abscess count and no increase in draining fistula count relative to Baseline.
3.3 Secondary Endpoints
Key Secondary Endpoints
The following ranked secondary endpoints will be evaluated at the time points listed.
1.
Proportion of subjects achieving at least 30% reduction and at least 1 unit reduction from 
Baseline in Numerical Rating Scale (NRS30) in Patient's Global Assessment of Skin Pain (PGA Skin 
Pain) at Week 8 among subjects with Baseline Numerical Rating Scale (NRS) ≥ 3.  NRS30 is based 
on worst skin pain in a 24-hour recall period (maximal daily pain).
2.
Proportion of subjects achieving NRS30 in PGA Skin Pain at Week 16 among subjects with 
Baseline NRS ≥ 3.
3.
Proportion of subjects who experience at least 25% increase in AN counts with a minimum 
increase of 2 relative to Baseline during Period A.
4.
Change from Baseline in Dermatology Life Quality Index (DLQI) at Week 16.
5.
Change from Baseline in HS-related swelling – assessed based on the Hidradenitis Suppurativa 
Symptom Assessment (HSSA) at Week 16.
6.
Change from Baseline in HS-related odor – assessed based on the HSSA at Week 16.
7.
Change from Baseline in HS-related worst drainage – assessed based on the HSSA at Week 16.
Additional Endpoints
All variables listed as primary or ranked secondary endpoints will also be analyzed at all visits collected 
in addition to those listed above.  The following endpoints will also be evaluated at all visits collected:

Change and percent change from Baseline in PGA Skin Pain at worst (maximal daily pain), among 
subjects who have Baseline NRS ≥ 3.

Proportion of subjects achieving a total AN count of 0, 1, or 2.

Proportion of subjects achieving complete elimination of inflammatory lesions by lesion type, 
among subjects who had the corresponding lesion type at Baseline.

Proportion of subjects who experience at least 25% increase in inflammatory lesion counts with 
a minimum increase of 2 relative to Baseline, by lesion type.

Change from Baseline in inflammatory lesion counts by lesion type.

Percent change from Baseline in lesion counts by inflammatory lesion type, among subjects who 
had at least 3 of the corresponding lesion type at Baseline.

Proportion of subjects achieving DLQI = 0 or 1.
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
Proportion of subjects achieving a DLQI improvement (reduction) of ≥ 4 points among subjects 
with DLQI ≥ 4 at Baseline.

Change from Baseline in symptoms assessed based on HSSA questionnaire.

Change from Baseline in Hidradenitis Suppurativa Impact Assessment (HSIA) questionnaire.

Change from Baseline in EuroQol 5 Dimensions 5 Levels Health State Instrument (EQ-5D-5L).

Change from Baseline in Work Productivity and Activity Impairment (WPAI).

Proportion of subjects achieving at least 1 grade improvement from Baseline in Patient Global 
Impression of Severity (PGIS) scale among subjects with Baseline PGIS of at least "Minimal."

Proportion of subjects who report symptoms to be "Minimal" or "Absent" on the PGIS scale.

Proportion of subjects achieving "much improved" or "very much improved" on the Patient 
Global Impression of Change (PGIC) scale.

Change from Baseline in Hospital Anxiety and Depression Scale (HADS).

Change from Baseline in high-sensitivity C-reactive protein (hsCRP).

Proportion of subjects who experience worsening by at least 1 Hurley Stage in at least 1 affected 
anatomic region.
3.4 Safety Endpoints
The following safety evaluations will be performed during the study: treatment emergent adverse 
events (TEAEs), serious adverse events (SAEs), areas of safety interest (ASI), and AEs leading to 
discontinuation; vital signs; and laboratory tests.
3.5 Pharmacokinetic and Immunogenicity Endpoints
Serum risankizumab concentrations, antidrug antibodies (ADA), and neutralizing antibodies (NAb) will be 
determined from blood collected by venipuncture at the visits indicated in the Activity Schedule.
3.6 Biomarker Research
Optional blood samples will be collected to investigate changes in biomarkers following treatment with 
risankizumab, such as proteins and/or genes involved in the IL-23 pathways and biomarkers of HS 
disease activity.  Prognostic, surrogate, predictive and pharmacodynamics biomarkers 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, or lipids.  This research is exploratory in 
nature, and the results may not be included with the clinical study report.
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4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to 
evaluate the safety and efficacy of 2 dose levels of risankizumab in adult subjects with moderate to 
severe HS diagnosed at least 1 year before the Baseline visit.
The duration of the study will be up to 85 weeks and will include an approximately 35-day screening 
period followed by 2 treatment periods.  In Period A, subjects who meet the study's eligibility criteria 
(Section 5.1) will be randomized at the Baseline visit, in a 1:1:1 ratio, to receive either risankizumab
180 mg or 360 mg via a subcutaneous (SC) injection, or matching placebo up to Week 16.  Study drug 
administration for Period A will occur at visits Weeks 0 (Baseline), 1, 2, 4, and 12.  The final efficacy 
evaluation of Period A will be at Week 16.
In Period B, subjects who were initially randomized to placebo will then receive blinded risankizumab 
360 mg at Weeks 16, 17, and 18, while subjects who were initially randomized to risankizumab will 
receive blinded matching placebo at the same time points to keep the treatment of Period A blinded.  
Starting at Week 20, all subjects will receive open-label risankizumab 360 mg every eight weeks (q8w), 
at Weeks 20, 28, 36, 44, 52, and 60.  The final efficacy evaluation of Period B will take place at Week 68.  
A follow up call will be conducted approximately 20 weeks after last dose of study drug.
A schematic of the study is shown in Figure 1.  Further details regarding study procedures are located in 
the Operations Manual.
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Figure 1.
Study Schematic
PBO = placebo; RZB = risankizumab; W = week
This study plans to enroll approximately 220 subjects from approximately 60 sites in the US, EU, Canada, 
Japan, and Australia, although the number, allocation, and location of sites may vary depending on 
operational aspects of the study.
Once a sufficient number of subjects to fulfill the enrollment target have entered the screening process, 
no further subjects will be screened.  Once 220 subjects have been randomized, subjects who have 
started screening but have not yet been randomized will be allowed to enroll in the study if eligible.
The study team will remain blinded until the Week 16 Primary Analysis.  In addition, the study will have 
an external independent data monitoring committee (IDMC) to review unblinded safety data 
(Section 6.2).  Independent committees to assess cardio- and cerebro-vascular events (Cardiovascular 
Adjudication Committee [CAC]) and suspected anaphylactic reactions (Anaphylaxis Adjudication 
Committee [AAC]) will also be formed (Section 6).
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4.2 Discussion of Study Design
Choice of Control Group
A placebo control has been selected as the appropriate control group for this study to establish an 
unbiased efficacy and safety profile of risankizumab in subjects with HS.
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 HS.  All clinical 
and laboratory procedures in this study are standard and generally accepted.
Suitability of Subject Population
Adult subjects with moderate to severe HS (defined as a total AN count of ≥ 5 at Baseline, presence of 
HS lesions in at least 2 distinct anatomic areas, and draining fistula count of ≤ 20 at Baseline) for at least 
1 year prior to Baseline, as determined by the investigator are eligible for this study.  The criteria relating 
to safety have been selected to allow subjects to be safely enrolled and treated with risankizumab based 
on the current knowledge of this drug.  The study population selected reflects a standard population for 
moderate to severe HS studies with new treatment intervention.
Selection of Doses in the Study
Hidradenitis suppurativa is considered a high inflammatory disease with deep-seated lesions and an 
abundance of innate and adaptive immune cells.  Two doses of risankizumab (180 mg and 360 mg) were 
selected for evaluation in this study.  A 180 mg SC dose administered q8w has maintained efficacy in the 
Phase 2 Crohn's disease study and is likely to be efficacious in subjects with HS.  The additional higher 
dose of 360 mg SC is also being tested as the high-maintenance dose level in the Phase 3 Crohn's disease 
studies based on the preliminary exposure-response analyses of the Phase 2 Crohn's disease study, 
indicating greater efficacy at a higher dose above 180 mg.  Evaluating both doses in this study is 
expected to provide dose/exposure-response data and to allow for evaluation if an efficacy plateau can 
be achieved at 360 mg dose level.  Both doses are within the range of doses safely administered in 
previous risankizumab clinical studies.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the questions below will result in exclusion from study participation.
Consent
1. Subjects or their legally authorized representative must voluntarily sign and date an informed 
consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), 
prior to the initiation of any screening or study-specific procedures.
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Demographic and Laboratory Assessments
2. Adult male or female, at least 18 years old and functionally able to read and understand 
study questionnaires.
3. Laboratory values meeting the following criteria within the Screening period prior to the 
first dose of study drug:

Serum aspartate transaminase (AST) < 2 × upper limit of normal (ULN);

Serum alanine transaminase (ALT) < 2 × ULN;

Serum total bilirubin ≤ 2.0 mg/dL; except for subjects with isolated elevation of indirect 
bilirubin relating to Gilbert syndrome;

Total white blood cell (WBC) count > 3,000/μL;

Absolute neutrophil count (ANC) > 1,500/μL;

Platelet count > 100,000/μL;

Hemoglobin > 8.0 g/dL.
4. Subjects are willing or able to comply with procedures required in this protocol.
5. Subject is not an employee or a family member of the sponsor and/or study sites.
Disease Activity
6. Adults with moderate to severe HS for at least 1 year prior to Baseline, as determined by the 
investigator (i.e., through medical history, interview of subject).
7. Subject must have a total AN count of ≥ 5 at Baseline.
8. HS lesions must be present in at least 2 distinct anatomic areas.
9. Draining fistula count of ≤ 20 at Baseline.
10. Inadequate response (or intolerant) to an adequate trial of oral antibiotics for treatment of HS 
as determined by local guidelines.
Subject History
11. No history of active skin disease other than HS that could interfere with the assessment of 
HS, including skin infections (bacterial, fungal, or viral) requiring systemic treatment within 
4 weeks of the Baseline visit.
12. No evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as:

HBV:  Hepatitis B surface antigen (HBs Ag) positive (+) test or detected sensitivity on the HBV 
DNA polymerase chain reaction (PCR) qualitative test for subjects who are hepatitis B core 
antibody (HBc Ab) positive (+) (and for hepatitis B surface antibody [HBs Ab] positive [+] 
subjects where mandated by local requirements).

HCV:  HCV RNA detectable in any subject with anti-HCV antibody (HCV Ab).
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13. No evidence of HIV, defined as confirmed positive anti-HIV antibody (HIV Ab) test.  (Note:  In 
case a screened subject has a confirmed positive HIV Ab test, Eligibility Criterion #22 should be 
selected in the eCRF for documentation of reason for screening failure.)
14. No active TB or concurrent treatment for latent TB.  (Note:  TB antibiotic prophylaxis is 
prohibited due to potential impact on efficacy assessments.)  Subjects with a positive 
QuantiFERON® TB gold test (or IGRA equivalent) or purified protein derivative (PPD) test result 
may participate in the study if further work up (according to local practice/guidelines) 
establishes conclusively that the subject has no evidence of active TB and the subject does not 
require the use of prophylactic anti-TB therapy during the conduct of the study.  If anti-TB 
therapy has been previously completed by the subject, the last dose of anti-TB therapy must 
have been completed at least 4 weeks prior to the Baseline visit.
15. No history of active systemic infection during the last 2 weeks prior to the Baseline visit 
(exception: common cold), as assessed by the Investigator.
16. No documented active or suspected malignancy or history of any malignancy within the 
last 5 years except for successfully treated non-melanoma skin cancer (NMSC) or localized 
carcinoma in situ of the cervix.
17. No history of organ transplantation.
18. No major surgery performed within 12 weeks prior to randomization or planned during the 
conduct of the study (e.g., hip replacement, aneurysm removal, stomach ligation).
19. No history or concurrent clinically significant medical conditions or any other reason, including 
any physical, psychological, or psychiatric condition that in the opinion of the Investigator would 
compromise the safety or interfere with the subject's participation in this study or would make 
the subject an unsuitable candidate to receive study drug or would put the subject at risk by 
participating in the protocol; as well as being permanently wheelchair-bound or bedridden or 
having very poor functional status that is preventing the ability to perform self-care.
20. No history of clinically significant (per Investigator's judgment) drug or alcohol abuse within 
the last 6 months, including medicinal or recreational cannabis or cannabinoids.
21. 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.
22. Subject is judged to be in good general health, as determined by the Principal Investigator 
based upon the results of a medical history, physical examination, laboratory profile, and a 
12-lead electrocardiogram (ECG) performed during the Screening period.
Contraception
23. For all females of child-bearing potential; a negative serum pregnancy test at the Screening 
visit and a negative urine pregnancy test at Baseline prior to the first dose of study drug.
24. If female, subject must be of non-childbearing potential OR a female of childbearing 
potential practicing at least 1 protocol-specified method of birth control, that is effective from 
Baseline through at least 140 days (20 weeks or as guided by the local risankizumab label if 
approved, whichever is longer) after the last dose of study drug (local practices may require 
2 methods of birth control).
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25. Female is not pregnant, breastfeeding, or considering becoming pregnant during the study 
or for approximately 140 days (20 weeks or as guided by the local risankizumab label if 
approved, whichever is longer) after the last dose of study drug.
Prior Medication Restrictions
26. Subjects with prior exposure to biologic agents that block IL-12/23 (e.g., ustekinumab), IL-23 
(e.g., risankizumab, guselkumab), or IL-17 (e.g., secukinumab) are eligible, provided that the last 
drug administration occurred at least 6 months prior to Baseline.  Overall, no more than 10% of 
the study population will be subjects with prior exposure to these biologic agents.
27. Subjects who have had prior exposure to anti-TNF therapy (e.g., adalimumab, infliximab) for 
any indication are not eligible, unless they received anti-TNF therapy for HS and demonstrated 
inadequate response (TNF-IR).  The last anti-TNF treatment administration must have occurred 
at least 2 months prior to Baseline. 
28.No exposure to other immunomodulatory biologic therapies, including anti-IL-1 
(e.g., anakinra, canakinumab), within 3 months or 5 half-lives, whichever is longer, prior to 
Baseline.
29. No previous treatment with any cell-depleting therapies including but not limited to anti-CD20 
(e.g., rituximab) within 12 months prior to Baseline or until B cell count returns to normal level.
30. No use of traditional Chinese medicines within 4 weeks prior to the Baseline visit.
31. Subjects must not have received prescription topical therapies (including topical antibiotics) 
that can also be used to treat HS within 14 days prior to the Baseline visit.
32. Subjects must not have received systemic non-biologic therapies (e.g., spironolactone) that 
can also be used to treat HS within 4 weeks prior to the Baseline visit.
33. Subjects must not have received any systemic (including oral) antibiotic treatment for HS or 
any other inflammatory disorder within 4 weeks prior to the Baseline visit.
34. Subjects are required to use a daily antiseptic wash on their HS lesions starting at least 
14 days (2 weeks) prior to Baseline.  Allowable antiseptic washes are limited to one of the 
following:  chlorhexidine gluconate, benzoyl peroxide, benzalkonium chloride, benzethonium 
chloride, or dilute bleach in bath water.
35. For HS and non-HS related pain, subjects must not have received oral concomitant 
analgesics (including opioids) within 14 days prior to the Baseline visit.
Exception:  Subjects may continue on non-opioid analgesics provided that the dose and dosing 
regimen have been stable for at least 14 days preceding the Baseline visit and are expected to 
remain stable at least until Week 16 visit.  Note:  For HS-related pain, analgesic therapy is limited 
to ibuprofen (as per local labeling, but not exceeding a dose of 800 mg orally every 6 hours and 
3.2 g orally every 24 hours) AND/OR acetaminophen (paracetamol) as per local labeling 
(Section 5.4).
36. Subject must not have received any live vaccine within 6 weeks prior to the first dose of 
study drug (Baseline), or expect the need for live vaccination during study participation including 
at least 140 days (20 weeks or as guided by the local risankizumab label if approved, whichever 
is longer) after the last dose of study drug.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
37. Subject must not have been treated with any other 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 (FSH) level > 40 IU/L.

Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).

Females, of Childbearing Potential

Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 140 days (20 weeks or as guided by the local risankizumab label if approved, 
whichever is longer) after the last dose of study drug.

Females must commit to one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, injectable, transdermal) associated with inhibition of ovulation initiated at 
least 1 month prior to study Baseline;

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 1 month prior to study Baseline;

Bilateral tubal occlusion/ligation [can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure];

Intrauterine device (IUD);

Intrauterine hormone-releasing system (IUS);

Vasectomized sexual partner(s) (provided the vasectomized partner has received 
medical assessment of the surgical success and is the sole sexual partner of the study 
subject);

True abstinence: Refraining from heterosexual intercourse when this is in line with the 
preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, 
ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable).
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
If required per local guidelines, male or female condom with or without spermicide OR cap, diaphragm 
or sponge with spermicide should be used in addition to one of the birth control methods listed above 
(excluding true abstinence).
Contraception recommendations related to use of concomitant therapies prescribed per standard of 
care should be based on the local label.
5.3 Prohibited Concomitant Medications and Therapy
Use of the following treatments is prohibited throughout the study:
1.
Use of any biologic immunomodulation agent, including but not limited to anti-TNF 
(e.g., adalimumab, infliximab), anti-IL-1 (e.g., anakinra, canakinumab), anti-IL-12/23 
(e.g., ustekinumab), other anti-IL-23 (e.g., guselkumab), or anti-IL-17 (e.g., secukinumab) 
throughout the study.
2.
Any other systemic therapy that can also be used to treat HS, including but not limited to 
apremilast, corticosteroids, methotrexate (MTX), cyclosporine, retinoids, acitretin/etretinate, 
hormonal therapy (except for contraception), zinc gluconate, intramuscular gamma-globulin, 
colchicine, metformin (except for continuous treatment of pre-existing diabetes), and fumaric 
acid esters throughout the study.
3.
Injectable corticosteroids.  Exception:  Rescue treatment (intralesional triamcinolone acetonide 
injection) initiated after Week 16 assessment.  
4.
Non-antibiotic topical therapies or changes in the concentration/frequency of such treatments 
that may be used to treat HS (e.g., zinc pyrithione, resorcinol, dapsone, and delgocitinib).  Other 
non-antibiotic topical treatments (e.g., corticosteroids, antifungals, etc.) are permitted, provided 
these are not being used in anatomic regions where HS lesions are located.
5.
Deroofing or skin-tissue-saving excision with electrosurgical peeling (STEEP), laser therapy, 
intense pulse light, local/wide/radical excision, incision and/or draining of lesions is prohibited.  
Exception:  Rescue treatment (local incision/draining) performed after Week 16 assessment.
6.
Any antibiotic therapy (topical and/or systemic) during study participation.  Systemic and/or 
topical antibiotic use is only allowed for the treatment of acute, non-HS related infections.
7.
Use of any treatments for HS-related pain, other than ibuprofen or acetaminophen 
(paracetamol), including but not limited to antiepileptics (e.g., gabapentin), tricyclics (e.g., 
nortriptyline), or selective serotonin norepinephrine reuptake inhibitors (e.g., duloxetine, 
venlafaxine). Use of any opioid is prohibited, regardless of the indication.
8.
Over-the-counter topical antiseptic washes, creams, ointments, gels, and liquids containing 
antibacterial agents to treat HS, other than those allowed as per concomitant therapy section.
9.
Phototherapy treatment (ultraviolet B [UVB] or ultraviolet A [UVA] phototherapy, including 
psoralen and ultraviolet A [PUVA]), tanning booth, or extended sun exposure.
10. Receipt of any live vaccine expected during study participation, including at least 140 days 
(20 weeks or as guided by the local risankizumab label if approved, whichever is longer) after 
the last dose of study drug.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
11. Live attenuated vaccines are not permitted during study participation and including up to 
140 days (20 weeks or as guided by the local risankizumab label if approved, whichever is 
longer) after the last dose of study drug.  Examples of live attenuated vaccines include, but are 
not limited to, the following:

Bacille Calmette-Guérin (BCG)

Zoster vaccine live (Zostavax)

Measles-mumps-rubella or measles mumps rubella varicella

Monovalent live attenuated influenza A (intranasal)

Oral polio vaccine

Rotavirus

Seasonal trivalent live attenuated influenza (intranasal)

Smallpox

Oral typhoid vaccine

Varicella (chicken pox)

Yellow fever

Dengue (Dengvaxia®)
12. Treatment with any investigational drug.
13. Medicinal and recreational cannabis or cannabinoid use.
14. Traditional Chinese medicines.
5.4 Prior and Concomitant Therapy
Required Concomitant Medications/Therapies
Subjects are required to use a daily antiseptic wash on their HS lesions.  Allowable antiseptic washes are 
limited to one of the following:  chlorhexidine gluconate, benzoyl peroxide, benzalkonium chloride, 
benzethonium chloride, or dilute bleach in bath water.
Allowed Concomitant Medications/Therapies
Stable doses of other concomitant therapies for chronic conditions, for which neither the condition nor 
the treatment are judged to exclude the subject from participation, are permissible.  All concomitant 
medications should be carefully evaluated by the investigator.
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject has received from 4 weeks prior to screening or receives during 
the study must be recorded along with the reason for use; date(s) of administration, including start and 
end dates; and dosage information including dose, route, and frequency on the appropriate electronic 
case report form (eCRF).
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact. Information regarding potential drug interactions with risankizumab can be located in the 
risankizumab IB.
Subjects must be able to safely discontinue any prohibited medications as specified in the eligibility 
criteria; where not specified, discontinuation must occur 5 half-lives or 4 weeks, whichever is longer, 
prior to initial study drug administration.  Subjects must be consented for the study prior to 
discontinuing any prohibited medications for the purpose of meeting study eligibility.
The following categories of concomitant medications/therapies are allowed during the study:

Antibiotics.  Concomitant use of oral antibiotics is only allowed for the treatment of acute non-
HS related infections.  Dosing and/or frequency need to be reported in the eCRF documentation; 
"as needed" (PRN) use is not permitted.  Use of topical or systemic antibiotics to treat HS or 
other chronic inflammatory disorders is prohibited.  Subjects who receive antibiotics for HS-
related infections will be considered treatment failures; however they will continue to receive 
the study treatment assigned at randomization.

Over-the-counter shampoos and soaps containing antibacterial agents.

Wound care.  Use of wound care dressings on HS wounds is allowed.  Recommended options 
include alginates, hydrocolloids, and hydrogels.

Analgesic therapy.  If a subject experiences pain (HS- related or non-HS-related) after Baseline, 
they may initiate analgesic treatment.  For HS-related pain, analgesic therapy is limited to 
ibuprofen (as per local labeling, but not exceeding a dose of 800 mg orally every 6 hours and 
3.2 g orally every 24 hours) AND/OR acetaminophen (paracetamol) as per local labeling.  For 
non-HS-related pain, all other non-opioid analgesics are allowed at the recommended or 
prescribed dose.  Use of opioid analgesics for HS-related or non-HS related pain is prohibited in 
the context of this study.
Subjects will complete a daily diary of their HS-related analgesic use.  Subjects will be required 
to record their analgesic use daily through Week 16; after Week 16, subjects will fill out 
analgesic use information for 7 days leading up to the visit.  Any changes in dosing and/or 
frequency need to be reported in the daily diary; documentation of only PRN use is not 
permitted.  Dose adjustments of ibuprofen or acetaminophen for HS-related pain up to the 
maximum permitted dose and frequency per local label are allowed during the study.
Subjects who are on a documented stable dose and dosing regimen of non-opioid analgesic 
treatment for at least 14 days prior to the Baseline visit may not adjust their regimen at least 
until the Week 16 assessment.
Rescue Medications/Therapy
Rescue treatment is allowed to start only after the Week 16 assessments.  Rescue treatment is limited 
to an injection with intralesional triamcinolone acetonide suspension OR local incision and draining.
In the event that an acutely painful HS lesion that requires immediate intervention occurs after the 
Week 16 assessment, 2 protocol-allowed interventions per subject are permissible for the remainder of 
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
the study.  An intervention can occur at a maximum on 2 different lesions at the same visit or on the 
same lesion at 2 different study visits.  The same lesion cannot be treated 2 times at the same visit.
All study visit evaluations have to occur before interventions are performed.  If incision and draining is 
performed, antiseptic creams/liquids are allowed to be administered on the specific lesions upon which 
an intervention had been performed for as many days as considered medically necessary by the 
investigator.
When counting the total lesions in each body region, the site will be required to count any lesion that 
undergoes an intervention as permanently present from the date of the intervention, regardless of the 
outcome of the intervention performed.
5.5 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study drug and/or study at any time for 
reasons including, but not limited to, the following:

Clinically significant abnormal laboratory result(s) or AE(s) that preclude continuation of the 
study medication, as determined by the Investigator and the TA MD (as applicable).

The Investigator believes withdrawal from the study is in the best interest of the subject.

The subject requests withdrawal from the study.

Eligibility criteria violation(s) are noted after the subject started study drug, if continuation of 
the study drug would place the subject at risk as determined by the AbbVie TA MD, after 
consultation with the Investigator.

Introduction of prohibited medications 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.

Subject becomes pregnant while participating in the study.

Subject is diagnosed with a malignancy.  Exception:  Localized NMSC or carcinoma in-situ of the 
cervix, where discontinuation is at the discretion of the Investigator.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the study.

Subject requires > 2 protocol-allowed HS interventions.

Post-Baseline occurrence of one or more of the following hepatic test abnormalities (confirmed 
on a second separate sample at least 48 hours apart):

ALT or AST > 8 × ULN;

ALT or AST > 5 × ULN for more than 2 weeks;

ALT or AST > 3 × ULN and Total Bilirubin > 2 × ULN or international normalized ratio [INR] 
> 1.5;

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (> 5%).
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made and 1 certified 
letter must be sent and documented in the subject's source documentation.
AbbVie may terminate this study prematurely, either in its entirety or at any site.  The investigator may 
also stop the study at his/her site if he/she has safety concerns.  If AbbVie terminates the study for 
safety reasons, AbbVie will promptly notify the investigator.
COVID-19 Pandemic-Related Acceptable Protocol Modification
During the COVID 19 pandemic, it has been necessary to employ mitigation strategies to enable the 
investigator to ensure subject safety and continuity of care.  Acceptable mitigation strategies are 
identified and included in the Operations Manual in Appendix F.
The investigator should contact the sponsor medical contact before discontinuing a subject from the 
study for a reason other than "planned per protocol," to ensure all acceptable mitigation steps have 
been explored.
Refer to the Operations Manual in Appendix F for details on how to handle study activities/procedures.
Interruption/Discontinuation of Study Drug Due to COVID-19 Infection
For subjects with documented COVID-19, the timing of next administration of study drug or possibility of 
premature discontinuation from study drug should be discussed with the AbbVie Medical Contact.  
Follow subsequent protocol Section 5.6 for subjects who discontinued study drug.
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, the procedures outlined for the Premature 
Discontinuation visit should be completed as soon as possible, preferably within 2 weeks.  In addition, if 
subject is willing and has not withdrawn consent, a 20-week follow-up phone call after the last dose of 
study drug may be completed to ensure all treatment-emergent AEs/SAEs 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, 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 from optional biomarker research, before subject withdrawal of consent, will remain 
part of the study results.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5.7 Study Drug
Information about the study drug and placebo used in this study is presented in (Table 1).
Table 1.
Identity of Investigational Product
Study Drug
Dosage Form
Formulation
Route of 
Administration
Manufacturer
Risankizumab (ABBV-066)
Solution for injection in 
pre-filled syringe (PFS)
90 mg/mL
SC injection
Boehringer-
Ingelheim Pharma 
GmbH & Co. KG
Placebo for risankizumab 
(ABBV-066)
Solution for injection in 
PFS
N/A
SC injection
Boehringer-
Ingelheim Pharma 
GmbH & Co. KG
N/A = not applicable; PFS = pre-filled syringe; SC = subcutaneous
Through Week 12 of Period A, study site staff will administer study drug subcutaneously as follows:

Risankizumab 180 mg (2 × 90 mg PFS and 2 × placebo PFS)

Risankizumab 360 mg (4 × 90 mg PFS), or

Matching placebo (4 × placebo PFS).
At Weeks 16, 17, and 18 in Period B, subjects who were originally randomized to receive risankizumab 
180 mg or 360 mg in Period A will receive placebo.  Subjects who were originally randomized to receive 
placebo will receive risankizumab 360 mg.
Beginning with Week 20 in Period B, study site staff will administer open-label risankizumab 360 mg 
subcutaneously as described above q8w until the end of the study.
Risankizumab and matching placebo will be packaged in quantities sufficient to accommodate study 
design.  Each kit will be labeled per local requirements, and this label must remain affixed to the kit.  
Upon receipt, study drug should be kept in the original packaging in a secured limited access storage 
area according to the recommended storage conditions on the medication label.  No extemporaneous 
dose preparation is required.
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.
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.
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5.8 Randomization/Drug Assignment
Each subject will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who rescreen, the screening number assigned by the IRT at the initial screening visit should be 
used.  Subjects may only be rescreened one time.  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 who meet the study's eligibility criteria will be initially randomized to receive either 
risankizumab 180 mg or 360 mg as an SC injection or matching placebo up to Week 16 in a 1:1:1 ratio.  
Subjects who have been treated with anti-TNF therapy and had inadequate response to this therapy 
(TNF- IR) will be eligible.  Subjects will be randomized by their anti-TNF use (yes or no) prior to Baseline.  
TNF-naïve (no) subjects will be further stratified by the worst Hurley stage across all affected anatomic 
regions.  Therefore, there will be 4 strata in total:

Prior exposure to anti-TNF (yes)

Prior exposure to anti-TNF (no) with the worst Hurley Stage as I

Prior exposure to anti-TNF (no) with the worst Hurley Stage as II

Prior exposure to anti-TNF (no) with the worst Hurley Stage as III
All AbbVie personnel with direct oversight of the conduct and management of the study (with the 
exception of AbbVie Drug Supply Management Team) will remain blinded until the Primary Analysis at 
Week 16 is available.  The investigator, study site personnel, and the subject will remain blinded to each 
subject's initial treatment throughout the study.  To maintain the blind, the risankizumab kits and 
placebo kits provided for the study will be identical in appearance.  The IRT will provide access to 
unblinded subject treatment information in the case of a medical emergency.
5.9 Protocol Deviations
The investigator is responsible for complying with all protocol requirements, written instructions, and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when 
necessary to eliminate an immediate hazard to study subjects.  If a protocol deviation occurs (or is 
identified, including those that may be due to the COVID-19 pandemic), the investigator is responsible 
for notifying IEC/IRB, regulatory authorities (as applicable), and AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.  Product complaints occurring during the 
study will be followed up to a satisfactory conclusion.
Medical Complaints/Adverse Events and Serious Adverse Events
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
"special situations" as accidental or intentional overdose, medication error, occupational or accidental 
exposure, off-label use, drug abuse, drug misuse or drug withdrawal, all which must be reported 
whether associated with an adverse event or not.  Any worsening of a pre-existing condition or illness is 
considered an AE.  Worsening in severity of a reported AE should be reported as a new AE.  Laboratory 
abnormalities and changes in vital signs are considered to be an AE only if they result in discontinuation 
from the study, necessitate therapeutic medical intervention, meet protocol-specific criteria, and/or the 
investigator considers it to be an AE.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and/or the surgery/procedure has 
been pre planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an AE.
If an AE, whether associated with study drug or not, meets any of the following criteria, it is to be 
reported to AbbVie clinical pharmacovigilance 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):
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Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not been 
taken.  This does not include an event that would have been fatal if it 
had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length 
of time or prolongs the subject's hospital stay.  This does not include 
an emergency room visit or admission to an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with 
the activities of daily living of a study subject.  Disability is not 
intended to include experiences of relatively minor medical 
significance such as headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle).
Important Medical Event 
Requiring Medical or Surgical 
Intervention to Prevent 
Serious Outcome
An important medical event that may not be immediately life-
threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require 
medical or surgical intervention to prevent any of the outcomes 
listed above (i.e., death of subject, life threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent or 
significant disability/incapacity).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or 
drug abuse.
All AEs reported from the time of study drug administration until 20 weeks (140 days) after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, SAEs and protocol-related nonserious AEs will be collected from 
the time the subject signs the study-specific informed consent.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product 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.
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
Grade 2 (Moderate):  Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living.

Grade 3 (Severe):  Medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living.

Grade 4 (Severe):  Life-threatening consequences; urgent intervention indicated.

Grade 5 (Severe):  Death related to AE.
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Pregnancy
While not an AE, pregnancy in a study subject must be reported to AbbVie within 24 hours after the site 
becomes aware of the pregnancy.  Subjects who become pregnant during the study must be 
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 Independent Data Monitoring Committee
An external IDMC will review unblinded safety data on a cohort level, at approximate 6-month intervals 
throughout the course of the study.

A separate IDMC charter will be prepared outside of the protocol and will describe the roles and 
responsibilities of the IDMC members, frequency and triggers of data reviews, and relevant 
safety data to be assessed.  Unblinded adjudicated cardio-cerebrovascular events will be 
presented to the IDMC for review on a periodic basis.

Communications from the IDMC to the Study Teams will not contain information that could 
potentially unblind the team to subject treatment assignments.
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6.3 Cardiovascular Adjudication Committee
An independent adjudication committee will be adjudicating all observed cardio- and cerebro-vascular 
events and will remain blinded to treatment allocation.  The events that are adjudicated and the 
adjudication process will be detailed in the CAC 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.
6.4 Anaphylaxis Adjudication Committee
While no concerns with systemic hypersensitivity have been identified with the use of risankizumab, the 
sponsor has established the AAC to adjudicate events of anaphylaxis based on pre-specified definitions.  
This independent, external committee will adjudicate suspected anaphylactic reactions and will remain 
blinded to treatment allocation.  The event terms to be adjudicated and the adjudication process are 
detailed in the AAC Charter.  A supplemental Hypersensitivity Reactions Signs and Symptoms eCRF will 
be used to collect information pertinent to the events (Table 2).  In addition, the site may be contacted 
for additional source documentation for relevant events.
If a suspected systemic hypersensitivity reaction occurs at the investigative site, subjects should be 
tested for tryptase and histamine levels.  In addition to testing tryptase and histamine levels, 
pharmacokinetic (PK) and ADA/NAb samples will also be collected.  If a systemic hypersensitivity 
reaction such as anaphylaxis is suspected while the subject is not at the investigative site, every effort 
should be made to obtain tryptase and histamine levels from the treating facility to help better 
characterize the diagnosis.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The Primary Analysis will be conducted after all continuing subjects complete Week 16 and all data 
pertaining to Period A are cleaned.  This will be the only and final analysis for efficacy in Period A.  Study 
sites and subjects will remain blinded to their initial treatment assignment for the duration of the entire 
study.
The statistical analysis will be described and fully documented in the SAP, which will be finalized prior to 
the start of the study.  All statistical tests, between each risankizumab dose and placebo, will be 
performed at a two-sided alpha level of 0.025.
The statistical analyses will be performed using SAS (SAS Institute Inc., Cary, North Carolina, USA).
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7.2 Definition for Analysis Populations
The intent-to-treat (ITT) Population, which includes all randomized subjects, will be used for all efficacy 
analyses.  Subjects who are randomized to placebo in Period A and do not continue into Period B will be 
excluded from the analysis in Period B.
In order to evaluate the impact of major protocol deviations on the primary efficacy endpoint, additional 
sensitivity analyses may be performed on a per-protocol population, which excludes subjects with major 
protocol deviations that potentially affect the primary efficacy endpoint.  If it is decided that this analysis 
should be performed, the criteria for exclusion of subjects from the per-protocol population will be fully 
defined in the classification plan, and the exclusion of subjects from the per-protocol population will be 
finalized before blind break and before the database lock for the primary analysis.
The following populations will be used for the safety analysis:

The Safety Population in Period A (Safety_A) is defined as all subjects who are randomized and 
received at least one dose of study drug in Period A.

The Safety Population in Period B (Safety_B) is defined as all subjects who received at least 
one dose of study drug in Period B.

The all risankizumab treated (ALL_RZB) Population is defined as subjects who received at least 
one dose of risankizumab in the study.  This population will be used to provide a comprehensive 
summary of safety.
7.3 Statistical Analyses for Efficacy
Analysis of all efficacy endpoints in Period A will be conducted on the ITT Population, based on 
treatment as randomized for Period A.  In addition, the primary efficacy endpoint will be analyzed in the 
per-protocol population, if defined.
Comparison of the primary endpoint will be made between each risankizumab dose and placebo using
the Cochran-Mantel-Haenszel (CMH) test, adjusting for stratification factors.  Non-responder imputation 
(NRI) will be the primary approach to handle missing values.  To account for impact of COVID-19 
pandemic, the NRI will be adjusted to NRI-C, Non-Responder Imputation incorporating multiple 
imputation to handle missing data due to COVID-19.
The overall type-I error rate will be strongly controlled using a graphical multiple testing procedure. The 
primary and ranked secondary endpoints will be first tested in the ranked order specified in Section 3
between each risankizumab dose and placebo, with a 2-sided significance level of 0.025.  Continued 
testing will follow a pre-specified α transfer path which includes downstream transfer along the 
endpoint sequence. More details of the graphical procedure will be specified in the SAP.
Details on the primary and other efficacy analyses will be provided in the SAP.
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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 of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, 
applicable regulations, and guidelines governing clinical study conduct and the ethical principles that 
have their origin in the Declaration of Helsinki.  Responsibilities of the investigator are specified in 
Appendix B.
In the event of a state of emergency due to the COVID-19 pandemic leading to difficulties in performing 
protocol-specified procedures, AbbVie will engage with study site personnel in efforts to ensure the 
safety of subjects, maintain protocol compliance, and minimize risks to the integrity of the study while 
trying to best manage subject continuity of care.  This may include alternative methods for assessments 
(e.g., phone contacts or virtual site visits), alternative locations for data collection (e.g., use of a local lab 
instead of a central lab), and study visit schedule modification.  Refer to the Operations Manual in 
Appendix F for additional details.  In all cases, these alternative measures must be allowed by local 
regulations and permitted by IRB/IEC.  Investigators should notify AbbVie if any urgent safety measures 
are taken to protect the subjects against any immediate hazard.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
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 
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requirement(s).  During the COVID-19 pandemic, remote monitoring of data may be employed if allowed 
by the local regulatory authority, IRB/IEC, and the study site.
Supplemental study case report forms should be completed in the event of COVID -19-related 
missed/virtual visits, study drug interruptions or discontinuations, or adverse events (including capture 
of specific signs/symptoms of infection and testing results).
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
11
COMPLETION OF THE STUDY
The end of study is defined as the date of the last subject's last contact, which will be a follow-up phone 
call 20 weeks after the last dose.
12
REFERENCES
1.
Zouboulis CC, Del Marmol V, Mrowietz U, et al. Hidradenitis suppurativa/acne inversa: criteria for 
diagnosis, severity assessment, classification and disease evaluation. Dermatology. 2015;231(2):184-
90.
2.
Fimmel S, Zouboulis CC. Comorbidities of hidradenitis suppurativa (acne inversa). 
Dermatoendocrinol. 2010;2(1):9-16.
3.
Fitzsimmons JS, Guilbert PR, Fitzsimmons EM. Evidence of genetic factors in hidradenitis 
suppurativa. Br J Dermatol. 1985;113(1):1-8.
4.
Jemec GB. The symptomatology of hidradenitis suppurativa in women. Br J Dermatol. 
1988;119(3):345-50.
5.
Lookingbill DP. Yield from a complete skin examination: findings in 1157 new dermatology patients. 
J Am Acad Dermatol. 1988;18(1 Pt 1):31-7.
6.
Jemec GB, Heidenheim M, Nielsen NH. The prevalence of hidradenitis suppurativa and its potential 
precursor lesions. J Am Acad Dermatol. 1996;35(2 Pt 1):191-4.
7.
Revuz JE, Canoui-Poitrine F, Wolkenstein P, et al. Prevalence and factors associated with hidradenitis 
suppurativa: results from two case-control studies. J Am Acad Dermatol. 2008;59(4):596-601.
8.
Saunte DML, Jemec GBE. Hidradenitis suppurativa: advances in diagnosis and treatment. JAMA. 
2017;318(20):2019-32.
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9.
Saunte DM, Boer J, Stratigos A, et al. Diagnostic delay in hidradenitis suppurativa is a global 
problem. Br J Dermatol. 2015;173(6):1546-9.
10. von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppurativa. Br J Dermatol. 
2001;144(4):809-13.
11. Sampogna F, Abeni D, Gieler U, et al. Impairment of sexual life in 3,485 dermatological outpatients 
from a multicentre study in 13 European countries. Acta Derm Venereol. 2017;97(4):478-82.
12. Janse IC, Deckers IE, van der Maten AD, et al. Sexual health and quality of life are impaired in 
hidradenitis suppurativa: a multicentre cross-sectional study. Br J Dermatol. 2017;176(4):1042-7.
13. Thorlacius L, Cohen AD, Gislason GH, et al. Increased suicide risk in patients with hidradenitis 
suppurativa. J Invest Dermatol. 2018;138(1):52-7.
14. Vangipuram R, Vaidya T, Jandarov R, et al. Factors contributing to depression and chronic pain in 
patients with hidradenitis suppurativa: results from a single-center retrospective review. 
Dermatology. 2016;232(6):692-5.
15. Shavit E, Dreiher J, Freud T, et al. Psychiatric comorbidities in 3207 patients with hidradenitis 
suppurativa. J Eur Acad Dermatol Venereol. 2015;29(2):371-6.
16. Miller IM, McAndrew RJ, Hamzavi I. Prevalence, risk factors, and comorbidities of hidradenitis 
suppurativa. Dermatol Clin. 2016;34(1):7-16.
17. Egeberg A, Gislason GH, Hansen PR. Risk of major adverse cardiovascular events and all-cause 
mortality in patients with hidradenitis suppurativa. Jama dermatol. 2016;152(4):429-34.
18. Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis 
suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29(4):619-44.
19. Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis 
suppurativa. N Engl J Med. 2016;375(5):422-34.
20. Prens E, Deckers I. Pathophysiology of hidradenitis suppurativa: an update. J Am Acad Dermatol. 
2015;73(5 Suppl 1):S8-11.
21. Hotz C, Boniotto M, Guguin A, et al. Intrinsic defect in keratinocyte function leads to inflammation in 
hidradenitis suppurativa. J Invest Dermatol. 2016;136(9):1768-80.
22. van der Zee HH, de Ruiter L, van den Broecke DG, et al. Elevated levels of tumour necrosis factor 
(TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting 
TNF-alpha and IL-1beta. Br J Dermatol. 2011;164(6):1292-8.
23. Kelly G, Hughes R, McGarry T, et al. Dysregulated cytokine expression in lesional and nonlesional 
skin in hidradenitis suppurativa. Br J Dermatol. 2015;173(6):1431-9.
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24. Shah A, Alhusayen R, Amini-Nik S. The critical role of macrophages in the pathogenesis of 
hidradenitis suppurativa. Inflamm Res. 2017;66(11):931-45.
25. Schlapbach C, Hanni T, Yawalkar N, et al. Expression of the IL-23/Th17 pathway in lesions of 
hidradenitis suppurativa. J Am Acad Dermatol. 2011;65(4):790-8.
26. Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a 
search for potential biomarkers in serum. Br J Dermatol. 2016;174(4):839-46.
27. Prussick L, Rothstein B, Joshipura D, et al. Secukinumab for patients with moderate-to-severe 
hidradenitis suppurativa. Abstract #610.  In: Program and abstracts from IID 2018, International 
Investigative Dermatology Meeting; Orlando, FL:May 16-19, 2018.
28. Khader SA, Pearl JE, Sakamoto K, et al. IL-23 compensates for the absence of IL-12p70 and is 
essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-
specific IFN-gamma responses if IL-12p70 is available. J Immunol. 2005;175(2):788-95.
29. O'Garra A, Redford PS, McNab FW, et al. The immune response in tuberculosis. Annu Rev Immunol. 
2013;31:475-527.
30. Qian X, Gu L, Ning H, et al. Increased Th17 cells in the tumor microenvironment is mediated by IL-23 
via tumor-secreted prostaglandin E2. J Immunol. 2013;190(11):5894-902.
31. Baird AM, Leonard J, Naicker KM, et al. IL-23 is pro-proliferative, epigenetically regulated and 
modulated by chemotherapy in non-small cell lung cancer. Lung Cancer. 2013;79(1):83-90.
32. Hu WH, Chen HH, Yen SL, et al. Increased expression of interleukin-23 associated with progression of 
colorectal cancer. J Surg Oncol. 2017;115(2):208-12.
33. AbbVie. Data on File, RRT165055.
34. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0 27 November 2017 [Available from: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer
ence_8.5x11.pdf.
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APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AAC
Anaphylaxis Adjudication Committee
Ab
antibody
ADA
antidrug antibody
AE
adverse event
Ag
antigen
ALT
alanine transaminase
AN
abscess and inflammatory nodule
ANC
absolute neutrophil count
ASI
areas of special interest
AST
aspartate transaminase
BCG
Bacilli Calmette-Guérin
CAC
Cardiovascular Adjudication Committee
CMH
Cochran-Mantel-Haenszel
CTC
Common Toxicity Criteria
CTCAE
Common Terminology Criteria for Adverse Events
COVID-19
Coronavirus Disease – 2019
CV
cardiovascular
DLQI
Dermatology Life Quality Index
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
EQ-5D-5L
EuroQol 5 Dimensions 5 Levels Health State Instrument
EU
European Union
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
HADS
Hospital Anxiety and Depression Scale
HB
hepatitis B
HBV
hepatitis B virus
HCV
hepatitis C virus
HCV Ab
hepatitis C virus antibody
HiSCR
Hidradenitis Suppurativa Clinical Response
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HIV
human immunodeficiency virus
HIV Ab
HIV antibody
HS
hidradenitis suppurativa
hsCRP
high-sensitivity C-reactive protein
HSIA
Hidradenitis Suppurativa Impact Assessment
HSSA
Hidradenitis Suppurativa Symptom Assessment
IB
Investigator's Brochure
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IgG1
immunoglobulin G1
IGRA
interferon gamma release assay
IL
interleukin
INR
international normalized ratio
IRB
institutional review board
IRT
interactive response technology
ITT
intent-to-treat
IUD
intrauterine device
IUS
Intrauterine hormone-releasing system
mAb
monoclonal antibody
MACE
major adverse cardiac event
MedDRA
Medical Dictionary for Regulatory Activities
MI
myocardial infarction
MTX
methotrexate
NAb
neutralizing antibody
NCI
National Cancer Institute
NMSC
non-melanoma skin cancer
NRI
non-responder imputation
NRS
numerical rating scale
NRS30
at least 30% reduction and at least 1 unit reduction from Baseline in Patient's Global 
Assessment of Skin Pain
NSAID
nonsteroidal anti-inflammatory drug
PCR
polymerase chain reaction
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PFS
pre-filled syringe
PGA
Patient's Global Assessment of Skin Pain
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetic(s)
PPD
purified protein derivative
PRN
as needed
PT
preferred term
PRO
patient-reported outcome
PUVA
psoralen and ultraviolet A
q8w
every 8 weeks
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SOC
system organ class
STEEP
skin-tissue-saving excision with electrosurgical peeling
SUSAR
suspected unexpected serious adverse reaction
TA MD
Therapeutic Area Medical Director
TB
tuberculosis
TEAE
treatment-emergent adverse event
Th17
T helper 17
TNF
tumor necrosis factor
ULN
upper limit of normal
US
United States
UVA
ultraviolet A
UVB
ultraviolet B
WBC
white blood cell
WPAI
Work Productivity and Activity Impairment
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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M16-833 - Hidradenitis Suppurativa:  Risankizumab versus Placebo for Adult Subjects with 
Moderate to Severe Hidradenitis Suppurativa
Protocol Date: 15 December 2020
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation 
of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practices (GCP) and 
local 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
Pharmaceutical Development
Pharmaceutical Development
Pharmacovigilance and Patient Safety
Clinical Program Development
Data and Statistical Sciences
Data and Statistical Sciences
Data and Statistical Sciences
Clinical Pharmacology & Pharmacometrics
Medical Writing
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APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities across the Screening, 6 Period A, 10 Period B, and 
Study Follow-up subject encounters.  The individual activities and allowed modifications due to 
COVID-19 are described in detail in the Operations Manual.
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APPENDIX E. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions 
Protocol
Date
Version 1.0
04 March 2019
Version 1.1 (VHP countries only)
28 June 2019
Version 2.0
19 August 2019
Version 3.0
26 March 2020
Version 4.0
09 June 2020
The purpose of Protocol Version 5.0 is to update the following sections below and incorporate necessary 
protocol modifications due to the COVID-19 pandemic and per revised Risankizumab Safety Standards 
(v7.0) as follows:
Modifications to the Protocol and Operations Manual due to State-of Emergency or Pandemic 
Situations 
One of the purposes of this version is to provide flexibility during state-of emergency or pandemic 
situations so subjects may safely enroll and continue study participation as follows:

Included information in Section 2.2 on the re-evaluation of the benefit and risk to subjects 
participating in the study.  The benefit-risk profile of various immunomodulatory therapies is 
being evaluated.
Rationale: To clarify the benefit-risk balance to participating subjects in this study in light of the 
COVID-19 pandemic.

Modify the following sections to account for state-emergency or pandemic situations:

Update Section 5.5 to permit mitigation strategies for 
withdrawal/interruption/discontinuation of study drug.

Update Section 5.9 to define protocol deviations to include those due to the COVID-19 
pandemic.

Updated Section 7.3 to clarify that in the efficacy analysis, Non-Responder Imputation 
incorporating multiple imputation will be utilized to handle missing data due to COVID-19.

Update Section 8.2 with a reference to the Operations Manual to permit modifications to 
the study protocol as necessary due to state-of emergency or pandemic situations and note 
investigators should also notify AbbVie if any urgent safety measures are taken.

Update Section 9 to note that remote monitoring may be employed as needed.

Update Appendix D to add reference to Operations Manual for allowed modifications.
Rationale:  To provide flexibility during state-of emergency or pandemic situations to ensure the 
safety of subjects, maintain protocol compliance, and minimize risk to the integrity of the study 
while trying to best manage continued care of study subjects.
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STUDY M16-833  |  Version 5.0  |  EudraCT 2019-000122-21
CONFIDENTIAL INFORMATION
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
The following modifications were made in the Operations Manual to account for state-of 
emergency or pandemic situations:

Update Section 2 and Section 2.1 with specifics regarding activities that may be affected by 
state-of emergency or pandemic situations, including details in Section 2.1 specifying virtual 
visits that may be performed and modifications for laboratory and central testing.

Update Section 3.1 to clarify subject information and informed consent in case of state-of 
emergency or pandemic situations.

Update Section 3.4 to clarify patient reported outcomes (PROs) that may be conducted via 
phone or video conference in the case of state-of emergency or pandemic situations.  
Details instructions regarding PROs conducted over the phone or video conference are also 
provided.

Update Section 3.13 with instructions on performing laboratory work in the case of a 
state-of emergency or pandemic situation.

Update Section 4.3 to add COVID-19 as an event necessitating a supplemental eCRF.
Rationale:  To provide flexibility for subject activities while ensuring subject safety during 
state-of emergency or pandemic situations.
Protocol

In the Synopsis and Section 2.1, replaced the term/abbreviation "inflammatory nodule (AN)"
with "abscess and inflammatory nodule (AN)."
Rationale: To align with the full term/abbreviation defined in Appendix A.

In the Section 2.2, updated that subjects with active systemic infection or clinically important 
infection will not be included in the study.
Rationale: To update benefit-risk text according to revised risankizumab safety standard 
language.

In the Section 2.2, removed text stating that there are no cases of active TB, including no 
reactivation of TB in subjects diagnosed with latent TB, across the entire risankizumab 
development program to date.
Rationale: To update benefit-risk text according to revised risankizumab safety standard 
language.

In the Section 2.2, updated that subjects with positive QuantiFERON-TB testing/TB skin test who 
have latent TB and are considered at low risk for reactivation are not required to be treated with 
TB prophylaxis.
Rationale: To update benefit-risk text according to revised risankizumab safety standard 
language.

Clarified in Section 3.3 that the additional endpoint with respect to the proportion of subjects 
achieving at least 1 grade improvement from Baseline in PGIS scale is among subjects with 
Baseline PGIS of at least "minimal."
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STUDY M16-833  |  Version 5.0  |  EudraCT 2019-000122-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Rationale: To clarify this additional endpoint is only applicable among subjects with Baseline 
PGIS of at least "minimal" (i.e., who have room for "at least 1 grade improvement").

In Section 5.3, removed text for new topical therapies and clarified the use of non-antibiotic 
topical therapies or changes in the concentration/frequency of such treatments for the 
treatment of HS.
Rationale:  To clarify the restriction regarding non-antibiotic topical therapies and changes the 
in the concentration/frequency of topical therapies.

In Section 5.3, added in addition to systemic antibiotic use, "and/or topical" antibiotic use is only
allowed for the treatment of acute, non-HS related infections.
Rationale:  To clarify the restriction of both systemic and/or topical antibiotic use is only allowed 
for the treatment of acute, non-HS related infections.

In Section 5.3, added Dengue (Dengvaxia®) to the list of examples of live attenuated vaccines 
that are not permitted during study participation and including up to 140 days after the last 
dose of study drug.
Rationale:  To clarify the restriction of live attenuated vaccines as prohibited concomitant 
medications and therapies according to revised risankizumab safety standard language.

In Section 5.5, added hepatic test abnormalities confirmed by a second sample should be at 
least 48 hours apart.
Rationale:  To clarify the minimum timing between samples for hepatic test abnormalities that 
would constitute withdrawal of subject from study drug and/or study according to revised 
risankizumab safety standard language.

In Section 6.1 for product complaints and pregnancies, replaced the reporting period from 
'1 business day' or '1 working day' (respectively) to '24 hours.'
Rationale:  To update the safety reporting period according to revised risankizumab safety 
standard language.

In Section 6.1, update the text 'areas of safety interest' to 'areas of safety interest/safety topics 
of interest' and rename Table 2 'Areas of Safety Interest' to 'Supplemental Adverse Events 
eCRFs.'
Rationale:  To update the safety reporting terms according to revised risankizumab safety 
standard language.

In Section 6.1, removed text that infections, especially opportunistic infections, are a potential 
risk with immunomodulators.
Rationale:  To update the areas of safety interest text according to revised risankizumab safety 
standard language.

In Appendix C, updated protocol signatories and titles.
Rationale:  To update due to personnel changes for this protocol amendment.

In Appendix D, removed "PGA Skin Pain and Analgesic Use" as an assessment performed at the 
Week 36 visit.
Rationale:  To correct a typographical error.
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STUDY M16-833  |  Version 5.0  |  EudraCT 2019-000122-21
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Operations Manual

In Section 1 and Section 4.3, updated the safety team contact information.
Rationale:  To correct per current safety contact information.
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