Clinical trial NCT03628924
Conditions: Hidradenitis Suppurativa
Sponsor: Janssen Research & Development, LLC
Start date: 2018-09-04; Completion date: 2020-05-22
Enrollment: 184 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy, safety, and tolerability of guselkumab in adult participants with moderate to severe hidradenitis suppurativa (HS).

Detailed description:

Arms: arm 1: Participants will receive guselkumab dose 1 administered Intravenously (IV) followed by guselkumab dose 2 administered subcutaneously. arm 2: Participants will receive guselkumab dose 2 subcutaneously. arm 3: Participants will receive placebo IV and SC and an additional SC placebo dose at Week 12 then cross over at Week 16 to receive guselkumab dose 2 and dose 3 SC and placebo SC.
Interventions: intervention 1: Guselkumab dose 1 intervention 2: Guselkumab dose 2 intervention 3: Guselkumab dose 3 intervention 4: Placebo
Intervention descriptions: intervention 1: Participants will receive guselkumab dose 1 IV. intervention 2: Participants will receive guselkumab dose 2 SC in Group 1, 2 and Group 3. intervention 3: Participants will receive guselkumab dose 3 SC in Group 3. intervention 4: Participants will receive matched placebo SC and IV in group 1, 2 and 3 with an additional placebo SC dose in Group 3.

Protocol documents:
Prot_000.pdf: 
1
Status: Approved,  Date: 2 May 2019
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept 
Study to Evaluate Guselkumab for the Treatment of Subjects with Moderate to Severe 
Hidradenitis Suppurativa
NOVA
Short Title
A Proof-of-Concept Study of Guselkumab in the Treatment of Subjects with Moderate to 
Severe Hidradenitis Suppurativa
Protocol CNTO1959HDS2001; Phase 2
AMENDMENT 1
CNTO 1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development 
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen 
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen 
Sciences Ireland UC; or Janssen Research & Development, LLC. The term “sponsor” is used throughout 
the protocol to represent these various legal entities; the sponsor is identified on the Contact Information 
page that accompanies the protocol.
US sites of this study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
EudraCT NUMBER: 2018-001176-38
Status:
Approved
Date:
2 May 2019
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-ERI-156454263 version 4.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03628924


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 1
2 May 2019
Original Protocol
14 May 2018
Amendment 1 [02 May 2019]
Overall Rationale for the Amendment: The overall rationale for the changes implemented in the 
protocol amendment was to include an additional urine pregnancy test at Week 48 of the study, increase 
the percentage of total participants who are in Hurley Stage III, make necessary corrections to the total 
blood volume to be collected from each participant during the study, eliminate certain laboratory tests 
identified as not needed, resolve inconsistencies identified in the duration of continued contraception after 
the subject receives their last dose, and other minor typographical issues.
Section number
and Name
Description of Change
Brief Rationale
1.1 Synopsis
Objectives and 
Endpoints
Other Secondary 
Endpoints
Added the following word where indicated:

The proportion of participants with HS-IGA 
(investigator’s global assessment) score of 
inactive (0), almost inactive (1), or mild activity
(2) and with at least 2-grade improvement 
relative to baseline at Week 16.
•
The proportion of participants with HS-IGA 
score of inactive (0) or almost inactive (1) at 
Week 16 among participants with HS-IGA score 
of moderate activity (3) or severe activity (4) at 
baseline.
Included the word “activity” to be 
consistent with terminology used in 
the HS-IGA assessment tool.
1.1 Synopsis
Efficacy Analyses
Added the following text: “If a given comparison is 
not significant at the 2-sided α level of 0.05, 
nominal p values will be provided for the 
subsequent treatment group comparisons and the 
subsequent treatment group comparisons will be 
considered as supportive.”
Provide clarification of multiple 
testing procedure.
1.3 Schedule of 
Activities
Study Procedures
Urine pregnancy test
Included an additional urine pregnancy test to be 
performed at Week 48 or at early termination 
visit.
Added based on health authority 
feedback.
3. Objectives and 
Endpoints
Other Secondary 
Endpoints
Added the following word where indicated:

The proportion of participants with HS-
Investigator’s Global Assessment (HS-IGA) 
score of inactive (0), almost inactive (1), or mild 
activity (2) and with at least 2-grade 
improvement relative to baseline at Week 16.
•
The proportion of participants with HS-IGA 
score of inactive (0) or almost inactive (1) at 
Week 16 among participants with HS-IGA score 
of moderate activity (3) or severe activity (4) at 
baseline.
Included the word “activity” to be 
consistent with terminology used in 
the HS-IGA assessment tool.
4.2.1. Study-Specific 
Ethical Design 
Considerations
Revised the amount for the total blood volume in the 
following sentence: “The total blood volume to be 
collected from each participant in each group 
The total blood volume to be 
collected from each participant in 
each group over the course of the 


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Clinical Protocol CNTO1959HDS2001
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Section number
and Name
Description of Change
Brief Rationale
(approximately 150  approximately 181.5 mL over 
approximately 48 weeks) is far less than the 
American Red Cross standard limit for whole blood 
donation (approximately 475 mL q8w) and is 
therefore considered an acceptable amount of blood 
to be collected over this time period.”
study was updated.
5.1 Inclusion 
Criteria
Criterion #16a
Corrected to the appropriate units:
a. Hemoglobin 10 g/dL (SI: 100 g/Lmmol/L)
Editorial correction: SI units 
corrected to mmol/L.
6.3 Measures to 
Minimize Bias: 
Randomization and 
Blinding
Intervention 
Allocation
Procedures for 
Randomization and 
Stratification
Revised the percentage provided in the following 
sentence: “Additionally, the number of participants 
in Hurley stage III should be limited to 
approximately 30% 50% of the total planned 
number of participants.”
The percentage of participants in 
Hurley stage III out of the total 
number of study participants was 
increased due to fewer than expected 
subjects with Hurley stage I status
screened or randomized at the time 
of this protocol amendment.
6.5.5. Prohibited 
Therapy
Added some clarification text to the following 
bullets:
Concomitant use of oral antibiotic therapy for HS 
or inflammatory disorders. Systemic antibiotic 
use (including oral) is allowed for the treatment 
of acute infections such as bacterial, viral, or 
fungal. 
Oral 
or 
injectable 
corticosteroids 
for 
the 
treatment of HS, except for protocol allowed 
intralesional rescue therapy as outlined in 
Section 6.5.1.
Clarification related to the 
prohibited therapy.
6.5.6      
Concomitant 
Corticosteroid use 
for Conditions Other 
than HS
Added a new section regarding Concomitant 
Corticosteroid use for Conditions Other than HS.
The use of systemic corticosteroids for indications 
other than HS should be limited to situations for 
which, in the opinion of the treating physician, 
there are no adequate alternatives. They should 
be used on a short-term basis, preferably for ≤2 
weeks. Longer-term use of corticosteroids should
be discussed with the medical monitor or 
designee and may require discontinuation of 
study drug. Inhaled, otic, ocular, nasal or other 
routes of mucosal delivery of corticosteroids are 
allowed throughout the study.
Clarification related to the 
Concomitant Corticosteroid use for 
Conditions Other than HS 
8. Study 
Assessments and 
Procedures
Blood Sample 
Collection
Revised the amount for the total blood volume in the 
following sentence: “The total blood volume to be 
collected from each participant through Week 48 of 
the study will be approximately 150 approximately 
181.5 mL.”
The total blood volume to be 
collected from each participant over 
the course of the study was updated.
8.2.4 Clinical Safety 
Laboratory 
Assessments
Added the following information to the end of the 
sentence: “Female participants of childbearing 
potential will undergo a urine pregnancy test at 
screening, before each study intervention 
administration, and at the Week 48 or early 
termination visit.”
Added based on health authority 
feedback.


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Section number
and Name
Description of Change
Brief Rationale
9.4.1 Statistical 
Method
Added the following sentence: “In case the number 
of subjects that are Hurley Stage I at baseline is 
much less than was expected, subjects that were
Hurley Stage I will be pooled with subjects that 
were Hurley Stage II at baseline when baseline 
Hurley Stage is adjusted for in analyses.”
New text added due to few Hurley I 
subjects screened or randomized at 
the time of this protocol amendment.
9.4.2.1 Primary 
Analysis
Deleted text where indicated: “To address the 
primary objective, a CMH chi-squared statistic 
stratified by baseline weight (≤95 kg, >95 kg) and 
baseline Hurley stage (I, II, and III) at an alpha level 
of 0.05 will be used for each of the following 
hypotheses:”
Text deleted since Hurley Stage I
and II could be pooled in the 
analyses. This was already clarified 
in Section 9.4.1.
9.4.2.2 Major 
Secondary Analyses
Added the following text: “With the sequential 
analyses specified above within each dose group vs 
placebo, each of the hypotheses will be tested at a 2-
sided α level of 0.05 provided that the significance is 
achieved for the preceding hypothesis test in the 
specified order shown in Figure 2. If a given 
comparison is not significant at the 2-sided α level of 
0.05, nominal p values will be provided for the 
subsequent treatment group comparisons and the 
subsequent treatment group comparisons will be 
considered as supportive.”
Provided clarification of multiple 
testing procedure.
9.4.2.3 Other 
Efficacy Analyses
Added the following word where indicated:

The proportion of participants with HS-IGA 
score of inactive (0), almost inactive (1), or mild 
activity (2) and with at least 2-grade 
improvement relative to baseline at Week 16 will 
be compared between each of the guselkumab 
groups and the placebo group.
•
The proportion of participants with HS-IGA 
score of inactive (0), almost inactive (1) at Week 
16 among participants with HS-IGA score of 
moderate activity (3) or severe activity (4) at 
baseline will be compared between each of the 
guselkumab groups and the placebo group.
Included the word “activity” to be 
consistent with terminology used in 
the HS-IGA assessment tool.
9.4.3 Safety 
Analyses
Adverse Events
Modified the following text:

The incidence and type of AEs temporally 
associated with infusion (defined as an AE that 
occurred on the same day of infusion, with a 
start time during infusion or ≤ 60 minutes 
after the end of infusion). infusion reactions.
Clarified the definition of AEs 
temporally associated with infusion 
of study intervention.
10.3 Appendix 3: 
Clinical Laboratory 
Tests
Protocol-Required 
Safety Laboratory 
Assessments
Other Laboratory 
Tests
The following tests were deleted:
•
serum antibody titers to varicella, measles, 
mumps, and rubella)
•
Serum IgG, IgM, IgA levels
Laboratory tests identified as not 
performed were deleted.
10.7 Appendix 7: 
Contraceptive and 
Barrier Guidance 
and Collection of 
Changed the text as follows: “As noted in Inclusion 
Criterion 8, study participants who are women of 
childbearing potential must be practicing a highly 
effective method of contraception and remain on a 
The duration of continuing to 
practice contraception after 
receiving the last dose of study 
intervention was changed to 


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Section number
and Name
Description of Change
Brief Rationale
Pregnancy 
Information
highly effective method while receiving study 
intervention and until 16 weeks12 weeks after last 
dose.”
12 weeks to align with Inclusion 
Criterion 8.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted and 
corrected.


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Clinical Protocol CNTO1959HDS2001
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TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 6
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1.
PROTOCOL SUMMARY ..................................................................................................................... 9
1.1.
Synopsis........................................................................................................................................... 9
1.2.
Schema .......................................................................................................................................... 13
1.3.
Schedule of Activities (SoA)........................................................................................................... 14
2.
INTRODUCTION................................................................................................................................ 17
2.1.
Study Rationale.............................................................................................................................. 17
2.2.
Background .................................................................................................................................... 18
2.3.
Benefit/Risk Assessment ............................................................................................................... 21
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 21
4.
STUDY DESIGN ................................................................................................................................ 23
4.1.
Overall Design................................................................................................................................ 23
4.2.
Scientific Rationale for Study Design............................................................................................. 24
4.2.1.
Study-Specific Ethical Design Considerations ........................................................................... 25
4.3.
Justification for Dose...................................................................................................................... 25
4.4.
End of Study Definition................................................................................................................... 26
5.
STUDY POPULATION ...................................................................................................................... 27
5.1.
Inclusion Criteria ............................................................................................................................ 27
5.2.
Exclusion Criteria ........................................................................................................................... 30
5.3.
Lifestyle Considerations................................................................................................................. 34
5.4.
Screen Failures .............................................................................................................................. 35
6.
STUDY INTERVENTION................................................................................................................... 36
6.1.
Study Interventions Administered .................................................................................................. 36
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 36
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 37
6.4.
Study Intervention Compliance...................................................................................................... 39
6.5.
Concomitant Therapy..................................................................................................................... 39
6.5.1.
Rescue Therapy ......................................................................................................................... 40
6.5.2.
Antiseptic Therapy...................................................................................................................... 40
6.5.3.
Wound Care................................................................................................................................ 40
6.5.4.
Analgesic Therapy...................................................................................................................... 41
6.5.5.
Prohibited Therapy ..................................................................................................................... 41
6.5.6.
Concomitant Corticosteroid use for Conditions Other than HS.................................................. 42
6.6.
Dose Modification........................................................................................................................... 42
6.7.
Intervention After the End of the Study.......................................................................................... 43
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 43
7.1.
Discontinuation of Study Intervention ............................................................................................ 43
7.2.
Participant Discontinuation/Withdrawal from the Study................................................................. 45
7.2.1.
Withdrawal from the Use of Research Samples......................................................................... 45
7.3.
Lost to Follow-up............................................................................................................................ 45
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 46
8.1.
Efficacy Assessments .................................................................................................................... 47
8.1.1.
Hidradenitis Suppurativa Investigator’s Global Assessment...................................................... 47
8.1.2.
Lesion Counts............................................................................................................................. 47


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8.1.3.
Hurley Staging ............................................................................................................................ 47
8.1.4.
Hidradenitis Suppurativa Symptom Diary................................................................................... 47
8.1.5.
Dermatological Life Quality Index............................................................................................... 48
8.1.6.
Hospital Anxiety and Depression Scale...................................................................................... 48
8.1.7.
Patient Global Impression of Change of Hidradenitis Suppurativa Severity .............................. 48
8.1.8.
Photographs of Skin Lesions...................................................................................................... 48
8.2.
Safety Assessments....................................................................................................................... 48
8.2.1.
Physical Examination.................................................................................................................. 49
8.2.2.
Vital Signs................................................................................................................................... 49
8.2.3.
Electrocardiogram....................................................................................................................... 49
8.2.4.
Clinical Safety Laboratory Assessments .................................................................................... 49
8.2.5.
Columbia-Suicide Severity Rating Scale (C-SSRS)................................................................... 50
8.2.6.
Immunogenicity Assessments .................................................................................................... 51
8.2.7.
Concomitant Medication ............................................................................................................. 52
8.2.8.
Allergic Reactions ....................................................................................................................... 52
8.2.9.
Adverse Events Temporarily Related to Infusion ....................................................................... 53
8.2.10.
Injection-site Reactions............................................................................................................... 53
8.2.11.
Tuberculosis Evaluation(s) ......................................................................................................... 53
8.2.11.1.
Initial Tuberculosis Evaluation................................................................................................. 53
8.2.11.2.
Ongoing Tuberculosis Evaluation............................................................................................ 53
8.3.
Adverse Events and Serious Adverse Events ............................................................................... 54
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information.................................................................................................................................. 55
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 55
8.3.3.
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 55
8.3.4.
Pregnancy................................................................................................................................... 56
8.3.5.
Events of Special Interest........................................................................................................... 56
8.4.
Treatment of Overdose .................................................................................................................. 56
8.5.
Pharmacokinetics........................................................................................................................... 56
8.6.
Genetics ......................................................................................................................................... 57
8.7.
Biomarkers ..................................................................................................................................... 57
8.8.
Health Economics .......................................................................................................................... 58
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 58
9.1.
Statistical Hypotheses.................................................................................................................... 58
9.2.
Sample Size Determination ........................................................................................................... 58
9.3.
Populations for Analyses................................................................................................................ 60
9.4.
Statistical Analyses ........................................................................................................................ 60
9.4.1.
Statistical Method ....................................................................................................................... 60
9.4.2.
Efficacy Analyses........................................................................................................................ 61
9.4.2.1.
Primary Analysis...................................................................................................................... 61
9.4.2.2.
Major Secondary Analyses...................................................................................................... 62
9.4.2.3.
Other Efficacy Analyses .......................................................................................................... 63
9.4.3.
Safety Analyses .......................................................................................................................... 64
9.4.4.
Other Analyses ........................................................................................................................... 66
9.5.
Interim Analysis.............................................................................................................................. 67
9.6.
Data Monitoring Committee ........................................................................................................... 67
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 68
10.1.
Appendix 1: Abbreviations and Trademarks.................................................................................. 68
10.2.
Appendix 2: Anticipated Events ..................................................................................................... 70
10.3.
Appendix 3: Clinical Laboratory Tests ........................................................................................... 71
10.4.
Appendix 4: Tuberculin Skin Testing ............................................................................................. 72
10.5.
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations......................................... 73
REGULATORY AND ETHICAL CONSIDERATIONS .......................................................................... 73
FINANCIAL DISCLOSURE .................................................................................................................. 76
INFORMED CONSENT PROCESS ..................................................................................................... 76
DATA PROTECTION ........................................................................................................................... 77


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LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH...................... 78
COMMITTEES STRUCTURE .............................................................................................................. 78
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA........................................... 78
DATA QUALITY ASSURANCE ............................................................................................................ 80
CASE REPORT FORM COMPLETION ............................................................................................... 80
SOURCE DOCUMENTS ...................................................................................................................... 81
MONITORING ...................................................................................................................................... 81
ON-SITE AUDITS................................................................................................................................. 82
RECORD RETENTION ........................................................................................................................ 82
STUDY AND SITE CLOSURE ............................................................................................................. 83
10.6.
Appendix 6: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting............................................................................................................... 84
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS.............................................................. 84
ATTRIBUTION DEFINITIONS.............................................................................................................. 85
SEVERITY CRITERIA .......................................................................................................................... 85
SPECIAL REPORTING SITUATIONS ................................................................................................. 86
PROCEDURES .................................................................................................................................... 86
CONTACTING SPONSOR REGARDING SAFETY............................................................................. 87
PRODUCT QUALITY COMPLAINT HANDLING.................................................................................. 87
10.7.
Appendix 7: Contraceptive and Barrier Guidance and Collection of Pregnancy Information........ 89
10.8.
Appendix 8: Guselkumab Predicted Exposure Margins ................................................................ 92
10.9.
Appendix 9: Hepatitis B Virus (HBV) Screening With HBV DNA Testing...................................... 93
10.10.
Appendix 10: Hidradenitis Suppurativa Investigator’s Global Assessment ................................... 94
10.11.
Appendix 11: Hidradenitis Suppurativa Symptom Diary................................................................ 96
10.12.
Appendix 12: Dermatology Life Quality Index................................................................................ 97
10.13.
Appendix 13: Hospital Anxiety and Depression Scale................................................................... 99
10.14.
Appendix 14: Patient Global Impression of Change of Hidradenitis Symptom Severity ............. 100
10.15.
Appendix 15: Columbia-Suicide Severity Rating Scale (Baseline/Screening)............................. 101
10.16.
Appendix 16: Columbia-Suicide Severity Rating Scale (Since Last Visit) ................................... 104
10.17.
Appendix 17: Protocol Amendment History ................................................................................. 107
11.
REFERENCES................................................................................................................................. 108
INVESTIGATOR AGREEMENT ............................................................................................................... 110
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Statistical Power for the HiSCR Response Rate Comparing to Placebo at Week 16.............. 60
Table 2:
Eligibility Based on Hepatitis B Virus Test Results................................................................... 93
FIGURES
Figure 1: Schematic Overview of CNTO1959HDS2001 ............................................................................. 13
Figure 2:
Diagram for Multiple Testing Procedure for Primary and Secondary Hypotheses................... 63


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1.
PROTOCOL SUMMARY
1.1.
Synopsis
A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept Study to 
Evaluate Guselkumab for the Treatment of Subjects with Moderate to Severe Hidradenitis Suppurativa
Protocol number: CNTO1959HDS2001
Guselkumab (CNTO 1959) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody 
that binds to the p19 protein subunit of human interleukin (IL)-23 with high specificity and affinity. The 
binding of guselkumab to the IL-23p19 subunit blocks the binding of extracellular IL-23 to the cell 
surface IL-23 receptor, inhibiting IL-23-specific intracellular signaling and subsequent activation and 
cytokine production. Guselkumab has been studied in Phase 1, Phase 2, and ongoing Phase 3 studies for 
the treatment of moderate to severe plaque psoriasis in adults. Guselkumab has been approved for the 
treatment of adults with moderate to severe plaque psoriasis in the United States, Europe, Canada, and 
several other countries. Guselkumab is also being studied globally for the treatment of psoriatic arthritis
(PsA), Crohn’s disease, and pediatric psoriasis.
OBJECTIVES AND ENDPOINTS
Objectives
Primary Objective
The primary objective of this study is to evaluate the initial efficacy, safety, and tolerability of 
guselkumab in adult participants with moderate to severe hidradenitis suppurativa (HS).
Secondary Objectives
The secondary objectives of this study are:

To evaluate the efficacy of guselkumab in adult participants with moderate to severe HS during the 
maintenance phase.

To evaluate the effect of guselkumab on the dermatologic health-related quality of life in adult
participants with moderate to severe HS.

To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of 
guselkumab therapy in adult participants with moderate to severe HS.
Endpoints
Primary Endpoint
The proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at 
Week 16
Major Secondary Endpoints

The change from baseline in total abscess and inflammatory nodule (AN) count at Week 16.

The change from baseline in Dermatology Life Quality Index (DLQI) score at Week 16.

The change from baseline in HS-related pain in the past 24 hours based on Hidradenitis Suppurativa 
Symptom Diary (HSSD) at Week 16.


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Other Secondary Endpoints

The proportion of participants achieving at least 50%, 75%, 90%, and 100% reduction in total AN 
count at Week 16.

The proportion of participants achieving an AN count of 1 and 2, respectively, at Week 16.

The proportion of participants achieving complete elimination of abscesses at Week 16 among those 
participants with abscesses at baseline.

The change from baseline in the number of abscesses at Week 16.

The change from baseline in HSSD symptom scale score (other than pain the past 24 hours) at 
Week 16.

The change from baseline in HSSD total symptom score at Week 16.

The proportion of participants achieving complete elimination of draining fistulas at Week 16 among 
those participants with draining fistulas at baseline.

The change from baseline in number of draining fistulas at Week 16.

The proportion of participants achieving complete elimination of inflammatory nodules at Week 16
among those participants with inflammatory nodules at baseline.

The change from baseline in number of inflammatory nodules at Week 16.

The proportion of participants with HS-IGA (investigator’s global assessment) score of inactive (0), 
almost inactive (1), or mild activity (2) and with at least 2-grade improvement relative to baseline at 
Week 16.

The proportion of participants with HS-IGA score of inactive (0) or almost inactive (1) at Week 16 
among participants with HS-IGA score of moderate activity (3) or severe activity (4) at baseline.

The change from baseline in Hospital Anxiety and Depression Scale (HADS) scores at Week 16.

The change from baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 16.

The distribution of the Patient Global Impression of Change (PGIC) of HS severity at Week 16.
Hypotheses
The primary hypothesis is that guselkumab treatment is superior to placebo as assessed by the proportion 
of participants achieving HiSCR at Week 16.
The major secondary hypotheses are that guselkumab treatment is:

Superior to placebo as assessed by the change from baseline in AN count at Week 16.

Superior to placebo as assessed by the improvement in patient-reported outcomes (PRO) as 
measured by:

The change from baseline in DLQI score at Week 16.

The change from baseline in HS-related pain in the past 24 hours based on HSSD at Week 16.
OVERALL DESIGN
This is a Phase 2, multicenter, randomized, placebo-controlled, double-blind study evaluating the efficacy, 
safety, PK, and immunogenicity of subcutaneous (SC) and intravenous (IV) administered guselkumab for 
the treatment of moderate to severe HS in adult participants. The participant population will comprise 
men and women who have had moderate to severe HS for at least 1 year.


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Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
Two database locks (DBLs) are planned for this study at Week 16 and Week 48, respectively. An interim 
analysis will be conducted when a subset of participants have completed the Week 16 visit.
An independent Data Monitoring Committee (DMC) will be commissioned for this study for safety 
evaluation.
NUMBER OF PARTICIPANTS
180 participants, ≥18 years of age, with HS, that is moderate to severe, and has been present for at least 1 
year before the first administration of study intervention, and stable for at least 1 month (28 days) prior to 
screening as determined by the investigator through patient interview and/or review of the medical 
history. Participants must also have HS lesions in at least 2 distinct anatomic areas, had an inadequate 
response to an adequate course of oral antibiotics for treatment of HS in the investigator’s opinion, and 
have a total AN count of ≥3 at the screening and baseline visits. Participants must agree to daily use of 
soap and water, or a topical antiseptic wash containing chlorhexidine gluconate, triclosan, or benzoyl 
peroxide, or a dilute bleach bath to all areas affected by HS throughout the study.
INTERVENTION GROUPS AND DURATION
All participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment groups as described below:
Group 1: Guselkumab Regimen 1 (1200 mg IV q4w x 3 → 200 mg SC q4w)
Participants will receive guselkumab 1200 mg IV at Week 0, Week 4, and Week 8 (ie, a total of 3 IV 
guselkumab doses and 3 SC placebo doses). At Week 12, participants will continue treatment with 
guselkumab 200 mg SC q4w through Week 36.
Group 2: Guselkumab Regimen 2 (200 mg SC q4w x 3 → 200 mg SC q4w)
Participants will receive guselkumab 200 mg SC at Week 0, Week 4, and Week 8 (ie, a total of 3 SC 
guselkumab doses and 3 IV placebo doses). At Week 12, participants will switch treatment to guselkumab 
200 mg SC q4w through Week 36.
Group 3: Placebo
Participants will receive placebo IV and SC at Week 0, Week 4, and Week 8 (ie, a total of 3 IV and 3 SC 
placebo doses) and an additional SC placebo dose at Week 12. At Week 16, participants will be 
rerandomized at a 1:1 ratio to either guselkumab 200 mg SC q4w through Week 36 or guselkumab 
100 mg SC at Weeks 16, 20, 28, 36 and placebo at Weeks 24 and 32.
A screening period will take approximately 4 weeks. All participants will enter safety follow-up after 
Week 36 through Week 48.
EFFICACY EVALUATIONS
Efficacy evaluations include:

HS-Investigator’s Global Assessment

Lesion Counts

Hurley Staging

HSSD

DLQI


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Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019

HADS

PGIC of HS Severity

Photographs of HS lesions 
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Venous blood samples will be collected for the measurement of serum guselkumab concentrations and 
detection of antibodies to guselkumab at the time points presented in the Schedule of Activities. Serum 
samples will also be collected at the final visit from participants who terminate study participation early.
BIOMARKER EVALUATIONS
Biomarker assessments will include the evaluation of relevant markers in serum for all participants and 
will be collected at the time points presented in the Schedule of Activities.
Serum samples will be analyzed for circulating factors such as cytokines and other inflammatory markers 
(eg, IL-17A, IL-17F, IL-23, TNFα, IL-6, IL-22), and other categories of biomarkers potentially associated 
with the development and progression of HS or related to the guselkumab mechanism of action.
SAFETY EVALUATIONS
Safety evaluations conducted at each study visit will include the assessment of adverse events (AEs, at the 
visit and those occurring between evaluation visits), a tuberculosis evaluation and other infection 
assessment, clinical laboratory blood tests (complete blood count and serum chemistries), physical 
examinations, vital sign measurements, echocardiogram, suicidality assessment measured using C-SSRS, 
concomitant medication review, and observations for injection-site reactions, reactions temporally 
associated with an infusion, and/or allergic reactions.
STATISTICAL METHODS
Sample Size Determination
This study is designed to enroll approximately 180 participants, in order to have sufficient power 
achieving the primary efficacy endpoint. The assumptions for the sample size and power calculations 
were based on the clinical data from the 2 adalimumab (Humira®) Phase 3 clinical studies M11-313 
(PIONEER I) and M11-810 (PIONEER II) that evaluated the safety and efficacy of adalimumab in the 
treatment of adult participants with moderate to severe HS. With 60 participants in each of the 
guselkumab treatment group and 60 participants in the placebo group, there will be more than 90% power 
to detect a treatment difference of 30% between each guselkumab group and the placebo group for the 
primary efficacy endpoint with a significance level of 0.05.
Efficacy Analyses
All randomized participants who received at least 1 dose of study intervention will be included in the 
efficacy analyses. Participants will be analyzed according to the treatment group to which they were 
randomized, regardless of the treatment they actually received.
For response efficacy endpoints, treatment comparisons will be performed using a Cochran-Mantel-
Haenszel (CMH) test stratified by the baseline weight (≤95 kg, >95 kg) and baseline Hurley stage (I, II, 
and III). For continuous efficacy endpoints, treatment comparisons will be performed using either a 
Mixed-Effect Model Repeated Measure (MMRM) model or an analysis of covariance (ANCOVA) model. 
All of the models will have treatment group, baseline weight (≤95 kg, >95 kg), baseline Hurley stage (I, 
II, and III), and baseline value as explanatory factors. MMRM models will additionally include visit, 
treatment by visit, and baseline value by visit interaction terms. All statistical tests will be performed at a 


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
2-sided significance level of α=0.05. In addition, graphical data displays (eg, line plots) and participant 
listings may also be used to summarize/present the data.
In order to control the overall Type 1 error rate for comparisons between each guselkumab group and the 
placebo group, the primary analysis and major secondary analyses will be tested in a fixed sequence for 
the comparisons at an alpha level of 0.05. If a given comparison is not significant at the 2-sided α-level of 
0.05, nominal p values will be provided for the subsequent treatment group comparisons and the 
subsequent treatment group comparisons will be considered as supportive.
Analyses for other efficacy endpoints will be performed and nominal p-values will be provided.
Safety Analyses
Safety data, including but not limited to, AE, serious adverse events (SAE), infections, serious infections, 
mortality, suicidality assessment, changes in laboratory assessments, and changes in vital signs will be 
summarized. Intervention-emergent AEs will be summarized by treatment group and Medical Dictionary 
for Regulatory Activities (MedDRA) system organ class and preferred terms.
1.2.
Schema
Figure 1: Schematic Overview of CNTO1959HDS2001


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Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
1.3.
Schedule of Activities (SoA)
From Screening through Week 48
Period
Screeninga
Placebo-Controlled Period
Blinded Active Treatment Period
Safety Follow-up
Week
0
2
4
8
12
16
20
24
28
32
36
40
44
48 or Early 
Termination 
Visitb
Study Proceduresc
Screening/Administrative
Informed consent
X
Medical history 
and demographics
X
Inclusion/ 
exclusion criteria
X
X
Nicotine Use
X
X
X
Alcohol Use
X
X
X
Study Intervention Administration
Randomization
X
Xd
Study intervention
IV administratione
X
X
X
Study intervention
SC administratione
X
X
X
X
X
X
X
X
X
X
Safety Assessments
Physical 
examination 
(including skin)
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Waist 
Circumference
X
X
Tuberculosis 
evaluation
X
X-------------------------------------------------------------------------------------------------------------------------------------------X
Columbia-Suicide 
Severity Rating 
Scale (C-SSRS)f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest radiograph
X
12-lead ECG
X


CNTO 1959 (guselkumab)
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Approved, Date: 2 May 2019
From Screening through Week 48
Period
Screeninga
Placebo-Controlled Period
Blinded Active Treatment Period
Safety Follow-up
Week
0
2
4
8
12
16
20
24
28
32
36
40
44
48 or Early 
Termination 
Visitb
Study Proceduresc
Urine pregnancy 
testg
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
Concomitant 
therapy
X------------------------------------------------------------------------------------------------------------------------------------------X
Adverse events
X------------------------------------------------------------------------------------------------------------------------------------------X
Efficacy Assessments
Hurley stage
X
X
X
X
Lesion Counts
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HS-IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQIf
X
X
X
HADSf
X
X
X
Hidradenitis 
Suppurativa 
Symptom Diary 
(HSSD)f
X
X
X
X
X
X
X
Patient global 
impression of 
change (PGIC) of 
HS severityf
X
X
X
X
Photographs of 
skin lesionsh
X
X
X
Clinical Laboratory Assessment
QuantiFERON®-
TB testi
X
Hepatitis B and C 
serology
X
HIV antibody test
X
Hematology
X
X
X
X
X


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
From Screening through Week 48
Period
Screeninga
Placebo-Controlled Period
Blinded Active Treatment Period
Safety Follow-up
Week
0
2
4
8
12
16
20
24
28
32
36
40
44
48 or Early 
Termination 
Visitb
Study Proceduresc
Chemistry
X
X
X
X
X
Lipid panelj
X
High sensitivity C-
reactive protein 
(hs-CRP)
X
X
X
X
Pharmacokinetics and Immunogenicityk,l
Serum guselkumab
concentration 
X
X
X
X
X
X
X
X
X
X
Antibodies to 
guselkumab
X
X
X
X
X
X
X
X
Biomarkers
Serum biomarkersc
X
X
X
X
X
Footnotes:
a.
The screening visit should occur no more than 4 weeks before the Week 0 visit.
b. The Early Termination Visit should occur approximately 12 weeks after the last administration of study intervention (unless consent is withdrawn).
c.
All study procedures and evaluations are to be completed before study intervention is administered except where otherwise indicated.
d. Randomization at Week 16 is for placebo group only and will not affect blinding.
e.
IV infusions and SC injections for Weeks 0, 4, 8 and SC injections for Weeks 12 through 36.
f.
The C-SSRS should be completed as the first assessment at screening after signing informed consent and before any tests, procedures, or other consultations, with the exception of 
the urine pregnancy test, and as the first assessment for baseline and all post-baseline visits, before any tests, procedures, or other consultations, with the exception of the urine 
pregnancy test, to prevent influencing participant perceptions. DLQI, HADS, HSSD, and PGIC should be performed before any tests, procedures, or other evaluations (Hurley stage,
HS-IGA, Lesion counts), with the exception of the urine pregnancy test, for that visit.
g. Women of childbearing potential must have a negative urine pregnancy test result before randomization and before receiving study intervention at all study intervention 
administration visits, and at Week 48 or early termination visit.
h. Photographs to be taken at selected sites for participants who provide an additional consent; if such participants discontinue administration of study intervention early, however, 
photographs are not required at the final study visit.
i.
A tuberculin skin test is additionally required if the QuantiFERON®-TB test is not approved/registered in the country in which this study is being conducted.
j.
Participants must fast (ie, no food or beverages [except water]) for at least 8 hours before blood is drawn for lipid panel.
k. For all visits where study intervention will be administrated, one blood sample should be collected prior to study intervention administration for evaluation of serum concentration of 
guselkumab and/or antibodies to guselkumab. In addition, for IV infusion-related visits (ie, Weeks 0, 4, and 8), another blood draw should be taken approximately 60 minutes after 
completion of the infusion for serum concentration of guselkumab.
l.
Participants who terminated study participation early should have a safety follow-up visit approximately 12 weeks after their last administration of study intervention. Serum samples 
should be collected at this visit for serum drug concentration measurement and antibody to drug assessment.


CNTO 1959 (guselkumab)
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2.
INTRODUCTION
Guselkumab (CNTO 1959) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal 
antibody (mAb) that binds to human interleukin (IL)-23 with high specificity and affinity. The 
binding of guselkumab to the IL-23p19 subunit blocks the binding of extracellular IL-23 to the 
cell surface IL-23 receptor, inhibiting IL-23-specific intracellular signaling and subsequent 
activation and cytokine production. In this manner, guselkumab inhibits the biological activity 
of IL-23 in all in vitro assays examined.
Guselkumab has been approved in the United States, the European Union, Canada, and several
other countries for the treatment of adult patients with moderate to severe plaque psoriasis. Data 
supporting the approval of the plaque psoriasis indication in adults included safety and efficacy 
data from 2,700 participants from 3 global Phase 3 studies (CNTO1959PSO3001 [VOYAGE 1], 
CNTO1959PSO3002 [VOYAGE 2], and CNTO1959PSO3003 [NAVIGATE]). Studies 
CNTO1959PSO3001 and CNTO1959PSO3002 have ongoing long-term extensions (LTE). In 
addition, guselkumab is being studied globally for the treatment of psoriatic arthritis (PsA),
Crohn’s disease, and pediatric psoriasis.
The approved dosage in the moderate to severe adult plaque psoriasis indication is 100 mg 
administered by subcutaneous (SC) injection at Week 0, Week 4, and every 8 weeks (q8w) 
thereafter. Guselkumab is not currently approved for use for the treatment of adult patients with 
moderate to severe hidradenitis suppurativa (HS).
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator's Brochure (IB) for guselkumab.
The term "sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
2.1.
Study Rationale
This is a proof-of-concept (POC) study to evaluate the efficacy, safety, and tolerability of 
guselkumab for the treatment of moderate to severe HS in adult participants by means of:

Comparing the initial efficacy of 2 dose regimens (intravenous [IV] and SC) of guselkumab 
to placebo

Evaluating the longer-term efficacy resulting from the initial IV vs. SC dose regimens of 
guselkumab

Collecting safety and tolerability data for guselkumab in these HS participants
In addition, this study will evaluate the pharmacokinetics (PK), immunogenicity, and 
pharmacodynamics (PD) of guselkumab therapy in patients with HS.


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Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
2.2.
Background
Hidradenitis suppurativa is a chronic skin disease of unclear etiology that affects 1% to 4% of the 
general population.5,10,21,23 HS typically manifests as recurrent, inflamed, tender, subcutaneous 
nodules that are generally restricted to the axillary, inguinal, and anogenital regions.5,10,21 While 
some nodules resolve spontaneously, others progress to form sterile abscesses, which then 
rupture into the skin, leading to the formation of fistulas and sinus tracts that can spontaneously 
release purulent drainage.5,10,21 Over time, chronic inflammation can lead to irreversible scarring 
and fibrosis, which in severe cases can result in contractures and limitations in limb mobility, 
especially in the axilla.5,10,21 Disease onset is typically after puberty and women are affected 2 to 
5 times more commonly than men.5,10 Multiple factors including genetics, cigarette smoking, and 
obesity are believed to predispose a person to HS.5,23
The chronic pain, drainage, and progressive, irreversible scarring associated with HS has been 
shown to have a particularly profound effect on patients’ health-related quality of life relative to 
other common skin disorders.23 Patients with HS experience considerable impact on activities of 
daily living, work/school attendance and productivity, physical activities, and emotional state.20
Although a variety of treatments are utilized to manage HS, including medical treatments (eg, 
systemic combination therapy with clindamycin and rifampicin, tetracyclines, intralesional 
steroids, systemic cyclosporine, anti-androgen treatment in women, systemic dapsone, systemic 
retinoids and metformin)20 and surgical treatments (eg, incision and drainage of active lesions, 
local marsupialization and deroofing procedures, and radical excision), most have not been well 
studied and none appear particularly effective. The biologic anti-TNF inhibitor adalimumab 
(Humira®) has recently been approved to treat moderate to severe HS, but even this agent has 
not shown satisfactory treatment effects in many patients. Across two Phase 3 studies, the 
primary endpoint of Hidradenitis Suppurativa Clinical Response (HiSCR), defined as at least 
50% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess 
count and no increase in draining fistula count relative to baseline,4,9 was achieved in 42% and 
59%, respectively, of adalimumab-treated patients compared with 26% and 28%, respectively, of
placebo-treated patients.8 Therefore, a substantial, unmet medical need exists for safe and more 
effective HS management options with alternative mechanisms of action.
Although the pathogenesis of HS remains somewhat unclear, there is evidence that inflammation 
associated with increased IL-17 pathway activity mediated by IL-23 may be involved. Genetic 
variations within the gene encoding the common IL-12βR1 subunit of the IL-12/IL-23 receptor 
have been shown to be associated with a more severe course of HS, and tissue obtained from HS 
lesions showed increased IL-23/Th17 pathway gene expression and distinct infiltration of IL-17-
producing T helper cells compared with healthy skin.3,22 Moreover, an uncontrolled, open-label, 
investigator-initiated clinical study of ustekinumab (STELARA®), a monoclonal antibody that 
inhibits both IL-12 and IL-23, using the standard weight-based psoriasis dosage, demonstrated 
that the primary outcome (a moderate to marked improvement based on the modified Sartorius 
Score) was achieved in 82% of participants at Week 40.1 Furthermore, in a post-hoc analysis, 
47% of participants achieved a HiSCR.1 These results suggest that reducing IL-23-mediated 


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
inflammation with guselkumab may improve the signs and symptoms of active HS and 
potentially allow for better treatment of this distressing disease.
Nonclinical Studies
A comprehensive overview of the nonclinical development program for guselkumab is available 
in Section 3 of the latest version of the guselkumab IB.
This section provides a summary of the sponsor's assessment of how the overall nonclinical data 
support the safety of the proposed dosing for guselkumab in this Phase 2 program in HS. Details 
regarding the proposed dose regimen and dose rationale are described in Section 4.3 of this 
protocol.
To place the proposed clinical dosing for guselkumab in HS participants into perspective relative 
to the existing preclinical data, the predicted cumulative human exposures during the placebo-
controlled phase (1200 mg IV given at Weeks 0, 4, 8) were compared to the exposure at the no-
observed-adverse-effect level (NOAEL) in cynomolgus monkeys following weekly IV 
administration in the 5-week arm of the subchronic toxicology study. In addition, predicted 
cumulative 12-week human exposures during the induction phase were compared to the exposure 
at the NOAEL in cynomolgus monkeys following weekly SC administration in the 24-week arm 
of the subchronic toxicology study. Thereafter, the predicted human exposure at steady-state 
(based on the highest SC dose being tested in this protocol, ie, 200 mg SC q4w) was compared 
with the exposure at the NOAEL in cynomolgus monkeys following weekly SC administration 
in the 24-week arm of the subchronic toxicology study. These data are presented in Appendix 8 
(Section 10.8).
From a nonclinical perspective, the risk to HS patients is considered low when guselkumab is 
administered IV once every 4 weeks at doses up to 1200 mg (approximately 16 mg/kg in 
humans) followed by the proposed maintenance doses of up to 200 mg SC q4w, based on no 
adverse findings observed in cynomolgus monkeys following 5 weeks of once-weekly 
subchronic IV dosing at 50 mg/kg and 24 weeks of chronic once-weekly SC dosing. As 
summarized above, the actual exposure data (area under the serum concentration versus time 
curve [AUC]) achieved in monkeys relative to the predicted Week 8 to Week 12 IV clinical 
induction dosing interval AUC, or steady-state SC maintenance interval AUC (both normalized 
to weekly dosing to compare with the monkey dosing interval) provide ample exposure margins 
for the proposed clinical doses. This is further supported by the fact that guselkumab is an 
approved biotherapeutic with a good clinical safety profile in patients with plaque or other types 
of psoriasis, administered guselkumab at a dose of 100 mg SC, but also at doses up to 300 mg 
SC and 10 mg/kg IV in a limited number of patients with plaque psoriasis and in healthy normal 
volunteers, respectively, during Phase 1 of clinical development.


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
Clinical Studies
This protocol represents the first study of guselkumab in participants with HS.
This section provides a summary of the sponsor’s assessment of how the overall clinical 
experience with guselkumab across various indications supports the investigation of guselkumab 
in HS. Details about the guselkumab clinical development programs across various indications 
are provided in Section 4 of the latest version of the guselkumab IB.
Guselkumab is currently approved in the United States, European Union, Canada, and several 
other countries for the treatment of moderate to severe plaque psoriasis. Also, Japan recently 
approved guselkumab for the treatment of patients with psoriasis, generalized pustular psoriasis 
(GPP), erythrodermic psoriasis (EP), and PsA.
In addition, guselkumab is being evaluated in adult PsA, Crohn’s disease, and pediatric psoriasis 
globally, and in palmoplantar pustular psoriasis (PPP) in Japan.
Through the current IB cutoff date of 30 June 2017, 2,805 participants have been exposed to 
guselkumab across all indications in completed and ongoing clinical studies, including 185 
healthy participants, 2,336 participants with psoriasis, 129 participants with PsA, and 155 
participants in other indications.
The largest clinical experience to date with guselkumab has been in plaque psoriasis, primarily 
based on dosing at 100 mg SC q8w in the global Phase 2 and Phase 3 clinical development 
program (n=1,748), but also at doses up to 300 mg SC in a small number of participants (n=10) 
during Phase 1 clinical development. The safety profile of guselkumab in participants with 
moderate to severe plaque psoriasis based on data from the Phase 2 study (CNTO1959PSO2001) 
and 
three
Phase 
3 
studies 
(CNTO1959PSO3001, 
CNTO1959PSO3002, 
and 
CNTO1959PSO3003) is described in Section 4.4 of the latest version of the guselkumab IB. 
Briefly, of the 1,748 guselkumab-treated participants in the Phase 2 and Phase 3 studies, 1,393 
participants were exposed for at least 6 months and 728 participants were exposed for at least 
1 year. The LTEs of two of the Phase 3 studies (CNTO1959PSO3001 and CNTO1959PSO3002) 
are ongoing and will evaluate the safety and efficacy of guselkumab through up to 5 years of 
follow-up.
The totality of the safety data available to date show that guselkumab, administered SC at doses 
of 100 mg q8w in participants with plaque psoriasis, is well tolerated, has a safety profile 
comparable to placebo over 16 weeks, and safety remained favorable when referenced versus an 
active comparator (adalimumab) over 1 year. Additional safety data in other indications (in 
participants who also receive concomitant immunomodulators as background therapy) with
guselkumab doses as high as 200 mg SC q8w (in a Phase 2 rheumatoid arthritis study; n=54) did 
not identify any clinically significant safety signals through 1 year. Finally, a limited number of 
healthy participants (n=30) received single doses of IV guselkumab between 0.03 mg/kg and up 
to 10 mg/kg. Of the 6 participants in the 10 mg/kg dose group, the highest dose received was 
987 mg in 1 participant. No clinically significant safety signals were identified.


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
2.3.
Benefit/Risk Assessment
Based on the available data and the proposed safety measures discussed below, the risks of the 
dose regimens of guselkumab to be investigated in this protocol appear to be acceptable relative 
to the potential benefit.
Guselkumab has undergone extensive nonclinical and clinical development in inflammatory 
diseases such as PsA, Crohn’s disease, GPP, EP, PPP, and pediatric psoriasis, as summarized in 
the latest version of the IB and described briefly in Section 2.2. The collective efficacy and 
safety results of the Phase 1, Phase 2, and Phase 3 clinical studies in healthy volunteers and 
patients with plaque psoriasis, and the recent regulatory approval for the adult plaque psoriasis 
indication, established a favorable benefit-risk profile for guselkumab in the treatment of plaque 
psoriasis. 
There is evidence that inflammation associated with increased IL-17 pathway activity mediated 
by IL-23 may be involved in the pathogenesis of HS. Efficacy from an open-label ustekinumab 
study further suggested that reducing IL-23-mediated inflammation may improve the signs and 
symptoms of active HS (Section 2.2).
The approved dose regimen for guselkumab in psoriasis (100 mg SC at Week 0 and Week 4, and 
then q8w) has a favorable benefit/risk profile, and dose regimens as high as 200 mg SC q8w 
have been shown to be safe in a Phase 2 trial in rheumatoid arthritis. Clinical evidence suggests 
that meaningful efficacy in HS may require higher drug doses and exposures than psoriasis 
(Section 4.3). To determine the efficacy of guselkumab that results from the maximum exposure
feasible, while maintaining an adequate safety margin to the available guselkumab nonclinical 
toxicology data (Section 2.2), a dose of 1200 mg IV given q4w for 3 doses will be utilized for 
this POC study in HS. Of note, this 1200 mg IV dose regimen is also being utilized and 
evaluated in a large ongoing Crohn’s disease Phase 2b/3 clinical program. Unblinded safety will 
be evaluated on an ongoing basis throughout this trial by an independent Data Monitoring 
Committee (DMC), in addition to the standard safety oversight performed by the sponsor.
Details about the safety evaluations that will be utilized to continue or modify the protocol as the 
trial progresses are outlined in Section 9.6 and in the DMC charter.
More detailed information about the known and expected benefits and risks of guselkumab may 
be found in the IB.
3.
OBJECTIVES AND ENDPOINTS
OBJECTIVES
Primary Objective
The primary objective of this study is to evaluate the initial efficacy, safety, and tolerability of 
guselkumab in adult participants with moderate to severe HS.


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959HDS2001
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Approved, Date: 2 May 2019
Secondary Objectives
The secondary objectives of this study are:

To evaluate the efficacy of guselkumab in adult participants with moderate to severe HS
during the maintenance phase.

To evaluate the effect of guselkumab on the dermatologic health-related quality of life in 
adult participants with moderate to severe HS.

To evaluate the PK, immunogenicity, and PD of guselkumab therapy in adult participants
with moderate to severe HS.
ENDPOINTS
Primary Endpoint

The proportion of participants achieving HiSCR at Week 16
Major Secondary Endpoints

The change from baseline in total abscess and inflammatory nodule (AN) count at Week 16.

The change from baseline in Dermatology Life Quality Index (DLQI) score at Week 16.

The change from baseline in HS-related pain in the past 24 hours based on Hidradenitis 
Suppurativa Symptom Diary (HSSD) at Week 16.
Other Secondary Endpoints

The proportion of participants achieving at least 50%, 75%, 90%, and 100% reduction in
total AN count at Week 16.

The proportion of participants achieving an AN count of 1 and 2, respectively, at Week 16.

The proportion of participants achieving complete elimination of abscesses at Week 16
among those participants with abscesses at baseline.

The change from baseline in the number of abscesses at Week 16.

The change from baseline in HSSD symptom scale score (other than pain in the past 24 
hours) at Week 16.

The change from baseline in HSSD total symptom score at Week 16.

The proportion of participants achieving complete elimination of draining fistulas at 
Week 16 among those participants with draining fistulas at baseline.

The change from baseline in number of draining fistulas at Week 16.

The proportion of participants achieving complete elimination of inflammatory nodules at 
Week 16 among those participants with inflammatory nodules at baseline.

The change from baseline in number of inflammatory nodules at Week 16.


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
The proportion of participants with HS-Investigator’s Global Assessment (HS-IGA) score of 
inactive (0), almost inactive (1), or mild activity (2) and with at least 2-grade improvement 
relative to baseline at Week 16.

The proportion of participants with HS-IGA score of inactive (0) or almost inactive (1) at 
Week 16 among participants with HS-IGA score of moderate activity (3) or severe activity
(4) at baseline.

The change from baseline in Hospital Anxiety and Depression Scale (HADS) scores at 
Week 16.

The change from baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 16.

The distribution of the Patient Global Impression of Change (PGIC) of HS severity at 
Week 16.
Refer to Section 8, Study Assessments and Procedures, for evaluations related to endpoints.
HYPOTHESES
The primary hypothesis is that guselkumab treatment is superior to placebo as assessed by the 
proportion of participants achieving HiSCR at Week 16.
The major secondary hypotheses are that guselkumab treatment is:

Superior to placebo as assessed by the change from baseline in AN count at Week 16.

Superior to placebo as assessed by the improvement in patient-reported outcomes (PRO) as 
measured by:

The change from baseline in DLQI score at Week 16.

The change from baseline in HS-related pain in the past 24 hours based on HSSD at 
Week 16.
4.
STUDY DESIGN
4.1.
Overall Design
This is a Phase 2, multicenter, randomized, placebo-controlled, double-blind, POC study 
evaluating the efficacy, safety, PK, and immunogenicity of SC and IV administered guselkumab 
for the treatment of moderate to severe HS in adult participants. The participant population will 
comprise men and women who have had moderate to severe HS for at least 1 year.
A diagram of the study design (Figure 1) is provided in Section 1.2, Schema.
As depicted in Figure 1, approximately 180 participants who satisfy all inclusion and exclusion 
criteria will be randomized in a 1:1:1 ratio to 1 of 3 groups:


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Group 1: Guselkumab Regimen 1 (1200 mg IV q4w x 3 → 200 mg SC q4w)
Participants will receive guselkumab 1200 mg IV at Week 0, Week 4, and Week 8 (ie, a total of 
3 IV guselkumab doses and 3 SC placebo doses). At Week 12, participants will continue 
treatment with guselkumab 200 mg SC q4w through Week 36.
Group 2: Guselkumab Regimen 2 (200 mg SC q4w x 3 → 200 mg SC q4w)
Participants will receive guselkumab 200 mg SC at Week 0, Week 4, and Week 8 (ie, a total of 3
SC guselkumab doses and 3 IV placebo doses). At Week 12, participants will switch treatment to
guselkumab 200 mg SC q4w through Week 36.
Group 3: Placebo
Participants will receive placebo IV and SC at Week 0, Week 4, and Week 8 (ie, a total of 3 IV 
and 3 SC placebo doses) and an additional SC placebo dose at Week 12. At Week 16, 
participants will be rerandomized in a 1:1 ratio to either guselkumab 200 mg SC q4w through 
Week 36 or guselkumab 100 mg SC at Weeks 16, 20, 28, and 36, and placebo at Weeks 24 and 
32.
A screening period will take approximately 4 weeks. All participants will enter safety follow-up 
after Week 36 through Week 48. Two planned database locks (DBLs) will occur, at Week 16 and 
at Week 48.
Efficacy assessments (HS-IGA, lesion counts, Hurley staging, HSSD, DLQI, HADS, and PGIC) 
will be performed according to the Schedules of Activities. Serum samples for PK,
immunogenicity, and biomarker analyses will be collected at the timepoints shown in the 
Schedules of Activities (Section 1.3).
An interim analysis is planned and an independent DMC will be commissioned for this study for 
safety evaluation. Refer to Section 9.5 (Interim Analysis) and Section 9.6 (Data Monitoring 
Committee) for details.
4.2.
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Intervention Groups
Blinded treatment for guselkumab and placebo will be used to reduce potential bias during data 
collection and evaluation of endpoints. A placebo control will be used to establish the frequency 
and magnitude of changes in clinical endpoints that may occur in the absence of active treatment. 
Randomization will be used to minimize bias in the assignment of participants to treatment 
groups, to increase the likelihood that known and unknown participant attributes (eg, 
demographic and baseline characteristics) are evenly balanced across treatment groups, and to 
enhance the validity of statistical comparisons across treatment groups.


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4.2.1.
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during 
the study, participants will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may be 
withdrawn at any time with no reason given and without penalty or loss of benefits to which they 
would otherwise be entitled. Only participants who are fully able to understand the risks, benefits, 
and potential adverse events (AEs) of the study and provide their consent voluntarily will be 
enrolled.
The total blood volume to be collected from each participant in each group (181.5 mL over 
approximately 48 weeks) is far less than the American Red Cross standard limit for whole blood 
donation (approximately 475 mL q8w) and is therefore considered an acceptable amount of blood 
to be collected over this time period. For more details regarding blood collection, see Blood 
Sample Collection in Section 8.
4.3.
Justification for Dose
The following guselkumab dose regimens are selected for this Phase 2 POC study in participants 
with moderate to severe HS:

Guselkumab 1200 mg IV at Weeks 0, 4, and 8, followed by 200 mg SC q4w through 
Week 36

Guselkumab 200 mg SC q4w from Week 0 through Week 36

Placebo IV and SC administration through Week 16. At Week 16, participants in the 
placebo group will cross over to:

Guselkumab 200 mg SC (q4w from Week 16 to Week 36), or

Guselkumab 100 mg SC (Weeks 16, 20, 28 and 36; placebo SC at Weeks 24 and 32).
These guselkumab dose regimens were selected based on existing safety information from 
relevant preclinical and clinical studies, the approved dose regimen for psoriasis, and the 
objective of determining the maximum efficacy of guselkumab possible for treatment of HS. 
Published information about adalimumab (an anti-TNFα monoclonal antibody) on relative 
dosing requirements among Crohn’s disease, psoriasis, and HS patients also contributed to the 
choice of these dose regimens, along with data from an open-label HS clinical trial using 
ustekinumab (an anti-IL-12/IL-23 monoclonal antibody).1,2,17,18,19
This is a POC study, therefore, the maximum feasible dose (1200 mg IV), based on safety 
margins from preclinical and clinical studies, is being evaluated to define the maximum efficacy 
of guselkumab possible in HS. Single IV doses of guselkumab as high as 10 mg/kg, with the 
highest IV single dose tested being 987 mg, have been previously studied in a Phase 1 plaque 
psoriasis study. Additionally, guselkumab IV doses of up to 50 mg/kg weekly for 5 weeks, and 
guselkumab SC doses of up to 50 mg/kg weekly for 24 weeks, were well tolerated in 
cynomolgus monkeys (Section 2.2). These data support an acceptable exposure margin between 


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the predicted guselkumab exposures at the proposed dose regimens compared to those observed 
in toxicology studies; the estimated safety margins are approximately 4-to-6-fold for the 
1200 mg IV dosing (See Appendix 8 [Section 10.8]). Of note, the 1200 mg IV dose is the same 
as
the high guselkumab dose to be studied in Crohn’s disease (NCT01369355, 
ClinicalTrials.gov). The 1200 mg IV dose regimen will help assess if incremental HS efficacy is 
possible with guselkumab exposure exceeding what can be practicably achieved with SC dosing.
A guselkumab 200 mg SC q4w dose, approximately 4-fold of the approved psoriasis dose (ie,
100 mg SC at Weeks 0 and 4, then 100 mg SC q8w thereafter), is also included in this POC 
study to determine the HS efficacy resulting from the maximally practicable SC dose of 
guselkumab.
Participants randomized to placebo will cross over to blinded guselkumab treatment at Week 16,
including the 200 mg SC q4w dose and a lower 100 mg SC dose at Weeks 16 and 20, followed 
by q8w through Week 36, which is the approved psoriasis dose. Based on the results from an 
open-label ustekinumab HS study, it is likely that the psoriasis dose regimen could provide some 
clinical benefits.1 Comparison of the relative efficacy of these two dose groups will provide 
useful data for determining if a dose higher than the optimal psoriasis dose provides incremental 
efficacy in HS.
Available preclinical observations and clinical data from other therapies suggest that a dose 
higher than the psoriasis dose may be needed in HS to achieve optimal efficacy. For example, 
IL-17+ CD4 T cells were shown to be enriched more than 40-fold in HS-involved skin compared
with normal skin,11 while the ratio was only approximately 2-fold for psoriasis.6 IL-17A gene 
expression and protein levels have been reported to be highly up-regulated in HS affected skin 
compared to unaffected skin.7 Additionally, studies have shown similar IL-23/Th17 pathway 
gene expression in HS- and Crohn’s disease-affected tissues, indicating potential commonality in 
the pathophysiology of these autoinflammatory conditions.16,22 Moreover, an adalimumab 
Phase 2 dose-ranging HS study found that an adalimumab dosage comparable with that used for 
Crohn’s disease and ulcerative colitis, and essentially twice the psoriasis dose, provided better 
efficacy compared with the approved psoriasis dose,8 and ultimately became the adalimumab 
dose approved for HS treatment. Finally, HS patients are generally heavier than patients with 
psoriasis (median body weight of approximately 94 kg and 89 kg, respectively)12,14 and 
guselkumab exposure has been shown to be lower in heavier participants.
4.4.
End of Study Definition
A participant will be considered to have completed the study if he or she has completed all 
scheduled study interventions through Week 36 and has completed all assessments at Week 48 of 
the safety follow-up period.
The end of study is considered as the last visit for the last participant in the study. The final data 
from the study-site will be sent to the sponsor (or designee) after completion of the final 
participant assessment at that study-site, in the time frame specified in the clinical trial 
agreement.


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5.
STUDY POPULATION
A target of 180 participants will be enrolled under the CNTO1959HDS2001 protocol.
Screening for eligible participants will be performed within 4 weeks before administration of the 
study intervention. Refer to Section 5.4, Screen Failures for conditions under which the repeat of 
any screening procedures is allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described below. 
If there is a question about these criteria, the investigator must consult with the appropriate 
sponsor representative and resolve any issues before enrolling a participant in the study. Waivers 
are not allowed.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2, 
Sample Size Determination.
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1.
Be a man or a woman at least 18 years of age (or the legal age of consent in the 
jurisdiction in which the study is taking place).
2.
Have moderate to severe HS for at least 1 year (365 days) prior to the baseline visit as 
determined by the investigator through patient interview and/or review of the medical 
history.
3.
Have HS lesions present in at least 2 distinct anatomic areas (examples include but are 
not limited to left and right axilla; or left axilla and left inguinocrural fold).
4.
Had an inadequate response to an adequate course of appropriate oral antibiotics for 
treatment of HS (or demonstrated intolerance to, or had a contraindication to, oral 
antibiotics for treatment of their HS) in the investigator’s opinion.
5.
Have stable HS for at least 1 month (28 days) prior to the screening visit as 
determined by the investigator through patient interview and/or review of the medical 
history.
6.
Have a total abscess and inflammatory nodule (AN) count of ≥3 at the screening and 
baseline visit.
7.
Must agree to daily use (throughout the entirety of the study) of one of the following 
over-the-counter treatments to the body areas affected with HS lesions: either soap and 
water, or a topical antiseptic wash containing chlorhexidine gluconate, triclosan, or 
benzoyl peroxide, or a dilute bleach bath.


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8.
Before randomization, a woman must be either:

Not of childbearing potential: premenarchal; postmenopausal (>45 years of age 
with amenorrhea for at least 12 months or any age with amenorrhea for at least 
6 months and a serum follicle-stimulating hormone (FSH) level >40 IU/L); 
permanently 
sterilized 
(eg, 
tubal 
occlusion, 
hysterectomy, 
bilateral 
salpingectomy); or otherwise be incapable of pregnancy.

Of childbearing potential and practicing a highly effective (failure rate of <1% 
per year when used consistently and correctly) method of birth control, prior to 
receiving study intervention, during the study and for at least 12 weeks after 
receiving the last administration of study intervention, consistent with local 
regulations regarding the use of birth control methods for participants 
participating in clinical studies: eg, established use of oral, injected or implanted 
hormonal methods of contraception; placement of an intrauterine device or 
intrauterine system; barrier methods: condom or occlusive cap (diaphragm or 
cervical/vault caps) plus spermicidal foam/gel/film/cream/suppository (if 
available in their locale); male partner sterilization (the vasectomized partner 
should be the sole partner for that participant); true abstinence (when this is in 
line with the preferred and usual lifestyle of the participant).
Note: If a female participant’s childbearing potential changes after start of the study 
(eg, a woman who is not heterosexually active becomes active, a premenarchal 
woman experiences menarche), she must begin practicing a highly effective method 
of birth control, as described above.
9.
A woman of childbearing potential must have a negative urine pregnancy test (β-
human chorionic gonadotropin [β-hCG]) at screening and at Week 0 prior to 
administration of study intervention.
10.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for at least 12 weeks after receiving the last 
administration of study intervention.
11.
A man who is sexually active with a woman of childbearing potential and who has not 
had a vasectomy must agree to use a barrier method of birth control (eg, either a 
condom [with spermicidal foam/gel/film/cream/suppository if available in their 
locale] or a partner with an occlusive cap [diaphragm or cervical/vault caps] plus 
spermicidal foam/gel/film/cream/suppository if available in their locale), during the 
study and for at least 12 weeks after receiving the last administration of study 
intervention. 
12.
All men must also agree to not donate sperm during the study and for at least 12 
weeks after receiving the last administration of study intervention.


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13.
Are considered eligible according to the following tuberculosis (TB) screening 
criteria:
a.
Have no history of latent or active TB before screening. An exception is made 
for participants who have a history of latent TB and
o
are currently receiving treatment for latent TB,
o
will initiate treatment for latent TB before the first administration of 
study intervention,
o
or have documentation of having completed appropriate treatment for 
latent TB within 5 years before the first administration of study 
intervention. It is the responsibility of the investigator to verify the 
adequacy of previous anti-TB treatment and provide appropriate 
documentation. 
b. Have no signs or symptoms suggestive of active TB upon medical history 
and/or physical examination.
c.
Have had no recent close contact with a person with active TB or, if there has 
been such contact, will be referred to a physician specializing in TB to 
undergo additional evaluation and, if warranted, receive appropriate treatment 
for latent TB before the first administration of study intervention.
d. Within 2 months before the first administration of study intervention, have a 
negative QuantiFERON®-TB test result, or have a newly identified positive 
QuantiFERON®-TB test result (see laboratory manual) in which active TB has 
been ruled out and for which appropriate treatment for latent TB has been 
initiated before the first administration of study intervention. Within 2 months 
before the first administration of study intervention, a negative tuberculin skin 
test, or a newly identified positive tuberculin skin test in which active TB has 
been ruled out and for which appropriate treatment for latent TB has been 
initiated before the first administration of study intervention, is additionally 
required if the QuantiFERON®-TB test is not approved/registered in that 
country or the tuberculin skin test is mandated by local health authorities.
NOTE: The QuantiFERON®-TB test and the tuberculin skin test are not 
required at screening for participants with a history of latent TB and ongoing 
treatment for latent TB or documentation of having completed adequate 
treatment as described above; participants with documentation of having 
completed adequate treatment as described above are not required to initiate 
additional treatment for latent TB.
e.
Have a chest radiograph (both posterior-anterior and lateral views, or per 
country regulations where applicable), taken within 3 months before the first 
administration of study intervention and read by a qualified radiologist, with 
no evidence of current, active TB or old, inactive TB.
14.
Agree not to receive a live virus or live bacterial vaccination during the study, or 
within 12 weeks after the last administration of study intervention. For information on 
Bacille Calmette-Guérin (BCG) vaccination, see Inclusion Criterion 15.


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15.
Agree not to receive a BCG vaccination during the study, or within 12 months after 
the last administration of study intervention.
16.
Have screening laboratory test results within the following parameters, if one or more 
of the laboratory parameters is out of range, a single retest of laboratory values is 
permitted:
a.
Hemoglobin
≥10 g/dL
(SI: ≥100 mmol/L)
b. White blood cells
≥3.5 x 103/µL
(SI: ≥3.5 GI/L)
c.
Neutrophils
≥1.5 x 103/µL
(SI: ≥1.5 GI/L)
d. Platelets
≥100 x 103/µL
(SI: ≥100 GI/L)
e.
Serum creatinine
≤1.5 mg/dL
(SI: ≤137 μmol/L)
f.
Aspartate aminotransferase ≤2 × upper limit of normal (ULN)
g. Alanine aminotransferase ≤2 × ULN
h. Alkaline phosphatase 
≤2 × ULN
17.
Be willing and able to adhere to the prohibitions and restrictions specified in this 
protocol.
18.
Must sign an informed consent form (ICF) indicating that he or she understands the 
purpose of and procedures required for the study and is willing to participate in the 
study.
5.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the study:
1.
Any other active skin disease or condition (eg, bacterial, fungal or viral infection) that 
could have interfered with assessment of HS.
2.
Has a draining fistula count of >20 at the baseline visit.
3.
Receipt of prescription topical therapies for the treatment of HS within 14 days prior
to the baseline visit.
4.
Receipt of systemic non-biologic therapies for the treatment of HS <4 weeks prior to 
the baseline visit.


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5.
Receipt of immunomodulatory biologic therapies (eg monoclonal antibodies) within 
3 months or 5 half-lives prior to the baseline visit, whichever is longer (refer to 
Section 6.5.5).
6.
Receipt of any oral antibiotic treatment for HS or inflammatory disorders within 4 
weeks prior to the baseline visit.
7.
Receipt of opioid analgesics (including tramadol) within 14 days prior to the baseline
visit, or if it is anticipated that the participant will require initiation of opioid 
analgesics (excluding tramadol) for any reason during the study period. 
8.
Receipt of oral concomitant analgesics (including opioids) for HS-related pain within 
14 days prior to the baseline visit.
9.
Receipt of “PRN” or “as needed” non-opioid analgesics for treatment of a chronic 
pain condition other than HS within 14 days prior to the baseline visit (participants
may be receiving non-opioid analgesics for treatment of chronic non-HS-related pain 
but must be on a stable dose for at least 14 days prior to the baseline visit and be 
expected to continue use throughout the study).
10.
Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled 
renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, 
hematologic, rheumatologic, psychiatric, or metabolic disturbances.
11.
Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg, 
unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac 
hospitalization within the last 3 months.
12.
Currently has a malignancy or has a history of malignancy within 5 years before 
screening (with the exception of a non-melanoma skin cancer that has been adequately 
treated with no evidence of recurrence for at least 3 months before the first study 
intervention administration or cervical carcinoma in situ that has been treated with no 
evidence of recurrence for at least 3 months before the first study intervention
administration).
13.
Has a history of lymphoproliferative disease, including lymphoma; a history of 
monoclonal gammopathy of undetermined significance; or signs and symptoms 
suggestive of possible lymphoproliferative disease, such as lymphadenopathy or 
splenomegaly.


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14.
Has a history of chronic or recurrent infectious disease, including but not limited to 
chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary 
tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), fungal 
infection (mucocutaneous candidiasis), or open, draining, or infected skin wounds or 
ulcers.
15.
Has a transplanted organ (with exception of a corneal transplant >3 months before the 
first administration of study intervention).
16.
Has a history of an infected joint prosthesis or has received antibiotics for a suspected 
infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
17.
Has or has had a serious infection (eg, sepsis, pneumonia, or pyelonephritis), or has 
been hospitalized or received IV antibiotics for an infection during the 2 months 
before screening.
18.
Has or has had herpes zoster within the 2 months before screening.
19.
Is pregnant, nursing, or planning a pregnancy (both men and women) while enrolled 
in the study or within 12 weeks following the last administration of study intervention.
20.
Has previously received guselkumab.
21.
Has received any therapeutic agent directly targeted to IL-17 or IL-23 within 6 months 
of the first administration of study intervention (including but not limited to 
ustekinumab, 
tildrakizumab, 
risankizumab, 
secukinumab, 
ixekizumab, 
or 
brodalumab).
22.
Has received natalizumab, belimumab, or agents that modulate B cells or T cells (eg, 
rituximab, alemtuzumab, abatacept, or visilizumab) within 12 months of the first 
administration of study intervention.
23.
Has received any systemic immunosuppressants (eg, methotrexate
[MTX], 
azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, 
tacrolimus) or anakinra within 4 weeks of the first administration of study 
intervention.
24.
Has received an experimental antibody or biologic therapy within the previous 
6 months or received any other experimental therapy or new investigational agent 
within 30 days or 5 half-lives (whichever is longer) of any study intervention
administration or is currently enrolled in another study using an investigational agent, 
device, or procedure.


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25.
Has received, or is expected to receive, any live virus or bacterial vaccination within 
12 weeks before the first administration of study intervention. For BCG vaccine, see 
Exclusion Criterion 26.
26.
Has had a BCG vaccination within 12 months of screening.
27.
Has suicidal ideation or suicidal behavior in the last 6 months that may be defined as a 
Columbia-Suicide Severity Rating Scale (C-SSRS) rating at screening of: Suicidal 
Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with Specific Plan 
and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, interrupted 
suicide attempt, aborted suicide attempt, or preparatory behaviors for making a suicide 
attempt), and is considered to be at risk by the investigator based on an evaluation by a 
mental health professional. In addition, participants with C-SSRS ratings of Wish to be 
Dead (“Ideation level 1”), Non-Specific Active Suicidal Thoughts (“Ideation level 2”), 
Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act (“Ideation 
level 3”) or non-suicidal self-injurious behavior who are determined to be at risk by the 
investigator may not be randomized.
28.
Has known intolerance or hypersensitivity to any biologic medication, or known 
allergies or clinically significant reactions to murine, chimeric, or human proteins, 
mAbs, or antibody fragments.
29.
Participant has known allergies, hypersensitivity, or intolerance to guselkumab or its 
excipients (refer to IB).
30.
Has a history of active granulomatous infection, including histoplasmosis or 
coccidioidomycosis before screening. Refer to Inclusion Criterion 13 for information 
regarding eligibility with a history of latent TB.
31.
Has a chest radiograph within 3 months before the first administration of study 
intervention that shows an abnormality suggestive of a malignancy or current active 
infection, including TB.
32.
Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg, 
cytomegalovirus, pneumocystosis, aspergillosis).
33.
Has two indeterminate (on repeat sampling) QuantiFERON®-TB test results.
34.
Is infected with human immunodeficiency virus (HIV), positive serology for HIV 
antibody).
35.
Tests positive for hepatitis B virus (HBV) infection (see Appendix 9, [Section 10.9])
or who are seropositive for antibodies to hepatitis C virus (HCV) at screening.


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36.
Has had major surgery (eg, requiring general anesthesia and hospitalization) within 
8 weeks before screening, or has not fully recovered from such surgery, or has such 
surgery planned during the time the participant is expected to participate in the study 
(48 weeks).
Note: Participants with planned surgical procedures to be conducted under local 
anesthesia may participate.
37.
Is known to have had a substance abuse (drug or alcohol) disorder within the previous 
12 months.
38.
Is unable or unwilling to undergo multiple venipunctures because of poor tolerability 
or lack of easy access to veins.
39.
Lives in an institution on court or authority order.
40.
Has any condition for which, in the opinion of the investigator, participation would 
not be in the best interest of the participant (eg, compromise the well-being) or that 
could prevent, limit, or confound the protocol-specified assessments.
41.
Is an employee of the investigator or study-site, with direct involvement in the 
proposed study or other studies under the direction of that investigator or study-site, as 
well as family members of the employees or the investigator.
NOTE: Investigators should ensure that all screening assessments have been completed and all 
study enrollment criteria have been met at screening. If a participant's clinical status changes 
(including any available laboratory results or receipt of additional medical records) after 
screening but before the first dose of study intervention is given such that he or she no longer
meets all eligibility criteria, then the participant should be excluded from participation in the 
study. Section 5.4, Screen Failures, describes options for retesting. The required source 
documentation to support meeting the enrollment criteria are noted in Appendix 5 (Section 10.5), 
Regulatory, Ethical, and Study Oversight Considerations.
5.3.
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions 
during the course of the study to be eligible for participation:
1.
A woman of childbearing potential who is heterosexually active must remain on a 
highly effective method of birth control (Inclusion Criterion 8) during the study and 
for at least 12 weeks after receiving the last administration of study intervention.
2.
A woman must agree not to donate eggs (ova, oocytes) during the study and for a 
period of at least 12 weeks following the last administration of study intervention.


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3.
A man who is sexually active with a female of childbearing potential and has not had 
a vasectomy must agree to use a barrier method of birth control (See Inclusion 
Criterion 11) during the study and for at least 12 weeks after receiving the last 
administration of study intervention.
4.
A man must agree to not donate sperm during the study and for at least 12 weeks after 
receiving the last administration of study intervention.
5.
Participants must not receive a live virus or bacterial vaccination during the study and 
for 3 months after the last administration of any study intervention. See Lifestyle 
Consideration 6 for information regarding BCG vaccination.
6.
Participants must not receive a BCG vaccination during the study and for 12 months 
after the last administration of any study intervention.
7.
Participants must comply with restrictions on concomitant medications and therapies 
specified in the protocol (refer to Section 6.5, Concomitant Therapy, for details).
8.
Participants must agree to follow all requirements that must be met during the study as 
noted in the Inclusion and Exclusion Criteria (eg, contraceptive requirements). 
5.4.
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy 
identification of each participant during and after the study. This document will be reviewed by 
the sponsor study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed 
by the investigator in the study file. To ensure participant confidentiality, no copy will be made. 
All reports and communications relating to the study will identify participants by participant 
identification number and age at initial informed consent. In cases where the participant is not 
randomized into the study, the date seen and age at initial informed consent will be used. 
Completion of screening and randomization procedures within the specified screening window 
of approximately 4 weeks is required.
Retesting
Retesting of abnormal laboratory values that may lead to exclusion will be allowed once. 
Retesting can occur at an unscheduled visit during the screening period, as long as this is done 
within the specified screening window of approximately 4 weeks.


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Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened 1 time. Rescreened participants will be assigned a new participant number, undergo 
the informed consent process, and then start a new screening period.
6.
STUDY INTERVENTION
6.1.
Study Interventions Administered
All participants will receive 1 IV infusion at Weeks 0, 4, and 8 (either active or placebo).
All participants will receive 2 SC injections at each visit (either active, active and placebo, or 
placebo) every 4 weeks from Weeks 0 to 36.
Intravenous study intervention should be administered over a period of not less than 1 hour, and 
not more than 2 hours. The infusion should be completed within 6 hours of preparation.
Since 2 SC injections will be administered at each administration visit, each SC injection should 
be given at a different location of the body.
Detailed instructions on the administration of IV and SC study intervention will be provided in 
the Site Investigational Product (IP) Binder.
Study intervention administration must be captured in the source documents and the electronic 
case report form (eCRF).
Guselkumab and placebo will be manufactured and provided under the responsibility of the 
sponsor. Refer to the IB for a list of excipients.
For details on rescue medications, refer to Section 6.5.1. For a definition of study intervention
overdose, refer to Section 8.4, Treatment of Overdose.
6.2.
Preparation/Handling/Storage/Accountability
Study intervention labels will contain information to meet the applicable regulatory 
requirements.
All study intervention must be stored at controlled temperatures ranging from 36°F to 46°F (2°C 
to 8°C), not frozen, and protected from light. Vigorous shaking of the product should be avoided. 
The sterile product does not contain preservatives and is designed for single use only. Prior to 
administration, the product should be inspected visually for particulate matter and discoloration. 
If discoloration (other than a slight yellow color), visible opaque particles, or other foreign 
particles are observed in the solution, the product should not be used. Study intervention in 
prefilled syringe assembled with the UltraSafe PLUS™Passive Needle Guard (PFS-U) format 
will be ready to use for SC administration and will need to be prepared for IV administration.
Aseptic procedures must be used during the preparation and administration of the study material. 


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Protection from ambient light is not required during dose preparation or administration; however, 
exposure to sunlight should be avoided.
Further details regarding the preparation and storage of IV and SC guselkumab and placebo will 
be provided in the Site IP Binder. The investigator is responsible for ensuring that all study 
intervention received at the site is inventoried and accounted for throughout the study. The study 
intervention administered to the participant must be documented on the drug accountability form. 
All study intervention will be stored and disposed of according to the sponsor's instructions.
Study intervention must be handled in strict accordance with the protocol and the container label
and must be stored at the study-site in a limited-access area or in a locked cabinet under 
appropriate environmental conditions. Unused study intervention must be available for 
verification by the sponsor's study-site monitor during on-site monitoring visits. The return to the 
sponsor of unused study intervention will be documented on the drug return form. When the 
study-site is an authorized destruction unit and study intervention supplies are destroyed on-site, 
this must also be documented on the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes. The study intervention boxes will be retained for 
inventory by the sponsor.
Study intervention should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a hospital/clinic pharmacist. Study intervention will be 
supplied only to participants participating in the study. Study intervention may not be relabeled 
or reassigned for use by other participants. The investigator agrees to neither dispense the study 
intervention from, nor store it at, any site other than the study sites agreed upon with the sponsor.
6.3.
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 3 intervention groups based on a computer-generated randomization schedule prepared 
under the supervision of the sponsor. Permuted block randomization with stratification by 
baseline weight (≤ 95 kg, > 95 kg) and baseline Hurley stage (I, II, and III) will be used. The 
number of participants in Hurley stage I should be limited to approximately 30% of the total 
planned number of participants. Additionally, the number of participants in Hurley stage III 
should be limited to approximately 50% of the total planned number of participants. The 
interactive web response system (IWRS) will assign a unique intervention code, which will 
dictate the intervention assignment and matching study intervention kits for the participant. The 
requestor must use his or her own user identification and personal identification number when 


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contacting the IWRS and will then give the relevant participant details to uniquely identify the 
participant.
At Week 16, participants randomized to placebo at Week 0 will be rerandomized using the 
IWRS either to guselkumab 200 mg SC q4w or guselkumab 100 mg SC at Weeks 16, 20, and
q8w thereafter (participants will receive placebo SC at Weeks 24 and 32) in a 1:1 ratio using 
permuted block randomization and the randomization and will be stratified by baseline weight 
(≤95 kg, >95 kg) and baseline Hurley stage (I, II, and III).
Blinding
To maintain the study blind, the study intervention container will have a label containing the 
study name, study intervention number, and reference number. The blinded label will not 
identify the specific study intervention in the container (ie, guselkumab or placebo). However, if 
it is necessary for a participant's safety, the study blind may be broken, and the identity of the 
study intervention ascertained. The study intervention number will be entered in the eCRF when 
the study intervention is administered. The guselkumab and placebo will be identical in 
appearance and will be packaged in identical containers.
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
Data that may potentially unblind the intervention assignment (ie, study intervention serum 
concentrations, anti-guselkumab antibodies, and intervention allocation) will be handled with 
special care to ensure that the integrity of the blind is maintained and the potential for bias is 
minimized. This can include making special provisions, such as segregating the data in question 
from view by the investigators, clinical team, or others as appropriate until the time of DBL and 
unblinding.
Under normal circumstances, the blind should not be broken until all participants have completed 
the study and the database is finalized. However, selected sponsor personnel will be unblinded 
for analysis after the Week 16 DBL has occurred. All site personnel and participants will remain 
blinded to the treatment assignments until the last participant completes Week 48 evaluations 
and the database has been locked. The investigator may, in an emergency, determine the identity 
of the intervention by contacting the IWRS. While the responsibility to break the intervention
code in emergency situations resides solely with the investigator, it is recommended that the 
investigator contact the sponsor or its designee if possible to discuss the particular situation, 
before breaking the blind. Telephone contact with the sponsor or its designee will be available 
24 hours per day, 7 days per week. In the event the blind is broken, the sponsor must be informed 
as soon as possible. The date and reason for the unblinding must be documented in the 
appropriate section of the eCRF, and in the source document. The documentation received from 
the IWRS indicating the code break must be retained with the participant's source documents in a 
secure manner.


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Participants who have had their intervention assignment unblinded by the investigator will not be 
eligible to receive further study intervention but should continue complete evaluations specified 
in the Schedule of Activities (Section 1.3).
For the planned interim analyses and the DMC, the randomization codes and the translation of 
randomization codes into intervention and control groups will be disclosed to those authorized 
and only for those participants included in the interim analysis.
6.4.
Study Intervention Compliance
Because study intervention will be administered at the investigational site for all randomized 
participants, intervention compliance will be ensured by site personnel.
When study intervention is administered as an IV infusion or SC injection by qualified staff, the 
details of each administration will be recorded in the eCRF. For IV infusions, these will include 
date and start and stop times of the IV infusion and volume infused; for SC injections, these will 
include date, body location and time of SC injection.
All visits through Week 36 should occur within ±7 days of the scheduled visit. If a study visit 
occurs outside this window, the sponsor should be consulted about how the participant should 
resume his/her normal dosing schedule relative to the baseline visit (Week 0).
Information regarding study intervention administrations that are administered outside of the 
scheduled windows or missed will be recorded. Source data will be reviewed and compared with 
the data entries on the eCRFs to ensure accuracy. Although it is understood that intervention may 
be interrupted for many reasons, compliance with the intervention schedule is strongly 
encouraged.
6.5.
Concomitant Therapy
Concomitant therapies must be recorded throughout the study from Week 0 through Week 48 or 
continuing until 12 weeks after the last dose of study intervention. Concomitant therapies on 
randomized participants should also be recorded beyond that point only in conjunction with 
serious adverse events (SAE) that meet the criteria outlined in Serious Adverse Events in 
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation) different from the 
study intervention must be recorded in the eCRF. Modification of an effective pre-existing
therapy should not be made for the explicit purpose of entering a participant into the study.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.


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6.5.1.
Rescue Therapy
In the event that a particularly painful HS lesion occurs that necessitates an acute intervention, 
investigators will have the option to perform protocol-allowed interventions.
Two types of interventions are allowed:

Injection with intralesional triamcinolone acetonide suspension (at a concentration of up to 
5 mg/mL, up to 1 cc)

Incision and drainage of the lesion
If incision and drainage is performed, the required over-the-counter soap and water or antiseptic
wash should continue to be used. New systemic and topical therapies following incision and 
drainage (including antibiotics) are prohibited. Concomitant use of wound care dressings is 
allowed; however, options are limited to alginates, hydrocolloids, and hydrogels. Participants 
should continue using any ongoing oral and topical therapies (as described in Section 6.5, 
Concomitant Therapy) during the study.
Concomitant therapies associated with the lesion intervention(s) must be captured in the source 
documentation and on the appropriate eCRF.
A total of 2 protocol-allowed interventions are permissible through Week 16. An intervention 
can occur maximally 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. If a participant requires 
more than 2 interventions within the first 16 weeks, then he or she must be discontinued from 
study interventions but continued for follow-up for approximately 12 weeks after last 
administration of study intervention.
After Week 16, interventions will not be permitted since all participants will receive active 
guselkumab treatment. If a participant requires an intervention after Week 16, he or she must be 
discontinued from study interventions, but continued for follow-up for approximately 12 weeks 
after last administration of study intervention.
All study visit evaluations must occur before any interventions are performed. Any lesion that 
undergoes an intervention will be documented in the source.
6.5.2.
Antiseptic Therapy
Participants are required to use a daily antiseptic wash on their HS lesions. Allowable antiseptic 
washes are limited to one of the following: soap and water, a topical antiseptic wash containing 
chlorhexidine gluconate, triclosan, or benzoyl peroxide, or a dilute bleach bath.
6.5.3.
Wound Care
Concomitant use of wound care dressings on HS wounds is allowed; however, options are
limited to alginates, hydrocolloids, and hydrogels.


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6.5.4.
Analgesic Therapy
Use of opioid analgesics is prohibited for 14 days prior to the baseline visit regardless of HS or 
non-HS reasons. During the study, concomitant use of opioid analgesics is also prohibited, with 
the exception of tramadol as detailed below.
Oral analgesics for HS-related pain are prohibited 14 days prior to the baseline visit. If a 
participant is on a stable dose of a non-opioid analgesic (PRN is not considered stable) for a non-
HS medical condition (eg, osteoarthritis), the participant may continue the analgesic, provided 
the dose is stable for 14 days prior to baseline and is anticipated to remain stable throughout 
study participation.
If a participant’s pain (HS-related or non-HS-related) worsens after baseline, they may initiate 
analgesic therapy at any time as follows:
For HS-related pain, permitted analgesics are limited to:

Ibuprofen (at a dose of up to 800 mg by mouth every 6 hours) not to exceed
3.2 grams/24 hours; AND/OR

Acetaminophen as per local labeling; AND/OR

If HS-related pain is uncontrolled with ibuprofen and/or acetaminophen at the above dosing 
regimens after the baseline visit, participants can be prescribed tramadol (at a dose of up to 
100 mg by mouth every 4 hours), not to exceed 400 mg/24 hours.
Dose adjustments of ibuprofen, acetaminophen, or tramadol, and use of these analgesics on an 
"as needed" (PRN) basis for HS-related pain up to the maximum permitted dose and frequency, 
are allowed during the study.
From Screening through Week 40, participants will not be permitted to use any analgesics 
related to HS pain within 24 hours of a scheduled study visit. All analgesics and dose 
adjustments will be captured in the source and on the appropriate eCRF.
For non-HS-related pain:

All other non-opioid analgesics and tramadol are allowed at the recommended or prescribed 
dose.
6.5.5.
Prohibited Therapy
Participants who initiate the following treatments during study participation must have their study 
intervention discontinued:

Phototherapy (PUVA and/or UVB)

All biologic therapy with a potential therapeutic impact on the disease being studied, 
including but not limited to the following:

Adalimumab (Humira®)

Anakinra (Kineret®)


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
Abatacept (Orencia®)

Natalizumab (Tysabri®)

Ustekinumab (STELARA)

Etanercept (Enbrel®)

Infliximab (REMICADE®)

Rituximab (Rituxan®)

Tocilizumab (Actemra®)

Efalizumab (Raptiva®)

Golimumab (SIMPONI®)

Certolizumab (Cimzia®)

Belimumab (Benlysta®)

Secukinumab (Cosentyx®)

Ixekizumab (Taltz®)

Brodalumab (Siliq®)

Tildrakizumab (Ilumya®)

Any investigational agents for the treatment of HS.

Any other systemic drug therapies for HS, including but not limited to MTX, cyclosporine, 
and retinoids.

Concomitant use of oral antibiotic therapy for HS or inflammatory disorders. Systemic 
antibiotic use (including oral) is allowed for the treatment of acute infections such as 
bacterial, viral, or fungal.

Oral or injectable corticosteroids for the treatment of HS, except for protocol allowed 
intralesional rescue therapy as outlined in Section 6.5.1.

Surgical or laser intervention for an HS lesion except as outlined in Section 6.5.1, Rescue 
Therapy.
6.5.6.
Concomitant Corticosteroid use for Conditions Other than HS
The use of systemic corticosteroids for indications other than HS should be limited to situations 
for which, in the opinion of the treating physician, there are no adequate alternatives. They 
should be used on a short-term basis, preferably for ≤2 weeks. Longer-term use of corticosteroids 
should be discussed with the medical monitor or designee and may require discontinuation of 
study drug. Inhaled, otic, ocular, nasal or other routes of mucosal delivery of corticosteroids are 
allowed throughout the study. 
6.6.
Dose Modification
No treatment/dose adjustment will be permitted through the study


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6.7.
Intervention After the End of the Study
No LTE is provided in this Phase 2 POC study. Participants and investigators will be informed
that study intervention will not be made available to them beyond this protocol and that they 
should return to their treating physician for guidance.
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
A participant will be considered to have completed the study if he or she has completed 
assessments through Week 48 as specified in the Schedule of Activities (Section 1.3).
7.1.
Discontinuation of Study Intervention
A participant's study intervention must be discontinued if any of the following occur:

The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the 
best interest of the participant to discontinue study intervention.

The participant has a serious adverse reaction that is temporally related to an injection or an 
infusion including an injection-site or infusion reaction, resulting in bronchospasm with 
wheezing and/or dyspnea that requires ventilatory support OR that results in symptomatic 
hypotension with a decrease in systolic blood pressure >40 mm Hg or blood pressure 
<90/60 mm Hg. This may include events of National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE) toxicity grade ≥3. In general, discontinuation of 
study intervention administration must be considered for participants who develop a severe 
injection-site or infusion reaction.

The participant or their legally acceptable representative withdraws consent/assent for 
administration of study intervention.

The participant becomes pregnant or plans a pregnancy during the study period. Refer to 
Appendix 7 (Section 10.7), Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information. 

The initiation of protocol-prohibited medications, treatments, or interventions (outlined in 
Section 6.5, Concomitant Therapy) that have an impact on HS efficacy evaluations.

The participant has a malignancy including squamous cell skin cancer. Consideration may 
be given to allow participants, who develop ≤2 basal cell skin cancers and who are 
adequately treated with no evidence of residual disease, to continue to receive study 
intervention.

A systemic opportunistic infection.

A recurrent or chronic serious infection.

The participant is deemed ineligible according to the following TB screening criteria:

A diagnosis of active TB is made.

A participant has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination or has had recent close contact with a person 
with active TB and cannot or will not undergo additional evaluation.


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
A participant undergoing evaluation has a chest radiograph with evidence of current 
active TB and/or a positive QuantiFERON®-TB test result and/or 2 indeterminate 
QuantiFERON®-TB test results on repeat testing (refer to Section 8.2.11, Tuberculosis 
Evaluations) (and/or a positive tuberculin skin test result in countries in which the 
QuantiFERON®-TB test is not approved/registered or the tuberculin skin test is 
mandated by local health authorities).

A participant receiving treatment for latent TB discontinues this treatment prematurely 
or is noncompliant with the therapy.

The participant is unable to adhere to the study visit schedule or comply with protocol 
requirements.

The participant has a reaction resulting in myalgia and/or arthralgia with fever and/or rash 
(suggestive of serum sickness and not representative of signs and symptoms of other 
recognized clinical syndromes) occurring 1 to 14 days after an injection of study 
intervention. These may be accompanied by other events including pruritus, facial, hand, or 
lip edema, dysphagia, urticaria, sore throat, and/or headache.

The participant has his/her treatment assignment unblinded by the investigator.

Sponsor decision.
Discontinuation of a participant’s study intervention should be considered for:

Participants with any type of suicidal ideation or behavior, or any self-injurious behavior, 
who are deemed to be at risk by the investigator. Discussion of such participants with the 
medical monitor or designee is required. For participants who report Suicidal Ideation with 
Intention to Act (“Ideation level 4”), suicidal ideation with specific plan and intent 
(“Ideation level 5”), suicidal behavior (actual suicide attempt, interrupted suicide attempt, 
aborted suicide attempt, or preparatory behaviors for making a suicide attempt) or any self-
injurious behavior on a post-baseline C-SSRS assessment, the investigator risk assessment 
must be based upon evaluation by a mental health professional (see Section 8.2.5).
Participants who decide to discontinue study intervention administration for reasons other than 
those outlined above must be interviewed by the investigator to determine if a specific reason for 
discontinuing study intervention can be identified. Participants should be explicitly asked about 
the possible contribution of AEs to their decision to discontinue study intervention; investigators 
should confirm that any AE information elicited has been documented. If a participant elects to 
discontinue study intervention due to an AE, the event should be recorded as the reason for study 
intervention discontinuation, even if the investigator’s assessment is that the AE would not 
require study intervention discontinuation. The reason for study intervention discontinuation 
must be documented in the eCRF and in source documents. Study intervention assigned to a 
participant who discontinues may not be assigned to another participant.
A participant will not be automatically withdrawn from the study if he or she must discontinue 
treatment before the end of the treatment regimen. Participants who discontinue study 
intervention but do not terminate study participation will continue to return for protocol-specified 
procedures and evaluations for approximately 12 weeks following the last dose of study 
intervention. The procedures and evaluations listed for the Early Termination Visit should also 
be performed approximately 12 weeks after the last dose of study intervention.


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All procedures and evaluations must be conducted prior to a participant’s withdrawal of 
consent.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant will be withdrawn from the study for any of the following reasons:

Lost to follow-up (Refer to Section 7.3)

Withdrawal of consent

Death
To ensure access for participant follow-up, study sites should try to obtain both primary and 
secondary telephone contact numbers from participants (eg, home, work, and mobile phones), as 
well as other contact information such as email addresses, and emphasize the importance of 
follow-up information to the participant, before randomization. For participants who withdraw 
from study participation, every effort should be made to conduct the Early Termination Visit 
assessments, as indicated in the Schedule of Activities (Section 1.3). If the reason for withdrawal 
from the study is withdrawal of consent, then no additional assessments are allowed. 
Withdrawal of consent should be a very unusual occurrence in a clinical trial; the investigator 
should make every effort to maintain good participant relationships to avoid withdrawals of 
consent. For participants who truly request withdrawal of consent, it is recommended that the 
participant withdraw consent in writing; if the participant or the participant’s representative 
refuses to do so or is physically unavailable, the study-site should document the reason for the 
participant’s failure to withdraw consent in writing, sign the documentation, and maintain it with 
the participant’s source records. When a participant withdraws before completing the study, the 
reason for withdrawal is to be documented in the eCRF and in the source document. Study 
intervention assigned to the withdrawn participant may not be assigned to another participant. 
Participants who withdraw will not be replaced.
7.2.1.
Withdrawal from the Use of Research Samples
The participant may withdraw consent for use of samples for research (refer to Long-Term 
Retention of Samples for Additional Future Research in Appendix 5 [Section 10.5], Regulatory, 
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after 
they are no longer needed for the clinical study. Details of the sample retention for research are 
presented in the main ICF. 
7.3.
Lost to Follow-up
If a participant fails to return for study visits (and thus is considered lost to follow-up), study-site 
personnel must make all reasonable efforts to contact the participant to determine the 
participant’s reason for discontinuation/withdrawal before considering the participant to be lost 
to follow-up. Such efforts should include repeated telephone calls, certified letters, email 
requests, etc. Measures taken to obtain follow-up information must be documented. Refer to 
Section 7.2, Participant Discontinuation/Withdrawal from the Study.


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8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Section 1.3) summarizes the frequency and timing of efficacy, PK, 
immunogenicity, biomarker, and safety measurements applicable to this study.
All PRO assessments should be conducted/completed before any tests, procedures, or other 
consultations, with the exception of a urine pregnancy test, to prevent influencing participant
perceptions.
Blood collections for PK and biomarker assessments should be kept as close to the specified time 
as possible. Actual dates of all assessments will be recorded in the source documentation; in 
addition, times of all blood collections will be recorded in the source documentation (laboratory 
requisition form).
Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the participation in the study. Results of all pregnancy testing should be documented in 
the participants’ source documents.
Blood Sample Collection
The total blood volume to be collected from each participant through Week 48 of the study will 
be approximately 181.5 mL. In addition, repeat or unscheduled samples may be collected for 
safety reasons or for technical issues with the samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded on the laboratory requisition 
form. Refer to the Schedule of Activities (Section 1.3) for the timing and frequency of all sample 
collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual.
Study-Specific Materials
The investigator will be provided with the following supplies:

Protocol

Investigator's Brochure for guselkumab

Site Investigational Product Binder

Laboratory manual

IWRS Manual

Sample ICF


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
PFS-U Instructions for Use

Participant Study Participation Card

Investigative Site File

IV Ancillary Supplies

Laboratory Kits

Recruitment materials, as needed
8.1.
Efficacy Assessments
Efficacy evaluations are consistent with those used to evaluate other therapies for HS and will 
include the following:
8.1.1.
Hidradenitis Suppurativa Investigator’s Global Assessment
The HS-IGA (Appendix 10 [Section 10.10]) documents the investigator’s assessment of the 
participant’s HS at a given timepoint. The anatomic region with the most severe HS activity at 
the baseline visit should be evaluated for erythema, drainage, and pain and/or tenderness to 
palpation for each participant. For each participant, the same anatomic site selected for 
evaluation at the baseline visit should be re-evaluated at each subsequent visit. The participant’s 
HS is assessed as inactive (0), almost inactive (1), mild activity (2), moderate activity (3), or 
severe activity (4). A higher score indicates more severe disease.
8.1.2.
Lesion Counts
Lesion counts are defined as the counting of abscesses, inflammatory nodules, non-inflammatory 
nodules, draining fistulas, and non-draining fistulas. Lesions will be counted during each visit.
8.1.3.
Hurley Staging
Hurley staging consists of 3 stages of disease that will be used to determine stratification:

Stage I: Abscess formation, single or multiple, without sinus tracts and scarring

Stage II: One or more widely separated recurrent abscesses with tract formation and scarring

Stage III: Multiple interconnected tracts and abscesses across the entire area, with diffuse or 
near diffuse involvement
8.1.4.
Hidradenitis Suppurativa Symptom Diary
The HSSD (Appendix 11 [Section 10.11]) is a 7-item patient self-reported questionnaire that 
assesses 5 HS-related symptoms including pain, tenderness, hot skin feeling, odor, and itchiness. 
The participants are asked to rate the severity of each symptom on a 0 to 10 numerical rating 
scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom 
experience. All 5 symptoms have a recall period of the past 7 days, except for 2 additional 
questions on pain which evaluate current pain and pain in the past 24 hours. Each individual 
symptom scale score, ranging from 0-10, will be summarized. A total symptom score, which will 


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also range from 0-10, will be derived by averaging the 5 individual scale scores that utilize the 
past 7-day recall period.
8.1.5.
Dermatological Life Quality Index
The DLQI (Appendix 12 [Section 10.12]) is a dermatology-specific quality of life instrument 
designed to assess the impact of the disease on a participant’s quality of life. It is a 10-item PRO 
questionnaire that, in addition to evaluating overall quality of life, can be used to assess 6 
different aspects that may affect quality of life: symptoms and feelings, daily activities, leisure, 
work or school performance, personal relationships, and treatment. The DLQI produces a 
numeric score that can range from 0 to 30. A higher score indicates more severe disease.
8.1.6.
Hospital Anxiety and Depression Scale
The HADS (Appendix 13 [Section 10.13]) consists of 2 subscales, one measuring anxiety (A-
scale) and one measuring depression (D scale), which are scored separately. A higher score 
indicates more severe disease.
8.1.7.
Patient Global Impression of Change of Hidradenitis Suppurativa 
Severity
The Patient Global Impression of Change (PGIC) of HS Severity (Appendix 14 [Section 10.14]) 
is a questionnaire that measures participants’ perceived change (improvement or deterioration) in 
severity of their HS. Participants will rate how his/her HS has changed since the beginning of the 
study using a 7-point scale ranging from “a lot better now” to “a lot worse now” with a neutral 
center point (“neither better nor worse”). PGIC will be used as an anchor to test reliability and
establish a clinical response criterion of other patient or physician reported outcomes for future 
reference.
8.1.8.
Photographs of Skin Lesions
Photographs of selected HS lesions will be taken at a subset of study sites in participants who 
provide additional consent. Consult the Trial Center File for photography instructions. 
8.2.
Safety Assessments
Details regarding the DMC are provided in Committees Structure in Section 9.6, Data 
Monitoring Committee.
Adverse events will be reported and followed by the investigator as specified in Section 8.3, 
Adverse Events and Serious Adverse Events and Appendix 6 (Section 10.6), Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse 
Event section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will 
be followed by the investigator until resolution or until a clinically stable condition is reached.


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The study will include the following evaluations of safety and tolerability according to the time 
points provided in the Schedule of Activities (Section 1.3):
8.2.1.
Physical Examination
Physical Examination
Physical examinations will be performed by the investigator or designated physician, nurse 
practitioner or physician assistant as specified in the Schedule of Activities (Section 1.3). Any 
new, clinically significant finding (in the opinion of the investigator) must be captured as an AE. 
In addition, resolution of any abnormal findings during the study will be noted in the source 
document and in the eCRF.
Height and Weight
Height and weight will be measured as specified in the Schedule of Activities (Section 1.3).
Participants will be instructed to remove shoes and outdoor apparel and gear prior to these 
measurements.
Waist Circumference
Waist Circumference will be measured as specified in the Schedule of Activities (Section 1.3).
8.2.2.
Vital Signs
Vital signs (including temperature, pulse/heart rate, respiratory rate, and blood pressure) will be 
obtained before and approximately every 30 minutes during every IV infusion, and at 
approximately 30 minutes after completion of the final IV infusion. 
8.2.3.
Electrocardiogram
A single 12-lead electrocardiogram (ECG) will be performed during screening to serve as a 
baseline reference for comparison, should a subsequent cardiovascular related safety event occur.
8.2.4.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in Section 8 and 
Appendix 3 (Section 10.3). The investigator must review the laboratory results, document this 
review, and record any clinically relevant changes occurring during the study in the AE section 
of the eCRF. The laboratory reports must be filed with the source documents.
The tests that will be performed by the central laboratory unless otherwise specified or approved 
by the medical monitor are specified in Appendix 3 (Section 10.3), Clinical Laboratory Tests.
Female participants of childbearing potential will undergo a urine pregnancy test at screening, 
before each study intervention administration, and at the Week 48 or early termination visit.


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A medical monitor or delegate and the clinical site will be notified if prespecified abnormal 
laboratory values defined in the laboratory manual are identified in any participant during the 
conduct of the study.
8.2.5.
Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS defines 5 subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as 
non-suicidal self-injurious behavior and completed suicide. It will be used as a screening tool to 
prospectively evaluate suicidal ideation and behavior in this study, as part of a comprehensive 
evaluation of safety. The C-SSRS is an investigator-administered questionnaire.13,15Two versions 
of it will be used in this study: the ‘Baseline/Screening’ version of the C-SSRS (see 
Appendix 15, [Section 10.15])will be conducted during the screening visit and the ‘Since Last 
Visit’ version of the C-SSRS (see Appendix 16, [Section 10.16]) will be completed at all other 
visits through the end of the study.
The investigator or trained study-site personnel will interview the participant and complete the 
C-SSRS. The C-SSRS will be provided in the local languages in accordance with local 
guidelines.
At screening and after obtaining informed consent, the C-SSRS will be the first assessment 
performed, before any other study procedure. At all subsequent visits, the C-SSRS will be 
performed according to the Schedule of Activities (Section 1.3) and should be performed before 
any tests, procedures, or other consultations, with the exception of the urine pregnancy test, to 
prevent influencing participant perceptions. Participants will be interviewed by the investigator 
or trained study-site personnel in a private, quiet place.
At the conclusion of each assessment, the trained personnel administering the C-SSRS will 
determine the level of suicidal ideation or behavior, if any. They will then determine the next 
course of action if any level of suicidal ideation or behavior is reported. The participant should 
not be released from the site until the C-SSRS has been reviewed by the investigator and the 
participant’s risk has been assessed and follow-up determined, as appropriate.
At screening (within the last 6 months) and Week 0, participants with a C-SSRS rating of 
Suicidal Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with Specific Plan 
and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, interrupted suicide 
attempt, aborted suicide attempt, or preparatory behaviors for making a suicide attempt), must be 
determined to not be at risk by the investigator based on an evaluation by a mental health 
professional (eg, psychiatrist, psychologist, or appropriately trained social worker or nurse) in 
order to be randomized.
Participants with C-SSRS ratings of Wish to be Dead (“Ideation level 1”), Non-Specific Active 
Suicidal Thoughts (“Ideation level 2”), Active Suicidal Ideation with Any Methods (Not Plan) 
without Intent to Act (“Ideation level 3”) or non-suicidal self-injurious behavior must be 
determined not to be at risk by the investigator in order to be randomized. Any questions 


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regarding eligibility of such participants should be discussed with the medical monitor or 
designee.
For each assessment after Week 0, the following actions should be taken, if applicable:

No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent): 
No further action is needed.

Suicidal ideation levels 1-3 or non-suicidal self-injurious behavior: Participant risk is 
assessed by the investigator.

Suicidal ideation levels 4 or 5 or any suicidal behavior: Participant risk assessed and referral 
to a mental health professional.
Interruption or the discontinuation of study intervention should be considered for any participant 
who reports Suicidal Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with 
Specific Plan and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, 
interrupted suicide attempt, aborted suicide attempt, or preparatory behaviors for making a 
suicide attempt) on a post-baseline C-SSRS assessment and who is deemed to be at risk by the 
investigator based upon evaluation by a mental health professional. If a participant can be 
adequately treated with psychotherapy and/or pharmacotherapy then the participant, at the 
discretion of the investigator, may be continued with treatment if agreed to by the medical 
monitor or designee. Discussion of such participants with the medical monitor or designee is 
required (see Section 7.1, Discontinuation of Study Intervention).
Any C-SSRS finding, which in the opinion of the investigator is new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF (see Appendix 6
[Section 10.6], Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting).
8.2.6.
Immunogenicity Assessments
Anti-guselkumab antibodies will be evaluated in serum samples collected from all participants 
according to the Schedule of Activities (Section 1.3). Additionally, serum samples should also be 
collected at the final visit or at the Early Termination Visit from participants who are 
discontinued from intervention or withdrawn from the study. These samples will be tested by the 
sponsor or sponsor's designee.
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed 
positive samples will be reported as applicable. Other analyses may be performed to further 
characterize the immunogenicity of guselkumab.
Samples collected for immunogenicity analyses may additionally be used to evaluate safety or 
efficacy aspects that address concerns arising during or after the study period. Genetic analyses 
will not be performed on these serum samples. Participant confidentiality will be maintained.


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Evaluations
At visits where antibodies to study intervention will be evaluated in addition to serum 
concentration of study intervention, 1 venous blood sample of sufficient volume should be 
collected. Each serum sample will be divided into 3 aliquots (1 each for serum concentration of 
study intervention, antibodies to study intervention, and a back-up).
Immunogenicity Analytical Procedures
The detection and characterization of anti-guselkumab antibodies will be performed using a 
validated assay method by or under the supervision of the sponsor. All samples collected for 
detection of anti-guselkumab antibodies will also be evaluated for guselkumab serum 
concentration to enable interpretation of the antibody data.
8.2.7.
Concomitant Medication
Concomitant medications will be reviewed at each visit and recorded in the source documents 
and eCRF.
8.2.8.
Allergic Reactions
Before any SC injection or IV infusion, appropriately trained personnel and medications must be 
available to treat allergic reactions, including anaphylaxis. All participants must be observed 
carefully for symptoms of an allergic reaction (eg, urticaria, itching, hives). If a mild or moderate 
allergic reaction is observed, acetaminophen, non-steroidal anti-inflammatory drugs, and/or 
diphenhydramine may be administered.
In the case of a severe allergic reaction (eg, anaphylaxis), SC aqueous epinephrine, 
corticosteroids, respiratory assistance, and other proper resuscitative measures may be essential 
and must be available at the location where the injections or infusions are being administered.
Participants who experience serious adverse reactions related to an injection or infusion should 
be discontinued from further study intervention administrations.
Participants who experience reactions following an injection or infusion that result in 
bronchospasm with wheezing and/or dyspnea that requires ventilatory support, or symptomatic 
hypotension with a decrease in systolic blood pressure >40 mm Hg or blood pressure <90/60 mm 
Hg will not be permitted to receive additional study intervention.
Participants who experience reactions suggestive of serum sickness-like reactions (resulting in 
symptoms such as myalgia and/or arthralgia with fever and/or rash that are not representative of 
signs and symptoms of other recognized clinical syndromes) occurring 1 to 14 days after an 
injection of study intervention, should be discontinued from further study intervention 
administrations. Note that these symptoms may be accompanied by other events including 
pruritus, facial, hand, or lip edema, dysphagia, urticaria, sore throat, and/or headache.


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8.2.9.
Adverse Events Temporarily Related to Infusion
Any AE that occurs during or within 1 hour after the IV infusion of study intervention will be 
carefully evaluated. Minor infusion-related AEs may be managed by slowing the rate of the IV 
infusion and/or treating with antihistamines and/or acetaminophen (paracetamol) as clinically 
indicated. If an IV infusion of study intervention is stopped because of an AE that, in the opinion of 
the investigator, is not severe or does not result in a SAE, the infusion may be restarted with caution.
8.2.10.
Injection-site Reactions
A study intervention injection-site reaction is any adverse reaction at an SC study intervention 
injection-site. The injection sites will be evaluated for reactions and any injection-site reactions 
will be recorded as an AE.
8.2.11.
Tuberculosis Evaluation(s)
8.2.11.1.
Initial Tuberculosis Evaluation
Participants must undergo testing for TB (refer to laboratory manual for QuantiFERON®-TB
test or Appendix 4 [Section 10.4] for tuberculin skin test) and their medical history assessment 
must include specific questions about a history of TB or known occupational or other personal 
exposure to individuals with active TB. The participant should be asked about past testing for 
TB, including chest radiograph results and responses to tuberculin skin or other TB testing. 
Investigators have the option to use both the QuantiFERON®-TB test and the tuberculin skin test 
to screen for latent TB if they believe, based on their judgment, that the use of both tests is 
clinically indicated in order to evaluate a participant who has high risk of having latent TB. If 
either the QuantiFERON®-TB test or the tuberculin skin test is positive, the participant is 
considered to have latent TB infection for the purposes of eligibility for this study.
Participants with a negative QuantiFERON®-TB test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON®-TB test is not approved/registered or the 
tuberculin skin test is mandated by local health authorities) are eligible to continue with pre-
randomization procedures. Participants with a newly identified positive QuantiFERON®-TB (or 
tuberculin skin) test result must undergo an evaluation to rule out active TB and initiate 
appropriate treatment for latent TB. Appropriate treatment for latent TB is defined according to 
local country guidelines for immunocompromised patients. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed, or the participant will be 
excluded from the study.
8.2.11.2.
Ongoing Tuberculosis Evaluation
Early Detection of Active Tuberculosis
To aid in the early detection of TB reactivation or new TB infection during study participation, 
participants must be evaluated for signs and symptoms of active TB at scheduled visits (refer to 
the Schedule of Activities in Section 1.3). The following series of questions is suggested for use 
during the evaluation:


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
“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”

“Have you had any of the following symptoms:

Persistent fever?

Unintentional weight loss?

Night sweats?”

“Have you had close contact with an individual with active TB?” (If there is uncertainty as 
to whether a contact should be considered “close,” a physician specializing in TB should be 
consulted.)
If the evaluation raises suspicion that a participant may have TB reactivation or new TB 
infection, an immediate and thorough investigation should be undertaken, including, where 
possible, consultation with a physician specializing in TB.
Investigators should be aware that TB reactivation in immunocompromised participants may 
present as disseminated disease or with extrapulmonary features. Participants with evidence of 
active TB should be referred for appropriate treatment.
Participants who experience close contact with an individual with active TB during the conduct 
of the study must have a repeat chest radiograph, a repeat QuantiFERON®-TB test, a repeat 
tuberculin skin test in countries in which the QuantiFERON®-TB test is not approved/registered 
or the tuberculin skin test is mandated by local health authorities, and, if possible, referral to a 
physician specializing in TB to determine the participant’s risk of developing active TB and 
whether treatment for latent TB is warranted.
Study intervention administration should be interrupted during the investigation. A positive 
QuantiFERON®-TB test or tuberculin skin test result should be considered for the detection of 
latent TB. If the QuantiFERON®-TB test result is indeterminate, the test should be repeated as 
outlined in the laboratory manual. Participants should be encouraged to return for all subsequent 
scheduled study visits according to the protocol. Participants who discontinue treatment for 
latent TB prematurely or who are noncompliant with therapy must immediately discontinue 
further administration of study intervention and be encouraged to return for all subsequent 
scheduled study visits according to the Schedule of Activities (Section 1.3).
8.3.
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of participants, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.


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Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally acceptable representative) for the duration of the study.
Anticipated events will be recorded and reported as described in Appendix 2 (Section 10.2), 
Anticipated Events.
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions; 
Severity Criteria; Special Reporting Situations; Procedures) as well as product quality 
complaints (PQCs), refer to Appendix 6 (Section 10.6), Adverse Events: Definitions and 
Procedures for Recording, Evaluating, Follow-Up, and Reporting.
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from 
the time a signed and dated ICF is obtained until completion of the participant's last study-related 
procedure, which may include contact for follow-up of safety. Serious adverse events, including 
those spontaneously reported to the investigator within 12 weeks after the last dose of study 
intervention, must be reported using the Serious Adverse Event Form. The sponsor will evaluate 
any safety information that is spontaneously reported by an investigator beyond the time frame 
specified in the protocol.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person 
by study-site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event 
Form and Safety Report Form of the eCRF, which must be completed and reviewed by a 
physician from the study-site and transmitted to the sponsor within 24 hours. The initial and 
follow-up reports of a serious adverse event should be transmitted electronically or by facsimile 
(fax).
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in 
Appendix 6 (Section 10.6), Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting.
8.3.3.
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute 
where required) all suspected unexpected serious adverse reactions (SUSARs). The investigator 
(or sponsor where required) must report SUSARs to the appropriate Independent Ethics 


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Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise 
required and documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities 
unblinded. Participating investigators and IEC/IRB will receive a blinded SUSAR summary, 
unless otherwise specified.
8.3.4.
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the 
event using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs and must be reported using the Serious Adverse Event Form. Any participant 
who becomes pregnant during the study must discontinue further study intervention (see 
Section 7, Discontinuation of Study Intervention).
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required
8.3.5.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first study intervention 
administration(s) in participants participating in this clinical study must be reported by the 
investigator according to the procedures in Appendix 6 (Section 10.6). Investigators are also 
advised that active TB is considered a reportable disease in most countries. These events are to 
be considered serious only if they meet the definition of an SAE.
8.4.
Treatment of Overdose
For this study, any dose of study intervention greater than the highest dose at a single dosing visit 
specified in this protocol will be considered an overdose. The sponsor does not recommend 
specific intervention for an overdose.
In the event of an overdose, the investigator or treating physician should:

Contact the medical monitor immediately.

Closely monitor the participant for AE/SAE and laboratory abnormalities.

Document the quantity of the excess dose in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5.
Pharmacokinetics
Blood samples will be collected for the measurement of serum guselkumab concentrations at the 
timepoints presented in the Schedules of Activities. Serum samples should also be collected at 
the final visit or at the Early Termination Visit from participants who are discontinued from 


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intervention or withdrawn from the study. Blood samples collected for serum guselkumab 
concentrations may also be used for exploratory biomarker analyses.
Evaluations
At visits in which only serum concentration of guselkumab will be evaluated (ie, no antibodies to 
guselkumab will be evaluated), 1 venous blood sample of sufficient volume should be collected, 
and each serum sample should be divided into 2 aliquots: 1 for serum concentration of 
guselkumab and a back-up. At visits where serum concentration of guselkumab and antibodies to 
guselkumab will be evaluated, 1 venous blood sample of sufficient volume should be collected. 
Each serum sample will be divided into 3 aliquots: 1 for serum concentration of guselkumab, 1 
for antibodies to guselkumab, and 1 back-up. The exact dates and times of blood sample 
collection must be recorded in the laboratory requisition form. See the laboratory manual for 
further information regarding collection, handling, and shipment of biological samples. Genetic 
analyses will not be performed on these serum samples. Participant confidentiality will be 
maintained.
Pharmacokinetic Analytical Procedures
Serum samples will be analyzed to determine serum guselkumab concentrations using a 
validated, specific, and sensitive immunoassay method by the sponsor’s bioanalytical facility or 
under the supervision of the sponsor. The sponsor, or its designee, under conditions in which the 
participants’ identity remains blinded, will assay these samples.
8.6.
Genetics
Samples for DNA analysis will not be collected in this study.
8.7.
Biomarkers
Biomarker assessments will include the evaluation of relevant markers in serum for all 
participants. The samples will be used to better understand the biology of HS in the following 
ways: to provide mechanistic assessment of the pharmacodynamic response of participants to 
treatment with guselkumab, to analyze differences between responders and nonresponders, and 
to determine if the markers can be used to classify participants as potential responders prior to 
treatment. Samples will be collected pre-dose at Week 0, and at Weeks 4, 16, 40, and 48 for 
serum biomarkers. Instructions for the collection and shipment of these samples are found in the 
laboratory manual.
Serum samples will be analyzed for circulating factors such as cytokines and other inflammatory 
markers (eg, IL-17A, IL-17F, IL-23, TNFα, IL-6, IL-22), and other categories of biomarkers 
potentially associated with the development and progression of HS or related to the guselkumab 
mechanism of action.


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Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and 
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the 
end of the study, it becomes clear that the analysis will not have sufficient scientific value for 
biomarker evaluation, or if there are not enough samples or responders to allow for adequate 
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy, 
completion of biomarker assessments is based on justification and intended utility of the data.
8.8.
Health Economics
Health Economics parameters are not evaluated in this study.
9.
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the SAP.
9.1.
Statistical Hypotheses
The primary hypothesis is that guselkumab treatment is superior to placebo as assessed by the 
proportion of participants achieving HiSCR at Week 16. More specifically, considering 2
guselkumab treatment arms in the study, the study will be considered positive if one of the 
following hypotheses are true:

Guselkumab Regimen 1 (1200 mg IV q4w x3 → 200 mg SC q4w) demonstrates superior 
efficacy compared with placebo as measured by HiSCR at Week 16

Guselkumab Regimen 2 (200 mg SC q4w x3 → 200 mg SC q4w) demonstrates superior 
efficacy compared with placebo as measured by HiSCR at Week 16
The major secondary hypotheses are that guselkumab treatment is:

Superior to placebo as assessed by the change from baseline in total AN count at Week 16.

Superior to placebo as assessed by the improvement in PROs as measured by:

The change from baseline in DLQI score at Week 16.

The change from baseline in HS-related pain in the past 24 hours based on HSSD at Week 
16.
9.2.
Sample Size Determination
This study is designed to enroll approximately 180 participants, primarily in order to provide 
adequate information to have sufficient power for the primary efficacy endpoint. The rationale 
for the study sample size is based on the hypothesis tests for the primary efficacy endpoint.


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Two adalimumab (Humira®) Phase 3 clinical studies have been conducted to evaluate the safety 
and efficacy of adalimumab in the treatment of adult participants with moderate to severe HS. 
The response rates observed in Study M11-313 (PIONEER I) and M11-810 (PIONEER II) for 
HiSCR at Week 12 were 42% vs 26% and 59% vs 28% in the adalimumab weekly group and 
placebo group, respectively.
Therefore, the assumptions to calculate sample size and power shown in Table 1 are:

The proportion of placebo participants achieving HiSCR at Week 16 is approximately 25%

The difference between guselkumab treatment group and placebo group on proportion of 
participants achieving HiSCR at Week 16 is approximately 30%
Based on the above assumptions, with 60 participants in each of the guselkumab treatment group 
and 60 participants in the placebo group, there will be more than 90% power to detect a 
treatment difference of 30% with a significance level of 0.05.


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Table 1:
Statistical Power for the HiSCR Response Rate Comparing to Placebo at Week 16
Treatment group
Sample size
HiSCR
Δ (difference)
Power
1
Placebo
60
20%
25%
85%
Guselkumab 
60
45%
2
Placebo
60
20%
30%
94%
Guselkumab 
60
50%
3
Placebo
60
20%
35%
98%
Guselkumab 
60
55%
4
Placebo
60
25%
25%
82%
Guselkumab 
60
50%
5
Placebo
60
25%
30%
93%
Guselkumab 
60
55%
6
Placebo
60
25%
35%
98%
Guselkumab 
60
60%
HiSCR=Hidradenitis Suppurativa Clinical Response
9.3.
Populations for Analyses
For the efficacy analyses in this study, the full analysis set (FAS) will be used according to the 
participants’ assigned treatment to which they were randomized, regardless of the treatment they 
actually received. The FAS includes all randomized participants who receive at least one 
administration of study intervention. The FAS will be used for all primary and secondary 
efficacy analyses.
Safety analyses will include all participants who received at least 1 dose (complete or partial) of 
study intervention and participants will be analyzed based on the treatment they actually
received, regardless of the treatment groups to which they were assigned.
Pharmacokinetics analyses for guselkumab will include participants who receive at least one 
complete dose of guselkumab and have at least one post-dose sample collection. Antibodies to 
guselkumab will be analyzed for participants who receive at least one dose of guselkumab and 
have at least one post-dose sample collection.
9.4.
Statistical Analyses
9.4.1.
Statistical Method
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the SAP.


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In general, efficacy and participant information analyses will include all randomized participants
who received at least 1 dose (complete or partial) of study intervention and will be analyzed 
based on the randomized treatment groups, regardless of the treatment they actually received.
Simple descriptive summary statistics, such as n, mean, standard deviation (SD), median, inter 
quantile range, minimum, and maximum for continuous variables, and counts and percentages 
for discrete variables will be used to summarize most data.
In general, for response efficacy endpoints, treatment comparisons will be performed using a 
Cochran-Mantel-Haenszel (CMH) test stratified by the baseline weight (≤95 kg, >95 kg) and 
baseline Hurley stage (I, II, and III). For continuous efficacy endpoints, treatment comparisons 
will be performed using either a Mixed-Effect Model Repeated Measure (MMRM) model or an 
analysis of covariance (ANCOVA) model. All of the models will have treatment group, baseline 
weight (≤95 kg, >95 kg), baseline Hurley stage (I, II, and III), and baseline value as explanatory 
factors. The MMRM model will also include visit, treatment group by visit interaction, and 
baseline value by visit interaction as additional explanatory factors. In addition, treatment 
differences and their associated 95% confidence intervals will be presented.
In case the number of subjects that are Hurley Stage I at baseline is much less than was expected, 
subjects that were Hurley Stage I will be pooled with subjects that were Hurley Stage II at 
baseline when baseline Hurley Stage is adjusted for in analyses.
In general, all statistical tests will be performed at a 2-sided significance level of α=0.05. In 
addition, graphical data displays (eg, line plots) and participant listings may also be used to 
summarize/present the data.
Participants who discontinue study intervention due to lack of efficacy or an AE of worsening of 
HS, or who started a protocol-prohibited medication or therapy during the study that could 
improve HS are considered treatment failures. The baseline values will be assigned regardless of 
the observed data for continuous endpoints, zero will be assigned to improvement and percent 
improvement, and nonresponders status will be assigned to binary response variables. Lesions 
that received intervention will be counted as present after the visit of intervention. After applying 
the treatment failure rules, the remaining missing data will be assigned nonresponders status for 
binary variables. For the longitudinal analyses, missing data handling rules will not be applied.
9.4.2.
Efficacy Analyses
9.4.2.1.
Primary Analysis
The primary efficacy endpoint is the proportion of patients with a clinical response at Week 16, 
defined according to the HiSCR measure as at least a 50% reduction from baseline in the total 
abscess and inflammatory- nodule count, with no increase in the abscess or draining fistula 
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In the primary efficacy analysis, data from all randomized participants who received at least 1 
administration of study intervention will be analyzed according to their assigned treatment 
group. Participants who meet treatment failure criteria prior to Week 16 will be considered 
nonresponders for the primary endpoint at Week 16. In addition, participants who do not return 
for evaluation at Week 16 will be considered nonresponders at Week 16.
In this primary analysis, the number and proportion of participants who achieve a HiSCR at 
Week 16 will be summarized for each treatment group. To address the primary objective, a CMH
chi-squared statistic stratified by baseline weight (≤95 kg, >95 kg) and baseline Hurley stage at 
an alpha level of 0.05 will be used for each of the following hypotheses:
1.
Guselkumab Regimen 1 (1200 mg IV q4w x 3 → 200 mg SC q4w) versus placebo in HiSCR 
at Week 16.
2.
Guselkumab Regimen 2 (200 mg SC q4w x 3 → 200 mg SC q4w) versus placebo in HiSCR 
at Week 16.
The study is considered positive if at least one of the hypotheses is tested as significant.
9.4.2.2.
Major Secondary Analyses
The major secondary analyses are:

The change from baseline in total AN count at Week 16 will be compared between each of 
the guselkumab groups and the placebo group.

The change from baseline in DLQI at Week 16 will be compared between each of the 
guselkumab groups and the placebo group.

The change from baseline in HS-related skin pain in the past 24 hours based on HSSD at 
Week 16 will be compared between each of the guselkumab groups and the placebo group.
The primary and major secondary hypotheses will be tested in the specified order and the order
and procedure are shown in Figure 2.


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Figure 2:
Diagram for Multiple Testing Procedure for Primary and Secondary Hypotheses
With the sequential analyses specified above within each dose group vs placebo, each of the 
hypotheses will be tested at a 2-sided α-level of 0.05 provided that the significance is achieved 
for the preceding hypothesis test in the specified order shown in Figure 2. If a given comparison 
is not significant at the 2-sided α-level of 0.05, nominal p values will be provided for the 
subsequent treatment group comparisons and the subsequent treatment group comparisons will 
be considered as supportive.
9.4.2.3.
Other Efficacy Analyses
In addition to the primary and major secondary analyses, the analyses for other efficacy 
endpoints will be performed and nominal p-values will be provided. The efficacy endpoints 
(including primary and major secondary endpoints) will also be summarized over time. 
Additional efficacy analyses may be performed and will be documented in the SAP.

The proportion of participants achieving at least 50%, 75%, 90%, and 100% reduction in 
total AN count at Week 16 will be compared between each of the guselkumab groups and 
the placebo group.


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
The proportion of participants achieving an AN count of 1 and 2, respectively at Week 16 
will be compared between each of the guselkumab groups and the placebo group.

The proportion of participants who achieved complete elimination of abscesses at Week 16 
will be compared between each of the guselkumab groups and the placebo group.

The change from baseline in number of abscesses at Week 16 will be compared between 
each of the guselkumab groups and the placebo group.

The proportion of participants who achieved complete elimination of draining fistulas at 
Week 16 will be compared between each of the guselkumab groups and the placebo group
among those with draining fistulas at baseline.

The change from baseline in number of draining fistulas at Week 16 will be compared 
between each of the guselkumab groups and the placebo group.

The proportion of participants who achieved complete elimination of inflammatory nodules 
at Week 16 will be compared between each of the guselkumab groups and the placebo group
among those with inflammatory nodules at baseline.

The change from baseline in number of inflammatory nodules at Week 16 will be compared 
between each of the guselkumab groups and the placebo group.

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1), or 
mild activity (2) and with at least 2-grade improvement relative to baseline at Week 16 will 
be compared between each of the guselkumab groups and the placebo group.

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1) at 
Week 16 among participants with HS-IGA score of moderate activity (3) or severe activity
(4) at baseline will be compared between each of the guselkumab groups and the placebo 
group.

The change from baseline in HSSD symptom scale score (other than pain in the past 24 
hours) at Week 16 will be compared between each of the guselkumab groups and the 
placebo group.

The change from baseline in HSSD total symptom score at Week 16 will be compared 
between each of the guselkumab groups and the placebo group.

The change from baseline in HADS at Week 16 will be compared between each of the 
guselkumab groups and the placebo group.

The change from baseline in high-sensitivity-C-reactive protein (hs-CRP) at Week 16 will 
be compared between each of the guselkumab groups and the placebo group.

The distribution of the PGIC at Week 16 will be compared between each of the guselkumab 
groups and the placebo group.
9.4.3.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, infections, serious infections, mortality, 
changes in laboratory assessments, and changes in vital signs will be summarized. Intervention-
emergent AEs will be summarized by treatment group and Medical Dictionary for Regulatory 


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Activities (MedDRA) system organ class and preferred terms. Details will be specified in the 
SAP.
Safety Definition
Injection-Site Reactions
An injection-site reaction is any unfavorable or unintended sign that occurs at an injection-site 
and will be recorded as an AE. Detailed instructions for the evaluation of injection-site reactions 
are in the Trial Center File.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
MedDRA. Intervention-emergent AEs are AEs with onset during the intervention period or that 
are a consequence of a pre-existing condition that has worsened since baseline. All intervention-
emergent AEs will be included in the analysis. For each AE, the percentage of participants who 
experience at least 1 occurrence of the given event will be summarized by intervention group. In 
addition, comparisons between intervention groups will be provided if appropriate.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those 
participants who die, who discontinue intervention due to an AE, or who experience a severe or a 
SAE.
The following analyses will also be used to assess the safety of participants in the study:

The incidence and type of AEs.

The incidence and type of SAEs.

The incidence and type of infections.

The incidence and type of reasonably related AEs.

The incidence and type of injection-site reactions.

The incidence and type of AEs temporally associated with infusion (defined as an AE that 
occurred on the same day of infusion, with a start time during infusion or ≤ 60 minutes after 
the end of infusion).

The laboratory parameters and change from baseline in selected laboratory parameters
(hematology and chemistry).

The incidence of abnormal laboratory parameters (hematology and chemistry).
Listings of participants with SAEs and anaphylactic reaction/serum sickness reactions will also 
be provided. All safety analyses will be based on the population of participants who received at 
least 1 administration of study intervention; participants will be summarized by the intervention
they received.


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Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test (eg, hematology, clinical 
chemistry). Selected laboratory parameters will be summarized by treatment groups. Common 
Terminology Criteria (CTC) will be used to identify abnormal laboratory test results, and the 
incidence and severity of abnormal laboratory parameters (hematology and chemistry) will be 
summarized by treatment group.
In addition, a listing of participants with grade 3 or higher laboratory test results (based on the 
CTC criteria) will also be provided.
Vital Signs
Descriptive statistics of heart rate and blood pressure (systolic and diastolic) values and changes 
from baseline will be summarized at each scheduled time point.
Weight and Waist Circumference
Descriptive statistics of changes from baseline will be summarized at selected scheduled time 
points.
9.4.4.
Other Analyses
Pharmacokinetic Analyses
Serum guselkumab concentrations over time will be summarized for treated participants. 
Descriptive statistics, including arithmetic mean, SD, median, interquartile range, minimum, and 
maximum will be calculated at each nominal sampling timepoint. All concentrations below the 
lowest quantifiable concentration of the assay (BQL) or missing data will be labeled as such in 
the concentration data listing or statistical analysis dataset. The BQL concentrations will be 
treated as zero in the summary statistics.
Population PK modeling may be conducted when appropriate. The analysis will be presented in a 
separate technical report when applicable.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum guselkumab concentrations and PD and/or efficacy measures 
may be examined when appropriate.
Immunogenicity Analyses
The incidence and titers of anti-guselkumab antibodies will be summarized for all participants 
who receive at least 1 dose of guselkumab and have appropriate samples for detection of 
antibodies to guselkumab (ie, participants with at least 1 sample obtained after their first dose of 
guselkumab). A listing of participants who are positive for antibodies to guselkumab will be 
provided. The maximum titers of antibodies to guselkumab will be summarized for participants 
who are positive for antibodies to guselkumab.


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The incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized for 
participants who are positive for antibodies to guselkumab and have samples evaluable for NAbs 
to guselkumab.
Biomarker Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of 
providing useful scientific information. Any biomarker samples received by the contract vendor 
or sponsor after the cutoff date will not be analyzed, and therefore, excluded from the biomarker 
analysis.
Changes in serum analytes obtained over time will be summarized by treatment group. 
Associations between baseline levels and changes from baseline in select markers and response 
to treatment will be explored. The analyses will aim to identify biomarker relevant to treatment. 
Results of serum biomarker analyses will be reported in separate technical reports.
9.5.
Interim Analysis
Before the first DBL at Week 16, an interim analysis will be conducted when a subset of the 
participants has completed the Week 16 visit. Details of the plan for the interim analysis will be 
specified in a separate interim analysis plan before the time at which the interim analysis is 
performed. The interim analysis will be used to determine whether the efficacy of 
guselkumab 1200 mg IV and guselkumab 200 mg SC doses, as measured by the primary 
endpoint, is sufficiently low to consider terminating the study based on prespecified criteria from
the data accrued up to the interim analysis. Interim analysis results will not be disseminated to 
investigators or individuals associated with the conduct of the study.
A sponsor’s committee otherwise not involved in the study conduct will be responsible for 
reviewing the results of this interim analysis. The interim analysis plan will define the 
organization and roles and responsibilities of the committee, possible recommendations or 
requests, and the communication following this review.
9.6.
Data Monitoring Committee
An independent DMC will be responsible for monitoring safety data on an ongoing basis to 
ensure the continuing safety of the participants enrolled in this study. The committee will meet 
regularly
to review unblinded safety
data. After the review, the DMC will make 
recommendations to the sponsor regarding the conduct of the study. The details will be provided 
in the DMC charter. The DMC will consist of at least one clinical physician with relevant 
therapeutic expertise (dermatology) and one statistician. DMC responsibilities, authorities, and 
procedures will be documented in the DMC charter.


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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.
Appendix 1: Abbreviations and Trademarks
AE
Adverse Events
AN 
Abscess and inflammatory nodule
ANCOVA
Analysis of covariance
ARC
Anticipated Event Review Committee
AUC
area under the serum concentration versus time curve
BCG
Bacille Calmette-Guérin
BQL
Below the lowest quantifiable concentration of the assay
CMH
Cochran-Mantel-Haenszel
CTC
Common Terminology Criteria
DBL
Database Lock
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EP
Erythrodermic psoriasis
FAS
Full analysis set
FSH
Follicle-stimulating hormone
GCP
Good Clinical Practice
GPP
Generalized pustular psoriasis
HADS
Hospital Anxiety and Depression Scale
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human immunodeficiency virus
HiSCR
Hidradenitis Suppurativa Clinical Response
HRT
Hormonal replacement therapy
HS
Hidradenitis suppurativa
HSSD
Hidradenitis Suppurativa Symptom Diary
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Conference on Harmonisation
ICMJE
International Committee of Medical Journal Editors
IGA
Investigator’s global assessment
IP
Investigational Product
IWRS
Interactive Web Response System
IV
Intravenous
LTE
Long-term extensions
mAb
Monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed-Effect Model Repeated Measure
MTX
Methotrexate
NAb
Neutralizing antibody
NOAEL
No-observed-adverse-effect level
PD
Pharmacodynamics
PFS-U
Prefilled syringe with an UltraSafe PLUS™ Passive Needle Guard
PGIC
Patient Global Impression of Change
PK
Pharmacokinetics
POC
Proof-of-concept
PPD
Purified protein derivative
PPP
Palmoplantar pustular psoriasis
PQC
Product quality complaint
PRO
Patient-reported outcomes
PsA
Psoriatic arthritis


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SAE
Serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
Standard deviation
SUSAR
Suspected unexpected serious adverse reactions
TB
Tuberculosis
TU
Tuberculin units
Definitions of Terms
Electronic source 
system
Contains data traditionally maintained in a hospital or clinic record to document medical 
care or data recorded in a CRF as determined by the protocol. Data in this system may be 
considered source documentation.


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10.2.
Appendix 2: Anticipated Events
Anticipated Event
An anticipated event is an adverse event (serious or non-serious) that commonly occurs as a 
consequence of the underlying disease or condition under investigation (disease-related) or 
background regimen.
For the purposes of this study the following events will be considered anticipated events:

Worsening of HS
Reporting of Anticipated Events
All AEs will be recorded in the eCRF regardless of whether considered to be anticipated events 
and will be reported to the sponsor as described under All Adverse Events in Section 8.3.1, Time 
Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information. 
Any anticipated event that meets serious adverse event criteria will be reported to the sponsor as 
described under Serious Adverse Events in Section 8.3.1, Time Period and Frequency for 
Collecting Adverse Event and Serious Adverse Event Information. These anticipated events are 
exempt from expedited reporting as individual single cases to health authorities. However, if
based on an aggregate review, it is determined that an anticipated event is possibly related to 
study intervention, the sponsor will report these events in an expedited manner.
Anticipated Event Review Committee
An Anticipated Event Review Committee (ARC) will be established to perform reviews of 
prespecified anticipated events at an aggregate level. The ARC is a safety committee within the 
sponsor’s organization that is independent of the sponsor’s study team. The ARC will meet to aid 
in the recommendation to the sponsor’s study team as to whether there is a reasonable possibility 
that an anticipated event is related to the study intervention.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and 
threshold to trigger an aggregate analysis of anticipated events will be provided in a separate 
Anticipated Events Safety Monitoring Plan.


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10.3.
Appendix 3: Clinical Laboratory Tests
The following tests will be performed according to the Schedule of Activities (Section 1.3) by 
the central laboratory:
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet count
Red blood cell count
Hemoglobin
Hematocrit
RBC Indices:
MCV
MCH
White Blood Cell (WBC) 
count with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Bands
Clinical 
Chemistry
Sodium
Potassium
Chloride
Blood urea nitrogen (BUN)
Creatinine
Glucose
Aspartate aminotransferase (AST)/Serum 
glutamic-oxaloacetic
Alanine aminotransferase (ALT)/Serum 
glutamic-oxaloacetic
Total bilirubin
Indirect bilirubin
Alkaline phosphatase
Calcium
Phosphate
Albumin
Total protein
Other 
Laboratory
Tests

Urine pregnancy testing for women of childbearing potential only

Lipids (Week 0 only)

High-sensitivity C-reactive protein

Serology (HIV antibody, hepatitis B surface antigen [HBsAg], hepatitis B 
surface antibody [anti-HBs], hepatitis B core antibody [anti-HBc], and hepatitis 
C virus antibody


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10.4.
Appendix 4: Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis. Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled. Tuberculin 
skin testing is both safe and reliable throughout the course of pregnancy. The Mantoux tuberculin test is performed 
by placing an intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm. The test must be 
performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) of standard purified 
protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as recommended by the World Health 
Organization. PPD strengths of 1 TU or 250 TU are not acceptable (Menzies, 2000). Using a disposable tuberculin 
syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the skin. This 
should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter. To prevent needle-stick 
injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, or otherwise 
manipulated by hand. After they are used, disposable needles and syringes should be placed in puncture-resistant 
containers for disposal. Institutional guidelines regarding universal precautions for infection control (eg, the use of 
gloves) should be followed. A trained health care worker, preferably the investigator, should read the reaction to the 
Mantoux test 48 to 72 hours after the injection. Participants should never be allowed to read their own tuberculin 
skin test results. If a participant fails to show up for the scheduled reading, a positive reaction may still be 
measurable up to 1 week after testing. However, if a participant who fails to return within 72 hours has a negative 
test, tuberculin testing should be repeated. The area of induration (palpable raised hardened area) around the site of 
injection is the reaction to tuberculin. For standardization, the diameter of the induration should be measured 
transversely (perpendicular) to the long axis of the forearm. Erythema (redness) should not be measured. All 
reactions should be recorded in millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the 
likelihood of detecting latent TB, even though the participants may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is 
considered to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed.
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB. If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
References
Centers for Disease Control and Prevention. Core curriculum on tuberculosis: What the clinician should know 
(Fourth Edition). Atlanta, GA: Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86.
Menzies RI. Tuberculin skin testing. In: Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach. 2nd ed. New York, NY: Marcel Dekker, Inc; 2000:279-322.


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10.5.
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current International Conference on Harmonisation (ICH) guidelines on Good Clinical 
Practice (GCP), and applicable regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human participants. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study participants are protected, consistent with the principles that originated in the Declaration 
of Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the participants, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involve only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative listed in the Contact Information page(s), which will be provided as a separate 
document. Except in emergency situations, this contact should be made before implementing any 
departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the eCRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
to the study-site:


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
Protocol and amendment(s), if any, signed and dated by the principal investigator.

A copy of the dated and signed (or sealed, where appropriate per local regulations), 
written IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, 
and if applicable, participant compensation programs. This approval must clearly identify 
the specific protocol by title and number and must be signed (or sealed, where 
appropriate per local regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator 
or a member of the study-site personnel is a member of the IEC/IRB, documentation 
must be obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.

Regulatory authority approval or notification, if applicable.

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable.

Documentation of investigator qualifications (eg, curriculum vitae).

Completed investigator financial disclosure form from the principal investigator, where 
required.

Signed and dated clinical trial agreement, which includes the financial agreement.

Any other documentation required by local regulations.
The following documents must be provided to the sponsor before enrollment of the first 
participant:

Completed investigator financial disclosure forms from all sub-investigators

Documentation of sub-investigator qualifications (eg, curriculum vitae)

Name and address of any local laboratory conducting tests for the study, and a dated copy 
of current laboratory normal ranges for these tests, if applicable

Local laboratory documentation demonstrating competence and test reliability 
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the participants)

IB (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials


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
Information on compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other 
potential conflicts of interest, and incentives for participants

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and participant compensation programs, and the sponsor has received a copy 
of this approval. This approval letter must be dated and must clearly identify the IEC/IRB and 
the documents being approved.
Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to participants

If applicable, new or revised participant recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

New edition(s) of the IB and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of AEs that are serious, unlisted/unexpected, and associated with the study 
intervention

New information that may adversely affect the safety of the participants or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the participants

Report of deaths of participants under the investigator's care

Notification if a new investigator is responsible for the study at the site


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
Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct), the amendment and applicable ICF 
revisions must be submitted promptly to the IEC/IRB for review and approval before 
implementation of the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 4.2.1, Study-Specific Ethical Design 
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
FINANCIAL DISCLOSURE
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS
Each participant must give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any study-
related activity. The ICF(s) that is/are used must be approved by both the sponsor and by the 
reviewing IEC/IRB and be in a language that the participant can read and understand. The 
informed consent should be in accordance with principles that originated in the Declaration of 
Helsinki, current ICH and GCP guidelines, applicable regulatory requirements, and sponsor 
policy.


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Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential participants the aims, methods, reasonably anticipated 
benefits, and potential hazards of the study, and any discomfort participation in the study may 
entail. Participants will be informed that their participation is voluntary and that they may 
withdraw consent to participate at any time. They will be informed that choosing not to 
participate will not affect the care the participant will receive. Finally, they will be told that the 
investigator will maintain a participant identification register for the purposes of long-term 
follow-up if needed and that their records may be accessed by health authorities and authorized 
sponsor personnel without violating the confidentiality of the participant, to the extent permitted 
by the applicable law(s) or regulations. By signing the ICF the participant is authorizing such 
access. It also denotes that the participant agrees to allow his or her study physician to re-contact
the participant for the purpose of obtaining consent for additional safety evaluations, and 
subsequent disease-related treatments, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded 
by means of the participant's personally dated signature. After having obtained the consent, a 
copy of the ICF must be given to the participant.
A participant may be rescreened 1 time. Participants who are rescreened are required to sign a 
new ICF.
Completion of screening and randomization procedures within the specified approximately 4-
week window is required. If a participant is approaching the completion of that period, the 
medical monitor can be contacted to discuss eligibility.
If any delay leads to the expiration of time-specific assessments (eg, TB, chest radiograph), the 
participant will be considered a screen failure because he/she will not meet eligibility criteria, 
and the expired assessments (along with the non-time-specific laboratory tests) will have to be 
repeated on rescreening.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of participants confidential.


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The informed consent obtained from the participant includes explicit consent for the processing 
of personal data and for the investigator/institution to allow direct access to his or her original 
medical records (source data/documents) for study-related monitoring, audit, IEC/IRB review, 
and regulatory inspection. This consent also addresses the transfer of the data to other entities 
and to other countries.
The participant has the right to request through the investigator access to his or her personal data 
and the right to request rectification of any data that are not correct or complete. Reasonable 
steps will be taken to respond to such a request, taking into consideration the nature of the 
request, the conditions of the study, and the applicable laws and regulations.
Exploratory biomarker, PK, and immunogenicity research is not conducted under standards 
appropriate for the return of data to participants. In addition, the sponsor cannot make decisions 
as to the significance of any findings resulting from exploratory research. Therefore, exploratory 
research data will not be returned to participants or investigators, unless required by law or local 
regulations. Privacy and confidentiality of data generated in the future on stored samples will be 
protected by the same standards applicable to all other clinical data.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand guselkumab, to 
understand HS, to understand differential intervention responders, and to develop tests/assays 
related to guselkumab and HS. The research may begin at any time during the study or the post-
study storage period. The start of the storage period will be the time at which the Clinical Study 
Report is issued.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Participants may withdraw their consent for their samples to be 
stored for research (refer to Section 7.2.1, Withdrawal from the Use of Research Samples).
COMMITTEES STRUCTURE
Data Monitoring Committee
Details regarding the DMC are presented in Section 9.6
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding guselkumab or the sponsor's 
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the sponsor to the investigator and not 
previously published, and any data, including exploratory biomarker research data, generated as 
a result of this study, are considered confidential and remain the sole property of the sponsor. 
The investigator agrees to maintain this information in confidence and use this information only 


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to accomplish this study, and will not use it for other purposes without the sponsor's prior written 
consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of guselkumab, and thus may be 
disclosed as required to other clinical investigators or regulatory agencies. To permit the 
information derived from the clinical studies to be used, the investigator is obligated to provide 
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator for the study. Results of exploratory
biomarker analyses performed after the Clinical Study Report has been issued will be reported in 
a separate report and will not require a revision of the Clinical Study Report.
Study participant identifiers will not be used in publication of results. Any work created in 
connection with performance of the study and contained in the data that can benefit from 
copyright protection (except any publication by the investigator as provided for below) shall be 
the property of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary 
(multicenter) data and information without approval from the investigator. The investigator has 
the right to publish study-site-specific data after the primary data are published. If an investigator 
wishes to publish information from the study, a copy of the manuscript must be provided to the 
sponsor for review at least 60 days before submission for publication or presentation. Expedited 
reviews will be arranged for abstracts, poster presentations, or other materials. If requested by 
the sponsor in writing, the investigator will withhold such publication for up to an additional 
60 days to allow for filing of a patent application. In the event that issues arise regarding 
scientific integrity or regulatory compliance, the sponsor will review these issues with the 
investigator. The sponsor will not mandate modifications to scientific content and does not have 
the right to suppress information. For multicenter study designs and sub-study approaches, 
secondary results generally should not be published before the primary endpoints of a study have 
been published. Similarly, investigators will recognize the integrity of a multicenter study by not 
submitting for publication data derived from the individual study-site until the combined results
from the completed study have been submitted for publication, within 18 months after the study 
end date, or the sponsor confirms there will be no multicenter study publication. Authorship of 
publications resulting from this study will be based on the guidelines on authorship, such as 
those described in the ICMJE Recommendations for the Conduct, Reporting, Editing and 
Publication of Scholarly Work in Medical Journals, which state that the named authors must 
have made a significant contribution to the conception or design of the work; or the acquisition, 
analysis, or interpretation of the data for the work; and drafted the work or revised it critically for 
important intellectual content; and given final approval of the version to be published; and 


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agreed to be accountable for all aspects of the work in ensuring that questions related to the 
accuracy or integrity of any part of the work are appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as 
required by law.
DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study-site personnel before the study, periodic monitoring visits by the sponsor, and direct 
transmission of clinical laboratory data from a central laboratory into the sponsor's data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples.
The sponsor or designee will review the eCRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with 
the investigator or designee, as appropriate. After upload of the data into the study database they 
will be verified for accuracy and consistency with the data sources.
CASE REPORT FORM COMPLETION
Case report forms are prepared and provided by the sponsor for each participant in electronic 
format. All data relating to the study must be recorded in the eCRF. All eCRF entries, 
corrections, and alterations must be made by the investigator or authorized study-site personnel. 
The investigator must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the participant's source documents. Data must be entered 
into the eCRF in English. The eCRF must be completed as soon as possible after a participant 
visit and the forms should be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed 
after the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and 
study-site personnel.


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SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study-site as a basis for standard medical care must be available for the 
following: participant identification, eligibility, and study identification; study discussion and 
date and time of signed informed consent; dates of visits; results of safety and efficacy 
parameters as required by the protocol; record of all AEs and follow-up of AEs; concomitant 
medication; intervention receipt/dispensing/return records; study intervention administration 
information; and date of study completion and reason for early discontinuation of study 
intervention or withdrawal from the study, if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or another equivalent document).
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and 
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by participant interview or other protocol-required assessment (eg, physical 
examination, laboratory assessment) and documented in the source documents.
An electronic source (eSource) system may be utilized, which contains data traditionally 
maintained in a hospital or clinic record to document medical care (eg, electronic source 
documents) as well as the clinical study-specific data fields as determined by the protocol. This 
data is electronically extracted for use by the sponsor. If eSource is utilized, references made to 
the eCRF in the protocol include the eSource system but information collected through eSource 
may not be limited to that found in the eCRF.
MONITORING
The sponsor designee will perform on-site monitoring visits as frequently as necessary. This will 
include blinded site monitors who will perform source data verification and review drug 
preparation and dispensation. The monitor will record dates of the visits in a study-site visit log 
that will be kept at the study-site, as allowed by local regulation. The first post-initiation visit 
will be made as soon as possible after enrollment has begun. At these visits, the monitor will 
compare the data entered into the eCRF (as defined in the monitoring guidelines) with the source 
documents (eg, hospital/clinic/physician’s office medical records). The nature and location of all 


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source documents will be identified to ensure that all sources of original data required to 
complete the eCRF are known to the sponsor and study-site personnel and are accessible for 
verification by the sponsor study-site contact. If electronic records are maintained at the study-
site, the method of verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review will be discussed with the study-site personnel. The sponsor expects that, during 
monitoring visits, the relevant study-site personnel will be available, the source documents will 
be accessible, and a suitable environment will be provided for review of study-related 
documents. The monitor will meet with the investigator on a regular basis during the study to 
provide feedback on the study conduct.
In addition to on-site monitoring visits, remote contacts will occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site.
ON-SITE AUDITS
Representatives of the sponsor's clinical quality assurance department may visit the study-site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Participant privacy must, however, be 
respected. The investigator and study-site personnel are responsible for being present and 
available for consultation during routinely scheduled study-site audit visits conducted by the 
sponsor or its designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
RECORD RETENTION
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF 
and all source documents that support the data collected from each participant, as well as all 
study documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IP. These documents will be retained for a longer 


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period if required by the applicable regulatory requirements or by an agreement with the sponsor. 
It is the responsibility of the sponsor to inform the investigator/institution as to when these 
documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
STUDY AND SITE CLOSURE
Study Termination
The sponsor reserves the right to close the study-site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A 
study-site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study-site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development


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10.6.
Appendix 6: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered 
a medicinal (investigational or non-investigational) product. An adverse event does not 
necessarily have a causal relationship with the intervention. An adverse event can therefore be 
any unfavorable and unintended sign (including an abnormal finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational or non-investigational) 
product, whether or not related to that medicinal (investigational or non-investigational) product. 
(Definition per ICH)
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.3.1, Time Period and Frequency for Collecting Adverse Events and Serious 
Adverse Events Information, for time of last adverse event recording).
Serious Adverse Event
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require intervention to prevent one of the other outcomes listed in the 
definition above. These should usually be considered serious.


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Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For guselkumab, the expectedness of an adverse 
event will be determined by whether or not it is listed in the IB.
Adverse Event Associated with the Use of the Intervention
An adverse event is considered associated with the use of the intervention if the attribution is 
possible, probable, or very likely by the definitions listed below (see Attribution Definitions).
ATTRIBUTION DEFINITIONS
Not Related
An adverse event that is not related to the use of the intervention.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant 
treatment(s), concomitant disease(s), or the relationship in time suggests that a causal 
relationship is unlikely.
Possible
An adverse event that might be due to the use of the intervention. An alternative explanation, 
eg, concomitant treatment(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the intervention. The relationship in time is 
suggestive (eg, confirmed by dechallenge). An alternative explanation is less likely, 
eg, concomitant treatment(s), concomitant disease(s).
Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation, eg, concomitant treatment(s), concomitant disease(s). The 
relationship in time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
SEVERITY CRITERIA
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.


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Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the participant (eg, laboratory abnormalities).
SPECIAL REPORTING SITUATIONS
Safety events of interest on a sponsor study intervention in an interventional study that may 
require expedited reporting or safety evaluation include, but are not limited to:

Overdose of a sponsor study intervention

Suspected abuse/misuse of a sponsor study intervention

Accidental or occupational exposure to a sponsor study intervention

Medication error involving a sponsor product (with or without participant/patient exposure 
to the sponsor study intervention, eg, name confusion)

Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the eCRF.
PROCEDURES
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study intervention, must 
be recorded using medical terminology in the source document and the eCRF. Whenever 
possible, diagnoses should be given when signs and symptoms are due to a common etiology 
(eg, cough, runny nose, sneezing, sore throat, and head congestion should be reported as "upper 
respiratory infection"). Investigators must record in the eCRF their opinion concerning the 
relationship of the adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to sponsor 
instructions.
For all studies with an outpatient period, including open-label studies, the participant must be 
provided with a "wallet (study) card" and instructed to carry this card with them for the duration 
of the study indicating the following:

Study number

Statement, in the local language(s), that the participant is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Local sponsor's name and 24-hour contact telephone number (for medical staff only)

Site number


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
Participant number

Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the participant's participation in the study, must be followed until any of the 
following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study intervention or to factors unrelated 
to study conduct

It becomes unlikely that any additional information can be obtained (participant or health 
care practitioner refusal to provide additional information, lost to follow-up after 
demonstration of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a 
serious adverse event. Any event requiring hospitalization (or prolongation of hospitalization) 
that occurs during the course of a participant's participation in a study must be reported as a 
serious adverse event, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons 
such as pending placement in long-term care facility).

Surgery or procedure planned before entry into the study (must be documented in the 
eCRF). Note: Hospitalizations that were planned before the signing of the ICF, and where 
the underlying condition for which the hospitalization was planned has not worsened, will 
not be considered SAEs. Any adverse event that results in a prolongation of the originally 
planned hospitalization is to be reported as a new serious adverse event.
The cause of death of a participant in a study within 16 weeks of the last dose of study 
intervention, whether or not the event is expected or associated with the study intervention, is 
considered a serious adverse event.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
PRODUCT QUALITY COMPLAINT HANDLING
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or 
packaging, ie, any dissatisfaction relative to the identity, quality, durability, or reliability of a 
product, including its labeling or package integrity. A PQC may have an impact on the safety and 


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efficacy of the product. Timely, accurate, and complete reporting and analysis of PQC 
information from studies are crucial for the protection of participants, investigators, and the 
sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established 
procedures in conformity with regulatory requirements worldwide to ensure appropriate 
reporting of PQC information; all studies conducted by the sponsor or its affiliates will be 
conducted in accordance with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with a serious adverse event, the study-site personnel must report the 
PQC to the sponsor according to the serious adverse event reporting timelines (refer to 
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information). A sample of the suspected product should be maintained for further 
investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.


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10.7.
Appendix 7: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria. 
Pregnancy information will be collected and reported as noted in Section 8.3.4, Pregnancy and 
Appendix 6 (Section 10.6), Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
Woman Not of Childbearing Potential

premenarchal
A premenarchal state is one in which menarche has not yet occurred.

postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high FSH level (>40 IU/L or mIU/mL) in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT), however in the absence of 12 months of amenorrhea, 
a single FSH measurement is insufficient. If there is a question about menopausal status in 
women on HRT, the woman will be required to use one of the non-estrogen-containing 
hormonal highly effective contraceptive methods if she wishes to continue HRT during the 
study.

permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral 
tubal occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
As noted in Inclusion Criterion 8, study participants who are women of childbearing potential 
must be practicing a highly effective method of contraception and remain on a highly effective 
method while receiving study intervention and until 12 weeks after last dose. Examples of highly 
effective methods of contraception are provided below; however, the method selected must meet 
local/regional regulations/guidelines for highly effective contraception.


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Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER-INDEPENDENT
Highly Effective Methods That Are User-Independent Failure rate of ≤1% per year when used 
consistently and correctly.

Implantable progestogen-only hormone contraception associated with inhibition of ovulationb

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion

Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 74 days.)
USER-DEPENDENT
Highly Effective Methods That Are User-Dependent Failure rate of <1% per year when used 
consistently and correctly.

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb
oral
intravaginal
transdermal
injectable

Progestogen-only hormone contraception associated with inhibition of ovulationb
oral
injectable

Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not 
considered to be highly effective - failure rate of >1% per year).

Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action.

Male or female condom with or without spermicidec

Cap, diaphragm, or sponge with spermicide

A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus-interruptus)

Spermicides alone


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
Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in 
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may 
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception 
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).
Pregnancy During the Study
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor or designee by the study-site personnel within 24 hours of their 
knowledge of the event using the appropriate pregnancy notification form. Abnormal pregnancy 
outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic 
pregnancy) are considered SAEs and must be reported using the Serious Adverse Event Form. 
Any participant who becomes pregnant during the study must discontinue further study 
intervention.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.


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10.8.
Appendix 8: Guselkumab Predicted Exposure Margins
Parameters
Mean Cmax
(µg/mL)
Mean AUC 
(µg.day/mL)
(a) 1200 mg IV Loading Dosing at Weeks 0, 4 and 8
Cynomolgus Monkey Exposure at the NOAEL (50 
mg/kg/week) Following 4 Weekly IV Doses 
1432a
4817b
Human Predicted IV Exposure 
250c
1070d
Predicted Exposure Margine
5.7
4.5
(b) 200 mg SC q4w Dosing
Cynomolgus Monkey Exposure at the NOAEL (50 
mg/kg/week) Following 24 Weekly SC Doses
993a
5412b
Human Predicted SC Exposure
19.5c
92.8d
Predicted Exposure Margine
50.9
58.3
a Highest observed concentration following the fourth 50 mg/kg IV dose or the twenty-fourth 50 mg/kg SC dose, 
respectively
b For IV, AUC from Day 21 through 28 (one week after the last 50 mg/kg dose); for SC, AUC from Day 161 through 168 
(one week after the last 50 mg/kg dose)
c Highest predicted concentration after the third 1200 mg IV guselkumab dose, or at steady-state following the 200 mg 
q4w SC regimen
d Predicted human AUC after the third 1200 mg IV guselkumab dose (from Week 8 through Week 12), or at steady-state 
following 200 mg SC administration. Each value was divided by 4 to obtain the AUC over one week, which in turn 
corresponds to the AUC interval for cynomolgus monkeys.
e Exposure margins represent the ratio between guselkumab exposure metrics in the cynomolgus monkey compared to 
those predicted in humans.
Abbreviations: AUC= area under the curve; Cmax= maximum serum concentration; IV = intravenous; NOAEL = non-
observed adverse effect level; SC= subcutaneous. 


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10.9.
Appendix 9: Hepatitis B Virus (HBV) Screening With HBV DNA Testing
Participants must undergo screening for HBV. At a minimum, this includes testing for HBsAg (HBV 
surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core antibody total):

Participants who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and 
anti-HBs-) are eligible for this protocol.

Participants who test negative for surface antigen (HBsAg-) and test positive for core 
antibody (anti-HBc+) and surface antibody (anti-HBs+) are eligible for this protocol.

Participants who test positive only for surface antibody (anti-HBs+) are eligible for this 
protocol.

Participants who test positive for surface antigen (HBsAg+) are NOT eligible for this 
protocol, regardless of the results of other hepatitis B tests.

Participants who test positive only for core antibody (anti-HBc+) must undergo further 
testing for the presence of hepatitis B virus deoxyribonucleic acid (HBV DNA) test. If the 
HBV DNA test is negative, the participant is eligible for this protocol. If the HBV DNA test 
is positive, the participant is NOT eligible for this protocol. In the event the HBV DNA test 
cannot be performed, the participant is NOT eligible for this protocol.
These eligibility criteria based on HBV test results are also represented in Table 2 below.
Table 2:
Eligibility Based on Hepatitis B Virus Test Results
HEPATITIS B TEST RESULT
Hepatitis B
surface antigen
(HBsAg)
Hepatitis B
surface antibody
(anti-HBs)
Hepatitis B
core antibody
(anti-HBc total)
STATUS
negative
negative
negative
Eligible
negative
(+)
negative
negative
(+)
(+)
(+)
negative or (+)
negative or (+)
Not eligible
negative
negative
(+)
(Require testing for presence of 
HBV DNA*)
* If HBV DNA is detectable, the participant is not eligible for this protocol. If HBV DNA testing cannot be performed, or there 
is evidence of chronic liver disease, the participant is not eligible for the protocol.
For participants who are not eligible for this protocol due to HBV test results, consultation with a 
physician with expertise in the treatment of hepatitis B virus infection is recommended.


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10.10.
Appendix 10: Hidradenitis Suppurativa Investigator’s Global 
Assessment
HS-IGA
0=Inactive – no erythema, hypopigmentation or hyperpigmentation may be present; no drainage, 
areas are dry following palpation; no pain and/or tenderness with palpation.
1=Almost inactive – faint, barely perceptible erythema; scant amount of drainage or discharge 
with palpation; slight pain and/or tenderness with palpation.
2=Mild activity – light red color; mild spontaneous drainage; mild pain and/or tenderness with 
palpation.
3=Moderate activity - moderate red color; moderate amount of spontaneous drainage; moderate 
pain and/or tenderness with palpation, participant winces.
4= Severe activity - bright red coloration; severe spontaneous drainage occurring over broad 
area(s); severe pain and/or tenderness with palpation, participant winces and attempts to 
withdraw
Erythema
0=no erythema, hypopigmentation or hyperpigmentation may be present
1= faint, barely perceptible erythema
2= light red color
3= moderate red color
4= bright red coloration
Drainage
0= no drainage, areas are dry following palpation
1= scant amount of discharge with palpation
2= mild spontaneous drainage
3= moderate amount of spontaneous drainage
4= severe spontaneous drainage occurring over broad area(s)


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Pain and/or tenderness to gentile palpation (excluding scarring area)
0=no pain and/or tenderness with palpation
1= slight pain and/or tenderness with palpation
2= mild pain and/or tenderness with palpation
3= moderate pain and/or tenderness with palpation, participant winces
4= severe pain and/or tenderness with palpation, participant winces and attempts to withdraw


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10.11.
Appendix 11: Hidradenitis Suppurativa Symptom Diary
Hidradenitis Suppurativa Symptoms Diary
Individuals with Hidradenitis Suppurativa (HS) may experience a range of symptoms. Please 
indicate the severity of each symptom, paying close attention to the timeframe for each question. 
Please select only one number for each item on a scale of 0 to 10 (0 = None, and 10 = Worst 
possible).
1.
What is the severity of pain from your HS affected area(s) right now?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 
2.
What was the severity of the worst pain from your HS affected area(s) in the past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 
3.
What was the severity of the worst pain from your HS affected area(s) in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 
4.
What was the severity of the worst tenderness (pain when touching) from your HS affected area(s) in the past 7 
days?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 
5.
What was the severity of itch from your HS affected area(s) in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 
6.
What was the severity of hot feelings from your HS affected area(s) in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 
7.
What was the severity of odor coming from your HS affected area(s) in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
None
Worst 
possible 


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10.12.
Appendix 12: Dermatology Life Quality Index
DERMATOLOGY LIFE QUALITY INDEX
DLQI
Hospital No:
Date:
Score:
Name:
Diagnosis:
Address:
The aim of this questionnaire is to measure how much your skin problem has affected 
your life OVER THE LAST WEEK. Please check one box for each question.
1. Over the last week, how itchy, sore, painful
or stinging has your skin been?
Very much
A lot
A little
Not at all




2. Over the last week, how embarrassed or 
self conscious have you been because of 
your skin?
Very much
A lot
A little
Not at all




3. Over the last week, how much has your 
skin interfered with you going shopping or 
looking after your home or yard?
Very much
A lot
A little
Not at all



Not relevant 
4. Over the last week, how much has your 
skin influenced the clothes you wear?
Very much
A lot
A little
Not at all



Not relevant 
5. Over the last week, how much has your 
skin affected any social or leisure
activities?
Very much
A lot
A little
Not at all



Not relevant 
6. Over the last week, how much has your 
skin made it difficult for you to do any 
sport?
Very much
A lot
A little
Not at all



Not relevant 
7. Over the last week, has your skin prevented 
you from working or studying?
Yes
No

Not relevant 
If "No", over the last week how much has 
your skin been a problem at work or 
studying?
A lot
A little
Not at all 





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8. Over the last week, how much has your skin 
created problems with your partner or any 
of your close friends or relatives? 
Very much
A lot
A little
Not at all



Not relevant 
9. Over the last week, how much has your skin 
caused any sexual difficulties?
Very much
A lot
A little
Not at all



Not relevant 
10 Over the last week, how much of a problem 
has the treatment for your skin been, for 
example by making your home messy, or by 
taking up time?
Very much
A lot
A little
Not at all



Not relevant 
Please check you have answered EVERY question. Thank you.


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10.13.
Appendix 13: Hospital Anxiety and Depression Scale
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10.14.
Appendix 14: Patient Global Impression of Change of Hidradenitis 
Symptom Severity
Patient’s Global Impression of Change (PGIC)
of Hidradenitis Suppurativa Severity
Compared to when you received the first treatment in this study, how has your Hidradenitis 
Suppurativa changed? (Please select one response)
1. A lot better now
2. Moderately better now
3. A little better now
4. Neither better, nor worse (no change)
5. A little worse now
6. Moderately worse now
7. A lot worse now
PGIC_HS_v1.0


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10.15.
Appendix 15: Columbia-Suicide Severity Rating Scale 
(Baseline/Screening)
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PPD
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10.16.
Appendix 16: Columbia-Suicide Severity Rating Scale (Since Last Visit)
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10.17.
Appendix 17: Protocol Amendment History
This is the first amendment to the original protocol.


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11.
REFERENCES
1.
Blok JL, Li K, Brodmerkel C, Horvátovich P, Jonkman MF, Horváth B. Ustekinumab in hidradenitis 
suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol. 2016; 174(4):839-
846.
2.
Deckers IE, Benhadou F, Koldijk MJ, et al. Inflammatory bowel disease is associated with hidradenitis 
suppurativa: Results from a multicenter cross-sectional study. J Am Acad Dermatol. 2017; 76(1):49-53.
3.
Giatrakos S, Huse K, Kanni T, et al. Haplotypes of IL-12RB1 impact on the clinical phenotype of hidradentis 
suppurativa. Cytokine. 2013; 62:297-301.
4.
Ingram JR, Hadjieconomou S, Piguet V. Development of core outcome sets in hidradenitis suppurativa: 
systematic review of outcome measure instruments to inform the process. Br J Dermatol. 2016; 175:263-272. J 
Eur Acad Dermatol Venereol. 2016; 30:989-994.
5.
Jemec GBE. Hidradenitis suppurativa. N Engl J Med 2012; 366:158-164.
6.
Keijsers RR, van der Velden HM, van Erp PE, de Boer-van Huizen RT, Joosten I, Koenen HJ, van de Kerkhof 
PC. Balance of Treg vs. T-helper cells in the transition from symptomless to lesional psoriatic skin. Br J 
Dermatol. 2013; 168(6):1294-302.
7.
Kelly G, Hughes R, McGarry T, et al. Dysregulated cytokine expression in lesional and nonlesional skin in 
hidradenitis suppurativa. Br J Dermatol. 2015; 173:1431-1439.
8.
Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 trials of adalimumab for hidradenitis suppurativa. N 
Engl J Med. 2016; 375:422-434.
9.
Kimball AB, Sobell JM, Zouboulis CC, et al. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel 
clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-
controlled portion of a phase 2 adalimumab study. J Eur Acad Dermatol Venereol. 2016; 30(6):989-994.
10.
Margesson LJ. Hidradenitis suppurativa. Best Pract Res Clin Obstet Gynaecol. 2014; 28(7):1013-1027.
11.
Moran B, Sweeney CM, Hughes R, et al. Hidradenitis suppurativa is characterized by dysregulation of the 
Th17:Treg cell axis, which is corrected by anti-TNF therapy. J Invest Dermatol. 2017;137(11):2389-2395.
12.
Mostafa NM, Nader AM, Noertersheuser P, Okun M, Awni WM. Impact of immunogenicity on 
pharmacokinetics, efficacy and safety of adalimumab in adult patients with moderate to severe chronic plaque 
psoriasis. J Eur Acad Dermatol Venereol. 2017;31(3):490-497.
13.
Mundt, JC, Greist, JH, Jefferson, JW, et al. Prediction of suicidal behavior in clinical research by lifetime 
suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin 
Psych. 2013; 74(9):887-893.
14.
Nader A, Beck D, Noertersheuser P, Williams D, Mostafa N4. Population Pharmacokinetics and 
Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa. Clin 
Pharmacokinet. 2017; 56(9):1091-1102.
15.
Posner, K, Brown, GK, Stanley, B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 
2011;168(12):1266-1277.
16.
Schlapbach C, Hänni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of 
hidradenitis suppurativa. J Am Acad Dermatol. 2011; 65(4):790-798.
17.
Seksik P, Contou J-F, Cosnes A, Cosnes J. Hidradenitis suppurativa and Crohn’s disease. In: Jemec G, Revuz 
J, Leyden J, eds. Hidradenitis Suppurativa. Heidelberg, Germany: Spring; 2006:50-57.
18.
van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour 
necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting 
TNF-α and IL-1β. Br J Dermatol. 2011; 164(6):1292-1298.
19.
van der Zee HH, de Winter K, van der Woude CJ, Prens EP. The prevalence of hidradenitis suppurativa in 
1093 patients with inflammatory bowel disease. Br J Dermatol. 2014; 171(3):673-675.


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20.
Vekic DA, Cains GD. Hidradenitis suppurativa, a review of pathogenesis, associations and management. Part 
2. Australas J Dermatol. 2018 Jan 23. doi: 10.1111/ajd.12766. [Epub ahead of print]
21.
Vekic DA, Frew J, Cains GD. Hidradenitis suppurativa, a review of pathogenesis, associations and 
management. Part 1. Australas J Dermatol. 2018 Jan 21. doi: 10.1111/ajd.12770. [Epub ahead of print]
22.
Yao Y, Thomsen SF. The role interleukin-17 in the pathogenesis of hidradenitis suppurativa. Dermatol Online 
J. 2017; 23(7). pii: 13030/qt8rw2j9zv.
23.
Zouboulis CC, Desai N, Emtestam L, et al. European Dermatology Forum Guideline on Hidradenitis 
Suppurativa/Acne Inversa (HS)-S1 Guideline. Available at: http://www.euroderm.org/edf/index.php/edf-
guidelines/category/5-guidelines-miscellanous. Accessed 03 Apr 2018.


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INVESTIGATOR AGREEMENT
PPD

SAP_001.pdf: 
1
Approved, Date: 31 May 2019
Janssen Research & Development
Statistical Analysis Plan
A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept 
Study to Evaluate Guselkumab for the Treatment of Subjects with Moderate to Severe 
Hidradenitis Suppurativa
Protocol CNTO1959HDS2001; Phase 2  
CNTO1959  (Guselkumab)
Status:
Approved
Date:
31 May 2019
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-ERI-168719194
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03628924


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
ABBREVIATIONS ........................................................................................................................................ 5
1.
INTRODUCTION.................................................................................................................................. 6
1.1.
Trial Objectives ................................................................................................................................ 6
1.2.
Trial Design ...................................................................................................................................... 6
1.3.
Statistical Hypotheses for Trial Objectives....................................................................................... 8
1.4.
Sample Size Justification ................................................................................................................. 8
1.5.
Randomization and Blinding ............................................................................................................ 9
1.5.1.
Procedures for Randomization and Stratification ......................................................................... 9
1.5.2.
Maintenance of Blind .................................................................................................................. 10
2.
GENERAL ANALYSIS DEFINITIONS .............................................................................................. 11
2.1.
Imputation Rules for Partial or Missing AE Dates.......................................................................... 11
2.2.
Visit Windows................................................................................................................................. 12
2.3.
Pooling Algorithm for Analysis Centers.......................................................................................... 12
2.4.
Analysis Sets.................................................................................................................................. 12
2.4.1.
Efficacy Analysis Set(s) .............................................................................................................. 12
2.4.1.1.
Full Analysis Set ...................................................................................................................... 12
2.4.1.2.
Per Protocol Analysis Set........................................................................................................ 13
2.4.2.
Safety Analysis Set..................................................................................................................... 13
2.4.3.
Pharmacokinetics Analysis Set .................................................................................................. 13
2.4.4.
Immunogenicity Analysis Set...................................................................................................... 14
2.5.
Definition of Subgroups.................................................................................................................. 14
2.6.
Study Day and Relative Day .......................................................................................................... 15
2.7.
Baseline and Endpoint ................................................................................................................... 15
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 15
3.1.
Interim Analysis.............................................................................................................................. 15
3.2.
Data Monitoring Committee ........................................................................................................... 16
4.
SUBJECT INFORMATION................................................................................................................ 16
4.1.
Demographics and Baseline Characteristics ................................................................................. 16
4.1.1.
Demographic .............................................................................................................................. 16
4.1.2.
Baseline Disease Characteristics and Medical History .............................................................. 17
4.2.
Disposition Information................................................................................................................... 17
4.3.
Treatment Compliance................................................................................................................... 18
4.4.
Extent of Exposure......................................................................................................................... 18
4.5.
Protocol Deviations ........................................................................................................................ 18
4.6.
Prior and Concomitant Medications/Surgeries............................................................................... 19
5.
EFFICACY ......................................................................................................................................... 19
5.1.
General Method of Analysis........................................................................................................... 19
5.2.
Analysis Specifications................................................................................................................... 20
5.2.1.
Level of Significance................................................................................................................... 20
5.2.1.1.
Multiplicity Adjustment for Testing Procedures ....................................................................... 20
5.2.2.
Definition of the Efficacy Endpoints and Calculation of the Efficacy Instruments ...................... 21
5.2.2.1.
Hidradenitis Suppurativa Clinical Response (HiSCR)............................................................. 21
5.2.2.2.
Lesion Counts.......................................................................................................................... 21
5.2.2.3.
Hurley Staging ......................................................................................................................... 21
5.2.2.4.
Hidradenitis Suppurativa Investigator’s Global Assessment................................................... 21
5.2.2.5.
Patients Reported Outcomes .................................................................................................. 22
5.2.2.5.1.
Hidradenitis Suppurativa Symptom Diary ............................................................................ 22
5.2.2.5.2.
Dermatology Life Quality Index............................................................................................ 22
5.2.2.6.
Hospital Anxiety and Depression ............................................................................................ 23
5.2.3.
Data Handling Rules................................................................................................................... 23


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5.2.3.1.
Treatment Failure Criteria........................................................................................................ 23
5.2.3.2.
Treatment Failure Rules .......................................................................................................... 24
5.2.3.2.1.
Treatment Failure Rule for HSSD Pain Related Endpoints ................................................. 24
5.2.3.3.
Missing Data Imputation.......................................................................................................... 24
5.2.3.3.1.
Missing Data Binary Endpoints ............................................................................................ 25
5.2.3.3.2.
Missing Data Remain as Missing for Continuous Endpoints ............................................... 25
5.2.4.
Estimand..................................................................................................................................... 25
5.2.4.1.
Composite Strategy................................................................................................................. 25
The composite strategy will be used for analyzing all efficacy endpoints. ........................................................... 26
5.2.5.
Treatment Groups....................................................................................................................... 26
5.3.
Primary Efficacy Endpoint(s).......................................................................................................... 27
5.3.1.
Definition..................................................................................................................................... 27
5.3.2.
Analysis Methods........................................................................................................................ 27
5.3.3.
Data Handling ............................................................................................................................. 27
5.3.4.
Sensitivity Analysis ..................................................................................................................... 28
5.3.5.
Subgroup Analysis...................................................................................................................... 28
5.3.6.
Per-protocol Analysis.................................................................................................................. 28
5.4.
Major Secondary Endpoints........................................................................................................... 28
5.4.1.
Definition..................................................................................................................................... 29
5.4.2.
Analysis Methods........................................................................................................................ 29
5.4.2.1.
The Change from Baseline in Total AN Count at Week 16..................................................... 29
5.4.2.2.
The Change from Baseline in DLQI at Week 16 ..................................................................... 29
5.4.2.3.
The Change from Baseline in HS-related Skin Pain in the Past 24 Hours Based on 
HSSD at Week 16. .................................................................................................................. 29
5.4.3.
Data Handling ............................................................................................................................. 29
5.5.
Other Efficacy Variable(s) .............................................................................................................. 30
5.5.1.
Definition..................................................................................................................................... 30
5.5.2.
Analysis Methods........................................................................................................................ 30
5.5.2.1.
At Week 16 .............................................................................................................................. 30
5.5.2.2.
Over Time Summaries............................................................................................................. 31
5.5.3.
Data Handling Rule..................................................................................................................... 31
5.5.4.
Analysis Related to HiSCR......................................................................................................... 32
5.5.5.
Analysis Related to Lesion Count............................................................................................... 32
5.5.6.
Analysis Related to HS-IGA ....................................................................................................... 33
5.5.7.
Analysis Related to Patient Reported Outcome ......................................................................... 34
5.5.7.1.
DLQI ........................................................................................................................................ 34
5.5.7.2.
Hidradenitis Suppurativa Symptoms Diary (HSSD) ................................................................ 35
5.5.7.3.
Other Patients Reported Outcomes ........................................................................................ 35
5.5.8.
Other........................................................................................................................................... 35
6.
SAFETY............................................................................................................................................. 36
6.1.
Adverse Events .............................................................................................................................. 37
6.2.
Clinical Laboratory Tests................................................................................................................ 39
6.3.
Vital Signs and Physical Examination Findings ............................................................................. 39
6.4.
Other Safety Parameters ............................................................................................................... 39
6.5.
Columbia-Suicide Severity Rating Scale (C-SSRS) ...................................................................... 39
7.
PHARMACOKINETICS/PHARMACODYNAMICS ........................................................................... 41
7.1.
Pharmacokinetics........................................................................................................................... 41
7.1.1.
Serum Guselkumab Concentrations........................................................................................... 41
7.1.1.1.
Data Handling Rules................................................................................................................ 42
7.1.2.
PK vs Efficacy/Safety.................................................................................................................. 43
7.1.3.
Population PK Analysis............................................................................................................... 43
7.2.
Immunogenicity.............................................................................................................................. 43
7.2.1.
Antibodies to Guselkumab.......................................................................................................... 43
7.2.2.
Neutralized Antibodies to Guselkumab ...................................................................................... 44
7.2.3.
Antibody vs PK/Efficacy/Safety .................................................................................................. 44
7.3.
Pharmacokinetic vs Efficacy Relationships.................................................................................... 44


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7.4.
Biomarkers ..................................................................................................................................... 44


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ABBREVIATIONS
ADA
anti-drug antibody
AE
adverse event
ALT/SGPT
alanine aminotransferase
ANCOVA
analysis of covariance
AST/SGOT
aspartate aminotransferase
ATC
anatomic and therapeutic Class
AUC
area under the curve
BMI
body mass index
BSA
body surface area
CI
confidence interval
CL
total systemic clearance
Cmax
maximum concentration
CRF
case report form
CSR
Clinical Study Report
CMH
Cochran-Mantel-Haenszel
CV
coefficient of variation
DBL
Database Lock
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
ECG
electrocardiogram
eCRF
electronic case report form
FAS
full analysis set
FCS
Full Conditional Specification 
FDA
Food and Drug Administration
HADS
Hospital Anxiety and Depression Scale
HiSCR
Hidradenitis Suppurativa Clinical Response
HS
Hidradenitis Suppurativa
HS-IGA
Hidradenitis Suppurativa Investigator’s Global Assessment
HSSD
Hidradenitis Suppurativa Symptom Diary
ICH
International Conference on Harmonization
IQ
interquartile
IWRS
interactive web response system
LLOQ
lower limit of quantification
LOCF
last observation carried forward
LS means
Least square means
MAR
missing at random
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed-Effect Model Repeated Measure
NAb
neutralizing antibodies
NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse Events
PD
pharmacodynamic
PGIC
Patient’s Global Impression of Change
PK
pharmacokinetic(s)
PP
per protocol
q4w
every 4 weeks
q8w
every 8 weeks
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
TEAE
treatment-emergent adverse event
WHO
World Health Organization
WHO-DD
World Health Organization Drug Dictionary


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Statistical Analysis Plan CNTO1959HDS2001
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1.
INTRODUCTION
This statistical analysis plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical
methods 
for 
the 
analysis 
of 
efficacy, 
safety, 
pharmacokinetics 
(PK), 
pharmacodynamics (PD),
Immunogenicity
and health-related quality of life in the 
CNTO1959HDS2001 study.
1.1.
Trial Objectives
Primary Objective
The primary objective of this study is to evaluate the initial efficacy, safety, and tolerability of 
guselkumab in adult participants with moderate to severe hidradenitis suppurativa (HS).
Secondary Objectives
The secondary objectives of this study are:

To evaluate the efficacy of guselkumab in adult participants with moderate to severe HS 
during the maintenance phase.

To evaluate the effect of guselkumab on the dermatologic health-related quality of life in 
adult participants with moderate to severe HS.

To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of 
guselkumab therapy in adult participants with moderate to severe HS.
1.2.
Trial Design
This is a Phase 2, multicenter, randomized, placebo-controlled, double-blind, proof-of-concept 
(POC) study evaluating the efficacy, safety, PK, and immunogenicity of SC and IV administered 
guselkumab for the treatment of moderate to severe HS in adult participants. The participant 
population will comprise men and women who have had moderate to severe HS for at least 1 
year.
A diagram of the study design (Figure 1) is provided below and as depicted in Figure 1, 
approximately 180 participants who satisfy all inclusion and exclusion criteria will be 
randomized in a 1:1:1 ratio to 1 of 3 groups:
Group 1: Guselkumab Regimen 1 (1200 mg IV q4w x 3 → 200 mg SC q4w)
Participants will receive guselkumab 1200 mg IV at Week 0, Week 4, and Week 8 (ie, a total of 
3 IV guselkumab doses and 3 SC placebo doses). At Week 12, participants will continue 
treatment with guselkumab 200 mg SC q4w through Week 36.
Group 2: Guselkumab Regimen 2 (200 mg SC q4w x 3 → 200 mg SC q4w)
Participants will receive guselkumab 200 mg SC at Week 0, Week 4, and Week 8 (ie, a total of 3 
SC guselkumab doses and 3 IV placebo doses). At Week 12, participants will switch treatment to
guselkumab 200 mg SC q4w through Week 36.


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Group 3: Placebo
Participants will receive placebo IV and SC at Week 0, Week 4, and Week 8 (ie, a total of 3 IV 
and 3 SC placebo doses) and an additional SC placebo dose at Week 12. At Week 16, 
participants will be rerandomized in a 1:1 ratio to either guselkumab 200 mg SC q4w through 
Week 36 or guselkumab 100 mg SC at Weeks 16, 20, 28, and 36, and placebo at Weeks 24 
and 32.
A screening period will take approximately 4 weeks. All participants will enter safety follow-up 
after Week 36 through Week 48. Two planned database locks (DBLs) will occur, at Week 16 and 
at Week 48.
Efficacy assessments (HS-IGA, lesion counts, Hurley staging, Hidradenitis Suppurativa 
Symptom Diary [HSSD], Dermatology Life Quality Index [DLQI], Hospital Anxiety and 
Depression Scale [HADS], and Patient’s Global Impression of Change [PGIC] will be performed 
according to the Schedules of Activities. Serum samples for PK, immunogenicity, and biomarker
analyses will be collected at the timepoints shown in the Schedules of Activities (Section 1.3 of 
the protocol).
An interim analysis is planned. A sponsor’s committee, otherwise not involved in the study 
conduct, will be responsible for reviewing the results of this interim analysis. In addition, a 
separate, external independent DMC will be commissioned for this study for safety evaluation.
Refer to Section 9.5 of the protocol (Interim Analysis) and Section 9.6 of the protocol (Data 
Monitoring Committee) for details.
Figure 1:
Schematic Overview of CNTO1959HDS2001


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1.3.
Statistical Hypotheses for Trial Objectives
The primary hypothesis is that guselkumab treatment is superior to placebo as assessed by the 
proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at 
Week 16.

HiSCR is defined as at least 50% reduction in total abscess and inflammatory nodule count 
(AN count) with no increase in abscess count and no increase in draining fistula count 
relative to baseline.
The major secondary hypotheses are that guselkumab treatment is:

Superior to placebo as assessed by the change from baseline in AN count at Week 16.

Superior to placebo as assessed by the improvement in patient-reported outcomes (PRO) as 
measured by:

The change from baseline in DLQI score at Week 16.

The change from baseline in HS-related pain in the past 24 hours based on HSSD at 
Week 16.
1.4.
Sample Size Justification
This study is designed to enroll approximately 180 participants in order to have sufficient power 
to detect a difference between the guselkumab groups and the placebo group for the primary 
efficacy endpoint. The rationale for the study sample size is based on the hypothesis tests for the 
primary efficacy endpoint.
Two adalimumab (Humira®) Phase 3 clinical studies have been conducted to evaluate the safety 
and efficacy of adalimumab in the treatment of adult participants with moderate to severe HS. 
The response rates observed in Study M11-313 (PIONEER I) and M11-810 (PIONEER II) for 
HiSCR at Week 12 were 42% vs 26% and 59% vs 28% in the adalimumab weekly group and 
placebo group, respectively.
Therefore, based on the data from these studies, various assumptions to calculate sample size and 
power are shown in Table 1. 
Based on these assumptions, with 60 participants in each of the guselkumab treatment group and 
60 participants in the placebo group, there will be more than 80% power to detect a treatment 
difference with a 2-sided significance level of 0.05.


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Table 1:
Statistical Power for the HiSCR Response Rate Comparing to Placebo at Week 16
Treatment group
Sample size
HiSCR
Δ (difference)
Power
1
Placebo
60
20%
25%
85%
Guselkumab 
60
45%
2
Placebo
60
20%
30%
94%
Guselkumab 
60
50%
3
Placebo
60
20%
35%
98%
Guselkumab 
60
55%
4
Placebo
60
25%
25%
82%
Guselkumab 
60
50%
5
Placebo
60
25%
30%
93%
Guselkumab 
60
55%
6
Placebo
60
25%
35%
98%
Guselkumab 
60
60%
HiSCR=Hidradenitis Suppurativa Clinical Response
1.5.
Randomization and Blinding
1.5.1.
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 3 intervention groups based on a computer-generated randomization schedule prepared 
under the supervision of the sponsor. Permuted block randomization with stratification by 
baseline weight (≤ 95 kg, > 95 kg) and baseline Hurley stage (I, II, and III) will be used. The 
number of participants in Hurley stage I should be limited to approximately 30% of the total 
planned number of participants. Additionally, the number of participants in Hurley stage III 
should be limited to approximately 50% of the total planned number of participants. The 
interactive web response system (IWRS) will assign a unique intervention code, which will 
dictate the intervention assignment and matching study intervention kits for the participant. The 
requestor must use his or her own user identification and personal identification number when 
contacting the IWRS, and will then be given the relevant participant details to uniquely identify 
the participant.
At Week 16, participants randomized to placebo at Week 0 will be rerandomized using the 
IWRS either to guselkumab 200 mg SC q4w or guselkumab 100 mg SC at Weeks 16, 20, and 
q8w thereafter (participants will receive placebo SC at Weeks 24 and 32) in a 1:1 ratio using 
permuted block randomization and the randomization and will be stratified by baseline weight 
(≤95 kg, >95 kg) and baseline Hurley stage (I, II, and III).


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1.5.2.
Maintenance of Blind
The study blind will be maintained for the duration of the study, until after the Final (Week 48) 
DBL.
To maintain the study blind, the study intervention container will have a label containing the 
study name, study intervention number, and reference number. The blinded label will not 
identify the specific study intervention in the container (ie, guselkumab or placebo). However, if 
it is necessary for a participant's safety, the study blind may be broken and the identity of the 
study intervention ascertained. The study intervention number will be entered in the eCRF when 
the study intervention is administered. The guselkumab and placebo will be identical in 
appearance and will be packaged in identical containers.
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
Data that may potentially unblind the intervention assignment (ie, study intervention serum 
concentrations, anti-guselkumab antibodies, and intervention allocation) will be handled with 
special care to ensure that the integrity of the blind is maintained and the potential for bias is 
minimized. This can include making special provisions, such as segregating the data in question 
from view by the investigators, clinical team, or others as appropriate until the time of DBL and 
unblinding.
Under normal circumstances, the blind should not be broken until all participants have completed 
the study and the database is finalized. However, selected sponsor personnel will be unblinded 
for analysis after the Week 16 DBL has occurred. All site personnel and participants will remain 
blinded to the treatment assignments until the last participant completes Week 48 evaluations 
and the database has been locked. The investigator may, in an emergency, determine the identity 
of the intervention by contacting the IWRS. While the responsibility to break the intervention 
code in emergency situations resides solely with the investigator, it is recommended that the 
investigator contact the sponsor or its designee if possible to discuss the particular situation, 
before breaking the blind. Telephone contact with the sponsor or its designee will be available 
24 hours per day, 7 days per week. In the event the blind is broken, the sponsor must be informed 
as soon as possible. The date and reason for unblinding must be documented in the appropriate 
section of the eCRF, and in the source document. The documentation received from the IWRS 
indicating the code break must be retained with the participant's source documents in a secure 
manner.
Participants who have had their intervention assignment unblinded by the investigator will not be 
eligible to receive further study intervention, but should continue to complete evaluations 
specified in the Schedule of Activities (Section 1.3 of the protocol).


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An independent, external DMC will monitor the safety of the study in an unblinded fashion on a 
regular basis and whenever deemed necessary.  In addition, the Sponsor Medical Monitor will 
review safety data in a blinded manner as the study is ongoing.  The DMC’s roles and 
responsibilities, the safety data for DMC review, and other related information (such as, the 
general procedures, communications, etc.) are defined and documented in the DMC charter.
In addition, an internal Sponsor Interim Analysis Committee and the statistical supporting group 
(SSG) otherwise not involved in the study conduct will have access to the unblinded data when 
approximately 30% of the participants have completed their Week 16 visit or have terminated 
their study participation before Week 16
For the planned interim analyses and the DMC review, the randomization codes and the 
translation of randomization codes into intervention and control groups will be disclosed to those 
authorized.
2.
GENERAL ANALYSIS DEFINITIONS
This analysis plan provides the general analysis definitions and describes the planned subject
information, efficacy, safety, pharmacokinetics, and antibody analyses for the two planned
DBLs.
2.1.
Imputation Rules for Partial or Missing AE Dates
Partial AE onset dates will be imputed as follows:

If the onset date of an adverse event is missing day only, it will be set to:

First day of the month that the AE occurred, if month/year of the onset of AE is 
different than the month/year of the study agent start 

The day of study agent start, if the month/year of the onset of AE is the same as 
month/year of the study agent start date and month/year of the AE resolution date is 
different

The day of study agent start or day of AE resolution date, whichever is the earliest, if 
month/year of the onset of AE and month/year of the study agent start date and 
month/year of the AE resolution date are same

If the onset date of an adverse event is missing both day and month, it will be set to the 
earliest of:

January 1 of the year of onset, as long as this date is on or after the study agent start 
date 

Month and day of the study agent start date, if this date is in the same year that the AE 
occurred

Last day of the year if the year of the AE onset is prior to the year of the study agent 
start date, 

The AE resolution date.

Completely missing onset dates will not be imputed.


CNTO1959  (Guselkumab)
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Partial AE resolution dates not marked as ongoing will be imputed as follows:

If the resolution date of an adverse event is missing day only, it will be set to the earliest of 
the last day of the month of occurrence of resolution or the date of death, if the death 
occurred in that month.

If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year.

Completely missing resolution dates will not be imputed.
2.2.
Visit Windows
Nominal visits will be used for all by-visit analyses in the study. The study visits scheduled post 
randomization should occur at the times delineated in the Schedule of Activities.  The study 
visits through Week 36 should occur within ± 7 days of the scheduled visit. The sponsor must be 
contacted for any significant deviation in the scheduling of a visit outside the appropriate 
window and determine how the subject should resume his/her normal dosing schedule relative to 
the baseline visit (Week 0). 
2.3.
Pooling Algorithm for Analysis Centers
Unless otherwise specified, data from all investigational centers/sites will be pooled for analyses. 
2.4.
Analysis Sets
There will be at least two database locks at Weeks 16 and 48 respectively, but additional locks 
may be performed.
Week 16 database lock
Week 16 database lock will include all data through Week 16 for all randomized participants. In 
addition, the available data through Week 48 by the time the last participant completes Week 16 
visit will also be included. The additional data will be primarily used to assess the maintenance 
of clinical response through week 48 in planning for future clinical development in HS; selected 
efficacy, safety, and PK/PD analyses (Section 5.5, 6.1, and 7.1.1) with the data through Week 48
will be included in Week 16 database lock.
Week 48 database lock
Week 48 DBL would include all data through Week 48 for all randomized participants.
2.4.1.
Efficacy Analysis Set(s)
2.4.1.1.
Full Analysis Set
The full analysis set (FAS) includes all randomized participants who received at least 1 dose 
(complete or partial) of study agent.  This analysis set will be used for the efficacy analyses of 
the endpoints through Week 48, unless otherwise specified.


CNTO1959  (Guselkumab)
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In the efficacy analyses, participants will be analyzed according to the randomized treatment 
groups they were assigned to, regardless of the treatments they actually received.  
2.4.1.2.
Per Protocol Analysis Set
The primary endpoint will also be analyzed using the per-protocol population, which includes 
participants who are generally compliant with the protocol.
Specifically, the per protocol population includes participants in FAS except those

who did not meet the inclusion criteria 6 in the protocol as listed below:

Have a total abscess and inflammatory nodule (AN) count of ≥3 at the screening and 
baseline.

who met the exclusion criteria 2 in the protocol as listed below:

Has a draining fistula count of >20 at the baseline visit.

who did not complete the specified exposure to study agent as outline below

participants randomized to placebo at Week 0 who received guselkumab prior to 
Week 16.

participants randomized to guselkumab 1200 mg at Week 0 but did not receive all 
scheduled guselkumab administrations prior to Week 16.

participants randomized to guselkumab 200 mg at Week 0 but did not receive all 
scheduled guselkumab administrations prior to Week 16.
However, for those who did not complete the specified exposure to study agent as outline above, 
participants who discontinued the study agent due to unsatisfactory therapeutic effect (lack of 
efficacy) or an adverse event (AE) of worsening of HS, or participants who started prohibited 
medications and continued receiving study agents prior to the specified timepoint for the 
endpoints will be included in the per protocol analysis and the treatment failure rules specified in 
Section 5.2.3.2 will apply.
Participants who were excluded from the per protocol analyses will also be summarized.
2.4.2.
Safety Analysis Set
The safety analysis set includes all randomized participants who received at least 1 (partial or 
complete) dose of study agent, i.e., the treated population.
In the safety analyses, participants will be analyzed according to the treatment they actually 
received, regardless of the treatments they are randomized to.
2.4.3.
Pharmacokinetics Analysis Set
The pharmacokinetic (PK) analysis set includes all participants who received at least 1 complete 
dose of guselkumab and had at least 1 valid blood sample drawn for PK analysis after their first 
dose of guselkumab.


CNTO1959  (Guselkumab)
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In the PK analyses, participants will be analyzed according to the treatment they actually 
received, regardless of the treatments they are randomized to.
2.4.4.
Immunogenicity Analysis Set
The immunogenicity analysis set includes all participants who received at least 1 (partial or 
complete) dose of guselkumab and who have at least 1 sample obtained after their first dose of
guselkumab for the detection of antibodies to guselkumab.
In the immunogenicity analyses, participants will be analyzed according to the treatment they 
actually received, regardless of the treatments they are randomized to.
2.5.
Definition of Subgroups
To evaluate the consistency in the primary efficacy endpoint (proportion of participants who 
achieve HiSCR at Week 16) over demographics, baseline characteristics, prior and baseline 
medication use, subgroup analyses will be performed when sample sizes are permitted.  The 
subgroups include, but are not limited to, the following:
Baseline demographics:

Sex (male, female)

Race 

Baseline Age (<40 years, 40 to <65 years, 65 years)

Baseline weight (95 kg, >95 kg) 

BMI (Normal [<25], Overweight [25 -<30], Obese [≥ 30])
Baseline disease characteristics:

Baseline Hurley stage status (I, II, and III)

Age at diagnosis (years) (< median, ≥ median)

HS disease duration (years) (< median, ≥ median)

Baseline high-sensitivity C-reactive protein (hs-CRP) (< median, ≥ median)

Baseline AN count category (3 to 5, 6 to 10, ≥11) 

Baseline AN count (< median, ≥ median)

Baseline HS-IGA (<3, 3, 4)
HS medication and surgery history:

Systemic immunomodulatory biologics (adalimumab, infliximab, other-anti-TNF inhibitors, 
ustekinumab)

Never used

Ever Used


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
Hidradenitis Suppurativa related surgery (Deroofing Surgery, Laser Surgery, Excision 
Surgery)

Never had 

Ever had
2.6.
Study Day and Relative Day
Study day is defined as the number of days from the study reference date to the event/visit date.  
It will be calculated as follows: 

If the event/assessment occurs on or after the reference date, then study day = 
event/assessment date – reference date + 1.

If the event/assessment occurs before the reference date, then study day = 
event/assessment date – reference date.
Hence, the day of reference date is Study Day 1; the previous day is Study Day -1.
2.7.
Baseline and Endpoint
In general, the baseline measurement is defined as the closest measurement taken prior to or at 
the time of the first study agent administration date unless otherwise specified.
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
3.1.
Interim Analysis
Before the first DBL at Week 16, an interim analysis will be conducted when a subset of the 
participants who received at least one administration of study agent (including a partial dose) 
have completed their Week 16 visit or have terminated their study participation before Week 16. 
Details of the plan for the interim analysis will be specified in a separate IAC charter and interim 
analysis plan document before the interim analysis is performed. The interim analysis will be 
used to determine whether the efficacy of guselkumab 1200 mg IV and guselkumab 200 mg SC 
doses, as measured by the primary endpoint, is sufficiently low to consider terminating the study 
based on prespecified guidelines from the data accrued up to the interim analysis. Interim 
analysis results will not be disseminated to investigators or individuals involved with the conduct 
of the study.
An interim analysis committee otherwise not involved in the study conduct will be responsible 
for reviewing the results of this interim analysis. Detail of the organization and roles and 
responsibilities of the committee, interim analysis procedure, analysis methods, possible 
recommendations or requests, and the communication following this review will be specified in 
interim analysis committee charter and analysis plan document.


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3.2.
Data Monitoring Committee
An independent, external DMC has been established to monitor data on an ongoing basis to 
ensure the continuing safety of the participants enrolled in this study. The DMC consists of 
3 members who are independent of the sponsor. None of the members is participating as an 
investigator in the current study.
The major function of the DMC is to monitor the safety of the study agent by reviewing the 
serious adverse events (SAEs) each month and by reviewing the study safety data approximately 
every 3/4 months.  The content of the safety summaries for this study are defined and 
documented in the DMC SAP developed by the sponsor. No hypothesis testing will be 
conducted. An independent statistical supporting group, provided by COVANCE (Chiltern), 
supports the DMC and is the liaison between sponsor and the DMC.
After each review, the DMC is to make recommendations regarding the continuation of the study
as planned or, in the event that any unanticipated concerning safety events or issues occur,
placing the study on hold or stopping the study. In addition, the DMC roles and responsibilities, 
and the general procedures (including communications) are defined and documented in the Data 
Monitoring Committee charter developed by the sponsor detailing the safety data monitoring to 
be conducted by the DMC.
4.
SUBJECT INFORMATION
Unless specified otherwise, FAS will be used for the subject information analyses and 
participants will be analyzed according to the treatment group to which they were randomized at 
Week 0, regardless of the treatment they actually received. The number of participants in FAS
will be summarized by treatment group and overall. 
Simple descriptive statistics, such as mean, median, standard deviation, interquartile range, 
maximum, and minimum for continuous variables, and counts and percentages for discrete 
variables will be used to summarize most data and no formal hypothesis testing for treatment 
comparisons will be performed. In addition, subject listings will also be used to present the data.
4.1.
Demographics and Baseline Characteristics
The full analysis set will be used for all tabulations. Participants’ demographic data and baseline 
disease characteristics will be summarized by treatment group.  In addition, summaries of 
participants’ medical history and current diagnoses, alcohol intake, and smoking status will be 
provided by treatment group.  If imbalances are found at baseline, then additional analyses may 
be performed adjusting for baseline differences.
4.1.1.
Demographic
Table 2 presents a list of the demographic variables that will be summarized by treatment group, 
and overall for the FAS.


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Table 2:
Demographic Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median and 
range [minimum and maximum], 
and IQ range).
Weight (kg) 
Height (cm)
Categorical Variables:
Age (<40 years, 40 to <65 years, and 65 years)  
Frequency distribution with the 
number and percentage of 
participants in each category.
Sex (male, female)
Weight (kg) (≤95 kg, > 95 kg)
Race (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Multiple)
Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
BMI (Normal [<25], Overweight [25 -<30], Obese [30])
4.1.2.
Baseline Disease Characteristics and Medical History
Baseline disease characteristics (e.g., duration of HS disease, baseline Hurley stage status, 
baseline AN count, inflammatory nodule count, abscess count, and draining fistula, HS-IGA, and 
PRO related measurements) will be summarized by treatment group. In addition, summaries of 
participants’ medical history and current diagnoses, alcohol intake, and smoking status will be 
provided by treatment group and the distribution of participants by Hurley stage status (I, II, and 
III) and weight category (≤95 kg, >95 kg) will also be provided.
4.2.
Disposition Information
Disposition data will be summarized through the study periods that include the following:

Through Week 16 

Through Week 48
The number of participants in the following disposition categories will be summarized by 
treatment group and overall:

Participants randomized 

Participants who received study agent

Participants who discontinued study agent 

Reasons for discontinuation of study agent 


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
Participants who completed the study

Participants who terminated study prematurely

Reasons for termination of study
Listings of participants will be provided for the following categories:

Participants who discontinued study agent

Participants who terminated study prematurely

Participants who were unblinded during the study period 

Participants who were randomized yet did not receive study agent

In addition, screened participants will be summarized overall.
4.3.
Treatment Compliance
Study agent compliance will be summarized descriptively through Week 36 for the FAS. 
Number of participants by randomized treatment versus actual treatment will be presented in a 
summary table. Number of the participants receiving each scheduled treatment will be 
summarized. In addition, treatment compliance will also be assessed by protocol deviations 
related to study agent administration (i.e., incorrect study agent or dose received). 
4.4.
Extent of Exposure
The exposure data through Week 16 and through Week 36 will be summarized. The number and 
percentage of participants who receive study agent will be summarized by treatment group for 
the safety analysis set. Descriptive statistics will be presented for the following parameters:

Number of administrations

Cumulative total dose 
Study agent lots received by treatment, including matching placebo for active treatment will be 
summarized.
In addition, the average exposure (number of administrations) and average duration of follow-up 
(weeks) will also be summarized by treatment group in the safety tables through different study 
time periods.
4.5.
Protocol Deviations
In general, the following list of major protocol deviations may have the potential to impact 
participants’ rights, safety or well-being, or the integrity and/or result of the clinical trial. 
Participants with major protocol deviations will be identified prior to database lock and will be 
summarized by category by treatment group through Week 48 for the FAS.

Entered but did not satisfy criteria

Developed withdrawal criteria but not withdrawn


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
Received a disallowed concomitant treatment

Received wrong treatment or incorrect dose

Other: to be defined in the major protocol deviation criteria document
In addition, a listing of participants with major protocol deviations and a listing of participants
who missed scheduled study agent administrations (including SC injections and/or IV infusions) 
will also be provided by randomized treatment group.
4.6.
Prior and Concomitant Medications/Surgeries
Prior and concomitant medications will be summarized by treatment group. Prior medications 
are defined as any therapy used before the day of first dose (partial or complete) of study agent. 
Concomitant medications are defined as any therapy used on or after the same day as the first 
dose of study agent, including those that started before and continue on after the first dose of 
study agent.
Prior HS treatment received (including prior HS related surgery) and the reasons for which 
participants discontinued these treatments will be summarized by randomized treatment group 
for the FAS. In addition, a summary of concomitant analgesic therapy for HS, a list of 
participants who received a protocol-prohibited concomitant treatment meeting the definition of 
a treatment failure and a listing of participants who received concomitant analgesic therapy 
meeting the definition of a treatment failure of pain related endpoints will also be provided.
Participants who received concomitant systemic corticosteroids for indications other than HS and 
participants with concomitant prophylactic treatments for latent TB infection will be listed.
5.
EFFICACY
5.1.
General Method of Analysis
Unless specified otherwise, efficacy data summaries will be provided by treatment group for the 
FAS. Statistical comparisons will be made between each of the guselkumab treatment groups
(1200 mg IV, 200 mg SC q4w) and the placebo treatment group.
In general, for response efficacy endpoints, treatment comparisons will be performed using a 
Cochran-Mantel-Haenszel (CMH) test stratified by the baseline weight (≤95 kg, >95 kg) and 
baseline Hurley stage (I, II, and III). For continuous efficacy endpoints, treatment comparisons 
will be performed using either a Mixed-Effect Model Repeated Measure (MMRM) model or an 
analysis of covariance (ANCOVA) model. All of the models will have treatment group, baseline 
weight (≤95 kg, >95 kg), baseline Hurley stage (I, II, and III), and baseline value as explanatory 
factors. The MMRM model will also include visit, treatment group by visit interaction, and 
baseline value by visit interaction as additional explanatory factors. In addition, treatment 
differences and their associated 95% confidence intervals will be presented.
If the total number of participants that are Hurley stage I at baseline is less than 18, participants
that are Hurley stage I will be pooled with the participants that are Hurley stage II, when 
analyses are adjusted by Hurley stage. Descriptive statistics, such as mean, median, standard 


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deviation, minimum and maximum, interquartile range for continuous variables, and counts and 
percentages for categorical variables will be used to summarize the data. Graphical data displays 
and subject listings may also be used to summarize the data.
5.2.
Analysis Specifications
5.2.1.
Level of Significance
Unless otherwise specified, all statistical testing procedures will be performed at a 2-sided 
significance level of 0.05. This study is designed to maintain an overall Type I error of 0.1 or 
less for the primary analysis and major secondary analyses. Nominal p-values will be reported 
for other secondary analyses.
5.2.1.1.
Multiplicity Adjustment for Testing Procedures
This study has 1 primary endpoint (proportion of participants who achieved Hidradenitis 
Suppurativa Clinical Response (HiSCR) at Week 16) and 3 major secondary endpoints.  With 2 
treatment comparisons for each of these endpoints, there are a total of 8 hypotheses to be tested.
The primary and major secondary hypotheses will be tested in the specified order and the order 
and procedure are shown in Figure 2.
Figure 2:
Diagram for Multiple Testing Procedure for Primary and Secondary Hypotheses


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With the sequential analyses specified above within each dose group vs placebo, each of the 
hypotheses will be tested at a 2-sided α-level of 0.05 provided that the significance is achieved 
for the preceding hypothesis test in the specified order shown in Figure 2. If a given comparison 
is not significant at the 2-sided α-level of 0.05, nominal p values will be provided for the 
subsequent treatment group comparisons within each dose group vs placebo and these 
comparisons will be considered as supportive.
5.2.2.
Definition of the Efficacy Endpoints and Calculation of the Efficacy 
Instruments
5.2.2.1.
Hidradenitis Suppurativa Clinical Response (HiSCR)
HiSCR responder status is defined as at least a 50% reduction from baseline in the total abscess 
and inflammatory nodule count, with no increase in abscess or draining fistula count.
5.2.2.2.
Lesion Counts
Lesion counts are defined as the number of abscesses, inflammatory nodules, non-inflammatory 
nodules, draining fistulas, and non-draining fistulas. Lesions will be counted during each visit.
AN Count

AN count is defined as total abscess and inflammatory nodule count.

AN50 is defined as at least a 50% reduction in AN count relative to baseline.

AN75 is defined as at least a 75% reduction in AN count relative to baseline.

AN90 is defined as at least a 90% reduction in AN count relative to baseline.

AN100 is defined as a 100% reduction in AN count relative to baseline (ie, AN count = 0).
5.2.2.3.
Hurley Staging
Hurley staging consists of 3 stages of disease:

Stage I: Abscess formation, single or multiple, without sinus tracts and scarring

Stage II: One or more widely separated recurrent abscesses with tract formation and scarring

Stage III: Multiple interconnected tracts and abscesses across the entire area, with diffuse or 
near diffuse involvement
5.2.2.4.
Hidradenitis Suppurativa Investigator’s Global Assessment
The HS-IGA documents the investigator’s assessment of the participant’s HS at a given 
timepoint. The anatomic region with the most severe HS activity at baseline visit should be 
evaluated for erythema, drainage, and pain and/or tenderness to palpation for each participant. 
For each participant, the same anatomic site selected for evaluation at baseline visit should then 
be evaluated at each subsequent visit.


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The participant’s HS-IGA is assessed as inactive (0), almost inactive (1), mild activity (2), 
moderate activity (3), or severe activity (4). A higher score indicates more severe disease.
The participant’s HS-IGA of erythema is assessed as no erythema, hypopigmentation or 
hyperpigmentation may be present (0), faint, barely perceptible erythema (1), light red color (2), 
moderate red color (3), or bright red coloration (4). A higher score indicates more severe disease.
The participant’s HS-IGA of drainage is assessed as no drainage, areas are dry following 
palpation (0), slight pain and/or tenderness with palpation (1), mild pain and/or tenderness with 
palpation (2), moderate amount of spontaneous drainage (3), or severe spontaneous drainage 
occurring over broad area(s) (4). A higher score indicates more severe disease.
The participant’s HS-IGA of pain and/or tenderness to palpation is assessed as no pain and/or 
tenderness with palpation (0), slight pain and/or tenderness with palpation (1), mild pain and/or 
tenderness with palpation (2), moderate pain and/or tenderness with palpation, participant winces
(3), or severe pain and/or tenderness with palpation, participant winces and attempts to withdraw
(4). A higher score indicates more severe disease.
5.2.2.5.
Patients Reported Outcomes 
5.2.2.5.1.
Hidradenitis Suppurativa Symptom Diary
The HSSD (Section 10.11 of the protocol [Appendix 11]) is a 7-item patient self-reported 
questionnaire that assesses 5 HS-related symptoms including pain, tenderness, hot skin feeling, 
odor, and itchiness. The participants are asked to rate the severity of each symptom on a 0 to 
10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst 
possible symptom experience. All 5 symptoms have a recall period of the past 7 days, except for 
2 additional questions on pain which evaluate current pain and pain in the past 24 hours. Each
individual symptom scale score, ranging from 0-10, will be summarized. A total symptom score, 
which will also range from 0-10, will be derived by averaging the 5 individual scale scores that 
utilize the past 7-day recall period.
5.2.2.5.2.
Dermatology Life Quality Index 
The DLQI is a dermatology-specific quality of life instrument designed to assess the impact of 
the disease on a subject’s quality of life.  It is a 10-item questionnaire that, in addition to 
evaluating overall quality of life, can be used to assess 6 different aspects that may affect quality 
of life:  symptoms and feelings, daily activities, leisure, work or school performance, personal 
relationships, and treatment. The DLQI is calculated by summing the score of each question 
resulting in a maximum of 30 and a minimum of 0. A higher score indicates more severe disease. 
A score of ≤1 indicates no effect at all of disease on subject’s health related quality of life, and a 
reduction of 5 points or more in total DLQI score is considered clinically meaningful 
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For a partially answered questionnaire (eg, not all 10 answers in the DLQI questionnaire were 
available):

If one question’s answer is not available, this question will be scored 0.  The total score will 
then be calculated.

If two or more questions’ answers are unavailable, the questionnaire is not scored.  Hence, 
the total score and each of the 6 component scores will be set to missing.

If one question from one of the 6 component scores is missing, the affected component score 
will be set to be missing.
5.2.2.6.
Hospital Anxiety and Depression 
The Hospital Anxiety and Depression Scale (HADS), a self-assessment scale, was developed to 
detect states of depression, anxiety and emotional distress amongst patients who were being 
treated for a variety of clinical problems. The HADS consists of 2 subscales, one measuring 
Anxiety (A-scale) and one measuring Depression (D scale), which are scored separately. 
The HADS is a 14-item questionnaire. Seven of the items relate to anxiety and seven relate to 
depression. Each item on the questionnaire is scored from 0-3 resulting in a score between 0 and 
21 for either anxiety or depression. 
If one or more of the items within each domain are left unanswered, that HADS component score 
will be considered missing.
5.2.3.
Data Handling Rules
The following treatment failure rules and data handling rules will be applied to the efficacy 
analyses in this study. 
5.2.3.1.
Treatment Failure Criteria
Participants who discontinue study intervention due to lack of efficacy or an AE of worsening of 
HS, or who started a protocol-prohibited medication or therapy during the study that could 
improve HS, are considered treatment failures. 
The particular protocol-prohibited medications/therapies include:
Systemic Therapies:

Any immunodulatory biologic therapy

Any conventional systemic immunosuppressive therapy

Any systemic corticosteroid for HS

Any systemic antibiotic therapy for HS or any indications other than infection

Any systemic retinoid


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
Investigational Agents for HS

Analgesic therapy for HS (Section 5.2.3.2.1) 

Phototherapy (PUVA and/or UVB) for any indications and other phototherapies for 
indication of HS
5.2.3.2.
Treatment Failure Rules
A participant who meets one or more of the treatment failure criteria specified in Section 5.2.3.1
will be considered a treatment failure from that point onward. The baseline values will be used 
for all directly measured endpoints regardless of the actual measurements. Zero will be assigned 
to improvement, and non-responder status will be assigned to binary response variables. 
However, treatment failure rules for the HSSD pain related endpoints will be handle differently 
and are specified in Section 5.2.3.2.1.
Treatment failure is assumed to have occurred at the earlier of the following dates:  

Date of discontinuation of study treatment due to lack of efficacy or an AE of worsening of 
HS or 

Date of initiation of a protocol-prohibited medication/therapy during the study that could 
improve HS.
In addition, lesions that received intervention as rescue therapy will be counted as present after 
the visit of intervention. 
5.2.3.2.1.
Treatment Failure Rule for HSSD Pain Related Endpoints
Participants who received analgesic therapy for HS within 1 day of a scheduled visit, will be 
considered a treatment failure for the HSSD past 24 hours pain and current pain endpoints at that 
visit. Treatment failure rules will not be applied throughout the study for analyses of the HSSD 7 
days recall pain component.
5.2.3.3.
Missing Data Imputation
For the following binary and continuous composite endpoints, participants with missing data on 
component(s) but not all components, a last observation carried forward (LOCF) imputation will 
be performed for the missing component(s) and response status or change from baseline will then 
be determined.

HiSCR (abscess, inflammatory nodule, and draining fistula counts)

Endpoints related to total AN count (abscess and inflammatory nodule counts)

Endpoints related to total inflammatory and non-inflammatory nodule counts

HSSD total symptom score (pain, tenderness, hot skin feeling, odor, and itchiness)
After the treatment failure rules are applied, the remaining missing data will be handled as 
follows for all of the efficacy analyses including the analyses at key visit Week 16 and over time
unless otherwise specified.


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5.2.3.3.1.
Missing Data Binary Endpoints
For binary efficacy endpoints, participants with missing response status will be considered non-
responders for all of the efficacy analyses at key visit of Week 16 and over time summaries.
5.2.3.3.2.
Missing Data Remain as Missing for Continuous Endpoints
For continuous endpoints for which longitudinal data were collected prior to the analysis visits, 
efficacy analyses or over time summaries are performed using a Mixed-Effect Model Repeated 
Measures (MMRM) model and all available data from the 3 treatment groups through Week 16 
or from Week 16 through Week 48 will be included. Missing data will not be imputed after 
treatment failure rules are applied. Under the assumption of MAR, the missing data will be 
accounted for through correlation of repeated measures in the model.
For the MMRM model, an unstructured covariance matrix for repeated measure within a subject 
will be used. In case that convergence cannot be achieved, first order Autoregressive Moving 
Average will be used.
In addition, for the continuous endpoints with no post baseline data scheduled to be collected 
prior to the analysis visit (eg, change from baseline in DLQI at Week 16), under the assumption 
of missing at random (MAR), multivariate response modeling approach will be performed with 
SAS Proc Mixed. With this approach, baseline and post-baseline AN count data that potentially 
can be predictive of missingness will be included in the model and marginal means of change 
from baseline will be compared between the treatment groups.
In addition, no imputation will be done with missing data for efficacy analyses and over time 
summaries for other continuous endpoints.
5.2.4.
Estimand
The same population, ie, all participants with moderate to severe HS for at least one year and
meet inclusion/exclusion criteria will be used for all estimands defined below. The FAS 
(Section 2.4.1.1) will be used to analyze the data.
5.2.4.1.
Composite Strategy
The Composite Strategy assesses the treatment effects not only based on the variable 
measurements, but also based on intercurrent event defined in TF criteria. If a participant meets 
TF criteria, participant will be a non-responder for binary response variables and no 
improvement will be assigned for continuous variables. 

Composite Estimand (Continuous)
Variables: The endpoint is defined as change for baseline score. No improvement (zero 
change) will be assigned after a subject meets one or more treatment failure criteria.
Intercurrent Events: the intercurrent events are captured through variable definition.


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Population level summary: difference in mean changes from baseline between a 
guselkumab group and placebo group.

Composite Estimand (Binary)
Variables: The endpoint (e.g. HiSCR) is defined as the proportion of participants achieving 
a response. No responder status will be assigned after a subject meets one or more TF 
criteria. 
Intercurrent Events: the intercurrent events are captured through variable definition.
Population level summary: difference in proportion of responders between a guselkumab 
group and placebo group.
The composite strategy will be used for analyzing all efficacy endpoints.
5.2.5.
Treatment Groups
In the efficacy analyses, full analysis set will be used and the participants will be analyzed 
according to the randomized treatment groups they were assigned to, regardless of the treatments 
they actually received. Unless otherwise specified, efficacy analyses during each of study periods 
below are in general displayed as follows:

Analysis through Week 16 

Efficacy analyses for placebo comparison at Week 16 or through Week 16 will be 
summarized by randomized treatment group at Week 0:
o
Placebo:  Participants randomized to placebo group at Week 0.
o
Guselkumab 200 mg SC:  Participants randomized to guselkumab 200 mg SC 
group at Week 0.
o
Guselkumab 1200 mg IV: Participants randomized to guselkumab 1200 mg IV 
group at Week 0.

Efficacy data from Week 16 through Week 48 will be summarized by the following 
treatment groups:  
o
Placebo Guselkumab 100 mg SC: Participants randomized to placebo group at 
week 0 and re-randomized at Week 16 to receive guselkumab SC 100 mg. 

Only placebo participants who were re-randomized to guselkumab 100 mg SC 
and received guselkumab 100 mg at Week 16 will be included in the summary 
for the visits after Week 16.
o
Placebo Guselkumab 200 mg SC: Participants randomized to placebo group at 
week 0 and re-randomized at Week 16 to receive guselkumab SC 200 mg. 

Only placebo participants who were re-randomized to guselkumab 200 mg SC 
and received guselkumab 200 mg at Week 16 will be included in the summary 
for the visits after Week 16.


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o
Guselkumab 200 mg SC: Participants randomized to guselkumab 200 mg SC 
group at Week 0.
o
Guselkumab 1200 mg IV: Participants randomized to guselkumab 1200 mg IV at 
Week 0.
These presentations allow assessment of efficacy over time between treatment groups. 
5.3.
Primary Efficacy Endpoint(s)
5.3.1.
Definition
The primary efficacy endpoint is the proportion of patients achieve a HiSCR at Week 16. Refer 
to Section 5.2.2.1 for the definition of a HiSCR responder.
5.3.2.
Analysis Methods
The primary endpoint will be compared between the each guselkumab group and the placebo 
group. The primary endpoint will be analyzed at Week 16 based on the composite estimand 
(Section 5.2.4.1) and the data from all participants in FAS (Section 2.4.1.1) will be analyzed 
according to randomized treatment group regardless of the treatment actually received.
Participants who meet treatment failure criteria prior to Week 16 will be considered 
nonresponders for the primary endpoint at Week 16. In addition, participants who do not return 
for evaluation at Week 16 will be considered nonresponders at Week 16.
In this primary analysis, the number and proportion of participants who achieve a HiSCR at 
Week 16 will be summarized for each treatment group. To address the primary objective, a CMH 
chi-square statistic stratified by baseline weight (≤95 kg, >95 kg) and baseline Hurley stage
status at an alpha level of 0.05 will be used for each of the following hypotheses:
1.
Guselkumab 1200 mg IV versus placebo in HiSCR at Week 16.
2.
Guselkumab 200 mg SC versus placebo in HiSCR at Week 16.
The study is considered positive if at least one of the hypotheses is tested as significant.
5.3.3.
Data Handling
The data handling rules specified in Section 5.2.3.3 and 5.2.3.3.1 will be applied to the primary 
analysis. In the case of participants with missing components (abscess, inflammatory nodule, or 
draining fistula counts) at Week 16, LOCF will be applied for the missing lesion count(s). This 
partial component missing data imputation rule will be applied to all the following analyses
related to the primary endpoint.
Participants who meet treatment failure criteria specified in Section 5.2.3.2 prior to Week 16 will 
be considered not achieving HiSCR at Week 16. In addition, for participants who do not return 
for evaluation at Week 16 will be considered as non-responders. 


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5.3.4.
Sensitivity Analysis
Sensitivity Analysis 1
For participants who do not return for evaluation at Week 16, the analysis will be performed 
using observed data after applying treatment failure rules (as defined in Section 5.2.3.2).
Sensitivity Analysis 2
A second sensitivity analysis will be performed by using multiple imputations (MI) by treatment 
group based HiSCR responses respectively. The fully conditional specification (FCS) method 
will be used to impute the missing data after applying treatment failure for the HiSCR response 
at Week 16. 
More specifically, the missing HiSCR response status will be imputed using FCS method with 
50 imputed data sets with seed = 1231 to fill in the missing HiSCR responses through Week 16
in each of the 50 copies of datasets. The proportion difference of HiSCR at Week 16 adjusted for 
baseline weight (≤95 kg, >95 kg) and baseline Hurley stage using Mantel-Haenszel weight 
between the guselkumab groups and the placebo group and its 95% CI combining multiple 
datasets will be provided. In addition, the p-value for testing the treatment difference will be 
obtained from SAS PROC MIANALYZE based on these combined Mantel-Haenszel estimates 
from the multiple imputation datasets.
5.3.5.
Subgroup Analysis
For each of the subgroups defined in Section 2.5, the difference between each of the guselkumab 
treatment group and placebo group in the proportion of participants achieving HiSCR at 
Week 16 and its 95% continuity adjusted confidence interval (when the number of participants
permits) will be calculated.  Subgroup analyses will not be stratified by baseline weight (≤95 kg, 
>95 kg) and baseline Hurley stage status. 
In addition, the proportion of participants achieving HiSCR at Week 16 by investigator 
site/region will be summarized.
5.3.6.
Per-protocol Analysis
The primary analyses for primary endpoint will also be performed on per-protocol analysis set 
(Section 2.4.1.2). Similar treatment failure rules and data handling rules specified in 
Section 5.2.3 will apply.
5.4.
Major Secondary Endpoints
There are 3 major secondary endpoints with 6 corresponding major secondary analyses. They 
will be performed in the order listed in Figure 2. 

The change from baseline in total AN count at Week 16.

The change from baseline in DLQI at Week 16.


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
The change from baseline in HS-related skin pain in the past 24 hours based on HSSD at 
Week 16.
This section outlines the definition and analyses of these major secondary endpoints.  Data from 
all participants in FAS (Section 2.4.1.1) will be included and analyzed according to the 
randomized treatment groups.
5.4.1.
Definition
Refer to Section 5.2.2 for the definition of the major secondary endpoints
5.4.2.
Analysis Methods
5.4.2.1.
The Change from Baseline in Total AN Count at Week 16
For the change from baseline in AN count at Week 16, treatment comparisons will be performed 
using a Mixed-Effect Model Repeated Measures (MMRM) Model. The MMRM model will 
include baseline weight (≤95 kg, >95 kg), baseline Hurley stage status baseline values, visit, 
treatment group by visit interaction, and baseline value by visit interaction as explanatory 
factors. 
The model will be performed based on all available data from the 3 treatment groups through 
Week 16. The treatment difference between a guselkumab group and the placebo group will be 
estimated by the difference in the least squares means (LSmeans). The 95% CIs for the 
differences in LSmeans and p-values will be calculated.
5.4.2.2.
The Change from Baseline in DLQI at Week 16
The change from baseline in DLQI at Week 16 will be analyzed based on a mixed model 
(Section 5.2.3.3.2). under the assumption of missing at random (MAR). Marginal mean model 
will account for treatment group, baseline weight (≤95 kg, >95 kg), baseline Hurley stage status, 
baseline DLQI score, and AN count at each visit up to Week 16 through correlations among 
these variables. Marginal means will be compared between each of the guselknumab groups and 
placebo.
In addition, treatment differences and their associated 95% confidence intervals will be 
presented.
5.4.2.3.
The Change from Baseline in HS-related Skin Pain in the Past 24 
Hours Based on HSSD at Week 16.
The change from baseline in HS-related skin pain in the past 24 hours based on HSSD at 
Week 16 will be analyzed based on the analysis approach as specified in Section 5.4.2.1.
5.4.3.
Data Handling
Unless otherwise specified, data handling rules specified in Sections 5.2.3.3, 5.2.3.3.2, will be 
applied to the major secondary analyses.


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5.5.
Other Efficacy Variable(s)
In addition to the primary and major secondary analyses, the analyses for other efficacy 
endpoints will be performed and nominal p-values will be provided. Other efficacy endpoints 
include the endpoints related to 

HiSCR

Lesion Count

HS-IGA 

Patient-reported Outcomes 

HSSD

DLQI

HADS

Patient’s Global Impression of Change (PGIC) of Hidradenitis Suppurativa Severity
The other secondary efficacy analyses outlined in the following sections in general will be 
carried out at key endpoint (Week 16) and over time.
5.5.1.
Definition
Refer to Section 5.2.2 for the definitions of the secondary endpoints described in the following 
sections.
5.5.2.
Analysis Methods
Most of the secondary efficacy analyses described in sections below will be based on FAS. For 
participants randomized to placebo, only participants who crossed over to receive guselkumab at 
Week 16 will be included in the efficacy summaries for the visits after Week 16. All statistical 
testing will be performed at the 2-sided 0.05 significance level. Nominal p-values will be 
presented.
5.5.2.1.
At Week 16
For continuous endpoints related to lesion count and HSSD; where longitudinal data were 
collected prior to the analysis visits; treatment comparisons will be performed using Mixed-
Effect Model Repeated Measure (MMRM) model
as specified in Section 5.1
and 
Section 5.2.3.3.2. For the other continuous endpoints (DLQI components and HADS) with no 
post baseline data is scheduled to be collected prior to the analysis visit, treatment comparisons
will be performed using analysis specified in Section 5.4.2.2.
For binary response endpoints treatment comparisons will be performed using a Cochran-
Mantel-Haenszel (CMH) test stratified by the baseline weight (≤95 kg, >95 kg) and baseline 
Hurley stage status with missing data imputed with Non-Responder Imputation (NRI) defined in 
Section 5.1.


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5.5.2.2.
Over Time Summaries
In general, all endpoints with over time analyses will be descriptively summarized by treatment 
groups using descriptive statistics, such as mean, median, standard deviation, interquartile range, 
minimum and maximum for continuous variables, and counts and percentages for categorical 
variables.
Through Week 16
For selected continuous endpoints (change from baseline in AN count, abscess, inflammatory 
nodule, and draining fistula), Mixed-Effect Model Repeated Measure (MMRM) model will be 
used and Least Square means (LS means), LS means differences and their corresponding 95% 
confidence interval will be provided overtime through Week 16 by visit and treatment group in 
addition to the descriptive summary statistics based on observed data after treatment failures.
From Week 16 through Week 48
For selected continuous endpoints (change from baseline in AN count, abscess, inflammatory 
nodule, and draining fistula), Mixed-Effect Model Repeated Measure (MMRM) model will be 
used, Least Square means (LS means) and the corresponding 95% confidence intervals will be 
provided over time from Week 16 through Week 48 by visit and treatment group in addition to 
the descriptive summary statistics based on observed data after treatment failures.
Furthermore, for the over time summaries in proportion of participants achieving HiSCR and
HS-IGA score of 0 or 1, the corresponding 95% CIs will also be provided for each treatment 
group at Week 40.
Additionally, the following overtime analyses will be performed at Week 16 DBL with the data 
available at the time of Week 16 database lock. These analyses will be performed based on the 
observed data without applying treatment failure rules.

The proportion of participants who achieved HiSCR from Week 16 through Week 48.

The change from baseline in total AN count from Week 16 through Week 48.

The proportion of participants with HS-IGA score of inactive (0), HS-IGA score of 
inactive (0) or almost inactive (1), and the proportion of participants achieving HS-IGA 
score of mild activity or better (≤2) from Week 16 through Week 48.

The change from baseline for the past 24 hours pain from Week 16 through Week 48.
5.5.3.
Data Handling Rule
Unless otherwise specified, data handling rules specified in Section 5.2.3.3 will be applied to 
these secondary analyses. Over time summaries for continuous endpoints will be based on the 
observed data after treatment failure rules. For binary endpoints, participants with missing 
response status after applying treatment failures rules will be considered non-responders for the 
over time analyses.


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5.5.4.
Analysis Related to HiSCR

The proportion of participants who achieved HiSCR, the proportion of participants who 
achieved HiSCR by baseline weight (≤95 kg, >95 kg), and the proportion of participants 
who achieved HiSCR by baseline Hurley stage status will be summarized by treatment 
group over time.
The proportion of participants who achieved HiSCR will also be summarized over time by 
treatment groups using observed data after applying treatment failure rules and observed data 
without considering treatment failure rules respectively as sensitivity analyses.
In addition, the HiSCR will be summarized over time from Week 20 through Week 48 with 
Week 16 as baseline for the placebo participants who are re-randomized to either guselkumab 
100 mg q8w or guselkumab 200 mg q4w group.
5.5.5.
Analysis Related to Lesion Count
AN Count

The change from baseline in total AN count, the change from baseline in total AN count by 
weight, and the change from baseline in total AN count by Hurley stage status will be 
summarized by treatment groups over time.

The proportion of participants achieving at least 50%, 75%, 90%, and 100% reduction in 
total AN count at Week 16 will be compared between each of the guselkumab groups and 
the placebo group.

The proportion of participants achieving at least 50%, 75%, 90%, and 100% reduction in 
total AN count will be summarized by treatment group over time.

The proportion of participants achieving AN count of 0, 0/1, and 0/1/2 respectively at 
Week 16 will be compared between each of the guselkumab groups and the placebo group.

The proportion of participants achieving AN count of 0, 0/1, and 0/1/2, respectively will be 
summarized by treatment group over time.

The proportion of participants who experience at least one flare (defined as at least a 25% 
increase in AN count with a minimum increase of 2 AN relative to baseline) over 16 weeks
will be compared between each of the guselkumab groups and the placebo group at
Week 16. Furthermore, the proportion of participants who experience at least one flare over 
48 weeks will be summarized at Week 48 by treatment groups.
In addition, the change from baseline in AN count by prespecified anatomic region and treatment 
group will be summarized at Week 16 and Week 40.
Abscess

The proportion of participants who achieved complete elimination of abscesses at Week 16 
will be compared between each of the guselkumab groups and the placebo group among 
participants who had any abscess at baseline.

The change from baseline in number of abscesses at Week 16 will be compared between 
each of the guselkumab groups and the placebo group.


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
The change from baseline in number of abscesses will be summarized by treatment group 
over time.
Fistulas

The proportion of participants who achieved complete elimination of draining fistulas at 
Week 16 will be compared between each of the guselkumab groups and the placebo group
among those with draining fistulas at baseline.

The change from baseline in number of draining fistulas at Week 16 will be compared 
between each of the guselkumab groups and the placebo group.

The change from baseline in number of draining fistulas will be summarized by treatment 
group over time.
Inflammatory and non-inflammatory Nodules

The proportion of participants who achieved complete elimination of inflammatory nodules 
at Week 16 will be compared between each of the guselkumab groups and the placebo group
among those with inflammatory nodules at baseline.

The change from baseline in number of inflammatory nodules at Week 16 will be compared 
between each of the guselkumab groups and the placebo group.

The change from baseline in number of inflammatory nodules will be summarized by 
treatment group over time.

The change from baseline in number of non-inflammatory nodules at Week 16 will be 
compared between each of the guselkumab groups and the placebo group among pts with 
non-inflammatory nodules at baseline.

The change from baseline in number of non-inflammatory nodules will be summarized by 
treatment group over time.
5.5.6.
Analysis Related to HS-IGA

The proportion of participants with HS-IGA score of inactive (0), HS-IGA score of inactive 
(0) or almost inactive (1), and the proportion of participants achieving HS-IGA score of mild
activity or better (≤2) and with at least 2-grade improvement relative to baseline at Week 16 
will be compared between each of the guselkumab groups and the placebo group.

The proportion of participants with HS-IGA score of inactive (0), HS-IGA score of inactive 
(0) or almost inactive (1), and the proportion of participants achieving HS-IGA score of mild
activity or better (≤2) will be summarized by treatment groups over time. In addition, the 
proportion of participants with 1 -grade and 2-grade improvement in HS-IGA scores from 
baseline will be summarized over time respectively.

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1) at 
Week 16 among participants with HS-IGA score of moderate activity (3) or severe activity 
(4) at baseline will be compared between each of the guselkumab groups and the placebo 
group and will also be summarized by treatment groups over time.


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
The proportion of participants with HS-IGA erythema score of (0), erythema score of (0) or
(1), and the proportion of participants with HS-IGA erythema score of light red color or 
better (≤2) at Week 16 will be compared between each of the guselkumab groups and the 
placebo group and will also be summarized by treatment groups over time.

The proportion of participants with HS-IGA erythema score of 0, erythema score of 0 or 1, 
and the proportion of participants with HS-IGA erythema score of light red color or better 
(≤2) will be summarized by treatment groups over time.

The proportion of participants with HS-IGA drainage score of 0, drainage score of 0 or 1, 
and the proportion of participants with HS-IGA drainage score of mild spontaneous drainage
or better (≤2) at Week 16 will be compared between each of the guselkumab groups and the 
placebo group and will also be summarized by treatment groups over time.

The proportion of participants with HS-IGA drainage score of 0, drainage score of 0 or 1, 
and the proportion of participants with HS-IGA drainage score of mild spontaneous drainage 
or better (≤2) will be summarized by treatment groups over time.

The proportion of participants with HS-IGA pain and/or tenderness to gentile palpation 
(excluding scarring area) score of 0, score of 0 or 1, and the proportion of participants with 
HS-IGA pain and/or tenderness to gentile palpation (excluding scarring area) score of mild 
pain and/or tenderness with palpation or better (≤2) at Week 16 will be compared between 
each of the guselkumab groups and the placebo group and will also be summarized by 
treatment groups over time.

The proportion of participants with HS-IGA pain and/or tenderness to gentile palpation 
(excluding scarring area) score of 0, score of 0 or 1, and the proportion of participants with 
HS-IGA pain and/or tenderness to gentile palpation (excluding scarring area) score of mild 
pain and/or tenderness with palpation or better (≤2) will be summarized by treatment groups 
over time.
In addition, an IGA score derived from the evaluation for erythema, drainage, and pain and/or 
tenderness to palpation will be summarized over time.
5.5.7.
Analysis Related to Patient Reported Outcome
5.5.7.1.
DLQI

The proportions of participants with DLQI score of 0 and 1 at Week 16 for the participants
with baseline DLQI score >1 and the proportion of participants with a reduction of 5 or 
more points in DLQI score for the participants with baseline DLQI score ≥ 5 at Week 16 
will be compared between each of the guselkumab groups and the placebo group.

The change from baseline in DLQI component scores at Week 16 will be compared between 
each of the guselkumab groups and the placebo group.

The proportions of participants with DLQI score of 0 and 1 at Week 40 for the participants
with baseline DLQI score >1 and the proportion of participants with a reduction of 5 or 
more points in DLQI score at Week 40 for the participants with baseline DLQI score ≥ 5 
will be summarized.


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5.5.7.2.
Hidradenitis Suppurativa Symptoms Diary (HSSD)

The change from baseline in each HSSD symptom scale score (7 days recall) and the change 
from baseline in current pain at Week 16 will be compared between each of the guselkumab 
groups and the placebo group.

The change from baseline in HSSD total symptom score at Week 16 will be compared 
between each of the guselkumab groups and the placebo group.

Number of participants with a reduction of ½ SD or more from baseline in HSSD total 
symptom score at week 16 will be compared between each of the guselkumab groups and 
the placebo group.

The change from baseline in each HSSD symptom scale score (7 days recall), the change 
from baseline for the past 24 hours pain and current pain, and the change from baseline in 
HSSD total symptom score will be summarized over time.
5.5.7.3.
Other Patients Reported Outcomes
Hospital Anxiety and Depression

The change from baseline in Hospital Anxiety and Depression scale (HADs) at Week 16 
will be compared between each of the guselkumab groups and the placebo group.

The change from baseline in Hospital Anxiety and Depression scale will be summarized at 
Week 16 and Week 40.

The proportion of participants with hospital anxiety scale <8 and depression scale <8 at 
Week 16 will be compared between each of the guselkumab groups and placebo groups, 
among participants with a baseline hospital anxiety scale and depression scale >=8.

Hospital anxiety scale and depression scale shift from baseline to Week 16 and Week 40 
with respect to the hospital anxiety and depression scale category (<8, >=8) will be 
summarized.
Patient’s Global Impression of Change (PGIC) of Hidradenitis Suppurativa Severity

The distribution of the PGIC at Week 16 will be compared between each of the guselkumab 
groups and the placebo group.
5.5.8.
Other
In addition to the above efficacy analyses, the follow efficacy analyses and summaries will be 
explored by using the observed data without considering treatment failure rules:

The change from baseline in high-sensitivity-C-reactive protein (hs-CRP) at Week 4, 
Week 16, and Week 40 will be summarized by treatment groups.

Hurley stage status shift from baseline to Week 16 and Week 40 will be summarized
respectively.


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6.
SAFETY
Safety will be assessed by summarizing the incidence and type of AEs and examining changes in 
laboratory parameters (hematology and chemistry), vital signs, and suicidal ideation and 
behavior as measured by the C-SSRS (Columbia-Suicide Severity Rating Scale).
In all the safety analysis, randomized participants who received at least 1 (partial or complete) 
dose of study agent administration will be included and analyzed according to the treatment they 
actually received, regardless of the treatments they are randomized to. No formal statistical 
comparison is planned.
Depending on the safety data categories, the cumulative safety data will be analyzed through 
different study periods through Week 16 and Week 48. Unless otherwise specified, tabular 
summaries of safety events for key study periods are in general presented as following:
Summaries through Week 16 (placebo controlled): 
Safety data through Week 16 will be summarized by treatment groups
1. Placebo   
2. Guselkumab 200 mg SC
3. Guselkumab 1200 mg IV 
4. Combined Guselkumab
This allows between-group comparisons of safety between the guselkumab regimens and the 
placebo group based on similar follow-up period in each group.
Summaries through Week 48
Safety data through Week 48 will be summarized by treatment groups including 
1. Placebo → guselkumab 100 mg SC
2. Placebo → guselkumab 200 mg SC 
3. Guselkumab 200 mg SC 
4. Guselkumab 1200 mg IV 
5. Combined Guselkumab
This allows safety comparisons between each guselkumab regimen through Week 48 based on 
the similar follow-up time in each group. 
The list of actual treatment groups for safety analyses and inclusions of participants and safety 
events/measurements in each group are defined as follows:
1.
Placebo: all participants who were randomized to placebo at Week 0 and received treatment 
with placebo only or received treatment with placebo prior to receiving treatment with 
guselkumab. For participants who started treatment with placebo but later received 


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guselkumab, the safety events/measurements on and after the first dose of guselkumab will 
be excluded from this group.  Only the safety events/measurements that occurred while the 
participants had been receiving placebo only will be included in this group.  
2.
Placebo → guselkumab 100 mg SC: all participants who were randomized to placebo at 
Week 0 started treatment with placebo only and later randomized to treatment with 
guselkumab 100 mg SC q8w.  Only the safety events/measurements from these participants
that occurred on and after their first administration of guselkumab will be included in this 
group.
3.
Placebo → guselkumab 200 mg SC: all participants who were randomized to placebo at 
Week 0 started treatment with placebo only and later randomized to treatment with 
guselkumab 200 mg SC q4w.  Only the safety events/measurements from these participants
that occurred on and after their first administration of guselkumab will be included in this 
group.
4.
Guselkumab 200 mg SC: all participants who were randomized to guselkumab 200 mg SC 
q4w at Week 0 and received guselkumab. All the safety events/measurements from these 
participants that occurred from Week 0 will be included in this group.
5.
Guselkumab 1200 mg IV: all participants who were randomized to guselkumab 1200 mg 
IV q4w at Week 0 and received guselkumab. All the safety events/measurements from these 
participants that occurred from Week 0 will be included in this group.
6.1.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE starting at or after 
the initial administration of study agent through the end of the trial is considered to be treatment 
emergent. If the event occurs on the day of the initial administration of study agent, and either 
event time or time of administration are missing, then the event will be assumed to be treatment 
emergent. If the event date is recorded as partial or completely missing, then the event will be 
considered to be treatment emergent unless it is known to be prior to the first administration of 
study agent based on partial onset date or resolution date. All reported treatment-emergent 
adverse events will be included in the analysis. 
Infusion Reactions
A comprehensive clinical review of all AEs that occurred on the same day of infusion, with a start 
time during infusion or ≤ 60 minutes after the end of IV infusion of study agent (AEs temporally 
related to infusion), with the exception of laboratory abnormalities, will be performed to identify the 
occurrence of potential infusion reactions.  Specifically, the reported AEs temporally related to 
infusion will be reviewed to identify participants with a contemporaneous constellation of AE terms 
that are consistent with the signs or symptoms that typically occur during hypersensitivity 
reactions or cytokine release syndromes (eg, anaphylaxis, fever, chills, rigors, hypotension, 


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hypertension, bronchospasm, laryngospasm, wheezing, dyspnea, syncope, pre-syncope, urticaria, 
angioedema, generalized pruritus, flushing, rash, and nausea), to identify all participants with 
potential infusion reactions.  
Injection-site Reactions
A study intervention injection-site reaction is any adverse reaction at an SC study intervention 
injection-site. The injection sites will be evaluated for reactions and any injection-site reactions 
will be recorded as an AE.
Any unfavorable or unintended sign that occurs at the injection (infusion) site is an injection site 
reaction and will be recorded as an injection site reaction by the investigator on the eCRF
Infection
An infection is defined as any AE that was recorded as an infection by the investigator on the 
eCRF.
The following analyses will also be used to assess the safety of participants in the study:

The incidence and type of AEs.

The incidence and type of SAEs.

The incidence and type of infections.

The incidence and type of reasonably related AEs.

The incidence and type of AEs temporally associated with infusion (defined as an AE that 
occurred on the same day of infusion, with a start time during infusion or ≤ 60 minutes after 
the end of infusion).

The incidence and type of injection-site reactions.
These summary tables will provide the count and percentage of participants with 1 or more of the 
specified AEs by treatment group. In addition to the summary tables, listings will be provided for 
participants who:

Had SAEs.

Had AEs leading to discontinuation of study agent administration.

Had AEs of severe intensity.

Had treatment-emergent adverse events temporally associated with infusion.

Had anaphylactic or serum sickness-like reactions.
Since safety should be assessed relative to exposure and follow-up, most AE summary tables 
will include average weeks of follow-up and average number of study agent administrations, 
infusions and injections for each treatment group. A listing of participants who died will be 
provided.


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6.2.
Clinical Laboratory Tests
All clinical laboratory reports will be displayed for the participants included in the safety 
analysis set. The clinical laboratory parameters to be evaluated by the central laboratory include 
but are not limited to:

Hematology: hemoglobin, hematocrit, lymphocytes, neutrophils, platelets, red blood cell 
(RBC) count and white blood cell (WBC) count.

Chemistry: 
albumin, 
alkaline 
phosphatase, 
alanine 
aminotransferase, 
aspartate 
aminotransferase, total bilirubin, blood urea nitrogen/urea, calcium, chloride, creatinine, 
glucose, potassium, total protein, sodium.
Box plots of laboratory measurements and change from baseline will be provided for the selected 
laboratory measurement. 
Applicable laboratory results will be graded according to National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0). The worst NCI-CTCAE 
will be summarized by treatment group. 
For non-fasting glucose, the screening measurement will be used as the baseline measurement. A 
listing of participants with 1 or more NCI-CTCAE toxicity grade 2 in hematology and clinical 
chemistry laboratory measurements will be provided
6.3.
Vital Signs and Physical Examination Findings
Vital signs variables including heart rate and blood pressure (systolic and diastolic) will be 
measured at visits as per the schedule of activities in the protocol. Descriptive statistics of the 
observed value and change from baseline of the vital signs will be summarized by treatment 
group.
Physical exam findings will not be analyzed. When physical exam findings are captured as AEs, 
those will be included in the analyses of AEs.
6.4.
Other Safety Parameters
Weight and Waist Circumference
Descriptive statistics of changes from baseline will be summarized at selected scheduled time 
points.
6.5.
Columbia-Suicide Severity Rating Scale (C-SSRS)
The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used as a screening tool to 
prospectively evaluate the potential of guselkumab to induce suicidal ideation and behavior. The 
C-SSRS defines five subtypes of suicidal ideation and behavior in addition to self-injurious
behavior with no suicidal intent and is a fully-structured subject self-report questionnaire, 
including standardized questions, follow-up prompts, error handling routines, and scoring 
conventions. The Screening version of the C-SSRS will be conducted at Screening followed by 
the Since Last Visit version of the C-SSRS at all other visits through the end of study.


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The C-SSRS will be performed during each evaluation visit according to the assessment 
schedule. The C-SSRS will be performed at screening after signing informed consent, and before 
study agent administration, and as the first assessment for all post-baseline visits. The baseline is 
defined as the most severe/maximum C-SSRS score at either screening or Week 0.
In addition, potential suicide related adverse events including suicidal ideation, suicidal behavior
excluding completed suicide, and completed suicide will be identified by the investigators and 
collected in the eCRF. 
The following are C-SSRS categories and have binary responses (yes/no). A “yes” response to 
any C-SSRS category will be assigned a score as below:
Suicidal Ideation (1-5)
1 = Wish to be Dead
2 = Non-specific Active Suicidal Thoughts
3 = Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
4 = Active Suicidal Ideation with Some Intent to Act, without Specific Plan
5 = Active Suicidal Ideation with Specific Plan and Intent
Suicidal Behavior (6-10)
6 = Preparatory Acts or Behavior
7 = Aborted Attempt
8 = Interrupted Attempt
9 = Actual Attempt (non-fatal)
10 = Completed Suicide
If no events qualify for a score of 1 to 10, a score of 0 will be assigned (0 = “Negative result [no 
suicidal ideation or behavior]”). Higher scores indicate greater severity.
The summary for suicidal ideation and behavior will be based on the safety analysis set. Suicidal 
ideation and behavior will be summarized based on the most severe/maximum post baseline 
C-SSRS outcome or AE of suicidal ideation, suicidal behavior excluding completed suicide, or 
completed suicide through Week 48. 
The maximum score assigned for each subject will also be summarized into one of three broad 
categories: No suicidal ideation or behavior, suicidal ideation, suicidal behavior. A shift table for 
change in C-SSRS categories of no suicidal ideation or behavior, suicidal ideation, and suicidal 


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behavior from baseline through Week 48 will be presented, where the baseline category is based 
on C-SSRS score and the post baseline is based on C-SSRS and/or AE data.
7.
PHARMACOKINETICS/PHARMACODYNAMICS
7.1.
Pharmacokinetics
All PK analyses will be based on the PK analysis set (Section 2.4.3). Unless otherwise specified, 
tabular summaries of PK for key study periods are in general presented as following:
Summaries through Week 16:
PK data through Week 16 will be summarized by treatment groups

Guselkumab 200 mg SC

Guselkumab 1200 mg IV 
Summaries through Week 48:
PK data through Week 48 will be summarized by treatment groups including 

Placebo → 100 mg SC 

Placebo → 200 mg SC 

Guselkumab 200 mg SC 

Guselkumab 1200 mg IV 
7.1.1.
Serum Guselkumab Concentrations
Blood samples for measuring serum guselkumab concentrations will be collected from all 
participants at the specified visits as shown in the schedule of activities in the protocol. Serum 
samples will also be collected at the final visit from participants who terminate study 
participation early. Samples must be collected before study agent administration at visits when a 
study agent administration is scheduled.  In addition, for IV infusion-related visits (i.e., Weeks 0, 
4, and 8), another blood draw should be taken approximately 60 minutes after completion of the 
infusion for serum concentration of guselkumab.
Serum guselkumab concentrations will be summarized using descriptive statistics, including n, 
arithmetic mean, SD, coefficient of variation (%CV), median, interquartile range, range 
(minimum and maximum), by treatment group at each PK sampling time where appropriate.  PK 
data may be displayed graphically.  The following analyses will be performed as appropriate:

Summary of serum guselkumab concentrations at each visit by treatment group

Proportion of participants without detectable serum guselkumab concentration (below the 
lower limit of quantification) at each visit by treatment group

Summary of serum guselkumab concentrations at each visit by treatment group and baseline 
body weight (quartiles). Other covariates may also be applied, e.g. Diabetes or BMI status 
(normal, overweight, obese).


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
Summary of serum guselkumab concentrations at each visit by treatment group and baseline 
Hurley stage status  

Summary of serum guselkumab concentrations by baseline AN count category (3 to 5, 6 to 
10, ≥11)

Plot of median serum guselkumab concentrations over time by treatment group

Plot of median serum guselkumab concentrations over time by treatment group by baseline 
body weight (≤median, > median)
7.1.1.1.
Data Handling Rules
Unless otherwise specified, the following data handling rules will apply to PK analyses:

Participants will be analyzed according to the treatment groups that they actually received. 

All serum concentration summaries for a particular timepoint will include data obtained 
from treated participants at the timepoint of interest without imputing any missing data. 

A concentration not quantifiable (below the lower limit of quantification) will be treated as 0 
in the summary statistics and shown as the lower limit of quantification (< LLOQ) in the 
data listings. 

The data from a subject who meets 1 of the following dosing deviation criteria will be 
excluded from the by-visit data analyses from that point onwards:

Discontinue guselkumab administrations.

Skipped a guselkumab administration.

Received an incomplete/ incorrect dose.

Received an incorrect study agent.

Received an additional guselkumab dose.
In addition, if a subject has an administration outside of dosing windows (Table 3), the 
concentration data collected at and after that visit will be excluded from the by-visit data 
analyses. Additional exclusions for incongruous PK data to be implemented based on Janssen 
SOP-07948. All participants and samples excluded from the analysis will be clearly documented
in the Clinical Study Report.
Table 3:
Dosing Window
Visit
Window
Week 0 through Week 36
± 7 days from scheduled visit day
Final Safety and Efficacy Follow-up visits
± 14 days from scheduled visit day


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7.1.2.
PK vs Efficacy/Safety 
The relationship between serum guselkumab concentrations and safety or efficacy endpoints may 
be explored, e.g.: 

The relationship between serum guselkumab concentrations (quartiles) and proportion of 
participants achieving HiSCR and change from baseline in AN count at Week 16, and
Week 40 will be explored. Summaries by baseline body weight (≤median, > median) or 
baseline Hurley stage status may also be provided.
7.1.3.
Population PK Analysis
When appropriate, population PK analysis will be performed using serum guselkumab 
concentration-time data in all randomized participants with the nonlinear mixed-effects modeling 
(NONMEM) approach.  Details will be provided in a separate technical report.
7.2.
Immunogenicity
Immunogenicity analyses will be based on the Immunogenicity Analysis Set (Section 2.4.4).
Participants will be analyzed according to the treatment groups that they actually received. 
No imputation for missing concentration data will be performed.
Unless otherwise specified, tabular summaries of immunogenicity for key study periods are in 
general presented as following:
Summaries through Week 16:
PK data through Week 16 will be summarized by treatment groups

Guselkumab 200 mg SC

Guselkumab 1200 mg IV 

Combined Guselkumab 
Summaries through Week 48:
PK data through Week 48 will be summarized by treatment groups including 

Placebo → 100 mg SC 

Placebo → 200 mg SC 

Guselkumab 200 mg SC 

Guselkumab 1200 mg IV 

Combined Guselkumab
7.2.1.
Antibodies to Guselkumab
Blood samples will be collected to examine the formation of antibodies to guselkumab at the 
specified visits as shown in the schedule of activities in the protocol. Serum samples will also be 
collected at the final visit from participants who terminate study participation early. 


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The antibodies to guselkumab status (positive at any time, negative) and titers will be 
summarized by treatment group for participants who receive at least one dose of guselkumab and 
have appropriate samples for detection of antibodies to guselkumab. The maximum titers of 
antibodies to guselkumab will be provided for participants who are positive for antibodies to 
guselkumab.
A listing of participants who are positive for antibodies to guselkumab will be provided. This 
listing will provide information regarding dose administered, injection-site/infusion reactions, 
guselkumab serum concentration, and antibody status for all visits. 
7.2.2.
Neutralized Antibodies to Guselkumab
The incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized for 
participants who are positive for antibodies to guselkumab and have samples evaluable for NAbs 
to guselkumab.
7.2.3.
Antibody vs PK/Efficacy/Safety
To explore the relationship between antibodies to guselkumab status and serum guselkumab
concentrations, efficacy and safety, the following analysis may be performed if sufficient 
numbers of participants are positive for antibodies:  

Summary of serum guselkumab concentrations by antibodies to guselkumab status

Plots of median trough serum guselkumab concentrations over time by antibodies to 
guselkumab status 

Summary of clinical response status (e.g., proportion of participants achieving HiSCR and 
change from baseline in AN count) at Week 16 and/or Week 40 by antibodies to 
guselkumab status 

Summary of injection-site reactions by antibodies to guselkumab status

List of antibodies to guselkumab status in participants who discontinued study agent early 
7.3.
Pharmacokinetic vs Efficacy Relationships 
If data permit, the relationships between serum guselkumab concentration and efficacy may be 
analyzed graphically. If any visual trend is observed, a suitable population PK/PD model may be 
developed to describe the exposure-response relationship. Details will be given in a population 
PK/PD analysis plan and results of the population PK/PD analysis will be presented in a separate 
technical report.
7.4.
Biomarkers
Biomarker assessments will include the evaluation of relevant markers in serum for all 
participants. The samples will be used to better understand the biology of HS in some or all of 
the following ways: to provide mechanistic assessment of the pharmacodynamic response of 
participants to treatment with guselkumab, to analyze differences between responders and 
nonresponders, and to determine if the markers might be used to classify participants as potential 
responders prior to treatment.


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Serum samples will be analyzed for circulating factors such as cytokines and other inflammatory 
markers (eg, IL-17A, IL-17F, IL-23, TNFα, IL-6, IL-22), and other categories of biomarkers 
potentially associated with the development and progression of HS or related to the guselkumab 
mechanism of action. These analyses are considered exploratory and will be summarized in a 
separate biomarker technical report.