Clinical trial NCT03926169
Conditions: Hidradenitis Suppurativa
Keywords: Hidradenitis Suppurativa Risankizumab Placebo
Sponsor: AbbVie
Start date: 2019-06-03; Completion date: 2021-08-02
Enrollment: 243 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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 hidradenitis suppurativa (HS) in adult participants diagnosed for at least one year before the Baseline visit.

Detailed description:

Arms: arm 1: In Period A, participants receive blinded risankizumab 180 mg via a subcutaneous (SC) injection at Weeks 0 (Baseline), 1, 2, 4, and 12. arm 2: In Period A, participants receive blinded risankizumab 360 mg via a SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12. arm 3: In Period A, participants receive blinded placebo via a SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12. arm 4: In Period A, participants receive blinded risankizumab 180 mg via a subcutaneous (SC) injection at Weeks 0 (Baseline), 1, 2, 4, and 12.

In Period B, participants receive blinded placebo at Weeks 16, 17, and 18. Starting at Week 20, participants receive open-label risankizumab 360 mg every 8 weeks (q8w) at Weeks 20, 28, 36, 44, 52, and 60. arm 5: In Period A, participants receive blinded risankizumab 360 mg via a SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12.

In Period B, participants receive blinded placebo at Weeks 16, 17, and 18. Starting at Week 20, participants receive open-label risankizumab 360 mg q8w at Weeks 20, 28, 36, 44, 52, and 60. arm 6: In Period A, participants receive blinded placebo via a SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12.

In Period B, participants receive blinded risankizumab 360 mg at Weeks 16, 17, and 18. Starting at Week 20, participants receive open-label risankizumab 360 mg q8w at Weeks 20, 28, 36, 44, 52, and 60.
Interventions: intervention 1: Risankizumab intervention 2: Placebo for risankizumab
Intervention descriptions: intervention 1: Risankizumab is administered as a SC injection in pre-filled syringe (PFS) intervention 2: Placebo for risankizumab is administered as a SC injection in PFS

Protocol documents:
Prot_000.pdf: 


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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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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
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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No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
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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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.
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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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.
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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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.
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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STUDY M16-833  |  Version 5.0  |  EudraCT 2019-000122-21
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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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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.
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.
Page 43 of 111
 










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.
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.
Page 48 of 111
 


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.

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.
Page 50 of 111
 


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.
Page 51 of 111
 

SAP_001.pdf: 
Risankizumab
M16-833 – Statistical Analysis Plan
Version 4.0 – 19 January 2021
1
Statistical Analysis Plan for Study M16-833
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
Date:  19 January 2021
Version 4.0
NCT03926169


Risankizumab
M16-833 – Statistical Analysis Plan
Version 4.0 – 19 January 2021
2
Table of Contents
1.0
Introduction .............................................................................5
2.0
Study Design and Objectives..................................................5
2.1
Objectives, Hypotheses and Estimands .....................................................5
2.2
Study Design Overview .............................................................................9
2.3
Treatment Assignment and Blinding .......................................................10
2.4
Sample Size Determination......................................................................11
3.0
Endpoints................................................................................12
3.1
Primary Endpoint.....................................................................................12
3.2
Secondary Endpoint .................................................................................12
3.3
Additional Endpoints ...............................................................................13
3.4
Safety Endpoints ......................................................................................14
3.5
Pharmacokinetic Endpoints .....................................................................14
4.0
Analysis Populations .............................................................14
5.0
Subject Disposition................................................................16
6.0
Study Drug Duration and Compliance................................16
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ....................17
7.1
Demographics and Baseline Characteristics............................................17
7.2
Medical History .......................................................................................18
7.3
Prior and Concomitant Medications ........................................................18
8.0
Handling of Potential Intercurrent Events for the 
Primary Endpoint..................................................................19
9.0
Efficacy Analyses...................................................................20
9.1
General Considerations............................................................................20
9.2
Handling of Missing Data........................................................................21
9.2.1
Categorical Endpoints..............................................................................22
9.2.2
Continuous Endpoints..............................................................................24
9.3
Primary Efficacy Endpoint and Analyses ................................................24
9.3.1
Primary Efficacy Endpoint ......................................................................24
9.3.2
Main Analysis of Primary Efficacy Endpoint..........................................25


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9.3.3
Sensitivity and Supplementary Analyses of the Primary Efficacy 
Endpoint...................................................................................................26
9.4
Secondary Efficacy Analyses...................................................................26
9.4.1
Key Secondary Efficacy Endpoints .........................................................26
9.4.2
Main Analyses of Key Secondary Efficacy Endpoints............................27
9.4.3
Sensitivity and Supplementary Analyses for Key Secondary 
Efficacy Endpoints...................................................................................31
9.5
Additional Efficacy Analyses ..................................................................32
9.6
Efficacy Subgroup Analyses....................................................................33
10.0
Safety Analyses ......................................................................34
10.1
General Considerations............................................................................34
10.2
Adverse Events ........................................................................................34
10.2.1
Treatment-Emergent Adverse Events ......................................................34
10.2.2
Adverse Event Overview .........................................................................35
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT .......................36
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure ..................................................................................................36
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation...............................................................................38
10.2.6
Area of Safety Interest .............................................................................38
10.3
Analysis of Laboratory Data....................................................................38
10.4
Analysis of Vital Signs ............................................................................40
10.5
Safety Subgroup Analyses .......................................................................40
10.6
Other Safety Analyses..............................................................................41
11.0
Other Analyses.......................................................................41
12.0
Interim Analyses....................................................................41
12.1
Data Monitoring Committee....................................................................41
13.0
Overall Type-I Error Control ..............................................41
14.0
Version History......................................................................42
15.0
References...............................................................................43


Risankizumab
M16-833 – Statistical Analysis Plan
Version 4.0 – 19 January 2021
4
List of Tables
Table 1.
Power under a 1:1:1 randomization .........................................................12
Table 2.
Summary of the Estimand Attributes of the Primary Efficacy 
Endpoint...................................................................................................25
Table 3.
Summary of the Estimand Attributes of the Sensitivity Analysis of 
the Primary Efficacy Endpoint among the PP Population.......................26
Table 4.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints...................................................................................29
Table 5.
SAP Version History Summary...............................................................42
List of Figures
Figure 1.
Study Schematic.......................................................................................10
List of Appendices
Appendix A.
Protocol Deviations..................................................................................44
Appendix B.
Definition of Area of Safety Interest........................................................45
Appendix C.
Potentially Clinically Important Criteria for Safety Endpoints ...............46
Appendix D.
Criteria for Potentially Clinically Important Vital Sign Values ..............48
Appendix E.
Non-Responder Imputation Incorporating Multiple Imputation to 
Handle Missing Data Due to COVID-19 Pandemic for 
Dichotomized Outcome Variables...........................................................49


Risankizumab
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Version 4.0 – 19 January 2021
5
1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for risankizumab 
Study M16-833, 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 (HS). 
Study M16-833 evaluates the efficacy and safety 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. 
This SAP provides summaries of the planned statistical analyses for safety and efficacy 
endpoints, and overall type-I error control strategies.
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analysis.
Unless noted otherwise, all analyses will be performed using SAS Version 9.4 (SAS 
Institute Inc., Cary, NC  27513) or later under the UNIX operating system.
2.0
Study Design and Objectives
2.1
Objectives, Hypotheses and Estimands
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.
The primary efficacy objective is based on the achievement of Hidradenitis Suppurativa 
Clinical Response (HiSCR; 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) 
at Week 16 of treatment with risankizumab 360 mg or 180 mg when compared to placebo 
among the Intent-to-Treat (ITT) Population, which consists of all randomized subjects 
(Section 5.0). 


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The corresponding null hypothesis for the primary endpoint is:
●
There is no difference between each risankizumab dose and placebo, with 
respect to the proportion of subjects who achieved HiSCR at Week 16. 
The estimand corresponding to the primary endpoint is defined using composite variable 
strategy: 
●
Achievement of HiSCR at Week 16 without the initiation of any antibiotics for 
HS-related infections and without premature discontinuation of study drug due 
to lack of efficacy prior to Week 16.
The secondary efficacy objectives are based on the ranked secondary endpoints as defined 
in Section 3.2.
The null hypothesis for the first ranked secondary endpoint is:
●
There is no difference between each risankizumab dose and placebo, in the 
proportion of subjects achieving NRS30 in PGA Skin Pain at Week 8 among 
subjects with Baseline NRS ≥ 3.
The corresponding estimand is 
●
Achievement of NRS30 in PGA Skin Pain at Week 8 among subjects with 
Baseline NRS ≥ 3 without the initiation of any antibiotics for HS-related 
infections, without the impact of analgesics for HS-related skin pain at Week 8 
and without premature discontinuation of study drug due to lack of efficacy 
prior to Week 8.
The null hypothesis for the second ranked secondary endpoint is:
●
There is no difference between each risankizumab dose and placebo, in the 
proportion of subjects achieving NRS30 in PGA Skin Pain at Week 16 among 
subjects with Baseline NRS ≥ 3.


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The corresponding estimand is 
●
Achievement of NRS30 in PGA Skin Pain at Week 16 among subjects with 
Baseline NRS ≥ 3 without the initiation of any antibiotics for HS-related 
infections, without the impact of analgesics for HS-related skin pain at Week 
16 and without premature discontinuation of study drug due to lack of efficacy 
prior to Week 16.
The null hypothesis for the third ranked secondary endpoint is:
●
There is no difference between each risankizumab dose and placebo in the 
proportion of subjects who experience flare, defined as an increase in AN count 
of at least a 25% with a minimum increase of 2 relative to Baseline (flare), 
during Period A.
The corresponding estimand is 
●
Experience of flare during Period A.
The null hypothesis for the fourth ranked secondary endpoint is:
●
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in Dermatology Life Quality Index (DLQI) at Week 16.
The corresponding estimand is 
●
Change from Baseline in DLQI at Week 16.
The null hypothesis for the fifth ranked secondary endpoint is: 
●
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in HS-related worst swelling - assessed based on the Hidradenitis 
Suppurativa Symptom Assessment (HSSA) at Week 16.


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The corresponding estimand is 
●
Change from Baseline in HS-related worst swelling - assessed based on the 
HSSA at Week 16.
The null hypothesis for the sixth ranked secondary endpoint is: 
●
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in HS-related worst odor - assessed based on the HSSA at Week 
16.
The corresponding estimand is 
●
Change from Baseline in HS-related worst odor - assessed based on the HSSA 
at Week 16.
The null hypothesis for the seventh ranked secondary endpoint is: 
●
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in HS-related worst drainage- assessed based on the HSSA at 
Week 16.
The corresponding estimand is 
●
Change from Baseline in HS-related worst drainage - assessed based on the 
HSSA at Week 16.
The Primary Analysis will be performed after the last ongoing subject has completed the 
Week 16 visit, and the data up to Week 16 cutoff date have been cleaned.  The cutoff date 
will be specified in the statistical programming plan (SPP) before the database lock for the 
Primary Analysis and before unblinding of subject randomization.


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9
2.2
Study Design Overview
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. 
●
Period A: Subjects who meet the study's eligibility criteria (protocol 
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 Baseline, Weeks 1, 2, 4, and 12.  The final efficacy evaluation of 
Period A will be at Week 16.  
●
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.
The schematic of the study is shown in Figure 1.


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10
Figure 1.
Study Schematic
2.3
Treatment Assignment and Blinding
All subjects will be assigned a unique identification number by the interactive response
technology (IRT) system at the screening visit.  For subjects who rescreen, the screening 
number assigned by the IRT at the initial screening visit should be used.  The IRT will 
assign a randomization number that will encode the subject's treatment group assignment 
according to the randomization schedule generated by the statistics department at AbbVie.
Subjects 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.


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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 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.
2.4
Sample Size Determination
Under the study design with a 1:1:1 randomization, with the assumed Week 16 HiSCR 
response rate as summarized in Table 1, a total sample size of 222 subjects will provide 
80% to 90% power to detect at least one risankizumab dose is different from placebo 
(with a 2-sided significance level of 0.025 for the test of each risankizumab dose versus 
placebo).


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Table 1.
Power under a 1:1:1 randomization
Assumed Dose Response 
Model
Assumed HiSCR Rate at Week 16 (%)
Power1
Placebo
(N = 74)
Risankizumab
180 mg (N = 74)
Risankizumab
360 mg (N = 74)
Linear
26%
39.5%
53%
83.9%
EMax
26%
46.5%
53%
87.6%
EMax (with early plateau)
26%
50%
53%
90.6%
1.
Power to detect at least one risankizumab dose is different from placebo, under a 2-sided significance level of 
0.025 for each risankizumab dose.
3.0
Endpoints
3.1
Primary Endpoint
The primary endpoint is the proportion of subjects achieving 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.
3.2
Secondary Endpoint
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 flare, defined as an increase in AN count of 
at least a 25% with a minimum increase of 2 relative to Baseline (flare), during 
Period A.
4.
Change from Baseline in DLQI at Week 16.


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5.
Change from Baseline in HS-related swelling – assessed based on the 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.
3.3
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 PGA Skin Pain 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.
●
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.


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●
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 evaluations will be included in the safety analyses:
●
Treatment emergent adverse events (TEAEs);
●
Serious adverse events (SAEs);
●
Areas of safety interest (ASI);
●
Adverse events (AEs) leading to discontinuation;
●
Vital signs and laboratory tests.
3.5
Pharmacokinetic Endpoints
The pharmacokinetic endpoints will be analyzed separately.
4.0
Analysis Populations
The intent-to-treat (ITT) Population, which includes all randomized subjects, will be used 
for all efficacy analyses.  Subjects who are randomized to placebo in Period A and do not 


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continue into Period B will be excluded from the analysis in Period B.  Subjects will be 
analyzed according to treatment as randomized.
The Per-Protocol (PP) Population will include ITT subjects who meet all the following 
criteria:
●
Receive at least 75% of the planned study drug prior to Week 16.
●
Provide at least one post Baseline assessment on lesion count.
●
Have Baseline AN count ≥ 5.
●
Have Baseline draining fistula count ≤ 20.
●
Do not take protocol prohibited medications that could potentially impact the 
efficacy assessment for the primary endpoint at Week 16.
The final criteria and the exclusion of subjects from the PP Population will be finalized 
before unblinding data for the Primary Analysis.  Subjects in the PP population will be 
analyzed by treatment group as randomized.
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.
For safety analysis, subjects will be analyzed as treated (determined by the first dose of 
study drug that the subject received).


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5.0
Subject Disposition
A summary of subject accountability will be provided where the number of subjects in 
each of the following categories will be summarized for each treatment group:
●
Subjects randomized in the study;
●
Subjects who received randomized study drug in each period;
●
Subjects who completed study;
●
Subjects who discontinued study drug in each period (all reasons and primary 
reason);
For end of study participation, the number and percentage of subjects who completed each 
study period (or did not with associated reasons) will be summarized overall and by 
treatment group.
6.0
Study Drug Duration and Compliance
For the ITT population, the duration of treatment will be summarized by treatment groups 
in each period.  The duration of treatment for each period is defined as follows:
Period A: the minimum of (the last dose date in Period A + 56 days, the end of study 
date + 1 day, and the first dose date in Period B if not missing [and cutoff date during the 
Primary Analysis + 1 day]) minus the first dose date in Period A. 
Period B: the minimum of (the last dose date in Period B + 56 days, and the end of study 
date + 1 day [and cutoff date during the Primary Analysis + 1 day]) minus the first dose 
date in Period B. 
The All-Risankizumab Treated Period: the duration of treatment will be summarized by 
the following two groups:
●
Any risankizumab: the minimum of (the last dose date of risankizumab + 56 
days, and the end of study date + 1 day [and cutoff date during the Primary 
Analysis + 1 day]) minus the first dose date of risankizumab. 


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●
Risankizumab 360 mg: the minimum of (the last dose date of risankizumab 
360 mg + 56 days, and the end of study date + 1 day [and cutoff date during the 
Primary Analysis + 1 day]) minus the first dose date of risankizumab 360 mg. 
Duration of treatment will be summarized by descriptive statistics of mean, standard 
deviation, median, minimum and maximum, among the number of subjects treated in each 
period.  
Treatment compliance will be summarized by treatment groups among the ITT 
population.  The compliance will be summarized by the percentage of planned injections 
which are administered at each study drug administration visit.  The cumulative summary 
of compliance in each period will also be provided.  When computing the compliance at 
each study drug administration visit for each treatment group, the denominator will 
include all ITT subjects in this treatment group who have not prematurely discontinued 
the study drug prior to that scheduled visit.  
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications
7.1
Demographics and Baseline Characteristics
Continuous demographic variables include age, weight, height, waist circumference, and 
body mass index (BMI).  Categorical demographic variables include sex, ethnicity, race, 
age (<40, 40 – 65, ≥ 65 years), weight (≤ 100 or > 100 kg), BMI (< 25, ≥ 25 – < 30, ≥ 30 
kg/m2), tobacco user (current, former, never, unknown), and alcohol user (current, former, 
never, unknown).
Baseline disease characteristics include prior exposure to TNF antagonists (yes, no), prior 
exposure to biologic agents that block IL-12/23/17 (yes, no), Baseline lesion counts (by 
lesion type), Baseline skin pain NRS (among all subjects and among subjects with 
baseline value ≥ 3), duration of HS (in years), Baseline Hurley stage (I, II, III), Baseline 
DLQI, Baseline HSSA, Baseline HSIA, Baseline WPAI, Baseline PGIS, Baseline EQ-5D-
5L, Baseline HADS, Baseline hsCRP. 


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Demographics and baseline characteristics will be summarized among the ITT Population, 
overall and by treatment group.  Categorical variables will be summarized with the 
number and percentage of subjects; percentages will be calculated based on the number of 
non-missing observations.  Continuous variables will be summarized with descriptive 
statistics (number of non missing observations, mean, standard deviation, median, 
minimum, and maximum).
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The actual version of the MedDRA coding dictionary will be noted in the 
statistical tables and clinical study report.  The number and percentage of subjects in each 
medical history category (by MedDRA system organ class and preferred term) will be 
summarized overall and by treatment group.  The system organ class (SOC) will be 
presented in alphabetical order, and the preferred terms will be presented in alphabetical 
order within each SOC.  Subjects reporting more than one condition/diagnosis will be 
counted only once in each row (SOC or preferred term).  Subjects with cardiovascular 
history and CV risk factors will also be summarized. 
Medical history will be summarized among the ITT Population.
7.3
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by generic name.  A prior 
medication is defined as any medication taken prior to the date of the first dose of study 
drug.  A concomitant medication is defined as any medication that started prior to the date 
of the first dose of study drug and continued to be taken on or after the first dose of study 
drug or any medication that started on or after the date of the first dose of study drug, but 
not after the date of the last dose of study drug plus 140 days.  The number and percentage 
of subjects taking medications will be summarized by generic drug name based on the 
World Health Organization (WHO) Drug Dictionary for both prior and concomitant 
medications.


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In addition, subjects' prior exposure to TNF antagonists and prior exposure to biologic 
agents that block IL-12/23/17 will also be summarized by the reason for discontinuation.
Prior and concomitant medications will be summarized among the ITT Population.
8.0
Handling of Potential Intercurrent Events for the 
Primary Endpoint
The primary efficacy endpoint, achievement of HiCSR at Week 16 (defined in 
Section 3.1), will be analyzed in the ITT Population and the following method will be 
used to address potential intercurrent events:
●
Intercurrent events of either initiation of any antibiotics for HS-related 
infections or discontinuation of study drug due to lack of efficacy before Week 
16 are included in the definition of primary endpoint; subjects who have either 
intercurrents above will be considered not achieving the response.  No other 
intercurrent events are considered.
The first and second ranked secondary endpoints of HS-related skin pain (defined in 
Section 3.2), will be analyzed in the ITT Population and the following method will be 
used to address potential intercurrent events:
●
Intercurrent events of either initiation of any antibiotics for HS-related 
infections or discontinuation of study drug due to lack of efficacy before Week 
8 for the first ranked or before Week 16 for the second ranked secondary 
endpoint, as well as the intercurrent event of under the impact of analgesic use 
for HS-related skin pain (defined in Section 9.4.2) at Week 8 for the first 
ranked or at Week 16 for the second ranked secondary endpoint, are included in 
the definition of endpoint; subjects who have any of the intercurrents above 
will be considered not achieving the response. 
The third ranked secondary endpoint, experiencing flare during Period A will be analyzed 
in the ITT Population based on observed flares.  No intercurrent events are considered.


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The fourth, fifth, sixth and seventh ranked secondary endpoints on changes from Baseline 
(defined in Section 3.2), will be analyzed in the ITT Population and the following method 
will be used to address potential intercurrent events:
●
Intercurrent events of either initiation of any antibiotics for HS-related 
infections or discontinuation of study drug due to lack of efficacy before Week 
16 are considered; subjects' observations after either intercurrents above will be 
considered as missing and handled by the MMRM model.
9.0
Efficacy Analyses
9.1
General Considerations
All efficacy analyses will be conducted in the ITT Population.  In addition, Per-protocol 
analysis for primary endpoint will be performed.  All statistical tests, between each 
risankizumab dose and placebo, will be performed at a two-sided alpha level of 0.025.
The Primary Analysis will be performed after the last ongoing subject has completed the 
Week 16 visit, and the data up to Week 16 have be cleaned.  This will be the only and 
final analysis for the primary and ranked secondary endpoints.  Study sites and subjects 
will remain blinded to their initial treatment assignment for the duration of the entire 
study.
For categorical endpoints, comparisons will be made between each risankizumab dosing 
group and placebo using the Cochran-Mantel-Haenszel (CMH) test, adjusting for the 
actual values of stratification factors.  In case of any stratum with zero subject in either 
treatment group, no stratification factor will be controlled.  Non-responder imputation 
(NRI) will be the primary approach to handle missing values.  To account for the 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.
For continuous endpoints, comparisons will be made between each risankizumab dosing 
group and placebo based on the fixed term of treatment from a Mixed-effect Model 


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Repeat Measurement (MMRM) model including the Baseline value and observed 
measurements at all post-baseline visits, adjusting for the fixed effects of treatment, actual 
values of stratification factors, visit and treatment-by-visit interaction as covariates.  The 
MMRM will be the primary approach to handle missing values.
For variables other than PGA Skin Pain NRS and HSSA, "Baseline" refers to the last non-
missing observation on or before the date of the first administration of study drug or the 
date of randomization if no study drug is given.  The "Baseline" of PGA Skin Pain NRS 
and HSSA is defined as the last non-missing weekly average score, calculated based on 
the daily scores from the past 7 days, on or before the date of the first administration of 
study drug or the date of randomization if no study drug is given.  For variables where the 
assessment time is collected on the ePRO device, the baseline measurement must be prior 
to the time of the first administration of study drug.
9.2
Handling of Missing Data
Missing data could occur due to various reasons, including missing visits/assessments, 
early withdrawal from the study, or missing due to COVID-19 infection or logistic 
restriction.
The COVID-19 pandemic is interfering with the conduct of many ongoing trials, with 
potential impacts on treatment duration and the collection, analysis and the interpretation 
of clinical trial data.  Some protocol-specified visits in the clinical trials may be impacted 
due to COVID-19 infection or logistical restrictions during the pandemic.  For example, 
some scheduled visits may be missed due to self-quarantine or local government
restrictions on travel; some visits may also be delayed or canceled due to healthcare 
resource constraints during the pandemic.  Impacted visits due to COVID-19 will be 
recorded in the database.  The probability of having missed visits and missing data due to 
COVID-19 infection or logistical restrictions related to the COVID-19 pandemic can be 
reasonably assumed to be unrelated to the unobserved values.  Therefore, for the purpose 
of statistical analysis, it is reasonable to assume that these missing data are missing at 
random (MAR) and the statistical models that require MAR assumption are appropriate.  


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Sensitivity analyses will be performed to assess the impact of missing data and the 
robustness of the conclusion.
Handling of missing data for the efficacy analyses is described below.
9.2.1
Categorical Endpoints
Non-Responder Imputation incorporating multiple imputation to handle missing 
data due to COVID-19 (NRI-C) will be the primary approach for handling missing data 
in the analysis of categorical endpoints. 
For any categorical endpoints of achievement, the NRI-C will categorize any subject who 
does not have an evaluation during a pre-specified visit window as a non-responder for 
the visit.  The only exceptions are:  1) when the subject is a responder both before and 
after the visit window in the particular Study Period, the subject will be categorized as a 
responder for the visit;  2) missing data due to COVID-19 infection or logistical 
restriction will be handled by MI.  Subjects receiving any prohibited antibiotics for HS-
related infections or discontinued study drug due to lack of efficacy will be counted as 
non-responders at later visits.  Subjects whose change/percent change from Baseline 
cannot be calculated because of a missing Baseline will be considered as non-responders 
at all post-baseline visits.  The only exception is that when determining the HiSCR 
response status, a subject with missing Baseline value will be counted as a non-responder 
at any post-baseline visit unless a subject's abscess, inflammatory nodule, and draining 
fistula counts are all zero at a specific visit, then the subject will be a HiSCR responder at 
that visit.  More details are provided in Appendix E. 
For any categorical endpoints that connote worsening of disease, subjects with observed 
worsening outcomes, including those after receiving any prohibited antibiotics for HS-
related infections or discontinued study drug due to lack of efficacy, will be counted as 
experienced such worsening.  
Of note, during the Primary Analysis upon completion of Week 16, the NRI-C analysis 
will only be performed at all visits up to Week 16.  


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Multiple Imputation (MI) will be used as a sensitivity analysis for the primary endpoint 
(HiSCR at Week 16).  PROC MI with the Markov Chain Monte Carlo (MCMC) statement 
will be first applied to generate 30 augmented datasets with monotonic missing pattern.  
The random seed for the MCMC will be the SAS numerical value of the first subject 
randomization date.  PROC MI will then be used to impute 30 complete datasets using the 
regression method.  The random seed for this imputation step will be the SAS numerical 
value of the last subject randomization date.  Taking abscess count as an example, the 
variables to be included in the imputation model are: treatment group, prior exposure to 
anti-TNF category, Baseline worst Hurley Stage, Baseline abscess count, and abscess 
counts at each visit up to the end of the double blind Period A.  The imputed post-baseline 
abscess counts will be rounded to the same precision as the observed data to determine the 
responder status.  The same imputation strategy will be applied to the inflammatory 
nodule count and the draining fistula count.  HiSCR status will be determined 
accordingly.  Using the Cochran-Mantel-Haenszel (CMH) model adjusted by actual 
stratification factors, the imputed endpoints will be analyzed using each of the 30 datasets.  
SAS PROC MIANALYZE will be used to generate the final inferences of the risk 
difference between each risankizumab dose and placebo.  Note that measurements will be 
considered as missing after receiving any antibiotics for HS-related infections or 
discontinued study drug due to lack of efficacy before MI.  Regardless of MI imputed 
values, subjects receiving any antibiotics for HS-related infections or discontinued study 
drug due to lack of efficacy will be counted as non-responders at later visits.
Observed Case (OC) analysis will only be performed during the Primary Analysis for the 
summaries of categorical endpoints for visits after Week 16.  The OC analysis will not 
impute values for missing evaluations, and thus a subject who does not have an evaluation 
on a scheduled visit will not be included for that visit.  The OC analysis will not include 
values after receiving any prohibited antibiotics for HS-related infections or after 
discontinued study drug due to lack of efficacy. 


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9.2.2
Continuous Endpoints
Mixed-Effect Model Repeat Measurement (MMRM) will be the primary approach to 
handle missing data for continuous endpoints.  The MMRM will be conducted using 
mixed model including observed measurements at all visits, using all available data even 
if a subject has missing data at some post-baseline visits.  The mixed model includes the 
fixed effects of categorical variables of treatment, actual stratification factors, visit and 
treatment-by-visit interaction at all post-baseline visits in each Study Period, and the 
continuous variable of Baseline measurement as covariates.  Subjects' observations after 
receiving any prohibited antibiotics for HS-related infections or discontinued study drug 
due to lack of efficacy will be excluded from the model.  An unstructured variance 
covariance matrix (UN) will be used.  If the model cannot converge, an appropriate 
covariance structure matrix (e.g., autoregressive (1) or compound symmetry) will be used.  
The parameter estimations are based on the method of restrictive maximum likelihood 
(REML).  The fixed effects will be used to report model-based means at corresponding 
visits. 
Of note, during the Primary Analysis upon completion of Week 16, the MMRM analysis 
will only be performed at all visits up to Week 16.  
Observed Case (OC) analysis will only be performed during the Primary Analysis for the 
summaries of continuous endpoints for visits after Week 16.  The OC analysis will not 
impute values for missing evaluations, and thus a subject who does not have an evaluation 
on a scheduled visit will not be included for that visit.  The OC analysis will not include 
values after receiving any prohibited antibiotics for HS-related infections or after 
discontinued study drug due to lack of efficacy. 
9.3
Primary Efficacy Endpoint and Analyses
9.3.1
Primary Efficacy Endpoint
The primary endpoint is the proportion of subjects achieving HiSCR at Week 16 as 
defined in Section 3.1. 


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9.3.2
Main Analysis of Primary Efficacy Endpoint
The corresponding statistical null hypothesis to the primary endpoint is that there is no 
difference between each risankizumab dose and placebo, in the proportion of subjects 
achieving HiSCR at Week 16. 
Comparison of the primary endpoint will be made between each risankizumab dose and 
placebo using the Cochran-Mantel-Haenszel (CMH) test, adjusting for the actual values 
stratification factors under a two-sided alpha level 0.025 for each dose.  
The attributes of the estimand corresponding to the primary efficacy endpoint is 
summarized in Table 2.
Table 2.
Summary of the Estimand Attributes of the Primary Efficacy 
Endpoint
Estimand
Attributes of the Estimand
Treatment
Endpoint
Population
Intercurrent 
Events
Statistical 
Summary
Primary 
efficacy 
endpoint 
of HiSCR 
at Week 
16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Achievement of 
HiSCR at Week 
16 without the 
initiation of any 
antibiotics for 
HS-related 
infections and 
without 
discontinuation 
of study drug 
due to lack of 
efficacy
Patients with 
moderate to 
severe HS
The intercurrents 
of either initiation 
of any antibiotics 
for HS-related 
infections or 
discontinuation of 
study drug due to 
lack of efficacy 
are included in the 
endpoint attribute 
using composite 
variable strategy.  
No other 
intercurrent event 
is considered.
Difference in 
proportion of 
subjects 
achieving 
HiSCR at 
Week 16 
between each 
risankizumab 
dose and 
placebo
NRI-C will be the primary approach to handle missing data.


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9.3.3
Sensitivity and Supplementary Analyses of the Primary 
Efficacy Endpoint
A sensitivity analysis using MI to handle missing data will be performed on the primary 
endpoint, as defined in Section 9.2.1.
The primary endpoint will also be analyzed among a PP population as additional 
sensitivity analyses, using the same approaches to handle missing data. 
The attributes of the estimand corresponding to the sensitivity analysis of the primary 
efficacy endpoint among the PP Population is summarized in Table 3.
Table 3.
Summary of the Estimand Attributes of the Sensitivity Analysis of 
the Primary Efficacy Endpoint among the PP Population  
Estimand
Attributes of the Estimand
Treatment
Endpoint
Population
Intercurrent 
Events
Statistical 
Summary
Primary 
efficacy 
endpoint 
of HiSCR 
at Week 
16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Achievement of 
HiSCR at Week 
16 without the 
initiation of any 
antibiotics for 
HS-related 
infections and 
without 
discontinuation 
of study drug 
due to lack of 
efficacy
Patients with 
moderate to 
severe HS who 
have Baseline 
AN count ≥ 5, 
and have 
Baseline 
draining fistula 
count ≤20.
The intercurrents 
of either initiation 
of any antibiotics 
for HS-related 
infections or 
discontinuation of 
study drug due to 
lack of efficacy 
are included in 
the endpoint 
attribute using 
composite 
variable strategy.  
No other 
intercurrent event 
is considered.
Difference in 
proportion of 
subjects 
achieving 
HiSCR at 
Week 16 
between each 
risankizumab 
dose and 
placebo
9.4
Secondary Efficacy Analyses
9.4.1
Key Secondary Efficacy Endpoints
The ranked secondary endpoints are as defined in Section 3.2.


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9.4.2
Main Analyses of Key Secondary Efficacy Endpoints
Ranked secondary efficacy endpoints will be tested between each risankizumab dose and 
placebo in a hierarchical order only if the null hypothesis of the primary endpoint for the 
corresponding risankizumab dose has been rejected.
The corresponding null hypotheses for ranked secondary endpoints with respect to each 
risankizumab dose are:
1.
There is no difference between each risankizumab dose and placebo, in the 
proportion of subjects achieving NRS30 in PGA Skin Pain at Week 8 among 
subjects with Baseline NRS ≥ 3.
2.
There is no difference between each risankizumab dose and placebo, in the 
proportion of subjects achieving NRS30 in PGA Skin Pain at Week 16 among 
subjects with Baseline NRS ≥ 3.
3.
There is no difference between each risankizumab dose and placebo, in the 
proportion of subjects who experience flare during Period A.
4.
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in DLQI at Week 16.
5.
There is no difference between each risankizumab dose and placebo, in change 
rom Baseline in HS-related worst swelling – assessed based on the HSSA at Week 
16.
6.
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in HS-related worst odor – assessed based on the HSSA at Week 
16.
7.
There is no difference between each risankizumab dose and placebo, in change 
from Baseline in HS-related worst drainage– assessed based on the HSSA at Week 
16.


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Categorical endpoints will be analyzed, using the CMH test adjusting for the actual values 
of stratification factors.  NRI-C will be the primary approach to handle missing data. 
Continuous endpoints will be analyzed based on the fixed term of treatment from an 
MMRM model including the Baseline value and observed measurements at all post-
baseline visits, adjusting for the fixed effects of treatment, actual values of stratification 
factors, visit and treatment-by-visit interaction as covariates.
For the first and second ranked secondary endpoint of HS-related skin pain, any 
measurements under the impact of analgesic use for HS-related skin pain will be handled 
as follows:
●
Prohibited analgesic (including opioids): A subject will be counted as a non-
responder from the day that the subject initiates prohibited analgesic to 5 days 
after the end of such analgesic use.
●
Protocol-allowed analgesic use:
○
A subject who enter the study without concomitant analgesic will be 
counted as a non-responder from the day that the subject initiates a 
protocol-allowed analgesic to 2 days after the end of such analgesic use.
○
A subject who entered the study on a stable dose of a protocol-allowed 
concomitant analgesic will be counted as a non-responder from the first 
day of an analgesic dose increase to 2 days after the end of the dose 
increase.
The attributes of the estimands corresponding to the ranked secondary efficacy endpoints 
are summarized in Table 4.


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Table 4.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints
Estimand
Attributes of the Estimand
Treatment
Endpoint
Population
Intercurrent 
Events
Statistical 
Summary
Ranked 
secondary 
endpoint of 
NRS30 at 
Week 8 
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Achievement of 
NRS30 in PGA 
Skin Pain at 
Week 8 without 
the initiation of 
any antibiotics 
for HS-related 
infections, 
without the 
impact of 
analgesics for 
HS-related skin 
pain, and 
without 
discontinuation 
of study drug 
due to lack of 
efficacy
Patients with 
moderate to 
severe HS 
among 
Baseline 
NRS ≥ 3
The intercurrents 
of either initiation 
of any antibiotics 
for HS-related 
infections, under 
the impact of 
analgesics for 
HS-related skin 
pain, or 
discontinuation of 
study drug due to 
lack of efficacy 
are included in 
the endpoint 
attribute using 
composite 
variable strategy. 
Difference in 
proportion of 
subjects 
achieving 
NRS30 at 
Week 8 
between each 
risankizumab 
dose and 
placebo
Ranked 
secondary 
endpoint of 
NRS30 at 
Week 16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Achievement of 
NRS30 in PGA 
Skin Pain at 
Week 16 
without the 
initiation of any 
antibiotics for 
HS-related 
infections, 
without the 
impact of 
analgesics for 
HS-related skin 
pain, and 
without
discontinuation 
of study drug 
due to lack of 
efficacy
Patients with
moderate to 
severe HS
among 
Baseline 
NRS ≥ 3
The intercurrents
of either initiation 
of any antibiotics 
for HS-related
infections, under 
the impact of 
analgesics for 
HS-related skin 
pain, or
discontinuation of 
study drug due to 
lack of efficacy
are included in 
the endpoint 
attribute using 
composite 
variable strategy. 
Difference in 
proportion of 
subjects 
achieving 
NRS30 at 
Week 16 
between each 
risankizumab 
dose and 
placebo 


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Table 4.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints (Continued)
Estimand
Attributes of the Estimand
Treatment
Endpoint
Population
Intercurrent 
Events
Statistical 
Summary
Ranked 
secondary 
endpoint of 
flare during 
Period A
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Experiencing 
flare during 
Period A
Patients with
moderate to 
severe HS
No intercurrent 
event is 
considered.
Difference in 
proportion of 
subjects 
experiencing 
flare during 
Period A
between each 
risankizumab 
dose and 
placebo
Ranked 
secondary 
endpoint of 
change 
from 
Baseline in 
DLQI at 
Week 16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Change from 
Baseline in 
DLQI at Week 
16
Patients with
moderate to 
severe HS
Subjects'
observations after 
the intercurrents
of either initiation 
of any antibiotics 
for HS-related 
infections or 
discontinuation of 
study drug due to 
lack of efficacy 
will be considered 
as missing and 
handled by 
MMRM. 
Difference in 
change from 
Baseline in 
DLQI at Week 
16 between 
each 
risankizumab 
dose and 
placebo 
Ranked 
secondary 
endpoint of 
change 
from 
Baseline in 
HS-related
worst 
swelling at 
Week 16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Change from 
Baseline in HS-
related worst 
swelling at 
Week 16
Patients with
moderate to 
severe HS
Subjects'
observations after 
the intercurrents
of either initiation 
of any antibiotics 
for HS-related 
infections or 
discontinuation of 
study drug due to 
lack of efficacy 
will be considered 
as missing and 
handled by 
MMRM. 
Difference in 
change from 
Baseline in HS-
related worst 
swelling at 
Week 16 
between each 
risankizumab 
dose and 
placebo 


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Table 4.
Summary of the Estimand Attributes of the Ranked Secondary 
Efficacy Endpoints (Continued)
Estimand
Attributes of the Estimand
Treatment
Endpoint
Population
Intercurrent 
Events
Statistical 
Summary
Ranked 
secondary 
endpoint of 
change 
from 
Baseline in 
HS-related 
worst odor 
at Week 16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Change from 
Baseline in HS-
related worst 
odor at Week 
16
Patients with
moderate to 
severe HS
Subjects'
observations after 
the intercurrents
of either initiation 
of any antibiotics 
for HS-related 
infections or 
discontinuation of 
study drug due to 
lack of efficacy 
will be considered 
as missing and 
handled by 
MMRM.
Difference in 
change from 
Baseline in HS-
related worst 
odor at Week 
16 between 
each 
risankizumab 
dose and 
placebo 
Ranked 
secondary 
endpoint of 
change 
from 
Baseline in 
HS-related 
worst 
drainage at 
Week 16
Risankizumab 
180 mg / 
risankizumab 
360 mg / 
Placebo
Change from 
Baseline in HS-
related worst 
drainage at 
Week 16
Patients with
moderate to 
severe HS
Subjects'
observations after 
the intercurrents
of either initiation 
of any antibiotics 
for HS-related 
infections or 
discontinuation of 
study drug due to 
lack of efficacy 
will be considered 
as missing and 
handled by 
MMRM.
Difference in 
change from 
Baseline in HS-
related worst
drainage at 
Week 16 
between each 
risankizumab 
dose and 
placebo 
9.4.3
Sensitivity and Supplementary Analyses for Key Secondary 
Efficacy Endpoints
There are no additional supportive secondary efficacy analyses planned other than those 
described above.


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9.5
Additional Efficacy Analyses
Additional efficacy endpoints will be compared between each risankizumab dose and 
placebo among the ITT Population at each visit in Period A.  
Categorical endpoints will be analyzed, using the CMH test adjusting for the actual values 
of stratification factors.  NRI-C will be the primary approach to handle missing data. 
Continuous endpoints will be analyzed based on the fixed term of treatment from an 
MMRM model including the Baseline value and observed measurements at all post-
baseline visits, adjusting for the fixed effects of treatment, actual values of stratification 
factors, visit and treatment-by-visit interaction as covariates.
Summary statistics will be provided for the additional efficacy endpoints at each visit in 
Period B by treatment groups.  Categorical endpoints will be summarized by the number 
and proportion of subjects who achieved the endpoint, as well as the 95% confidence 
interval of that proportion.  Continuous endpoints will be summarized by descriptive 
statistics including the mean, standard error, and the 95% confidence interval of the mean.
For efficacy endpoints of HS-related skin pain:
●
Prohibited analgesic (including opioids): A subject will be counted as a non-
responder from the day that the subject initiates prohibited analgesic to 5 days 
after the end of such analgesic use for categorical endpoints, and will have the 
last assessment prior to the initiation of analgesic carried forward until 5 days 
after the end of such analgesic use for continuous endpoints.
●
Protocol-allowed analgesic use:
○
A subject who enter the study without concomitant analgesic will be 
counted as a non-responder from the day that the subject initiates a 
protocol-allowed analgesic to 2 days after the end of such analgesic use for 
categorical endpoints, and will have the last assessment prior to the 
initiation of analgesic carried forward until 2 days after the end of such 
analgesic use for continuous endpoints.


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○
A subject who entered the study on a stable dose of a protocol-allowed 
concomitant analgesic will be counted as a non-responder from the first 
day of an analgesic dose increase to 2 days after the end of the dose 
increase for categorical endpoints, and will have the last assessment prior 
to the dose increase carried forward until 2 days after the end of such 
analgesic dose increase for continuous endpoints.
9.6
Efficacy Subgroup Analyses
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, analyses will be performed for the following subgroups for the primary 
efficacy endpoint.
●
Age group (< 40 years, ≥ 40 – < 65 years, ≥ 65 years)
●
Sex (male, female)
●
Race (white, non-white)
●
Smoking (current, ex or never)
●
BMI (normal:  < 25, overweight:  ≥ 25 – < 30, obese:  ≥ 30)
●
Duration of HS (by median)
●
Baseline body weight (by median) 
●
Baseline CRP level (by median)
●
Baseline AN count category (5 – 10, 11+)
●
Prior exposure to TNF antagonists (yes, no)
●
Prior exposure to biologic agents that block IL-12/23/17 (yes, no)
●
Baseline Hurley stage (I, II, III)
In addition, the primary efficacy endpoint may also be summarized by anti-drug antibody 
(ADA) status and/or by neutralizing antibody (NAb) status, once the corresponding ADA 
and NAb data are completed.


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10.0
Safety Analyses
10.1
General Considerations
Safety analyses will include adverse events, laboratory, and vital sign measurements. 
Safety data will be summarized among the Safety_A and Safety_B populations by 
treatment groups.  For the safety analysis, subjects are analyzed based on the actual 
treatment group, determined by the first dose of study drug that the subject received. 
The overview of TEAEs, areas of safety interest (ASIs), and potentially clinically 
important (PCI) findings in laboratory variables and vital sign variables will be 
summarized among the ALL_RZB Population. 
Missing safety data will not be imputed.
10.2
Adverse Events
Adverse events (AEs) will be summarized and presented using primary MedDRA System 
Organ Classes (SOCs) and preferred terms (PTs) according to the version of the MedDRA 
coding dictionary used for the study at the time of database lock.  The actual version of 
the MedDRA coding dictionary used will be noted in the AE tables and in the clinical 
study report.  When summarizing the number and percentages of subjects, subjects with 
multiple occurrences of the same adverse event will be counted once, and only the 
maximum severity level will be presented in the severity summaries, and the 
worst/highest relationship level in the relationship summaries.
10.2.1
Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) for each safety period are defined as 
follows:
Period A: A TEAE in Period A is defined as any event with an onset date on or after the 
first dose date of study drug in Period A and within 20 weeks (140 days) after the last 


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dose date of study drug in Period A, as long as it does not exceed the first dose date in 
Period B.  
Period B: A TEAE in Period B is defined as any event with an onset date on or after the 
first dose date of study drug in Period B and within the minimum of (140 days after the 
last dose date of study drug in Period B, and the end of study date).
The All-Risankizumab Treated Period: TEAEs are defined in the following two 
groups:
●
Any risankizumab: Any event with an onset date on or after the first dose 
date of risankizumab and within the minimum of (140 days after the last dose
date of risankizumab, and the end of study date). 
●
Risankizumab 360 mg: Any event with an onset date on or after the first dose 
date of risankizumab 360 mg and the minimum of (140 days after the last dose 
date of risankizumab 360 mg, and the end of study date).
10.2.2
Adverse Event Overview
An overview of TEAEs by treatment groups in each period will be presented consisting of 
the number and percentage of subjects experiencing at least one event for each of the 
following AE categories:
●
Any treatment-emergent AE
●
Any treatment-emergent AE related to study drug according to the investigator
●
Any severe treatment-emergent AE
●
Any serious treatment-emergent AE
●
Any treatment-emergent AE leading to discontinuation of study drug
●
Any adjudicated MACE
●
Any adjudicated anaphylactic reaction
●
Any serious infection
●
Any tuberculosis


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●
Any malignant tumor
●
Any malignant tumor excluding NMSC
●
Any serious hypersensitivity 
●
Any treatment-emergent AE leading to death
All deaths will also be summarized:
●
Deaths occurring ≤ 140 days after last dose of study drug
●
Deaths occurring > 140 days after last dose of study drug.
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
Treatment-emergent adverse events will be summarized by SOC and PT; by maximum 
relationship to study drug as assessed by the investigator (e.g., reasonable possibility or no 
reasonable possibility) and by SOC and PT; by maximum severity and by SOC and PT; 
and by SOC and PT listing associated subject number.  When summarizing the number 
and percentages of subjects, subjects with multiple occurrences of the same adverse event 
will be counted once, and only the maximum severity level will be presented in the 
severity summaries, and the worst/highest relationship level in the relationship 
summaries. 
In addition, treatment-emergent adverse events will be summarized by PT and sorted by 
decreasing frequency for the active group.
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure
Exposure-adjusted TEAEs per 100 patient-years will be provided, where TEAEs per 100 
patient-years of exposure are defined as the number of TEAEs divided by the total 
exposure in 100 patient-years.
Note that one event per preferred term per day per subject will be counted in the 
calculation of the number of TEAEs (i.e., a preferred term will not be counted twice on 


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the same day for the same subject).  The exposure-adjusted TEAE rate per 100 patient-
years is calculated as:
100 × Number of TEAEs 
Total Patient Years,
where total patient years in each period are defined below. 
Total patient years in Period A: Sum of study drug exposure in Period A, defined as the 
minimum of (the last dose date in Period A + 140 days, the end of study date + 1 day, and 
the first dose date in Period B if not missing [and the cutoff date during the Primary 
Analysis + 1 day]) minus the first dose date in Period A, normalized by 365.25 and 
rounded to one decimal place. 
Total patient years in Period B: Sum of study drug exposure in Period B, defined as the 
minimum of (the last dose date in Period B + 140 days, and the end of study date + 1 day 
[and cutoff date during the Primary Analysis + 1 day]) minus the first dose date in Period 
B, normalized by 365.25 and rounded to one decimal place. 
Total patient years in the All-Risankizumab Treated Period: 
●
Any risankizumab: Sum of study drug of risankizumab exposure, defined as 
the minimum of (the last risankizumab dose date + 140 days, and the end of 
study date + 1 day [and cutoff date during the Primary Analysis + 1 day]) 
minus the first risankizumab dose date, normalized by 365.25 and rounded to 
one decimal place. 
●
Risankizumab 360 mg: Sum of study drug of risankizumab exposure, defined 
as the minimum of (the last risankizumab 360 mg dose date + 140 days, and the 
end of study date + 1 day [and cutoff date during the Primary Analysis + 1 
day]) minus the first risankizumab 360 mg dose date, normalized by 365.25 and 
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10.2.5
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Treatment-emergent SAEs (including deaths) and AEs leading to study drug 
discontinuation will be summarized by SOC and PT and in listing format.
A listing of pre-treatment SAEs with onset dates prior to the first dose of study drug will 
be provided.
10.2.6
Area of Safety Interest
Detailed information about the search criteria for areas of safety interest (ASIs) are 
provided in Appendix B.
The final list will be based on the most updated final version of risankizumab Product 
Safety Statistical Analysis Plan, which is consistent to the most updated risankizumab 
Risk Management Plan.
Tabular listings of selected area of safety interest will be provided.
10.3
Analysis of Laboratory Data
Data collected from central and local laboratories, including additional laboratory testing 
due to an SAE, will be used in all analyses, except for Baseline derivation where SAE-
triggered laboratory assessments on or before the first dose of study drug will be 
excluded.  The clinical laboratory tests defined in the protocol operations manual (e.g., 
hematology and clinical chemistry) will be summarized.
Mean change from Baseline to each applicable post-baseline visit will be summarized for 
selected laboratory variables.  The following descriptive statistics will be presented by 
treatment groups: number of observations, Baseline mean, visit mean, mean change from 
Baseline and its standard error, and the 95% confidence interval of the mean change from 
Baseline.


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In addition, laboratory parameters will be tabulated using shift tables from Baseline to 
minimum and maximum values in each period (Period A and Period B), categorized by 
the toxicity grade according to NCI CTCAE Version 4.031 of the laboratory used for each 
sample.  A similar shift table will also be provided to summarize shifts from Baseline to 
the final post-baseline value in each period.
Laboratory abnormalities meeting CTC criteria grade 3 and 4 at least once in each period 
will be summarized. 
Laboratory abnormalities will be evaluated based on Potentially Clinically Important 
(PCI) criteria (Appendix C).  For each laboratory PCI criterion, the number and 
percentage of subjects who have a laboratory value meeting the criteria at least once in 
each period will be summarized.  Listings will be provided to summarize subject-level 
laboratory data for subjects meeting PCI criteria.  
In addition, the frequencies and percentages of subjects with post baseline liver specific 
function test values in ALT/SGPT, AST/SGOT, alkaline phosphatase, and total bilirubin 
that meet the following criteria will be summarized by treatment groups:
●
ALT ≥ 3.0 × ULN
●
ALT ≥ 5.0 × ULN
●
ALT ≥ 10.0 × ULN
●
ALT ≥ 20.0 × ULN
●
AST ≥ 3.0 × ULN
●
AST ≥ 5.0 × ULN
●
AST ≥ 10.0 × ULN
●
AST ≥ 20.0 × ULN
●
Alkaline phosphatase ≥ 1.5 × ULN
●
Total bilirubin ≥ 2.0 × ULN
●
ALT and/or AST > 3× ULN and TBL ≥ 2× ULN


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A listing of potentially clinically important (PCI) liver function laboratory values will 
include all subjects who met any of the following four criteria:
●
ALT ≥ 3 × ULN, or
●
AST ≥ 3 × ULN, or
●
Alkaline phosphatase ≥ 1.5 × ULN, or 
●
Total bilirubin ≥ 2 × ULN.
A listing of possible Hy's Law cases, defined as those who meet all of the following 
conditions will be provided.  
●
ALT of > 3 × ULN or AST of > 3 × ULN, 
●
Total bilirubin ≥ 2 × ULN
10.4
Analysis of Vital Signs
Vital sign measurements of systolic and diastolic blood pressure will be summarized.
Change from baseline to each applicable post-baseline visit will be summarized for each 
vital sign variable.  The following descriptive statistics will be presented by treatment 
groups: number of observations, Baseline mean, visit mean, mean change from Baseline 
and its standard error, and the 95% confidence interval of the mean change from Baseline.
Vital sign variables will be evaluated based on potentially clinically important (PCI) 
criteria (Appendix D).  For each vital sign PCI criterion, the number and percentage of 
subjects who have a vital sign value meeting the criteria at least once in each period will 
be summarized.  Listings will be provided to summarize subject-level vital sign data for 
subjects meeting PCI criteria. 
10.5
Safety Subgroup Analyses
The number and percentage of subjects with treatment emergent hypersensitivity events or 
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and/or by neutralizing antibody (NAb) status, once the corresponding ADA and NAb data 
are completed.
10.6
Other Safety Analyses
No other safety analyses.
11.0
Other Analyses
No other analyses.
12.0
Interim Analyses
12.1
Data Monitoring Committee
An external data monitoring committee (DMC) composed of persons independent of 
AbbVie and with relevant expertise in their field will review unblinded safety data from 
the ongoing study.  The primary responsibility of the DMC will be to protect the safety of 
the subjects participating in this study.
A separate DMC charter describes the roles and responsibilities of the DMC members, 
frequency of data reviews, relevant data to be assessed, and general operations.
Since there are no efficacy analyses for early stopping, no alpha adjustment is needed.
13.0
Overall Type-I Error Control
For each risankizumab dose, the statistical comparisons for the primary efficacy variable 
and the ranked secondary variables will be carried out in the hierarchical order between 
the corresponding risankizumab dose and placebo, under a 2-sided significance level of 
0.025.  This means that for each risankizumab dose, statistically significant results for the 
comparison in the higher rank (primary, then ranked secondary variables) are necessary to 
initiate the testing of the next comparison in the lower rank.  Since a step-down procedure 
is used, each comparison will be tested at a significance level of 0.025 and overall alpha 
level of 0.025 will be preserved for each risankizumab dose.


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Therefore, the family-wised type-I error rate is controlled under a 2-sided significance 
level of 0.05.
14.0
Version History
Table 5.
SAP Version History Summary
Version
Date
Summary
1.0
7 Mar 2019
Original version
2.0
26 Jul 2019
Added more statistical analysis details.  
3.0
08 Oct 2020
Removed section about RAR & IERC and updated the control for overall 
type-I error rate throughout the SAP, to align with the same updates after 
protocol version 3.0.
Removed the stratification cap of TNF-IR population, to align with the 
same updates after protocol version 3.0.
Clarified the definition of HiSCR and NRS30 throughout the SAP, to 
align with the updated wording after protocol version 3.0.
Clarified the timing and scope of the Primary Analysis.
Updated the details about how to handle subjects who do not continue into 
Period B from the ITT Population in Section 4.0, to align with the same 
updates after protocol version 3.0. 
Updated the definition of concomitant medication in Section 7.3, to align 
with the most updated risankizumab PSSAP.
Clarified in Section 9.1 that the non-responder imputation (NRI) approach 
will be adjusted to NRI-C, Non-Responder Imputation incorporating 
multiple imputation to handle missing data due to COVID-19. 
Added more details about handling missing data in Section 9.2 and 
Appendix E, including how to handle missing data caused by COVID-19 
and subjects who received prohibited antibiotics or discontinued study 
drug to lack of efficacy.
Clarified shift tables, PCI, and ASI definitions for safety analysis in 
Section 10.0, Appendix B, Appendix C, and Appendix D, to align with 
the most updated risankizumab PSSAP.
Added estimands and their attributes for the primary endpoint and ranked 
secondary endpoints at Section 2.1, Section 8.0, Section 9.3, and 
Section 9.4. 


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Version
Date
Summary
4.0
19 Jan 2021
Clarified that study drug exposure will be calculated up to the study 
completion date for subjects who pre-maturely discontinued from study 
participation during Period A in Section 6.0 and Section 10.2.4.
Corrected an error in Section 7.1, as PGIC does not apply at Baseline.
Updated the definition of concomitant medication in Section 7.3, to align 
with the most updated risankizumab PSSAP.  
Included any adjudicated anaphylactic reaction to the AE overview table 
in Section 10.2.2 and Appendix B, to align with the most updated 
risankizumab PSSAP.
Updated the lab test shift table categories and liver functioning test 
categories in Section 10.3 and added the reference to CTCAE version 
4.03, to align with the most updated risankizumab PSSAP.
15.0
References
1.
Common Terminology Criteria for Adverse Events (CTCAE) v4.03 (2010).  
https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf.


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


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Appendix B.
Definition of Area of Safety Interest
Area of safety interest (ASI) will be identified using the following search criteria:
Area of Safety 
Interest
Search Criteria
Include in AE 
Overview (Y/N)
MACE
Adjudicated terms will be identified as described in PSSAP Table 3 
using CECAT and CETERM from the CE SDTM dataset.
Y
Extended MACE
Adjudicated terms will be identified as described in PSSAP Table 3 
(for MACE +) using CECAT and CETERM from the CE SDTM 
dataset.
N
Serious Infections
Serious AEs in the Infections and Infestations SOC 
Y
Tuberculosis
Active Tuberculosis CMQ (code 80000188)
Y
Opportunistic 
Infections
Opportunistic infection excluding tuberculosis and herpes zoster 
CMQ (code 80000189)
N
Fungal Infections
Fungal infections CMQ (code 80000063)
N
Herpes Zoster
Herpes Zoster CMQ (code 80000175)
Y
Malignant Tumours
Narrow
Malignant tumours (SMQ 20000194)
Y
Non-melanoma Skin 
Cancer (NMSC)
Broad
Skin malignant tumours (SMQ 20000204) excluding 
terms identified by the Melanoma CMQ (code 
80000119)
N
Malignant Tumours 
excluding NMSC
'Malignant Tumours excluding NMSC' is identified by the 
'Malignant Tumours' search excluding terms identified by the 'Non-
melanoma skin cancer (NMSC)' search.
Y
Hypersensitivity 
Narrow
Hypersensitivity (SMQ 20000214)
Y – serious events 
only
Adjudicated 
Anaphylactic 
Reaction*
Adjudicated terms will be identified using SDTM data (e.g., CE and 
PR domains).
Y
Hepatic Events 
Broad
Hepatic failure, fibrosis and cirrhosis and other liver 
damage-related conditions (SMQ 20000013)
N
Broad
Hepatitis, non-infectious (SMQ 20000010)
N
Broad
Cholestasis and jaundice of hepatic origin 
(SMQ 20000009)
N
Broad
Liver related investigations, signs and symptoms 
(SMQ 20000008)
N
Narrow
Liver-related coagulation and bleeding disturbances 
(SMQ 20000015)
N
*
Events will be identified for adjudication by Anaphylactic Reaction SMQ Broad search as specified in the RISA 
AAC Charter.


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


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


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


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Appendix E.
Non-Responder Imputation Incorporating Multiple Imputation to 
Handle Missing Data Due to COVID-19 Pandemic for 
Dichotomized Outcome Variables
1.0
Overview
1.1
Background and Justification for Missing at Random (MAR)
Assumption
The COVID-19 pandemic is interfering with the conduct of many ongoing trials, with 
potential impacts on treatment duration and the collection, analysis and the interpretation 
of clinical trial data.  Some protocol-specified visits in the clinical trials may be impacted 
due to COVID-19 infection or logistical restrictions during the pandemic.  For example, 
some scheduled visits may be missed due to self-quarantine or local government 
restrictions on travel; some visits may also be delayed or canceled due to healthcare 
resource constraints during the pandemic.  Impacted visits due to COVID-19 will be 
recorded in the database.  The probability of having missed visits and missing data due to 
COVID-19 infection or logistical restrictions related to the COVID-19 pandemic can be 
reasonably assumed to be unrelated to the unobserved values.  Therefore, for the purpose 
of statistical analysis, it is reasonable to assume that these missing data are missing at 
random (MAR) and the statistical models that require MAR assumption are appropriate.  
In some cases, sensitivity analyses may be performed to assess the impact of missing data 
and the robustness of the conclusion.
1.2
FDA Guidance
FDA provided two guidance documents1,2 in March 2020 and June 2020 on the efficacy 
collection and possible changes in the statistical analysis plan:
●
"With respect to efficacy assessments, FDA recommends consultation with the 
appropriate review division regarding protocol modifications for the collection 
of efficacy endpoints, such as use of virtual assessments, delays in assessments, 
and alternative collection of research-specific specimens, if feasible.  For 
individual instances where efficacy endpoints are not collected, the reasons for 
failing to obtain the efficacy assessment should be documented (e.g., 


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identifying the specific limitation imposed by COVID-19 leading to the 
inability to perform the protocol-specified assessment)."
●
"If changes in the protocol will lead to amending data management and/or 
statistical analysis plans, the sponsor should consider doing so in consultation 
with the applicable FDA review division.  Prior to locking the database, 
sponsors should address in the statistical analysis plan how protocol deviations 
related to COVID-19 will be handled for the prespecified analyses."
1.3
EMA Guidance
EMA provided guidance3 in March 2020: 
●
"At this point in time it is not possible to give general applicable advice on how 
the different aspects related to the pandemic should be handled, as implications 
on clinical trials are expected to be manifold.  Impact on the data collection, 
analysis and interpretation of results for each trial will need a thorough case-by-
case assessment."
●
"As a general principle, there are strong scientific reasons to conduct trials as 
planned and implement changes only when there is a convincing scientific 
reason that it improves interpretability of results."
1.4
Missing Data Handling for Missing Due to COVID-19 for 
Dichotomized Variables
In this document, a missing data handling method is proposed to handle missing data due 
to COVID-19 infection or logistical restrictions related to the COVID-19 pandemic under 
the general MAR framework.  In particular, we explain using multiple imputation (MI) to 
handle missing data due to COVID-19 in dichotomized variables in conjunction with non-
responder imputation (NRI) for missing data due to other reasons.


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2.0
Non-Responder Imputation incorporating multiple 
imputation to handle missing data due to COVID-19 
(NRI-C)
2.1
Overall Description of the Method 
For a dichotomized outcome variable with missing data, the NRI-C will categorize any 
subject who does not have evaluation during a pre-specified visit window as a non-
responder for the visit, with two exceptions: 
●
If the subject is a responder both before and after the pre-specified visit window 
in the particular Study Period, the subject will be categorized as a responder for 
the visit.
●
If the reason for missing (e.g., missed visits, incomplete visit, out-of-schedule 
visits, or discontinuations of study drug) is due to COVID-19, the information 
will be captured in the database and the subject's response status will be 
imputed using multiple imputation.
Of note, later visits of subjects receiving any antibiotics for HS-related infections or 
discontinued study drug due to lack of efficacy will be set as missing before imputation.  
As a result, these assessments will not contribute to the imputation and the subjects will 
be counted as non-responders for the analysis at later visits.  When determining the 
HiSCR response status, a subject with missing Baseline value will be counted as a non-
responder at any post-baseline visit unless a subject's abscess, inflammatory nodule, and 
draining fistula counts are all zero at a specific visit, then the subject will be a HiSCR 
responder at that visit.  NRI-C will be implemented as follows.
2.2
Multiple Imputation (MI) and MAR Assumption
When a dichotomized variable is derived from continuous scales, for example, HiSCR (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), 
the multiple imputation will be applied to the original scales of abscess, inflammatory 
nodule and draining fistula counts, assuming multivariate normal distributions.  Then the 


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dichotomized variable will be derived from the imputed values.  For demonstration 
purposes, we use HiSCR as an example in this Appendix E, and provide sample code for 
the imputation of abscess count in Appendix E Section 3.0.  The same imputation strategy 
will be applied to the inflammatory nodule count and the draining fistula count.  HiSCR 
status will be determined accordingly.
The MI procedure assumes that the data are missing at random (MAR).  That is, for an 
outcome variable Y, the probability that an observation is missing depends only on the 
observed values of other variables, not on the unobserved values of the outcome variable 
Y.  Statistical inference from the MI procedure is valid under the MAR assumption.
2.3
Imputation Algorithm 
It is reasonable to assume the missing values of the longitudinal data for an outcome 
variable (e.g., abscess count at each post-baseline visit) follows a monotone missing 
pattern.  In practice, the missing data of the outcome variable might have an arbitrary 
(non-monotone) missing data pattern.  An extra step may be added accordingly, to 
augment data into a monotone missing pattern.
For the outcome variable (e.g., abscess count at each visit), K 'complete' datasets can be 
generated in two steps: augmentation step and imputation step.  K, the number of 
repetitions, is determined below.
Augmentation Step
For datasets with non-monotone missing data pattern, the augmentation step will first 
impute enough values to augment the data into a monotonic missing pattern: 
Markov Chain Monte Carlo (MCMC) will be applied to augment the data using PROC MI 
with the MCMC IMPUTE=monotone statement, assuming a multivariate normal 
distribution.  The augmented data will be used in the subsequent imputation step to 
generate 'complete' datasets.  Covariates included in the model are treatment group, prior 
exposure to anti-TNF category, Baseline worst Hurley Stage, Baseline abscess count, all 


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post-baseline visits of abscess count up to the end of the Study Period.  Of note, 
categorical variables are included using the form of dummy variables. 
Repeat the imputation process K=30 times using the procedure described above to form 
K=30 monotone missing datasets, where K is determined as described in "Repetition of 
Imputations (K)."
Imputation Step
For missing data with monotone missing patterns, the choice of multiple imputation using 
a parametric regression model that assumes multivariate normality is appropriate. 
The imputation step is described below:
●
The imputation model for the missing data is a regression model, which 
controls for treatment group, prior exposure to anti-TNF category, Baseline 
worst Hurley Stage, Baseline abscess count, all post-baseline visits of abscess 
count up to the end of the Study Period.  The covariates included in the model 
and the order of these variables are consistent with the augmentation step. 
●
For each monotone missing dataset, using SAS PROC MI with MONOTONE 
REG model statement, the outcome variable at each post-baseline visit with 
missing values will be imputed sequentially with covariates constructed from 
their corresponding sets of preceding variables. 
A 'complete' dataset with imputed values for the missing data is generated after the 
augmentation and imputation steps are completed.
Repetition of Imputations (K)
Repetition of imputations, K, must be determined in advance.  When estimating the 
overall variance of multiple imputation, the additional sampling variance is the between-
imputation variance divided by K.  This value represents the sampling error associated 
with the overall or average coefficient estimates.  It is used as a correction factor for using 
a specific number of imputations.  The more imputations (K) are conducted, the more 


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precise the parameter estimates will be.  For example, with a 1% power falloff tolerance 
in multiple imputation, as compared to an infinite number of imputations, multiple 
imputation requires 20 repetitions of imputation for 30% missing information and 40 
repetitions for 50% missing information (Graham, Olchowski, and Gilreath 20074).  In the 
usual clinical settings expecting less than 30% missing information, K=30 repetitions are 
deemed sufficient.  When missingness exceeds 30%, depending on the power falloff 
tolerance level, number of repetitions may need to be increased.  Recent research4
suggested that the number of repetitions (K) should be at least equal to the percentage of 
missing (White et al., 20116)
2.4
Derivation of Response Status and Non-Responder 
Imputation
Same as the abscess count, we also impute to obtain complete datasets for the 
inflammatory nodule count and the draining fistula count.  For each 'complete' dataset, the 
imputed post-baseline values will be rounded to the same precision as the observed data.  
HiSCR status will be determined accordingly.  
The imputed response status for missing due to reasons other than COVID-19 will be 
overridden by non-responder imputation (Section 2.1) to ensure that multiple imputation 
is only applied to missing due to COVID-19:
●
Using NRI-C approach, all missing due to reasons other than COVID-19 will 
be categorized as non-responders, including visits after a subject receives any 
antibiotics for HS-related infections or discontinued study drug due to lack of 
efficacy.  When determining the HiSCR response status, a subject with missing 
Baseline value will be counted as a non-responder at any post-baseline visit 
unless a subject's abscess, inflammatory nodule, and draining fistula counts are 
all zero at a specific visit, then the subject will be a HiSCR responder at that 
visit. 
●
The only exception is that a subject will be categorized as a responder for the 
visit if the subject is a responder both before and after an SAP-specified visit 
window in the particular Study Period.


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2.5
Analysis
The statistical analysis will use the Cochran-Mantel-Haenszel (CMH) test adjusted by the 
actual stratification factors.
2.5.1
Analysis of Each Dataset
For each of the K 'complete' datasets, the CMH test will be used to estimate the treatment 
difference versus placebo and the corresponding standard error.
2.5.2
Synthesis of Results for Statistical Inference
The results from the K 'complete' datasets will be synthesized using the SAS procedure 
PROC MIANALYZE, following Rubin's formula (Rubin, 19875), to derive the MI 
estimator of the treatment difference for the final inferences.
Rubin's formula
We fit the analysis model to the kth 'complete' dataset, denoting the estimate of the 
treatment difference q by  from the kth 'complete' dataset, and denoting the 
corresponding estimate of the variance as Vk.
The MI estimator of q (point estimator obtained from PROC MIANALIZE), , is the 
average of the K individual estimators:
 = 1
! " .
$
%&
The estimated variance of , is a combination of the between- and within-imputation 
variability as follows:
' = ( + (1 +
&
$),,
where ( =
&
$ ∑
'
$
%&
is the within-imputation variability and , =
&
$.& ∑
( −)0
$
%&
is the between-imputation variance. 


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It has been shown5 that the statistic
1 =  −
2'
has an approximate 34 distribution where 5 = (! −1)(1 +
6
7)0. Statistical inference, 
including hypothesis testing and confidence intervals for the treatment effect, will be 
based on this T-statistic.
3.0
Sample SAS Code
/**********************/
/*IMPUTATION ALGORITHM*/
/**********************/
/*NOTE: THIS APPROACH REQUIRES NO MISSING IN CATEGORICAL COVARIATES AND 
REQUIRES AT LEAST ONE OBSERVATION IN BASELIBE OR ONE OF THE POST-
BASELINE VISIT*/
/*PRE-AUGMENTATION – CREATE DUMMY FOR CATEGORICAL VARIABLES*/
/********************************************/
DATA COUNT_2; SET COUNT;
  /*THE MCMC STATMENT BELOW ASSUMES MULTI-VARIATE NORMAL*/
  /*  USE ALL DATA IN THE IMPUTATION MODEL*/
  IF TRT01P="180mg" THEN TRT1=1; ELSE TRT1=0; /* CREATE DUMMY TREATMENT 
VARIABLE FOR THE ANALYSIS STAGE*/
  IF TRT01P="360mg" THEN TRT2=1; ELSE TRT2=0; /* CREATE DUMMY TREATMENT 
VARIABLE FOR THE ANALYSIS STAGE*/
  IF HURLEY=1 THEN HURLEY1 = 1 ELSE HURLEY1 = 0; /* CREATE DUMMY 
VARIABLE FOR HURLEY STAGE 1*/
  IF HURLEY=2 THEN HURLEY2 = 1 ELSE HURLEY2 = 0; /* CREATE DUMMY 
VARIABLE FOR HURLEY STAGE 2*/
RUN;
/*AUGMENTATION STEP -- TO HAVE 30 MONOTONE MISSING DATASETS*/
PROC MI DATA= COUNT_2 OUT= COUNT_MONO NIMPUTE=30 SEED= 21423 /*RANDOM 
SEED PRE-DEFINED*/
  ROUND=. . . . . 1 1 1 1 1 1 1 /*VALUE ROUND TO INTEGER*/
  MIN=. . . . . 0 0 0 0 0 0 0  /*MINIMUM VALUE OF COUNT IS 0*/
  MAX=. . . . . . . . . . . .   /*MAXIMUM VALUE*/
MCMC IMPUTE=MONOTONE ;
/*NOTE: CATEGORICAL VARIABLES SUCH AS TRT1 TRT2 HURLEY1 HURLEY2 ARE 
DUMMY, CREATED ABOVE*/
/*NOTE: ALL OTHER NON-DUMMIED COVARIATES MUST BE CONTINUOUS*/
VAR TRT1 TRT2 TNFN HURLEY1 HURLEY2 BASE WK1 WK2 WK4 WK8 WK12 WK16;
/*CAUTION TO USE THE "BY" STATEMENT IN MCMC: */


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/*MVN MODEL IS FITTED WITHIN EACH 'BY' GROUP, INSTEAD OF ACROSS ALL 
GROUPS*/
RUN;
/*IMPUTATION STEP – DETERMINE IMPUTATION DISTRIBUTION AND RANDOMLY 
IMPUTE MISSING VALUE TO GENERATE 'COMPLETE' DATASETS*/
/***************************************************/
PROC MI DATA= COUNT_MONO OUT= COUNT_FULL NIMPUTE=1 SEED= 21931  /*RANDOM 
SEED PRE-DEFINED*/
  ROUND=. . . 1 1 1 1 1 1 1 /*VALUE ROUND TO INTEGER*/
  MIN=. . . 0 0 0 0 0 0 0  /*MINIMUM VALUE OF COUNT IS 0*/
  MAX=. . . . . . . . . .   /*MAXIMUM VALUE*/
  MINMAXITER=1000;
  /*CLASS CATEGORICAL VARIABLES TRT1 AND REG2*/
  CLASS TRT01P TNFN HURLEY;
  VAR TRT01P TNFN HURLEY BASE WK1 WK2 WK4 WK8 WK12 WK16;
  MONOTONE REG (WK1 WK2 WK4 WK8 WK12 WK16);  /* IMPUTED SEQUENTIALLY, 
FROM WK 1 TO 16, WITH COVARIATES CONSTRUCTED FROM THE CORRESPONDING 
PRECEDING VARIABLES*/
  BY _IMPUTATION_;                   /*FOR EACH OF THE 30 MONOTONE 
MISSING DATASETS, IMPUTE A 'COMPLETE' DATASET*/
RUN;
/*We will get the imputed "complete" datasets for abscess, inflammatory 
nodule, and draining fistula counts.  For sample code below, we denote 
the following variables: ABS16, INF16 and DRA16 as the corresponding 
lesion count at Week 16; and AN16 as the sum of ABS16 and INF16.  
Determine the HiSCR status at Week 16.  */
DATA ALL; SET COUNT_FULL;
    IF 0<= AN16 <=0.5*AN_BASE AND ABS16<=ABS_BASE AND DRA16 <= DRA_BASE 
THEN HISCR_16=1;
    ELSE HISCR_16=0;
RUN; 
/***********************************************************************
*/
/*         DATA HANDLING STEPS TO MERGE COVID-19 STATUS OMITTED         
*/
/*            PLACE TO ADD DATA HANDLING AND MERGING STEPS              
*/
/***********************************************************************
*/
/*FOR MI, SKIP THE FOLLOWING CODE, PROCEED TO THE CODE AFTER ANALYSIS 
MODEL *//*OVERRIDE MISSING VALUES NOT DUE TO COVID-19 WITH TRADITIONAL 
NRI*/
DATA ALLF; SET ALL;


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  /*COVID19_XX='Y' IF MISSING AT WEEK XX IS DUE TO COVID-19; IF NOT, 
OVERRIDE WITH TRADITIONAL NRI*/
  /*VARIABLE HISCR_NRI_16: TRADITIONAL NRI DATA AT WEEK 16, WHICH COVERS 
THE SPECIAL HANDLING SUCH AS THE BEFORE-AND-AFTER EXCEPTION IN THE 
PARTICULAR STUDY PERIOD*/
  IF COVID19_MISS NE 'Y' THEN HISCR_16 = HISCR_NRI_16;
RUN;
PROC SORT DATA=ALLF; BY _IMPUTATION_ SUBJID; RUN;
/****************/
/*ANALYSIS MODEL*/
/****************/
/*KEY CODE: ANALYZING EACH 'COMPLETE' DATASET*/
/***********************************/
/*COMPARE TREATMENT PLACEBO AND 360mg ONLY*/
DATA ALL; SET ALL;
WHERE TRT01P NE "180mg";
RUN;
/***********************************/
/*INDIVIDUAL-LEVEL DATA --> # OF RESPONDERS & # OF SUBJECTS, TO BE READ-
IN TO PROC STDRATE */
PROC FREQ DATA=ALL;
  BY _IMPUTATION_;
  TABLES TRT2*STRATA*HISCR_16/LIST NOCUM NOPRINT OUT=COUNT_TABLE;
  /*TRT2 = 1 as 360mg and 0 as placebo*/
RUN;
DATA COUNT_TABLE; SET COUNT_TABLE;
  DROP PERCENT;
RUN;
PROC TRANSPOSE DATA=COUNT_TABLE OUT=FREQ_TABLE PREFIX=RESP;
ID HISCR_16;
BY _IMPUTATION_ TRT2 STRATA;
VAR COUNT;
RUN;  
DATA FREQ_TABLE1; SET FREQ_TABLE;
  CASE=RESP1;
  SIZE=SUM(RESP0, RESP1);
  KEEP _IMPUTATION_ TRT2 STRATA CASE SIZE;
RUN;
/*CALCULATE THE COMMON RISK DIFF FOR EACH COMPLETE DATASET*/
PROC STDRATE DATA=FREQ_TABLE2
  METHOD=MH STAT=RISK EFFECT=DIFF;
  BY _IMPUTATION_;
  POPULATION GROUP=TRT2 EVENT=CASE TOTAL=SIZE;
  STRATA STRATA / ORDER=DATA STATS(CL=NONE) EFFECT;
  ODS OUTPUT EFFECT=EFFECT;


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RUN;
/*COMBINING RESULTS USING PROC MIANALYZE*/
/****************************************/
PROC MIANALYZE DATA=EFFECT;
  ODS OUTPUT PARAMETERESTIMATES=RISK_DIFF_MH;  
  MODELEFFECTS RiskDiff;
  STDERR StdErr;
RUN;
4.0
Reference
1.
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-
19 Pandemic - Guidance for Industry, Investigators, and Institutional Review 
Boards.  FDA.  2020. 
2.
Statistical Considerations for Clinical Trials During the COVID-19 Public Health 
Emergency - Guidance for Industry.  FDA.  2020. 
3.
Points to consider on implications of Coronavirus disease (COVID-19) on 
methodological aspects of ongoing clinical trials.  EMA.  2020.
4.
Graham JW, Olchowski AE, Gilreath TD.  How many imputations are really 
needed?  Some practical clarifications of multiple imputation theory.  Prev Sci.  
2007;8(3):206-13. 
5.
Rubin DB, Schenker N.  Interval estimation from multiply-imputed data: a case 
study using agriculture industry codes.  J Am Stat Assoc.  1987;81:366-74.
6.
White IR, Royston P, Wood AM.  Multiple imputation using chained equations: 
Issues and guidance for practice.  Stat Med.  2011;30(4):377-99.