Clinical trial NCT04988308
Conditions: Hidradenitis Suppurativa
Sponsor: Janssen Research & Development, LLC
Start date: 2021-10-12; Completion date: 2022-11-23
Enrollment: 151 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the clinical efficacy of bermekimab in participants with moderate to severe Hidradenitis Suppurativa (HS).

Detailed description:
Hidradenitis suppurativa (HS) is a chronic skin disease of unclear etiology that affects 1 percent (%) to 4% of the general population. JNJ-77474462 (bermekimab) is a recombinant human immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb) that binds with high affinity and selectivity for human interleukin-1 alpha (IL-1 alpha) and is an effective blocker of IL-1 alpha biological activity. IL-1 alpha is a key mediator of sterile inflammatory responses. Skin is a significant reservoir of preformed IL-1 alpha, and it has been postulated that IL-1 alpha may play a role in the pathophysiology of multiple inflammatory skin disorders, including HS. Part 1 of this study contains 4 study periods: up to 6 weeks screening period (Period 1), 16-week placebo-controlled period (Period 2), 16-week cross over period (Period 3), and 4-week safety follow-up (Period 4). Part 2 of this study also contains 4 study periods: up to 6 weeks screening period (Period 1), 12-week placebo-controlled period (Period 2), 20-week cross over period (Period 3), and 4-week safety follow up (Period 4). Safety will be assessed by adverse events (AEs), serious adverse event (SAEs), physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, allergic reaction, injection-site reactions, and tuberculosis evaluations. The total duration of study participation will be up to 42 weeks.

Arms: arm 1: Participants will receive placebo subcutaneously (SC) at Week 0 through Week 15. At Week 16, participants will cross over to receive bermekimab dose 1 SC every week thereafter through Week 31. arm 2: Participants will receive adalimumab 160 milligrams (mg) SC at Week 0, placebo SC at Week 1, followed by adalimumab 80 mg SC and placebo SC at Weeks 2 and 3. Participants will then receive adalimumab 40 mg SC and placebo SC at Week 4 and every week thereafter through Week 31. arm 3: Participants will receive bermekimab dose 1 SC and placebo SC at Week 0, followed by bermekimab dose 1 SC at Week 1 and every week thereafter through Week 31. arm 4: Participants will receive placebo SC from Week 0 through Week 11. At Week 12, participants will cross over to receive bermekimab dose 1 SC weekly through Week 31. arm 5: Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 31. arm 6: Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 1 SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31. arm 7: Participants will receive bermekimab dose 2 SC and placebo SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 2 SC and placebo SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31.
Interventions: intervention 1: Bermekimab intervention 2: Adalimumab intervention 3: Placebo
Intervention descriptions: intervention 1: Bermekimab will be administered subcutaneously. intervention 2: Adalimumab will be administered subcutaneously. intervention 3: Placebo will be administered subcutaneously.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 12 August 2022
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Phase 2a/2b, Multicenter, Randomized, Placebo and Active Comparator-controlled, 
Double-Blind, Dose-ranging Study to Evaluate the Safety and Efficacy of Bermekimab 
(JNJ-77474462) for the Treatment of Subjects with Moderate to Severe Hidradenitis 
Suppurativa.
LYRA
Short Title
A Dose-ranging Study of Bermekimab (JNJ-77474462) in the Treatment of Subjects with 
Moderate to Severe Hidradenitis Suppurativa
Protocol 77474462HDS2001; Phase 2a/2b
AMENDMENT 2
JNJ-77474462 (bermekimab)
*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; Janssen Biopharma Inc.; 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.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s):
IND: 112459
EudraCT NUMBER: 2020-002607-19
Status:
Approved  
Date:
12 August 2022
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-68949, 4.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04988308


JNJ-77474462 (bermekimab)
Clinical Protocol 77474462HDS2001 Amendment 2
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 12 August 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY
Document
Date
Amendment 2
12 August 2022
Amendment 1
08 July 2021
Original Protocol
26 April 2021
Amendment 2 (12 August 2022)
Overall Rationale for the Amendment: The overall rationale for the amendment is to change the 
prospective dose regimens in Part 2 based on the emerging Phase 1 PK information on bermekimab as well 
as the interest to test the q2w regimen. Since the newly proposed q2w regimen in Part 2 starts after Week 12, 
the timing of the primary endpoint for analysis in Part 2 was updated to Week 12 from Week 16 while 
keeping the Week 16 primary endpoint in Part 1. The number of dose regimens and total sample size to be 
studied in Part 2 will be determined in an adaptive fashion based on PK results from Part 1.
The changes made to the clinical protocol 77474462HDS2001 as part of Protocol Amendment 2 are listed 
below, including the rationale of each change and a list of all applicable sections. Changes made in previous 
protocol amendment are listed in Section 10.20 Appendix 20: Protocol Amendment History.
Section number
and Name
Description of Change
Brief Rationale
Throughout the 
protocol 

Updated the timing of the primary, secondary, 
and exploratory endpoints for Part 2 to
Week 12.

Modified dose regimens in Part 2.

Updated dose justification.

Added DBL at IA 2.

Modified sample size in Part 2 and associated 
sample size/power calculations and efficacy 
evaluation.
To investigate relevant dose 
regimens for further development 
based on the emerging information 
on bermekimab. Updated the 
timing of primary endpoint based 
on the newly proposed q2w 
regimens.
To remove “dose response” from 
objectives to reflect the elimination 
of the lower dose arm(s). 
Synopsis; 3. 
Objectives and
Endpoints; 4.3. 
Justification for 
Dose; 9.1. Statistical 
Hypotheses 
Removed “dose-response” from primary objectives 
and hypothesis.
Throughout the 
protocol

Removed active comparator, adalimumab, from 
Part 2.

Added EC #45 to add washout period for 
adalimumab.
To include adalimumab-
experienced participants in Part 2 
of the study.
Synopsis; 4.1. 
Overall Design; 9.5. 
Interim Analysis

Added futility for the first IA.
To consider termination of the 
study if bermekimab does not 
provide benefit for participants. 
1.3.1. Screening 
Through Week 16, 
Part 1; 1.3.2. 
Screening Through 
Week 16, Part 2

Updated time point for medical
history/demographics.

Updated footnote k for Population PK sample.

Removed footnote “s” in Amendment 1 and 
renumbered the footnotes after it in 
Amendment 2.
To correct errors.


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Status: Approved,  Date: 12 August 2022
Section number
and Name
Description of Change
Brief Rationale
1.3.1. Screening 
Through Week 16, 
Part 1; 1.3.2. 
Screening Through 
Week 16, Part 2; 
5.1. Inclusion 
Criteria; 8.2.4. 
Clinical Safety 
Laboratory 
Assessments; 10.3. 
Appendix 3
Changed “Urine pregnancy test” to “Pregnancy 
test” in Schedule of Activities and updated IC #15 
and Clinical Laboratory Tests to cover both serum 
and urine pregnancy tests
To correct an error.
1.3.2. Screening 
Through Week 16, 
Part 2; 8.1.3. Lesion 
Counts; 8.1.11. HS 
Lesion Monitoring
Using Medical 
Infrared 
Thermography; 
10.17. Appendix 17
Reduced collection time points for lesion counts, 
HS-IGA, and images of skin lesions in Part 2.
To decrease burden for participants 
while collecting sufficient efficacy 
data.
1.3.2. Screening 
through Week 16, 
Part 2; 10.3. 
Appendix 3
Added fasting lipid panel to clinical laboratory tests 
in Part 2.
To further investigate the timing 
and the magnitude of the possible 
changes in lipid levels during the 
course of the current study. 
A mild elevation of serum 
triglycerides was observed in some 
participants in the bermekimab 
Phase 1 study.
2.2. Background; 11. 
References
Added 2 references for HiSCR.
References missed in original 
protocol and Amendment 1.
5.1. Inclusion 
Criteria; 5.2. 
Exclusion Criteria
Added IC #22 and EC #43 for BCG vaccination.
To correct an error (missing in 
original protocol and Amendment 
1).
5.2. Exclusion 
Criteria; 5.3. 
Lifestyle 
Considerations

Modified EC #12 to refer to IC #13.

Modified Criterion #3 to refer to IC #17.
To correct an error.
5.2. Exclusion 
Criteria
Added EC #44 for congenital conditions including 
Down syndrome.
To maintain consistent 
demographics.
5.3. Lifestyle 
Considerations
Modified lifestyle consideration #1
To be consistent with the labeling 
for adalimumab in Part 1.
6.7.1. Rescue 
Medication
Included the correct formulation of the rescue 
medication.
To correct an error in dosage form.
6.7.4. Analgesic 
Therapy
Modified use of NSAIDs. 
To provide flexibility in 
compliance with local labeling 
recommendations.
9.4.2.1. Primary 
Endpoint 
Changed the analysis strategy for addressing 
Intercurrent Event 3 (Discontinuation of study 
intervention due to COVID-19 related reasons 
[excluding COVID-19 infection]) to Treatment 
Policy strategy and combined it with Intercurrent 
Event 4.
Since COVID-19 can no longer be 
viewed as a temporary problem, all 
COVID-19 related reasons will be 
treated similarly to 
“Discontinuations of study 
intervention due to other reasons 
(excluding reasons indicative of 
lack of efficacy)” for which 


JNJ-77474462 (bermekimab)
Clinical Protocol 77474462HDS2001 Amendment 2
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Status: Approved,  Date: 12 August 2022
Section number
and Name
Description of Change
Brief Rationale
treatment policy strategy was used 
in the past.
10.6. Appendix 6
Updated examples of contraceptives not allowed as 
sole method of contraception during the study.
To be consistent with IC #17 and 
current guidance on contraception.
10.19.2. Follow up 
Assessments
Added guidelines for rechallenge.
For clarification.
Throughout the 
protocol
Minor grammatical, formatting, or spelling errors 
and inconsistencies were corrected.
Minor errors were noted.


JNJ-77474462 (bermekimab)
Clinical Protocol 77474462HDS2001 Amendment 2
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Status: Approved,  Date: 12 August 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1.
PROTOCOL SUMMARY ..................................................................................................................... 9
1.1.
Synopsis........................................................................................................................................... 9
1.2.
Schema .......................................................................................................................................... 18
1.3.
Schedules of Activities ................................................................................................................... 19
1.3.1.
Screening Through Week 16, Part 1 .......................................................................................... 20
1.3.2.
Screening Through Week 16, Part 2 .......................................................................................... 23
1.3.3.
Week 17 Though Week 36, Part 1 and Part 2............................................................................ 26
2.
INTRODUCTION................................................................................................................................ 28
2.1.
Study Rationale.............................................................................................................................. 28
2.2.
Background .................................................................................................................................... 29
2.3.
Benefit-Risk Assessment ............................................................................................................... 31
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 32
4.
STUDY DESIGN ................................................................................................................................ 36
4.1.
Overall Design................................................................................................................................ 36
4.2.
Scientific Rationale for Study Design............................................................................................. 38
4.2.1.
Study-Specific Ethical Design Considerations ........................................................................... 39
4.3.
Justification for Dose...................................................................................................................... 39
4.4.
End of Study Definition................................................................................................................... 41
5.
STUDY POPULATION ...................................................................................................................... 41
5.1.
Inclusion Criteria ............................................................................................................................ 41
5.2.
Exclusion Criteria ........................................................................................................................... 45
5.3.
Lifestyle Considerations................................................................................................................. 50
5.4.
Screen Failures .............................................................................................................................. 51
6.
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 52
6.1.
Study Interventions Administered .................................................................................................. 52
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 53
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 54
6.4.
Study Intervention Compliance...................................................................................................... 57
6.5.
Dose Modification........................................................................................................................... 57
6.6.
Treatment of Overdose .................................................................................................................. 57
6.7.
Concomitant Therapy..................................................................................................................... 58
6.7.1.
Rescue Medication ..................................................................................................................... 58
6.7.2.
Antiseptic Therapy...................................................................................................................... 59
6.7.3.
Wound Care................................................................................................................................ 59
6.7.4.
Analgesic Therapy...................................................................................................................... 59
6.7.5.
Prohibited Therapy ..................................................................................................................... 60
6.7.6.
Concomitant Corticosteroid use for Conditions Other than HS.................................................. 61
6.7.7.
Drugs Metabolized by Cytochrome P450................................................................................... 61
6.8.
Intervention After the End of the Study.......................................................................................... 61
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 61
7.1.
Discontinuation of Study Intervention ............................................................................................ 61
7.2.
Participant Discontinuation/Withdrawal From the Study................................................................ 63
7.2.1.
Withdrawal From the Use of Research Samples ....................................................................... 64
7.3.
Lost to Follow-up............................................................................................................................ 64


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 65
8.1.
Efficacy Assessments .................................................................................................................... 66
8.1.1.
Hidradenitis Suppurativa Investigator’s Global Assessment...................................................... 66
8.1.2.
Hidradenitis Suppurativa Activity and Severity Index ................................................................. 67
8.1.3.
Lesion Counts............................................................................................................................. 67
8.1.4.
Images of Skin Lesions............................................................................................................... 67
8.1.5.
Hurley Staging ............................................................................................................................ 67
8.1.6.
Hidradenitis Suppurativa Symptom Diary (HSSD) ..................................................................... 67
8.1.7.
Dermatological Life Quality Index (DLQI)................................................................................... 68
8.1.8.
Patient Global Impression of Change (PGIC) of Hidradenitis Suppurativa Severity.................. 68
8.1.9.
Patient Global Impression of Severity (PGIS) of Hidradenitis Suppurativa................................ 68
8.1.10.
Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29).................... 68
8.1.11.
HS Lesion Monitoring Using Medical Infrared Thermography.................................................... 68
8.2.
Safety Assessments....................................................................................................................... 69
8.2.1.
Physical Examinations................................................................................................................ 69
8.2.2.
Vital Signs................................................................................................................................... 69
8.2.3.
Electrocardiograms..................................................................................................................... 69
8.2.4.
Clinical Safety Laboratory Assessments .................................................................................... 70
8.2.5.
Concomitant Medication ............................................................................................................. 70
8.2.6.
Allergic Reactions ....................................................................................................................... 70
8.2.7.
Injection-site Reactions............................................................................................................... 70
8.2.8.
Tuberculosis Evaluation(s) ......................................................................................................... 70
8.2.8.1.
Initial Tuberculosis Evaluation................................................................................................. 70
8.2.8.2.
Ongoing Tuberculosis Evaluation............................................................................................ 71
8.3.
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 72
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information.................................................................................................................................. 73
8.3.2.
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 73
8.3.3.
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 74
8.3.4.
Regulatory Reporting Requirements for Serious Adverse Events and Anticipated 
Events......................................................................................................................................... 74
8.3.5.
Pregnancy................................................................................................................................... 75
8.3.6.
Adverse Events of Special Interest............................................................................................. 75
8.4.
Pharmacokinetics and Immunogenicity ......................................................................................... 75
8.5.
Genetics and Pharmacogenomics................................................................................................. 76
8.6.
Biomarkers ..................................................................................................................................... 76
8.6.1.
Skin Biomarkers.......................................................................................................................... 77
8.6.2.
Serum Biomarkers...................................................................................................................... 77
8.6.3.
Plasma Biomarkers..................................................................................................................... 77
8.6.4.
Flow Cytometry Analysis ............................................................................................................ 77
8.6.5.
Gene Expression Analysis in Whole Blood ................................................................................ 78
8.7.
Health Economics .......................................................................................................................... 78
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 78
9.1.
Statistical Hypotheses.................................................................................................................... 78
9.2.
Sample Size Determination ........................................................................................................... 78
9.3.
Populations for Analysis Sets ........................................................................................................ 81
9.4.
Statistical Analyses ........................................................................................................................ 82
9.4.1.
Statistical Methods...................................................................................................................... 82
9.4.2.
Efficacy Analyses........................................................................................................................ 82
9.4.2.1.
Primary Endpoint ..................................................................................................................... 82
9.4.2.1.1.
Primary Estimand 1.............................................................................................................. 82
9.4.2.1.2.
Primary Estimand 2.............................................................................................................. 83
9.4.2.1.3.
Primary Endpoint Analysis ................................................................................................... 84
9.4.2.2.
Secondary Endpoints .............................................................................................................. 85
9.4.2.3.
Exploratory Endpoints ............................................................................................................. 86
9.4.3.
Safety Analyses .......................................................................................................................... 87
9.4.4.
Other Analyses ........................................................................................................................... 88


JNJ-77474462 (bermekimab)
Clinical Protocol 77474462HDS2001 Amendment 2
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Status: Approved,  Date: 12 August 2022
9.5.
Interim Analysis.............................................................................................................................. 90
9.6.
Data Monitoring Committee ........................................................................................................... 90
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 92
10.1.
Appendix 1: Abbreviations ............................................................................................................. 92
10.2.
Appendix 2: Anticipated Events ..................................................................................................... 94
10.3.
Appendix 3: Clinical Laboratory Tests ........................................................................................... 95
10.4.
Appendix 4: Regulatory, Ethical, and Study Oversight Considerations......................................... 96
10.4.1.
Regulatory and Ethical Considerations ...................................................................................... 96
10.4.2.
Financial Disclosure.................................................................................................................... 99
10.4.3.
Informed Consent Process ......................................................................................................... 99
10.4.4.
Data Protection ......................................................................................................................... 100
10.4.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 101
10.4.6.
Committees Structure............................................................................................................... 101
10.4.7.
Publication Policy/Dissemination of Clinical Study Data .......................................................... 101
10.4.8.
Data Quality Assurance............................................................................................................ 103
10.4.9.
Case Report Form Completion................................................................................................. 103
10.4.10.
Source Documents ................................................................................................................... 104
10.4.11.
Monitoring ................................................................................................................................. 104
10.4.12.
On-Site Audits........................................................................................................................... 105
10.4.13.
Record Retention...................................................................................................................... 105
10.4.14.
Study and Site Start and Closure ............................................................................................. 106
10.5.
Appendix 5: Adverse Events, Serious Adverse Events, Product Quality Complaints, and 
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting............................................................................................................................... 107
10.5.1.
Adverse Event Definitions and Classifications ......................................................................... 107
10.5.2.
Attribution Definitions................................................................................................................ 108
10.5.3.
Severity Criteria ........................................................................................................................ 108
10.5.4.
Special Reporting Situations .................................................................................................... 108
10.5.5.
Procedures ............................................................................................................................... 109
10.5.6.
Product Quality Complaint Handling......................................................................................... 110
10.5.7.
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 111
10.6.
Appendix 6: Contraceptive Guidance .......................................................................................... 112
10.7.
Appendix 7: Hepatitis B Virus (HBV) Screening with HBV DNA Testing..................................... 115
10.8.
Appendix 8: Tuberculin Skin Testing ........................................................................................... 117
10.9.
Appendix 9: Hidradenitis Suppurativa Investigator’s Global Assessment ................................... 118
10.10.
Appendix 10: Hidradenitis Suppurativa Activity and Severity Index (HASI) ................................ 120
10.11.
Appendix 11: Hidradenitis Suppurativa Symptom Diary (HSSD) (7-Day Version) ...................... 121
10.12.
Appendix 12: Hidradenitis Suppurativa Symptom Diary (HSSD) (24-hour Version) ................... 123
10.13.
Appendix 13: Dermatology Life Quality Index.............................................................................. 125
10.14.
Appendix 14: Patient Global Impression of Change (PGIC) of Hidradenitis Suppurativa 
Severity ........................................................................................................................................ 127
10.15.
Appendix 15: Patient Global Impression of Severity (PGIS) of Hidradenitis Suppurativa........... 128
10.16.
Appendix 16: Patient-Reported Outcomes Measurement Information System-29...................... 129
10.17.
Appendix 17: HS Lesion Monitoring Using Imaging (Visible Light Photography and 
Medical Infrared Thermography................................................................................................... 132
10.18.
Appendix 18: Guidance on Study Conduct during the COVID-19 Pandemic.............................. 133
10.19.
Appendix 19: Liver Safety: Suggested Actions and Follow-up Assessments.............................. 135
10.19.1.
Stopping Algorithm ................................................................................................................... 135
10.19.2.
Follow up Assessments............................................................................................................ 135
10.20.
Appendix 20: Protocol Amendment History ................................................................................. 139
11.
REFERENCES................................................................................................................................. 142
INVESTIGATOR AGREEMENT ............................................................................................................... 144


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Status: Approved,  Date: 12 August 2022
LIST OF IN-TEXT TABLES AND FIGURES 
TABLES
Table 1:
Power to detect a treatment difference in HiSCR50 at Week 16 in Part 1............................... 80
Table 2:
Confidence interval for the treatment difference in HiSCR at Week 16 in Part 1..................... 80
Table 3: 
Power to detect a treatment difference in HiSCR50 at Week 12 Combining Part 1 and 
Part 2......................................................................................................................................... 81
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 18


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Status: Approved,  Date: 12 August 2022
1.
PROTOCOL SUMMARY
1.1.
Synopsis
Protocol number: 77474462HDS2001
A Phase 2a/2b, Multicenter, Randomized, Placebo and Active Comparator-controlled, Double-Blind, Dose-
ranging Study to Evaluate the Safety and Efficacy of Bermekimab (JNJ-77474462) for the Treatment of 
Subjects with Moderate to Severe Hidradenitis Suppurativa.
JNJ-77474462 (bermekimab) is a recombinant human immunoglobulin G1 kappa (IgG1k) monoclonal 
antibody (mAb) that binds with high affinity and selectivity for human interleukin-1 alpha (IL-1α) and is 
an effective blocker of IL-1α biological activity. Interleukin-1 alpha is a key mediator of sterile 
inflammatory responses. Skin is a significant reservoir of preformed IL-1α, and it has been postulated that 
IL-1α may play a role in the pathophysiology of multiple inflammatory skin disorders, including 
hidradenitis suppurativa (HS). 
Bermekimab has been investigated in dermatologic clinical studies and in other indications. Two Phase 2 
studies in atopic dermatitis (AD) and HS were recently completed.
Bermekimab was initially developed by XBiotech, Inc and is currently being developed by Janssen 
Research and Development, LLC (sponsor).
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the clinical efficacy of bermekimab in 
participants with moderate to severe HS.

Proportion of participants achieving 
HiSCR50 at Week 16 in Part 1.

Proportion of participants achieving 
HiSCR50 at Week 12 in Part 2.
Secondary

To evaluate the clinical efficacy of bermekimab in 
participants with moderate to severe HS.

Proportion of participants achieving 
HiSCR75 and HiSCR90 at Week 16 
in Part 1, and at Week 12 in Part 2.

Change from baseline in the abscess 
and inflammatory nodule (AN) count 
at Week 16 in Part 1, and at Week 12 
in Part 2.

Proportion of participants achieving 
at least 50%, 75%, 90%, and 100% 
reduction in total AN count at 
Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion of participants achieving 
an AN count of 0/1 and 0/1/2 at 
Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion of participants achieving 
complete elimination of abscesses at
Week 16 in Part 1, and at Week 12 in 


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Status: Approved,  Date: 12 August 2022
Objectives
Endpoints
Part 2 among those participants with 
abscesses at baseline.

Change in the number of abscesses 
from baseline to Week 16 in Part 1, 
and at Week 12 in Part 2.

Proportion of participants achieving 
complete elimination of draining 
fistulas at Week 16 in Part 1, and at 
Week 12 in Part 2 among those 
participants with draining fistulas at 
baseline.

Change in number of draining 
fistulas from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants achieving 
complete elimination of 
inflammatory nodules at Week 16 in 
Part 1, and at Week 12 in Part 2
among those participants with 
inflammatory nodules at baseline.

Change in number of inflammatory 
nodules from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Change of International Hidradenitis 
Suppurativa Severity Score System 
(IHS4) score from baseline to 
Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion of participants with HS-
Investigator’s Global Assessment 
(HS-IGA) score of inactive (0), 
almost inactive (1), or mild (2) and 
with at least 2-grade improvement 
relative to baseline at Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants with HS-
IGA score of inactive (0) or almost 
inactive (1) at Week 16 in Part 1, and 
at Week 12 in Part
2 among 
participants with HS-IGA score of 
moderate (3) or severe (4) at 
baseline.

To characterize additional patient-reported outcome 
efficacy measures of bermekimab in participants with 
moderate to severe HS. 

Change in Dermatology Life Quality 
Index (DLQI) score from baseline to 
Week 16 in Part 1, and at Week 12 in 
Part 2.


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Status: Approved,  Date: 12 August 2022
Objectives
Endpoints

Change in Hidradenitis Suppurativa 
Symptom Diary (HSSD-24h) score 
from baseline to Week 16 in Part 1, 
and at Week 12 in Part 2.

Change in pain scale score of HSSD-
24h from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Change in itch scale score of HSSD-
24h from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

To assess the safety and tolerability of bermekimab in 
participants with moderate to severe HS.

Number/proportion of participants 
with treatment-emergent adverse 
events (TEAEs).

Number/proportion of participants 
with 
treatment-emergent 
serious 
adverse events (SAEs).

Number/proportion of participants 
with abnormal safety laboratory 
values.

To 
evaluate 
the 
pharmacokinetics 
(PK) 
and 
immunogenicity of bermekimab in participants with 
moderate to severe HS. 

Bermekimab concentration will be 
summarized for treated participants 
over time.

The incidence of antibodies to 
bermekimab will be summarized.
Exploratory

To evaluate the clinical efficacy of bermekimab in 
participants with moderate to severe HS.

Change of Hidradenitis Suppurativa 
Area and Severity Index (HASI) 
score from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants achieving 
HiSCR50, HiSCR75, and HiSCR90 
over time.

Change from baseline in AN count 
over time.

Proportion of participants achieving 
at least 50%, 75%, 90%, and 100% 
reduction in total AN count over
time.

Change in the number of abscesses, 
draining fistulas, and inflammatory 
nodules from baseline over time.

Change of HASI score from baseline 
over time.


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
Objectives
Endpoints

Change of IHS4 score from baseline 
over time.

Proportion 
of 
participants 
with 
HS-IGA score of inactive (0), almost 
inactive (1), or mild (2) and with at 
least 2-grade improvement relative 
to baseline over time.

Proportion of participants with HS-
IGA score of inactive (0) or almost 
inactive (1) over
time among 
participants with HS-IGA score of 
moderate (3) or severe (4) at 
baseline.

Change 
in 
high-sensitivity 
C-reactive protein (hs-CRP) from 
baseline to Week 16 in Part 1 and 
from baseline to Week 12 in Part 2.

To characterize additional patient-reported outcome 
efficacy measures of bermekimab in participants with 
moderate to severe HS.

Change in DLQI score from baseline 
over time.

Change in Hidradenitis Suppurativa 
Symptom Diary (HSSD-24h) score 
from baseline over time.

Change in pain scale score of HSSD-
24h from baseline over time.

Change in itch scale score of HSSD-
24h from baseline over time.

The distribution of the Patient Global 
Impression of Change (PGIC) of HS 
at Week 16 in Part 1, and at Week 12
in Part 2.

The distribution of the Patient Global 
Impression of Severity (PGIS) of HS 
at Week 16 in Part 1, and at Week 12 
in Part 2. 

Change in PROMIS 29 total score 
and sub-scores from baseline to 
Week 16 in Part 1, and at Week 12 in 
Part 2 and over time.

Change in Hidradenitis Suppurativa 
Symptom Diary (HSSD-7d) score 
from baseline over time.

To assess the impact of treatment with bermekimab on 
selected biomarkers.

Changes in cellular and molecular 
biomarkers in skin and blood from 
baseline.


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
Hypothesis
The primary hypothesis of this study is that bermekimab is superior to placebo as assessed by the proportion 
of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 16 in Part 1, and 
at Week 12 in Part 2.
OVERALL DESIGN
This is a randomized, double-blind, placebo- and active-comparator-controlled, dose-ranging, multicenter 
study to assess the efficacy, safety, PK, and immunogenicity of subcutaneously (SC) administered 
bermekimab for the treatment of moderate to severe HS in adult participants. The participant population 
will comprise men and women ≥18 years of age, with HS, that is moderate to severe, Hurley Stage II or 
Hurley Stage III, and has been present for at least 1 year prior to the baseline visit as determined by the 
investigator through participant interview and/or review of the medical history. Participants must also have 
HS lesions present in at least 2 distinct anatomic areas, had an inadequate response to an adequate course 
of appropriate oral antibiotics for treatment of HS in the investigator’s opinion and have a total abscess and 
inflammatory nodule (AN) count of ≥5 at the screening and baseline visit. Participants 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, a dilute bleach bath, or a topical antiseptic wash 
containing chlorhexidine gluconate or benzoyl peroxide.
Part 1 of this study contains 4 study periods: Screening (Period 1), 16-week placebo-controlled period
(Period 2), 16-week cross over period (Period 3), and 4-week safety follow up (Period 4). Part 2 of this 
study also contains 4 study periods: Screening (Period 1), 12-week placebo-controlled period (Period 2), 
20-week cross over period (Period 3), and 4-week safety follow up (Period 4). A screening period will take 
approximately 6 weeks. At baseline, enrollment of this Phase 2a/Phase 2b design study will be divided in 
2 parts. Part 1 will enroll approximately 150 participants, and Part 2 will enroll approximately 100 or 150 
additional participants, depending on the number of dose regimens to be studied. Enrollment of Part 2 of 
the study will only begin after a positive benefit risk assessment is confirmed either at Interim Analysis 1 
or Interim Analysis 2. Therefore, a total number of approximately 250 or 300 participants will be enrolled 
in the study.
During Part 1 of the study, 150 participants will be randomized to receive bermekimab 1050 mg, 
adalimumab, or placebo in a 1:1:1 ratio. Two interim analyses are planned. The first interim analysis will 
occur after approximately 75 participants complete 16 weeks of treatment. The second interim analysis will 
occur when approximately 150 participants complete 16 weeks of treatment. The goal of the interim 
analyses is to assess efficacy and safety of bermekimab before enrollment of Part 2 of this study. 
The details of the planned interim analyses will be defined in a separate statistical analysis plan (SAP). In 
summary, if results from Interim Analysis 1 show a positive benefit-risk assessment for bermekimab, 
enrollment of Part 2 of this Phase 2a/2b design study will proceed. If results from Interim Analysis 1 are 
inconclusive, enrollment of Part 2 will only be initiated after results from Interim Analysis 2 confirm a 
positive benefit-risk assessment for bermekimab. If the results from Interim Analysis 1 meet the futility 
criteria, the totality of the data including other efficacy analyses provided for the first interim analysis will 
be reviewed, before the decision is made on whether to terminate the trial for futility. If futility criteria are 
met following the Interim Analysis 2, enrollment will remain paused while the sponsor considers whether 
to terminate the study at that point for insufficient efficacy, to resume enrollment as planned, or to resume 
the study with modification.
An internal Interim Analysis Committee (IAC) composed of members that are not involved with the clinical 
program will be established to review the interim data and recommend actions to the study team in 
accordance with the objectives of the interim analyses.
If a positive benefit-risk is observed in either the first or the second planned interim analysis based on data 
in Part 1, screening and randomization of participants will resume as planned in Part 2 of the study, with 


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
additional participants being randomized to receive placebo, bermekimab 1050 mg qw, bermekimab 
1050 mg qw through Week 11 and from Week 12, bermekimab 1050 mg q2w (bermekimab 1050 mg 
qw→q2w) or bermekimab 700 mg qw through Week 11 and from Week 12, bermekimab 700 mg q2w 
(bermekimab 700 mg qw→q2w), in a 1:1:2:2 ratio (approximately 25 participants randomized to receive 
bermekimab 1050 mg qw and placebo, respectively, and approximately 50 participants randomized to 
receive bermekimab 1050 mg qw→q2w and bermekimab 700 mg qw→q2w, respectively). Based on the 
interim analysis result, the bermekimab 700 mg qw→q2w arm may not be included in Part 2. Thus, Part 2 
will enroll approximately 100 or 150 participants, depending on the number of dose regimens to be studied.
During Study Period 3 (Weeks 16 to 32 in Part 1 and Weeks 12 to 32 in Part 2), the participants receiving 
placebo will crossover to receive bermekimab 1050 mg at Week 16 in Part 1 and Week 12 in Part 2 and 
weekly thereafter through Week 31. Participants receiving bermekimab will continue to receive their 
assigned treatment through Week 31.
All participants who complete Week 31 of the study will enter safety follow-up (Week 31 through 
Week 36). The total duration of study participation will be approximately 42 weeks.
In addition to the 2 interim analyses described above (database lock [DBL] is planned at the Interim 
Analysis 2 for Part 1), 2 planned DBLs will occur at Week 12 and at Week 36.
The end of study is considered as the last visit for the last participant in the study.
An external independent Data Monitoring Committee (iDMC), whose members are not directly involved 
in the conduct of Study 77474462HDS2001, will review unblinded safety data to ensure the safety of the 
participants enrolled in this study. A prespecified look at safety will be implemented after a minimum of 
12 participants have received 4 weekly doses. Furthermore, the iDMC will review the unblinded safety data 
at the time of the interim analysis and will be kept informed of any interim analysis results impacting the 
benefit-risk considerations for the study.
NUMBER OF PARTICIPANTS
Approximately 250 or 300 participants are targeted for enrollment in this study.
INTERVENTION GROUPS AND DURATION
Part 1:
Group 1: Placebo
Participants will receive 4 placebo SC injections at Week 0. Participants will receive 3 placebo SC 
injections at Week 1 and every week thereafter through Week 15. 
At Week 16, participants will cross over to receive 3 bermekimab 350 mg SC injections weekly through 
Week 31. 
Group 2: Adalimumab
Participants will receive 4 adalimumab 40 mg SC injections at Week 0. Participants will receive 3 placebo 
SC injections at Week 1. Participants will receive 2 adalimumab 40 mg SC injections and 1 placebo SC 
injection at Week 2. Participants will receive 3 placebo SC injections at Week 3. Participants will receive 
1 adalimumab 40 mg SC injection and 2 placebo SC injections at Week 4 and every week thereafter through 
Week 31.
Group 3: Bermekimab 1050 mg SC qw


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
Participants will receive 3 bermekimab 350 mg SC injections and 1 placebo SC injection at Week 0. 
Participants will receive 3 bermekimab 350 mg SC injections at Week 1 and every week thereafter through 
Week 31.
Part 2:
Group 1: Placebo
Participants will receive 3 placebo SC injections from Week 0 through Week 11. At Week 12, participants 
will cross over to receive 3 bermekimab 350 mg SC injections weekly through Week 31. 
Group 2: Bermekimab 1050 mg SC qw
Participants will receive 3 bermekimab 350 mg SC injections at Week 0 and every week thereafter through 
Week 31.
Group 3: Bermekimab 1050 mg SC qw→q2w
Participants will receive 3 bermekimab 350 mg SC injections at Week 0 and every week thereafter 
through Week 11. From Week 12, participants will receive 3 bermekimab 350 mg SC injections every 
other week thereafter through Week 30. During weeks in which bermekimab is not administered, 
participants will receive 3 placebo SC injections through Week 31.
Group 4: Bermekimab 700 mg SC qw→q2w
Participants will receive 2 bermekimab 350 mg SC injections and 1 placebo SC injection at Week 0 and 
every week thereafter through Week 11. From Week 12, participants will receive 2 bermekimab 350 mg 
SC and 1 placebo SC injection every other week thereafter through Week 30. During weeks in which 
bermekimab is not administered, participants will receive 3 placebo SC injections through Week 31.
Description of Interventions
The study intervention presentation to be used in this study is a sterile liquid formulation of 175 mg/mL of 
bermekimab in a prefilled syringe with an injectable volume of 2.0 mL (350 mg of bermekimab per 
syringe). Bermekimab will be manufactured and provided under the responsibility of the sponsor. Refer to 
the Investigator’s Brochure (IB) for a list of excipients.
Placebo and adalimumab will be provided centrally by the sponsor.
EFFICACY EVALUATIONS
Efficacy assessments (Hidradenitis Suppurativa Investigator’s Global Assessment [HS-IGA], lesion counts, 
Hurley Staging, Hidradenitis Suppurativa Symptom Diary [HSSD], Dermatological Life Quality Index 
[DLQI], Patient Global Impression of Change [PGIC] of Hidradenitis Suppurativa Severity, Hidradenitis 
Suppurativa Area and Severity Index (HASI), and Patient Global Impression of Severity [PGIS]) and 
Patient-Reported Outcomes Measurement Information System-29 [PROMIS-29] will be performed at visits 
according to the Schedules of Activities. 
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Venous blood samples will be collected for the measurement of serum bermekimab concentrations and 
detection of antibodies to bermekimab at the time points presented in the Schedule of Activities. Serum 
samples will also be collected at the final visit from participants who early terminate study participation.


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
BIOMARKER EVALUATIONS
Biomarker samples will be collected to evaluate the pharmacodynamics (PD) and mechanism of action of 
bermekimab or help to explain interindividual variability in clinical outcomes or may help to identify 
population subgroups that respond differently to the intervention.
PHARMACOGENOMIC (DNA) EVALUATIONS
A pharmacogenomic blood sample will be collected to allow for pharmacogenomic research, as necessary 
(where local regulations permit). Participation in the pharmacogenomic research is optional.
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, weight, concomitant medication review and observations for
injection-site reactions and/or allergic reactions.
STATISTICAL METHODS
Sample Size Determination
This study is designed to enroll approximately 250 or 300 participants, in order to provide sufficient data 
to have adequate power to detect a treatment difference for the proportion of participants achieving 
HiSCR50 at Week 16 between the bermekimab treatment group and the placebo group in Part 1 and at 
Week 12 between bermekimab treatment groups and placebo group combining Part 1 and Part 2.
The assumptions for the sample size and power calculations specified below were mainly based on the 
clinical data from the 77474462HDS2002 (PT-047) Phase 2 clinical study with reference from 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. 
The response rates observed in the 77474462HDS2002 (PT-047) study for HiSCR50 at Week 12/Week 16
were 55%/57% (bermekimab qw group), 44%/52% (bermekimab q2w group), and 44%/44% (placebo 
group), respectively. In addition, the HiSCR50 response rates in adalimumab Phase 3 Studies M11-313 and 
M11-810 at Week 12 were 42% vs 26% and 59% vs 28% in the adalimumab weekly group and placebo 
group, respectively.
Comparisons between treatment groups at Week 16 using Part 1 data (all comparisons are at a 2-sided 
type 1 error rate of 0.10).

For comparison between bermekimab with placebo using data from Part 1 only for the primary 
endpoint at Week 16, the study sample size provides 83% power to detect a 25% treatment 
difference (50% vs 25%) with 50 participants per arm.

Greater than 99% power to detect a 40% (75% vs 35%) difference between the bermekimab 
1050 mg treatment group and the placebo group with 50 participants per arm.

For comparison between adalimumab with placebo using data from Part 1 only for the primary 
endpoint, the study sample size provides 83% power to detect a 25% (50% vs 25%) treatment 
difference with 50 participants per arm.


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
No formal comparisons will be performed between the bermekimab 1050 mg qw group and the adalimumab 
group from Part 1, however the treatment difference and its 2-sided 80% CI for the primary endpoint at 
Week 16 between these 2 groups will be provided. A sample size of 50 participants in each of the treatment 
groups will produce a 2-sided 80% CI for the treatment difference with a width of approximately 29%.
Comparisons between treatment groups at Week 12 with combining Part 1 and Part 2 data
Assuming HiSCR50 response rates at Week 12 are 25% to 35% for placebo and 50% to 75% for the 
bermekimab groups, respectively; based on these assumptions, approximately 250 participants across Part 
1 and Part 2 are planned to be randomized to the placebo (n=75), bermekimab 700 mg qw to q2w (n=50), 
bermekimab 1050 mg qw to q2w (n=50), and bermekimab 1050 mg qw (n=75) treatment groups. 
Comparisons between the bermekimab groups and the placebo groups will be based on data combining Part 
1 and Part 2. 
For comparisons between bermekimab groups with placebo combining Part 1 and Part 2 for the primary 
endpoint at Week 12, the study sample size provides:

At least 87% power to detect a 25% treatment difference between the bermekimab 700 mg treatment 
groups (n=50) and the placebo group (n=75).

97% power to detect a 25% (50% vs 25%) treatment difference between the bermekimab 1050 mg
treatment group (n=125) and the placebo group (n=75). 

Greater than 99% power to detect a 40% (75% vs 35%) difference between the bermekimab 1050 mg 
treatment group (n=125) and the placebo group (n=75) or between 700 mg treatment groups (n=50) 
and the placebo group (n=75).
Efficacy Analysis
All randomized participants who received at least 1 administration 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.
In general, treatment comparisons for binary endpoints will be performed using a Cochran-Mantel-Haenszel 
(CMH) test stratified by baseline Hurley stage status. For continuous efficacy endpoints, treatment 
comparisons will be performed using a Mixed-Effect Model Repeated Measure (MMRM) model. The 
MMRM will include treatment, visit, baseline value for the corresponding efficacy endpoint, baseline 
Hurley stage status, baseline value by visit interaction, baseline Hurley stage status by visit interaction and 
the treatment-by-visit interaction, if applicable. The Least Square mean (LSmean) estimates and their 
corresponding 95% confidence interval (CI) will be provided at each time point. In addition, the estimates 
of LSmean difference and 95% CIs between treatment groups will be provided. 
In general, all statistical testing will be performed at a significance level of 0.05 (2-sided) unless otherwise 
specified. Nominal p-values will be displayed for all treatment comparisons.
Safety Analysis
Safety data, including but not limited to, AEs, SAEs, AEs leading to study intervention discontinuation, 
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.


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
1.2.
Schema
Figure 1:
Schematic Overview of the Study


JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
1.3.
Schedules of Activities 
Two Schedules of Activities (SoAs) are presented below, one for the study period from screening 
through Week 16 and the second from Week 17 through Week 36.






JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
Abbreviations: DLQI=Dermatological Life Quality Index; DNA=deoxyribonucleic acid; ECG=electrocardiogram; HASI=Hidradenitis Suppurativa Activity and 
Severity Index; HIV=human immunodeficiency virus; HS-IGA=Hidradenitis Suppurativa Investigator’s Global Assessment; HSSD-24h=Hidradenitis Suppurativa 
Symptom Diary-24-hour version; HSSD-7d=Hidradenitis Suppurativa Symptom Diary-7-day version; PBMC=peripheral blood mononuclear cells; PGIC=Patient 
Global Impression of Change; PGIS=Patient Global Impression of Severity; PK=pharmacokinetics; PROMIS-29=Patient-reported Outcomes Measurement Information 
System-29; RNA=ribonucleic acid; TB=tuberculosis.
Footnotes:
a.
The screening visit should occur no more than 6 weeks prior to and no less than 7 days before the Week 0 visit.
b.
Study visit dates in Weeks 1 through 32 must be calculated from the first study intervention administration visit in Week 0. Visit and study intervention administrations should 
occur within +/-3 days of scheduled visit.
c.
All study procedures and evaluations are to be completed before study intervention is administered except where otherwise indicated.
d.
Must be signed before first study-related activity. Separate informed consents are required for participants who chose to participate in the optional biomarkers, optional imaging, 
and optional pharmacogenetics substudies.
e.
Study intervention administrations must occur no less than 4 days apart.
f.
Women of childbearing potential must have a negative pregnancy test result before randomization and before receiving study intervention at all study intervention administration 
visits. This assessment can be performed any other time during the study visit including prior to patient-reported outcome (PRO) collection.
g.
All PROs should be collected during the study visit prior to all other assessments, unless otherwise specified
h.
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
i.
For all visits where study intervention will be administrated, all blood samples should be collected prior to study intervention administration for evaluation of serum 
concentration of bermekimab and/or antibodies to bermekimab. 
j.
Participants who terminated study participation early should have a safety follow-up visit 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
k.
An additional visit is necessary such that a random venous blood sample for population PK analysis will be collected from all participants on any day between Weeks 2 to 12, 
except on the days of the scheduled study visits. Additionally, this blood sample must be collected at least 24 hours prior to or after the actual time of study intervention 
administration. Each population PK serum sample will be divided into 2 aliquots: 1 for serum concentration of bermekimab and a back-up.
l.
Blood sample will be taken pre-dose.
m.
Participation is optional.
n.
The pharmacogenomic (DNA) sample should be collected at the specified time point; however, if necessary, it may be collected at a later time point without constituting a 
protocol deviation. Blood samples for pharmacogenomics will be collected only from participants who give informed consent indicating willingness to participate in this optional 
component of the study.
o.
Skin biopsies to be collected pre-dose. At Week 0, lesional (nodule) and non-lesional skin samples will be collected. At Week 16 and/or Week 32, lesional (nodule) skin samples 
will be collected.
p.
Ultrasound guided deep tunnel biopsy will be collected at Week 16 and Week 32 if available.
q.
Exudate will be collected if draining fistulas are present.
r.
Skin swab will be collected at the time of skin biopsy. Two swabs will be collected – one from the lesional nodule from where skin biopsy will be taken and the second one from 
the adjacent non-lesional area, 10 cm away from the lesional margin area.
s.
FibroTx Patch will be collected pre-dose. Lesional and non-lesional skin will be sampled at baseline. Lesional skin will be sampled at Week 6 and Week 16.
t.
Daily administration.






JNJ-77474462 (bermekimab)
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Status: Approved,  Date: 12 August 2022
From Screening through Week 16
  Period
Screeninga
Blinded, Placebo-controlled Period
Blinded Active 
Treatment Phase
Weekb
-6 to 0
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Skin Swab for 
microbiomem,r
X
X
Abbreviations: DLQI=Dermatological Life Quality Index; DNA=deoxyribonucleic acid; ECG=electrocardiogram; HASI=Hidradenitis Suppurativa Activity and 
Severity Index; HIV=human immunodeficiency virus; HS-IGA=Hidradenitis Suppurativa Investigator’s Global Assessment; HSSD-24h=Hidradenitis Suppurativa 
Symptom Diary-24-hour version; HSSD-7d=Hidradenitis Suppurativa Symptom Diary-7-day version; PBMC=peripheral blood mononuclear cells; PGIC=Patient 
Global Impression of Change; PGIS=Patient Global Impression of Severity; PK=pharmacokinetics; PROMIS-29=Patient-reported Outcomes Measurement Information 
System-29; RNA=ribonucleic acid; TB=tuberculosis.
Footnotes:
a.
The screening visit should occur no more than 6 weeks prior to and no less than 7 days before the Week 0 visit.
b.
Study visit dates in Weeks 1 through 32 must be calculated from the first study intervention administration visit in Week 0. Visit and study intervention administrations should 
occur within +/-3 days of scheduled visit.
c.
All study procedures and evaluations are to be completed before study intervention is administered except where otherwise indicated.
d.
Must be signed before first study-related activity. Separate informed consents are required for participants who chose to participate in the optional biomarkers, optional imaging, 
and optional pharmacogenetics substudies.
e.
Study intervention administrations must occur no less than 4 days apart.
f.
Women of childbearing potential must have a negative pregnancy test result before randomization and before receiving study intervention at all study intervention administration 
visits. This assessment can be performed any other time during the study visit including prior to patient-reported outcome (PRO) collection.
g.
All PROs should be collected during the study visit prior to all other assessments, unless otherwise specified
h.
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
i.
For all visits where study intervention will be administrated, all blood samples should be collected prior to study intervention administration for evaluation of serum 
concentration of bermekimab and/or antibodies to bermekimab. 
j.
Participants who terminated study participation early should have a safety follow-up visit 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
k.
An additional visit is necessary such that a random venous blood sample for population PK analysis will be collected from all participants on any day between Weeks 2 to 12, 
except on the days of the scheduled study visits. Additionally, this blood sample must be collected at least 24 hours prior to or after the actual time of study intervention 
administration. Each population PK serum sample will be divided into 2 aliquots: 1 for serum concentration of bermekimab and a back-up.
l.
Blood sample will be taken pre-dose.
m.
Participation is optional.
n.
The pharmacogenomic (DNA) sample should be collected at the specified time point; however, if necessary, it may be collected at a later time point without constituting a 
protocol deviation. Blood samples for pharmacogenomics will be collected only from participants who give informed consent indicating willingness to participate in this optional 
component of the study.
o.
Skin biopsies to be collected pre-dose. At Week 0, lesional (nodule) and non-lesional skin samples will be collected. At Week 12 and/or Week 32, lesional (nodule) skin samples 
will be collected.
p.
Ultrasound guided deep tunnel biopsy will be collected at Week 12 and Week 32 if available.
q.
Exudate will be collected if draining fistulas are present.
r.
Skin swab will be collected at the time of skin biopsy. Two swabs will be collected – one from the lesional nodule from where skin biopsy will be taken and the second one from 
the adjacent non-lesional area, 10 cm away from the lesional margin area.
s.
FibroTx Patch will be collected pre-dose. Lesional and non-lesional skin will be sampled at baseline. Lesional skin will be sampled at Week 6 and Week 12.
t.
Daily administration.






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2.
INTRODUCTION
JNJ-77474462 (bermekimab) is a recombinant human immunoglobulin G1 kappa (IgG1k) 
monoclonal antibody (mAb) that binds with high affinity and selectivity for human interleukin-1 
alpha (IL-1α) and is an effective blocker of IL-1α biological activity. Interleukin-1 alpha is a key 
mediator of sterile inflammatory responses. Skin is a significant reservoir of preformed IL-1α, and 
it has been postulated that IL-1α may play a role in the pathophysiology of multiple inflammatory 
skin disorders, including hidradenitis suppurativa (HS). 
Bermekimab is not currently approved for any therapeutic indications. Fourteen clinical studies to 
date have been conducted using bermekimab including 2 recently completed studies in HS and 
atopic dermatitis (AD). Bermekimab has previous been administered intravenously (IV) at doses 
ranging from 0.25 mg/kg to 7.5 mg/kg and subcutaneously (SC) at doses from 100 mg to 800 mg. 
For the most comprehensive nonclinical and clinical information regarding bermekimab, refer to 
the latest version of the Investigator's Brochure (IB) for bermekimab.
The term “study intervention” throughout the protocol, refers to bermekimab as defined in 
Section 6.1, Study Interventions Administered. 
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.
The term "participant" throughout the protocol refers to the common term "subject".
2.1.
Study Rationale
This is a Phase 2a/2b randomized, placebo- and active-comparator-controlled, parallel-group, 
multicenter, dose-ranging study to assess the safety and efficacy of bermekimab in adult 
participants with moderate to severe HS by means of: 

Assessing efficacy across all treatment groups through Week 16 in Part 1, and through 
Week 12 combining Part 1 and Part 2.

Evaluating the longer-term efficacy resulting from the SC dose regimens of bermekimab 
through 32 weeks.

Evaluating safety and tolerability data for bermekimab in these HS participants.
In addition, this study will evaluate the pharmacokinetics (PK), immunogenicity and 
pharmacodynamics (PD) of bermekimab therapy in participants with HS.
The scientific rationale in support of the study as well as relevant background information on 
nonclinical and clinical studies of bermekimab are summarized in Section 2.2.
An overview of the protocol design and supportive rationale is described in Section 4.


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2.2.
Background
Hidradenitis suppurativa (HS) is a chronic skin disease of unclear etiology that affects 1% to 4% 
of the general population (Jemec 2012, Margesson 2014, Vekic 2018b, Zouboulis 2018). HS 
typically manifests as recurrent, inflamed, tender, SC nodules that are generally restricted to the 
axillary, inguinal, and anogenital regions (Jemec 2012, Margesson 2014, Vekic 2018b). 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 (Jemec 2012, Margesson 2014, Vekic 2018b). 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. Disease onset is typically after puberty and 
women are affected 2 to 5 times more commonly than men (Jemec 2012, Margesson 2014).
Multiple factors including genetics, cigarette smoking, and obesity are believed to predispose a 
person to HS (Jemec 2012, Zouboulis 2018).
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 (Zouboulis 2018). Patients with HS experience considerable impact 
on activities of daily living, work/school attendance and productivity, physical activities, and 
emotional state (Vekic 2018a).
The biologic anti-TNF inhibitor adalimumab (Humira®) has been approved to treat moderate to 
severe HS, but even this agent has not shown satisfactory treatment effects in many patients. 
Across 2 Phase 3 studies, the primary endpoint of Hidradenitis Suppurativa Clinical Response 
(HiSCR) 50, 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, was achieved in 42% and 59%, respectively, of adalimumab-treated patients compared 
with 26% and 28%, respectively, of placebo-treated patients (Ingram 2016; Kimball 2014; Kimball 
2016a; Kimball 2016b; Okun 2013). Therefore, a substantial, unmet medical need exists for safe 
and more effective HS management options with alternative mechanisms of action.
Bermekimab is a recombinant human IgG1 mAb that binds the cytokine IL-1α with high affinity 
and is an effective blocker of IL-1α biological activity. IL-1α is a key mediator of sterile 
inflammatory responses and has been implicated in the pathology of advanced cancer, 
cardiovascular disease, and rheumatologic disease. Clinical evidence generated to date suggests 
that targeting IL-1α may be an effective treatment in undermining the inflammatory process that 
drives a wide array of diseases, including dermatologic conditions.
To date, there have been 14 clinical studies using bermekimab in a wide range of therapeutic areas. 
Bermekimab has been studied in both IV and SC formulations in several dose levels and dosing 
schedules to evaluate safety and efficacy.
Nonclinical Studies
A comprehensive overview of the nonclinical development program for bermekimab is available 
in Section 3 of the latest version of the bermekimab IB.


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This section provides a summary of the sponsor's assessment of how the overall nonclinical data 
support the safety of the proposed dosing for bermekimab in this Phase 2 program in HS. 
Bermekimab binds with high affinity and specificity to human IL-1α with a dissociation constant
(KD) of 0.059 nM. No binding to human IL-1β or interleukin-1 receptor antagonist (IL-1Ra) was 
detected up to the highest concentrations tested. In addition, bermekimab was shown to effectively 
neutralize the ability of human IL-1α to induce endothelial cell expression of adhesion molecules 
and fibroblast expression of interleukin-6 (IL-6). Bermekimab was bound by cynomolgus monkey 
IL-1α with a KD of 1.3 nM and did not bind with mouse, rat, or pig IL-1α at the highest 
concentrations tested.
A 1-month repeat intraperitoneal dose mouse study tested bermekimab up to 3 doses of 
312 mg/kg/week. No treatment-related adverse effects were observed.
The potential toxicity of bermekimab was also evaluated in a 6-week, repeat IV and SC exploratory 
and tolerability study with toxicokinetics in female cynomolgus monkeys, at dose levels of 0, 50 
(IV), 300 (IV), and 300 (SC) mg/kg/week for 6 weeks. The toxicology evaluations included 
mortality, clinical observation, body weight, food consumption, veterinary physical examination, 
ophthalmology, clinical pathology (hematology, chemistry, coagulation and urinalysis), organ 
weight, gross necropsy and histopathology. In addition, safety pharmacology and physiology 
endpoints (electrocardiogram [ECG], blood pressure, heart rate, respiratory rate, and body 
temperature) were evaluated. There was a transient decrease in blood pressure only at the high 
dose for both IV and SC administrations on Day 6 and the values returned to baseline at the end 
of dosing period (Day 37). There were no other treatment-related findings at any dose levels. The 
no observed adverse effect level (NOAEL) was 300 mg/kg for both IV and SC administrations. At 
the NOAEL dose, the exposures Cmax and AUC for IV administration were 9050 µg/mL and
26300 µg·day/mL respectively and Cmax and AUC for SC administration were 4480 µg/mL and 
22800 µg·day/mL respectively following dosing on Day 36.
Clinical Studies
Five Phase 2 studies sponsored by XBiotech have been completed in dermatologic indications 
(psoriasis 
[NCT01384630], 
acne 
vulgaris 
[NCT01474798], 
pyoderma 
gangrenosum 
[NCT01965613], AD [NCT03496974], and HS [NCT03512275]), along with one investigator 
sponsored study in HS.
The investigator-initiated Phase 2 randomized-controlled study among patients not eligible for
treatment 
with
adalimumab 
(EudraCT 
number 
2015-002321-20; 
ClinicalTrials.gov 
NCT02643654) was first completed and showed promising results for activity of bermekimab in 
HS. Twenty patients with severe HS and with either primary or secondary failure of previous anti-
TNF agents, or who were unwilling to receive SC adalimumab treatment, were randomly allocated 
(1:1) to receive, in a blinded fashion, every other week treatment with placebo or bermekimab at 
a dose of 7.5 mg/kg IV. Treatment was administered intravenously for 12 weeks. The primary 
efficacy endpoint was the HiSCR50 score, which is defined as achieving at least a 50% reduction 
in the total nodule and abscess counts with no worsening in abscess or draining fistulae count, that 


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was achieved among 10% of patients allocated to placebo and 60% of patients allocated to 
bermekimab. The odds ratio for positive HiSCR50 after 12 weeks of treatment was 13.50 (95% 
confidence intervals [CIs] 1.19-152.51, p=0.035; Kanni, 2018).
Data from XBiotech’s 2018-PT045 open-label Phase 2 study of bermekimab treating HS 
corroborated the positive results generated from the investigator led study. Twenty-four patients
who had failed previous anti-TNF treatment (Group A) and 18 patients with no prior treatment 
with anti-TNF treatment (Group B) were enrolled into the study and received 400 mg bermekimab 
SC weekly. A HiSCR50 response at Week 12 was again used as the primary efficacy endpoint. At 
Week 12, HiSCR50 was achieved in 63% of patients in Group A, and 61% of in Group B. In 
addition to patients achieving a meaningful clinical response, patients also experienced a marked 
reduction in pain, with Group A patients reporting a 54% reduction in pain and Group B Patients 
reports a 64% reduction in pain (Gottlieb 2020).
Data from a recently completed Phase 2 study, 77474462HDS2002 (PT-047) have recently 
become available,
and were used to inform
the dose regimens of this study.
Study 77474462HDS2002 (PT-047) is a double-blind, placebo-controlled, study of bermekimab 
in moderate to severe adult HS patients. The primary endpoint of this trial was the proportion of 
patients achieving HiSCR50 at Week 12. The primary endpoint from this trial was analyzed at the 
Week 16 database lock (DBL). Bermekimab 400 mg weekly and 400 mg q2w were both safe and 
well-tolerated in participants with HS through Week 36. A numerically higher response rate was 
observed in the bermekimab 400 mg weekly group relative to the placebo group on the primary 
endpoint of HiSCR50 at Week 12. Statistical superiority, however, was not achieved. At Week 12,
a numerically greater proportion of treated subjects randomized to bermekimab 400 mg q2w and 
400 mg qw groups achieved a HiSCR50 compared with placebo. These results suggest that 
bermekimab 400 mg weekly and q2w may have modest efficacy in participants with HS.
In addition, in clinical studies completed to date in psoriasis, acne, pyoderma gangrenosum, and 
AD, bermekimab was well-tolerated. For more information regarding completed clinical studies, 
see the IB. 
2.3.
Benefit-Risk Assessment
Based on the available data and the proposed safety measures discussed below, the risks of the 
dose regimens of bermekimab to be investigated in this protocol appear to be acceptable relative
to the potential benefit.
Bermekimab has undergone previous clinical development in diseases such as psoriasis, AD, HS, 
acne vulgaris, pyoderma gangrenosum and cancer, as summarized in the latest version of the IB. 
The collective efficacy and safety results of the Phase 1 and Phase 2 clinical studies in healthy 
volunteers and patients in dermatologic indications have indicated a favorable benefit-risk profile 
for further bermekimab development to date. In addition, nonclinical evidence that IL-1a may be 
an important component for inducing chronic skin inflammation (Abdel-Razzak 1993, Murphy 
2000). 


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Unblinded safety will be evaluated on an ongoing basis throughout this study by an independent
Data Monitoring Committee (iDMC), in addition to the standard safety oversight performed by 
the sponsor.
The risks for bermekimab are infections, hypersensitivity reactions and injection-site reactions. 
More detailed information about the known and expected benefits and risks of bermekimab may 
be found in the IB.
The important risks for adalimumab are: 
1.
serious infections which may be fatal and include opportunistic infections such as tuberculosis 
(TB) and invasive fungal infection (patients over 65 years of age were found to be at higher 
risk for infection);
2.
malignancies which may be fatal (including lymphoma and hepatosplenic T-cell lymphoma);
3.
anaphylaxis or serious allergic reactions; 
4.
Hepatitis B virus (HBV) reactivation; 
5.
demyelinating disease; 
6.
cytopenias and pancytopenia; 
7.
heart failure;
8.
Lupus-like syndrome;
9.
Concomitant administration of adalimumab with anakinra (human interleukin-1 receptor 
antagonist) is not recommended based on the possible increased risk for infections, including 
serious infections which were observed with anakinra  and etanercept (another TNF-blocker) 
studies (Humira SmPC 2021). Bermekimab has not been evaluated in clinical studies with 
TNF blockers.
The safety plan for bermekimab and adalimumab includes monitoring of AEs and safety laboratory
results, using sites adequately prepared for managing hypersensitivity reactions and patient 
education for recognizing signs of a serious hypersensitivity reaction such as anaphylaxis. In 
addition, participants will be screened for TB prior to study entry (Section 8.2.8.1) and receive 
regular ongoing evaluation (Section 8.2.8.2).
Taking into account the measures taken to minimize risk to participants of this study, the potential 
risks identified in association with bermekimab are justified by the anticipated benefits that may 
be afforded to participants with HS.
3.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the clinical efficacy of bermekimab in 
participants with moderate to severe HS.

Proportion of participants achieving 
HiSCR50 at Week 16 in Part 1.

Proportion of participants achieving 
HiSCR50 at Week 12 in Part 2.


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Objectives
Endpoints
Secondary

To evaluate the clinical efficacy of bermekimab in 
participants with moderate to severe HS.

Proportion of participants achieving 
HiSCR75 and HiSCR90 at Week 16 
in Part 1, and at Week 12 in Part 2.

Change from baseline in the abscess 
and inflammatory nodule (AN) count 
at Week 16 in Part 1, and at Week 12 
in Part 2.

Proportion of participants achieving 
at least 50%, 75%, 90%, and 100% 
reduction in total AN count at 
Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion of participants achieving 
an AN count of 0/1 and 0/1/2 at 
Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion of participants achieving 
complete elimination of abscesses at 
Week 16 in Part 1, and at Week 12 in 
Part 2 among those participants with 
abscesses at baseline.

Change in the number of abscesses 
from baseline to Week 16 in Part 1, 
and at Week 12 in Part 2.

Proportion of participants achieving
complete elimination of draining 
fistulas at Week 16 in Part 1, and at 
Week 12 in Part 2 among those 
participants with draining fistulas at 
baseline.

Change in number of draining 
fistulas from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants achieving 
complete 
elimination 
of 
inflammatory nodules at Week 16 in 
Part 1, and at Week 12 in Part 2 
among 
those 
participants 
with 
inflammatory nodules at baseline.

Change in number of inflammatory 
nodules from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Change of International Hidradenitis 
Suppurativa Severity Score System 
(IHS4) score from baseline to 


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Objectives
Endpoints
Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion of participants with HS-
Investigator’s Global Assessment 
(HS-IGA) score of inactive (0), 
almost inactive (1), or mild (2) and 
with at least 2-grade improvement 
relative to baseline at Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants with HS-
IGA score of inactive (0) or almost 
inactive (1) at Week 16 in Part 1, and 
at Week 12 in Part
2 among 
participants with HS-IGA score of 
moderate (3) or severe (4) at 
baseline.

To characterize additional patient-reported outcome 
efficacy measures of bermekimab in participants with 
moderate to severe HS.

Change in Dermatology Life Quality 
Index (DLQI) score from baseline to
Week 16 in Part 1, and at Week 12 in 
Part 2.

Change in Hidradenitis Suppurativa 
Symptom Diary (HSSD-24h) score 
from baseline to Week 16 in Part 1, 
and at Week 12 in Part 2.

Change in pain scale score of HSSD-
24h from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Change in itch scale score of HSSD-
24h from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

To assess the safety and tolerability of bermekimab in 
participants with moderate to severe HS.

Number/proportion of participants 
with treatment-emergent adverse 
events (TEAEs).

Number/proportion of participants 
with 
treatment-emergent 
serious 
adverse events (SAEs).

Number/proportion of participants 
with abnormal safety laboratory 
values.

To 
evaluate 
the 
pharmacokinetics 
(PK) 
and 
immunogenicity of bermekimab in participants with 
moderate to severe HS. 

Bermekimab concentration will be 
summarized for treated participants 
over time.

The incidence of antibodies to 
bermekimab will be summarized.


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Objectives
Endpoints
Exploratory

To evaluate the clinical efficacy of bermekimab in 
participants with moderate to severe HS.

Change of Hidradenitis Suppurativa 
Area and Severity Index (HASI)
score from baseline to Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants achieving 
HiSCR50, HiSCR75, and HiSCR90 
over time.

Change from baseline in AN count 
over time.

Proportion of participants achieving 
at least 50%, 75%, 90%, and 100% 
reduction in total AN count over 
time.

Change in the number of abscesses, 
draining fistulas, and inflammatory 
nodules from baseline over time.

Change of HASI score from baseline 
over time.

Change of IHS4 score from baseline 
over time.

Proportion 
of 
participants 
with 
HS-IGA score of inactive (0), almost 
inactive (1), or mild (2) and with at 
least 2-grade improvement relative 
to baseline over time.

Proportion of participants with HS-
IGA score of inactive (0) or almost 
inactive (1)
over time
among 
participants with HS-IGA score of 
moderate (3) or severe (4) at 
baseline.

Change 
in 
high-sensitivity 
C-reactive protein (hs-CRP) from 
baseline to Week 16 in Part 1 and 
from baseline to Week 12 in Part 2.

To characterize additional patient-reported outcome 
efficacy measures of bermekimab in participants with 
moderate to severe HS.

Change in DLQI score from baseline 
over time.

Change in Hidradenitis Suppurativa 
Symptom Diary (HSSD-24h) score 
from baseline over time.

Change in pain scale score of HSSD-
24h from baseline over time.


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Objectives
Endpoints

Change in itch scale score of HSSD-
24h from baseline over time.

The distribution of the Patient Global 
Impression of Change (PGIC) of HS 
at Week 16 in Part 1, and at Week 12
in Part 2.

The distribution of the Patient Global 
Impression of Severity (PGIS) of HS 
at Week 16 in Part 1, and at Week 12 
in Part 2. 

Change in PROMIS 29 total score 
and sub-scores from baseline to 
Week 16 in Part 1, and at Week 12 in 
Part 2 and over time.

Change in Hidradenitis Suppurativa 
Symptom Diary (HSSD-7d) score 
from baseline over time.

To assess the impact of treatment with bermekimab on 
selected biomarkers.

Changes in cellular and molecular 
biomarkers in skin and blood from 
baseline.
Refer to Section 8, for evaluations related to endpoints.
HYPOTHESIS
The primary hypothesis of this study is that bermekimab is superior to placebo as assessed by the 
proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at 
Week 16 in Part 1, and at Week 12 in Part 2.
4.
STUDY DESIGN
4.1.
Overall Design
This is a randomized, double-blind, placebo- and active-comparator-controlled, dose-ranging,
multicenter study to assess the efficacy, safety, PK, and immunogenicity of SC administered 
bermekimab 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
and are Hurley Stage II or Hurley Stage III as determined by the investigator.
This study will employ a Phase 2a/2b design, in which the decision to proceed to the Phase 2b 
portion of the study will depend on the results of the interim analyses. 
Part 1 of this study contains 4 study periods: Screening (Period 1), 16-week placebo-controlled 
period (Period 2), 16-week cross over period (Period 3), and 4-week safety follow up (Period 4). 
Part 2 of this study also contains 4 study periods: Screening (Period 1), 12-week placebo-controlled 
period (Period 2), 20-week cross over period (Period 3), and 4-week safety follow up (Period 4). 


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A screening period will take approximately 6 weeks. Enrollment of this Phase 2a/Phase 2b design 
study will be divided in 2 parts. Part 1 will enroll approximately 150 participants, and Part 2 will 
enroll approximately 100 or 150 additional participants, depending on the number of dose 
regimens to be studied. Enrollment of Part 2 of the study will only begin after a positive benefit 
risk assessment is confirmed either at Interim Analysis 1 or Interim Analysis 2. Therefore, a total 
number of approximately 250 or 300 participants will be enrolled in the study.
During Part 1 of the study, 150 participants will be randomized to receive bermekimab 1050 mg, 
adalimumab, or placebo in a 1:1:1 ratio. Two interim analyses are planned. The first interim 
analysis will occur after approximately 75 participants complete 16 weeks of treatment. The 
second interim analysis will occur when approximately 150 participants complete 16 weeks of 
treatment. The goal of the interim analyses is to assess efficacy and safety of bermekimab at the 
doses evaluated prior to enrollment of Part 2 of this study. 
The details of the planned interim analyses will be defined in a separate statistical analysis plan 
(SAP). In summary, if results from Interim Analysis 1 show a positive benefit-risk assessment for 
bermekimab, enrollment of Part 2 of this Phase 2a/2b design study will proceed. If results from 
Interim Analysis 1 are inconclusive, enrollment of Part 2 will only be initiated after results from 
Interim Analysis 2 confirm a positive benefit-risk assessment for bermekimab. If the results from 
interim analysis 1 meet the futility criteria, the totality of the data including other efficacy analyses 
provided for the first interim analysis will be reviewed before the decision is made on whether to 
terminate the trial for futility. If futility criteria are met following the Interim Analysis 2, 
enrollment will remain paused while the sponsor considers whether to terminate the study at that 
point for insufficient efficacy, to resume enrollment as planned, or to resume the study with 
modification.
An internal Interim Analysis Committee (IAC) composed of members that are not involved with 
the clinical program will be established to review the interim data and recommend actions to the 
study team in accordance with the objectives of the interim analyses. Refer to Section 9.5 for 
details. 
If a positive benefit-risk is observed in either the first or the second planned interim analysis based 
on data in Part 1, screening and randomization of participants will resume as planned in Part 2 of 
the study, with additional participants being randomized to receive placebo, bermekimab 1050 mg
qw, bermekimab 1050 mg qw through Week 11 and from Week 12, bermekimab 1050 mg q2w 
(bermekimab 1050 mg qw→q2w) or bermekimab 700 mg qw through Week 11 and from 
Week 12, bermekimab 700 mg q2w (bermekimab 700 mg qw→q2w), in a 1:1:2:2 ratio 
(approximately 25 participants randomized to receive bermekimab 1050 mg qw and placebo, 
respectively, and approximately 50 participants randomized to receive bermekimab 1050 mg 
qw→q2w and bermekimab 700 mg qw→q2w, respectively). Based on the interim analysis result, 
bermekimab 700 mg qw→q2w arm may not be included in Part 2. Thus, Part 2 will enroll 
approximately 100 or 150 participants, depending on the number of dose regimens to be studied.
During Study Period 3 (Weeks 16 to 32 in Part 1 and Weeks 12 to 32 in Part 2), the participants 
receiving placebo will crossover to receive bermekimab 1050 mg at Week 16 in Part 1 and 


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Week 12 in Part 2 and weekly thereafter through Week 31. Participants receiving bermekimab will 
continue to receive their assigned treatment through Week 31. 
All participants who complete Week 31 of the study will enter safety follow-up (Week 31 through 
Week 36). The total duration of study participation will be approximately 42 weeks.
In addition to the 2 interim analyses described above (DBL is planned at the Interim Analysis 2
for Part 1), 2 planned DBLs will occur at Week 12 and at Week 36.
The end of study is considered as the last visit for the last participant in the study.
Efficacy assessments (Hidradenitis Suppurativa Investigator’s Global Assessment [HS-IGA], 
lesion counts, Hurley Staging, Hidradenitis Suppurativa Symptom Diary [HSSD], Dermatological 
Life Quality Index [DLQI], Patient Global Impression of Change [PGIC] of Hidradenitis 
Suppurativa Severity, Hidradenitis Suppurativa Area and Severity Index (HASI), and Patient 
Global Impression of Severity [PGIS]) and Patient-Reported Outcomes Measurement Information 
System-29 [PROMIS-29] will be performed at visits according to the SoA. Serum samples for PK, 
immunogenicity and biomarker analyses will be collected at the time points in the SoA
(Section 1.3).
An external independent Data Monitoring Committee (iDMC), whose members are not directly 
involved in the conduct of Study 77474462HDS2001, will review unblinded safety data to ensure 
the safety of the participants enrolled in this study. A prespecified look at safety will be 
implemented after a minimum of 12 participants have received 4 weekly doses. Furthermore, the 
iDMC will review the unblinded safety data at the time of the interim analysis and will be kept 
informed of any interim analysis results impacting the benefit-risk considerations for the study.
Refer to Section 9.5 and Section 9.6 for details.
4.2.
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Intervention Groups
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 intervention. Adalimumab (HUMIRA) is 
approved for the treatment of moderate to severe HS and was selected as a reference arm to 
benchmark bermekimab efficacy relative to adalimumab. Randomization will be used to minimize 
bias in the assignment of participants to intervention groups, to increase the likelihood that known 
and unknown participant attributes (e.g., demographic and baseline characteristics) are evenly 
balanced across intervention groups, and to enhance the validity of statistical comparisons across 
intervention groups. Blinded intervention will be used to reduce potential bias during data 
collection and evaluation of clinical endpoints.
DNA and Biomarker Collection
It is recognized that genetic variation can be an important contributory factor to interindividual 
differences in intervention distribution and response and can also serve as a marker for disease 
susceptibility and prognosis. Pharmacogenomic research may help to explain interindividual 


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variability in clinical outcomes and may help to identify population subgroups that respond 
differently to an intervention. The goal of the pharmacogenomic component is to collect DNA to 
allow the identification of genetic factors that may influence the PK, PD, efficacy, or safety, of 
bermekimab and to identify genetic factors associated with HS.
Biomarker samples will be collected to evaluate the mechanism of action of bermekimab or help 
to explain interindividual variability in clinical outcomes or may help to identify population 
subgroups that respond differently to an intervention. The goal of the biomarker analyses is to 
evaluate the PD of bermekimab and aid in evaluating the intervention-clinical response 
relationship. 
DNA and biomarker samples may be used to help address emerging issues and to enable the 
development of safer, more effective, and ultimately individualized therapies.
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 maximum amount of blood drawn from each participant in this study will not exceed 500 mL 
as per the standard of the American Red Cross. For more details regarding blood collection see 
Section 8.
There is a high unmet medical need for novel, effective treatments for Hidradenitis Suppurativa. 
A placebo control arm is needed to assess the efficacy and safety of the investigational product
(IP). Placebo subjects will cross over to active treatment after Week 16 in Part 1 and Week 12 in 
Part 2. The protocol allows for lesion intervention(s) for painful lesions as well as the use of certain 
analgesics. In addition, subjects have the option of discontinuing from the study at any time for 
any reason.
4.3.
Justification for Dose
Three bermekimab dose regimens were originally selected to be evaluated in this study: 350 mg 
SC qw, 700 mg SC qw, and 1050 mg SC qw. These dose regimens were chosen based on 
bermekimab PK, efficacy, and safety data from a Phase 2 open-label study (2018-PT045, 
NCT03512275) and a Phase 2 placebo-controlled study (2019-PT047/77474462HDS2002, 
NCT03512275) in participants with HS. 
Results from the open-label study (2018-PT045) of bermekimab demonstrated evidence of clinical 
activity in participants with HS. The HiSCR50 responses at Week 12 were achieved by 63% and 
61% of anti-TNF failure and anti-TNF naïve patients with HS, respectively, following bermekimab 
400 mg SC qw injection for 13 weeks. Based on these findings, a Phase 2 placebo-controlled study 


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(77474462HDS2002) was conducted to further evaluate the 400 mg SC qw and 400 mg SC q2w 
dose regimens in participants with HS. At Week 12, the proportion of participants who achieved a 
HiSCR50 response was numerically higher in the bermekimab 400 mg qw group compared with 
the placebo group (54.8% vs 44.2%), while comparable HiSCR50 response was observed between 
the 400 mg q2w group and the placebo group (44.0% vs 44.2%, respectively). Since the 400 mg 
qw dose regimen suggested clinical efficacy in these 2 HS studies, a similar dose regimen of 350 
mg qw (350 mg x 1 SC injection) was selected as a dose to assess the minimally effective dose in 
this Phase 2b study. The formulation for 350 mg SC (175 mg/mL in 2 mL) is less viscous compared 
to the formulation for 400 mg SC (200 mg/mL in 2 mL). The 350 mg qw dose is expected to result 
in only slightly lower PK exposure compared with the 400 mg qw dose.
In the Phase 2 placebo-controlled study (77474462HDS2002), an E-R trend for HiSCR50 response
at Weeks 12 and 16 was observed in the 400 mg qw group, albeit a small sample size. This E-R 
trend indicated that higher PK exposure may result in higher efficacy. As such, 2 higher dose 
regimens of 700 mg qw (350 mg x 2 SC injections) and 1050 mg qw (350 mg x 3 SC injections) 
were also selected to support evaluation of dose-response in this Ph2b study. The dose regimens 
of 700 mg qw and 1050 mg qw will provide 2- and 3-fold higher exposure than 350 mg qw and 
are anticipated to achieve higher efficacy in HS.
The weekly dose frequency was selected based on bermekimab half-life (T1/2). Bermekimab T1/2 
was estimated to be approximately 1 week so that a weekly dose regimen would maintain adequate 
drug exposure over the entire dosing interval. Given that the initial intensive treatment with weekly 
doses of bermekimab for 12 weeks is expected to reduce participants’ inflammatory burden, a less 
frequent dose regimen may be sufficient for maintenance therapy. In addition, less frequent dosing 
interval will decrease participant burden. Therefore, instead of testing 700 mg qw and 350 mg qw
regimens in Part 2, bermekimab 1050 mg qw→q2w (starting at Week 12) or 700 mg qw→q2w 
(starting at Week 12) regimens will be implemented. Whether 700 mg qw→q2w will be included 
in Part 2 will be based on interim analysis results from Part 1. Details will be described in the 
interim analysis plan.
Bermekimab was well-tolerated in the 2018-PT045 study (400 mg SC qw for 13 weeks) with no 
safety concerns. In the completed Phase 2 AD and HS studies 77474462HDS2002 
(NCT04019041) study and 77474462ADM2002 (NCT04021862), bermekimab 800 mg at 
Week 0, 1 followed by 400 mg qw or 400 mg q2w were both safe and well-tolerated in participants 
with HS through Week 36. The highest dose of bermekimab studied was 7.5 mg/kg IV q2w for 12 
weeks in HS (10 participants; Kanni, 2018), with no safety concerns. The 7.5 mg/kg IV dose is 
equivalent to a 1125 mg SC dose for a 90 kg (average body weight of HS patients, 
77474462HDS2002) individual assuming an SC bioavailability of 60%. Based on the preliminary 
PK simulation, the median Cmax for the highest dose of 1050 mg SC qw would be lower (0.83-
fold) than that for the 7.5 mg/kg IV q2w dose regimen while the median AUC2weeks would be 
higher (1.85-fold) than that for the 7.5 mg/kg IV q2w dose regimen. Given the safety margins 
calculated based on predicted human PK exposure at 1050 mg SC qw (ie., 40-fold for Cmax,ss and 
33-fold for AUC1week,ss) relative to that at monkey NOAEL (300 mg/kg SC qw, Section 2.2), dose 


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regimens of up to 1050 mg SC qw proposed in this Phase 2 study would have adequate safety 
margins.
To actively monitor unblinded safety data on ongoing basis, an independent DMC will be 
commissioned in this study (Section 9.6, Data Monitoring Committee). 
Overall, the 3 proposed dose regimens are expected to have an acceptable safety profile. The 
inclusion of 3 different active dose regimens of bermekimab in this study would provide an 
opportunity to explore PK/PD relationships to enable optimal dose selection for subsequent 
clinical trials in participants with moderate to severe HS.
4.4.
End of Study Definition
End of Study Definition
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 
visit at that study site, in the time frame specified in the Clinical Trial Agreement.
Study Completion Definition
A participant will be considered to have completed the study if he or she has completed all 
scheduled study interventions through Week 31 and has completed all assessments at Week 36 of 
the safety follow-up period.
5.
STUDY POPULATION
A target of 250 or 300 participants will be enrolled under the 77474462HDS2001 protocol.
Screening for eligible participants will be performed within 6 weeks before administration of the 
study intervention. Refer to Section 5.4, for conditions under which the repeat of any screening 
procedures are 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.
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1.
Be a male or female 18 (or the legal consent in the jurisdiction in which the study is taking 
place) years of age or older.
2.
Be otherwise healthy on the basis of physical examination, medical history, vital signs, 
and 12-lead ECG performed at screening. Any abnormalities, must be consistent with the 


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underlying illness in the study population and this determination must be recorded in the 
participant's source documents and initialed by the investigator.
3.
Have HS for at least 1 year (365 days) prior to the baseline visit as determined by the 
investigator through participant interview and/or review of the medical history.
4.
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) at screening 
and baseline visits.
5.
Have Hurley Stage II or Hurley Stage III HS as determined by the investigator at 
screening and baseline visits. 
6.
Had an inadequate response to a 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.
7. 
Criterion modified per Amendment 2.
7.1. Be considered, in the opinion of the investigator, a suitable candidate for adalimumab 
(HUMIRA®) therapy according to their country's approved HUMIRA product labeling.
This criterion only applies to participants enrolling in Part 1 of the study, where 
adalimumab is one of the possible randomization arms. This criterion does not apply to 
participants enrolling in Part 2.
8.
Have stable HS for at least 60 days prior to the screening visit and at baseline as 
determined by the investigator through patient interview and/or review of the medical 
history.
9.
Have a total AN count of ≥5 at the screening and baseline visit.
10.
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 g/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


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11.
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, or benzoyl peroxide, or 
a dilute bleach bath.
12.
Criterion modified per Amendment 1:
12.1. Agree not to receive a live virus or live bacterial vaccination during the study and 
for 90 days after the last administration of study intervention.
13.
Are considered eligible according to the following 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,
OR
o
will initiate treatment for latent TB before the first administration of study 
intervention,
OR
o
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. Participants with a 
history and documentation of having completed appropriate treatment for 
latent TB more than 5 years before the first administration of study 
intervention are not eligible.
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 (or T-SPOT® for sites in Japan) test result, or have 
a newly identified positive QuantiFERON®-TB (or T-SPOT® for sites in Japan)
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.


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NOTE: A negative tuberculin skin test result (see Section 10.8) is additionally required 
if the QuantiFERON-TB® test is not approved/registered in the country in which this 
protocol is being conducted. The QuantiFERON®-TB (or T-SPOT® for sites in Japan) 
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, if active TB has been ruled out, and if 
appropriate treatment has been initiated/completed as described above in Inclusion 
Criterion 13a.
e.
Have a chest radiograph (both posterior-anterior and lateral views, or per country 
regulations where applicable), or a chest CT scan taken within 3 months before 
the first administration of study intervention and read by a qualified radiologist
or pulmonologist, with no evidence of current, active TB or old, inactive TB.
14.
Before randomization, a woman must be either:

Not of childbearing potential.

Of childbearing potential and practicing a highly effective method of contraception 
(failure rate of <1% per year when used consistently and correctly) and agrees to 
remain on a highly effective method while receiving study intervention and until 12 
weeks after last dose - the end of relevant systemic exposure. The investigator should 
evaluate the potential for contraceptive method failure (e.g., noncompliance, recently 
initiated) in relationship to the first administration of study intervention. Examples 
of highly effective methods of contraception are located in Section 10.6.
15.
Criterion modified per Amendment 2.
15.1. A woman of childbearing potential must have a negative highly sensitive serum (β-
human chorionic gonadotropin [β-hCG]) at screening and a negative urine pregnancy test 
at Week 0 prior to administration of study intervention.
16.
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 administration of study 
intervention.
17.
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 intervention.
18.
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.
19.
Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.


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20.
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.
21.
Must sign a separate ICF if he or she agrees to provide an optional DNA sample for 
research (where local regulations permit) or participate in one of the substudies. Refusal 
to give consent for the optional DNA research sample does not exclude a participant from 
participation in the study.
22.
Agree not to receive a Bacille Calmette-Guérin (BCG) vaccination during the study, and 
for 12 months after the last administration of study intervention.
5.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the study:
1.
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.
2.
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.
3.
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.
4.
A history of malignancy within 5 years before screening (exceptions are squamous and 
basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, 
which is considered cured with no evidence of recurrence for at least 3 months prior to 
the first administration of study intervention and with minimal risk of recurrence).
5.
Has a history of chronic or recurrent infectious disease, including but not limited to 
chronic renal infection, chronic chest infection (e.g., bronchiectasis), recurrent urinary 
tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), fungal 
infection (mucocutaneous candidiasis), or open, draining, or infected skin wounds or 
ulcers (not related to HS).
6.
Has or has had a serious infection (e.g., sepsis, pneumonia, or pyelonephritis), or has 
been hospitalized or received IV antibiotics for an infection during the 2 months before 
screening.
7.
Has or has had herpes zoster within the 2 months before screening.


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8.
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.
9.
Is infected with human immunodeficiency virus (HIV), positive serology for HIV 
antibody).
10.
Tests positive for HBV infection (see Section 10.7) or who are seropositive for 
antibodies to hepatitis C virus (HCV) at screening.
11.
Criterion modified per Amendment 1:
11.1. During the 6 weeks prior to baseline, have had any of (a) confirmed SARS-CoV-
2 (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection 
(clinical features without documented test results), OR (c) close contact with a person 
with known or suspected SARS-CoV-2 infection.
An exception to this criterion may be granted if a participant has a documented 
negative result for a validated SARS-CoV-2 test:
(i)
Obtained at least 2 weeks after conditions (a), (b), and (c) above (timed 
from resolution of key clinical features if present, eg, fever, cough, 
dyspnea)
AND
(ii)
with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit.
NOTES on COVID-related exclusion:

The field of COVID-related testing (for presence of, and immunity to, the SARS-
CoV-2 virus) is rapidly evolving. Additional testing may be performed as part of 
screening and/or during the study if deemed necessary by the investigator and in 
accordance with current regulations / guidance from authorities / standards of care.

Precaution: for those who may carry a higher risk for severe COVID-19 illness, 
follow guidance from local health authorities when weighing the potential benefits 
and risks of enrolling in the study, and during participation in the study.
12.
Criterion modified per Amendment 2.
12.1. Has a history of latent or active granulomatous infection, including 
histoplasmosis 
or 
coccidioidomycosis, 
before 
screening.
Participants 
with 
radiographic evidence of possible prior histoplasmosis or coccidioidomycosis will be 


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excluded. Refer to Inclusion Criterion 13 for information regarding eligibility with a 
history of latent TB.
13.
Has a chest radiograph or a chest CT scan within 3 months before the first 
administration of study intervention that shows an abnormality suggestive of a 
malignancy or current active infection, including TB.
14.
Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg, 
cytomegalovirus, pneumocystis, aspergillosis).
15.
Has 2 indeterminate (on repeat sampling) QuantiFERON -TB test results.
16.
Has had major surgery (e.g., 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.
NOTE: Participants with planned surgical procedures to be conducted under local 
anesthesia may participate.
17.
Has a transplanted organ (with exception of a corneal transplant >3 months before the 
first administration of study intervention).
18.
Has known allergies, hypersensitivity, or intolerance to bermekimab or adalimumab or 
its excipients (refer to IB).
19.
Criterion modified per Amendment 2.
19.1. Has previously received adalimumab. This criterion only applies to participants 
enrolling in Part 1 of the study, where adalimumab is one of the possible randomization 
arms. This criterion does not apply to participants enrolling in Part 2.
20.
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 continue to 
undergo additional evaluation.

A participant undergoing evaluation has a chest radiograph with evidence of 
current active TB and/or a positive QuantiFERON-TB® (or T-SPOT® for sites 
in Japan) test result (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), unless active TB 
can be ruled out and appropriate treatment for latent TB can be initiated prior 
to the next study intervention administration and continued to completion (see 
also Section 8.2.8.1 and Section 10.8). Indeterminate QuantiFERON-TB® (or 


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borderline T-SPOT® for sites in Japan) test results should be handled as 
described in Section 8.2.8.1. Participants with persistently indeterminate 
QuantiFERON-TB® (or borderline T-SPOT® for sites in Japan) test results 
may continue without treatment for latent TB if active TB is ruled out, their 
chest radiograph shows no abnormality suggestive of TB (active or old, 
inactive TB) and the participant has no additional risk factors for TB as
determined by the investigator. This determination must be promptly reported 
to the medical monitor or designee and recorded in the participant's source 
documents and initialed by the investigator.

A participant receiving treatment for latent TB discontinues this treatment 
prematurely or is noncompliant with the therapy.
21.
Has received an immunomodulating biology therapy within the previous 3 months of 
study intervention administration (including, but not limited to, anti-cytokine, anti-
complement antibodies, anti-Ig antibodies, etc).
22.
Has received phototherapy or any systemic medications/treatments that could affect 
HS or IGA evaluations within 4 weeks of the first administration of any study 
intervention.
23.
Has any other active skin disease or condition (e.g., bacterial, fungal or viral infection) 
that could have interfered with assessment of HS.
24.
Has a draining fistula count of >20 at the baseline visit.
25.
Receipt of prescription topical therapies for the treatment of HS within 14 days prior
to the baseline visit.
26.
Receipt of systemic non-biologic therapies for the treatment of HS within 28 days prior 
to the baseline visit.
27.
Receipt of any oral antibiotic treatment for HS or inflammatory disorders within 28 
days prior to the baseline visit.
28.
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.
29.
Receipt of PRN or “as needed” dose of oral concomitant analgesics for HS-related pain 
within14 days prior to the baseline visit. (participants may be receiving non-opioid 
analgesics for treatment of chronic HS-related pain but must be on a stable 
dose/regimen for at least 14 days prior to the baseline visit and be expected to continue 
use throughout the study).


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30.
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/regimen for at least 14 days prior to the baseline visit and be
expected to continue use throughout the study).
31.
Has ever received any IL-1 antagonist (e.g. including but not limited to anakinra, 
rilonacept).
32.
Has received any non-biologic investigational therapy within 30 days or 5 half-lives 
(whichever is longer) of study intervention administration or is currently enrolled in 
another study using an investigational agent, device, or procedure.
33.
Has received immune-cell depleting therapy (including rituximab) within 6 months of 
the first administration of study intervention.
34.
Has received any systemic immunosuppressants (eg, methotrexate [MTX], 
azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, 
tacrolimus) within 4 weeks of the first administration of study intervention.
35.
Has received, or is expected to receive, any live virus or bacterial vaccination within
12 weeks before the first administration of study intervention.
36.
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.
37.
Is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this 
study or within 12 weeks after the last administration of study intervention.
38.
Plans to father a child while enrolled in this study or within 12 weeks after the last 
administration of study intervention.
39.
Is known to have had a substance abuse (drug or alcohol) disorder within the previous 
12 months.
40.
Lives in an institution on court or authority order.
41.
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.
42.
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.


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43.
Has had a BCG vaccination within 12 months of screening.
44.
Has congenital conditions including Down syndrome that may impact the clinical 
course of HS.
45.
Has received an anti-TNF drug such as adalimumab within 3 months of the first 
administration of study intervention. This criterion only applies to participants 
enrolling in Part 2 of the study. In Part 1, participants previously exposed to 
adalimumab are excluded.
NOTE: Investigators should ensure that 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 administration 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 Section 10.4.
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.
Criterion modified per Amendment 2.
1.1. A woman of childbearing potential who is heterosexually active must remain on a 
highly effective method of birth control (Inclusion Criterion 14) during the study 
and after receiving the last administration of study intervention for at least 5 months
if participating in Part 1 (due to potential exposure to adalimumab) and for at least 
12 weeks if participating in Part 2.
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.
3.
Criterion modified per Amendment 2.
3.1. 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 17) 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 comply with restrictions on concomitant medications and therapies 
specified in the protocol (see Section 6.7.5).


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6.
Participants are required to use a daily antiseptic wash on their HS lesions before 
randomization and continue the treatment throughout the study (including the safety 
follow-up period) (see Section 6.7.2).
7.
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.
8.
Agree to follow all requirements that must be met during the study as noted in the 
Inclusion and Exclusion Criteria (e.g., contraceptive requirements).
9.
It is recommended that participants are up-to-date on age-appropriate vaccinations prior 
to screening as per routine local medical guidelines. For study participants who received 
locally-approved (and including emergency use-authorized) COVID-19 vaccines 
recently prior to study entry, follow applicable local vaccine labelling, guidelines, and 
standards of care for patients receiving immune-targeted therapy when determining an 
appropriate interval between vaccination and study enrolment (see also Section 6.7
concomitant medications).
5.4.
Screen Failures
If, during the screening phase, the subject has not met all inclusion criteria or met any exclusion 
criteria, or is unable or unwilling to adhere to the prohibitions and restrictions of the study, the 
subject is considered to be a screen failure and is not eligible to be randomized at that time.
Retesting of abnormal laboratory values that may lead to exclusion will be allowed once. Retesting 
can occur at an unscheduled visit during the specified screening period of 6 weeks.
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.
Completion of screening and randomization procedures within the specified screening window of 
approximately 6 weeks is required.
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 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.


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6.
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1.
Study Interventions Administered
The study intervention presentation to be used in this study is a sterile liquid formulation of 
175 mg/mL of bermekimab in a prefilled syringe with an injectable volume of 2.0 mL (350 mg of 
bermekimab per syringe). Bermekimab will be manufactured and provided under the responsibility 
of the sponsor. Refer to the IB for a list of excipients.
Placebo will be provided centrally by the sponsor.
Commercially available adalimumab will be provided by the sponsor as a sterile liquid containing 
40 mg/0.4 mL per vial for SC injection in a PFS.  
Part 1:
All participants will receive 4 SC injections at the Week 0 visit (either 4 active, 3 active and 1 
placebo, 2 active and 2 placebo, 1 active and 3 placebo, or 4 placebo). From Weeks 1 through 31, 
all participants will receive 3 SC injections at each administration visit (either 3 active, 2 active 
and 1 placebo, 1 active and 2 placebo, or 3 placebo). Since 4 SC injections at the Week 0 visit and 
3 SC injections will be administered at each administration visit thereafter, each SC injection 
should be given at a different location of the body. Participants randomized to placebo will receive 
bermekimab 1050 mg beginning at Week 16 and continuing through Week 31.
Group 1: Placebo
Participants will receive 4 placebo SC injections at Week 0. Participants will receive 3 placebo SC 
injections at Week 1 and every week thereafter through Week 15. At Week 16, participants will
cross over to receive 3 bermekimab 350 mg SC injections weekly through Week 31. 
Group 2: Adalimumab
Participants will receive 4 adalimumab 40 mg SC injections at Week 0. Participants will receive 3 
placebo SC injections at Week 1. Participants will receive 2 adalimumab 40 mg SC injections and 
1 placebo SC injection at Week 2. Participants will receive 3 placebo SC injections at Week 3. 
Participants will receive 1 adalimumab 40 mg SC injection and 2 placebo SC injections at Week 4 
and every week thereafter through Week 31. 
Group 3: Bermekimab 1050 mg SC qw
Participants will receive 3 bermekimab 350 mg SC injections and 1 placebo SC injection at 
Week 0. Participants will receive 3 bermekimab 350 mg SC injections at Week 1 and every week 
thereafter through Week 31.
Part 2:
Group 1: Placebo


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Participants will receive 3 placebo SC injections from Week 0 through Week 11. At Week 12, 
participants will cross over to receive 3 bermekimab 350 mg SC injections weekly through 
Week 31. 
Group 2: Bermekimab 1050 mg SC qw
Participants will receive 3 bermekimab 350 mg SC injections at Week 0 and every week thereafter 
through Week 31.
Group 3: Bermekimab 1050 mg SC qw→q2w
Participants will receive 3 bermekimab 350 mg SC injections at Week 0 and every week thereafter 
through Week 11. From Week 12, participants will receive 3 bermekimab 350 mg SC injections 
every other week thereafter through Week 30. During weeks in which bermekimab is not 
administered, participants will receive 3 placebo SC injections through Week 31.
Group 4: Bermekimab 700 mg SC qw→q2w
Participants will receive 2 bermekimab 350 mg SC injections and 1 placebo SC injection at Week 0 
and every week thereafter through Week 11. From Week 12, participants will receive 2 
bermekimab 350 mg SC and 1 placebo SC injection every other week thereafter through Week 30. 
During weeks in which bermekimab is not administered, participants will receive 3 placebo SC 
injections through Week 31.
Study intervention administration must be captured in the source documents and the case report 
form (CRF).
For details on rescue medications, refer to Section 6.7.1. For a definition of study intervention 
overdose, refer to Section 6.6.
Guidelines for study intervention administrations affected by the COVID-19 pandemic are found 
in Section 10.17.
6.2.
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
Study intervention labels will contain information to meet the applicable regulatory requirements.
Bermekimab (JNJ-77474462) and placebo PFS must be stored at controlled temperatures ranging 
from 36°F to 46°F (2°C to 8°C) and protected from light according to the product label.
Adalimumab must be stored as indicated on the product-specific labeling.
Refer to the Site IP Binder for additional guidance, including instructions for use, on study 
intervention preparation, handling, and storage.


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Accountability
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 intervention accountability form. All study intervention 
will be stored and disposed of according to the sponsor's instructions. Study-site personnel must 
not combine contents of the study intervention containers.
The dispensing of study intervention to the participant, and the return of study intervention from 
the participant (if applicable), must be documented on the intervention accountability form. 
Participants must be instructed to return all original containers, whether empty or containing study 
intervention.
If rescue medication or other medication is also supplied by the sponsor, inclusion of this 
medication on the intervention accountability form is required. The participants must return unused 
study intervention to the study site.
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, and study intervention returned by the 
participant, 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, or used returned study 
intervention for destruction, will be documented on the intervention 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 intervention 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. Returned study intervention must not be 
dispensed again, even to the same participant. Study intervention may not be relabeled or 
reassigned for use by other participants. The investigator agrees neither to 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
Dynamic central randomization will be implemented in this study. 


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The randomization method will be a minimization procedure with biased-coin assignment for both 
randomizations, which minimizes the imbalance in the distribution of the number of participants 
across treatment groups within the levels of each individual stratification factor: investigational 
site and baseline Hurley stage status (II, III). Based on the algorithm, each participant will be 
assigned to the treatment group which will produce minimum total imbalance score with a high 
probability, where the total imbalance score is a weighted average of the imbalance scores for each 
stratification factor and for the whole study. The Interactive Web Response System (IWRS) will 
assign a unique treatment code, which will dictate the treatment assignment and matching study 
drug for the participant.
At first, approximately 150 participants in Part 1 will be randomized to receive bermekimab 1050 
mg, adalimumab, or placebo in a 1:1:1 ratio. Enrollment will pause once approximately 150 
participants are randomized. Two interim analyses will be performed. The first interim analysis 
will be performed when approximately 75 participants have completed Week 16 or have 
terminated study participation. The objective of this interim analysis is to assess whether favorable 
efficacy is seen in the 1050 mg bermekimab dose group. 
The second planned interim analysis will take place once the 150 participants have completed 
study participation to Week 16 or have terminated study participation. The objectives of the second 
interim analysis are to assess whether a favorable efficacy is seen in the 1050 mg bermekimab 
dose group if not determined as favorable at the first interim analysis or confirm the favorable 
efficacy observed from the first interim analysis, or efficacy is low enough to consider termination 
of the study or the observed efficacy suggests modification to study. 
If favorable efficacy is observed in either the first or the second interim analysis, screening and 
randomization of participants will resume in Part 2 as planned, with additional participants being 
randomized to receive bermekimab 1050 mg qw, placebo, bermekimab 1050 mg qw→q2w, or 
bermekimab 700 mg qw→q2w in a 1:1:2:2 ratio (approximately 25 participants randomized to 
receive bermekimab 1050 mg qw and placebo, respectively, and approximately 50 participants 
randomized to receive bermekimab 1050 mg qw→q2w and bermekimab 700 mg qw→q2w, 
respectively).
However, if 700 mg qw→q2w is not included in Part 2 based on PK results from Part 1, screening 
and randomization of participants will resume with additional participants being randomized to 
receive bermekimab 1050 mg qw, placebo, or bermekimab 1050 mg qw→q2w in a 1:1:2 ratio 
(approximately 25 participants randomized to receive bermekimab 1050 mg qw and placebo, 
respectively, and approximately 50 participants randomized to receive bermekimab 1050 mg 
qw→q2w). Thus, if the study continues, a total number of approximately 250 or 300 participants 
will be enrolled in the study.
Otherwise, enrollment will remain paused while the sponsor considers whether to terminate the 
study at that point for insufficient efficacy, to resume enrollment as planned, or to resume the study 
with modification.


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The requestor must use his or her own user identification and personal identification number when 
contacting the IWRS and will then give the relevant participant details to uniquely identify the 
participant.
Blinding
Active study intervention and placebo will be prepared by an unblinded pharmacist or an unblinded 
qualified member of the investigational staff. The volume of the placebo will match the volume of 
the active intervention within each group. Prepared doses will be covered to mask potential visual 
differences between the active study intervention and placebo. The participants and other site staff 
members, including the investigator, will be blinded to study intervention allocation through study 
completion to reduce bias in the assessment of efficacy, safety, and tolerability data.
To ensure that no unintentional unblinding occurs during study intervention administration, at least 
one qualified site staff member will be designated to perform all SC injections of the IP. This 
unblinded administrator will have no other contact with the participant during the study and will 
not discuss the participant’s treatment with the participant, the investigator, or other site personnel 
at any time. The unblinded administrator(s) will be documented in the source documents at each 
dosing day.
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 (i.e., study intervention serum 
concentrations, antibodies to bermekimab, 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 database 
lock 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 12 DBL from Part 2 has occurred. All site personnel and participants will 
remain blinded to the treatment assignments until the last participant completes Week 36
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 SoA (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. For more information, see Sections 9.5
and 9.6.
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 SC injection by qualified staff, the details of each 
administration will be recorded in the eCRF. These will include date, body location, and time of 
SC injection.
All visits through Week 32 should occur within ±3 days of the scheduled visit throughout the 
study. Study intervention administration should not occur within 4 days of the last administration 
of study intervention. 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.
Dose Modification
No treatment/dose adjustment will be permitted through the study.
6.6.
Treatment of Overdose
For this study, any dose of bermekimab greater than the highest dose at a single dosing visit will 
be considered an overdose. The sponsor does not recommend specific treatment 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/serious adverse event (SAE) and laboratory 
abnormalities.

Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
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.


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6.7.
Concomitant Therapy
Prestudy therapies administered up to 30 days before first administration of study intervention 
must be recorded at screening. 
Concomitant therapies must be recorded throughout the study from Week 0 through Week 36 or 
continuing until 5 weeks after the last administration of study intervention. Concomitant therapies 
on randomized participants should also be recorded beyond that point only in conjunction with 
SAEs that meet the criteria outlined Section 8.3.1.
When considering use of locally-approved (and including emergency use-authorized) COVID-19 
vaccines in study participants, follow applicable local vaccine labelling, guidelines, and standards 
of care for participants receiving immune-targeted therapy. For study participants receiving a 
locally-approved (and including emergency use-authorized) COVID-19 vaccine, in order to help 
identify acute reactions potentially related to COVID-19 vaccine, it is recommended where 
possible that vaccine and study drug be administered on different days, separated by as large an 
interval as is practical within the protocol.
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 CRF. If a medication is temporarily discontinued because of 
abnormal laboratory values, side effects, concurrent illness, or the performance of a procedure, the 
change and reason for it should be clearly documented in the participant’s medical records. 
Modification of an effective preexisting 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.
6.7.1.
Rescue Medication
Rescue interventions are not allowed during the study. However, 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 starting at Week 2. Otherwise, the use of rescue 
interventions should be avoided during the study.
When necessary, 2 types of interventions may be used as rescue:

Injection with intralesional triamcinolone acetonide suspension (at a concentration of 
10 mg/mL, up to 0.5 mL)

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 6.7) during 
the study.


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Concomitant therapies associated with the lesion intervention(s) must be captured in the source 
documentation and on the appropriate eCRF.
The number of interventions allowed during the 32 weeks of the study is defined by the number 
of lesions present at baseline:

For participants with an AN count of 5-8 at baseline, it is permissible to perform a single 
lesion intervention. If a participant with 5-8 lesions at baseline, requires more than 1 
intervention during the study, then he or she must be discontinued from IP but continued for 
follow-up for approximately 5 weeks after last administration of IP.

For subjects with an AN count >8 at baseline, a total of 2 rescue interventions are permissible. 
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 during the study, then he or she must be 
discontinued from IP but continued for follow-up for approximately 5 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.
6.7.2.
Antiseptic Therapy
Participants 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, a 
dilute bleach bath, or a topical antiseptic wash containing chlorhexidine gluconate or benzoyl 
peroxide.
6.7.3.
Wound Care
Concomitant use of wound care dressings on HS wounds is allowed; however, options are limited 
to alginates, hydrocolloids, and hydrogels.
6.7.4.
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, except 
for tramadol as detailed below.
If a participant is on a stable dose/regimen of a non-opioid analgesic (PRN is not considered stable) 
for a HS-related condition or non- HS medical condition (e.g., 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:


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For HS-related pain, permitted analgesics are limited to:

Non-steroidal anti-inflammatory drugs (NSAIDs, such as Ibuprofen) as per local labeling; 
AND/OR

Acetaminophen (paracetamol) 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.
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.
6.7.5.
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:

TNF αblockers (adalimumab, etanercept, certolizumab, infliximab, golimumab)

IL 1 blockers (anakinra, canakinumab, rilonacept)

IL 6 blockers (tocilizumab, sarilumab)

IL 23 blockers (ustekinumab, guselkumab, tildrakizumab)

IL 17 blockers (secukinumab, ixekizumab, brodalumab)

CD20- directed cytolytic antibody (rituximab)

Inhibitor of B-Lymphocyte stimulator-specific (belimumab)

Integrin receptor antagonist (natalizumab)

Inhibitor of T cell activation (abatacept)

JAK inhibitor (systemic and topical)

Any investigational agents for the treatment of HS.

Any other systemic drug therapies for HS, including but not limited to MTX, cyclosporine, 
and retinoids.


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
Concomitant use of oral antibiotic therapy for HS or inflammatory disorders. Systemic 
antibiotic use (including oral) is allowed for the treatment of AEs other than a worsening of 
HS. 

Oral or injectable corticosteroids for the treatment of HS, except for protocol-allowed 
intralesional rescue therapy as outlined in Section 6.7.1.

Surgical or laser intervention for an HS lesion except as outlined in Section 6.7.1.
6.7.6.
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. 
Intra-articular, or routes of delivery of corticosteroids such as inhaled, otic, ocular, nasal, or other 
routes of mucosal delivery are allowed throughout the study. 
6.7.7.
Drugs Metabolized by Cytochrome P450
In vitro studies have shown that IL-1 could impact cytochrome (CYP) enzyme expression and 
activities (Renton 2005; Abdel-Razzak 1993). As such, suppression of IL-1α by bermekimab, a 
cytokine modulator, may potentially alter the hepatic metabolism and clearance of drugs that are 
substrates for CYP enzymes (FDA Guidance 2020). Therefore, upon initiation or discontinuation 
of bermekimab in patients being treated with CYP substrates with a narrow therapeutic index, 
monitoring of the effect (eg, warfarin) or drug concentration (eg, theophylline) is recommended 
and the individual dose of the drug may be adjusted as needed.
6.8.
Intervention After the End of the Study
No long-term extension is provided in this Phase 2 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
7.1.
Discontinuation of Study Intervention
A participant's study intervention must be discontinued if:

The participant withdraws consent to receive study intervention.

The participant or their legally acceptable representative withdraws consent/assent for 
administration of study intervention.

The investigator believes that for safety reasons or tolerability reasons (e.g., AE) it is in the 
best interest of the participant to discontinue study intervention.

The participant has a serious adverse reaction that is related to an injection including a 
hypersensitivity reaction. In general, discontinuation of study intervention administration 


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must be considered for participants who develop a nonserious but severe injection-site 
reaction.

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) 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 becomes pregnant or plans a pregnancy during the study period. Refer to 
Section 10.6.

The initiation of protocol-prohibited medications, treatments, or interventions (outlined in 
Section 6.7) 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.

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 8.2.8) (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.
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 


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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 5 weeks following the last administration of study intervention. 
The procedures and evaluations listed for the Early Termination Visit should also be performed 
approximately 5 weeks after the last administration of study intervention.
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

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 (e.g., 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 SoA (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.


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7.2.1.
Withdrawal From the Use of Research Samples
A participant who withdraws from the study will have the following options regarding the optional 
research samples:

The collected samples will be retained and used in accordance with the participant's original 
separate informed consent for optional research samples.

The participant may withdraw consent for optional research samples, in which case the 
samples will be destroyed, and no further testing will take place. To initiate the sample 
destruction process, the investigator must notify the sponsor study site contact of withdrawal 
of consent for the optional research samples and to request sample destruction. The sponsor 
study site contact will, in turn, contact the biomarker representative to execute sample 
destruction. If requested, the investigator will receive written confirmation from the sponsor 
that the samples have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The participant may withdraw consent for optional research samples while remaining in the study. 
In such a case, the optional research samples will be destroyed. The sample destruction process 
will proceed as described above.
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Section 10.4.5). 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 and in the separate ICF for 
optional research samples.
7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed 
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the 
participant are deemed futile. The following actions must be taken if a participant fails to return to 
the study site for a required study visit:

The study-site personnel must attempt to contact the participant to reschedule the missed visit 
as soon as possible, to counsel the participant on the importance of maintaining the assigned 
visit schedule, to ascertain whether the participant wishes to or should continue in the study.

Before a participant is deemed lost to follow up, the investigator or designee must make every 
reasonable effort to regain contact with the participant (where possible, 3 telephone calls, 
e-mails, text, and, if necessary, a certified letter to the participant’s last known mailing 
address, or local equivalent methods). These contact attempts should be documented in the 
participant’s medical records.

Should the participant continue to be unreachable, they will be considered to have withdrawn 
from the study.


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Should a study site close, e.g., for operational, financial, or other reasons, and the investigator 
cannot reach the participant to inform them, their contact information will be transferred to another 
study site.
8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA (Section 1.3) summarizes the frequency and timing of efficacy, PK, immunogenicity, 
biomarker, pharmacogenomic, and safety measurements applicable to this study.
During screening, each participant will be provided with an electronic device to enter patient-
reported outcome (PRO) data. Study-site personnel will train the participants on how to use the 
electronic device (ePRO), including instructions to capture the data according to the study design 
and not to wait until the study-site visit to record information. Participants will be provided with 
written instructions on how to get 24-hour technical support, if needed, for operation of the ePRO 
device.
All visit-specific PRO assessments should be conducted/completed before any tests, procedures or 
other clinical assessments, except for a urine pregnancy test, to prevent influencing participant 
perceptions.
Electrocardiograms (ECGs) should precede vital signs and both procedures should be completed 
prior to any invasive procedures. Vital signs should be recorded from the opposite arm from which 
blood samples are being taken.
All samples (including safety, efficacy, PK and biomarkers) must be obtained after the PRO and 
ECG assessments but prior to study intervention administration. 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.
Guidelines for handling of assessments affected by the COVID-19 pandemic are found in 
Section 10.18.  
Blood Sample Collection
The maximum amount of blood drawn from each participant in this study will not exceed 500 mL 
as per the standard of the American Red Cross.
In addition, repeat or unscheduled samples may be collected for safety reasons or for technical 
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Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF or laboratory 
requisition form. Refer to the SoA (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 that will be provided.
Study-Specific Materials
The investigator will be provided with the following supplies:

Protocol

IB for bermekimab

Site IP Binder

Laboratory Manual

Laboratory Kits

IWRS Manual

Sample CRF

eCRF Completion Guidelines

ePRO equipment (tablet device questionnaires, completion instructions)

Patient Diary

Participant Study Participation Card

Investigative Site File

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 (refer to Section 10.9) documents the investigator’s assessment of the participant’s 
HS at a given time point. 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.


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8.1.2.
Hidradenitis Suppurativa Activity and Severity Index
The HASI is a clinician reported outcomes tool that assesses HS severity by incorporating signs 
of inflammation and surface area involved. The HASI includes 4 domains to assess the severity of 
HS disease activity: inflammatory color change, inflammatory induration, open skin surface. and 
extent of tunnels. Each of these variables is scored on a Likert Scale from 0 to 3 (0=none; 
1=limited/mild, 2=moderate, 3=severe/extensive) based on the average intensity for each body 
site. A higher score indicates more severe disease. See Section 10.10, Appendix 10 for more 
details. 
8.1.3.
Lesion Counts
Lesion counts are defined as the counting of abscesses, inflammatory nodules, non-inflammatory 
nodules, draining fistulas, and non-draining fistulas. 
8.1.4.
Images of Skin Lesions
Images of selected HS lesions of the axilla will be taken at a subset of study sites in participants 
who provide additional consent. Consult the Trial Center File for instruction manual.
8.1.5.
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.
Only participants with Hurley Stage II and Hurley Stage III will be enrolled in this study. 
8.1.6.
Hidradenitis Suppurativa Symptom Diary (HSSD)
The HSSD (refer to Section 10.11 and Section 10.12) is an 8-item patient self-reported 
questionnaire that assesses symptoms (including pain, tenderness, pressure, itch, heat, and odor)
and signs (including swelling and drainage) of HS. 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. Two versions are available: one with a 
24-hour recall (HSSD-24h; see Section 10.12) and one with a 7-day recall (HSSD-7d; see 
Section 10.11). Each individual symptom (including pain and itch) and sign scale score, ranging 
from 0-10, will be summarized. A total symptom score will be derived by averaging the 6
individual symptom scale scores. A total sign score will be derived by averaging the 2 individual 
sign scale scores. An overall total score will be derived by averaging all 8 individual items. The 
last item included in the HSSD is an optional item for patients to assess systemic symptoms of HS 
(flu-like symptoms). It will be assessed as a separate item and not included in HSSD overall total 
score. The psychometric properties of the HSSD will be evaluated for scale validation using the 
data from this study.


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8.1.7.
Dermatological Life Quality Index (DLQI)
The DLQI (refer to Section 10.13) is a dermatology-specific health-related quality of life (HRQoL)
instrument designed to assess the impact of the disease on a participant’s HRQoL (Finlay 1994). 
It is a 10-item questionnaire that assesses HRQoL over the past week and in addition to evaluating 
overall HRQoL, 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 total score ranges from 0 to 30 with a higher score indicating greater impact on 
QoL (Finlay 1994).
8.1.8.
Patient Global Impression of Change (PGIC) of Hidradenitis 
Suppurativa Severity
The PGIC of HS Severity (refer to 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.
8.1.9.
Patient Global Impression of Severity (PGIS) of Hidradenitis 
Suppurativa
The PGIS of HS (refer to Section 10.15) is a one-item questionnaire that measures participants’ 
perceived severity of HS. Participants will rate the severity of their HS using a 5-point scale 
ranging from “none” to “very severe”. PGIS will be used as an anchor to establish a clinical 
response criterion of other patient or physician reported outcomes for future reference. The 
questionnaire will be administered at time points according to the SoA (Section 1.3).
8.1.10.
Patient-Reported Outcomes Measurement Information System-29 
(PROMIS-29)
The PROMIS-29 (refer to Section 10.16) is a 29 item generic HRQoL survey, assessing each of 
the 7 PROMIS domains (depression; anxiety; physical function; pain interference; fatigue; sleep 
disturbance; and ability to participate in social roles and activities) with 4 questions. The questions 
are ranked on a 5-point Likert Scale. There is also one 11-point rating scale for pain intensity
(PROMIS -29). Participants will undergo this assessment at time points according to the SoA
(Section 1.3).
8.1.11.
HS Lesion Monitoring Using Medical Infrared Thermography
Medical imaging can be used in the clinical assessment of HS to complement manual palpation 
(Elkin 2020). As part of the 77474462HDS2001 study, visible light photography and medical 
infrared thermography (MIT) will be used to acquire images of lesions in HS participants. At 
baseline and throughout the study, sites will collect images from both axillae (left and right), 
regardless of presence of HS lesions. Images will be analyzed by computer vision-based 
algorithms to understand if the images can be used to identify lesion features and lesion heat 
distribution, which may be indicative of the levels of inflammation in lesions. Finally, imaging 


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derived metrics will be compared to clinical evaluations of HS axilla lesions to determine the 
suitability of imaging for objective clinical assessment of HS. Imaging will be conducted in a 
limited number of participants who consent to this optional substudy at some clinical sites. Details 
are provided in Appendix 17 (Section 10.17) and instructions for acquiring photographs and 
completing assessments are provided in the imaging manual. At visits when images are collected, 
imaging should be completed prior to clinical disease assessment by the investigator. The results 
of these analyses will be presented in a separate report.
8.2.
Safety Assessments
Details regarding the internal independent DMC are provided in Sections 10.4.1 and 10.4.6.
AEs will be reported and followed by the investigator as specified in Sections 8.3 and 10.5.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event 
section of the CRF.
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. 
The study will include the following evaluations of safety and tolerability according to the time 
points provided in the SoA (Section 1.3).
8.2.1.
Physical Examinations
Physical Examination
Physical examinations will be performed by the investigator or designated physician, nurse 
practitioner or physician assistant as specified in the SoA (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 SoA (Section 1.3). Participants will be 
instructed to remove shoes and outdoor apparel and gear prior to these measurements.
8.2.2.
Vital Signs
Vital signs (including temperature, pulse/heart rate, respiratory rate, and blood pressure) will be 
obtained before prior to study intervention administration at visits specified in the SoA
(Section 1.3).
8.2.3.
Electrocardiograms
A single 12-lead ECG will be performed at screening and at Week 16 in Part 1 and Week 12 in 
Part 2.


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8.2.4.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in 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 adverse event section of the CRF. 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 Section 10.3.
Female participants of childbearing potential will undergo a pregnancy test at screening, before 
each study intervention administration, and at the Week 36 or Early Termination Visit.
8.2.5.
Concomitant Medication
Concomitant medications will be reviewed at each visit and recorded in the source documents and 
eCRF.
8.2.6.
Allergic Reactions
Before any SC injection, 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 (e.g., urticaria, itching, hives). If a mild or moderate allergic reaction is 
observed, acetaminophen
(paracetamol), non-steroidal anti-inflammatory drugs, and/or 
diphenhydramine may be administered.
In the case of a severe allergic reaction (eg, anaphylaxis), IM or SC aqueous epinephrine, 
corticosteroids, respiratory assistance, and other proper resuscitative measures may be essential 
and must be available at the study site where the injections or infusions are being administered
(Sampson 2006).
Participants who experience serious adverse reactions related to an injection should be 
discontinued from further study intervention administrations (see Section 7.1).
8.2.7.
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. Participants should be monitored for the occurrence of injection-site 
reactions for 30 minutes after the study intervention administration.
8.2.8.
Tuberculosis Evaluation(s)
8.2.8.1.
Initial Tuberculosis Evaluation
Participants must undergo testing for TB (refer to laboratory manual for QuantiFERON®-TB test 
or Section 10.8 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 


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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® (or T-SPOT® for sites in Japan) 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 is mandated by local health authorities) are eligible to 
continue with pre-randomization procedures. Participants with a newly identified positive 
QuantiFERON-TB® (or T-SPOT® for sites in Japan 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 
should be followed, or the participant will be excluded from the study. 
A participant whose first QuantiFERON-TB® test result is indeterminate should have the test 
repeated. In the event that the second QuantiFERON-TB® test result is also indeterminate, the 
participant may be enrolled without treatment for latent TB if active TB is ruled out, their chest 
radiograph shows no abnormality suggestive of TB (active or old, inactive TB) and the participant 
has no additional risk factors for TB as determined by the investigator. For sites in Japan, a 
participant whose first T-SPOT® test result is borderline should have the test repeated. In the event 
that the second T-SPOT® (for sites in Japan) test result is also borderline, the participant may be 
enrolled without treatment for latent TB if active TB is ruled out, their chest radiograph shows no 
abnormality suggestive of TB (active or old, inactive TB) and the participant has no additional risk 
factors for TB as determined by the investigator. This determination must be promptly reported to 
the medical monitor or designee and recorded in the participant's source documents and initialed 
by the investigator.
8.2.8.2.
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 SoA in Section 1.3). The following series of questions is suggested for use during the 
evaluation:

“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?”


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
“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.
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 (or T-SPOT® for sites 
in Japan) 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 is warranted. Study intervention administration should be 
interrupted during the investigation. A positive QuantiFERON®-TB (or T-SPOT® for sites in 
Japan) test or tuberculin skin test result should be considered detection of latent TB. Participants 
with a newly identified positive QuantiFERON-TB® (or T-SPOT® for sites in Japan 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 should be followed, or the participant will be excluded from the study. 
If the QuantiFERON-TB® test result is indeterminate, the test should be repeated. For sites in 
Japan, a participant whose first T-SPOT® test result is borderline should have the test repeated. 
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 
SoA (Section 1.3).
8.3.
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs, 
and product quality complaints (PQCs), from clinical studies are crucial for the protection of 
participants, investigators, and the sponsor, and are mandated by regulatory agencies worldwide. 


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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.
AEs 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 related to HS exacerbation will be recorded and reported as described in 
Section 10.2.
Further details on AEs, SAEs and PQC can be found in Section 10.5.
8.3.1.
Time Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information
All Adverse Events
All adverse events 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
All serious adverse events, as well as PQC, 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.
Serious adverse events, including those spontaneously reported to the investigator within 12 weeks 
after the last administration 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.
A possible Hy’s law Case is defined by the occurrence of alanine transaminase/aspartate 
transaminase ≥3 x upper limit of normal (ULN), alkaline phosphatase <2 x ULN together with 
total bilirubin ≥2 x ULN or international normalized ratio >1.5 (if measured). Any possible Hy’s 
Law case is considered an important medical event and should be reported to the sponsor in an 
expedited manner, even before all other possible causes of liver injury have been excluded.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event 
Form and Safety Report Form of the CRF, 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 an SAE should be transmitted electronically or by facsimile (fax). Telephone reporting should 
be the exception and the reporter should be asked to complete the appropriate form(s) first.
8.3.2.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading 
verbal questioning of the participant is the preferred method to inquire about AE occurrence. 


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Solicited Adverse Events
Solicited AEs are predefined local at the injection site and systemic events for which the participant 
is specifically questioned and which are noted by participants in their diary (see Section 8).
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the 
participant diary.
8.3.3.
Follow-up of Adverse Events and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and evaluations as medically indicated to elucidate the nature and causality of the AE, SAE or 
PQC as fully as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. AEs, 
including pregnancy, will be followed by the investigator as specified in Section 10.5.
8.3.4.
Regulatory Reporting Requirements for Serious Adverse Events and 
Anticipated 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 
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. 
An anticipated event is an AE that commonly occurs in the study population independent of 
exposure to the drug under investigation. For the purposes of this study the following SAEs will 
be considered anticipated events: 

Worsening of HS
These anticipated events will be periodically analyzed in aggregate by the sponsor during study 
conduct. The sponsor will prepare a safety report in narrative format if the aggregate analysis 
indicates that the anticipated event occurs more frequently in the intervention group than in the 
control group and the sponsor concludes there is a reasonable possibility that the drug under 
investigation caused the anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated 
Events Safety Monitoring Plan. The assessment of causality will be made by the sponsor’s 
unblinded safety assessment committee.
The sponsor assumes responsibility for appropriate reporting of the listed anticipated events 
according to the requirements of the countries in which the studies are conducted.


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8.3.5.
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 (e.g., 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs and must be reported using a serious adverse event reporting form. Any 
participant who becomes pregnant during the study must discontinue further study intervention 
(see Section 7.1).
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
8.3.6.
Adverse 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 Section 10.5. 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.
Pharmacokinetics and Immunogenicity
Blood samples will be collected for the measurement of serum bermekimab concentrations and 
antibodies to bermekimab at the time points presented in the SoA.
At visits in which serum bermekimab concentration and/or antibodies to bermekimab will be 
evaluated, 1 venous blood sample of sufficient volume should be collected, and each serum sample 
should be divided into 3 aliquots: 1 for serum concentration of bermekimab and a back-up. Each 
serum sample will be divided into 3 aliquots: 1 for serum concentration of bermekimab, 1 for 
antibodies to bermekimab, and 1 back-up. 
Blood 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. Blood samples 
collected for serum bermekimab concentrations may also be used for exploratory biomarker 
analyses.
A random venous blood sample for population PK analysis will be collected from all participants
on any day between Weeks 2 to 12, except on the days of the scheduled study visits. Additionally, 
this blood sample must be collected at least 24 hours prior to or after the actual time of study 
intervention administration. Each population PK serum sample will be divided into 2 aliquots: 1 
for serum concentration of bermekimab and a 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.


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Pharmacokinetic Analytical Procedures
Serum samples will be analyzed to determine serum bermekimab concentrations using a validated, 
specific, and sensitive immunoassay method under the supervision of the sponsor. The sponsor, or 
its designee, under conditions in which the participants’ identity remains blinded, will assay these 
samples.
Immunogenicity Analytical Procedures
The detection and characterization of antibodies to bermekimab will be performed using a 
validated, drug-tolerant immunoassay method by or under the supervision of the sponsor. Serum 
samples will be screened for antibodies binding to bermekimab and the titer of confirmed positive 
samples will be reported. Antibodies to bermekimab may be further characterized and/or evaluated 
for their ability to neutralize the activity of bermekimab.
8.5.
Genetics and Pharmacogenomics
Genetic and epigenetic variation can be an important contributory factor to interindividual 
differences in drug disposition and response and may also serve as a marker for disease 
susceptibility and prognosis. Pharmacogenomic research consists of the analysis of one or more 
candidate genes or of the analysis of markers throughout the genome (as appropriate) in relation 
to bermekimab or HS clinical endpoints. The goal of the pharmacogenomic/epigenomic 
component is to explore factors that may influence the PK, PD, efficacy, or tolerability of 
bermekimab and to evaluate genetic factors previously reported to be associated with HS or help 
identify new associations. These DNA samples may be used to help address emerging issues and 
to enable the development of safer, more effective, and more precisely applied therapies. 
A pharmacogenomic blood sample will be collected from participants who consent separately to 
this component of the study to allow for pharmacogenomic research, as necessary (where local 
regulations permit). Genotyping or sequencing techniques will be used to assess variation genome-
wide. Participation in pharmacogenomic research is optional.
8.6.
Biomarkers
Biomarker samples will be collected to evaluate the PD and mechanism of action of bermekimab 
or help to explain interindividual variability in clinical outcomes or may help to identify population 
subgroups that respond differently to the intervention. The goal of the biomarker analyses is to 
evaluate the PD of and aid in evaluating the intervention-clinical response relationship. 
Biomarker assessments will include the evaluation of relevant markers in blood and wound 
exudate (when present) for all participants. Genetic analysis, skin biopsies, FibroTx Transdermal
Patch analysis (when kits are available), and skin swabs will also be collected from participants 
who consent to this optional part of the study. The samples will be used to better understand the 
biology of HS; to provide biological assessment of the response of participants to treatment with 
bermekimab; 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. Blood 
samples will be separated into serum, plasma, and peripheral blood mononuclear cells (PBMCs)


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for biomarker analysis. Samples for serum biomarkers, flow cytometry and gene expression from 
blood will be collected at time points according to the SoA (Section 1.3). Instructions for the 
collection and shipment of these samples are found in the Laboratory Reference Manual and 
Biopsy Collection Manual.
8.6.1.
Skin Biomarkers
Wound exudates (from all participants when present) and FibroTx Patch assessments (from 
participants who consent to this optional part of the study and when kits are available) will be 
collected at time points specified in the SoA (Section 1.3). Protein analysis will be done to monitor 
the PD effect and to understand mechanism of action of bermekimab.
Participants may participate in collection of biopsies (nodule and ultrasound guided deep tunnel 
biopsy) and/or skin swabs for microbiome analysis in this optional part of the study.
Skin biopsy samples will be collected from participants that consent to this optional part of the 
study at time points specified in the SoA (Section 1.3). At baseline, biopsy samples will be 
collected from both lesional (nodule) and adjacent non-lesional areas (10 cm away from the 
lesional nodule). At subsequent time points (Week 16 and Week 32 in Part 1, and Week 12 and 
Week 32 in Part 2), only lesional areas will be sampled. At Week 16 in Part 1 and Week 12 in 
Part 2, 2 nodules and 1 tunnel (if present) will be sampled. If a participant consents to undergoing 
Week 32 biopsies, 1 nodule and 1 tunnel biopsy will be sampled at Week 32. Gene expression 
analysis of skin biopsy samples will be performed to investigate differential gene expression 
during treatment compared to baseline to explore PD, mechanism of action, and differences in 
responders versus nonresponders. Proteomic analysis will be used to explore the target occupancy 
and the treatment effect on the affected skin. All skin biopsies and sampling should be completed 
after completion of the disease severity assessments by the investigator/sub-investigator. In 
addition, the tissue biopsies may be analyzed for histological readouts and immunohistochemistry 
to explore the effects of study intervention on cellular composition within skin tissue. Skin swabs 
will be collected to study the effect of intervention on microbiome composition on affected skin.
8.6.2.
Serum Biomarkers
Serum samples will be collected from all participants at time points specified in the SoA
(Section 1.3). Potential circulating factors to be evaluated may include cytokines and other 
inflammatory markers (eg, IL-6, IL-8, TNFα, SAA), and other categories of biomarkers potentially 
associated with HS or related to the mechanism of action of bermekimab.
8.6.3.
Plasma Biomarkers
Plasma samples will be collected from all participants at time points specified in the SoA 
(Section 1.3). Potential circulating factors to be evaluated may include complements and other 
biomarkers potentially associated with HS or related to the mechanism of action of bermekimab. 
8.6.4.
Flow Cytometry Analysis
Whole blood samples will be collected from all participants at time points specified in the SoA 
(Section 1.3), and PBMC will be isolated. Flow cytometry analysis of blood cell samples will be 


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utilized to monitor the effects of bermekimab on circulating immune cell populations. Cell surface 
markers such as, but not limited to, those for T cell subsets (eg, Th1, Th2), dendritic cells, and B
cells will be assessed. 
8.6.5.
Gene Expression Analysis in Whole Blood
Whole blood samples will be collected from all participants at time points specified in the SoA 
(Section 1.3). Total RNA will be isolated and used for differential gene expression analyses to 
better understand the pathologic mechanisms involved in HS and to potentially identify a treatment 
response signature to bermekimab.
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.
8.7.
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 of this study is that bermekimab is superior to placebo as assessed by the 
proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at 
Week 16 in Part 1, and at Week 12 in Part 2.

HiSCR50 is defined as at least 50% reduction in total abscess and inflammatory nodule 
counts (AN count) with no increase in abscess count and no increase in draining fistula 
count relative to baseline.
9.2.
Sample Size Determination
This study is designed to enroll approximately 250 or 300 participants, in order to provide 
sufficient data to have adequate power for the primary endpoint. 
The sample size of 250 or 300 participants was also chosen in order to:

Have sufficient power to detect a difference between the bermekimab groups and the placebo 
group for the primary endpoint of the proportion of participants achieving HiSCR50 at 
Week 16 between the bermekimab treatment group and the placebo group in Part 1 and at 


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Week 12 between bermekimab treatment groups and placebo group combining Part 1 and Part 
2.

Have an adequate confidence level for the treatment difference between the bermekimab high 
dose group and the adalimumab group in HiSCR50 at Week 16 in Part 1. 

Provide greater precision for the interim analysis efficacy analysis with more participants in 
the bermekimab 1050 mg, adalimumab, and placebo groups. 
The assumptions for the sample size and power calculations specified below were mainly based 
on the clinical data from the 77474462HDS2002 (PT-047) Phase 2 clinical study and from 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. 
The response rates observed in the 77474462HDS2002 (PT-047) study for HiSCR50 at 
Week 12/Week 16 were 55%/57% (bermekimab qw group), 44%/52% (bermekimab q2w group), 
and 44%/44% (placebo group), respectively. In addition, the HiSCR50 response rates in the 
adalimumab Phase 3 Studies M11-313 and M11-810 at Week 12 were 42% vs 26% and 59% vs 
28% in the adalimumab weekly and placebo groups, respectively. 
Comparisons between treatment groups at Week 16 with Part 1 data (all comparisons are at a 2-
sided type 1 error rate of 0.10; Table 1 and Table 2)

For comparison between bermekimab with placebo using data from Part 1 only for the primary 
endpoint at Week 16, the study sample size provides 83% power to detect a 25% treatment 
difference (50% vs 25%) with 50 participants per arm.

Greater than 99% power to detect a 40% (75% vs 35%) difference between the bermekimab 
1050 mg treatment group (n=50) and the placebo group (n=50).

From comparison between adalimumab with placebo using data from part 1 only for the 
primary endpoint, the study sample size provides 83% power to detect a 25% (50% vs 25%) 
treatment difference with 50 participants per arm.
No formal comparisons will be performed between the bermekimab 1050 mg qw group and the 
adalimumab group from Part 1, however the treatment difference and its 2-sided 80% CI for the 
primary endpoint at Week 16 between these 2 groups will be provided. A sample size of 
50 participants in each of the treatment groups will produce a 2-sided 80% CI for the treatment 
difference with a width of approximately 29%.
Comparisons between treatment groups at Week 12 with combining Part 1 and Part 2 data
Assuming HiSCR50 response rates at Week 12 are 25% to 35% for placebo and 50% to 75% for 
the bermekimab groups, respectively; based on these assumptions, approximately 250 participants 
across Part 1 and Part 2 are planned to be randomized to the placebo (n=75), bermekimab 700 mg 
qw to q2w (n=50), bermekimab 1050 mg qw to q2w (n=50), and bermekimab 1050 mg qw (n=75) 
treatment groups. Comparisons between the bermekimab groups and the placebo groups will be 
based on data combining Part 1 and Part 2. 


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For comparisons between bermekimab groups with placebo combining Part 1 and Part 2 for the 
primary endpoint, bermekimab 1050 mg qw and 1050 mg qw q2w groups will be grouped
together as bermekimab 1050 mg group (n=125) and 700 mg qw q2w group will be denoted as 
bermekimab 700 mg group, the study sample size provides:

At least 87% power to detect a 25% treatment difference between the bermekimab 700 mg
treatment group (n=50) and the placebo group (n=75).

97% power to detect a 25% (50% vs 25%) treatment difference between the bermekimab 1050 
mg treatment group (n=125) and the placebo group (n=75).

Greater than 99% power to detect a 40% (75% vs 35%) difference between the bermekimab 
1050 mg treatment group (n=125) and the placebo group (n=75) or between 700 mg treatment 
group (n=50) and the placebo group (n=75).
in HiSCR50 at Week 12 combining Part 1 and Part 2 based on a 2-sample Z-test at a Type I error 
rate of 0.10 (2-sided; Table 3).
Table 1:
Power to detect a treatment difference in HiSCR50 at Week 16 in Part 1
Placebo
Treatment Group
Difference
Power
Bermekimab 1050 mg (n=50)/Adalimumab (n=50) vs placebo (n=50)
25%
50%
25%
83%
25%
55%
30%
93%
25%
60%
35%
97%
25%
65%
40%
99%
25%
70%
45%
>99%
25%
75%
50%
>99%
30%
55%
25%
81%
30%
60%
30%
92%
30%
65%
35%
97%
30%
70%
40%
99%
30%
75%
45%
>99%
35%
60%
25%
81%
35%
65%
30%
92%
35%
70%
35%
97%
35%
75%
40%
99%
Table 2:
Confidence interval for the treatment difference in HiSCR at Week 16 in Part 1
HiSCR (P1)
HiSCR (P2)
Difference
(P1 − P2)
Width
Confidence 
Limit
Confidence
Level
Bermekimab 1050 mg qw dose regimen (n=50; P1) vs adalimumab (n=50; P2)
60%
50%
10%
29.3%
(-4.7%,24.6%)
80%
65%
50%
15%
29.0%
(0.5%,29.5%)
80%
70%
50%
20%
28.6%
(5.7%,34.3%)
80%
75%
50%
25%
27.9%
(11.0%, 38.9%)
80%


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Table 3: 
Power to detect a treatment difference in HiSCR50 at Week 12 Combining Part 1 and Part 2
Placebo
Treatment Group
Difference
Power
Bermekimab 1050 mg (n=125) vs placebo (n=75)
25%
50%
25%
97%
25%
55%
30%
>99%
25%
60%
35%
>99%
25%
65%
40%
>99%
25%
70%
45%
>99%
25%
75%
50%
>99%
30%
55%
25%
97%
30%
60%
30%
99%
30%
65%
35%
>99%
30%
70%
40%
>99%
30%
75%
45%
>99%
35%
60%
25%
96%
35%
65%
30%
99%
35%
70%
35%
>99%
35%
75%
40%
>99%
Bermekimab 700 mg (n=50) vs placebo (n=75)
25%
50%
25%
89%
25%
55%
30%
96%
25%
60%
35%
99%
25%
65%
40%
>99%
25%
70%
45%
>99%
25%
75%
50%
>99%
30%
55%
25%
87%
30%
60%
30%
95%
30%
65%
35%
99%
30%
70%
40%
>99%
30%
75%
45%
>99%
35%
60%
25%
87%
35%
65%
30%
95%
35%
70%
35%
99%
35%
75%
40%
>99%
9.3.
Populations for Analysis Sets
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 administration 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.


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Pharmacokinetics analyses for bermekimab will include participants who receive at least one 
administration of bermekimab and have at least one post-dose sample collection. Antibodies to 
bermekimab will be analyzed for participants who receive at least one dose of bermekimab and 
have at least one post-dose sample collection.
9.4.
Statistical Analyses
9.4.1.
Statistical Methods
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, treatment comparisons for binary endpoints will be performed using a Cochran-Mantel-
Haenszel (CMH) test stratified by baseline Hurley stage status. For continuous efficacy endpoints, 
treatment comparisons will be performed using a Mixed-Effect Model Repeated Measure 
(MMRM) model. The MMRM will include treatment, visit, baseline value for the corresponding 
efficacy endpoint, baseline Hurley stage status, baseline value by visit interaction, baseline Hurley 
stage status by visit interaction and the treatment-by-visit interaction, if applicable. The Least 
Square mean (LSmean) estimates and their corresponding 95% CIs will be provided at each time 
point. In addition, the estimates of LSmean difference and 95% CIs between treatment groups will 
be provided.
In general, all statistical testing will be performed at a significance level of 0.05 (2-sided) unless 
otherwise specified. Nominal p-values will be displayed for all treatment comparisons.
9.4.2.
Efficacy Analyses
9.4.2.1.
Primary Endpoint
The primary efficacy endpoint is the proportion of participants with a clinical response at Week 
16 in Part 1, and at Week 12 in Part 2, defined according to the HiSCR50 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 count.
9.4.2.1.1.
Primary Estimand 1
Primary Estimand 1: The primary estimand 1 (ie, a precise definition of the primary targeted 
treatment effect) is defined by the following 5 attributes:

Population: adult participants with moderate to severe HS.

Variable/endpoint: HiSCR50 binary responder variable at Week 16 in Part 1.

Treatment:

Experimental: Bermekimab1050 mg qw. 

Active Comparator: Adalimumab

Control: Placebo


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
Intercurrent Events and Corresponding Analysis Strategies:
Intercurrent Events
Analysis Strategy for Addressing Intercurrent Events
1. Discontinuation 
of 
study
intervention due to lack of
efficacy
or 
an
AE
of
worsening of HS. 
2. Initiation 
of
a
protocol-
prohibited
medication
or
therapy that could improve
H S during the study.
Composite Strategy: Participants are considered 
HiSCR50 nonresponders at the time of primary 
endpoint if they experience this intercurrent event prior 
to Week 16 in Part 1.
3. Discontinuation 
of 
study 
intervention for other reasons.
Treatment policy strategy: Observed data will be 
used regardless of whether or not this intercurrent event 
had occurred.
Note: For participants experiencing multiple intercurrent events (ICEs), ICE 2 will override ICE 3.

Population level summary: Difference in the proportions of participants achieving HiSCR50
at Week 16 in Part 1, between the bermekimab and placebo treatment groups.
9.4.2.1.2.
Primary Estimand 2
Primary Estimand 2: The primary estimand 2 is also defined by the following 5 attributes as 
the primary estimand 1:

Population: adult participants with moderate to severe HS.

Variable/endpoint: HiSCR50 binary responder variable at Week 12 based on the combined 
data from Part1 and Part 2. 

Treatment:

Experimental: Bermekimab 700 mg qw→q2w (starting at Week 12), 1050 mg qw→q2w 
(starting at Week 12), and 1050 mg qw. For the primary analysis, bermekimab 1050 mg 
qw q2w and 1050 mg qw groups will be combined as 1050 mg group and bermekimab 
700 mg qw q2w group will be denoted as 700 mg group.

Control: Placebo 

Intercurrent Events and Corresponding Analysis Strategies:
Intercurrent Events
Analysis Strategy for Addressing Intercurrent Events
1
Discontinuation 
of 
study
intervention due to lack of
efficacy
or 
an
AE
of
worsening of HS. 
2
Initiation 
of
a
protocol-
prohibited
medication
or
Composite Strategy: Participants are considered 
HiSCR50 nonresponders at the time of primary 
endpoint if they experience this intercurrent event prior 
to Week 12 in Part 1 and Part 2


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therapy that could improve
H S during the study.
3
Discontinuation 
of 
study 
intervention for other reasons.
Treatment policy strategy: Observed data will be 
used regardless of whether or not this intercurrent event 
had occurred.
Note: For participants experiencing multiple ICEs, ICE 2 will override ICE 3.

Population level summary: Difference in the proportions of participants achieving HiSCR50 
at Week 12 based on the combined data from both Part 1 and Part 2 of the study between the 
bermekimab and placebo treatment groups.
9.4.2.1.3.
Primary Endpoint Analysis
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.
In this primary analysis, the proportion of participants who achieve a HiSCR50 at Week 16 in 
Part 1, and at Week 12 based on the combined data from Part 1 and Part 2 will be summarized for 
each treatment group. To address the primary objective, a CMH chi-squared statistic stratified by 
baseline Hurley stage status (II, III) at an alpha level of 0.1 will be used for each of the comparisons 
between bermekimab treatment groups and placebo group.
There will be 3 comparisons for the primary analyses. The proportion of participants who achieve 
HiSCR50 will be compared between bermekimab treatment groups and the placebo group based 
on the fixed-sequence testing approach. To maintain an overall Type I error rate of 0.1, the 3-
pairwise comparisons will be performed sequentially at a two-sided alpha level of 0.1 in the 
following order:  
1.
Bermekimab 1050 mg group versus Placebo at Week 12 based on the combined data from   
Part 1 and Part 2
2.         Bermekimab 1050 mg group versus Placebo at Week 16 based on the data from Part 1
3.
Bermekimab 700 mg group versus Placebo at Week 12 based on the combined data from   
Part 1 and Part 2
With the pre-specified sequential analyses, whenever a prior comparison is not significant at a 
two-sided alpha level of 0.1, the remaining treatment group comparisons will be considered 
nonsignificant and the p-values from the remaining treatment group comparison will be considered 
nominal.
In addition, the comparison between adalimumab and placebo for the primary endpoint at Week 16 
in Part 1 will also be performed.


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This method is to control the type-1 error at 10% level or less and will only be implemented for 
the primary efficacy analysis. The study will be considered positive if one of the hypotheses is 
tested as significant at a 2-sided alpha level of 0.10.
To examine the robustness of the primary endpoint analysis, additional analyses will be conducted 
using different missing data approaches; these analyses will be described in the SAP. In addition, 
sensitivity analyses will be performed for the primary endpoint using the per-protocol population, 
which includes participants who are generally compliant with the protocol.
To evaluate the consistency of the efficacy, subgroup analyses of the primary endpoint will be 
performed.
9.4.2.2.
Secondary Endpoints
In addition to the primary endpoint analysis, the analyses for secondary efficacy endpoints will be 
performed. No adjustments for multiple comparisons will be made for the secondary endpoints 
and nominal p-values will be provided. The efficacy endpoints will also be summarized over time. 
Additional efficacy analyses may be performed and will be documented in the SAP.

The proportion of participants who achieved HiSCR75 and HiSCR90 at Week 16 in Part 1, 
and at Week 12 in Part 2 will be compared between each of the bermekimab groups and the 
placebo group.

The change from baseline in AN count at Week 16 in Part 1, and at Week 12 in Part 2 will be 
compared between each of the bermekimab groups and the placebo group.

The proportion of participants achieving at least 50%, 75%, 90%, and 100% reduction in total 
AN count at Week 16 in Part 1, and at Week 12 in Part 2 will be compared between each of 
the bermekimab groups and the placebo group.

The proportion of participants achieving AN count of 0/1 and 0/1/2 at Week 16 in Part 1, and 
at Week 12 in Part 2 will be compared between each of the bermekimab groups and the 
placebo group.

The proportion of participants who achieved complete elimination of abscesses at Week 16 in 
Part 1, and at Week 12 in Part 2 will be compared between each of the bermekimab groups 
and the placebo group among participants who had any abscess at baseline.

The change from baseline in number of abscesses at Week 16 in Part 1, and at Week 12 in 
Part 2 will be compared between each of the bermekimab groups and the placebo group.

The proportion of participants who achieved complete elimination of draining fistulas at 
Week 16 in Part 1, and at Week 12 in Part 2 will be compared between each of the bermekimab 
groups and the placebo group among those with draining fistulas at baseline.

The change from baseline in number of draining fistulas at Week 16 in Part 1, and at Week 12 
in Part 2 will be compared between each of the bermekimab groups and the placebo group.

The proportion of participants who achieved complete elimination of inflammatory nodules 
at Week 16 in Part 1, and at Week 12 in Part 2 will be compared between each of the 
bermekimab groups and the placebo group among those with inflammatory nodules at 
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
The change from baseline in international hidradenitis suppurativa severity score (IHS4) at 
Week 16 in Part 1, and at Week 12 in Part 2 will be compared between each of the bermekimab 
groups and the placebo group.

The change from baseline in number of inflammatory nodules at Week 16 in Part 1, and at 
Week 12 in Part 2 will be compared between each of the bermekimab groups and the placebo 
group.

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1), or mild 
(2) and with at least 2-grade improvement relative to baseline at Week 16 in Part 1, and at 
Week 12 in Part 2 will be compared between each of the bermekimab groups and the placebo 
group.

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1) at 
Week 16 in Part 1, and at Week 12 in Part 2 among participants with HS-IGA score of 
moderate (3) or severe (4) at baseline will be compared between each of the bermekimab
groups and the placebo group.

The change from baseline in DLQI at Week 16 in Part 1, and at Week 12 in Part 2 will be 
compared between each of the bermekimab groups and the placebo group. 

The change from baseline in HSSD-24h total symptom score at Week 16 in Part 1, and at 
Week 12 in Part 2 will be compared between each of the bermekimab groups and the placebo 
group.

The change from baseline in pain scale score of HSSD-24h at Week 16 in Part 1, and at 
Week 12 in Part 2 will be compared between each of the bermekimab groups and the placebo 
group.

The change from baseline in itch scale score of HSSD-24h at Week 16 in Part 1, and at 
Week 12 in Part 2 will be compared between each of the bermekimab groups and the placebo 
group.
The comparison between the adalimumab and placebo groups for the secondary endpoints at 
Week 16 in Part 1 listed above will also be performed at a 2-sided significance level of 0.1.
Nominal p-values will be reported. No adjustments for multiple comparisons will be made for the 
secondary endpoints.
In addition, to assess the relative efficacy between the bermekimab and adalimumab groups, for 
selected binary endpoints (including HiSCR50 at Week 16), the difference in proportion of 
participants achieving these endpoints at Week 16 and Week 32 in Part 1 between the bermekimab 
group and the adalimumab group, and the corresponding 80% CIs, will be calculated. No 
hypothesis testing will be performed.
9.4.2.3.
Exploratory Endpoints
The following endpoints will be explored as exploratory endpoints. The secondary efficacy 
endpoints specified in Section 9.4.2.2 and selected efficacy endpoints in this section will also be 
summarized over time as exploratory analyses based on the combined data from Part 1 and Part 2. 
Detailed analyses will be specified in the SAP.

The change from baseline in HASI at Week 16 in Part 1, and at Week 12 in Part 2 will be 
compared between each of the bermekimab groups and the placebo group.


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
The distribution of the PGIS scale at Week 16 in Part 1, and at Week 12 in Part 2 will be 
compared between each of the bermekimab groups and the placebo group.

The distribution of the PGIC scale at Week 16 in Part 1, and at Week 12 in Part 2 will be 
compared between each of the bermekimab groups and the placebo group.

The change from baseline in PROMIS-29 total score and sub-scores at Week 16 in Part 1, and 
at Week 12 in Part 2 will be compared between each of the bermekimab groups and the 
placebo group.

Change from baseline in HSSD-7d score at Week 16 in Part 1, and at Week 12 in Part 2 will 
be compared between each of the bermekimab groups and the placebo group.

Change in high-sensitivity C-reactive protein (hs-CRP) from baseline to Week 16 in Part 1, 
and at Week 12 in Part 2.
9.4.3.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, discontinuation of study intervention due to 
AEs, changes in laboratory assessments, changes in vital signs, and changes in weight 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. 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 preexisting 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.
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 severe AEs.

The incidence and type of reasonably related AEs as assessed by the investigator.

The incidence and type of AEs leading to discontinuation of study.

The incidence and type of injection-site reactions.


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Listings of participants with SAEs, severe AEs, AEs leading to discontinuation of study 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.
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 2 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
Descriptive statistics of changes from baseline will be summarized at selected scheduled time 
points.
9.4.4.
Other Analyses 
Pharmacokinetic Analyses 
The PK evaluable population is defined as all the participants who received at least 1 complete 
dose of bermekimab and had at least 1 valid blood sample drawn for PK analysis after their first 
dose of bermekimab.
Serum bermekimab concentrations will be summarized by visit and treatment group. Descriptive 
statistics will be calculated at each sampling time point. Concentrations below the lowest 
quantifiable concentration will be treated as zero in the summary statistics. All serum 
concentrations below the lowest quantifiable concentration or missing data will be labeled as such 
in the concentration database. PK data may also be displayed graphically.
If feasible, population PK analysis of serum concentration-time data of bermekimab may be 
performed using nonlinear mixed-effects modeling. Data may be combined with those of other 
selected studies to support a relevant structural model. Available baseline participant 
characteristics (demographics, laboratory variables, genotypes, race, etc.) will be tested as 
potential covariates affecting PK parameters. Details will be given in a population PK analysis 
plan and the results of the population PK analysis will be presented in a separate report.


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Pharmacokinetic/Pharmacodynamic Analyses 
If data permit, the relationships between serum bermekimab concentration and efficacy may be 
examined when appropriate. If a relationship is observed, a suitable PK/PD model may be 
developed to describe the exposure-response relationship and will be presented in a separate 
technical report.
Immunogenicity Analyses 
The incidence and titers of antibodies to bermekimab will be summarized for all participants who 
receive at least 1 dose of bermekimab and have appropriate samples for detection of antibodies to 
bermekimab (i.e., participants with at least 1 sample obtained after their first dose of bermekimab).
A listing of participants who are positive for antibodies to bermekimab will be provided. The 
maximum titers of antibodies to bermekimab will be summarized for participants who are positive 
for antibodies to bermekimab.
The incidence of neutralizing antibodies (NAbs) to bermekimab will be summarized for 
participants who are positive for antibodies to bermekimab and have samples evaluable for NAbs 
to bermekimab.
Other immunogenicity analyses may be performed to further characterize the immune responses 
that are generated.
Biomarkers 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 biomarkers 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 biomarker 
analyses will be reported in separate technical reports.
Pharmacogenomic Analyses 
DNA samples will be used for research related to bermekimab or HS. They may also be used to 
develop tests/assays related to bermekimab and HS. Pharmacogenomic research may consist of 
the analysis of one or more candidate genes or of the analysis of genetic markers throughout the 
genome or analysis of the entire genome (as appropriate) in relation to bermekimab or HS clinical 
endpoints.
Results will be presented in a separate report.


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9.5.
Interim Analysis
An internal independent IAC will be established to review the interim data and formulate 
recommended decisions and/or actions in accordance with the objectives of the interim analyses. 
The IAC will consist of a clinician and a statistician (neither of whom are involved in study conduct 
or compound development), one of whom will chair the committee, and other members as required.
The details will be provided in a separate IAC charter.
The IAC will review the unblinded efficacy data and provide recommendations about the next step 
of study conduct based upon the results of the first (approximately n=75) and/or second 
(approximately n=150) interim efficacy analyses. Interim analyses will be performed based on the
primary endpoint, which is the proportion of participants achieving HiSCR50 at Week 16, and 
other selected efficacy endpoints. PK and biomarker analyses may also be performed at the interim 
analysis. Details of the plan for the interim analyses will be specified in the Interim Analysis SAP. 
The unblinded results will be limited to specific sponsor personnel not involved in the study. 
Interim analysis results will be not disseminated to investigators or individuals associated with the 
conduct of the study.
As specified in Section 4.1, this study will employ a Phase 2a/2b design, in which the decision to 
proceed to the Phase 2b portion of the study will depend on the results of 2 interim analyses.
At first, approximately 150 participants will be randomized to receive bermekimab 1050 mg, 
adalimumab, or placebo in a 1:1:1 ratio. Enrollment will pause once approximately 150 
participants are randomized. Two interim analyses will be performed. The first analysis will be 
performed when approximately 75 participants have completed Week 16 or have terminated study 
participation. The objective of this interim analysis is to assess whether favorable efficacy is seen 
in the 1050 mg bermekimab dose group or efficacy is low enough to consider termination of the 
study. Details will be specified in Interim Analysis Plan.
The second planned interim analysis will take place once the 150 participants have completed 
study participation to Week 16 or have terminated study participation. The objectives of the second 
interim analysis are to assess whether a favorable efficacy is seen in the 1050 mg bermekimab 
dose group if not determined as favorable at the first interim analysis or confirm the favorable 
efficacy observed from the first interim analysis, or efficacy is low enough to consider termination 
of the study or the observed efficacy suggests modification to study. Additional interim analysis 
for PK may take place based on the available PK samples when 150 participants reach Week 8 to 
enable coordinating output with efficacy at Week 16.
9.6.
Data Monitoring Committee
An external iDMC whose members are not directly involved in the conduct of 77474462HDS2001 
Phase 2a/2b study, will review unblinded safety data to ensure the safety of the participants 
enrolled in this study. The iDMC will convene for a prespecified look at safety after at least 12 
participants have received 4 weekly doses. The committee will also 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 DMC will consist of at least one clinical physician and 


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one statistician, not involved in the conduct of the study. 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
AD
atopic dermatitis
AE
adverse event
AN 
Abscess and inflammatory nodule
ARC
Anticipated Event Review Committee
BCG
Bacille Calmette-Guérin
β-hCG
Beta-human chorionic gonadotropin
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
CRF
case report form(s) (paper or electronic as appropriate for this study)
CTC
Common Terminology Criteria
CYP
cytochrome
DBL
database lock
DLQI
Dermatological Life Quality Index
ECG
Electrocardiogram
eDC
electronic data capture
FAS
full analysis set
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
HASI
Hidradenitis Suppurativa Activity and Severity Index
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HiSCR
Hidradenitis Suppurativa Clinical Response
HIV
human immunodeficiency virus
HRQoL
health-related quality of life
HRT
hormonal replacement therapy
HS
hidradenitis suppurativa
hs-CRP
high-sensitivity-C-reactive protein
HS-IGA
Hidradenitis Suppurativa Investigator’s Global Assessment
HSSD
Hidradenitis Suppurativa Symptom Diary
HSSD-24h
Hidradenitis Suppurativa Symptom Diary 24-hour recall 
HSSD-7d
Hidradenitis Suppurativa Symptom Diary 7-day recall
IAC
Interim Analysis Committee
IB
Investigator’s Brochure
ICE
intercurrent event
ICF
informed consent form
ICH
International Council for Harmonisation
iDMC
independent Data Monitoring Committee
IEC
Independent Ethics Committee
IgG1k
immunoglobulin G1 kappa
IHS4
International Hidradenitis Suppurativa Severity Score System
IL-1α
interleukin-1 alpha
IP
Investigational Product
IRB
Institutional Review Board
IV
Intravenous(ly)
IWRS
interactive web response system
LSmean
Least Square mean
mAb
monoclonal antibody
MCP-Mod
Multiple Comparison Procedures with modeling
MedDRA
Medical Dictionary for Regulatory Activities
MIT
medical infrared thermography
MMRM
Mixed-Effect Model Repeated Measure
MTX
methotrexate
NABs
neutralizing antibodies


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NSAIDs
non-steroidal anti-inflammatory drugs
PBMC
peripheral blood mononuclear cells
PD
pharmacodynamic(s)
PFS
prefilled syringe
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetic(s)
PQC
Product Quality Complaint
PRO
patient-reported outcome(s) 
PROMIS-29
Patient-Reported Outcomes Measurement Information System-29
QoL
quality of life
SAE
serious adverse event
SAP
statistical analysis plan
SC
Subcutaneous(ly)
SD
standard deviation
SoA
Schedule of Activities
SUSAR
suspected unexpected serious adverse reaction 
ULN
upper limit of normal
TB
tuberculosis
TEAE
treatment-emergent adverse events
TNF
tumor necrosis factor


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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 hidradenitis suppurativa
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 
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10.4.
Appendix 4: Regulatory, Ethical, and Study Oversight Considerations
10.4.1.
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current 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 CRF 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.


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Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
to the study site:

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 subinvestigators

Documentation of subinvestigator 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)


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
IB (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials

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 adverse events 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.
10.4.2.
Financial Disclosure
Investigators and subinvestigators 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.
10.4.3.
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.
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. 
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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 recontact 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.
Participants who are rescreened are required to sign a new ICF.
Participants will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the participant 
will be asked to sign and personally date a separate ICF indicating agreement to participate in the
optional research component. Refusal to participate in the optional research will not result in 
ineligibility for the study. A copy of this signed ICF will be given to the participant.
Completion of screening and randomization procedures within the specified approximately 6-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.
10.4.4.
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 DNA, 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.
10.4.5.
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 bermekimab, to understand 
hidradenitis suppurativa, to understand differential intervention responders, and to develop 
tests/assays related to bermekimab and hidradenitis suppurativa. The research may begin at any 
time during the study or the post-study storage period. 
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).
10.4.6.
Committees Structure
Details regarding the DMC are presented in Section 9.6.
10.4.7.
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding bermekimab 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 pharmacogenomic or 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 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 
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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 
pharmacogenomic or 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 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.


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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. The disclosure of the final study results will be performed after the end of study in order 
to ensure the statistical analyses are relevant.
10.4.8.
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. 
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review CRF 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. 
10.4.9.
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 CRF. All CRF 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 CRF 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 CRF. Any 
such worksheets will become part of the participant's source documents. Data must be entered into 
the eCRF in English. The CRF 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 a CRF are needed after 
the initial entry into the CRF, 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-
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10.4.10.
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 of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all adverse events and follow-up of adverse events; 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. Given that PROs are reports 
of a patient's health condition that come directly from the patient, without interpretation by a 
clinician or anyone else, the responses to PRO measures entered by trial participants into source 
records cannot be overridden by site staff or investigators.
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 other 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 CRF in the protocol include the eSource system, but information collected through eSource 
may not be limited to that found in the CRF.
10.4.11.
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 


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(eg, hospital/clinic/physician’s office medical records). The nature and location of all 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 can 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.
10.4.12.
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.
10.4.13.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF 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 investigational product. These documents will be retained for a longer period 


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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.
10.4.14.
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study/Site 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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10.5.
Appendix 5: Adverse Events, Serious Adverse Events, Product Quality 
Complaints, and Other Safety Reporting: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.5.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered 
a pharmaceutical (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 
International Council for Harmonisation [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 adverse events 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 
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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 bermekimab, the expectedness of an adverse event will 
be determined by whether or not it is listed in the IB.
10.5.2.
Attribution Definitions
Assessment of Causality
The causal relationship to study intervention is determined by the Investigator. The following 
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study intervention administration and the AE.
Not Related
There is not a reasonable causal relationship between study intervention administration and the 
AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.5.3.
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.
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).
10.5.4.
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, intercepted medication error, or potential medication error involving a 
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson & 


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Johnson medicinal product, eg, product name confusion, product label confusion, intercepted 
prescribing or dispensing errors)

Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the CRF.
10.5.5.
Procedures
All Adverse Events
All adverse events, regardless of seriousness, severity, or presumed relationship to study 
intervention, must be recorded using medical terminology in the source document and the CRF. 
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 CRF 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 phase, 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 personnel only)

Site number

Participant number

Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All serious adverse events that have not resolved by the end of the study, or that have not resolved 
upon the participant's discontinuation from 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 
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
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 CRF). 
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 serious adverse events. 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 4 weeks of the last administration of study 
intervention, whether or not the event is expected or associated with the study intervention, is 
considered a serious adverse event.
Information regarding serious adverse events will be transmitted to the sponsor using a serious 
adverse event reporting form and safety report form of the CRF, which must be completed and 
reviewed by a physician from the study site and transmitted in a secure manner to the sponsor 
within 24 hours. The initial and follow-up reports of a serious adverse event should be transmitted 
in a secure manner electronically or by facsimile (fax). Telephone reporting should be the 
exception and the reporter should be asked to complete the appropriate form(s) first.
10.5.6.
Product Quality Complaint Handling
Definition
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, reliability, or
performance of a distributed product, including its labeling, drug delivery system, or package 
integrity. A PQC may have an impact on the safety and efficacy of the product. In addition, it 
includes any technical complaints, defined as any complaint that indicates a potential quality issue 
during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage 
or distribution of the product or the drug delivery system.
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 


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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.
A sample of the suspected product should be maintained under the correct storage conditions until 
a shipment request is received from the sponsor.
10.5.7.
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues, PQC, or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.


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10.6.
Appendix 6: Contraceptive Guidance
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria. 
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and 
Appendix 3 Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other 
Safety Reporting: 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 follicle stimulating hormone (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 (for the purpose of this study)
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, 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.
Contraceptive (birth control) use by men or women should be consistent with local regulations 
regarding the acceptable methods of contraception for those participating in clinical studies.
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.


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Examples of Contraceptives 
EXAMPLES OF CONTRACEPTIVESa ALLOWED FOR FEMALE PARTICIPANTS 
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)

Tubal closure (eg, bilateral tubal occlusion, bilateral tubal ligation)

Azoospermic partner (vasectomized or due to medical cause)
(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.

Female condom with or without spermicidec

Cap, diaphragm, or sponge with spermicide

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus-interruptus)

Spermicides alone

Lactational amenorrhea method (LAM)


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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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10.7.
Appendix 7: Hepatitis B Virus (HBV) Screening with HBV DNA Testing
Participants must undergo screening for hepatitis B virus (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 study.

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 study. If 
required by local guidelines, only subjects who have undergone HBV DNA testing and 
confirmed negative will be eligible.

Participants who test positive only for surface antibody (anti-HBs+) are eligible for this 
study. If required by local guidelines, only subjects who have undergone HBV DNA testing 
and confirmed negative will be eligible.

Participants who test positive for surface antigen (HBsAg+) are NOT eligible for this study, 
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 positive, the subject is NOT eligible for this study. If the HBV DNA test is 
negative, the subject is eligible for this study. In the event the HBV DNA test cannot be 
performed, the subject is NOT eligible for this study. 
For participants who are not eligible for this study due to HBV test results, consultation with 
a physician with expertise in the treatment of hepatitis B virus infection is recommended. For 
subjects who are eligible with surface antigen (HBsAg) negative, core antibody (anti-HBc) 
and/or surface antibody (anti-HBs) positive, and HBV DNA test is negative, HBV DNA 
quantitation should be monitored according to local guidelines.
For Japan sites only: Participants with surface antigen (HBsAg) negative, core antibody (anti-
HBc), and/or surface antibody (anti-HBs) positive test results must undergo further HBV DNA 
testing. If the HBV DNA test is negative, the participant is eligible for this study and the HBV 
DNA testing should be performed every 4 weeks.




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10.8.
Appendix 8: 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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10.9.
Appendix 9: Hidradenitis Suppurativa Investigator’s Global Assessment
HS-IGA
Select a single unique category that best captures the subject’s HS global assessment
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
After the selection of the most appropriate IGA category, select the score that best captures each 
individual HS attribute most appropriately for the subject. The individual attribute numeric scores 
should not be utilized for calculating the overall IGA category score. 
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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10.10. Appendix 10: Hidradenitis Suppurativa Activity and Severity Index (HASI)


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10.11. Appendix 11: Hidradenitis Suppurativa Symptom Diary (HSSD) (7-Day 
Version)
Hidradenitis Suppurativa Symptoms Diary (7-Day Version)
Individuals with Hidradenitis Suppurativa (HS) may have lesions in several different 
parts of their body and may experience a range of symptoms. When answering the 
questions below, please consider your HS lesions in all of your affected areas.
Please indicate the severity of each symptom at its WORST during the past 7 days
using a scale of 0 to 10 (0=None and 10=Worst Possible).
1. How severe was the pain from your HS lesions at its WORST in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst 
Possible
2. How severe was the tenderness (sensitive to touch) from your HS lesions at its
WORST in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
3. How severe was the swelling from your HS lesions at its WORST in the past 7 
days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
4. How severe was the heat coming from your HS lesions at its WORST in the past 7 
days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
5. How severe was the pressure under your HS lesions at its WORST in the past 7 
days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
6. How severe was the itch from your HS lesions at its WORST in the past 7 days?


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0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
7. How severe was the odor from your HS lesions at its WORST in the past 7 days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
8. How severe was the drainage coming out from your HS lesions at its WORST in the 
past 7 days?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
In this next section, please indicate the severity of any flu-like symptoms due to your HS
during the past 7 days.
How severe were the flu-like symptoms (e.g., having body aches, feeling very tired, 
etc.) due to your HS at their WORST 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: Hidradenitis Suppurativa Symptom Diary (HSSD) (24-hour 
Version)
Hidradenitis Suppurativa Symptoms Diary (24-hour Version) 
Individuals with Hidradenitis Suppurativa (HS) may have lesions in several different 
parts of their body and may experience a range of symptoms. When answering the 
questions below, please consider your HS lesions in all of your affected areas.
Please indicate the severity of each symptom at its WORST during the past 24 hours
using a scale of 0 to 10 (0=None and 10=Worst Possible).
1. How severe was the pain from your HS lesions at its WORST in the past 24 
hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst 
Possible
2. How severe was the tenderness (sensitive to touch) from your HS lesions at its
WORST in the past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
3. How severe was the swelling from your HS lesions at its WORST in the past 24 
hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
4. How severe was the heat coming from your HS lesions at its WORST in the past 24 
hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
5. How severe was the pressure under your HS lesions at its WORST in the past 24 
hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible


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6. How severe was the itch from your HS lesions at its WORST in the past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
7. How severe was the odor from your HS lesions at its WORST in the past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
8. How severe was the drainage coming out from your HS lesions at its WORST in the 
past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
  None
Worst Possible
In this next section, please indicate the severity of any flu-like symptoms due to your HS
during the past 24 hours.
How severe were the flu-like symptoms (e.g., having body aches, feeling very tired, 
etc.) due to your HS at their WORST in the past 24 hours?
0
1
2
3
4
5
6
7
8
9
10
  None Worst Possible


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10.13. Appendix 13: 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 



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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 



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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10.14. Appendix 14: Patient Global Impression of Change (PGIC) of Hidradenitis 
Suppurativa 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


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10.15. Appendix 15: Patient Global Impression of Severity (PGIS) of Hidradenitis 
Suppurativa
Patient’s Global Impression of Severity (PGIS)
of Hidradenitis Suppurativa
Overall, how would you rate the severity of your Hidradenitis Suppurativa currently? 
(Please select one response)
1. None
2. Mild 
3. Moderate 
4. Severe 
5. Very Severe 


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10.16. Appendix 16: Patient-Reported Outcomes Measurement Information 
System-29


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10.17. Appendix 17: HS Lesion Monitoring Using Imaging (Visible Light
Photography and Medical Infrared Thermography
Medical imaging can be used in the clinical assessment of HS to complement manual palpation
(Elkin, 2020). As part of the 77474462HDS2001 study, visible light photography and medical 
infrared thermography (MIT) will be used to acquire images of lesions in HS patient. In the 
77474462HDS2001 study, the SWIFT medical solution will be used to perform the lesion imaging.
The SWIFT medical solution, which consists of the SWIFT app (installed on iPhone study phones 
provided to the sites), the SWIFT HEALX scientific calibrant stickers which allow for color and 
size calibration across images acquired at different time points and the SWIFT VISION thermal 
camera (which clips onto the study iPhones). Both visible light and MIT images will be acquired 
using the SWIFT solution.
At baseline and throughout the study, sites will collect images from both axillae (left and right), 
regardless of presence of HS lesions. Images will be analyzed by computer vision based algorithms 
to understand if the images can be used to identify lesion features and lesion heat distribution, 
which may be indicative of the levels of inflammation in lesions. Finally, imaging derived metrics 
will be compared to clinical evaluations of HS axilla lesions to determine the suitability of imaging 
for objective clinical assessment of HS. Imaging will be conducted in a limited number of 
participants who consent to this optional substudy at some clinical sites. Instructions for acquiring 
photographs and completing assessments are provided in the imaging manual. At visits when 
images are collected, imaging should be completed prior to clinical disease assessment by the 
investigator. The results of these analyses will be presented in a separate report.
References
Elkin, K., Daveluy, S., & Avanaki, K. (2020). Review of imaging technologies used in Hidradenitis Suppurativa. 
Skin Research and Technology, 26(1), 3–10. https://doi.org/10.1111/srt.12772


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10.18. Appendix 18: Guidance on Study Conduct during the COVID-19 Pandemic
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study-
related participant management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government requirements or the clinical judgment of the 
investigator to protect the health and well-being of participants and site staff. If, at any time, a 
participant’s safety is considered to be at risk, study intervention will be discontinued, and study 
follow-up will be conducted.
Scheduled visits that cannot be conducted in-person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study should 
be documented with the prefix “COVID-19-related” in the CRF. 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
If a participant has tested positive for COVID 19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report. 
ADDITIONAL ELEMENTS, WHERE APPLICABLE: 

Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the sponsor and investigator to maintain continuity of patient care and study integrity. Certain 
measures, such as those listed below, may be necessary and should be instituted in accordance 
with applicable (including local) laws, regulations, guidelines, and procedures:

remote (eg, by phone / telemedicine) or in-person, off-site (e.g. in-home) interactions 
between site staff (or designees) and patients for study procedures e.g. those related to 
safety monitoring / efficacy evaluation / study drug storage and administration (including 
training where pertinent)


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
procurement of study drug by patients (or designee) or shipment of study drug from the 
study site directly to patients for at-home administration (including the potential for 
patient self-administration of study drug)

laboratory assessments using a suitably accredited local laboratory; for selected measures 
(e.g. urine pregnancy), home testing may be employed

other procedures, eg, imaging, may be conducted at an appropriate facility

Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study 
should be documented with the prefix “COVID-19-related” in the CRF. 

other relevant study data elements impacted by the pandemic should also be documented 
/ labeled as “COVID-19-related” in CRFs and / or other study systems, as directed by 
detailed sponsor guidance. These may include missed / delayed / modified study visits / 
assessments / dosing, and instances where temporary measures such as those above are 
implemented. 

The sponsor will evaluate the totality of impact of COVID-19 on collection of key study data 
and additional data analyses will be outlined in study SAP(s). 

Precaution: for those who may carry a higher risk for severe COVID-19 illness (e.g. those 
aged over 65 years), follow guidance from local health authorities when weighing the potential 
benefits and risks of enrolling in the study, and during participation in the study.


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10.19. Appendix 19: Liver Safety: Suggested Actions and Follow-up 
Assessments
10.19.1.
Stopping Algorithm
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are 
met.
10.19.2.
Follow up Assessments
Phase 2 Liver Chemistry Stopping Criteria and Follow-up Assessments
Phase 2 liver chemistry stopping criteria are designed to assure participant safety and to evaluate 
liver event etiology. In patients with alternative clinical reasons for elevated liver enzymes (for 
example, patients experiencing exercise induced CPK elevation or cholelithiasis), rechallenge with 
investigational product may be possible after discussion with medical monitor.


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Liver Chemistry Stopping Criteria
ALT/AST-
absolute
ALT or AST- 5xULN
ALT/AST-
Increase
If cannot monitor:
ALT or AST- 3 x ULN and cannot be monitored weekly for 4 weeks
Or if able to monitor:
ALT or AST- 3xULN persists for 4 weeks
Total 
bilirubin1, 2
ALT or AST- 3xULN and total bilirubin 2xULN (or at least a doubling 
of direct bilirubin in known Gilbert’s syndrome)
INR2
ALT or AST- 3xULN and international normalized ratio (INR) >1.5, if 
INR measured
Symptomatic3
ALT or AST- 3xULN associated with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity
Suggested Actions, Monitoring and Follow-up Assessments
Actions
Follow-up Assessments
Immediately stop study intervention
Report the event to the sponsor within 
24 hours
Complete an SAE form2
Perform follow-up assessments as described in 
the Follow Up Assessment column
Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or return 
to baseline (see MONITORING)
MONITORING:
If ALP <2 x ULN ,ALT or AST- 3xULN 
AND total bilirubin 2xULN (or at least a 
doubling of direct bilirubin in known Gilbert’s 
syndrome) or INR >1.5 (if measured): 
Repeat liver chemistry tests (include ALT, 
aspartate transaminase [AST], alkaline 
phosphatase, total and direct bilirubin and 
INR) and perform liver event follow-up 
assessments within 24 hours
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, 
or return to baseline
A specialist or hepatology consultation is 
recommended
If ALT or AST- 3xULN AND total bilirubin 
<2xULN and INR 1.5: 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, total and direct 
Viral hepatitis serology4
Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show downward 
trend
Obtain blood sample for 
pharmacokinetic (PK) within 1 week 
of the event of ALT or AST ≥3xULN5
Obtain serum creatine phosphokinase 
(CPK), lactate dehydrogenase (LDH), 
gamma-glutamyltransferase [GGT], 
glutamate dehydrogenase [GLDH], 
and serum albumin
Fractionate bilirubin
Obtain complete blood count with 
differential to assess eosinophilia
Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the CRF as per 
CRF completion guidelines
Record use of concomitant 
medications (including 
acetaminophen, herbal remedies, 
recreational drugs and other over-the-
counter medications)
Record alcohol use on the CRF as per 
CRF completion guidelines


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bilirubin and INR) and perform liver chemistry 
follow-up assessments within 24 to 72 hours
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to baseline
RESTART/RECHALLENGE
If liver event causality is determined to be 
“not related”, restart may be permitted 
upon written approval of the sponsor. See 
restart guidelines
If ALT or AST 3xULN AND total 
bilirubin 2xULN or INR >1.5 (if 
measured) obtain the following in 
addition to the assessments listed above:
Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG) or gamma globulins
Serum acetaminophen adduct assay, 
when available, to assess potential 
acetaminophen contribution to liver 
injury in participants with definite or 
likely acetaminophen use in the 
preceding week
Liver imaging (ultrasound, magnetic 
resonance, or computerized 
tomography) and/or liver biopsy to 
evaluate liver disease; complete CRF 
as per CRF completion guidelines
Liver biopsy may be considered and 
discussed with local specialist if 
available:

In participants when serology 
raises the possibility of 
autoimmune hepatitis (AIH)

In participants when suspected 
DILI progresses or fails to resolve 
on withdrawal of study 
intervention

In participants with acute or 
chronic atypical presentation
If liver biopsy conducted complete 
CRF as per CRF completion 
guidelines
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention if ALT 3xULN and total bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable 
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
2. All events of ALP <2 x ULN, ALT or AST- 3 x ULN and total bilirubin 2xULN (or at least a doubling of 
direct bilirubin in known Gilbert’s syndrome) or ALP <2 x ULN , ALT or AST- 3 x ULN and INR >1.5 (if 
measured) may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported to sponsor in an 
expedited manner and as an SAE if SAE criteria are met (excluding studies of hepatic impairment or 
cirrhosis). The INR stated threshold value will not apply to participants receiving anticoagulants.
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).


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4. Includes: hepatitis A immunoglobulin M (IgM) antibody; HBsAgG and HBcAB; hepatitis C RNA; 
cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile 
antibody or monospot testing); and hepatitis E IgM antibody.
5. PK sample may not be required for participants known to be receiving placebo or non-comparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior 
to the blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the laboratory manual.


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10.20. Appendix 20: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment 1 (08 July 2021)
Overall Rationale for the Amendment: The overall rationale for the amendment is to make the FibroTx 
Patch assessment optional due to the potential unavailability of the FibroTx Patch kits.
Section number
and Name
Description of Change
Brief Rationale
1.3 Schedule of 
Activities (SoA)
Subheaders were added for each SoA as follows: 
Section 1.3.1. Period 1 and Period 2 (Screening 
Through Week 16), and Section 1.3.2. Period 3 and 
Period 4 (Week 17 Though Week 36).
To clarify that the study periods are 
in 2 SoAs and to align with 
protocol terminology.
1.3.1 Period 1 and 
Period 2 (Screening 
through Week 16)
1.3.2 Period 3 and 
Period 4 (Week 17 
through Week 36)
8.6 Biomarkers
8.6.1 Skin 
Biomarkers
Footnote m was added to the FibroTx Patch 
assessment to indicate that participation is 
optional.
Footnote j was added to the FibroTx Patch 
assessment to indicate that participation is 
optional.
It was clarified that the FibroTx Patch assessment 
is to be collected for participants who consent to 
this optional part of the study and when kits are 
available.
The FibroTx Patch assessment is 
optional due to the potential 
unavailability of the FibroTx Patch 
kits.
8.6 Biomarkers
8.6.1 Skin 
Biomarkers
The wound exudate assessment is to be collected 
only for those participants who have wound 
exudate.
To clarify that the wound exudate 
assessment can only be collected 
for those participants who have 
wound exudate.
1.3.1 Period 1 and 
Period 2 (Screening 
through Week 16)
A vital signs assessment was added to the 
screening period.
The assessment was inadvertently 
omitted.
1.3.1 Period 1 and 
Period 2 (Screening 
through Week 16)
The Hidradenitis Suppurativa Investigator’s Global 
Assessment was removed from the screening 
period.
To clarify that this assessment is 
not needed at screening.
1.3.1 Period 1 and 
Period 2 (Screening 
through Week 16)
Serum, plasma, and whole blood sample 
assessments for biomarkers were added at Week 6.
An Exudate Swab assessment was removed at 
Week 4 and added at Week 6.
A FibroTx Patch assessment was removed at Week 
4 and added at Week 6 in the SoA and in 
footnote t.
The time points of selected 
biomarker assessments were 
updated to support dosing 
decisions.
1.3.1 Period 1 and 
Period 2 (Screening 
through Week 16)
8.2.3 
Electrocardiograms
An electrocardiogram was added at Week 16.
To monitor any changes after 
participants have received study 
intervention.
1.1 Synopsis
3 Objectives and 
Endpoints
The endpoints in the Synopsis, and Objectives and 
Endpoints were updated.
To align on consistent terminology.


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Section number
and Name
Description of Change
Brief Rationale
2.2 Background
The bermekimab no observed adverse effect level 
dose exposures maximum concentration and area 
under the curve for intravenous administration and 
subcutaneous administration were updated.
To align with the bermekimab 
Investigator’s Brochure (IB).
4.2.1 Study-Specific 
Ethical Design 
Considerations
8 Study 
Assessments and 
Procedures
The expected total blood volume to be collected 
from each participant was removed.
A statement was added that the maximum amount 
of blood drawn per participant will not exceed 
500 mL.
Table 1: Volume of Blood to be Collected from 
Each Participant was removed.
To reduce the site-level operational 
burden.
5.1 Inclusion 
Criteria
Inclusion criterion 12 was modified to increase the 
interval during which the participant agrees not to 
receive a live virus or live bacterial vaccination 
after the last administration of study intervention 
from 5 weeks to 90 days.
To align with the bermekimab IB 
guidance on the use of live virus or 
live bacterial vaccination.
5.2 Exclusion 
Criteria
5.3 Lifestyle 
Considerations
Exclusion criterion 11 was modified to remove the 
recommendation on vaccinations in the NOTES on 
COVID-related exclusion, which was moved to 
lifestyle considerations.
To clarify that the vaccination 
recommendations are not intended 
to be eligibility criteria.
6.7.4 Analgesic 
Therapy
A statement that participants will not be permitted 
to use any analgesics related to hidradenitis 
suppurative pain within 24 hours of a scheduled 
study visit was removed.
The statement was not applicable 
because pain is recorded in the 
participant’s diary entries and not 
assessed at scheduled study visits.
7.1 Discontinuation 
of Study 
Intervention
8.2.6 Allergic 
Reactions
Detailed clinical specifications regarding 
hypersensitivity reactions were removed.
Revised clinical recommendations for assessing 
hypersensitivity reactions were consolidated in 
Section 7.1.
To provide flexibility for clinicians 
in assessing the severity of 
hypersensitivity reactions and 
consolidate clinical 
recommendations in a single 
section of the protocol. 
8.2.7 Injection-site 
Reactions
It was specified that participants should be 
monitored for the occurrence of injection-site 
reactions for 30 minutes after the study 
intervention administration.
To clarify the length of time of 
observation for injection-site 
reactions.
8.3.1 Time Period 
and Frequency for 
Collecting Adverse 
Event and Serious 
Adverse Event 
Information
10.3 Appendix 3: 
Clinical Laboratory 
Tests
The parameters and reporting requirements for a 
possible/potential Hy’s Law case were added.
To clarify reporting requirements.
10.6 Appendix 6: 
Contraceptive 
Guidance
Bilateral tubal occlusion was updated as an 
example of tubal closure.
To clarify that other types of tubal 
closure are considered highly 
effective, user independent methods 
of contraception.
10.7 Appendix 7: 
Hepatitis B Virus 
(HBV) Screening 
Guidelines for hepatitis B screening specific to 
participants from sites in Japan were added.
To provide guidance and the 
evaluations to be obtained in the 
setting of specific patterns of 


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Section number
and Name
Description of Change
Brief Rationale
with HBV DNA 
Testing
hepatitis B virus test abnormalities 
in Japan.
10.10 Appendix 10: 
Hidradenitis 
Suppurativa Activity 
and Severity Index 
(HASI)
The 2018 version of the HASI was replaced with 
the 2019/2020 version of the HASI.
A new version of the index was 
received from the developer.
10.17 Appendix 17: 
Hidradenitis 
Suppurativa Lesion 
Monitoring Using 
Imaging (Visible 
Light Photography
and Medical 
Infrared 
Thermography
The Spectron IR system was removed as an option 
to perform the lesion imaging.
The Spectron IR system is not 
available.
10.19 Appendix 19: 
Liver Safety: 
Suggested Actions 
and Follow-up 
Assessments
An appendix with the liver safety stopping 
algorithm and follow-up assessments was added.
The sponsor’s template was 
updated to provide guidance and 
evaluations to be obtained in the 
setting of specific patterns of liver 
enzymes abnormalities.
1.3.1 Period 1 and 
Period 2 (Screening 
through Week 16)
1.3.2 Period 3 and 
Period 4 (Week 17 
through Week 36)
Acronym definitions were added to the SoA.
The definitions were inadvertently 
omitted.
Throughout the 
protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.


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11.
REFERENCES
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Elkin, K., Daveluy, S., & Avanaki, K. (2020). Review of imaging technologies used in Hidradenitis Suppurativa. 
Skin Research and Technology, 26(1), 3–10.
FDA Guidance for Industry: Drug-Drug Interaction Assessment for Therapeutic Proteins (Draft Aug 2020). 
Available at: https://www.fda.gov/media/140909/download. Assessed 18 July 2022.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. 
Clin Experi Dermatol. 1994;19(3):210-216.
Gottlieb A, Natsis NE, Kerdel F, et al. A Phase II Open-Label Study of Bermekimab in Patients with Hidradenitis 
Suppurativa Shows Resolution of Inflammatory Lesions and Pain. J Invest Dermatol. 2020;140(8):1538-1545.e2.
Humira SmPC - https://www.ema.europa.eu/en/documents/product-information/humira-epar-product-
information_en.pdf, Accessed 23 Apr 2021.
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.
Jemec GBE. Hidradenitis suppurativa. N Engl J Med 2012; 366:158-164.
Kanni T, Argyropoulou M, Spyridopoulos T, et al. MABp1 Targeting IL-1α for Moderate to Severe Hidradenitis 
Suppurativa Not Eligible for Adalimumab: A Randomized Study. J Invest Dermatol. 2018;138(4):795-801. 
Kimball AB, Jemec GB, Yang M, et al. Assessing the validity, responsiveness and meaningfulness of the 
Hidradenitis Suppurative Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. 
Br J Dermatol. 2014;171:1434-1442.
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.
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.
Margesson LJ. Hidradenitis suppurativa. Best Pract Res Clin Obstet Gynaecol. 2014; 28(7):1013-1027.
Murphy JE, Robert C, Kupper TS. Interleukin-1 and cutaneous inflammation: a crucial link between innate and 
acquired immunity. J Invest Dermatol. 2000;114(3):602-608.
Okun M, Yang M, Sundaram M, Gu Y. Validation of the hidradenitis suppurative clinical response as a clinical 
endpoint for hidradenitis suppurative treatment evaluation. Journal of the American Academy of Dermatology.
2013;68(4): suppl. 1, AB68.
Renton KW. Regulation of drug metabolism and disposition during inflammation and infection. Expert Opin Drug 
Metab Toxicol. 2005;1(4):629-640. 
Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of 
anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and 
Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391-397. 
Vekic DA (2018a), Cains GD. Hidradenitis suppurativa, a review of pathogenesis, associations and management. 
Part 2. Australas J Dermatol. 2018;59(4):261-266.


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Vekic DA (2018b), Frew J, Cains GD. Hidradenitis suppurativa, a review of pathogenesis, associations and 
management. Part 1. Australas J Dermatol. 2018;59(4):267-277.
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.



SAP_001.pdf: 
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1
Status: Final, Date: 14 November 2022
Janssen Research & Development
Statistical Analysis Plan
A Phase 2b, Multicenter, Randomized, Placebo and Active Comparator-controlled, 
Double-Blind, Dose-ranging Study to Evaluate the Safety and Efficacy of Bermekimab 
(JNJ-77474462) for the Treatment of Subjects with Moderate to Severe Hidradenitis 
Suppurativa.
Protocol JNJ-77474462HDS2001; Phase 2b  
JNJ-77474462  (bermekimab)
Status:
Final
Date:
14 November 2022
Prepared by:
Janssen Research & Development, LLC  
Document No.: EDMS-EDMS-RIM-865471
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04988308


JNJ-77474462  (bermekimab)
Statistical Analysis Plan JNJ-77474462HDS2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Final, Date: 14 November 2022
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
VERSION HISTORY..................................................................................................................................... 4
1.
INTRODUCTION.................................................................................................................................. 5
1.1.
Objectives and Endpoints ................................................................................................................ 5
1.2.
Study Design.................................................................................................................................... 8
2.
STATISTICAL HYPOTHESES.......................................................................................................... 12
3.
SAMPLE SIZE DETERMINATION.................................................................................................... 12
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS..................................................................... 16
5.
STATISTICAL ANALYSES............................................................................................................... 16
5.1.
General Considerations ................................................................................................................. 16
5.1.1.
Visit Windows ............................................................................................................................. 16
5.1.2.
Reference Date, Study Day and Relative Day ........................................................................... 16
5.2.
Participant Dispositions.................................................................................................................. 17
5.3.
Primary Endpoint Analysis ............................................................................................................. 17
5.3.1.
Definition of Endpoint(s) ............................................................................................................. 17
5.3.2.
Estimand..................................................................................................................................... 18
5.3.2.1.
Primary Estimand (Composite Estimand) ............................................................................... 18
5.3.2.2.
Supplementary Estimand (Treatment Policy Estimand):......................................................... 19
5.3.3.
Analysis Methods for the Primary Estimand............................................................................... 19
5.3.4.
Analysis for Supplementary Estimand (Treatment Policy Estimand) ......................................... 19
5.4.
Secondary Endpoints Analysis ...................................................................................................... 20
5.4.1.
Multiplicity Adjustment for Testing Procedures .......................................................................... 20
5.4.2.
Definition of Secondary Endpoints ............................................................................................. 20
5.4.2.1.
Hidradenitis Suppurativa Clinical Response (HiSCR)............................................................. 20
5.4.2.2.
Lesion Count............................................................................................................................ 20
5.4.2.3.
International Hidradenitis Suppurativa Severity Score System (IHS4)................................... 20
5.4.2.4.
Hidradenitis Suppurativa Investigator’s Global Assessment................................................... 20
5.4.2.5.
Hidradenitis Suppurativa Symptom Diary (HSSD) .................................................................. 20
5.4.3.
Estimands for Secondary Endpoints .......................................................................................... 21
5.4.4.
Analysis Methods for Secondary Endpoints............................................................................... 22
Binary Endpoints ......................................................................................................................................... 22
Continues Endpoints ................................................................................................................................... 23
5.5.
Exploratory Endpoints.................................................................................................................... 24
5.5.1.
Endpoint Definitions.................................................................................................................... 24
5.5.1.1.
Hidradenitis Suppurativa Clinical Response (HiSCR)............................................................. 24
5.5.1.2.
Lesion Counts.......................................................................................................................... 24
5.5.1.3.
International Hidradenitis Suppurativa Severity Score System (IHS4)................................... 24
5.5.1.4.
Hidradenitis Suppurativa Investigator’s Global Assessment (HS-IGA)................................... 24
5.5.1.5.
Hidradenitis Suppurativa Symptom Diary (HSSD) .................................................................. 24
5.5.1.6.
Hidradenitis Suppurativa Activity and Severity Index (HASI).................................................. 24
5.5.2.
Analysis Methods........................................................................................................................ 25
5.5.2.1.
Analysis Related to HiSCR...................................................................................................... 25
5.5.2.2.
Analyses Related to Lesion Count .......................................................................................... 25
5.5.2.3.
Analysis Related to IHS4......................................................................................................... 25
5.5.2.4.
Analyses Related to HS-IGA ................................................................................................... 25
5.5.2.5.
Analyses Related to HASI ....................................................................................................... 25
5.5.2.6.
Analyses Related to HSSD...................................................................................................... 26


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Status: Final, Date: 14 November 2022
5.6.
Safety Analyses ............................................................................................................................. 26
5.6.1.
Extent of Exposure ..................................................................................................................... 26
5.6.2.
Adverse Events........................................................................................................................... 26
5.6.3.
Additional Safety Assessments .................................................................................................. 27
5.6.3.1.
Clinical Laboratory Tests......................................................................................................... 27
5.7.
Other Analyses............................................................................................................................... 28
5.7.1.
Pharmacokinetics ....................................................................................................................... 28
5.7.2.
Immunogenicity (Antibodies to Bermekimab)............................................................................. 29
5.8.
Interim Analyses............................................................................................................................. 29
5.9.
Data Monitoring Committee (DMC)................................................................................................ 30
6.
SUPPORTING DOCUMENTATION .................................................................................................. 31
6.1.
Appendix 1 List of Abbreviations.................................................................................................... 31
6.2.
Appendix 2 Changes to Protocol-Planned Analyses ..................................................................... 32
6.3.
Appendix 3 Demographics and Baseline Characteristics.............................................................. 33
6.4.
Appendix 4 Protocol Deviations ..................................................................................................... 34
6.5.
Appendix 5 Prior and Concomitant Medications............................................................................ 35
6.6.
Appendix 7 Intervention Compliance ............................................................................................. 36
6.7.
Appendix 8 Adverse Events of Special Interest............................................................................. 37
6.8.
Appendix 9 Medications of Special Interest................................................................................... 38
6.9.
Appendix 10 Laboratory Toxicity Grading...................................................................................... 39


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VERSION HISTORY
SAP Version History Summary
SAP Version
Approval Date
Change
Rationale
Final
Not Applicable
Initial release


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Status: Final, Date: 14 November 2022
1.
INTRODUCTION
The protocol JNJ-77474462HDS2001 is comprised of 2 parts, Phase 2a (Part 1) and Phase 2b (Part 
2). An interim analysis (IA) was performed when 50% participants in Part 1 have completed Week 
16 visit. The IA futility criterion was met and the decision was made to terminate the study on 
October 14, 2022. This Statistical Analysis Plan (SAP) contains definitions of analysis sets, 
derived variables, and statistical methods for all planned analyses of efficacy, safety, 
pharmacokinetics (PK), and immunogenicity of bermekimab for Part 1. 
1.1.
Objectives and Endpoints 
Objectives
Endpoints
Primary

To evaluate the clinical efficacy of 
bermekimab in participants with 
moderate to severe HS.

Proportion of participants achieving HiSCR50 at 
Week 16 in Part 1.

Proportion of participants achieving HiSCR50 at 
Week 12 in Part 2.
Secondary

To evaluate the clinical efficacy of 
bermekimab in participants with 
moderate to severe HS.

Proportion of participants achieving HiSCR75 and 
HiSCR90 at Week 16 in Part 1, and at Week 12 in Part 
2.

Change from baseline in the abscess and inflammatory 
nodule (AN) count at Week 16 in Part 1, and at Week 
12 in Part 2.

Proportion of participants achieving at least 50%, 
75%, 90%, and 100% reduction in total AN count at 
Week 16 in Part 1, and at Week 12 in Part 2.

Proportion of participants achieving an AN count of 
0/1 and 0/1/2 at Week 16 in Part 1, and at Week 12 in 
Part 2.

Proportion 
of 
participants 
achieving 
complete 
elimination of abscesses at Week 16 in Part 1, and at 
Week 12 in Part 2 among those participants with 
abscesses at baseline.

Change in the number of abscesses from baseline to 
Week 16 in Part 1, and at Week 12 in Part 2.

Proportion 
of 
participants 
achieving 
complete 
elimination of draining fistulas at Week 16 in Part 1, 
and at Week 12 in Part 2 among those participants with 
draining fistulas at baseline.

Change in number of draining fistulas from baseline to 
Week 16 in Part 1, and at Week 12 in Part 2.

Proportion of participants achieving complete 
elimination of inflammatory nodules at Week 16 in 
Part 1, and at Week 12 in Part 2 among those 
participants with inflammatory nodules at baseline.


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Status: Final, Date: 14 November 2022
Objectives
Endpoints

Change in number of inflammatory nodules from 
baseline to Week 16 in Part 1, and at Week 12 in Part 
2.

Change of International Hidradenitis Suppurativa 
Severity Score System (IHS4) score from baseline to 
Week 16 in Part 1, and at Week 12 in Part 2.

Proportion of participants with HS-Investigator’s 
Global Assessment (HS-IGA) score of inactive (0), 
almost inactive (1), or mild (2) and with at least 2-
grade improvement relative to baseline at Week 16 in 
Part 1, and at Week 12 in Part 2.

Proportion of participants with HS-IGA score of 
inactive (0) or almost inactive (1) at Week 16 in Part 
1, and at Week 12 in Part 2 among participants with 
HS-IGA score of moderate (3) or severe (4) at 
baseline.

To characterize additional patient-
reported outcome efficacy measures 
of bermekimab in participants with 
moderate to severe HS. 

Change in Dermatology Life Quality Index (DLQI)
score from baseline to Week 16 in Part 1, and at Week 
12 in Part 2.

Change in Hidradenitis Suppurativa Symptom Diary 
(HSSD-24h) score from baseline to Week 16 in Part 1, 
and at Week 12 in Part 2.

Change in pain scale score of HSSD-24h from 
baseline to Week 16 in Part 1, and at Week 12 in Part 
2.

Change in itch scale score of HSSD-24h from baseline 
to Week 16 in Part 1, and at Week 12 in Part 2.

To assess the safety and tolerability of 
bermekimab in participants with 
moderate to severe HS.

Number/proportion of participants with treatment-
emergent adverse events (TEAEs).

Number/proportion of participants with treatment-
emergent serious adverse events (SAEs).

Number/proportion of participants with abnormal 
safety laboratory values.

To evaluate the pharmacokinetics 
(PK) 
and 
immunogenicity 
of 
bermekimab in participants with 
moderate to severe HS. 

Bermekimab concentration will be summarized for 
treated participants over time.

The incidence of antibodies to bermekimab will be 
summarized.
Exploratory

To evaluate the clinical efficacy of 
bermekimab in participants with 
moderate to severe HS.

Change of Hidradenitis Suppurativa Area and Severity 
Index (HASI) score from baseline to Week 16 in Part 
1, and at Week 12 in Part 2.

Proportion of participants achieving HiSCR50, 
HiSCR75, and HiSCR90 over time.


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Objectives
Endpoints

Change from baseline in AN count over time.

Proportion of participants achieving at least 50%, 
75%, 90%, and 100% reduction in total AN count over
time.

Change in the number of abscesses, draining fistulas, 
and inflammatory nodules from baseline over time.

Change of HASI score from baseline over time.

Change of IHS4 score from baseline over time.

Proportion of participants with HS-IGA score of 
inactive (0), almost inactive (1), or mild (2) and with 
at least 2-grade improvement relative to baseline over 
time.

Proportion of participants with HS-IGA score of 
inactive (0) or almost inactive (1) over time among 
participants with HS-IGA score of moderate (3) or 
severe (4) at baseline.

Change in high-sensitivity C-reactive protein (hs-
CRP) from baseline to Week 16 in Part 1 and from 
baseline to Week 12 in Part 2.

To characterize additional patient-
reported outcome efficacy measures 
of bermekimab in participants with 
moderate to severe HS.

Change in DLQI score from baseline over time.

Change in Hidradenitis Suppurativa Symptom Diary 
(HSSD-24h) score from baseline over time.

Change in pain scale score of HSSD-24h from 
baseline over time.

Change in itch scale score of HSSD-24h from baseline 
over time.

The distribution of the Patient Global Impression of 
Change (PGIC) of HS at Week 16 in Part 1, and at 
Week 12 in Part 2.

The distribution of the Patient Global Impression of 
Severity (PGIS) of HS at Week 16 in Part 1, and at 
Week 12 in Part 2. 

Change in PROMIS 29 total score and sub-scores from 
baseline to Week 16 in Part 1, and at Week 12 in Part 
2 and over time.

Change in Hidradenitis Suppurativa Symptom Diary 
(HSSD-7d) score from baseline over time.

To assess the impact of treatment with 
bermekimab on selected biomarkers.

Changes in cellular and molecular biomarkers in skin 
and blood from baseline.


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1.2.
Study Design
This is a randomized, double-blind, placebo- and active-comparator-controlled, Phase 2a/2b, 
multicenter study to assess the efficacy, safety, PK, and immunogenicity of subcutaneous (SC)
administered bermekimab 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 and are Hurley Stage II or Hurley Stage III as determined by the investigator.
This study employs a Phase 2a/2b design, in which the decision to proceed to the Phase 2b portion 
of the study will depend on the results of the interim analyses. 
Enrollment of this Phase 2a/Phase 2b design study will be divided in 2 parts. Part 1 will enroll 
approximately 150 participants, and Part 2 will enroll approximately 100 or 150 additional 
participants, depending on the number of dose regimens to be studied. Enrollment of Part 2 of the 
study will only begin after a positive benefit risk assessment is confirmed either at Interim Analysis 
1 or Interim Analysis 2. Therefore, a total number of approximately 250 or 300 participants will 
be enrolled in the study.
Part 1 of this study contains 4 study periods: Screening (Period 1), 16-week placebo-controlled 
period (Period 2), 16-week cross over period (Period 3), and 4-week safety follow up (Period 4). 
Part 2 of this study also contains 4 study periods: Screening (Period 1), 12-week placebo-controlled 
period (Period 2), 20-week cross over period (Period 3), and 4-week safety follow up (Period 4). 
During Study Period 3 (Weeks 16 to 32 in Part 1 and Weeks 12 to 32 in Part 2), the participants 
receiving placebo will crossover to receive bermekimab 1050 mg at Week 16 in Part 1 and Week 
12 in Part 2 and weekly thereafter through Week 31. Participants receiving bermekimab will 
continue to receive their assigned treatment through Week 31.
All participants who complete Week 31 of the study will enter safety follow-up (Week 31 through 
Week 36). The total duration of study participation will be approximately 42 weeks.
During Part 1 of the study, 150 participants will be randomized to receive bermekimab 1050 mg, 
adalimumab, or placebo in a 1:1:1 ratio. Two interim analyses are planned. The first interim 
analysis will occur after approximately 50% of participants complete 16 weeks of treatment. The 
second interim analysis will occur when 100% (n=150) of the participants complete 16 weeks of 
treatment. The goal of the interim analyses is to assess efficacy and safety of bermekimab at the 
dose evaluated prior to enrollment of Part 2 of this study. 
An internal Interim Analysis Committee (IAC) composed of members that are not involved with 
the study conduct will be established to review the interim data and recommend actions to the 
study team in accordance with the objectives of the interim analyses.
If a positive benefit-risk is observed in either the first or the second planned interim analysis based 
on data in Part 1, screening and randomization of participants will resume as planned in Part 2 of 
the study, with additional participants being randomized to receive placebo, bermekimab 1050 mg 
qw, bermekimab 1050 mg qw through Week 11 and from Week 12, bermekimab 1050 mg q2w 


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(bermekimab 1050 mg qw→q2w) or bermekimab 700 mg qw through Week 11 and from Week 
12, bermekimab 700 mg q2w (bermekimab 700 mg qw→q2w), in a 1:1:2:2 ratio (approximately 
25 participants randomized to receive bermekimab 1050 mg qw and placebo, respectively, and 
approximately 50 participants randomized to receive bermekimab 1050 mg qw→q2w and 
bermekimab 700 mg qw→q2w, respectively). Based on the interim analysis result, the 
bermekimab 700 mg qw→q2w arm may not be included in Part 2.  Thus, Part 2 will enroll 
approximately 100 or 150 participants, depending on the number of dose regimens to be studied.
If the results from interim analysis 1 meet the futility criteria, the totality of the data including 
other efficacy analyses provided for the first interim analysis will be reviewed before the decision 
is made on whether to terminate the trial for futility. If futility criteria are met following the Interim 
Analysis 2, enrollment will remain paused while the sponsor considers whether to terminate the 
study at that point for insufficient efficacy, to resume enrollment as planned, or to resume the study 
with modification.
In addition to the 2 interim analyses described above (database lock [DBL] is planned at the Interim 
Analysis 2 for Part 1), 2 planned DBLs will occur at Week 12 and at Week 36.
The end of the study is considered as the last visit for the last participant in the study.
Efficacy assessments (Hidradenitis Suppurativa Investigator’s Global Assessment [HS-IGA], 
lesion counts, Hurley Staging, Hidradenitis Suppurativa Symptom Diary [HSSD], Dermatological 
Life Quality Index [DLQI], Patient Global Impression of Change [PGIC] of Hidradenitis 
Suppurativa Severity, Hidradenitis Suppurativa Area and Severity Index (HASI), and Patient 
Global Impression of Severity [PGIS]) and Patient-Reported Outcomes Measurement Information 
System-29 [PROMIS-29] will be performed at visits according to the SoA. Serum samples for PK, 
immunogenicity and biomarker analyses will be collected at the timepoints in the SoA of the 
protocol.
An external independent Data Monitoring Committee (iDMC), whose members are not directly 
involved in the conduct of Study 77474462HDS2001, will review unblinded safety data to ensure 
the safety of the participants enrolled in this study. A prespecified look at safety will be 
implemented after a minimum of 12 participants have received 4 weekly doses. Furthermore, the 
iDMC will review the unblinded safety data at the time of the interim analysis and will be kept 
informed of any IA results impacting the benefit-risk considerations for the study.
INTERVENTION GROUPS AND DURATION 
Part 1:
Group 1: Placebo
Participants will receive 4 placebo SC injections at Week 0. Participants will receive 3 placebo SC 
injections at Week 1 and every week thereafter through Week 15. 
At Week 16, participants will cross over to receive 3 bermekimab 350 mg SC injections weekly 
through Week 31. 


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Group 2: Adalimumab
Participants will receive 4 adalimumab 40 mg SC injections at Week 0. Participants will receive 3 
placebo SC injections at Week 1. Participants will receive 2 adalimumab 40 mg SC injections and 
1 placebo SC injection at Week 2. Participants will receive 3 placebo SC injections at Week 3. 
Participants will receive 1 adalimumab 40 mg SC injection and 2 placebo SC injections at Week 
4 and every week thereafter through Week 31.
Group 3: Bermekimab 1050 mg SC qw
Participants will receive 3 bermekimab 350 mg SC injections and 1 placebo SC injection at Week 
0. Participants will receive 3 bermekimab 350 mg SC injections at Week 1 and every week 
thereafter through Week 31.
Part 2:
Group 1: Placebo
Participants will receive 3 placebo SC injections from Week 0 through Week 11. At Week 12, 
participants will cross over to receive 3 bermekimab 350 mg SC injections weekly through Week 
31. 
Group 2: Bermekimab 1050 mg SC qw
Participants will receive 3 bermekimab 350 mg SC injections at Week 0 and every week thereafter 
through Week 31.
Group 3: Bermekimab 1050 mg SC qw→q2w
Participants will receive 3 bermekimab 350 mg SC injections at Week 0 and every week 
thereafter through Week 11. From Week 12, participants will receive 3 bermekimab 350 mg SC 
injections every other week thereafter through Week 30. During weeks in which bermekimab is 
not administered, participants will receive 3 placebo SC injections through Week 31.
Group 4: Bermekimab 700 mg SC qw→q2w
Participants will receive 2 bermekimab 350 mg SC injections and 1 placebo SC injection at Week 
0 and every week thereafter through Week 11. From Week 12, participants will receive 2 
bermekimab 350 mg SC and 1 placebo SC injection every other week thereafter through Week 30. 
During weeks in which bermekimab is not administered, participants will receive 3 placebo SC 
injections through Week 31.
A diagram of the study design is provided in Figure 1.


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Figure 1:
Schematic Overview of the Study


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2.
STATISTICAL HYPOTHESES
The primary hypothesis of this study is that bermekimab is superior to placebo as assessed by the 
proportion of participants achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at 
Week 16 in Part 1 subjects with moderately to severely Hidradenitis Suppurativa disease. 

HiSCR50 is defined as at least 50% reduction in total abscess and inflammatory nodule 
counts (AN count) with no increase in abscess count and no increase in draining fistula 
count relative to baseline.
The null hypothesis to be tested is that there is no difference between the bermekimab and the 
placebo in proportion of participants achieving HiSCR50 at Week 16 in Part 1 subjects with 
moderately to severely Hidradenitis Suppurativa disease.
3.
SAMPLE SIZE DETERMINATION
This study is designed to enroll approximately 250 or 300 participants, in order to provide 
sufficient data to have adequate power for the primary endpoint. 
The sample size of 250 or 300 participants was also chosen in order to:

Have sufficient power to detect a difference between the bermekimab groups and the placebo 
group for the primary endpoint of the proportion of participants achieving HiSCR50 at 
Week 16 between the bermekimab treatment group and the placebo group in Part 1 and at 
Week 12 between bermekimab treatment groups and placebo group combining Part 1 and Part 
2.

Have an adequate confidence level for the treatment difference between the bermekimab high 
dose group and the adalimumab group in HiSCR50 at Week 16 in Part 1. 

Provide greater precision for the interim analysis efficacy analysis with more participants in 
the bermekimab 1050 mg, adalimumab, and placebo groups. 
The assumptions for the sample size and power calculations specified below were mainly based 
on the clinical data from the 77474462HDS2002 (PT-047) Phase 2 clinical study and from 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. 
The response rates observed in the 77474462HDS2002 (PT-047) study for HiSCR50 at 
Week 12/Week 16 were 55%/57% (bermekimab qw group), 44%/52% (bermekimab q2w group), 
and 44%/44% (placebo group), respectively. In addition, the HiSCR50 response rates in the 
adalimumab Phase 3 Studies M11-313 and M11-810 at Week 12 were 42% vs 26% and 59% vs 
28% in the adalimumab weekly and placebo groups, respectively. 
Comparisons between treatment groups at Week 16 with Part 1 data (all comparisons are at a 2-
sided type 1 error rate of 0.10; Table 1 and Table 2)


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
For comparison between bermekimab with placebo using data from Part 1 only for the primary 
endpoint at Week 16, the study sample size provides 83% power to detect a 25% treatment 
difference (50% vs 25%) with 50 participants per arm.

Greater than 99% power to detect a 40% (75% vs 35%) difference between the bermekimab 
1050 mg treatment group (n=50) and the placebo group (n=50).

From comparison between adalimumab with placebo using data from part 1 only for the 
primary endpoint, the study sample size provides 83% power to detect a 25% (50% vs 25%) 
treatment difference with 50 participants per arm. 
No formal comparisons will be performed between the bermekimab 1050 mg qw group and the 
adalimumab group from Part 1, however the treatment difference and its 2-sided 80% CI for the 
primary endpoint at Week 16 between these 2 groups will be provided. A sample size of 
50 participants in each of the treatment groups will produce a 2-sided 80% CI for the treatment 
difference with a width of approximately 29%.
Comparisons between treatment groups at Week 12 with combining Part 1 and Part 2 data
Assuming HiSCR50 response rates at Week 12 are 25% to 35% for placebo and 50% to 75% for 
the bermekimab groups, respectively; based on these assumptions, approximately 250 participants 
across Part 1 and Part 2 are planned to be randomized to the placebo (n=75), bermekimab 700 mg 
qw to q2w (n=50), bermekimab 1050 mg qw to q2w (n=50), and bermekimab 1050 mg qw (n=75) 
treatment groups. Comparisons between the bermekimab groups and the placebo groups will be 
based on data combining Part 1 and Part 2. 
For comparisons between bermekimab groups with placebo combining Part 1 and Part 2 for the 
primary endpoint, bermekimab 1050 mg qw and 1050 mg qw q2w groups will be grouped 
together as bermekimab 1050 mg group (n=125) and 700 mg qw q2w group will be denoted as 
bermekimab 700 mg group, the study sample size provides:

At least 87% power to detect a 25% treatment difference between the bermekimab 700 mg 
treatment group (n=50) and the placebo group (n=75).

97% power to detect a 25% (50% vs 25%) treatment difference between the bermekimab 1050 
mg treatment group (n=125) and the placebo group (n=75). 

Greater than 99% power to detect a 40% (75% vs 35%) difference between the bermekimab 
1050 mg treatment group (n=125) and the placebo group (n=75) or between 700 mg treatment 
group (n=50) and the placebo group (n=75).
in HiSCR50 at Week 12 combining Part 1 and Part 2 based on a 2-sample Z-test at a Type I error 
rate of 0.10 (2-sided; Table 3).


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Table 1:
Power to detect a treatment difference in HiSCR50 at Week 16 in Part 1 
Placebo
Treatment Group
Difference
Power
Bermekimab 1050 mg (n=50)/Adalimumab (n=50) vs placebo (n=50)
25%
50%
25%
83%
25%
55%
30%
93%
25%
60%
35%
97%
25%
65%
40%
99%
25%
70%
45%
>99%
25%
75%
50%
>99%
30%
55%
25%
81%
30%
60%
30%
92%
30%
65%
35%
97%
30%
70%
40%
99%
30%
75%
45%
>99%
35%
60%
25%
81%
35%
65%
30%
92%
35%
70%
35%
97%
35%
75%
40%
99%
Table 2:
Confidence interval for the treatment difference in HiSCR at Week 16 in Part 1
HiSCR (P1)
HiSCR (P2)
Difference
(P1 − P2)
Width
Confidence 
Limit
Confidence
Level
Bermekimab 1050 mg qw dose regimen (n=50; P1) vs adalimumab (n=50; P2)
60%
50%
10%
29.3%
(-4.7%,24.6%)
80%
65%
50%
15%
29.0%
(0.5%,29.5%)
80%
70%
50%
20%
28.6%
(5.7%,34.3%)
80%
75%
50%
25%
27.9%
(11.0%, 38.9%)
80%


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Table 3: 
Power to detect a treatment difference in HiSCR50 at Week 12 Combining Part 1 and Part 2
Placebo
Treatment Group
Difference
Power
Bermekimab 1050 mg (n=125) vs placebo (n=75)
25%
50%
25%
97%
25%
55%
30%
>99%
25%
60%
35%
>99%
25%
65%
40%
>99%
25%
70%
45%
>99%
25%
75%
50%
>99%
30%
55%
25%
97%
30%
60%
30%
99%
30%
65%
35%
>99%
30%
70%
40%
>99%
30%
75%
45%
>99%
35%
60%
25%
96%
35%
65%
30%
99%
35%
70%
35%
>99%
35%
75%
40%
>99%
Bermekimab 700 mg (n=50) vs placebo (n=75)
25%
50%
25%
89%
25%
55%
30%
96%
25%
60%
35%
99%
25%
65%
40%
>99%
25%
70%
45%
>99%
25%
75%
50%
>99%
30%
55%
25%
87%
30%
60%
30%
95%
30%
65%
35%
99%
30%
70%
40%
>99%
30%
75%
45%
>99%
35%
60%
25%
87%
35%
65%
30%
95%
35%
70%
35%
99%
35%
75%
40%
>99%


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4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
The populations for analysis are defined in Table 4 below.
Table 4 Description of analysis sets used to analyze the data in the study
Analysis Sets
Description
Enrolled
All participants who sign the ICF
Randomized Analysis Set
The randomized analysis set includes all participants who were randomized at Week 
0 in the study.
Full Analysis Set (FAS)
The full analysis set (FAS) includes all participants who were randomized at Week 0 
and received at least 1 dose of study intervention.
Modified Full Analysis Set 
(mFAS)
The mFAS includes all FAS participants who could have reached a visit by the time 
of the decision was made to terminate the study on 14 October 2022.
projected visit (weeks) = (decision date of study termination – first dose date +1) /7
Participants will be excluded in the analysis after projected visit.
Safety
The safety analysis set includes all participants who received at least 1 dose of study 
intervention.
Pharmacokinetics Analysis 
Set
The PK analysis set is defined as participants who received at least 1 dose of 
bermekimab and have at least 1 valid blood sample drawn for PK analysis.
Immunogenicity Analysis 
Set
The immunogenicity analysis set is defined as all participants who received at least 1 
dose of bermekimab and who have at least 1 sample obtained after their first dose of 
bermekimab for the detection of antibodies to bermekimab.
5.
STATISTICAL ANALYSES
5.1.
General Considerations
The statistical analyses will include all data available through the end of the study. Unless 
otherwise specified, data from all investigational centers/sites will be pooled for analysis.
In general, baseline is defined as the last observation prior to or at the time of the first study agent 
administration, unless otherwise specified.
5.1.1.
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 32 should occur within ± 3 days of the scheduled visit. 
5.1.2.
Reference Date, Study Day and Relative Day
The Reference Date is the date of the first study agent administration. If the date of the first study 
agent administration is missing or the first study agent administration is not done, then the 
Reference Date equals the corresponding visit date (eg, Week 0 visit date). If the corresponding 
visit date is also missing, then the Reference Date equals the randomization date. 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.


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
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.
5.2.
Participant Dispositions
The number of participants screened, and the number of participants screen failed will be 
summarized for all enrolled participants.
The number of participants in the following disposition categories will be summarized throughout 
the study by intervention group and overall based on Full Analysis Set:

Participants randomized

Participants who received study intervention

Participants who completed the study

Participants who discontinued study intervention
–
Reasons for discontinuation of study intervention

Participants who terminated study prematurely
–
Reasons for termination of study
The above categories will include summaries over the placebo-controlled period (through Week 
16) and the entire study (through Week 36).
Listings of participants will be provided for the following categories:

Participants who discontinued study intervention

Participants who terminated study prematurely

Participants who were unblinded during the study period

Participants who were randomized yet did not receive study intervention. Participants who 
were randomized with incorrect stratum.
5.3.
Primary Endpoint Analysis
5.3.1.
Definition of Endpoint(s)
The primary efficacy endpoint is the proportion of participants achieve a HiSCR50 at Week 16 in 
Part 1. HiSCR50 is defined as a ≥ 50% reduction in inflammatory lesion AN count (sum of 


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abscesses and inflammatory nodules), and no increase in abscesses and draining fistulas in HS 
compared with the lesions counted at baseline. 
5.3.2.
Estimand
An estimand is a precise definition of the primary targeted treatment effect defined by the 
following 5 attributes: Study Intervention, population, variable (endpoint), intercurrent events 
(ICEs) and corresponding strategies, and population-level summary.
Primary Trial Objective: to evaluate the efficacy of bermekimab in participants with moderate 
to severe HS.
Estimand Scientific Question of interest: What is the proportion of participants considered to 
have benefited from bermekimab versus placebo assessed by the HiSCR50 at Week 16 in Part 1, 
administered together with the protocol allowed background standard-of-care medication.
5.3.2.1.
Primary Estimand (Composite Estimand)
Study intervention:

Bermekimab 1050 mg

Placebo 
  Population: adult participants with moderate to severe HS

Variable/endpoint:
Response binary variable, where a responder is defined as a 
participant achieving an HiSCR50 response at Week 16 in Part 1 without experiencing 
any of the ICEs in categories 1-2 as outlined below prior to the Week 16 visit. 
Intercurrent Events (ICEs)
Analysis Strategy for Intercurrent Events
1.
Discontinuation of study intervention due
to lack of efficacy, an AE of worsening of 
HS
2.
Initiation of a protocol-prohibited
medication or therapy during the study
that could improve H S
Composite Strategy: Participants with these intercurrent event are 
considered as HiSCR50 non-responders after these events, and 
prior to Week 16, as reflected in variable definition.
3.
Discontinuation of study intervention for 
reasons other than ICE 1
Treatment Policy: observed data will be used regardless of 
whether or not this intercurrent event had occurred.
Note: For participants experiencing multiple ICEs, ICE 2 will override ICE 3. 
The composite strategy assesses the treatment effects not only based on the variable measurements, 
but also based on ICEs. This estimand acknowledges that having an ICE in categories 1-2 is an 
unfavorable outcome. For participants experiencing an ICE in category 3, the treatment policy 


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strategy considers the occurrence of ICE 3 irrelevant in defining the treatment effect, and any data 
observed after the associated ICE event will be used for the analysis.
Population level summary: Difference in the proportions of participants achieving an HiSCR50
response at Week 16 between the bermekimab 1050 mg and placebo intervention groups.
5.3.2.2.
Supplementary Estimand (Treatment Policy Estimand):
The supplementary estimand has the same components as the primary estimand, except for the 
strategy used below for ICEs 1-3. 
Treatment policy strategy:  assess the treatment effect regardless of whether or not intercurrent 
events had occurred. Under the treatment policy strategy, observed data collected after ICEs will 
be used in analysis.
5.3.3.
Analysis Methods for the Primary Estimand
The primary endpoints will be analyzed based on the composite estimand (Section 5.3.2.1) and the 
data from all participants in mFAS (Section 4.4) will be analyzed according to randomized 
treatment group regardless of the treatment actually received. Participants whose projected Week 
16 visits occur after study termination will be excluded in the primary analysis. Participants with 
ICEs 1-2 before Week 16 will be considered as HiSCR50 non-responders at Week 16. Participants 
with ICE 3, observed lesion data after this ICE will be utilized in the analysis. For participants 
experiencing multiple ICEs, an ICE 2 will override an ICE 3. After accounting for the ICEs for 
the primary estimand, the remaining missing data of the primary endpoint at Week 16 will be 
considered as a non-responder.
In this primary analysis, the proportion of participants who achieve a HiSCR50 at Week 16 will 
be summarized for each treatment group. To address the primary objective, a CMH chi-squared 
statistic stratified by baseline Hurley stage status (II, III) at an alpha level of 0.1 will be used for 
each of the comparisons between bermekimab treatment groups and placebo group. The 
comparison between adalimumab and placebo for the primary endpoints will also be performed.
Difference in response rates between each of the active groups and the placebo group adjusted for 
baseline Hurley stage status (II, III) using Mantel-Haenszel weight and the corresponding 90% CI 
will be presented.
In addition, the proportion of participants achieving a HiSCR50 response at Week 16 by 
investigator regions and site will be summarized.
5.3.4.
Analysis for Supplementary Estimand (Treatment Policy Estimand)
To examine the robustness of the primary endpoint analysis, the primary endpoint will be analyzed 
utilizing the treatment policy estimand. For participants who experience an intercurrent event, the 
analysis will be performed using observed data regardless of intercurrent events. The HiSCR50 
values collected after intercurrent event will be used in analysis and missing data will not be 
imputed.


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5.4.
Secondary Endpoints Analysis
5.4.1.
Multiplicity Adjustment for Testing Procedures
No multiplicity adjustments will be made for the secondary endpoints. All statistical testing will 
be performed at the 2-sided 0.1 significance level. Nominal p-values will be presented.
5.4.2.
Definition of Secondary Endpoints
5.4.2.1.
Hidradenitis Suppurativa Clinical Response (HiSCR)

HiSCR75 is defined as a ≥ 75% reduction in inflammatory lesion AN count (sum of 
abscesses and inflammatory nodules) from baseline and no increase in abscesses or 
draining fistulas in HS compared with the lesions counted at baseline.

HiSCR90 is defined as a ≥ 90% reduction in inflammatory lesion AN count (sum of 
abscesses and inflammatory nodules) from baseline and no increase in abscesses or 
draining fistulas in HS compared with the lesions counted at baseline.
Please also refer to Section Error! Reference source not found. for the definition of the HiSCR50 
responder status.
5.4.2.2.
Lesion Count
Lesion counts are defined as the number of abscesses, inflammatory nodules, non-inflammatory 
nodules, draining fistulas, and non-draining fistulas respectively. Lesions will be counted during 
each visit. AN count is defined as total abscess and inflammatory nodule count.
5.4.2.3.
International Hidradenitis Suppurativa Severity Score System (IHS4)
IHS4 is a dynamic severity assessment of HS. IHS4 score is arrived at by the number of nodules 
(multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining 
tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 
or higher signifies severe disease.
5.4.2.4.
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 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.
5.4.2.5.
Hidradenitis Suppurativa Symptom Diary (HSSD)
The HSSD is an 8-item patient self-reported questionnaire that assesses symptoms (including pain, 
tenderness, pressure, itch, heat, and odor) and signs (including swelling and drainage) of HS. 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 


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experience. Two versions are available: one with a 24-hour recall (HSSD-24h) and one with a 7-
day recall (HSSD-7d). Each individual symptom (including pain and itch) and sign scale score, 
ranging from 0-10, will be summarized. A total symptom score will be derived by averaging the 6 
individual symptom scale scores. A total sign score will be derived by averaging the 2 individual 
sign scale scores. An overall total score will be derived by averaging all 8 individual items. The 
last item included in the HSSD is an optional item for patients to assess systemic symptoms of HS 
(flu-like symptoms). It will be assessed as a separate item and not included in HSSD overall total 
score. The psychometric properties of the HSSD will be evaluated for scale validation using the 
data from this study.
For the HSSD-24h rating scale, each component will be averaged into a weekly score respectively 
(ie 7 days [from day -7 to -1] prior to a visit). Four days out of 7 days (either consecutive or 
nonconsecutive) are necessary to derive a weekly score; otherwise data are considered missing for 
that week. The baseline is defined as the average score of last 7 days prior to Week 0 study agent 
administration. Similarly, if there are more than 3 days missing data, then baseline is set as missing. 
Missing baseline will not be imputed.
5.4.3.
Estimands for Secondary Endpoints
The secondary endpoints will be analyzed using the same attributes as the primary estimand 
described in section 5.3.2.1 except for the Variable (Endpoint) definition. The estimands for 
secondary endpoints will be considered for both binary and continuous secondary endpoints. 
Study intervention:

Bermekimab 1050 mg

Placebo 
  Population: adult participants with moderate to severe HS

Population level summary: Difference in the proportions of participants achieving a 
binary response, or difference in change from baseline of a continuous endpoint at Week 
16 between the bermekimab 1050 mg and placebo intervention groups.

Variable/endpoint:  variables defined as below, without experiencing any of the ICEs in 
categories 1-2 prior to the Week 16 visit. 
BINARY ENDPOINTS
Variable (endpoint): Binary response variable (response/non-response) with response defined as 
follows at Week 16.

The proportion of participants who achieved HiSCR75 and HiSCR90 

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1), or mild 
(2) and with at least 2-grade improvement relative to baseline 


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CONTINUOUS ENDPOINTS
Variable (endpoint): Continuous variables of change from baseline at Week 16 as defined below.

The change from baseline in AN count 

The change from baseline in number of abscesses 

The change from baseline in number of draining fistulas 

The change from baseline in number of inflammatory nodules 

The change from baseline in international hidradenitis suppurativa severity score (IHS4) 

The change from baseline in pain scale score of HSSD-24h 
Intercurrent Events (ICEs)
Analysis Strategy for Intercurrent Events
1.
Discontinuation of study intervention due
to lack of efficacy, an AE of worsening of 
HS
2.
Initiation of a protocol-prohibited
medication or therapy during the study
that could improve H S
Composite Strategy: Participants with these intercurrent event are 
considered as non-responders for binary endpoints and zero 
change from baseline for continuous endpoints after these events, 
as reflected in variable definition.
3.
Discontinuation of study intervention for 
reasons other than ICE 1
Treatment Policy: observed data will be used regardless of 
whether or not this intercurrent event had occurred.
Note: For participants experiencing multiple ICEs, ICE 2 will override ICE 3. 
5.4.4.
Analysis Methods for Secondary Endpoints
The secondary endpoints at Week 16 will be analyzed using the estimand described in section 
5.4.3 for mFAS. The endpoints will be summarized by intervention group. Simple descriptive 
statistics, such as n, mean, SD, median, IQ range, minimum and maximum for continuous variables 
and counts and percentages for discrete variables will be used to summarize the data. 
Binary Endpoints

The proportion of participants who achieved HiSCR75 and HiSCR90 at Week 16 in Part 1
will be compared between the bermekimab groups and the placebo group.

The proportion of participants with HS-IGA score of inactive (0), almost inactive (1), or mild 
(2) and with at least 2-grade improvement relative to baseline at Week 16 in Part 1 will be 
compared between the bermekimab groups and the placebo group.
The analysis strategy for ICEs and missing data for binary endpoints will be handled in the same 
manner as the primary estimand for the primary analysis. The Cochran-Mantel-Haenszel chi-
square statistic stratified by baseline Hurley stage status (II, III) at a 2-sided significance level of 
0.1 will be used. Difference in response rates between each of the active and placebo groups at 
Week 16 adjusted for baseline Hurley stage status (II, III) using Mantel-Haenszel weight and the 
corresponding 90% CI will be presented.


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In case of rare events, the Fisher’s Exact test will be used for treatment comparisons in binary 
response endpoints. The proportion differences between active treatment groups and placebo and 
the exact confidence intervals will be provided.
Continues Endpoints

The change from baseline in AN count at Week 16 in Part 1 will be compared between the 
bermekimab groups and the placebo group.

The change from baseline in number of abscesses at Week 16 in Part 1 will be compared 
between the bermekimab groups and the placebo group.

The change from baseline in number of draining fistulas at Week 16 in Part 1will be compared 
between the bermekimab groups and the placebo group.

The change from baseline in international hidradenitis suppurativa severity score (IHS4) at 
Week 16 in Part 1will be compared between the bermekimab groups and the placebo group.

The change from baseline in number of inflammatory nodules at Week 16 in Part 1 will be 
compared between the bermekimab groups and the placebo group.

The change from baseline in pain scale score of HSSD-24h at Week 16 in Part 1 will be 
compared between the bermekimab groups and the placebo group.
Unless otherwise specified, the analyses for continuous secondary endpoints at Week 16 will be 
based on the following strategies to handle ICEs and missing data. 
o
Participants experiencing ICEs 1-2 will have a zero change from baseline assigned from 
that point onward.
o
The analysis for participants with ICE3 will be performed using observed data regardless 
of intercurrent events. For participants experiencing multiple ICEs, an ICE in categories 2 
will override an ICE in category 3.
o
Missing data will not be imputed after applying the rules for intercurrent events, and
missing data will be accounted for through correlation of repeated measures in the Mixed-
Effect Model Repeated Measure (MMRM) model.
Treatment comparisons for the secondary continuous endpoints at Week 16 will be performed 
using a MMRM model under the assumption of missing at random (MAR) with intervention group,
visit, baseline Hurley stage status (II, III), baseline value for the efficacy endpoint, treatment by 
visit, baseline Hurley stage by visit and baseline value by visit interaction as explanatory factors, 
if appropriate. An unrestricted (UN) variance-covariance matrix for repeated measures within a 
participant will be used. If the model with unstructured covariance structure does not converge, 
alternative covariance structures will be tried in the following order, with the first structure that 
converges being used in the analysis: heterogeneous Toeplitz, standard Toeplitz, and 
autoregressive of order 1.


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5.5.
Exploratory Endpoints
In addition to the primary and secondary efficacy endpoints, the analyses for exploratory efficacy 
endpoints will be performed. 

HiSCR

Lesion Count

HS-IGA 

IHS4

HASI

HSSD pain
5.5.1.
Endpoint Definitions
5.5.1.1.
Hidradenitis Suppurativa Clinical Response (HiSCR)
Please also refer to Section 5.4.2.1 for the definition of the HiSCR50, HiSCR75, and HiSCR90
responder status.
5.5.1.2.
Lesion Counts
Details refer to Section 5.4.2.2for the definition of the lesion counts.
5.5.1.3.
International Hidradenitis Suppurativa Severity Score System (IHS4)
Details refer to Section 5.4.2.3.
5.5.1.4.
Hidradenitis Suppurativa Investigator’s Global Assessment (HS-IGA)
Details refer to Section 5.4.2.4.
5.5.1.5.
Hidradenitis Suppurativa Symptom Diary (HSSD)
Details refer to Section 5.4.2.5.
5.5.1.6.
Hidradenitis Suppurativa Activity and Severity Index (HASI)
The HASI is a clinician reported outcomes tool that assesses HS severity by incorporating signs 
of inflammation and surface area involved. The HASI includes 4 domains to assess the severity of 
HS disease activity: inflammatory color change, inflammatory induration, open skin surface. and 
extent of tunnels. Each of these variables is scored on a Likert Scale from 0 to 3 (0=none; 
1=limited/mild, 2=moderate, 3=severe/extensive) based on the average intensity for each body 
site. A higher score indicates more severe disease. See Section 10.10 of the JNJ-
77474462HDS2001 protocol, Appendix 10 for more details. The HASI score was the total for all 
body sites and ranged from 0 to 720, with higher scores indicating more severe disease activity.


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5.5.2.
Analysis Methods
The efficacy data from all participants in mFAS will be included and analyzed by study
intervention groups from Week 0 through Week 36. The analysis strategy for ICEs and missing 
data will be handled in the same manner as the secondary endpoints analyses.
All exploratory endpoints 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.
Additionally, graphical data displays may also be used to summarize the over time data if 
applicable.
5.5.2.1.
Analysis Related to HiSCR

The proportion of participants who achieved HiSCR50 and the proportion of participants who 
achieved HiSCR50 by baseline Hurley stage (II, III) will be summarized by treatment group 
over time.

The proportion of participants who achieved HiSCR75 and HiSCR90 will be summarized by 
treatment group over time.
5.5.2.2.
Analyses Related to Lesion Count

The change from baseline in total AN count will be summarized by treatment groups over 
time.

The change from baseline in number of abscesses will be summarized by treatment group over 
time.

The change from baseline in number of draining fistulas will be summarized by treatment 
group over time.

The change from baseline in number of inflammatory nodules will be summarized by 
treatment group over time.
5.5.2.3.
Analysis Related to IHS4

The change from baseline in IHS4 score will be summarized by treatment group over time.
5.5.2.4.
Analyses 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) with at least 2-grade improvement from baseline will be summarized 
by treatment groups over time. 
5.5.2.5.
Analyses Related to HASI

The change from baseline in HASI score over time will be summarized by treatment groups 
over time.


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5.5.2.6.
Analyses Related to HSSD

The change from baseline in HSSD pain score (24 hours recall) will be summarized over time.

The change from baseline in HSSD pain score (7 days recall) will be summarized over time.
5.6.
Safety Analyses
All safety analyses will be performed using safety analysis set based on actual intervention 
received. No formal statistical comparison is planned.
For all continuous safety variables, descriptive statistics by intervention group will include the N, 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized by intervention group using frequency counts and percentages.
5.6.1.
Extent of Exposure
The number and percentage of participants who receive study intervention (placebo, bermekimab, 
and adalimumab) will be summarized. The number and percentage of participants will also be 
summarized by visit.
Descriptive statistics will be presented by intervention group for the following parameters:

Number of administrations

Cumulative total dose

Duration of study intervention (weeks)
Study intervention duration is defined as (date of last dose of study intervention – date of first dose 
of study intervention +1)/7.
5.6.2.
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 occurring at or after the 
initial administration of study intervention is considered to be treatment emergent. If the event 
occurs on the day of the initial administration of study intervention, 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 intervention based on 
partial onset date or resolution date. All reported treatment-emergent adverse events will be 
included in the analysis.  For each adverse event, the number and percentage of participants who 
experience at least 1 occurrence of the given event will be summarized by intervention group.
Summary tables will be provided for treatment-emergent adverse events:

AEs


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
Serious AEs (SAEs)

AEs leading to discontinuation of study intervention

AEs of severe intensity

AEs related to study intervention

AEs of injection site reaction
In addition to the summary tables, listings will be provided for participants who:

Had SAEs

Had AEs leading to discontinuation of study intervention

Had AEs of severe intensity 

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 for each 
intervention group.
A listing of participants who died will be provided.
5.6.3.
Additional Safety Assessments 
5.6.3.1.
Clinical Laboratory Tests
Clinical laboratory tests will be displayed for the participants included in the safety analysis set.
Descriptive statistics of change from baseline through Week 36 will be summarized for selected 
chemistry, and hematology tests and displayed by intervention group. 

Hematology will include but are not limited to the following: Basophils, Eosinophils, 
Hemoglobin, Lymphocytes, Monocytes, Neutrophils, Platelets, WBC, CRP and ESR.

Chemistry will include but are not limited to the following: ALT, AST, Albumin, Alkaline 
Phosphatase, Bicarbonate (CO2), Calcium, Chloride, Creatinine, GGT, Glucose, Potassium, 
SGOT, SGPT, Sodium, Total Bilirubin, Total Protein, Urea Nitrogen.
Applicable laboratory results will be graded according to National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI-CTCAE). Participants with toxicity grades ≥2 will 
be listed.


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5.7.
Other Analyses
5.7.1.
Pharmacokinetics
All PK analyses will be performed on the PK analysis set, defined as participants who have 
received at least 1 dose of bermekimab and have at least 1 valid blood sample drawn for PK 
analysis. Participants will be analyzed according to the treatment groups they actually received.
No imputation for missing concentration data will be performed.
Blood samples for measuring bermekimab concentrations will be collected from all participants at 
the specified visits as shown in the schedule of activities in the protocol. 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.  
Bermekimab 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 bermekimab concentrations at each visit by treatment group.

Proportion of participants without detectable bermekimab concentration (below the lower 
limit of quantification) at each visit by treatment group.

Summary of bermekimab concentrations at each visit by treatment group and baseline 
body weight (>=95 or < 95 kg). 

Summary of bermekimab concentrations at each visit by treatment group and baseline 
Hurley stage status (II, III). 

Plot of median (IQ) bermekimab concentrations over time by treatment group.

Plot of median (IQ) bermekimab concentrations over time by baseline body weight and 
treatment group.
Unless otherwise specified, the following data handling rules will apply to PK analyses:

All 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 participant who meets 1 of the following dosing deviation criteria 
(if applicable) will be excluded from the by-visit data analyses from that point onwards:

Discontinue bermekimab administrations.

Skipped a bermekimab administration.

Received an incomplete/ incorrect dose (if applicable).

Received an incorrect study agent (if applicable).


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
Received an additional bermekimab dose.
In addition, if a participant has an administration outside of dosing windows (± 3 days from 
scheduled visit from Week 0 through Week 32), 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.
5.7.2.
Immunogenicity (Antibodies to Bermekimab)
Blood samples will be collected to examine the formation of antibodies to bermekimab at the 
specified visits as shown in the schedule of activities in the protocol. Samples will also be collected 
at the final visit from participants who terminate study participation early. 
Immunogenicity analyses will be based on the Immunogenicity Analysis Set (Section 4).
No imputation for missing concentration data will be performed.
The antibodies to bermekimab status (positive, negative) and titers will be summarized by 
treatment group for participants who receive at least one dose of bermekimab and have appropriate 
samples for detection of antibodies to bermekimab. The maximum titers of antibodies to 
bermekimab will be provided for participants who are positive for antibodies to bermekimab.
A listing of participants who are positive for antibodies to bermekimab will be provided. This 
listing will provide information regarding dose administered, bermekimab concentration, and 
antibody status for all visits.
In addition, to explore the relationship between antibodies to bermekimab status and serum
bermekimab concentrations, and safety, the following analysis may be performed as appropriate:

Summary of injection-site reactions by antibody to bermekimab status

Summary of serum bermekimab concentrations by antibody to bermekimab status

Plots of median (IQ) serum bermekimab concentrations over time by antibody to 
bermekimab status
5.8.
Interim Analyses
An internal independent interim analysis committee (IAC) will be established to review the interim 
data to formulate recommended decisions and/or actions in accordance with the objectives of the 
interim analyses. The IAC will consist of at least a clinician and a statistician (neither of whom are 
involved in study conduct), one of whom will chair the committee, and other members as required.
The IAC will review the unblinded efficacy data and provide recommendations about the next step 
of enrollment of Part 2 portion of this study based upon the results of the first (when approximately 
50% of the Part 1 participants reach Week 16) and/or second (when 100% of the Part 1participants 
reach Week 16) interim efficacy analyses. Both interim analyses will be performed to determine 


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whether the efficacy of bermekimab, as measured by the proportion of participants achieving 
HiSCR50 response at Week 16, is sufficient to open the enrollment of the Part 2 portion of the 
study. Other selected supportive efficacy endpoints could also be reviewed. Additionally, as part 
of both IAs, serum bermekimab concentration data available at the time of both database release 
will be used for PK concentration analyses and population PK analysis to support IAC data review 
and to inform dose regimens for Phase 2b portion of the study.
Based on the results from the first IA, consideration of termination of the study may be warranted 
if either the efficacy is sufficiently low based on the prespecified criteria or the efficacy is 
considered to be insufficient to outweigh specific safety findings observed in study participants. 
Furthermore, if the study is not terminated after the 1st IA, a database lock based on all available 
data when 100% of participants completed Week 16 from Part a portion of the study will be 
planned to support the end of phase 2 meeting. The unblinded results will be limited to specific 
sponsor personnel not involved in the study conduct. Interim analysis results will not be 
disseminated to investigators or individuals associated with the conduct of the study.
Following the first IA, the study was terminated due to futility.
5.9.
Data Monitoring Committee (DMC) 
An external iDMC whose members are not directly involved in the conduct of 77474462HDS2001 
Phase 2a/2b study, will review unblinded safety data to ensure the safety of the participants 
enrolled in this study. The iDMC will convene for a prespecified look at safety after at least 12 
participants have received 4 weekly doses. The committee will also 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 DMC will consist of at least one clinical physician and 
one statistician, not involved in the conduct of the study. DMC responsibilities, authorities, and 
procedures will be documented in the DMC charter.


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6.
SUPPORTING DOCUMENTATION
6.1.
Appendix 1 List of Abbreviations
ADA
anti-drug antibody
AE
adverse event
ALT/SGPT
alanine aminotransferase
AST/SGOT
aspartate aminotransferase
ATC
anatomic and therapeutic class
BMI
body mass index
BSA
body surface area
CI
confidence interval
CRF
case report form
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
eCRF
electronic case report form
FAS
full analysis set
FDA
Food and Drug Administration
IQ
interquartile
IWRS
interactive web response system
LLOQ
lower limit of quantification
MedDRA
MMRM
Medical Dictionary for Regulatory Activities
Mixed-Effect Model Repeated Measure 
NAb
neutralizing antibodies
PD
pharmacodynamic(s)
PI
principal investigator
PK
pharmacokinetic(s)
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
TEAE
treatment-emergent adverse event
US NCI
United States National Cancer Institute
WHO
World Health Organization


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6.2.
Appendix 2 Changes to Protocol-Planned Analyses
The IA futility criterion was met and the decision was made to terminate the study. The SAP has 
reduced efficacy, safety and PK analyses.


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6.3.
Appendix 3 Demographics and Baseline Characteristics
The number of participants in each analysis set will be summarized and listed by intervention 
group, combined active intervention group, and overall. In addition, the distribution of participants 
by region, country, and site ID will be presented unless otherwise noted.
Table 7 presents a list of the demographic variables that will be summarized by intervention group, 
combined active intervention group, and overall for the FAS analysis set.  
Table 7: 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)
Body Mass Index (BMI) (kg/m2)
Body Surface Area (BSA) (m2)
Categorical Variables
Age (<40 years, 40-64 years, and >=65 years)
Frequency distribution with the 
number and percentage of 
participants in each category.
Sex (male, female)
Weight (<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 kg/m2, overweight 25-<30 kg/m2, obese >=30 kg/m2])
aIf multiple race categories are indicated, the Race is recorded as 'Multiple'
Baseline disease characteristics (e.g., duration of HS disease, baseline Hurley stage status, baseline 
AN count, inflammatory nodule count, abscess count, and draining fistula, baseline IHS4, baseline 
HASI, 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 (II, and III) will also be provided.


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6.4.
Appendix 4 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 study. 
Participants with major protocol deviations will be identified prior to database lock and the 
participants with major protocol deviations will be summarized by category through Week 16 and 
through the end of study.

Developed withdrawal criteria but not withdrawn

Entered but did not satisfy criteria

Received a disallowed concomitant treatment

Received wrong treatment or incorrect dose

Other
A listing of participants with major protocol deviations and a listing of patients who missed 
scheduled study agent administration will also be provided by randomized treatment group. In 
addition, analyses of COVID-19 related protocol deviations will be provided.


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6.5.
Appendix 5 Prior and Concomitant Medications
Prior medications are defined as any therapy used before the day of first dose (partial or complete) 
of study intervention. Prior HS treatment received (including prior HS related surgery) will be 
summarized by randomized treatment group for the FAS.
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
(WHO-DD). Concomitant medications are defined as any therapy used on or after the same day as 
the first dose of study intervention, including those that started before and continue on after the 
first dose of study intervention.
Summaries of concomitant medications will be presented by anatomic and therapeutic class (ATC) 
term, and intervention group. The proportion of participants who receive each concomitant 
medication will be summarized as well as the proportion of participants who receive at least 1
concomitant medication.
In addition, a list of participants who received a protocol-prohibited medication or therapy meeting 
the definition of ICE 2 will be provided.


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6.6.
Appendix 7 Intervention Compliance
Study agent compliance will be summarized descriptively through Week 31 for the FAS. 
Compliance to randomized intervention versus actual intervention will be presented in a summary 
table. Number of the participants receiving each scheduled treatment will be summarized. 


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6.7.
Appendix 8 Adverse Events of Special Interest
Not Applicable.


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6.8.
Appendix 9 Medications of Special Interest
Not Applicable.


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6.9.
Appendix 10 Laboratory Toxicity Grading
The grading scale use for lab assessments is based on ‘Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0’.
If a laboratory value falls within the grading as specified below but also within the local laboratory 
normal limits, the value is considered to be normal and will be reset to grade 0.
Pre-baseline measurements will use the same grading ranges as applied to baseline measurements. 
In case a test has two sets of ranges – one for baseline normal and one for baseline abnormal, the 
one for baseline normal will be applied for all measurements taken pre-baseline and on baseline.