Clinical trial NCT02808975
Conditions: Hidradenitis Suppurativa (HS)
Keywords: Hidradenitis Suppurativa Axilla Inguinal region Hurley Stage I, II, or III Adalimumab Secondary intention Abcess and inflammatory nodule (AN) count
Sponsor: AbbVie
Start date: 2016-07-18; Completion date: 2019-10-16
Enrollment: 206 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of this study was to assess the safety and efficacy of adalimumab prior to surgery in participants with moderate to severe Hidradenitis Suppurativa (HS) who were surgical candidates.

Detailed description:
This was an interventional, randomized, double-blind (DB), placebo-controlled study. The study duration included a 30-day Screening Period, an initial 12-week DB treatment pre-surgery period (Period A), a 2-week peri-operative period with continuation of weekly DB study drug administration (Period B), and a subsequent 10-week DB treatment post-operative period (Period C). Randomization (in a 1:1 ratio) in Period A was stratified by baseline Hurley Stage (II versus III) and anatomical location of the planned surgical site (i.e., axilla versus inguinal region). The projected size of the surgical excision established by the designated surgeon during the Screening Period (calculated from a tracing of the outer perimeter onto an acetate sheet or equivalent) was recorded. In Period B, the designated surgeon measured and recorded the surface area of the actual surgery, with surgery occurring during Week 13. Surgery and post-operative management (e.g., hospitalization, surgical wound care) was per local practice. No study drug was administered at Week 24, the final study visit. Participants were able to begin commercial product (as prescribed by the participants's physician) after all Week 24 procedures were completed.

Arms: arm 1: Period A: Day 1- 4 subcutaneous (SC) injections; Week 2- 2 SC injections; Weeks 4-12- 1 SC injection each week

Period B: Weeks 13-14- 1 SC injection each week

Period C: Weeks 15-23- 1 SC injection each week arm 2: Period A: Day 1- 4 subcutaneous (SC) 40 mg injections; Week 2- 2 SC 40 mg injections; Weeks 4-12- 1 SC 40 mg injection each week

Period B: Weeks 13-14- 1 SC 40 mg injection each week

Period C: Weeks 15-23- 1 SC 40 mg injection each week
Interventions: intervention 1: Placebo intervention 2: Adalimumab
Intervention descriptions: intervention 1: Subcutaneous injections administered as described in arm description intervention 2: Subcutaneous injections administered as described in arm description

Protocol documents:
Prot_001.pdf: 
NCT02808975


Adalimumab
M15-574 Protocol Amendment 3
EudraCT 2015-005161-23
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1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol 
Date
Original
04 February 2016
Amendment 1
05 May 2016
Amendment 2
30 November 2016
The purpose of this amendment is to:
E
Section 1.2, Add the planned number of sites for this study of 56. 
Rationale:  Clarify number of sites in the study.  
E
Section 8.1.4.1, Add that the 95% confidence intervals of treatment difference 
will also be provided.
Rationale:  The protocol was updated to include clarifications requested by 
regulatory Authorities.
E
Section 8.1.4.1, Add a sensitivity analysis controlling for change from baseline 
in body weight using logistic regression models, for the primary efficacy 
endpoint.  Analysis details will be specified in the SAP prior to study 
unblinding and prior to database lock.
Rationale:  The protocol was updated to include clarifications requested by 
regulatory Authorities.
E
Update Study Designated Physician in Section 1.0 and Section 6.1.5
Rationale:  Update information from Administrative Change 1.
E
Update Alternate Contact in Section 7.0
Rationale:  Update information from Administrative Change 1.
E
Update List of Protocol Signatories in Appendix B
Rationale:  Update information from Administrative Change 1.
An itemized list of all changes made to this protocol amendment can be found in 
Appendix S.


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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M15-574
Name of Study Drug:  Adalimumab
Phase of Development:  4
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  13 December 2017
Protocol Title:  A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess 
the Safety and Efficacy of Adalimumab used in Conjunction with Surgery in Subjects with Moderate to 
Severe Hidradenitis Suppurativa
Objective:  Assess the safety and efficacy of adalimumab prior to surgery in subjects with moderate to 
severe Hidradenitis Suppurativa (HS) who are surgical candidates.
Investigators:  Multicenter
Study Sites:  The planned number of sites for this study is 56.
Study Population:  Male or female subjects between the ages of 18 and 65, inclusive, with moderate to 
severe HS having
!
at least 3 distinct anatomical regions involved with inflammatory HS lesions;
!
either one axilla or one inguinal region that requires excisional surgery with healing by 
secondary intention, and containing at least one active HS lesion; and
!
the non-surgical HS sites must have a total AN count J 3, with at least one of these sites rated 
Hurley Stage II or III.
Number of Subjects to be Enrolled:  200
The study is designed to enroll approximately 200 subjects.  Assuming the true treatment difference in 
this study population is at least 20%, 100 subjects per arm will provide at least 80% power to detect the 
treatment difference at the alpha level of 0.05.  The study also has at least 80% power to demonstrate the 
point estimate of the treatment difference of at least 15%.  
The response rates observed in combined PIONEER I and II studies (Studies M11-313 and M11-810) for 
the Hidradenitis Suppurativa Clinical Response (HiSCR, defined as at least a 50% reduction in the HS 
abscess plus inflammatory nodule [AN] count with no increase in abscess count and no increase in 
draining fistula count relative to Baseline) at Week 12 were 50.6% and 26.8% in the adalimumab every 
week group and placebo group, respectively.  Due to the potential differences between the population of 
moderate-to-severe HS patients who are surgical candidates and the general moderate-to-severe HS 
patient population, a conservative estimate of 20% treatment difference is used for the power calculation.
Methodology:  
This double-blind, placebo-controlled study consists of a 7 – 30-day Screening Period followed by 
24-weeks of active treatment.  The eligible subject must have a requirement for surgery of HS lesions in a 
single axilla or unilateral inguinal region.  Subjects will be randomised 1:1 with stratification for Hurley 
Stage (II versus III worst stage across all body regions) and anatomical location of the planned surgery 
for HS lesions (axilla versus inguinal region).  Study drug treatment will follow the approved dosage for 
HS, including loading doses at the beginning of the 12-week pre-surgery period (Period A), followed by a
2-week peri-surgery period (Period B) with surgery scheduled for Week 13 and a 10-week post-surgery 
period (Period C).


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Methodology (Continued):
Study visits will occur as follows:
!
Period A (pre-surgery) study visits will occur at Day 1 (Week 0) and Weeks 2, 4, 8, and 12.  
!
Period B (peri-surgery) the subject will be under the care of the designated surgeon.  
!
Period C (post-surgery) study visits will occur at Weeks 15, 17, 20, and 24.
Evaluation for safety and efficacy throughout the 24-week study period will include 
1)
clinical observations of the HS lesions (both in the planned surgical site and at least two other 
distinct anatomical regions with HS lesions),
2)
laboratory measurements of serum and plasma samples, and
3)
patient reported outcomes (PROs).
Optional participation in exploratory research and validation studies will include the collection of serum 
and plasma samples, and tissue samples (both of non-lesional skin and HS lesional skin, specifically at 
the planned surgical site) at specified various time points throughout the study.
In selected study sites Doppler ultrasound and digital imaging may be performed with optional 
participation by the study subject.
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion:  
1.
Male and female subjects between the ages of 18 and 65, inclusive;
2.
Subject must have a skin lesions that are diagnostic of HS for at least 1 year (365 days) prior to the 
Baseline visit;
3.
Subject must have at least 3 distinct anatomical regions involved with inflammatory (also termed 
'active') HS lesions; including
a.
either an axilla or unilateral inguinal region (limited to the inguino-crural fold and adjacent 
areas that requires excisional surgery (hereinafter designated the 'HS surgical site'), and
b.
with at least one of the other affected HS regions (e.g., contralateral axilla, contralateral 
inguinal region, buttocks, inframammary region; hereinafter designated the 'HS 
non-surgical sites') rated as Hurley Stage II or III;
4.
Subject must have a total abscess and inflammatory nodule (AN) count of greater than or equal to 
3 at the Baseline visit within the HS non-surgical sites;
5.
The HS surgical site must contain at least one active HS lesion;
6.
The HS surgical site must require excisional surgery and is large enough to require healing by 
secondary intention as assessed by the designated surgeon;


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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
7.
If female subject, is either
!
not of childbearing potential, defined as
o
postmenopausal for at least 1 year (365 days) or
o
surgically sterile (bilateral tubal ligation, bilateral oophorectomy, and/or hysterectomy);
!
of childbearing potential and is practicing an approved method of birth control throughout the 
study and for 150 days after last dose of study drug.
Examples of approved methods of birth control include the following (see local informed consent for 
more detail):
o
Intrauterine device (IUD) or Intrauterine hormone-releasing system (IUS); or
o
Hormonal contraceptives at least 30 days prior to study drug administration; and/or
o
A vasectomized partner; and/or
o
True abstinence.
8.
Females of childbearing potential must have a negative serum pregnancy test result (conducted at the 
central lab) at Screening and a negative urine pregnancy test (conducted at the site) at Day 1;
•
Females of non-childbearing potential (either postmenopausal or permanently surgically sterile 
as defined above) at Screening do not require pregnancy testing.
9.
Subject must agree to daily use of one of the following over-the-counter topical antiseptics on their 
HS lesions (excepting the post-surgical wound):  chlorhexidine gluconate, triclosan, benzoyl 
peroxide, or dilute bleach with shower or bath throughout the entirety of the study;
10. Subject has a negative tuberculosis (TB) screening assessment (see test to be performed in paragraph 
below) and negative chest x-ray (CXR) (posterior anterior and lateral view) at Screening.  If the 
subject has evidence of a latent TB infection; the subject must initiate and complete a minimum of 
12 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have 
documented completion of a minimum of 4 weeks of TB prophylaxis prior to the Baseline visit and 
should be evaluated by a physician experienced in the evaluation and treatment of TB patients before 
entering the trial;
!
In patients treated with corticosteroids (equivalent to Prednisone 5 mg or above – with ongoing 
treatment or treatment within 1 month prior to TB screening), TB screening must be performed 
using a QuantiFERON-TB Gold In-tube test or equivalent.
!
In patients NOT treated with corticosteroids (equivalent to Prednisone 5 mg or above – with 
ongoing treatment or treatment within 1 month prior to TB screening), PPD or QuantiFERON-
TB tests may be used.
11. Subject is judged to be in good general health, as determined by the Study Investigator based upon 
the results of a medical history, physical examination, laboratory profile, CXR and a 12-lead 
electrocardiogram (ECG) performed during the Screening period and confirmed at the Baseline visit;
12. Subject must be able and willing to self-administer subcutaneous (SC) injections or have a qualified 
person available to administer SC injections; and
13. Subject must be able and willing to provide written informed consent and comply with the 
requirements of this study protocol.


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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion:  
1.
Subject has a draining fistula count of greater than 20 at the Baseline visit;
2.
Subject requires surgery at any anatomical site other than an unilateral axilla or inguinal region site;
3.
Subject requires surgical management prior to Week 13; based on the designated surgeon's 
assessment;
4.
Subject requires, based on the designated surgeon's assessment, excisional surgery with primary 
closure, partial surgical reduction of the excised area with surgical suture, or reconstruction 
techniques as the method of closure being most beneficial for the subject;
5.
Subject has any other active skin disease or condition (e.g., bacterial, fungal or viral infection) that 
may interfere with assessment of HS;
6.
Subject is taking high-dose systemic corticosteroids at the Baseline visit (see Section 5.2.3.3), or has 
taken high-dose systemic corticosteroids (see Section 5.2.3.3) within five half-lives of that specific 
corticosteroid prior to the Baseline visit;
7.
Subject received biologic therapies with potential therapeutic impact for HS less than 6 months 
(178 days) prior to the Baseline visit;
8.
Subject received prescription  topical therapies (excluding over-the-counter topical antiseptics) for 
the treatment of HS within 14 days prior to the Baseline visit;
9.
Subject received systemic clindamycin or rifampin within 28 days prior to the Baseline visit;
10. Infection(s) requiring treatment with intravenous (IV) anti-infectives (antibiotics, antivirals, 
antifungals) within 30 days prior to the Baseline visit, except as required as part of an anti-TB 
regimen;
11. Prior exposure to biologics that have a potential or known association with progressive multifocal 
leukoencephalopathy (PML i.e., natalizumab or rituximab);
12. Subject has been treated with any investigational drug of chemical nature within a minimum of 
30 days or five half-lives (whichever is longer) of the drug prior to the Baseline visit;
13. Known hypersensitivity to adalimumab or its excipients;
14. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease;
15. Subject has suspicion of sepsis, cytomegalovirus infection, listeriosis or other opportunistic 
infections, or has history of invasive infection (e.g., listeriosis, histoplasmosis), human 
immunodeficiency virus (HIV);
16. Subject has an active systemic viral infection or any active viral infection that based on the Study 
Investigator's clinical assessment make the subject an unsuitable candidate for the study;
17. Hepatitis B:  HBsAg positive (+) or detected sensitivity on the HBV-DNA PCR qualitative test for 
HBcAb/HBsAb positive subjects;
18. Chronic recurring infections or active TB;
19. History of moderate to severe congestive heart failure (NYHA class III or IV), recent 
cerebrovascular accident, interstitial lung disease (ILD) and any other condition which, in the 
opinion of the investigator, would put the subject at risk by participation in the protocol;
20. Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a 
successfully treated non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma or 
localized carcinoma in situ of the cervix;


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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):  
21. Females who are breastfeeding or considering becoming pregnant during the study and during the 
5 months following the last dose of adalimumab;
22. History of clinically significant drug or alcohol abuse in the previous 12 months;
23. Clinically significant abnormal screening laboratory results as evaluated by the Investigator; and
24. Subject is considered by the Study Investigator, for any reason, to be an unsuitable candidate for the 
study.
Active Study Drug:
Adalimumab
Doses:
160 mg/3.2 mL Day 1 (Week 0), 80 mg/1.6 mL Day 15 (Week 2) and 
40 mg/0.8 mL every week from Week 4 to Week 23.
Mode of Administration:
Subcutaneously (SC)
Reference Therapy:
Placebo
Doses:
3.2 mL Day 1 (Week 0), 1.6 mL Day 15 (Week 2), and 0.8 mL every 
week from Week 4 to Week 23.
Mode of Administration:
Subcutaneously (SC)
Duration of Treatment:  23 weeks
Criteria for Evaluation:
Efficacy:
The primary efficacy variable is the proportion of subjects achieving HiSCR at Week 12.  The secondary 
endpoints include the proportion of subjects achieving HiSCR-es (defined as the HiSCR excluding the 
HS surgical site) at Weeks 12 and 24, the change in surface area of the HS surgical site at Week 12, and 
the proportion of subjects at Week 12 that require less extensive surgery than the surgical plan 
(determined at Baseline) or no surgery.  Other parameters will be collected and may be analysed, 
including C-reactive protein (CRP), active HS lesion count, and patient reported outcomes (PROs).
Pharmacokinetic:
Blood samples will be collected for the measurement of serum adalimumab concentrations at Baseline 
and Weeks 4, 8, 12, 15, 17, 20, 24/Premature Discontinuation visit if the subject discontinues prior to 
Week 24.  Blood samples will be collected for the measurement of anti-adalimumab antibody (AAA) at 
Baseline, and Weeks 4, 8, 12, 15, 20, and 24/Premature Discontinuation visit if the subject discontinues
prior to Week 24.
Safety:
Adverse events, adverse events of special interest and adverse events concerning the surgical site, 
laboratory data and vital signs will be assessed throughout the study.
Exploratory Research Variables and Validation Studies (Optional):
Prognostic, predictive, and pharmacodynamic biomarker signatures may be investigated.  Samples for 
different applications including, but not limited to, pharmacogenetic, epigenetic, transcriptomic, 
proteomic, and targeted investigations will be collected at various time points.


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Statistical Methods:
Efficacy:
The primary analysis will be the comparison of the adalimumab treatment group versus the placebo 
treatment group in the proportion of subjects achieving HiSCR at Week 12.
Ranked secondary endpoints with comparison of the adalimumab treatment group versus the placebo 
treatment group include:
1.
Proportion of subjects achieving HiSCR-es (HiSCR evaluation excluding the HS surgical site) at 
Week 12;
2.
Proportion of subjects achieving HiSCR-es at Week 24;
3.
Percent change in surface area of the planned surgical site from Baseline to Week 12; and
4.
Proportion of subjects that require a less extensive surgery than the surgical plan documented at 
Baseline, or no longer require surgery as determined by the designated surgeon.
Other efficacy endpoints for which data will be collected and may be analysed include:
1.
C-reactive protein (CRP) and white cell count;
2.
PROs including DLQI, EQ5D™, HS-PGA-SP, HS-PGIC, HSIA, HSSA, SF-12, TSQM (treatment 
efficacy subscale), and WPAI:SHP;
3.
Proportion of subjects that experience a flare of active HS lesions, during Period A and during the 
study; and
4.
Proportion of subjects that experience at least 25% increase in each lesion type relative to Baseline at 
each study visit, during Period A and during the study.
The primary efficacy analysis will be carried out in the Intent-to-Treat (ITT) Population in the Period A, 
defined as all patients who are randomised at the Baseline visit.  Treatment difference in response rates 
between adalimumab and placebo will be conducted by Cochran-Mantel-Haenszel (CMH) test, stratified 
by the stratification factors used for randomisation.  All other secondary efficacy variables in Period A 
will be analysed by ANCOVA (for continuous variables) with treatment, baseline value and stratification 
factors in the model, or by CMH (categorical variables) adjusting for stratification factors.  
Non-responder imputation will be used as the primary approach to impute the missing values with 
last-observation-carried-forward and Multiple Imputation as sensitivity analyses for the primary 
endpoint.
Pharmacokinetic:
Adalimumab trough serum concentrations will be summarized at each time point using descriptive 
statistics.  In addition, pharmacokinetic-pharmacodynamic (PK-PD) model-based analyses will be 
performed to evaluate adalimumab PK and exposure-response relationships.


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Statistical Methods (Continued):
Safety:
All adverse events (AE), serious adverse events (SAE), AEs leading to discontinuation, and pre-specified 
AEs of special interest and adverse events concerning the surgical site will be collected during the study 
and up to approximately 70 days after the last dose of study drug, for subjects who do not elect to treat 
his/her HS disease with commercial adalimumab.  
Safety analyses will be carried out using the Safety Population, which consists of subjects who received 
at least one dose of study drug.  Pretreatment AEs will be summarized.  A treatment-emergent AE 
(TEAE) is defined as an event with onset or worsening after the first study drug injection and within 
approximately 70 days after the last study drug injection, for subjects who do not elect to treat his/her HS 
disease with commercial adalimumab.  
The number and percent of subjects experiencing TEAEs will be tabulated using the Medical Dictionary 
for Drug Regulatory Activities (MedDRA®) system organ class and preferred term.  Comparisons of the 
percentages of subjects experiencing an AE in the adalimumab group versus the placebo group will be 
performed using Fisher's exact test for data collected in the entire study, and separately for Period A, 
Period B, and Period C.  Summaries (including percentages and event per 100 patient-years) of SAEs, 
deaths, AEs leading to discontinuation from the study, and pre-specified AEs of special interest will be 
provided as well.  Mean change in laboratory variables and vital sign variables at each visit will be 
summarized; the comparison between the adalimumab treatment group and placebo group will be carried 
out using a one-way ANOVA.  
Immunogenicity:
Anti-Adalimumab Antibody (AAA) will be evaluated for each subject and rates of AAA positive will be 
calculated.  As appropriate, the effect on adalimumab PK, efficacy, and treatment-emergent adverse 
events may be evaluated.


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1.3
List of Abbreviations and Definition of Terms
Abbreviations
AAA
Anti-Adalimumab Antibody
AE
Adverse Event 
AESI 
Adverse Event of Special Interest
ANCOVA
Analysis of covariance
ANOVA
Analysis of variance
AN
Abscess and inflammatory Nodule
ANA
Anti-Nuclear Antibody
BCG
Bacille Calmette-Guérin
CDA
Clinical Drug Accountability
CDC
Centers for Disease Control and Prevention
CO2
Carbon dioxide
CRA
Clinical Research Associate
CRF
Case Report Form
CRP
C-Reactive Protein
CXR
Chest X-Ray
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
dsDNA
Double-stranded deoxyribonucleic acid
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EMA
European Medicines Agency
EMEA
European Agency for the Evaluation of Medicinal Products
EQ-5D
EuroQoL™
EU
European Union
ew
Every Week
FDA
US Food and Drug Administration
GCP
Good Clinical Practice 
HbA1c
Hemoglobin A1c
HBcAb
Hepatitis B Core Antibody 
HbsAb
Hepatitis B Surface Antibody


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HbsAg
Hepatitis B Surface Antigen
HBV
Hepatitis B Virus
HIV
Human Immunodeficiency Virus
HS
Hidradenitis Suppurativa
HiSCR
Hidradenitis Suppurativa Clinical Response 
HiSCR-es
Hidradenitis Suppurativa Clinical Response excluding the HS surgical site
hsCRP
High Sensitivity C-Reactive Protein
HSIA
Hidradenitis Suppurativa Impact Assessment
HS-PGA-SP
Hidradenitis Suppurativa Patient's Global Assessment of Skin Pain
HS-PGIC
Hidradenitis Suppurativa Patient's Global Impression of Change
HSSA-7d
Hidradenitis Suppurativa Symptom Assessment-7 day recall
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IgG1
Immunoglobulin G1
IGRA
Interferon-Gamma Release Assay
ILD
Interstitial Lung Disease
IRB
Institutional Review Board
IRT
Interactive Response Technology
ITT
Intent-to-Treat
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous
LOCF
Last Observation Carried Forward
LOQ
Limit of Quantification
MedDRA
Medical Dictionary for Regulatory Activities
MI
Multiple Imputation
NONMEM
Linear Mixed Effect Modeling
NRI
Non-Responder Imputation
NRS
Numeric Rating Scale
NYHA
New York Heart Association
PA
posterior-anterior 
PBMC
Peripheral blood mononuclear cell
pH
Power of Hydrogen Ion Concentration
PK
Pharmacokinetic


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PML
Progressive Multifocal Leukoencephalopathy
POR
Proof of Receipt
PP
Per Protocol
PPD
Purified Protein Derivative
PRN
As Needed
RA
Rheumatoid Arthritis
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAS
Statistical Analysis Software
SC
Subcutaneous
SmPC
Summary of Product Characteristics
TB
Tuberculosis
TEAEs
Treatment-Emergent Adverse Events
TESAEs
Treatment-Emergent Serious Adverse Events
TNF
Tumor Necrosis Factor
TNF-U
Tumor Necrosis Factor-alpha
TSQM
Treatment Satisfaction Questionnaire – Medication
US
United States
Wk
Week
WPAI:SHP
Work Productivity and Activity Impairment Questionnaire:  Specific Health


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Definition of Terms
Abscess
A circumscribed collection of purulent exudate frequently associated with 
swelling and other signs of inflammation, such as fluctuance, tenderness and 
pain.
AN Count
The sum of abscesses and inflammatory nodules, each a lesion diagnostic of HS.
HiSCR
Hidradenitis Suppurativa Clinical Response, defined as at least a 50% reduction 
in the AN count with no increase in abscess count and no increase in draining 
fistula count relative to Baseline.
HiSCR-es
HiSCR calculated excluding the AN count contained within the HS surgical site.
Hurley Staging
Stage I:
Abscess formation, single or multiple, without sinus tracts and 
cicatrization (scarring)
Stage II:
One or more widely separated recurrent abscesses with tract 
formation and cicatrization (scars).
Stage III: Multiple interconnected tracts and abscesses across the entire area, 
with diffuse or near diffuse involvement.
Hypertrophic Scar
Enlargement or overgrowth of a scar so that it extends above the surrounding 
skin surface.
Inflammatory nodule
A tender, erythematous well-defined nodule.  The lesion has no evidence of 
fluctuance.  A pyogenic granuloma lesion is considered an inflammatory nodule; 
a papule or pustule is not considered an inflammatory nodule.
Fistula
Pathologic passageway connecting to the skin surface from dermis or 
subcutaneous tissue.  Draining fistulas are fistulas that drain serous or purulent 
fluid, either spontaneously or by gentle palpation.  Sinus tracts are a sub-type of 
(non-draining) fistula in which the passageway links two or more areas 
underneath the skin surface, but does not communicate with the skin surface.
Non-inflammatory 
nodule
Non-tender or minimally tender, non-erythematous nodule.
Protocol Allowed 
Intervention
A protocol-allowed intervention is defined as incision and drainage, or injection 
of intra-lesional triamcinolone acetonide suspension (at a dose of 5 mg/mL, up 
to 1 cc).


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2.0
Table of Contents
1.0
Title Page ...............................................................................1
1.1
Protocol Amendment:  Summary of Changes ......................................... 2
1.2
Synopsis................................................................................................. 3
1.3
List of Abbreviations and Definition of Terms...................................... 10
2.0
Table of Contents ................................................................ 14
3.0
Introduction......................................................................... 19
3.1
Hidradenitis Suppurativa ...................................................................... 19
3.2
Current Treatments............................................................................... 22
3.3
Adalimumab Overview......................................................................... 24
3.4
Safety Information................................................................................ 25
3.5
Differences Statement .......................................................................... 26
3.6
Benefits and Risks................................................................................ 26
4.0
Primary Study Objective .................................................... 33
4.1
Secondary Study Objectives ................................................................. 33
4.2
Objectives for Optional Exploratory Research and Validation
Studies ................................................................................................. 34
4.3
Objectives for Doppler Ultrasound Sub-Study...................................... 34
5.0
Investigational Plan.............................................................34
5.1
Overall Study Design and Plan:  Description ........................................ 34
5.1.1
Description of Study Periods and Study Schematic............................... 34
5.2
Selection of Study Population............................................................... 38
5.2.1
Inclusion Criteria.................................................................................. 38
5.2.2
Exclusion Criteria................................................................................. 40
5.2.3
Prior and Concomitant Therapy............................................................ 43
5.2.3.1
Prior Therapy ....................................................................................... 45
5.2.3.2
Concomitant Therapy........................................................................... 45
5.2.3.3
Prohibited Therapy............................................................................... 47
5.2.3.4
Rescue Therapy.................................................................................... 48
5.2.4
Contraception Recommendations and Pregnancy Testing ..................... 49
5.3
Efficacy, Safety, and Exploratory Research/Validation Studies 
Assessments/Variables ......................................................................... 50


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15
5.3.1
Efficacy, Safety, and Exploratory Research/Validation Studies 
Measurements Assessed and Flow Chart .............................................. 50
5.3.1.1
Study Procedures.................................................................................. 50
5.3.2
Drug Concentration and Anti-Adalimumab Antibody 
Measurements ...................................................................................... 68
5.3.2.1
Collection of Samples for Analysis....................................................... 68
5.3.2.2
Handling/Processing of Samples........................................................... 69
5.3.2.3
Disposition of Samples......................................................................... 69
5.3.2.4
Measurement Methods ......................................................................... 69
5.3.3
Efficacy Variables................................................................................ 70
5.3.3.1
Primary Variable .................................................................................. 70
5.3.3.2
Secondary Variables............................................................................. 70
5.3.4
Safety Variables ................................................................................... 71
5.3.5
Pharmacokinetic Variables ................................................................... 71
5.3.6
Exploratory Research Variables............................................................ 72
5.4
Removal of Subjects from Therapy or Assessment ............................... 72
5.4.1
Discontinuation of Individual Subjects ................................................. 72
5.4.2
Discontinuation of Entire Study............................................................ 74
5.5
Treatments ........................................................................................... 74
5.5.1
Treatments Administered...................................................................... 74
5.5.2
Identity of Study Drug.......................................................................... 77
5.5.2.1
Packaging and Labeling........................................................................ 77
5.5.2.2
Storage and Disposition of Study Drugs ............................................... 78
5.5.3
Method of Assigning Subjects to Treatment Groups............................. 78
5.5.4
Selection and Timing of Dose for Each Subject .................................... 78
5.5.5
Blinding ............................................................................................... 80
5.5.5.1
Blinding of Study Drug ........................................................................ 80
5.5.6
Treatment Compliance ......................................................................... 80
5.5.7
Drug Accountability ............................................................................. 81
5.6
Discussion and Justification of Study Design........................................ 82
5.6.1
Discussion of Study Design and Choice of Control Groups .................. 82
5.6.2
Appropriateness of Measurements........................................................ 83
5.6.3
Suitability of Subject Population .......................................................... 83


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5.6.4
Selection of Doses in the Study ............................................................ 84
6.0
Complaints........................................................................... 84
6.1
Medical Complaints ............................................................................. 84
6.1.1
Definitions ........................................................................................... 85
6.1.1.1
Adverse Event...................................................................................... 85
6.1.1.2
Serious Adverse Events........................................................................ 86
6.1.1.3
Adverse Events of Special Interest........................................................ 87
6.1.2
Adverse Event Severity ........................................................................ 88
6.1.3
Relationship to Study Drug................................................................... 89
6.1.4
Adverse Event Collection Period.......................................................... 89
6.1.5
Adverse Event Reporting...................................................................... 90
6.1.6
Pregnancy............................................................................................. 92
6.1.7
Toxicity Management........................................................................... 92
6.2
Product Complaint................................................................................ 93
6.2.1
Definition............................................................................................. 93
6.2.2
Reporting ............................................................................................. 93
7.0
Protocol Deviations ............................................................. 94
8.0
Statistical Methods and Determination of Sample 
Size ....................................................................................... 95
8.1
Statistical and Analytical Plans............................................................. 95
8.1.1
Analysis Populations ............................................................................ 95
8.1.2
Planned Methods of Statistical Analysis ............................................... 96
8.1.3
Demographic and Baseline Characteristics ........................................... 96
8.1.4
Statistical Analyses of Efficacy ............................................................ 97
8.1.4.1
Primary Analysis of Efficacy................................................................ 98
8.1.4.2
Secondary Analyses of Efficacy ........................................................... 98
8.1.5
Statistical Analyses of Safety................................................................ 99
8.2
Determination of Sample Size .............................................................100
8.3
Randomisation Methods......................................................................100
8.4
Pharmacokinetic Analysis....................................................................101
9.0
Ethics.................................................................................. 102
9.1
Independent Ethics Committee or Institutional Review Board .............102
9.2
Ethical Conduct of the Study...............................................................103


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9.3
Subject Information and Consent.........................................................103
10.0
Source Documents and Case Report Form 
Completion ........................................................................ 104
10.1
Source Documents...............................................................................104
10.2
Case Report Forms ..............................................................................105
11.0
Data Quality Assurance .................................................... 106
12.0
Use of Information ............................................................ 107
12.1
Use of Information ..............................................................................107
12.2
Publication ..........................................................................................108
13.0
Completion of the Study ................................................... 109
14.0
Investigator's Agreement.................................................. 110
15.0
Reference List.................................................................... 111
List of Tables
Table 1.
Clinical Laboratory Tests ..................................................................... 58
Table 2.
Identity of Study Drug.......................................................................... 77
Table 3.
Adverse Events of Special Interest........................................................ 88
List of Figures
Figure 1.
Study Schematic................................................................................... 37
Figure 2.
Adverse Event Collection..................................................................... 90
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.........................................116
Appendix B.
List of Protocol Signatories .................................................................118
Appendix C.
Schedule of Activities..........................................................................119
Appendix D.
Optional Exploratory Research and Validation Studies – Schedule 
of Activities.........................................................................................123
Appendix E.
Lesion Counts – Sample ......................................................................124
Appendix F.
Dermatology Life Quality Index (DLQI) – Example............................125


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Appendix G.
EuroQoL EQ-5D – Example................................................................127
Appendix H.
Hidradenitis Suppurativa Impact Assessment – Example.....................129
Appendix I.
Hidradenitis Suppurativa Patient's Global Assessment of Skin 
Pain – Example ...................................................................................130
Appendix J.
Hidradenitis Suppurativa Patient Global Impression Change –
Example ..............................................................................................131
Appendix K.
Hidradenitis Suppurativa Symptom Assessment – 7 Day Recall –
Example ..............................................................................................132
Appendix L.
Short Form-12 – Example....................................................................135
Appendix M.
Treatment Satisfaction Questionnaire for Medication – Example.........136
Appendix N.
Work Productivity and Activity Impairment Questionnaire:  
Specific Health Problem – Example ....................................................137
Appendix O.
Clinical Study Site Personnel – Study Drug Dispensing Table.............139
Appendix P.
Subject Injection Instructions – Example Pre-Filled Syringe................140
Appendix Q.
Subject Dosing Chart – Example .........................................................144
Appendix R.
Study Site Drug Accountability (by Subject) Log – Example...............145
Appendix S.
Protocol Amendment:  List of Changes ...............................................146


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3.0
Introduction
3.1
Hidradenitis Suppurativa
Hidradenitis suppurativa (HS), also known as acne inversa is a chronic systemic relapsing 
inflammatory disease primarily affecting the skin in intertriginuous areas, i.e., axillae, 
groin, and inframammary regions.1,2  Hidradenitis suppurativa is characterized by 
recurrent inflamed deep-seated acneiform nodules that result in abscesses, and chronic 
draining sinus tract formation leading to scarring, disfigurement, and life-altering 
disability.  Its negative impact on quality of life is extreme, mainly due to the lack of early 
recognition, accurate diagnosis, and appropriate management.  Hidradenitis suppurativa 
has a profoundly negative impact on patients' physical, social, and economic lives, with a 
higher morbidity index than urticarial, neurofibromatosis, psoriasis, atopic dermatitis, or 
alopecia.  Many become socially isolated or reclusive due to incorrect diagnosis, the 
numerous lesions, long and continuous duration, and pelvic area involvement.  Patients 
with HS, mainly women, lose an average of 2 – 7 days of work per year (or they lose their 
job).3
Hidradenitis suppurativa creates a substantial burden of disease, particularly in those 
subjects with more severe manifestations (in one study, mean Dermatology Life Quality 
Index (DLQI) scores were 5.77, 13.1, and 20.4 for Hurley Stages I, II, and III 
classifications, respectively).4  Comparing the DLQI scores of this study with other 
studies that employed this qualitative method illustrates that HS has a higher impairment 
in quality of life (QoL) than chronic skin diseases, such as the average patient with 
psoriasis, hair loss, pityriasis, rosacea, and bullous pemphigoid, just to name a few.  
Although HS, like other chronic skin diseases, is not imminently dangerous, its effect on 
the patient's QoL, society and the healthcare system is comparable to, if not greater than 
conditions such as hypertension or diabetes.5,6
As HS has been an orphan disease for decades and subsequently a highly misdiagnosed 
and underdiagnosed condition with significant diagnosis delay, the true prevalence has
been correspondingly challenging to estimate.  Prevalence rates are reported as low as 


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0.00033% and as high as 4.1%.7-12  Most authors report no racial differences but the 
female-to-male ratio is 3.3:1.  Comparisons of HS to psoriasis in terms of size and scope 
of the conditions are worth making.  The prevalence of HS may approach that of psoriasis, 
while the sex ratio in large-scale clinical trials for moderate to severe disease is inverted 
(i.e., 2:1 female-to-male for HS and 1:2 for psoriasis), patients with either condition are 
affected by comorbidities, social disability, obesity, and stigma.13-15
The mean age of onset is 22.1 years; it lasts about 19 years, can remit or partially remit 
with pregnancy and breastfeeding, and be very variable.  Usually a benign, mild, chronic 
but intermittently painful disease, HS has acute exacerbations, premenstrual flares, 
resolution after menopause, remission for weeks to months, or continuous or intermittent 
flares.  Solid plaques of coalescent nodules, sinuses, and scars host smelly discharge, pain, 
and debility.  New, deep, painful nodules last 10 to 30 days.  Patients may present with a 
certain degree of severity and remain in that range, severe disease usually starting with 
severe disease from the beginning.  The difficulty with mobility ranges from minor 
soreness to inability to walk or sit without pain.  Odor from drainage may be significant 
and require diapers, leading to social withdrawal, depression, and dysfunctional lives.16,17
The physical extent of HS can be classified using Hurley's clinical staging (Section 1.3) 
but remain unclear why HS may remain limited to Hurley Stage I, evolve to the more 
confluent (Hurley Stage II) or progress even further to the fully confluent (Hurley III).  
Other available clinical measures for assessing HS disease severity include the modified 
Sartorius (MSS) and the HS Physician's Global Assessment (HS-PGA).  Those scores 
were designed for an accurate assessment of the extent of inflammation within each stage.  
To support the development of effective anti-inflammatory treatments for HS, the clinical 
and research community has called for a validated assessment that can be used to identify 
treatment response.  Using data from a Phase 2 clinical trial that evaluated the safety and 
efficacy of adalimumab in adults with moderate to severe chronic HS (ClinicalTrials.gov 
Identifier:  NCT00918255) a new practical and straightforward clinical endpoint was 
proposed and validate:  the Hidradenitis Suppurativa Clinical Response (HiSCR).  The 
HiSCR is defined by the status of three types of lesions (defining criteria):  abscesses 


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(fluctuant, with or without drainage, tender or painful), inflammatory nodules (tender, 
erythematous, pyogenic granuloma lesion), and draining fistulas (sinus tracts, with 
communication to the skin surface, draining purulent fluid).  The proposed definition of 
responders to treatment (HiSCR achievers) is:  i) at least a 50% reduction in the total 
number of abscesses and inflammatory nodules (AN) count, ii) no increase in the number 
of abscesses, and iii) no increase in the number of draining fistulas, compared to 
baseline.18
Disease onset is typically after puberty.  It affects women from 2 to 5 times more 
commonly than men.  Several factors may predispose a person to HS, including genetics, 
cigarette smoking, and obesity.19  The histopathologic characteristics of HS include a 
dense inflammatory cell infiltrate of neutrophils, lymphocytes, and histiocytes.20  Tumor 
necrosis factor-alpha (TNF-U), which induces other pro-inflammatory cytokines and 
activates neutrophils and lymphocytes, may have a pathogenic role, based on the evident 
over-expression of tumor necrosis factor (TNF) in HS lesions.21
Giamarellos-Bourboulis and co-workers described an altered immune response in patients 
with HS, suggesting a role for TNF-U and the innate immune system in the pathogenesis 
of the disease.  Later, increased amounts of circulating, as well as bound TNF-U were 
found, support the previous observations.  In parallel, the use of TNF-U blockers for the 
treatment of HS was being studied in case series.22
Although the clinical presentation of HS is strongly reminiscent of bacterial infection, the 
role of bacteria remains controversial.  Studies have isolated an array of different bacterial 
specimens as well as biofilm formation in lesional HS skin.  Although the pathogenesis of 
inflammation in HS is not fully understood, different types of antibiotics 
(e.g., tetracyclines, rifampin, clindamycin) are widely and increasingly used to treat HS in 
the absence of validated efficacy data.  Considering the prevalence of HS, this issue is 
critical because potential antimicrobial resistance may hamper the efficacy of antibiotics 
and induce co-morbidities associated with altered commensal microflora.23


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3.2
Current Treatments
Prior to the Adalimumab Clinical Trial program, (Studies M10-467, M11-313, M11-810), 
the only placebo controlled trial of HS demonstrated modest efficacy with the use of 
topical clindamycin.24  Other treatments for HS include:  medical treatment (e.g., systemic 
combination therapy with clindamycin and rifampicin, intra-lesional triamcinolone, 
systemic cyclosporine, anti-androgen treatment in women, systemic dapsone, systemic 
retinoids, and metformin),25-29 surgical treatment (radical excision, marsupialization, and 
de-roofing),30-35 and laser treatment (carbon dioxide [CO2]  laser and neodymium-doped 
yttrium aluminum garnet [Nd:YAG] laser).36-39 It is difficult to evaluate the efficacy for 
these interventions because their use is described in open-label, frequently retrospective, 
case series and case reports, with variable, but typically short term follow-up.  Case series 
and case reports have shown that inhibitors of TNF-U are effective in treating HS.40-42  
Thus AbbVie conducted Phase 2 and Phase 3 clinical trials, demonstrating the clinical 
efficacy and safety of adalimumab in subjects with moderate to severe HS.43  In 2015 
adalimumab was approved for treatment of moderate to severe HS by the European 
Medicines Agency (EMA)44 and will be available for use in many countries with a 
recommended dose specific for the treatment of HS.
Surgical management is an essential modality of the treatment algorithm for HS, to be 
used concurrently with other treatments.12,45,46  Patients treated with surgery generally 
demonstrate one or more of the following:  extensive sinus tract and/or fistula, mutilating 
HS, contracted scars, and painful scars.  Multiple types of surgical procedures may be 
performed for HS treatment, from a simple incision and drainage to wide surgical excision 
of the lesions.  Use of technologies such as CO2 laser has also been used with success.  
Wide surgical excision is the most radical and invasive of the procedures, involving 
excision of the lesion and surrounding skin, sometimes extending down to deep fascial 
layers.  The remaining surgical area may be extensive, and closure may be primary or 
secondary.  Skin grafting may be utilized and for larger areas, flap repair may need to be 
performed.  Recurrence may still occur after surgical management, with rates ranging 
from 1% – 70% depending on the type of procedure performed.12  In addition, though 


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surgical management may be performed for the most severe lesions, patients may have 
lesions in other anatomical areas, and therefore require continued medical treatment while 
undergoing surgical management.  Patients undergoing surgery for HS lesions were not 
studied in the registration trials; therefore there are no placebo-controlled data that inform 
the physician regarding the impact of adalimumab on HS lesions in the patient who is 
undergoing surgery as part of therapy to manage the disease.
Surgery to remove HS lesional skin is a key treatment modality and adalimumab has 
recently been approved for the medical treatment of moderate to severe HS based on 
safety and efficacy data.
The European S1 HS guideline suggests that the disease should be treated based on its 
individual subjective impact and objective severity.  Locally recurring lesions can be 
treated by classical surgery or LASER techniques, whereas medical treatment either as 
monotherapy or in combination with radical surgery is more appropriate for widely spread 
lesions.12
When used in combination with radical resection of grossly evident disease, the 
immunosuppressive effects of biologics could potentially augment the results achievable 
through surgical intervention alone.  To date, however, there have been no randomized 
controlled trials investigating the role of neoadjuvant/adjuvant biologic therapy in 
reducing the size and/or disease progression in patients with moderate-severe HS.
There is a need to adopt a multidisciplinary treatment strategy that facilitates collaboration 
between the surgeon and dermatologist and integrates established surgical principles with 
therapy that targets underlying proinflammatory mechanisms that contribute to disease 
pathogenesis.
This study will be the first large prospective, randomized, double-blind, placebo-
controlled clinical trial to evaluate the use of anti-TNF therapy in conjunction with 
surgery of adults suffering with moderate to severe HS.  


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3.3
Adalimumab Overview
Adalimumab is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody 
containing only human peptide sequences.  Adalimumab is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  It 
consists of 1,330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  Adalimumab is composed of fully human heavy and light chain variable 
regions, which confer specificity to human TNF-U, and human IgG1 heavy chain and 
kappa light chain sequences.  Adalimumab binds with high affinity and specificity to 
soluble TNF-U but not to lymphotoxin-U (TNF-W).
TNF-U is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF-U are thought to play an important role in 
pathologic inflammation.  Adalimumab binds specifically to TNF-U and neutralizes the 
biological function of TNF-U by blocking its interaction with the p55 and p75 cell surface 
TNF-U receptors.  Adalimumab also modulates biological responses that are induced or 
regulated by TNF-U.  After treatment with adalimumab, levels of acute phase reactants of 
inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and 
serum cytokines rapidly decrease.
Adalimumab was first approved in the United States (US) and European Union (EU) for 
the treatment of rheumatoid arthritis in 2002 and 2003, respectively.  Additional 
indications have been approved in the US and EU, including, but not limited to HS, 
psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, 
polyarticular juvenile idiopathic arthritis, paediatric Crohn's disease, paediatric psoriasis, 
as well as paediatric enthesitis-related arthritis and non-radiographic axial 
spondyloarthritis in the EU, and intestinal bowel disease in Japan.  Adalimumab received 
approval in the EU for treatment of active moderate to severe HS in 2015.  Additional 
updates regarding approved indications can be found in the current edition of the Humira 
Summary of Product Characteristics (SmPC).44


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The adalimumab clinical development program that obtained efficacy and safety data for 
adalimumab in adult subjects with moderate to severe HS included a dose-ranging Phase 2 
study (Study M10-467) and two Phase 3 studies designated PIONEER I and PIONEER II 
(Study M11-313 and Study M11-810, respectively).  In addition subjects were eligible to 
enroll in an on-going Phase 3 open-label extension study (Study M12-555).  The Phase 2 
study demonstrated that after loading doses there was demonstrated HiSCR with 40 mg 
weekly dosing.  PIONEER I and II had similar placebo-controlled 36-week study designs 
and primary efficacy endpoint (i.e., proportion of subjects achieving HiSCR at Week 12).  
Following a 12-week two-arm period with adalimumab 40 mg weekly doses versus 
placebo (Period A), subjects in the active treatment arm were re-randomized to 
adalimumab 40 mg weekly dosing, adalimumab 40 mg every other week dosing, or 
placebo from Week 12 to Week 36 (Period B).  Subjects in the placebo arm were treated 
with adalimumab 40 mg weekly in PIONEER I or placebo (PIONEER II) from Week 12 
to Week 36.  A statistically significant greater proportion of adalimumab-treated subjects 
achieved HiSCR at Week 12 (Period A), regardless of Hurley Stage or concomitant 
antibiotic use.  At the end of Period B a higher proportion of subjects in the continuous 
adalimumab 40 mg weekly dose maintained HiSCR as compared to those subjects 
re-randomized to adalimumab every other week dosing or placebo dosing.  There were no 
safety differences across the treatment groups.43
3.4
Safety Information
Adalimumab therapy has a well-established and well-described safety profile based on 
extensive post-marketing experience and continued clinical trial patient exposure since the 
first approved indication in 2002 for rheumatoid arthritis.  A detailed discussion of the 
clinical toxicology, metabolism, pharmacology, and safety experience with adalimumab 
can be found in the current SmPC.  AbbVie is committed to continue to collect safety 
information including those events that may occur in this trial in order to confirm this 
established safety profile and to identify any unknown potential adverse reactions, rare 
events and those events with a long latency.  AbbVie is participating in the US Food and 
Drug Administration (FDA) requested, TNF inhibitor class-wide exploration of the rare 


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appearance of malignancy in subjects who are 30 years of age or younger at the time of 
diagnosis.  The risk of malignancy in this age group has not been established and is 
difficult to study due to its rarity.  AbbVie appreciates your attention to the additional 
reporting requirements needed in this unlikely event, outlined in Section 6.1.5 under 
Adverse Event Reporting.
3.5
Differences Statement
While several studies (i.e., Studies M10-467, M11-313, M11-810, and M12-555)  have 
been conducted evaluating the safety and efficacy of the use of adalimumab for the 
treatment of moderate to severe HS, to date no adequate and well controlled study has 
included patients who undergo surgical intervention for their HS while being treated with 
adalimumab.
3.6
Benefits and Risks
Adalimumab therapy has a well-established and well described safety profile based on 
extensive post-marketing experience and continued clinical trial patient exposure since the 
first approved indication in 2002 for rheumatoid arthritis.  More than 29,000 subjects 
participating in hidradenitis suppurativa, polyarticular juvenile idiopathic arthritis, 
pediatric enthesitis related arthritis, Crohn's disease, pediatric Crohn's disease, psoriasis, 
pediatric psoriasis, rheumatoid arthritis, ankylosing spondylitis, non-radiographic axial 
spondyloarthritis, peripheral spondyloarthritis, psoriatic arthritis, intestinal Behçet's 
disease, uveitis and ulcerative colitis clinical studies have been treated with adalimumab.  
The majority of side effects experienced following administration of adalimumab were 
mild to moderate in severity.
The most commonly reported adverse reactions are infections (such as nasopharyngitis, 
upper respiratory tract infection and sinusitis), injection site reactions (erythema, itching, 
haemorrhage, pain or swelling), headache and musculoskeletal pain.
Serious adverse reactions have been reported for Humira.  TNF-antagonists, such as 
Humira affect the immune system and their use may affect the body's defense against 


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infection and cancer.  Fatal and life-threatening infections (including sepsis, opportunistic 
infections and TB), HBV reactivation and various malignancies (including leukaemia, 
lymphoma and HSTCL) have also been reported with use of Humira.
Serious haematological, neurological and autoimmune reactions have also been reported.  
These include rare reports of pancytopenia, aplastic anaemia, central and peripheral 
demyelinating events and reports of lupus, lupus-related conditions and Stevens-Johnson 
syndrome.
Humira is contraindicated in patients with:
Y
Hypersensitivity to the active substance or to any of its excipients;
Y
Active tuberculosis or other severe infections such as sepsis, and 
opportunistic infections;
Y
Moderate to severe heart failure (NYHA class III/IV) 
In its Summary of Product Characteristics, Special warnings and 
precautions for use for Humira are the following:
Y
Infections
Patients taking TNF-antagonists are more susceptible to serious infections.  
Impaired lung function may increase the risk for developing infections. 
Y
Serious infections
Serious infections, including sepsis, due to bacterial, mycobacterial, 
invasive fungal, parasitic, viral, or other opportunistic infections such as 
listeriosis, legionellosis and pneumocystis have been reported in patients 
receiving Humira.
Y
Tuberculosis
Tuberculosis, including reactivation and new onset of tuberculosis, has 
been reported in patients receiving Humira.  Reports included cases of 
pulmonary and extra-pulmonary (i.e., disseminated) tuberculosis.
Y
Other opportunistic infections
Opportunistic infections, including invasive fungal infections have been 
observed in patients receiving Humira.  These infections have not 


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consistently been recognised in patients taking TNF antagonists and this 
resulted in delays in appropriate treatment, sometimes resulting in fatal 
outcomes.
Y
Hepatitis B reactivation
Reactivation of hepatitis B has occurred in patients receiving a TNF-
antagonist including Humira, who are chronic carriers of this virus 
(i.e., surface antigen positive). 
Y
Neurological events
TNF-antagonists including Humira have been associated in rare instances 
with new onset or exacerbation of clinical symptoms and/or radiographic 
evidence of central nervous system demyelinating disease including 
multiple sclerosis and optic neuritis, and peripheral demyelinating disease, 
including Guillain-Barré syndrome. 
Y
Allergic reactions
Serious allergic reactions associated with Humira were rare during clinical 
trials.  Non-serious allergic reactions associated with Humira were 
uncommon during clinical trials.  Reports of serious allergic reactions 
including anaphylaxis have been received following Humira 
administration. 
Y
Immunosuppression
In a study of 64 patients with rheumatoid arthritis that were treated with 
Humira, there was no evidence of depression of delayed-type 
hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector T-, B, - NK-cells, monocyte/macrophages, and 
neutrophils.
Y
Malignancies and lymphoproliferative disorders
In the controlled portions of clinical trials of TNF-antagonists, more cases 
of malignancies including lymphoma have been observed among patients 
receiving a TNF-antagonist compared with control patients.  However, the 
occurrence was rare. 
Y
Haematologic reactions


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Rare reports of pancytopaenia including aplastic anaemia have been 
reported with TNF-antagonists. 
Adverse events of the haematologic system, including medically 
significant cytopoenia (e.g., thrombocytopaenia, leucopaenia) have been 
reported with Humira. 
Y
Vaccinations
Patients on Humira may receive concurrent vaccinations, except for live 
vaccines. 
Y
Congestive heart failure
In a clinical trial with another TNF-antagonist worsening congestive heart 
failure and increased mortality due to congestive heart failure have been 
observed.  Cases of worsening congestive heart failure have also been 
reported in patients receiving Humira. 
Y
Autoimmune processes
Treatment with Humira may result in the formation of autoimmune 
antibodies.  The impact of long term treatment with Humira on the 
development of autoimmune diseases is unknown. 
Y
Concurrent administration of biologic DMARDS or TNF-antagonists
Concomitant administration of adalimumab with other biologic DMARDS 
(e.g, anakinra and abatacept) or other TNF-antagonists is not recommended 
based upon the possible increased risk for infections, including serious 
infections and other potential pharmacological interactions.
Y
Elderly patients
The frequency of serious infections among Humira treated subjects over 
65 years of age (3.6%) was higher than for those under 65 years of age 
(1.4%).  Some of those had a fatal outcome.  Particular attention regarding 
the risk for infection should be paid when treating the elderly.
Y
Surgery
There is limited safety experience of surgical procedures in patients treated 
with Humira. 
The SmPc states that the long half-life of adalimumab should be taken into 
consideration if a surgical procedure is planned.  A patient who requires 


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surgery while on Humira should be closely monitored for infections, and 
appropriate actions should be taken. 
Experience of adalimumab used peri-surgically: 
This will be the first randomised controlled study assessing the use of adalimumab peri-
surgically, and of assessing an anti-TNF therapy peri-surgically. 
A meta-analysis performed to conduct a systematic review of studies reporting on the 
post-operative complications of another anti-TNF use, infliximab, in the pre-operative 
period for Crohn's disease, concluded that pre-operative infliximab use was not shown to 
be associated with higher rates of major post-operative complications in patients with 
Crohn's Disease undergoing intra-abdominal surgery, and evaluated up to 90 days post-
surgery.47  Minor complications, the need for a repeat operation and mortality within the 
first 30 days were also not affected by pre-operative infliximab therapy.  A database 
analysis has examined the rate of postoperative morbidity in patients with Crohn's disease 
receiving anti TNF therapy in the perioperative period, including the use of adalimumab.48  
This retrospective analysis was performed in one center, the Division of Colon and Rectal 
Surgery, Mayo Clinic, Rochester.  All patients undergoing surgery for Crohn disease from 
2005 till 2008 were abstracted from a prospective database, and patients undergoing 
surgery which included a suture or staple line at risk for leaking were selected for the 
study.  A retrospective review of medical records was performed. 
The study compared the post-operative outcomes of patients treated with perioperative 
anti TNF therapy (defined as treatment within 8 weeks preoperatively or up to 30 days 
postoperatively) to those in patients without anti-TNF therapy.
Three hundred and seventy patients were selected for analysis in this study, of which 
119 received perioperative anti- TNF therapy (69 infliximab, 47 adalimumab 40 mg eow, 
3 Certolizumab), and 251 did not receive any anti-TNF therapy. 


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The groups were similar in baseline characteristics, perioperative risk factors and 
procedures.
There was no significant association of perioperative anti TNF therapy and any 
postoperative complications (27.9% in anti-TNF group versus 30.1% in no anti-TNF 
group, p = 0.63) nor intra-abdominal infectious complications (5.0% in anti-TNF group 
versus 7.2% in no anti-TNF group, p = 0.44).  Univariate analysis showed that the only 
factors associated with an increase in postoperative intra-abdominal infections were age 
and penetrating disease. 
The analysis concluded that the use of anti-TNF therapy in the perioperative period is safe 
and is not associated with an increase in overall or infectious complications in Crohn's 
disease patients undergoing surgery.
A further study examined the impact of pre-operative anti-TNF-U agents on postoperative 
outcomes 30 and 60 days after Crohn's disease surgery in a nationwide Danish cohort.  
Outcomes were death, reoperation, anastomosis leakage, intra-abdominal abscess and 
bacteraemia.49  Among surgical procedures for Crohn's disease, 214 were exposed to anti-
TNFs and 2079 were not.  During the study period, infliximab counted for most of the 
anti-TNF-U agents given before surgery with 57.0% (122/214), adalimumab with 27.1% 
(58/214) and other anti-TNF-U agents with 15.9% (34/214).
The authors found no increased relative risks of death or abscess drainage 30 or 60 days 
after follow-up.  Among exposed, 7.5% had a reoperation within 30 days vs. 8.6% among 
unexposed, adjusted odds ratio (OR) = 0.92, 95% confidence interval (CI):  0.52 – 1.63.  
Among exposed, 3.8% had an anastomosis leakage within 30 days after surgery vs. 2.8% 
among unexposed, adjusted OR = 1.33, 95% CI:  0.59 – 3.02.  No further cases of 
anastomosis leakages appeared within 60 days.
Sub-analyses indicated no increased risk of bacteraemia after 30 days and no increased 
risks when anti-TNF-U agents were given 14 days before surgery.


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In conclusion the authors found no significantly increased relative risks of post-operative 
complications after use of anti-TNF-U agents either 12 weeks or 14 days before surgery 
for Crohn's disease. 
The safety and efficacy of adalimumab in HS has been explored in the Phase 2 trial 
(Study M10-467) and in two Phase 3 trials (Studies M11-313 and M11-810, PIONEER I 
and II, respectively).  To date, 733 subjects with HS have been studied in adalimumab 
clinical studies in the HS clinical program, for a total of 836.3 patient-years of 
adalimumab exposure.  Treatment emergent adverse events (TEAEs) were reported in 
595 subjects (81.2%) for a rate of 417.6 events/100 patient-years.  Worsening 
hidradenitis, nasopharyngitis, headache, and upper respiratory tract infection were the 
most frequently reported TEAEs.50
The recommended adalimumab dose regimen for adult patients with moderate to severe 
HS (i.e., 160 mg initially on Day 1, 80 mg on Day 15, and beginning on Day 29, the 
regimen continues with a dose of 40 mg every week [ew]) was safe and well-tolerated, as 
evaluated by the incidence and severity of TEAEs, treatment-emergent serious adverse 
events (TESAEs), premature discontinuations due to TESAEs, and changes in laboratory 
and vital sign values.  The incidence and severity of TEAEs, TESAEs, and premature 
discontinuations due to TEAEs, as well as laboratory and vital sign results, were generally 
comparable between the adalimumab and placebo groups, and were consistent with a 
population of subjects with moderate to severe HS.  The rates of treatment-emergent 
adverse events of special interest (AESI) were generally consistent with previous studies 
in approved adalimumab indications.50
Efficacy data from the adalimumab HS clinical program demonstrate that the 
recommended adalimumab dosing regimen is an effective treatment for inflammatory 
lesions and skin pain of HS among moderate to severe HS subjects who had an inadequate 
response or were intolerant to oral antibiotic therapy.  The short-term efficacy of 
adalimumab (i.e., 12 weeks of therapy) was demonstrated with the primary efficacy 
measure Hidradenitis Suppurativa Clinical Response (HiSCR) rate; and key secondary 
efficacy measures including proportion of subjects with total abscess and inflammatory 


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nodule (AN) counts of 0, 1, or 2; proportion of subjects with clinically relevant pain 
reduction, and mean improvement in modified Sartorius score.  Other efficacy measures 
included improvement in lesion counts, reduced risk of flare, and improvement in 
dermatology-specific quality of life.  A high proportion of subjects who achieved at least a 
partial short-term improvement maintained treatment success with long-term therapy (up 
to 52 weeks).51
Subjects enrolled in this study will be eligible patients who will have surgical intervention 
as part of their routine care.  Standard practices regarding perioperative and operative care 
will be under the direction of the dermatologist and/or surgeon and will not be directed 
per this protocol.  It is expected the routine risks of surgery will be essentially unchanged 
by participation in this study.  The subject will be closely followed for any adverse events, 
adverse events of special interest, adverse events concerning the surgical site and the 
relationship to study drug as assessed by the Study Investigator will be recorded and 
analysed.  As described above for active HS lesions, there is the possibility that 
adalimumab may positively affect the active HS lesions in the planned surgical site, which 
might then allow for a less extensive surgical intervention.  Adalimumab is predicted to 
have neither a positive or negative impact on fibrotic lesions within the HS surgical site.
4.0
Primary Study Objective
Assess the safety and efficacy of adalimumab prior to surgery in subjects with moderate 
to severe HS who are surgical candidates, using HiSCR as the assessment measurement.
4.1
Secondary Study Objectives
Assess the impact of adalimumab specifically on the planned HS surgical site before 
surgery, evaluate the safety and efficacy of adalimumab continued during the 
perioperative period and after surgery, and evaluate Patient Reported Outcomes (PRO) 
related to health status, HS-related symptoms (e.g., drainage, swollen skin), physical 
functioning, treatment satisfaction, and work/activity impairment.  The pharmacokinetics 
(PK) and immunogenicity of adalimumab following subcutaneous (SC) injection in this 
HS surgical population will also be assessed.  The objective is to determine if the 


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inflammatory status of the HS surgical subject alters the PK profile both prior to and after 
surgery.
4.2
Objectives for Optional Exploratory Research and Validation 
Studies
The principal objective of the optional exploratory research and validation studies is to 
help improve our understanding of how individuals respond to adalimumab and our 
ability to predict which patient might benefit from receiving such treatment for HS.  In 
addition, exploratory research may help to improve our understanding of how to diagnose 
and assess/monitor HS by assessing association between disease characteristics, outcomes 
data, and biomarkers of interest.
4.3
Objectives for Doppler Ultrasound Sub-Study
The objective of the Doppler Ultrasound sub-study is to provide pilot data from a 
randomized double blind placebo-controlled trial to help determine if evaluation of HS 
lesions using Doppler ultrasound provides for more accurate staging and response to 
therapy of the disease than current standard medical diagnosis and evaluation.  These data 
will be evaluated separately from data derived from the main study.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
5.1.1
Description of Study Periods and Study Schematic
This interventional, randomised, double-blind, placebo-controlled study is designed to 
enroll 200 subjects to meet scientific and regulatory objectives without enrolling an undue 
number of subjects in alignment with ethical considerations.  Therefore, if the target 
number of subjects has been enrolled, there is a possibility that additional subjects in 
screening will not be enrolled.  Eligible subjects will have active HS disease with an axilla 
or unilateral inguinal region that requires excisional surgery plus two other anatomical 
regions with active HS lesions (at least one region at Hurley Stage II or III).


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The study duration will include a 30-day Screening Period, an initial 12-week 
double-blind treatment pre-surgery period (Period A), a 2-week peri-surgery period with 
continuation of weekly double-blind study drug administration (Period B), and a 
subsequent 10-week double-blind treatment post-surgery period (Period C).  
Screening Period:  The duration of the screening period will be a minimum of 7 days and 
a maximum of 30 days during which time all of the inclusion and exclusion criteria will 
be evaluated, and at referring sites, an eligibility visit with the designated surgeon will 
take place.  Subjects may enroll into the study after all screening procedures are complete 
and results are known and verified for eligibility at the Baseline visit (Day 1) to receive 
160 mg of adalimumab or matching placebo.
Subjects will have up to 30 days to return to the clinical study site for the Baseline visit 
from the date of the Screening visit.  Study visits will occur according the schedule in 
Appendix C.  In addition, all subjects will be contacted by telephone at Weeks 6 and 10 to 
monitor whether any signs or symptoms of infection are present at or near an HS lesion.  
If any signs or symptoms of infection are reported at the time of the call, an unscheduled 
study visit will be conducted to assess whether an infection is present.  The informed 
consent will include a description of signs and symptoms of infections along with the 
contact information so that the subject may contact the study site immediately if any such 
signs or symptoms develop at or near an HS lesion.
Subjects that initially screen fail for the study may be permitted to re-screen following 
re-consent.  All screening procedures with the possible exceptions noted below will be 
repeated.  The subject must meet all inclusion and none of the exclusion criteria at the 
time of re-screening in order to qualify for the study.  There is no minimum period of time 
a subject must wait to re-screen for the study.  If the subject had a complete initial 
screening evaluation including tuberculosis (TB) screening, chest x-ray (CXR, if 
applicable), and 12-lead electrocardiogram (ECG), these tests will not be required to be 
repeated for re-screening provided the conditions noted in Section 5.3.1.1 are met and no 
more than 3 months (90 days) have passed.  As appropriate, study sites are encouraged to 
contact the AbbVie Medical Monitor to confirm if subjects should or should not be 


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re-screened.  If the subject had a negative human immunodeficiency virus (HIV) result at 
screening but 30 days have elapsed prior to the re-screen, then the HIV screening test 
must be repeated and the result handled in a like manner as the original screening test (see 
Section 5.3.1.1).
Period A:  A 12-week double-blind, placebo-controlled treatment period during which 
subjects are randomised in a 1:1 ratio to receive adalimumab or matching placebo, 160 mg 
initially at Day 1 (or given as two 40 mg injections per day for 2 consecutive days), 
followed by 80 mg 2 weeks later at Day 15 (given as two 40 mg injections in 1 day).  
Two weeks later (Day 29) continue with a dose of 40 mg ew until Week 12.  The 
randomisation will be stratified by baseline Hurley Stage (II versus III) and anatomical 
location of the surgical site (i.e., axilla versus inguinal region).  A subject's Hurley Stage 
is determined by the worst Hurley Stage (i.e., II versus III) across all affected anatomic 
regions.  The projected size of the surgical excision established by the designated surgeon 
during the Screening Period (calculated from a tracing of the outer perimeter onto an 
acetate sheet or equivalent) will be recorded by the study physician in the CRF.  On each 
clinical study visit day, all study procedures scheduled for that visit will be completed 
prior to study drug administration.
Period B:  A 2-week double-blind, placebo-controlled treatment period consisting of 
Weeks 13 and 14 (the peri-operative period) in which subjects will continue the treatment 
on the first day of Weeks 13 and 14.  The designated surgeon will measure the surface 
area of the actual surgery and record in source document.  Surgery will occur during 
Week 13.  The surgery and post-operative management (e.g., hospitalisation, surgical 
wound care) will be as per local practice.
Period C:  A 10-week double-blind, placebo-controlled post-operative treatment period 
will occur from Week 15 through Week 24, during which the subject will continue the 
treatment assigned at Day 1 from Week 15 through Week 23.  No study drug will be 
administered at Week 24, the final study visit.  Subjects may begin commercial product 
(as prescribed by the subject's physician) after all Week 24 procedures have been 
completed.


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Study procedures throughout the study are listed in Appendix C.  Safety and efficacy 
measurements will be performed throughout the study as described in Section 5.3.1.
The study visit window will be ± 3 days for the Week 2 and Week 4 visits and ± 7 days, 
relative to Baseline, for all study visits from Week 8 through Week 24.  Surgery takes 
place at Week 13 after all Week 12 evaluations are completed.  A subject will be brought 
back to the original visit schedule (calculated from the Baseline visit [Day 1]) if the 
subject is out of the visit window.
Subjects may discontinue adalimumab treatment at any time during study participation.  
Subjects that end study participation early will have a Premature Discontinuation Visit 
unless consent to participate is withdrawn.  
Figure 1.
Study Schematic


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5.2
Selection of Study Population
Subjects will be screened to determine if they meet all of the inclusion criteria specified in 
Section 5.2.1 and none of the exclusion criteria specified in Section 5.2.2.
5.2.1
Inclusion Criteria
1.
Male and female subjects between the ages of 18 and 65, inclusive;
2.
Subject must have skin lesions that are diagnostic of HS for at least 1 year 
(365 days) prior to the Baseline visit;  
3.
Subject must have at least 3 distinct anatomical regions involved with 
inflammatory (also termed 'active') HS lesions; including
a.
either an axilla or unilateral inguinal region (limited to the inguino-crural fold and 
adjacent areas) that requires excisional surgery (hereinafter designated the "HS 
surgical site"), and
b. with at least one of the other affected HS regions (e.g., contralateral inguinal 
region, buttocks, inframammary region; hereinafter designated the 'HS 
non-surgical sites) rated as Hurley Stage II or III;
4.
Subject must have a total abscess and inflammatory nodule (AN) count of greater 
than or equal to 3 at the Baseline visit within the HS non-surgical sites;
5.
The HS surgical site must contain at least one active HS lesion;
6.
The HS surgical site must require excisional surgery and is large enough to require 
healing by secondary intention as assessed by the designated surgeon;
7.
If female subject, is either
E
not of childbearing potential, defined as  
Y
postmenopausal for at least 1 year (365 days) or 
Y
surgically sterile (bilateral tubal ligation/occlusion, bilateral oophorectomy, 
and/or hysterectomy); or


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E
of childbearing potential and is practicing at least one protocol-allowed 
method of birth control throughout the study and for 150 days after last dose of 
study drug.
Examples of allowed methods of birth control (see Section 5.2.4) include the 
following (see local informed consent for more detail):
Y
Intrauterine device (IUD) or Intrauterine hormone-releasing system (IUS); 
or
Y
Hormonal contraceptives initiated at least 30 days prior to study drug 
administration;
Y
A vasectomised partner; and/or
Y
True abstinence
8.
Females of childbearing potential must have a negative serum pregnancy test 
(conducted at central lab) result at Screening, and a negative urine pregnancy test 
(conducted at site) at Day 1;
E
Females of non-childbearing potential (either postmenopausal or permanently 
surgically sterile as defined above) at Screening do not require pregnancy 
testing
9.
Subject must agree to daily use of one of the following over-the-counter topical 
antiseptics on their HS lesions (excepting the post-surgical wound):  chlorhexidine 
gluconate, triclosan, benzoyl peroxide, or dilute bleach with shower or bath 
throughout the entirety of the study; 
10.
Subject has a negative TB screening assessment (see test to be performed in 
paragraph below) and negative CXR (posterior-anterior [PA] and lateral view) at 
Screening.  If the subject has evidence of a latent TB infection; the subject must 
initiate and complete a minimum of 12 weeks (or per local guidelines, whichever is 
longer) of an ongoing TB prophylaxis and have documented completion of a 
minimum of 4 weeks of TB prophylaxis prior to the Baseline visit (see 
Section 5.3.1) and should be evaluated by a physician experienced in the evaluation 
and treatment of TB patients before entering the trial;


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E
In patients treated with corticosteroids (equivalent to Prednisone 5 mg or 
above – with ongoing treatment or treatment within 1 month prior to TB 
screening), TB screening must be performed using a QuantiFERON-TB Gold 
In-tube test or equivalent.
E
In patients NOT treated with corticosteroids (equivalent to Prednisone 5 mg or 
above – with ongoing treatment or treatment within 1 month prior to TB 
screening), PPD or QuantiFERON-TB tests may be used.
11.
Subject is judged to be in good general health, as determined by the Study 
Investigator based upon the results of a medical history, physical examination, 
laboratory profile, CXR and a 12-lead ECG performed during the Screening period 
and confirmed at the Baseline visit;
12.
Subject must be able and willing to self-administer subcutaneous (SC) injections or 
have a qualified person available to administer SC injections; and
13.
Subject must be able and willing to provide written informed consent and comply 
with the requirements of this study protocol. 
Rationale for the Inclusion Criteria
1 – 6
To select the appropriate subject population with adequate disease 
severity for the evaluation
7 – 8
The impact of adalimumab on fetal development has not been formally 
established
9 – 12
For the safety of the study subject
13
In accordance with harmonised Good Clinical Practice (GCP)
5.2.2
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following 
criteria:
1.
Subject has a draining fistula count of greater than 20 at the Baseline visit;


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2.
Subject requires surgery at any anatomical site other than an unilateral axilla or 
inguinal region site;
3.
Subject requires surgical management prior to Week 13, based on the designated 
surgeon's assessment;
4.
Subject requires, based on the designated surgeon's assessment, excisional surgery 
with primary closure, partial surgical reduction of the excised area with surgical 
suture, or reconstruction techniques as the method of closure being most beneficial 
for the subject;
5.
Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) 
that may interfere with assessment of HS;
6.
Subject is taking high-dose systemic corticosteroids at the Baseline visit (see 
Section 5.2.3.3), or has taken high-dose systemic corticosteroids within five half-
lives of that specific corticosteroid (see Section 5.2.3.3) prior to the Baseline visit;
7.
Subject received biologic therapies with potential therapeutic impact for HS (see 
Section 5.2.3.3) less than 6 months (178 days) prior to the Baseline visit;
8.
Subject received prescription topical therapies (excluding over-the-counter topical 
antiseptics) for the treatment of HS within 14 days prior to the Baseline visit;
9.
Subject received systemic clindamycin or rifampin within 28 days prior to the 
Baseline visit;
10.
Infection(s) requiring treatment with intravenous (IV) anti-infectives 
(e.g., antibiotics, antivirals, antifungals) within 30 days prior to the Baseline, 
except as required as part of an anti-TB regimen;
11.
Prior exposure to biologics that have a potential or known association with 
Progressive Multifocal Leukoencephalopathy (PML; i.e., natalizumab or 
rituximab);


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12.
Subject has been treated with any investigational drug of chemical nature within a 
minimum of 30 days or five half-lives (whichever is longer) of the drug prior to the 
Baseline visit;
13.
Known hypersensitivity to adalimumab or its excipients as stated in Section 5.5.2, 
Table 2;
14.
History of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease;
15.
Subject has suspicion of sepsis, cytomegalovirus infection, listeriosis or other 
opportunistic infections, or has history of invasive infection 
(e.g., listeriosis,histoplasmosis) or human immunodeficiency virus (HIV);
16.
Subject has an active systemic viral infection or any active viral infection that 
based on the Study Investigator's clinical assessment make the subject an 
unsuitable candidate for the study;
17.
Hepatitis B:  HBsAg positive (+) or detected sensitivity on the HBV-DNA PCR 
qualitative test for HBc Ab/HBsAb positive subjects (see Section 5.3.1.1);
18.
Chronic recurring infections or active TB;
19.
History of moderate to severe congestive heart failure (New York Heart 
Association [NYHA] class III or IV), recent cerebrovascular accident, interstitial 
lung disease (ILD) and any other condition that would put the subject at risk by 
participation in the study;
20.
Evidence of dysplasia or history of malignancy (including lymphoma and 
leukemia) other than a successfully treated non-metastatic cutaneous squamous cell 
or basal cell carcinoma, or localized carcinoma in situ of the cervix;
21.
Female subject who is breastfeeding or is considering becoming pregnant during 
the study and during the 5 months following the last dose of adalimumab;
22.
History of clinically significant drug or alcohol abuse in the previous 12 months;


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23.
Clinically significant abnormal screening laboratory results as evaluated by the 
Investigator;
24.
Subject is considered by the Study Investigator, for any reason, to be an unsuitable 
candidate for the study.
Rationale for Exclusion Criteria
1 – 4
To select the appropriate subject population with adequate 
disease severity for the evaluation
5
To avoid enrollment of subjects who have concomitant skin 
disease that may interfere with HS assessment
6 – 10
To avoid bias for the evaluation of safety and efficacy by 
concomitant use of other medications
11 – 13, 19, 22 – 24
To ensure safety of the subject throughout the study
15 – 18, 20
To avoid a possibility of an infectious disease or a malignant 
tumor progression when administering an anti-TNF drug
14
Demyelinating disorders have been seen in subjects treated with 
TNF antagonists although a causal relationship has not been 
conclusively established
21
The impact of adalimumab on fetal development has not been 
formally established
5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject is receiving at the time of enrollment 
(i.e., date of signing the informed consent), and/or receives during the study, must be 
recorded along with the reason for use, date(s) of administration including start and end 
dates, and dosage information including dose, route and frequency on the appropriate 
electronic case report form (eCRF).


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All analgesics will be allowed as concomitant medications throughout the active phase of 
the trial.  Oral antibiotics (with the restriction of clindamycin and rifampin as described in 
Section 5.2.3.2) will be allowed as concomitant medications throughout the active phase 
of the trial provided the dosing regimen (dose and frequency) has been stable for at least 
4 consecutive weeks (28 days) prior to the Baseline visit.  The AbbVie Study Designated 
Physician identified in Section 1.0 should be contacted if there are any questions 
regarding concomitant or prior therapies.
In addition for subjects age ] 30 with a reported malignancy adverse event, prior to 
exposure to, or current of, anti-neoplastics, or other drugs that have a risk of malignancy 
as stated in their label and other relevant dosing information to estimate total exposure 
will be collected in the source documents and appropriate eCRF pages (also see 
Section 6.1.5).  At the time of the reported malignancy adverse event, the Study 
Investigator will be asked if any of the prior and concomitant medications contributed to 
the event.  Any medications used prior to the study will be captured on the appropriate 
eCRF.  Information on the reason for use, date(s) of administration including start and end 
dates, highest maintained dose, dosage information including dose, route, and frequency, 
and reason for stopping the medication will be collected in the source documents and 
appropriate eCRF pages.
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject is receiving at the time of enrollment, 
or receives during the study, must be recorded along with the reason for use, date(s) of 
administration including start and end dates, and dosage information including dose, route 
and frequency.
The AbbVie Study Designated Physician should be contacted if there are any questions 
regarding concomitant or prior therapies.


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5.2.3.1
Prior Therapy
Any treatments for HS (as determined through medical history records or through subject 
interview) prior to study enrollment will be recorded in the source and on the eCRF, along 
with the reason for discontinuation.
For subjects previously treated with biologics (e.g., infliximab, rituximab, ustekinumab, 
anakrina) the duration of therapy, maximum dose, reason for use and the reason(s) for 
termination of treatment with these products should be documented.
A detailed history of prior antibiotic use for HS (topical, oral, IV), response, and reason 
for discontinuation will be collected.
5.2.3.2
Concomitant Therapy
Antiseptic Therapy
Subjects are required to use a daily antiseptic wash on their active HS lesions beginning at 
enrollment and continuing throughout the study, except on the surgical wound (unless 
directed by the Study Investigator or designee).  Allowable antiseptic washes are limited 
to one of the following:  chlorhexidine gluconate, triclosan, benzoyl peroxide, or dilute 
bleach in bathwater.
Wound Care
Concomitant use of wound care dressings on HS wounds and the surgical wound (as per 
local practice) is allowed, and may include alginates, hydrocolloids, and hydrogels.
Antibiotic Therapy
All oral antibiotics are permitted throughout the study with the restrictions described in 
the following paragraphs.
Concomitant use of permitted oral antibiotic therapy for treatment of HS is allowed 
provided the dosing regimen (dose and frequency) has been stable for at least 


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4 consecutive weeks (28 days) prior to the Baseline visit (see Exclusion Criterion 10).  
Antibiotics taken on an "as needed" (PRN) basis are not considered a stable dose.
During the peri-operative period (Period B) an antibiotic regimen including systemic 
clindamycin and/or rifampin is allowed for a maximum of 5 days (see also 
Section 5.2.3.3).
See Section 6.1.7 for additional discussion on the use of concomitant medications if 
medically necessitated.
Lesion Intervention
In the event an acutely painful lesion occurs that requires an immediate intervention, the 
Study Investigator will have the option to perform protocol-allowed interventions.
Only two types of interventions are allowed:  injection with intra-lesional triamcinolone 
acetonide suspension (at a concentration of up to 5 mg/mL, up to 1 cc), and incision and 
drainage.
If incision and drainage is performed, the required over-the-counter antiseptic wash 
should continue to be used.  Concomitant use of wound care dressings is allowed, which 
may include alginates, hydrocolloids, and hydrogels.  The subject should continue using 
any ongoing oral and topical therapies during the study.  See Section 6.1.7 for additional 
discussion on the use of concomitant medications if medically necessitated.
Concomitant medications associated with the lesion intervention(s) must be recorded in 
the source and the appropriate eCRF.
A total of two protocol-allowed interventions are permissible during Period A.  An 
intervention can occur on maximally two different lesions at the same visit or on the same 
lesion at two different study visits.  The same lesion cannot be treated two times at the 
same visit.  If a subject requires more than two interventions within the first 12 weeks, 
then the subject must be discontinued from the study.


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During Period B (including during the excisional surgery) protocol-allowed interventions 
(i.e., intra-lesional injection, incision and drainage) are not permitted.
During Period C, maximally two interventions every 4 weeks are permitted.  An 
intervention can occur on two different lesions at the same visit or on the same lesion at 
two different study visits.  Within each 4-week period, the same type of intervention 
cannot be used two times on the same lesion.  If a subject requires more than 
two interventions within a 4-week period or has two of the same interventions on the same 
lesion within that same 4-weeek period, then a protocol deviation must be recorded in the 
source and on the appropriate eCRF.
All study visit evaluations must occur before any interventions are performed.  Any lesion 
that undergoes an intervention will be documented in the source.  The Study Investigator 
will be required to count any lesion that undergoes an intervention as permanently present 
from the date of the intervention, and must record this in the source and on the appropriate 
eCRF.
Study Drug
Study drug administration will be documented in a separate section of the eCRF.  All 
study visit evaluations must occur before the study drug is administered.
5.2.3.3
Prohibited Therapy
The following are prohibited medications during the study:
E
All biologic therapy with a potential therapeutic impact on HS, including but 
not limited to the following (generic name with brand name, or its biosimilar 
product):
Y
Abatacept (Orencia®);
Y
Anakinra (Kineret®);
Y
Belimumab (Benlysta®).
Y
Certolizumab (Cimzia®);


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Y
Etanercept (Enbrel®);
Y
Infliximab (Remicade®);
Y
Natalizumab (Tysabri®);
Y
Rituximab (Rituxan®);
Y
Tocilizumab (Actemra®);
Y
Ustekinumab (Stelara®).
E
Any investigational agent
E
Any other systemic drug therapies for HS, including but not limited to 
antibiotics (except as specified in Section 5.2.3.2), systemic cyclosporine, 
methotrexate, retinoids, and fumaric acid
E
Prescription topical therapies for HS, including prescription topical antibiotics
E
Surgical or laser intervention for an HS lesion except as outlined in 
Section 5.2.3.2
E
Live vaccine (during the study and for 70 days after the last dose of study 
drug)
E
High-dose oral or injectable corticosteroids 
High-dose systemic corticosteroids and five half-lives are defined as 
follows:
Steroid
High Dose (/Day)
t1/2
5 Half-Lives
Hydrocortisone
20 mg
12 hrs
3 days
Dexamethasone
1 mg
54 hrs
12 days
Methylprednisolone
7.5 mg
36 hrs
8 days
Prednisone
7.5 mg
36 hrs
8 days
Cortisone
25 mg
12 hrs
3 days
5.2.3.4
Rescue Therapy
If the Study Investigator, with agreement of the designated surgeon, determines the 
subject must undergo excision of the HS surgical site prior to the Week 13 study visit 
window (i.e., more than 7 days prior to the scheduled Week 13 study visit) all study 


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procedures scheduled for Week 12 must be performed and recorded, and the subject must 
be discontinued from the study.
5.2.4
Contraception Recommendations and Pregnancy Testing
If female, the subject must be either postmenopausal, defined as:
E
with no menses for 12 or more months without an alternative medical cause; or
E
permanently surgically sterile (bilateral oophorectomy, bilateral tubal 
occlusion, bilateral salpingectomy and/or hysterectomy).
OR
The female subject is of childbearing potential, is participating in heterosexual vaginal 
intercourse, and is practicing at least one of the following methods of birth control, on 
Day 1 (or earlier) through at least 150 days (or as dictated by local requirements) after the 
last dose of study drug:
E
Combined (estrogen and progestogen-containing) hormonal contraception 
(oral, intravaginal, transdermal) associated with the inhibition of ovulation, 
initiated at least 1 month prior to Day 1;
E
Progestogen-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation, excluding low-dose oral gestagens 
(mini-pills containing either lynestrenol or norestisteron) initiated at least 
1 month prior to Day 1;
E
Low-dose oral gestagens (mini-pills containing either lynestrenol or 
norestisteron) are not associated with inhibition of ovulation, and are not 
considered as effective contraception.
E
Vasectomised partner(s), provided the vasectomised partner has received 
medical assessment of the surgical success;
E
Intrauterine device (IUD); and/or
E
Intrauterine hormone-releasing system (IUS).


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If required per local practices, male or female condom with or without spermicide; or cap, 
diaphragm, or sponge with spermicide should be used in addition to one of the birth 
control methods listed above.  Barrier methods with or without foams and jellies (such as 
condom, sponge, and diaphragm, alone or in combination, are not protocol-specified birth 
control methods.
OR
The female is of childbearing potential and practicing true abstinence from heterosexual 
vaginal intercourse.  (Note:  Periodic abstinence [e.g., calendar, ovulation, symptothermal, 
post-ovulation methods] and withdrawal are not acceptable as abstinence.)
5.3
Efficacy, Safety, and Exploratory Research/Validation 
Studies Assessments/Variables
5.3.1
Efficacy, Safety, and Exploratory Research/Validation 
Studies Measurements Assessed and Flow Chart
Study procedures described are listed in the following section of this protocol and are 
summarized in tabular format in Appendix C.
Study procedures for the optional exploratory research/validation studies are listed in the 
following section of this protocol and are summarized in tabular format in Appendix D.
5.3.1.1
Study Procedures
The study procedures outlined in Appendix C are discussed in detail in this section, with 
the exception of drug concentration measurements (Section 5.3.2) and the collection of 
AE information (Section 6.0).
Informed Consent
An Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approved, 
study-specific ICF will be reviewed, signed and dated by the subject before any study 
procedures are undertaken, or before any medications are withheld from the subject in 


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order to participate in this study.  Because subjects are required to be candidates for 
excisional surgery in order to be eligible for the study (Inclusion Criterion 3), surgical 
consent is considered a separate, non-study procedure and will be conducted outside of 
the parameters of the study protocol, per standard of care, with the exception that consent 
for surgery must be obtained prior to any surgical intervention is undertaken.  Details 
about how informed consent will be obtained and documented are provided in Section 9.3.
Inclusion/Exclusion Criteria
Subjects will be evaluated to ensure they meet all inclusion criteria and none of the 
exclusion criteria at the Screening and Baseline visits.
Prior and Concomitant Therapy Assessment
See Section 5.2.3.
Medical and Surgical History
A complete medical history (which includes HS-related and non-HS-related medical and 
surgical history), including history of tobacco and alcohol use, will be obtained from each 
subject during the Screening visit with the Primary Investigator and designated surgeon.  
The medical history should also include a detailed history of prior therapies used to treat 
HS, including antibiotics.  Medical history will be reviewed and updated at the Baseline 
visit to ensure the subject remains qualified for the study.
A detailed medical history with respect to TB exposure needs to be documented.  This 
information needs to include Bacille Calmette-Guérin (BCG) vaccination, cohabitation 
with individuals who have had TB, and/or who reside or work in TB endemic locations.
If deemed eligible for the study by the Study Investigator, study site personnel will 
schedule a screening visit with the designated surgeon.  The surgeon will verify and 
complete, if necessary, the surgical history.  In addition, the surgeon will complete the 
surgical Screening assessment by evaluating the planned HS surgical site with regards to 
the surgical Inclusion and Exclusion Criteria.  The surgeon will develop a planned 


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surgical intervention (hereinafter termed 'surgical plan').  The evaluation and surgical plan 
will be recorded on the appropriate eCRF pages.  
Physical Examination
A full physical exam will be performed at the designated study visits listed in
Appendix C.  Physical examination findings that are related or part of each subject's 
medical history should be captured in the source and on the appropriate eCRF page.  The 
designated surgeon will verify and complete, if necessary, any findings regarding
examination of the HS surgical site at the Screening visit with the surgeon.  The surgeon 
will enter the findings in the source and on the appropriate eCRF page.
A symptom-directed physical examination should be performed at all other study visits, if 
warranted.  Abnormalities noted after the Baseline visit will be evaluated and documented 
by the Study Investigator as to whether they are AEs.
Findings from any pre-operative physical exam that is required per standard of care by the 
subject's personal physician/surgeon, Study Investigator, or designated surgeon, other than 
AEs/SAEs, will be maintained per local institution policy and will not be recorded on the 
eCRF.  Only those physical findings from the pre-operative physical exam that pertain to 
a new or ongoing AE/SAE will be recorded on the AE/SAE eCRF (see Section 6.1).
Vital Signs
Vital sign determinations of systolic and diastolic blood pressure, pulse rate (counted for 
at least 30 seconds after 5 minutes in sitting position), respiratory rate, body weight, and 
body temperature (oral) will be obtained at each study visit.  Blood pressure and pulse rate 
measurements should be performed prior to the collection of any laboratory specimens.
Height and Waist Circumference Measurements
Height will be measured at Baseline and waist circumference will be measured at Baseline 
and Week 12 (see Appendix C).  


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To measure waist circumference, locate the top of the right iliac crest.  Place a measuring 
tape in a horizontal plane around the abdomen at the level of the iliac crest.  Before 
reading the tape measure, ensure that the tape is snug but does not compress the skin and 
is parallel to the floor.  Measurement should be made at the end of a normal expiration.
Electrocardiogram 
A resting 12-lead ECG will be performed at the designated study visits listed in 
Appendix C.  A qualified physician will interpret, sign, and date each ECG.  Any 
clinically significant findings will be documented in the source documents and later 
transcribed on to the appropriate eCRF by the Primary Investigator.  Each signed original 
ECG will be monitored by the AbbVie Clinical Research Associate (CRA) and kept with 
subject's source documents onsite.
For subjects with a normal ECG taken within 90 days of Screening, a repeat ECG at 
Screening will not be required, provided all protocol required documentation is available.  
If there are other findings that are clinically significant, the Study Investigator must 
contact the Study Designated Physician before enrolling the subject.
Any pre-operative ECG that is required, per standard of care, will be conducted and 
results maintained per local institution policy and not recorded on the eCRF.  Only those 
findings from the pre-operative ECG that pertain to a new or on-going AE/SAE will be 
recorded on the AE/SAE eCRF.
Subjects can have a repeat ECG at any time during the study as warranted based on the 
opinion of the Study Investigator.
Chest X-Ray
All subjects will undergo a standard CXR (PA and lateral views) during the Screening
period to rule out the presence of TB or other clinically relevant findings.  The CXR will 
not be required if the subject had a previous normal CXR within 90 days of Screening, 


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provided all protocol required documentation is available at the study site (as outlined 
below).
Any pre-operative CXR that is required, per standard of care, will be maintained per local 
institution policy and will not be recorded on the eCRF.  Only those findings from the 
pre-operative CXR that pertain to a new or on-going AE/SAE will be recorded on the 
AE/SAE eCRF.
Subjects can have a repeat CXR at any time during the study as warranted based on the 
opinion of the Study Investigator.
In the assessment of the CXR, a radiologist must specifically note the presence or absence 
of 1) calcified granulomas, 2) pleural scarring/thickening, and 3) signs of active TB.  The 
Study Investigator will indicate the clinical significance of any findings and will sign and 
date the CXR report.  If the CXR demonstrates changes suggestive of previous TB 
(e.g., calcified nodule, fibrotic scar, apical or basilar pleural thickening) or other findings 
that are clinically significant, the Study Investigator must contact the AbbVie Study 
Designated Physician before enrolling the subject.
TB Screening
In patients treated with corticosteroids (equivalent to Prednisone 5 mg or above – with 
ongoing treatment or treatment within 1 month prior to TB screening), an Interferon-
Gamma Release Assay (IGRA; QuantiFERON-TB Gold In-Tube test or T-SPOT TB test) 
may be performed locally or by the central lab during the Screening Period for all 
subjects, including those with a prior history of Bacille Calmette-Guérin (BCG) 
administration.
In patients NOT treated with corticosteroids (equivalent to Prednisone 5 mg or above –
with ongoing treatment or treatment within one month prior to TB screening), a PPD skin 
test (alternatively, also known as tuberculin skin test) must be placed, or an Interferon-
Gamma Release Assay (IGRA; QuantiFERON-TB Gold In-Tube test or T-SPOT TB test) 


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may be performed locally or the central lab during the Screening Period for all subjects, 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration.
If a subject had a negative PPD or IGRA test within 90 days prior to Screening, and all 
protocol required documentation is available, the test does not need to be repeated, 
provided nothing has changed in the subject's medical history to warrant a repeat test, and 
that in patients treated with corticosteroids (equivalent to Prednisone 5 mg or above –
with ongoing treatment or treatment within 1 month prior to TB screening) the performed 
screening was an Interferon-Gamma Release Assay.  These cases must be discussed with 
the AbbVie Study Designated Physician.
For the PPD test:
The subject will be required to have the PPD skin test read by a licensed healthcare 
professional 48 to 72 hours after placement (or as per local guidelines), when the 
induration is maximal.  An induration (not erythema) of 5 mm or greater will be 
considered as PPD positive, regardless of BCG status or local guidelines.  The 
induration must be recorded in "mm," not as "positive" or "negative."  The absence of 
induration should be recorded, as "0 mm," not "negative."  (If required by specific 
countries a two-step test may be performed per local guidelines.  The result of the 
second test should be recorded.)
A subject, who has had an ulcerating reaction to a PPD skin test in the past, as 
documented in the medical history source and eCRF, should not be re-exposed and 
should not be tested at Screening but will be considered PPD positive.
If there are study sites where the available testing materials are not accepted, the 
method must be submitted and approved by the AbbVie Study Designated Physician 
prior to use with study subjects.
If the PPD or the IGRA test is positive, the subject has a prior history of active or latent 
TB, or the results of a CXR are indicative of latent TB (see Section 5.3.1.1), the subject 
will be required to initiate and have taken at least 4 weeks (or per local guideline, 


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whichever is longer) of an ongoing course of Centers for Disease Control and Prevention 
(CDC)-recommended prophylaxis or prophylaxis per local guidelines prior to starting 
study drug therapy and should be evaluated by a physician experienced in the evaluation 
and treatment of TB patients before entering the trial.  Subjects who have a documented 
completion of the CDC-recommended prophylaxis may be permitted to enroll.  The 
Principle Investigator should contact the AbbVie Study Designated Physician to discuss 
enrollment of this potential subject.
In the event both a PPD test and an IGRA test are performed, the result of the IGRA test 
will supersede the result of the PPD test.  If the IGRA test is performed and the result is 
indeterminate, the test should be repeated with a fresh blood sample or perform a PPD 
test.  If the repeat IGRA test is also indeterminate, this should be considered a positive test 
result and TB prophylaxis should be initiated.
Newly initiated prophylactic treatment should be recorded on the concomitant 
medications page in the eCRF and in the source documents.  Prior therapy should be 
recorded on the medical history page in the eCRF.
Clinical Laboratory Tests
Samples will be obtained for the laboratory tests listed in Table 1 at the designated study 
visits listed in Appendix C.  For the samples collected at Baseline, Week 12, and 
Week 24/Premature Discontinuation visits subjects should be fasting before the sample is 
collected.  Please refer to the laboratory manual for further instructions.  Blood draws 
should be performed after questionnaires and vital sign determinations have been 
completed, but prior to any study drug administration.  A certified central laboratory will 
be utilized to process and provide results for the general laboratory tests.  Instructions for 
urine pregnancy testing can be found in the laboratory manual.  All abnormal laboratory 
test results that are considered clinically significant by the Study Investigator will be 
followed to a satisfactory resolution.


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Any pre-operative laboratory testing that is required, per standard of care, will be read by 
the local lab and maintained per local institution policy and will not be recorded on the 
eCRF.  Only those findings from the pre-operative laboratory testing that pertain to a new 
or ongoing AE/SAE will be recorded on the AE/SAE eCRF.
Instructions regarding the collection, processing and shipping of these samples will be 
provided by the central laboratory.
Pregnancy Testing
A serum pregnancy test (conducted by the central lab) will be performed at the Screening 
visit for all female subjects of childbearing potential.  At the Baseline and Week 24 or 
Premature Discontinuation visits, female subjects of childbearing potential will have a 
urine pregnancy test (conducted at the site).  (If required by local regulatory authorities 
urine pregnancy tests will be performed monthly throughout the study.)  If any urine 
pregnancy test is positive, a serum pregnancy test will be analysed by the central 
laboratory.  If a serum pregnancy test is positive, the female subject is not eligible for 
participation or continuation in the study.  If the subject is discontinued from the study, 
every effort will be made to schedule the subject for a Premature Discontinuation Visit.
All female subjects of childbearing potential will have a repeat urine pregnancy test at the 
final Study Visit performed at the site by designated study personnel.
Females of non-childbearing potential, whether by being postmenopausal or permanently 
surgically sterile as defined above (Section 5.3.1.1), do not require pregnancy testing at 
Screening.
Urinalysis
Urine samples will be obtained for urinalysis and nicotine metabolite screening as listed in 
Appendix C.  For urine samples with abnormal macroscopic results, a microscopic test 
will be performed.


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Table 1.
Clinical Laboratory Tests
Hematology
Clinical Chemistry**
Urinalysis
Hematocrit
Hemoglobin
Red Blood Cell (RBC) count
White Blood Cell (WBC) count
Neutrophils
Bands
Lymphocytes
Monocytes
Basophils
Eosinophils
Platelet count (estimate not 
acceptable)
Blood Urea Nitrogen (BUN)
Creatinine
Total bilirubin
Serum glutamic-pyruvic 
transaminase (SGPT/ALT)
Serum glutamic-oxaloacetic 
transaminase (SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Total protein
Glucose
Albumin
Cholesterol*
Triglycerides*
LDL*
HDL*
Specific gravity
Ketones
pH
Protein
Glucose
Blood
Urobilinogen
Bilirubin
Microscopic examination, if 
needed 
Leukocytes
Nitrite
Other
Pregnancy Test
hsCRP
Hepatitis B Screening
HbA1c
Antinuclear Antibody (ANA)/Anti-dsDNA
Optional:  Exploratory Research/Validation Studies (if informed 
consent has been obtained)
HIV (testing to be conducted at local lab)
Serum HCG
Urine HCG
*
To be performed only at study visits designated for Lipid Testing.
**
Chemistry should be fasting at Baseline and Weeks 12 and 24.
Hepatitis B Screening
All subjects will be tested for the presence of the hepatitis B virus (HBV) at Screening.  A 
positive result for the hepatitis B surface antigen (HBs Ag) will be exclusionary.  Samples 
negative for HBs Ag will be tested for surface antibodies (HBs Ab) and core antibodies 
(HBc Ab Total).  Any subject with HBs Ag (–), HBs Ab (–), and HBc Ab Total (+) 


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requires PCR qualitative testing for HBV DNA.  Any HBV DNA PCR result that meets or 
exceeds detection sensitivity will be exclusionary.
Subjects with a negative HBs Ag test and tests showing the results below do not require 
HBV DNA PCR qualitative testing:
E
HBs Ab (–) and HBc Ab Total (–)
E
HBs Ab (+) and HBc Ab Total (–)
E
HBs Ab (+) and HBc Ab Total (+)
Human Immunodeficiency Virus Testing
If required by country regulatory authorities to confirm eligibility, subjects will be tested 
for antibodies to the HIV at Screening, and document that the test has been performed.  
The testing is to be done at a local lab.  A subject will not be eligible for study 
participation if test results indicate a positive HIV infection.  AbbVie will not receive 
results from the testing, and will not be made aware of any positive result.
High Sensitivity C-Reactive Protein Testing
Testing for high sensitivity C-reactive protein (hsCRP) will be performed on specimens 
collected at the designated study visits listed in Appendix C. 
Hemoglobin A1c Testing
All subjects will be tested for hemoglobin A1c (HbA1c) at the designated study visits 
listed in Appendix C.
Antinuclear Antibody/Anti-dsDNA Testing
Study personnel will collect a sample for antinuclear (ANA) and reflex double stranded 
DNA (dsDNA) antibody testing at the Screening visit.  A repeat ANA/Anti-dsDNA 
would be warranted if a subject has clinical signs and symptoms suggestive of lupus.  The 
Anti-dsDNA antibody testing will be performed in case of positive ANA result.  All 
samples will be sent to the central laboratory for processing.


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Exploratory Research and Validation Studies Samples
Subjects will have the option to provide samples for exploratory research and validation 
studies.  Subjects may still participate in the main study even if they decide not to 
participate in the optional exploratory research/validation studies.
Validation studies, including those related to the development of potential in vitro 
diagnostic tests, may be carried out retrospectively in order to assess associations between 
events of interest (i.e., efficacy and/or safety events) and candidate biomarkers.
AbbVie (or people or companies working with AbbVie) will store the exploratory 
research/validation studies samples in a secure storage space with adequate measures to 
protect confidentiality.  The samples will be retained while research on adalimumab (or 
drugs of this class) or this disease and related conditions continues, but for no longer than 
20 years after study completion. 
The following samples will be collected according to Appendix D from each subject who 
consents to provide samples for exploratory research/validation studies.  The procedures 
for obtaining and documenting informed consent are discussed in Section 9.3.
E
DNA samples for pharmacogenetic or epigenetic analyses
E
RNA samples for transcriptomic and/or epigenetic analyses
E
Serum and plasma samples for systemic analyses including, but not limited to, 
proteomic and metabolomics
E
Blood samples for peripheral blood mononuclear cell (PBMC) investigations 
including, but not limited to, immunophenotyping and protein expression 
profiles
E
A swab from HS lesional (or healed skin following therapy) and non-lesional 
skin for microbiome analysis
Samples will be shipped to AbbVie or a designated laboratory for DNA/RNA extraction, 
if applicable, and/or analyses or long-term storage.  Instructions for the preparation and 
shipment of the samples will be provided in the laboratory manual.


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For each subject who consents to provide skin tissue samples, two skin biopsies may be 
collected at the Baseline visit.  For those subjects not undergoing surgery, two additional 
skin biopsies may be collected at both the Week 12 and Week 24/Premature 
Discontinuation visit.  For those subjects who undergo surgery, remnant tissue will be 
collected from the excised surgical specimen at Week 13.  Six biopsies from HS lesional 
tissue and six biopsies from non-lesional tissue will be collected and preserved.  Also for 
those subjects who undergo surgery, an additional skin biopsy may be collected at 
Week 24/Premature Discontinuation visit.  Importantly, a subject may still participate in 
the optional exploratory research/validation studies if the subject decides not to participate 
in the optional biopsy collections.  The procedures for obtaining and documenting 
informed consent are discussed in Section 9.3.
Samples will be shipped to AbbVie or a designated laboratory for analyses and/or 
long-term storage of the skin biopsies.  Instructions for the preparation and shipment of 
the samples will be provided in the laboratory manual.
Dermatology Life Quality Index
Subjects will complete a Dermatology Life Quality Index (DLQI) questionnaire 
(Appendix F) at the designated study visits listed in Appendix C.  The DLQI will be used 
to assess the symptoms and the impact of skin problems on quality of life.  The DLQI can 
be used to evaluate six areas:  symptoms and feelings, daily activities, leisure, work and 
school, personal relationships, and treatment.  Subjects will be asked to respond to the 
10 items of the DLQI based on a recall period of 'last week.'  Decreased scores indicate 
improved health-related quality of life.
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.


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EuroQoL
Subjects will complete the EuroQoL™ (EQ-5D™) questionnaire (Appendix EG) at the 
designated study visits listed in Appendix C.  The EQ-5D™ is a simple generic measure 
that asks respondents about their current health state "today."  The EQ-5D™ contains 
five dimensions including "mobility," "self-care," "usual activities," "pain/discomfort," 
and "anxiety/depression."
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.
Hidradenitis Suppurativa Impact Assessment
The Hidradenitis Suppurativa Impact Assessment (HSIA) is an 18-item PRO 
questionnaire (Appendix H) developed to assess the impact of HS on the daily lives of 
subjects in the 7 days prior to the assessment.  Items 1 – 16 of the HSIA are scored on a 
0 to 10 numeric rating score where 0 represents no impact and 10 represents extreme 
impact.  In this way, item scores can be generated to characterize the patient's experience 
at an individual impact level.  Additionally, Items 1 – 16 characterize the overall impact 
of HS and can be scored together to create a weekly Overall HSIA score.  The Overall 
HSIA score is generated by summing the completed individual impact, item-level scores 
collected on the same day, and dividing that sum by the total number of completed 
responses (i.e., the Overall HSIA score is an average).  The Overall HSIA score will only 
be derived if eight or more (i.e., at least 50%) of responses are available (and adjusting the 
denominator to match the number of completed items).  Items 17 and 18 utilize an open 
field where patients are asked to fill in a number, and are not included in the Overall 
HSIA score.  Instead, a separate mean score for the hours worked (Item 17) or hours 
missed at school or work (Item 18) will be calculated.  If the response is "Non 
Applicable" for any of the Items 13 – 14 or 16 – 18 then the subject will be deemed as 
"not applicable" for calculating scores.


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The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.  
Hidradenitis Suppurativa Patient's Global Assessment of Skin Pain 
The Hidradenitis Suppurativa Patient's Global Assessment of Skin Pain (HS-PGA-SP) is a 
two-item PRO questionnaire (Appendix I) designed to assess daily skin pain due to HS at 
its worst and on the average.  The HS-PGA-SP – at worst is a numeric rating scale (NRS).  
The NRS is an 11-point scale consisting of a 0 – 10 range from which the subject selects 
the number most representative of his or her experience.  Subjects are asked to respond to 
the items based on a recall period of "the last 24 hours."  The scoring for the HS-PGA-SP 
is based on an 11-point NRS consisting of a 0 – 10 range.  Each item is scored 
independently from the other.
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.  
Hidradenitis Suppurativa Patient's Global Impression of Change 
Subjects will complete the Hidradenitis Suppurativa Patient's Global Impression of 
Change (HS PGIC) questionnaire (Appendix J) at the designated study visits listed in 
Appendix C.  The HS PGIC consists of one self-administered item that assesses change in 
the severity of skin pain due to HS.  Subjects are asked to indicate their impression of 
change compared with their last visit.
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.


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Hidradenitis Suppurativa Symptom Assessment
The Hidradenitis Suppurativa Symptom Assessment – 7 day recall (HSSA-7d) is a 
nine-item PRO questionnaire (Appendix K) developed to assess the primary symptoms of 
HS in the 7 days prior to assessment.  Each item of the HSSA is scored on a 0 to 10 NRS 
where 0 represents no symptoms and 10 represents extreme symptom experience.  In this 
way, item scores can be generated to characterize the patient's experience at a symptom 
level.  Additionally, Items 1 – 9 can be scored together to create a Total Symptom Score 
to characterize an overall symptom experience by averaging the scores collected from the 
non-missing items collected at the same assessment. 
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.  HSSA scores range from 0 – 90 with higher scores 
indicating worse symptoms.
Short Form 12
The acute Short Form-12v2™ Health Survey (SF-12) is a 7-day recall, 12-item subset of 
the Short Form-36v2™ questionnaire (Appendix L) that measures the same eight domains 
of health including physical functioning, role-function, bodily pain, general health, 
vitality, social functioning, role-emotional, and mental health.  SF-12 is a brief, reliable 
measure of overall health status with scores general for physical component and mental 
components.  Each item of the SF-12 is scored on 3- or 5-item Likert scales and the 
domains scales are standardized to a 0 to 100 scale where 0 represents lower quality of 
life and 100 represents higher quality of life.  
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.  SF-12 scores range from 0 – 100 with higher scores 
indicating better quality of life.


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Treatment Satisfaction Questionnaire – Medication
Subjects will complete the Treatment Satisfaction Questionnaire – Medication (TSQM) 
questionnaire (Appendix M) at the designated study visits listed in Appendix C.  The 
TSQM is a 14-item instrument and includes assessments of satisfaction with a 
medication's effectiveness (three items), lack of side effects (five items), convenience 
(three items) and the subject's global satisfaction (three items).
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.  TSQM scores range from 0 – 100 with higher scores 
indicating better satisfaction.
Work Productivity and Activity Impairment Questionnaire:  Specific Health 
Problem
The subjects will complete a Work Productivity and Activity Impairment Questionnaire:  
Specific Health Problem (WPAI:SHP) questionnaire (Appendix N) at the designated 
study visits listed in Appendix C.  The WPAI:SHP (6 items) evaluates four areas:  percent 
work time missed due to HS, percent impairment while working due to HS, percent 
overall work impairment due to HS, and percent activity impairment due to HS.
The subject should complete the questionnaire before study site personnel perform any 
clinic assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.
Lesion Counts
The number of inflammatory and non-inflammatory nodules, abscesses, draining and 
non-draining fistulas, and hypertrophic scars, as well as the physical location 
(e.g., right/left axilla, right/left inframammary, inframammary, right/left buttock, right/left 
inguino-crural fold, perianal, perineal, other) will be recorded (Appendix E) at the 
designated study visits listed in Appendix C.  The calculation of the HiSCR will be 
performed by AbbVie at the end of the study based on the lesion counts entered by the 


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Study Investigators on the appropriate CRFs; thus, treatment decisions made during the 
conduct of this study will not be based on the HiSCR.
The longest distance between two relevant lesions (if only one lesion, measure diameter 
of lesion) and whether the lesions are clearly separated by normal-appearing skin 
('yes'/'no') will be measured.
Hurley Stage
See Section 1.3 for definition of Hurley Stage.  The Study Investigator will determine the 
Hurley Stage in each affected anatomical region at the designated study visits listed in 
Appendix C.  If more than one stage is present in a region, the worst stage in each region 
should be entered.
The study site should make every attempt to have the same investigator conduct these 
assessments throughout the study for each subject.
Dispense Study Drug
Study drug will be dispensed (Appendix O) to subjects at the designated study visits listed 
in Appendix C.  Each subject will receive study drug packaged as described in 
Section 5.5.2, with adequate supply to be used for weekly injections until the next 
scheduled study visit.
Digital Imaging
Subjects at prospectively selected study sites will be asked to have photographs taken of 
their disease response during the study.  The study sites will be chosen by AbbVie for 
their expertise.  Subjects who consent will have photographs taken at the designated study 
visits listed in Appendix C.  The cameras for the photographs will be standardized and 
supplied to the study site by a central photography imaging vendor.  Study sites will 
submit the digital images to the centralized imaging vendor.  Training and detailed 
instructions will be provided by the central imaging vendor.  The digital images will be 


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stored for later reproduction and medical education, and exploratory analyses may be 
performed of the blinded, annotated digital images.
The designated surgeon (or Study Investigator, dependent on available camera and 
technical expertise) will photograph each subject's HS surgical site.  
Doppler Ultrasound
Subjects at prospectively selected study sites will be asked to have Doppler ultrasound 
examinations of the HS non-surgical sites throughout the study and the HS surgical site 
throughout Period A.  Subjects who consent will have these examinations performed at 
the designated study visits listed in Appendix C.  The study sites will be selected by 
AbbVie for their access to appropriate equipment, technical skills, and interpretative 
expertise to perform these examinations.  The results of these evaluations will not be used 
to count HS lesions (e.g., abscesses, inflammatory nodules, fistulas), calculate the Hurley 
Stage, or evaluate the HiSCR.
Follow-Up Telephone Calls
Week 6 and Week 10
Subjects will be contacted at Week 6 and Week 10 to obtain information on any signs of 
an infection at or near an HS lesion.  Subjects with signs or symptoms of an infection will 
be bought into the study site for an unscheduled visit to be evaluated.  Study procedures 
will be performed as outlined in Appendix C.
70 Days Following the Last Dose of Study Drug
Subjects will be contacted approximately 70 days following study drug discontinuation 
for an assessment of any new or ongoing AEs/SAEs, except for those subjects who 
continue on adalimumab not supplied in the context of the clinical trial after the end of 
study participation.  These subjects are not required to complete the 70-day follow-up 
telephone call and any new AEs should be reported through the mechanism used for all 
post-marketing adverse experience.


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5.3.2
Drug Concentration and Anti-Adalimumab Antibody 
Measurements
Blood samples for adalimumab and Anti-Adalimumab Antibody (AAA) assays will be 
collected by venipuncture at the designated study visits listed in Appendix C.
5.3.2.1
Collection of Samples for Analysis
Blood samples for PK adalimumab analysis will be collected by venipuncture into 
appropriately labeled 6 mL evacuated serum collection tubes without gel separator at the 
designated study visits listed in Appendix C (i.e., at Baseline, and Weeks 4, 8, 12, 14, 15, 
17, 20, and 24/Premature Discontinuation Visit if the subject discontinues prior to 
Week 24).  All samples will be obtained immediately prior to study drug administration.
Blood samples for AAA will be split from the PK sample collection after centrifugation to 
isolate serum.  Detailed information will be provided in the laboratory manual.  
Processing for AAA samples will be done at the designated study visits listed in 
Appendix C (i.e., at Baseline, and Weeks 4, 8, 12, 15, 20, and 24/Premature 
Discontinuation Visit if the subject discontinues prior to Week 24).
Collection of Samples for Adalimumab Analysis
A maximum of 8 samples are planned to be collected per subject for PK adalimumab 
analysis.  The total number of PK adalimumab samples planned will not exceed 
1600 (8 samples × 200 subjects) for the entire study.  Sample calculations are based on 
the maximum number of subjects.
Collection of Samples for Anti-Adalimumab Antibody Analysis
A maximum of 7 samples are planned to be split from the PK sample collection.  The total 
number of AAA samples planned will not exceed 1400 (7 samples × 200 subjects) for the 
entire study.  Sample calculations are based on the maximum number of subjects.


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5.3.2.2
Handling/Processing of Samples
Sufficient blood will be collected to provide approximately 3 mL serum from each 
sample.  The blood will be allowed to clot for 30 minutes at room temperature prior to 
centrifugation as described in the laboratory manual.  The time that each blood sample is 
collected will be recorded to the nearest minute in the source document and on the 
appropriate eCRF.  Samples will be analysed under the supervision of the AbbVie Drug 
Analysis Department.
Additional detailed instructions for the handling and processing of samples will be 
provided from the central laboratory.
5.3.2.3
Disposition of Samples
AbbVie will not supply dry ice for this study.  The frozen serum samples for the 
adalimumab PK and, where applicable, AAA assays will be packed in dry ice (pellet 
form) sufficient to last 3 days during transport and shipped from the study site to the 
Central Laboratory.  The two splits of each sample set (i.e., adalimumab, AAA) will be 
shipped in separate shipments in case of transportation problems (i.e., customs delays, 
damage or loss of shipment) as defined by the Central Laboratory.  
5.3.2.4
Measurement Methods
Serum concentrations of adalimumab will be determined using a validated assay 
methodology under the supervision of the AbbVie Drug Analysis Department.
Serum concentration of AAA will be determined using a validated assay methodology 
under the supervision of the AbbVie Drug Analysis Department.


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5.3.3
Efficacy Variables
5.3.3.1
Primary Variable
The primary efficacy variable is the proportion of subjects achieving HiSCR at Week 12.  
HiSCR is defined as at least a 50% reduction in the AN count with no increase in abscess 
count and no increase in draining fistula count relative to baseline.
5.3.3.2
Secondary Variables
Ranked Secondary Efficacy Variables
The following secondary efficacy variable will be analysed according to the rank order as 
follows:
1.
Proportion of subjects achieving HiSCR-es (defined as the HiSCR excluding the 
HS surgical site) at Week 12,
2.
Proportion of subjects achieving HiSCR-es at Week 24,
3.
Percent change in surface area of the HS surgical site from Baseline to Week 12, 
and
4.
Proportion of subjects at Week 12 that require a less extensive surgery than the 
surgical plan (determined at Baseline) or no surgery as determined by the 
designated surgeon.
Other Efficacy Variables 
Other efficacy variables to be analysed at each scheduled visit in Periods A and C, except 
for the ones included as the primary or ranked secondary variables that will be analysed 
for visits other than Weeks 12 and 24 include:
E
Change from Baseline in CRP
E
Proportion of subjects with DLQI = 0
E
Proportion of subjects with DLQI = 0 or 1


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E
Change from Baseline in DLQI score
E
Change from Baseline in EQ-5D index
E
Change from Baseline in HS-PGA-SP
E
Change from Baseline in HS PGIC
E
Change from Baseline in HSIA
E
Change from Baseline in HSSA-7d
E
Change from Baseline in SF-12
E
Change from Baseline in TSQM
E
Change from Baseline in WPAI:SHP
E
Proportion of subjects that experience a flare, defined as an at least 25% 
increase in AN count with a minimum increase of 2 relative to Baseline at each 
study visit, during Period A and during the study
E
Proportion of subjects that experience at least 25% increase in each lesion type 
with a minimum increase of 2 relative to Baseline at each study visit, during 
Period A and during the study
5.3.4
Safety Variables
Adverse events, laboratory data, physical examinations, and vital signs will be collected, 
monitored, assessed, and recorded at the designated study visits listed in Appendix C and 
as described in Section 6.0 and Table 1.
5.3.5
Pharmacokinetic Variables
Adalimumab trough serum concentrations will be summarized at each time point using 
descriptive statistics.  In addition, within subject comparison of adalimumab 
concentrations before and after surgery will be performed.  Percentage of subjects that 
develop immunogenicity during the 24-week study duration will be calculated.  The 
impact of immunogenicity development on adalimumab PK, efficacy, and safety will be 
evaluated through comparison of adalimumab concentrations, primary efficacy outcome, 
and incidence of AEs between AAA+ and AAA– subjects.


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5.3.6
Exploratory Research Variables
Biomarker assessments may be used to assess and generate prognostic, predictive, 
pharmacodynamics, or surrogate biomarker signatures.  These assessments may be 
explored in the context of HS or related conditions, and/or adalimumab or drugs of similar 
classes.  The results from these analyses are exploratory in nature and may not be 
included with the clinical study report.
The sample may also be used to develop new therapies, research methods, and 
technologies.  In addition, samples from this study may be banked for future use.  
Samples may then be used to validate putative biomarker signatures obtained from a 
prospective study, leading to the development of diagnostic tests.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
A subject may withdraw from the study at any time.  The Principle Investigator may 
discontinue any subject's participation for any reason, including an adverse event, safety 
concerns, of failure to comply with the protocol.
Subjects will be withdrawn from the study immediately if any one of the following 
occurs:
E
Clinically significant abnormal laboratory result(s) or adverse event(s), as 
determined by the Study Investigator in consultation with the AbbVie Study 
Designated Physician;
E
The Study Investigator believes it is in the best interest of the subject;
E
The subject requests withdrawal from the study;
Inclusion and exclusion criteria violation was noted after the subject started 
study drug, when continuation of the study drug would place the subject at risk 
as determined by the AbbVie Study Designated Physician (see Section 5.2 and 
Section 7.0);


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E
Introduction of prohibited medications or dosages when continuation of the 
study drug would place the subject at risk as determined by the AbbVie Study 
Designated Physician;
E
Subject is non-compliant with TB prophylaxis;
E
The subject develops tuberculosis, or any other significant or opportunistic 
infections;
E
The subject becomes pregnant while on study drug;
E
Subject has dysplasia of the gastrointestinal tract of a malignancy, except for 
localized non-melanoma skin cancer.  Discontinuation for carcinoma in situ of 
the cervix is at the discretion of the Study Investigator; 
E
Subject is diagnosed with lupus-like syndrome, multiple sclerosis, or 
demyelinating disease;
E
Subject is significantly non-compliant with study procedures that would put 
the subject at risk for continued participation in the trial, as determined by the 
Study Investigator, in consultation with the AbbVie Study Designated 
Physician.
If, during the course of study drug administration, the subject prematurely discontinues 
study drug use, the procedure outlined for the Premature Discontinuation Visit must be 
completed within 2 weeks of the last dose of study drug, and preferably prior to the 
initiation of another therapy.  However, these procedures should not interfere with the 
initiation of any new treatments or therapeutic modalities that the Study Investigator 
thinks are necessary to treat the subject's condition.  Following discontinuation of the 
study drug, the subject will be treated in accordance with the Study Investigator's best 
clinical judgment.
All attempts must be made to determine the date of the last dose of study drug and the 
primary reason for premature discontinuation.  The information will be recorded on the 
appropriate eCRF page.


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For subjects who are considered lost to follow-up, reasonable attempts must be made to 
obtain information on the final status of the subject.  At a minimum, two telephone calls 
must be made and one certified letter must be sent.
5.4.2
Discontinuation of Entire Study
AbbVie may terminate this study prematurely, either in its entirety or at any study site, for 
reasonable cause provided that written notice is submitted in advance of the intended 
termination.  The Study Investigator may also terminate the study at his/her study site for 
reasonable cause, after providing written notice to AbbVie in advance of the intended 
termination.  Advance notice is not required by either party if the study is stopped due to 
safety concerns.  If AbbVie terminates the study for safety reasons, AbbVie will 
immediately notify the Study Investigator by telephone and subsequently provide written 
instructions for study termination.
AbbVie reserves the right to discontinue the study at any time and to remove all study 
materials from the study site.  Possible reasons for termination of the study include, but 
are not limited to:
E
Safety concerns based on reported data
E
Unsatisfactory enrollment with respect to quantity or quality
E
Inaccurate or incomplete data collection
E
Falsification of records
E
Failure to adhere to the protocol
5.5
Treatments
5.5.1
Treatments Administered
All treatments administered will be assigned via Interactive Response Technology (IRT) 
in order to maintain blinding.  During Period A (Week 0 through Week 12), all subjects 
will receive 4 injections initially at Day 1 (or alternatively, given as two 0.8 mL injections 
per day on 2 consecutive days), 2 injections at Day 15 (Week 2), and one injection weekly 


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from Week 4 through Week 12.  During Period B, all subjects will receive one injection 
weekly from Week 13 through Week 14.  During Period C, all subjects will receive 
one injection weekly from Week 15 through Week 23.  No study drug will be 
administered at the Week 24 or Premature Discontinuation Visit.
Study drug will be provided as a sterile, preservative-free solution for subcutaneous (SC) 
administration in 1 mL pre-filled syringes containing adalimumab 40 mg/0.8 mL or 
placebo (0.8 mL).  The subject should be instructed to store the pre-filled syringe in the 
outer carton (in order to protect from light) in the refrigerator at 2° to 8°C/36° to 46°F, 
and that syringes should not be stored in a freezer.
Study drug will be administered SC using sterile technique by the subject or designee 
(e.g., family member, friend, health care professional) at the study site, or at home via 
self-injection following proper training (Appendix P) or by a qualified designee.  At each 
Study visit qualified research personnel will observe the subject or designee during the 
injection to ensure proper technique.  The subject should place the used syringe in the 
sharps disposal container, which will be provided to the subject at each study visit (unless 
prohibited by local regulations) or less frequently depending upon the size of the 
container.
Period A
Subjects randomised to Arm 1 will receive:
E
160 mg/3.2 mL adalimumab at the Baseline Study visit (Day 1) administered 
as four 40 mg injections SC (or two 0.8 mL injections on two consecutive 
days, i.e., Day 1 and Day 2)
E
80 mg/1.6 mL adalimumab at the Week 2 (Day 15) Study visit administered as 
two 40 mg injections SC
E
40 mg/0.8 mL adalimumab every week (ew) from Week 4 (Day 29) through 
Week 12 administered (either at the Study visit or at home as appropriate) as 
one 40 mg injection SC


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Subjects randomised to Arm 2 will receive:
E
3.2 mL placebo at the Baseline Study visit (Day 1) administered as four 40 mg 
injections SC (or two 0.8 mL injections on two consecutive days, i.e., Day 1 
and Day 2)
E
1.6 mL placebo at the Week 2 (Day 15) Study visit administered as 
two 0.8 mL injections SC
E
0.8 mL placebo every week (ew) from Week 4 (Day 29) through Week 12 
administered (either at the Study visit or at home as appropriate) as one 0.8 mL 
injection SC
Period B
Subjects randomised to Arm 1 will receive:
E
40 mg/0.8 mL adalimumab every week (ew) from Week 13 through Week 14 
administered (either at the Study visit in clinic, in hospital, or at home as 
appropriate) as one 40 mg injection SC
Subjects randomised to Arm 2 will receive:
E
0.8 mL placebo every week (ew) from Week 13 through Week 14 
administered (either at the Study visit in clinic, in hospital, or at home as 
appropriate) as one 0.8 mL injection SC
Period C
Subjects randomised to Arm 1 will receive:
E
40 mg/0.8 mL adalimumab every week (ew) from Week 15 through Week 23 
administered (either at the Study visit or at home as appropriate) as one 40 mg 
injection SC
Subjects randomised to Arm 2 will receive:


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E
0.8 mL placebo every week (ew) from Week 15 through Week 23 
administered (either at the Study visit or at home as appropriate) as one 0.8 mL 
injection SC
5.5.2
Identity of Study Drug
The individual study drug information is presented in Table 2.
Table 2.
Identity of Study Drug
Study Drug
Formulation
Manufacturer
Adalimumab
40 mg/0.8 mL pre-filled syringes
Adalimumab/Mannitol, Citric acid monohydrate, Sodium 
citrate, Disodium phosphate dehydrate, Sodium dihydrogen 
phosphate dehydrate, Sodium chloride, Polysorbate 80, Water 
for injection, Sodium hydroxide added as necessary to adjust pH
AbbVie
Placebo
0.8 mL pre-filled syringes
Mannitol, Citric acid monohydrate, Sodium citrate,  Disodium 
phosphate dehydrate, Sodium dihydrogen phosphate dehydrate, 
Sodium chloride, Polysorbate 80, Water for injection, Sodium 
hydroxide added as necessary to adjust pH
AbbVie
Each study site will be responsible for tracking the lot numbers and expiration dates for all 
non-investigational medicinal products (e.g., generic name and generic name) that are 
dispensed.
5.5.2.1
Packaging and Labeling
Adalimumab and placebo will be provided in a 1 mL pre-filled syringe containing 
adalimumab 40 mg/0.8 mL or matching placebo injection solution and will be packaged 
in two pre-filled syringes per carton.  Each adalimumab/placebo kit carton and syringe 
will be labeled and have a unique kit ID.  The labels for the adalimumab/placebo syringe 
kit carton will minimally contain the required country information.
Each label must remain affixed to the dosing unit.


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5.5.2.2
Storage and Disposition of Study Drugs
Adalimumab/placebo pre-filled syringes are to be stored protected from light at 2° to 
8°C/36° to 46°F.  Study drug must not be frozen at any time.  A storage temperature log 
is to be maintained to document proper storage conditions.  The refrigerator temperature 
must be recorded on a temperature log to record proper function.  Malfunctions or any 
temperature excursions must be reported to the Sponsor immediately upon identification.  
Study medications should be quarantined and not dispensed until AbbVie GPRD or 
Abbott Temperature Excursion Management System (ATEMS) deems the medications as 
acceptable.
All clinical supplies must be stored and locked in a secure place until they are dispensed 
for subject use or are returned to AbbVie.
Study drugs, syringes, and associated products are for investigational use only and are to 
be used only within the context of this study.
5.5.3
Method of Assigning Subjects to Treatment Groups
The randomisation schedules will be generated at AbbVie before the start of the study and 
will be provided to the IRT vendor.  Before the study site is initiated, the instructions for 
use of the IRT will be provided to the site.  All subjects will be assigned a unique 
identification number by IRT as they are screened for the study.  The subjects will be 
randomised centrally and stratified by Hurley Stage (II versus III) and anatomical location 
of the HS surgical site (i.e., axilla versus inguinal region) in a 1:1 ratio to either 
adalimumab or placebo at Day 1.  The number of subjects in Hurley Stage III is not to 
exceed 50% of the total planned number of subjects (100 subjects).  In addition the 
number of subjects with an AN count of 3 or 4 is not to exceed 40 (20% of the total 
planned number of subjects).
5.5.4
Selection and Timing of Dose for Each Subject
Subjects should take study medication as outline in Section 5.5.1.


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At the Baseline visit, after all assessments have been completed, subjects in Arm 1 will 
receive four injections of active study drug (40 mg/0.8 mL each) and subjects in Arm 2 
will receive four placebo injections (0.8 mL each) as detailed in Section 5.5.1.  
Appropriate study site personnel will train and then supervise the subject or designee 
administering at least one injection of the study drug to ensure proper understanding of 
injection technique (Appendix P).  The subject or designee will subsequently dose and be 
witnessed by study site personnel during their study visits to ensure continued proper 
technique.  When study drug is administered at the Day 1 (Week 0) and Week 2 study 
visits (see Appendix C), the subject should remain at the study site for approximately 
15 to 30 minutes after injection for observation.
For home administration of injection, subjects or qualified designee will be instructed to 
inject study medication on the same day of the week as their Baseline visit day as detailed 
in Section 5.5.1.  Every kit contains 2 syringes each.
If a subject should forget to administer the injection of study medication on their regularly 
scheduled dosing date, the subject should take the forgotten injection as soon as she/he 
remembers the dose was missed up to the day before the next scheduled dose.  The subject 
should not administer two doses on the same day.
Doses not administered (e.g., not taken before the next dose is scheduled), should be 
recorded as not taken in the source.  The extra dose should be returned in its entirety to the 
study site at the subject's next study visit.  Meanwhile, the subject should resume their 
regular dosing schedule based on the first dosing date at Baseline (Day 1).
In the event the incorrect dose is taken, the entire volume of study drug is not injected, or 
a dose is missed, the subject should be instructed to contact the study site to determine 
how to proceed with dosing.  The subject must record all dosing information on the 
Subject-Dosing Diary Sheet.


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5.5.5
Blinding
5.5.5.1
Blinding of Study Drug
All AbbVie personnel with direct oversight of the conduct and management of the trial 
(with the exception of AbbVie's Global Drug Supply Management Team); the Study 
Investigator, the designated surgeon, and study site personnel; and the subject will remain 
blinded to each subject's treatment throughout the study.  The IRT will provide access to 
blinded subject treatment information in the case of medical emergency.  The procedure 
for breaking the blind is referenced in the IRT Training Slides provided to each study site.
AbbVie must be notified before the blind is broken unless identification of the study drug 
is required for medical emergency, i.e., situation in which the knowledge of the specific 
blinded treatment will affect the immediate management of the subject/patient's 
conditions (e.g., antidote is available).  AbbVie must then be notified within 24 hours of 
the blind being broken.  See Section 7.0 for contact information, including 24/7 physician 
coverage.
The date and reason that the blind was broken must be conveyed to AbbVie and recorded 
in the source documentation and on the appropriate eCRF.
5.5.6
Treatment Compliance
The Study Investigator or his/her designated and qualified representatives will 
administer/dispense study drug only to subjects enrolled in the study in accordance with 
the protocol.  The study drug must not be used for reasons other than that described in the 
protocol.
The subject or his/her qualified designee will administer all doses of study drug after 
being appropriately trained (see Section 5.5.4).  Appropriate study site personnel will 
supervise the subject's administration of the study drug at required study visits (see 
Appendix C) to ensure proper injection technique.  In order to document compliance with 
the treatment regimen, the subject will be given a dosing sheet (Appendix Q) to record all 
injection dates and times.  Compliance information will be document on the appropriate 


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eCRF.  The subject will be counseled on missed doses of study drug.  If the subject does 
not return the dosing sheet, study drug boxes, and/or sharps containers (when applicable), 
study site personnel should question the subject and obtain as much information as 
possible as to the dosing of the study drug.
The information should be documented on the source documents as per "best recollection" 
and when possible, re-verified when the dosing sheet is returned before completing the 
applicable eCRF page.
If a subject is consistently not returning the dosing sheet, not providing accurate dosing 
information, or consistently missing doses and/or is deemed non-compliant with no 
explanation, the situation will be discussed with the AbbVie Study Designated Physician 
and the subject may be discontinued from the study.
5.5.7
Drug Accountability
The Study Investigator or designee will verify that study drug supplies are received intact, 
at the appropriate temperature, and in the correct amounts.  This will be accomplished by 
documenting the condition of the shipment, verifying kit numbers in the package against 
the Proof of Receipt (POR) or similar document included with each drug shipment, and 
documenting this verification by signing and dating the POR or similar document.  The 
original POR or similar document will be kept in the study site files as a record of what 
was received.
In addition, an accurate running inventory of study drug will be kept by the study site 
using the online clinical drug accountability (CDA) system provided by the IRT system.  
The CDA system will track the following:  date received, the lot number, the kit 
number(s), date dispensed, subject number, and the identification with date of the person 
dispensing the drug.
All empty study drug boxes and used pre-filled syringes will be inventoried by the study 
site personnel.  Each subject will be given his/her own sharps disposal container to store 
used pre-filled syringes.  Empty study drug boxes and sharps disposal containers should 


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be returned by the subject at each study visit for accountability and compliance purposes, 
and new containers will be issued as necessary.  Empty study drug boxes and returned 
sharps disposal containers will be retained (unless prohibited by local regulations) until 
the AbbVie Medical Monitor is at the study site to confirm the returned study drug.  The 
AbbVie CRA and study site personnel will complete study drug accountability using 
study drug logs, source documents, and subject dosing sheets plus visual inspection of 
empty study drug boxes and the syringes in the returned sharps disposal containers.  The 
returned sharps disposal containers should never be opened.  Once the AbbVie CRA has 
verified drug accountability, the study site personnel and AbbVie CRA will document that 
the used syringes have been destroyed, using appropriate biohazard precautions, when 
appropriate.  A copy of the destruction methodology should be maintained at the study 
site's facility.  Unused study drug will be returned by the AbbVie CRA after drug 
accountability has been completed at the study site.
In addition to overall drug accountability, the subject and study site will maintain subject 
dosing and subject drug accountability logs, Appendix Q and Appendix R, respectively.
Non-investigational medicinal and other treatment products (standard of care) 
(e.g., wound care supplies) must be obtained commercially.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
The design of this clinical trial is chosen to evaluate adalimumab in HS subjects with 
active HS lesions who require surgery as part of their standard care.  Adalimumab will be 
compared to placebo during a 12-week period (Period A) prior to surgery, to assess the 
impact on all anatomic regions with active HS lesions including the HS surgical site and 
at least two other anatomical regions, one of which is Hurley Stage II or III.  The impact 
on the HS surgical site will be also evaluated.  Period B is a 2-week period during which 
the subject undergoes surgery and immediate post-operative routine care and monitoring.  
The utility of Period C, a 10-week period, is to assess the impact the adalimumab as 
compared to placebo in HS subjects who have undergone surgery, including the continued 


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impact on active HS lesions not within the surgical site (i.e., HS non-surgical sites) and 
the impact on the surgical wound.  Previous clinical trials have not evaluated the use of 
adalimumab in concert with surgery.  This study design will allow direct evaluation of 
adalimumab in a HS population that requires excisional surgery as part of their routine 
disease management.  The placebo-controlled trial will allow a comparison of safety of 
adalimumab over a 24-week period including comparisons both before and after 
excisional surgery.
5.6.2
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be used in this study.  
Efficacy measurements have been selected to assess disease activity in subjects with 
chronic HS.  The primary efficacy endpoint (HiSCR, at least a 50% reduction in the AN 
count plus no increase in abscess count and no increase in draining fistulas) was designed 
and validated in the Adalimumab Clinical Development Program.  The HiSCR has been 
accepted as a useful score to measure the impact of therapeutic agents in clinical trials as 
evidenced by the use of this measure in other clinical studies sponsored by entities other 
than AbbVie.  All clinical and laboratory procedures in this study are standard and 
generally accepted.
5.6.3
Suitability of Subject Population
Males and females 18 years or older with moderate to severe HS requiring excisional 
surgery as part of routine disease management who meet all inclusion criteria but none of 
the exclusion criteria are eligible for this study.  Adalimumab is approved for the 
treatment of active moderate to severe HS in adult patients who have not responded to 
conventional systemic HS therapy.  This population in this study is similar to the 
moderate to severe HS population that was included in the Adalimumab Clinical 
Development Program, however this population will also have advanced HS lesions such 
that excisional surgery is required as part of their routine disease management.  The 
population being studied represents normal clinical practice with a spectrum of subjects 
with high medical need due to great disability and discomfort.  This ensures the activity of 


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adalimumab can be evaluated as part of the integrated medical-surgical management 
across a distribution of HS severity that has not been previously studied in a 
placebo-controlled clinical trial.
5.6.4
Selection of Doses in the Study
Adalimumab has been approved for the treatment of adult HS patients and the dose 
regimen used in this study will be the approved recommended dosing:  160 mg initially at 
Day 1, followed by 80 mg two weeks later at Day 15.  Two weeks later (Day 29) continue 
with a dose of 40 mg every week as documented in the current SmPC.
6.0
Complaints
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
The active study drug in this trial contains both a:
E
biologic compound and
E
pre-filled syringe
Complaints associated with any component of this study drug must be reported to the 
Sponsor (Section 6.2.2).  For adverse events, please refer to Section 6.1.  For product 
complaints, please refer to Section 6.2.
6.1
Medical Complaints
The Study Investigator will monitor each subject for clinical and laboratory evidence of 
AEs on a routine basis throughout the study.  The Study Investigator will assess and 
record any AE in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
AE to study drug, and any action(s) taken.  For an SAE considered as having "no 


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reasonable possibility" of being associated with study drug, the Study Investigator will 
provide another cause of the event.  For an AEs to be considered intermittent, the 
repetitive occurrences of the events must be of similar nature and severity.  An AE, 
whether in response to a query, observed by study site personnel, or reported 
spontaneously by the subject will be recorded.
All AEs will be followed to a satisfactory conclusion.
6.1.1
Definitions
6.1.1.1
Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or 
clinical investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal product, whether or not the 
event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Worsening in 
severity of a reported adverse event should be reported as a new AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if the event results 
in discontinuation from the study, necessitates therapeutic medical intervention, meets 
protocol specific criteria (see Section 6.1.7 regarding toxicity management) and/or if the 
Study Investigator considers the event to be an AE.
An elective surgery or procedure scheduled to occur during a study will not be considered 
an AE if the surgery or procedure is being performed for a pre-existing condition and the 
surgery/ or procedure has been pre planned prior to study entry.  However, if the 
pre-existing condition deteriorates unexpectedly during the study (e.g., surgery performed 


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earlier than planned), then the deterioration of the condition for which the elective 
surgery/procedure is being done will be considered an AE. 
In order to be eligible for this study a subject must require surgery due to HS and the 
surgery date will determined after enrollment.  The need for rescue surgery of the 
designated HS surgical site (i.e., surgery prior to Week 13) will not be recorded as an AE; 
rather the reason for surgery will be recorded on the appropriate eCRF as described in 
Section 5.3.2.4 and the subject will be withdrawn from the study.
6.1.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as a 
serious adverse event (SAE) within 24 hours of the study site being made aware of the 
SAE.
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have 
been fatal if it had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to an 
outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss.
Persistent or 
Significant 
Disability/Incapacity
An event that results in a condition that substantially 
interferes with the activities of daily living of a study subject.  
Disability is not intended to include experiences of relatively 
minor medical significance such as headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).


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Important Medical 
Event Requiring 
Medical or Surgical 
Intervention to 
Prevent Serious 
Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based 
on medical judgment may jeopardize the subject and may 
require medical or surgical intervention to prevent any of the 
outcomes listed above (i.e., death of subject, life-threatening, 
hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  
Additionally, any elective or spontaneous abortion or 
stillbirth is considered an important medical event.  Examples 
of such events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or 
drug abuse.
For SAEs with the outcome of death, the date and cause of death will be recorded on the 
appropriate case report form.
6.1.1.3
Adverse Events of Special Interest
Adverse events of special interest as defined in Table 3, and adverse events concerning 
the surgical site will be collected and analysed.


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Table 3.
Adverse Events of Special Interest
Serious and nonserious opportunistic infections, including the following bacterial, fungal, viral and 
parasitic infections:  Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcal, Cytomegalovirus, 
Histoplasma, Listeria, Nocardia, Paracoccidioides, Pneumocystis, Toxoplasma, Tuberculosis, Herpes, 
Bacillary angiomatosis, Mucormycosis, Progressive Vaccinia, Zygomycosis, BK virus, and JC virus
Lymphoma 
Hepatosplenic T-cell lymphoma
Leukemia
Non-melanoma skin cancer (NMSC)
Other malignancies (except lymphoma, leukemia and NMSC)
Immune reactions including lupus, lupus-like reactions, and severe allergic reactions
Congestive heart failure (CHF)
Cerebrovascular accident (CVA)
Myocardial infarction (MI)
CNS demyelinating disorders (including MS and Guillain-Barré syndrome)
Hepatic events that are serious or lead to permanent discontinuation of study drug (e.g., persistent liver 
function test abnormalities, acute liver failure and other serious hepatic events)
Hematologic events that are serious or lead to permanent discontinuation of study drug (e.g., aplastic 
anemia, granulocytopenia, Granulocyte Maturation Arrest, leukopenia, neutropenia, nancytopenia and 
thrombocytopenia)
Worsening of Psoriasis
Vasculitis
Diverticulitis
Intestinal perforation
6.1.2
Adverse Event Severity
The investigator will use the following definitions to rate the severity of each adverse 
event:
Mild
The adverse event is transient and easily tolerated by the subject.
Moderate
The adverse event causes the subject discomfort and interrupts 
the subject's usual activities.


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Severe
The adverse event causes considerable interference with the 
subject's usual activities and may be incapacitating or 
life-threatening.
6.1.3
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study drug:
Reasonable 
Possibility
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
No Reasonable 
Possibility
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event.
For causality assessments, events assessed as having a reasonable possibility of being 
related to the study drug will be considered "associated."  Events assessed as having no 
reasonable possibility of being related to study drug will be considered "not associated."  
In addition, when the investigator has not reported a causality or deemed it not assessable, 
AbbVie will consider the event associated.
If an investigator's opinion of no reasonable possibility of being related to study drug is 
given, an Other cause of event must be provided by the investigator for the serious 
adverse event.
6.1.4
Adverse Event Collection Period
All AEs reported from the time of study drug administration until either the final 
follow-up telephone call (approximately 70 days following discontinuation of study drug 
administration) or the date at which the subject initiated commercial adalimumab will be 
collected, whether solicited or spontaneously reported by the subject.  In addition, SAEs 
and protocol-related nonserious AEs will be collected from the time the subject signed the 
study-specific informed consent.  Adverse event information will be collected and 
recorded on the appropriate eCRFs.


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Subjects will contacted approximately 70 days following study drug discontinuation for 
an assessment of any new or ongoing AEs/AESI/SAEs as discussed in Section 5.3.1.1.
Adverse event information will be collected as shown in Figure 2.
Figure 2.
Adverse Event Collection
6.1.5
Adverse Event Reporting
In the event of an SAE, and additionally, any nonserious event of malignancy in subjects 
30 years of age and younger, whether related with study drug or not, the Study 
Investigator will notify AbbVie Clinical Pharmacovigilance within 24 hours of the study 
site being made aware of the serious adverse event by entering the SAE or nonserious 
event of malignancy in subjects 30 years of age or younger data into the electronic data 
capture (EDC) system.  All SAEs and nonserious events of malignancy in subjects 
30 years of age and younger that occur prior to the study site having access to the RAVE®
system or if RAVE® is not operable, should be documented on the SAE Non-CRF forms 
and emailed (preferred route) or faxed to AbbVie Clinical Pharmacovigilance within 
24 hours of the study site being made aware of the serious adverse event.
Email:  
FAX to:  
SAEs and
Protocol-Related 
Nonserious AEs
Consent
Signed
Study Drug 
Start
Study Drug 
Stopped
70 Days After 
Study Drug 
Stopped
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported




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IMP, also include:  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the SmPC.
6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the 
study site becoming aware of the pregnancy.  Subjects who become pregnant during the 
study must be discontinued (Section 5.4.1).  Pregnancies will be collected from the date of 
the first dose through 150 days following the last dose of study drug.
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or spontaneous abortion, stillbirth, or congenital anomaly is considered a SAE 
and must be reported to AbbVie within 24 hours of the study site becoming aware of the 
event.
6.1.7
Toxicity Management
Subjects who develop a new infection while undergoing treatment with adalimumab 
should be monitored closely.  Administration of study injections should be interrupted if 
subject develops an infection requiring IV anti-infective treatment or if an infection meets 
the definition of "serious" (refer to Section 6.0 for definitions).  Study medication may be 
restarted once the physician determines that the infection has been successfully treated.  
Otherwise prohibited concomitant medications may be given if medically necessitated.  
Specifically, if a subject develops an inter-current infection, then topical and/or oral 
antibiotic usage is permitted.  Prior to use, every attempt should be made to contact the 
AbbVie Study Designated Physician for direction on re-introduction of adalimumab 
therapy after prohibited medication administration.


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6.2
Product Complaint
6.2.1
Definition
A Product Complaint is any Complaint (see Section 6.0 for the definition) related to the 
biologic or drug component of the product or to the pre-filled syringe.
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device (i.e., syringe not working properly, or packaging
issues.
For a medical device (i.e., pre-filled syringe), a product complaint also includes deaths of 
a patient using the device, any illness, injury, or adverse event in the proximity of the 
device, an adverse event that could be a result of using the device, any event needing 
medical or surgical intervention including hospitalization while using the device and use 
errors.
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be recorded.
6.2.2
Reporting
Product Complaints concerning the study drug and/or pre-filled syringes must be reported 
to the Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 
Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.
Product Complaints may require return of the product (i.e., syringe) with the alleged 
complaint condition.  In instances where a return is requested, every effort should be 




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For the purposes of this protocol, reportable deviations are defined as:
E
subject entered into the study even though she/he did not satisfy entry criteria,
E
subject developed withdrawal criteria during the study but was not withdrawn,
E
subject received the wrong study drug or an incorrect dose of study drug, or
E
subject received excluded or prohibited concomitant treatment 
(e.g., medication, surgical intervention)
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
The objectives of the statistical analyses are to evaluate the clinical safety and efficacy of 
adalimumab compared to placebo in subjects with moderate to severe HS who are 
scheduled to undergo excisional surgery for the 12-week period prior to surgery 
(Period A), the 2-week perioperative period (Period B) and during a 10-week 
post-surgical period (Period C).  Complete, specific details of the statistical analysis will 
be described and fully documented in the Statistical Analysis Plan (SAP).  The SAP will 
be finalized prior to the database lock and blind break.
8.1.1
Analysis Populations
The Intent-to-Treat (ITT) Population is defined as all subjects who randomised at the 
Baseline visit.  A Per-protocol Population (PP), which excludes patients with significant 
protocol violations, will be defined if deemed necessary.  The ITT Population and the PP 
population, if defined, will be used for the efficacy analysis.  Of note, the surgery-related 
endpoints during Periods B and C will be analysed among the subjects who undergo 
surgery.
The Safety Population is defined as all subjects who are in the ITT Population and receive 
at least one dose of study drug.  The Safety Population in each period will be used for 


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safety analysis.  Of note, the surgery-related safety endpoints during Periods B and C will 
be analysed among the subjects who undergo surgery.
For efficacy analysis, subjects included in the ITT population will be analysed by 
treatment group as randomised.  That is, all subjects will be included in the treatment 
group to which they are randomised, regardless of which treatment the subject actually 
received.  Subjects included in the PP Population, if defined, will be analysed as treated.  
That is, if a subject receives that treatment that is not the randomised assignment during 
the entire participation of a period or study, the subject will be analysed according to the 
treatment that the subject actually received.
For safety analysis, subjects included in the Safety Population will be analysed by 
treatment group as treated.  That is, if a subject receives treatment that is not the 
randomized assignment during the entire participation of a period or study, the subject 
will be analysed according to the treatment the subject actually received.
8.1.2
Planned Methods of Statistical Analysis
All statistical tests will be two-tailed with the significance level 0.05.  All P values will be 
rounded to three decimal places.  Descriptive statistics will be provided.  These include 
the number of observations, mean, and standard deviation for continuous variables; and 
counts and percentages for discrete variables.
The analyses will be performed using Statistical Analysis Software (SAS®, SAS Institute 
Inc., Cary, NC, USA).
8.1.3
Demographic and Baseline Characteristics
Demographic and Baseline characteristics of the study subjects will be summarized for 
each arm of the study using descriptive statistics.  Statistical tests will be performed to 
assess the comparability of the two arms.  Continuous variable will be analysed using 
one-way analysis of variance (ANOVA), and discrete variable will be analysed using 
Fisher's exact test.


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8.1.4
Statistical Analyses of Efficacy
The efficacy analysis will be conducted in the ITT Population and PP Population, if 
defined.
Visit windows and the data handling convention for summarizing efficacy results will be 
defined in the SAP.
Missing data will be imputed using the following methods for the efficacy analyses in the 
ITT Population:
E
Non-Responder Imputation (NRI):  the NRI analysis will categorize any 
subject who has a missing value at a specific visit as non-responder for that 
visit.  The NRI will be the primary approach in the analyses of categorical 
variables.  For analyses up to Week 12, NRI will be applied using evaluations 
within the period.
E
Last Observation Carried Forward (LOCF):  The LOCF analyses will use the 
completed evaluation from the previous visit within the particular period for 
efficacy measures assessed to impute missing data at later visits in the same 
period.  Baseline efficacy evaluations will not be carried forward.  LOCF will 
be the primary approach in the analyses of continuous variables, and the 
secondary approach in the analyses of categorical variables.
E
As-Observed:  The As-observed analyses will not impute values for missing 
evaluations, and thus a subject who did not have an evaluation on a scheduled 
visit will be excluded from the As-observed analysis for that visit.  
As-observed analyses will be the secondary approach in the analyses of 
continuous variables.
Multiple Imputation (MI) for missing values will be performed for the primary efficacy 
variable.
Lesions that receive intervention (e.g., contained within the excised surgical specimen, 
protocol-allowed minor interventions including incision and drainage) will be counted as 
permanently present from the date of the intervention.


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In order to evaluate the impact of major protocol violations on the results of the trial, 
efficacy assessments obtained after the start of a major protocol-disallowed treatment will 
be excluded from the analysis.  Subjects will be counted as non-responders for the 
categorical variable from the date of the major protocol-disallowed treatment and have 
their LOCF for continuous variables.  The exclusion of efficacy assessments will be 
determined via classification prior to the database lock.
Additional analyses may be performed for the primary efficacy variable adjusting for 
baseline covariates in addition to the stratification factors.
8.1.4.1
Primary Analysis of Efficacy
The primary analysis will be the comparison of the adalimumab ew treatment group 
versus the placebo treatment group in the proportion of subjects achieving HiSCR at 
Week 12.  The number and percentage of subjects achieving HiSCR will be computed for 
each treatment arm and the difference in response rates (adalimumab – placebo) will be 
analysed using the Cochran-Mantel-Haenszel (CMH) test, stratified by the stratification 
factors used for randomization.  The 95% confidence intervals of treatment difference will 
also be provided.
The primary analysis will be carried out in the ITT Population and the PP Population, if 
defined.  Non-responder imputation will be used as the primary approach for missing 
values.  LOCF and MI will be performed as sensitivity analyses for the primary efficacy 
variable.
In addition, a sensitivity analysis controlling for change from baseline in body weight 
using logistic regression models, for the primary efficacy endpoint.  Analysis details will 
be specified in the SAP prior to study unblinding and prior to database lock.
8.1.4.2
Secondary Analyses of Efficacy
Categorical variables will be analysed by CMH adjusting for the stratification factors for 
randomisation.  Continuous variables will be analysed by analysis of covariance 


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(ANCOVA) with Baseline value and the stratification factors used randomization in the 
model.
The analyses of the adalilmumab ew group versus placebo group will be carried out in the 
ITT Population.
Additional analyses may be performed for the primary efficacy variable adjusting for 
baseline covariates.  Results from any additional analyses will not be used as a substitute 
for the planned analyses, but may be used as supplemental information for the study 
report.
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, summaries and analyses will be performed for selected subgroups for the 
primary endpoint and ranked secondary endpoints.  The detailed subgroups will be 
outlined in the SAP.
8.1.5
Statistical Analyses of Safety
All AEs, SAEs, AEs leading to discontinuation, pre-specified AEs of special interest 
(AESIs) and adverse events concerning the surgical site will be collected during the study 
and up to approximately 70 days after the last dose of the study drug for subjects who do 
not elect to treat his/her HS disease with commercial adalimumab.  
Safety analyses will be carried out using the Safety Population.  Pretreatment AEs will be 
summarized.  Any TEAE is defined as an event with onset or worsening after the first 
study drug administration and within approximately 70 days after the last study drug 
administration for subjects who do not elect to treat his/her HS disease with commercial 
adalimumab.  
The number and percent of subjects experiencing treatment-emergent TEAEs will be 
tabulated using the Medical Dictionary for Drug Regulatory Activities (MedDRA®) 
system organ class and preferred term.  Comparisons of the percentages of subjects 
experiencing an AE in the adalimumab group versus the placebo group will be performed 


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using Fisher's exact test for data collected in the entire study, and separately for Period A, 
Period B, and Period C.  Summaries (including percentages and event per 
100 patient-years) of SAEs, deaths, AEs leasing to discontinuation from the study, AESIs, 
and adverse events concerning the surgical site will also be provided.
8.2
Determination of Sample Size
The study is designed to enroll approximately 200 subjects.  Assuming the true treatment 
difference in this study population is at least 20%, 100 subjects per arm will provide at 
least 80% power to detect the treatment difference at the alpha level of 0.05.  The study 
also has at least 80% power to demonstrate the point estimate of the treatment difference 
of at least 15%.
The response rates observed in the combined PIONEER I and II studies (Studies M11-313 
and M11-810, respectively) for the HiSCR at Week 12 were 50.6% and 26.8% in the 
adalimumab ew group and placebo group, respectively.  Due to the potential differences 
between the population of moderate-to-severe HS patients who are surgical candidates 
and the general moderate-to-severe HS patient population, a conservative estimate of 20% 
treatment difference is used for the power calculation.
8.3
Randomisation Methods
An IRT will be used to determine the randomisation of subjects.  Detailed instructions for 
using the IRT will be provided to the study site personnel.
Subjects who are eligible based on inclusion and exclusion criteria and have had all 
pre-randomisation procedures performed will be randomised in a 1:1 double-blind fashion 
to adalimumab 40 mg or placebo using baseline Hurley Stage (II versus III) and anatomic 
location of planned HS surgical site (axilla versus inguinal region).  The number of 
subjects in Hurley Stage III is not to exceed 50% of the total planned number of subjects 
(100 subjects).  The randomisation schedule will be prepared by the Statistics Department 
of AbbVie, USA and provided to drug supply for adequate packaging.


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8.4
Pharmacokinetic Analysis
Adalimumab serum concentrations will be summarized by treatment group at each time 
point using descriptive statistics including number of subjects, number of non-missing 
observations (nnmiss), mean, median, standard deviation, coefficient of variation (CV), 
minimum, and maximum as appropriate.  Individual subject concentrations versus time 
plots and mean concentration versus time plots by treatment group will be provided.  Data 
listing will be generated for individual subjects.  For the calculation of summary statistics 
and plots, concentration values below limit of quantification (LOQ) will be set to zero.
Population-based pharmacokinetic analysis will be performed based on the actual 
sampling times, instead of using the protocol-specified times.  Pharmacokinetic models 
will be built using a non-linear mixed-effect modeling approach with the Non-Linear 
Mixed Effect Modeling (NONMEM) software (Version VII, or a higher version).  The 
evaluation criteria described below will be used to examine the performance of different 
models.
1.
The objective function value of the best model is significantly smaller than the 
alternative model(s) based on the Likelihood Ratio test.
2.
The observed and predicted serum adalimumab concentration levels from the 
preferred model are more randomly distributed across the line of unity (a straight 
line with zero intercept and a slope of one) than the base model.
3.
Visual inspection of model fits, standard errors of model parameters and change in 
inter-subject and random residual error.
Once appropriate base pharmacokinetic model (including inter- and intra-individual error 
models) is developed, empirical Bayesian estimates of individual model parameters will 
be calculated by the posterior conditional estimation technique (post-hoc) on NONMEM.  
Covariates (such as demographics) will be tested with NONMEM in a stepwise parameter 
addition and deletion method until no more significant covariate-parameter relationships 
are found.  For the stepwise inclusion step of the model-finding process, all covariates 


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will be assessed at a significant level of P ] 0.01 (corresponding to a decrease in objective 
function > 6.63 for 1 degree of freedom).
The final model will be used to produce empirical Bayesian estimates of the 
pharmacokinetic parameters for each individual, using the post-hoc option in NONMEM.  
Individual pharmacokinetic parameters will be listed and summarized with appropriate 
statistical methods.
9.0
Ethics
9.1
Independent Ethics Committee or Institutional Review 
Board
Good Clinical Practice (GCP) requires that the clinical protocol, any substantial protocol 
amendments, the SmPC (or package insert), the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  The IEC/IRB will review the 
ethical, scientific and medical appropriateness of study the before it is conducted.  
IEC/IRB approval of the protocol, informed consent, and subject information and/or 
advertising, as relevant, will be obtained prior to the authorization of drug shipment to a 
study site.
Any substantial amendments to the protocol will require IEC/IRB approval prior to 
implementation of any changes made to the study design.  The Study Investigator will be 
required to submit, maintain, and archive study essential documents according to 
International Conference on Harmonisation Good Clinical Practice (ICH GCP).
Any serious adverse events that meet the reporting criteria, as dictated by local 
regulations, will be reported to both responsible Ethics Committees and Regulatory 
Agencies, as required by local regulations.  During the conduct of the study, the Study 
Investigator should promptly provide written reports (e.g., ICH Expedited Reports, and 
any additional reports required by local regulations) to the IEC/IRB of any changes that 


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affect the conduct of the study and/or increase the risk to subjects.  Written documentation 
of the submission to the IEC/IRB should also be provided to AbbVie.
9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonisation (ICH) guidelines, applicable regulations and guidelines governing clinical 
study conduct and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical investigator are specified in Appendix A.
9.3
Subject Information and Consent
The Study Investigator or his/her representative will explain the nature of the study to the 
subject, and answer all questions regarding this study.  Prior to any study-related 
screening procedures being performed on the subject, the informed consent statement will 
be reviewed, signed, and dated by the subject, the person who administered the informed 
consent, and any other signatories according to local requirements.  A copy of the 
informed consent form will be given to the subject and the original will be placed in the 
subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
Information regarding incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation 
in the study can be found in the informed consent form.
Samples for exploratory research/validation studies will only be collected if the subject 
has voluntarily signed and dated the separate written consent for exploratory 
research/validation studies, approved by an IEC/IRB, after the nature of the testing has 
been explained and the subject has had an opportunity to ask questions.  The separate 
written consent must be signed before the exploratory research/validation study samples 
are collected and testing is performed.  If the subject does not consent to the exploratory 
research/validation studies, it will not impact the subject's participation in the main study.


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In the event a subject withdraws from the main study, optional exploratory 
research/validation studies samples will continue to be stored and analysed unless the 
subject specifically withdraws consent for the optional samples.  If consent is withdrawn 
for the optional sampling, the subject must inform their study investigator, and once 
AbbVie is informed, the optional samples will be destroyed.  However, if the subject 
withdraws his/her consent and the samples have already been tested, those results will still 
remain as part of the overall research data.
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data, and records.  These may 
include hospital records, clinical and office charts, laboratory data/information, subjects' 
diaries or evaluation checklists, paper PRO's, pharmacy dispensing and other records, 
recorded data from automated instruments, microfiches, photographic negatives, 
microfilm or magnetic media, and/or x-rays.  Data collected during this study must be 
recorded on the appropriate source documents.
The investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
The following paper assessments completed by the subject or Study Investigator will be 
considered source documentation:
E
Dermatology Life Quality Index (DLQI)
E
EuroQoL (EQ-5D™)
E
Hidradentis Suppurativa Patient's Global Impression of Change (HS-PGIC)
E
Hidradenitis Suppurativa Patient's Global Assessment Skin Pain (HS-PGA-SP)
E
Hidradenitis Suppurativa Impact Assessment (HSIA)
E
Hidradenitis Suppurativa Symptom Assessment – 7 day recall (HSSA-7d)
E
Short Form 12 (SF-12)


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E
Treatment Satisfaction Questionnaire (TSQM)
E
Work Productivity and Activity Impairment Questionnaire:  Specific Health 
Problem (WPAI:SHP)
Once collected, these outcome assessment sheets will be entered by delegated study site 
personnel into the EDC system and will be available for viewing by study site personnel.
The AE/SAE eCRF data segments of alternate etiology, severity, frequency, and 
relationship to study drug may also be used as source documentation and will require the 
Study Investigator's approval on the eCRF as verification of the accuracy of the 
information.
10.2
Case Report Forms
Electronic and paper CRFs must be completed for each subject screened/enrolled in this 
study.  These forms will be used to transmit information collected during the study to 
AbbVie and regulatory authorities, as applicable.  The CRF data for this study are being 
collected with an EDC system called Rave® provided by the technology vendor Medidata 
Solutions Incorporated, NY, USA.  The EDC system and the study-specific eCRFs will 
comply with Title 21 CFR Part 11.  The documentation related to the validation of the 
EDC system is available through the vendor, Medidata, while the validation of the 
study-specific CRFs will be conducted by AbbVie and will be maintained in the Trial 
Master File at AbbVie.
The Study Investigator will document subject data in his/her own subject files.  These 
subject files will serve as source data for the study.  All electronic and paper CRF data 
required by this protocol will be recorded by study site personnel in the EDC system.  All 
data entered into the EDC system will be supported by source documentation 
(Section 10.1).
The Study Investigator or an authorized member of the study site personnel will make any 
necessary corrections to the eCRF.  All change information, including the date and person 
performing the corrections, will be available via the audit trail, which is part of the EDC 


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system.  For any correction, a reason for the alteration will be provided.  The eCRFs will 
be reviewed periodically for completeness, legibility, and acceptability by AbbVie 
personnel (or their representatives).  AbbVie (or their representatives) will also be allowed 
access to all source documents pertinent to the study in order to verify eCRF entries.  The 
Study Investigator will review the eCRFs for completeness and accuracy, and provide 
his/her electronic signature and date to eCRFs as evidence thereof.
Medidata will provide access to the EDC system for the duration of the trial through a 
password-protected method of internet access.  Such access will be removed from study 
sites at the end of the site's participation in the study.  Data from the EDC system will be 
archived on appropriate data media (CD-ROM, etc.) and provided to the Study 
Investigator at that time as a durable record of the study site's CRF data.  It will be 
possible for the investigator to make paper printouts from that media.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
An Investigator's Meeting will be held with AbbVie personnel, the Study Investigator, 
study site coordinators, and the AbbVie CRAs for this study.  This meeting will include a 
detailed discussion of the protocol, performance of study procedures, CRFs, completion 
of logs, and specimen collection methods.  In addition to, or instead of, the Investigator's 
Meeting, the study site personnel may be trained on the study procedures by an AbbVie 
CRA at the study initiation visit.  Each study site will be given a CRF completion 
guideline and laboratory manual for reference.
The AbbVie CRAs will monitor each study site throughout the study.  Source document 
review will be performed against entries in the EDC system and a quality assurance check 
will be performed to ensure that the Study Investigator is complying with the protocol and 
all global and local regulations.


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All data recorded on paper CRFs will be hand-entered in the database and verified by a 
double-key entry procedure at AbbVie. 
All central laboratory results will be electronically transferred from the central laboratory 
to the study database.
A review of the data will be conducted by a physician and clinical review team at AbbVie 
as specified in the safety review plan.
12.0
Use of Information
12.1
Use of Information
All information concerning adalimumab and AbbVie's operations, such as AbbVie's 
patent applications, formulas, manufacturing processes, basic scientific data, or 
formulation information, supplied by AbbVie and not previously published is considered 
confidential information.
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by AbbVie in connection with the development of 
adalimumab.  This information is disclosed as deemed necessary by AbbVie to other 
clinical investigators, other pharmaceutical companies, and to regulatory agencies and 
other governmental agencies. To allow for the use of the information derived from this 
clinical study, and to ensure complete and thorough analyses, the Study Investigator is 
obligated to provide AbbVie with complete test results and all data developed in this 
study and to provide direct access to all source data/documents for trial-related 
monitoring, audits, IEC/IRB review, and regulatory inspection.
This confidential information shall remain the sole property of AbbVie, shall not be 
disclosed to others without the written consent of AbbVie.
The Study Investigator will maintain a confidential subject identification code list of all 
subjects enrolled in the study (by name and subject number).  This will be maintained at 
the study site and will not be retrieved by AbbVie.


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Any exploratory research/validation studies that may be done using samples from this 
study will be experimental in nature and the results will not be suitable for clinical 
decision making or patient management.  Hence, the Study Investigator, the designated 
surgeon, the subject, and the subject's physician (if different from the Study Investigator 
or designated surgeon) will not be informed of individual results should analyses be 
performed, nor will anyone not directly involved in this research.  Correspondingly, 
researchers will not have access to subject identifiers.  Individual results will not be 
reported to anyone not directly involved in this research other than for regulatory 
purposes.  Aggregate data from optional exploratory research/validation studies from this 
study may be used in scientific publications or presented at medical conventions.  
Exploratory research/validation studies data will be published or presented only in a way 
that does not identify any individual subject.
12.2
Publication
Core publication(s) will be authored by Study Investigator(s) and study designated 
surgeons specified by AbbVie who contribute significantly to the implementation and 
conduct of the study and non-study site personnel who contribute substantially to the 
design, interpretation, or analysis of the study (e.g., AbbVie personnel, consultants).  
AbbVie scientists making significant contributions to the study will be included in the list 
of authors.
Development of the core publication will be coordinated by a publication committee, 
whose membership will include Study Investigators and surgeons who provided 
significant input into study design, implementation, conduct, and interpretation, in 
addition to AbbVie personnel responsible for study conduct and/or analyses.
A name author approach will be utilized if this is a requirement of the journal selected for 
publication, or if additional publications are agreed (authors to be agreed upon by the 
publication committee).  The named author approach will need sanction of the publication 
committee.


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13.0
Completion of the Study
The investigator will conduct the study in compliance with the protocol and complete the 
study within the timeframe specified in the contract between the Study Investigator and 
AbbVie.  Continuation of this study beyond this date must be mutually agreed upon in 
writing by both the Study Investigator and AbbVie.  The Study Investigator will provide a 
final report to the IEC/IRB following conclusion of the study, and will forward a copy of 
this report to AbbVie.
AbbVie will select the Coordinating Investigator from the Study Investigators who 
participate in the study.  Selection criteria for this investigator will include level of 
participation as well as significant knowledge of the clinical research, study drug, and 
study protocol.  The Coordinating Investigator for the study will review and sign the final 
study report in accordance with the European Agency for the Evaluation of Medicinal 
Products (EMEA) Guidance on Investigator's Signature for Study Reports.
The end-of-study is defined as the date of the last subject's last visit or the actual date of 
follow-up contact, whichever is later.


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14.0
Investigator's Agreement
1.
I have received and reviewed the Summary of Product Characteristics for Humira.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title
A Phase 4, Double-Blind, Randomised, Placebo-Controlled 
Multicenter Study to Assess the Safety and Efficacy of Adalimumab 
Used in Conjunction with Surgery in Subjects with Moderate to 
Severe Hidradenitis Suppurativa
Protocol Date:
13 December 2017
Signature of Study Investigator
Date
Name of Study Investigator (printed or typed)


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15.0
Reference List
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2.
Riis PT, Søeby K, Saunte DM, et al.  Patients with hidradenitis suppurativa carry a 
higher systemic inflammatory load than other dermatological patients.  Arch 
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3.
Wolkenstein P, Loundou A, Barrau K, et al.  Quality of life impairment in 
hidradenitis suppurativa:  a study of 61 cases.  J Am Acad Dermatol.  
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4.
Matusiak e, Bieniek A, Szepietowski JC.  Hidradenitis suppurativa markedly 
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5.
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2015;16(1):61-5.
6.
Hong J, Koo B, Koo J.  The psychosocial and occupational impact of chronic skin 
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7.
Fitzsimmons JS, Guilbert PR, Fitzsimmons EM.  Evidence of genetic factors in 
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8.
Jemec GB.  The symptomatology of hidradenitis suppurativa in women.  Br J 
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Lookingbill DP.  Yield from a complete skin examination.  Findings in 1157 new 
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Jemec GB, Heidenheim M, Nielsen NH.  The prevalence of hidradenitis 
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1996;35(2 Pt 1):191-4.


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11.
Revuz JE, Canoui-Poitrine F, Wolkenstein P, et al.  Prevalence and factors 
associated with hidradenitis suppurativa:  results from two case-control studies.  
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12.
Zouboulis CC, Desai N, Emtestam L, et al.  European S1 guideline for the 
treatment of hidradenitis suppurativa/acne inversa.  J Eur Acad Dermatol Venereol.  
2015;29(4):619-44.
13.
Saunte DM, Boer J, Stratigos A, et al.  Diagnostic delay in hidradenitis suppurativa 
is a global problem.  Br J Dermatol.  2015;173(6):1546-9.
14.
Miller IM, McAndrew RJ, Hamzavi I.  Prevalence, risk factors, and comorbidities 
of hidradenitis.  Dermatol Clin.  2016;34(1):7-16.
15.
Jemec GB, Kimball AB.  Hidradenitis suppurativa:  epidemiology and scope of the 
problem.  J Am Acad Dermatol.  2015;73 (5 Suppl):S4-7.
16.
von der Werth JM, Williams HC.  The natural history of hidradenitis suppurativa.  
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17.
Onderdijk AJ.  Depression in patients with hidradenitis suppurativa.  J Eur Acad 
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18.
Kimball AB, Jemec GB, Yang M, et al.  Assessing the validity, responsiveness and 
meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the 
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19.
Jemec GB, Revuz J.  Treatment.  In:  Jemec GB, Revuz J, Leyden J, editors.  
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Layton A.  Pathology of Hidradenitis Suppurativa.  In:  Jemec GB, Revuz J, 
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21.
van der Zee HH, de Ruiter L, van den Broecke DG, et al.  Elevated levels of 
tumour necrosis factor (TNF)-U, interleukin (IL)-1W and IL-10 in hidradenitis 
suppurativa skin:  a rationale for targeting TNF-U and IL-1W.  Br J Dermatol.  
2011;164(6):1292-8.


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22.
Jemec GB.  Predicting response to anti-TNF-alpha treatment in hidradenitis 
suppurativa.  Br J Dermatol.  2013;168(2):233.
23.
Bettoli V, Join-Lambert O, Nassif A.  Antibiotic treatment of hidradenitis 
suppurativa.  Dermatol Clin.  2016;34(1):81-9.
24.
Clemmensen OJ.  Topical treatment of hidradenitis suppurativa with clindamycin.  
Int J Dermatol.  1983;22(5):325-8.
25.
Boer J, van Gemert MJ.  Long-term results of isotretinoin in the treatment of 
68 patients with hidradenitis suppurativa.  J Am Acad Dermatol.  1999;40(1):73-6.
26.
Blok JL, van Hattem S, Jonkman MF, et al.  Systemic therapy with 
immunosuppressive agents and retinoids in hidradenitis suppurativa:  a systematic 
review.  Br J Dermatol.  2013;168(2):243-52.
27.
Scheinfeld N.  Hidradenitis suppurativa:  a practical review of possible medical 
treatments based on over 350 hidradenitis patients.  Dermatol Online J.  
2013;19(4):1.
28.
Jemec GB.  Clinical practice.  Hidradenitis suppurativa.  N Engl J Med.  
2012;366(2):158-64.
29.
Verdolini R, Clayton N, Smith A, et al.  Metformin for the treatment of hidradenitis 
suppurativa:  a little help along the way.  J Eur Acad Dermatol Venereol.  
2013;27(9):1101-8.
30.
Watson JD.  Hidradenitis suppurativa--a clinical review.  Br J Plast Surg.  
1985;38(4):567-9.
31.
Mandal A, Watson J.  Experience with different treatment modules in hidradenitis 
suppurativa:  a study of 106 cases.  Surgeon.  2005;3(1):23-6.
32.
Morgan WP, Harding KG, Hughes LE.  A comparison of skin grafting and healing 
by granulation, following axillary excision for hidradenitis suppurativa.  Ann R 
Coll Surg Engl.  1983;65(4):235-6.
33.
Ritz JP, Runkel N, Haier J, et al.  Extent of surgery and recurrence rate of 
hidradenitis suppurativa.  Int J Colorectal Dis.  1998;13(4):164-8.


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34.
van der Zee HH, Prens EP, Boer J.  Deroofing:  a tissue-saving surgical technique 
for the treatment of mild to moderate hidradenitis suppurativa lesions.  J Am Acad 
Dermatol.  2010;63(3):475-80.
35.
Balik E, Eren T, Bulut T, et al.  Surgical approach to extensive hidradenitis 
suppurativa in the perineal/perianal and gluteal regions.  World J Surg.  
2009;33(3):481-7.
36.
Tierney E, Mahmoud BH, Hexsel C, et al.  Randomized controlled trial for the 
treatment of hidradenitis suppurativa with a neodymium-doped yttrium aluminum 
garnet laser.  Dermatol Surg.  2009;35(8):1188-98.
37.
Lapins J, Marcusson JA, Emtestam L.  Surgical treatment of chronic hidradenitis 
suppurativa:  CO2 laser stripping-secondary intention technique.  Br J Dermatol.  
1994;131(4):551-6.
38.
Lapins J, Sartorius K, Emtestam L.  Scanner-assisted carbon dioxide laser surgery:  
a retrospective follow-up study of patients with hidradenitis suppurativa.  J Am 
Acad Dermatol.  2002;47(2):280-5.
39.
Patel SH, Robbins JR, Hamzavi I.  Radiation therapy for chronic hidradenitis 
suppurativa.  J Nucl Med Radiat Ther.  2013;4(146):2.
40.
Adams DR, Gordon KB, Devenyi AG, et al.  Severe hidradenitis suppurativa 
treated with infliximab infusion.  Arch Dermatol.  2003;139(12):1540-2.
41.
Moul DK, Korman NJ.  Severe hidradenitis suppurativa treated with adalimumab.  
Arch Dermatol.  2006;142(9):1110-2.
42.
Giamarellos-Bourboulis EJ, Pelekanou E, Antonopoulou A, et al.  An open-label 
phase II study of the safety and efficacy of etanercept for the therapy of 
hidradenitis suppurativa.  Br J Dermatol.  2008;158(3):567-72.
43.
Kimball AB.  Evaluating optimal medium-term dosing strategy for adalimumab in 
patients with moderate-to-severe hidradenitis suppurativa based on analysis of 
integrated results from the PIONEER I and II Phase 3, randomized, 
placebo-controlled trials.  World Congress Dermatology 2015;Abstract.


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44.
Humira.  [Summary of Product Characteristics.]  Available from:  
www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000481/WC500.  Accessed on:  24 June 2016.
45.
Alharbi Z, Kauczok J, Pallua N.  A review of wide surgical excision of hidradenitis 
suppurativa.  BMC Dermatol.  2012;12:9.
46.
Ellis LZ.  Hidradenitis suppurativa:  surgical and other management techniques.  
Dermatol Surg.  2012;38(4):517-36.
47.
Rosenfeld G, Qian H, Bressler B.  The risks of post-operative complications 
following pre-operative infliximab therapy for Crohn's disease in patients 
undergoing abdominal surgery:  a systematic review and meta-analysis.  J Crohns 
Colitis.  2013;7(11):868-77.
48.
Nasir BS, Dozois EJ, Cima RR, et al.  Perioperative anti-tumor necrosis factor 
therapy does not increase the rate of early postoperative complications in Crohn's 
disease.  J Gastrointest Surg.  2010;14(12):1859-66.
49.
Nørgard BM, Nielsen J, Qvist N, et al.  Pre-operative use of anti-TNF-a agents and 
the risk of post-operative complications in patients with Crohn's disease – a 
nationwide cohort study.  Aliment Pharmacol Ther.  2013;37(2):214-24.
50.
Adalimumab Integrated Summary of Safety R&D/13/1033, October 2014 
[information on file].
51.
Adalimumab Integrated Summary of Efficacy R&D/13/1032, September 2014 
[information on file].


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Appendix A.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the Good Clinical Practices 
(GCP) and local regulations and guidelines governing the study at the site location.  In 
signing the Investigator Agreement in Section 14.0 of this protocol, the investigator is 
agreeing to the following:
1.
Conducting the study in accordance with the relevant, current protocol, making 
changes in a protocol only after notifying AbbVie, except when necessary to 
protect the safety, rights or welfare of subjects.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed 
consent and ethics committees (e.g., independent ethics committee [IEC] or 
institutional review board [IRB]) review and approval of the protocol and 
substantial amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
Reading the information in the Summary of Product Characteristics (or local 
regulatory label), including the instructions for use and the potential risks and side 
effects of adalimumab.
5.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
6.
Maintaining adequate and accurate records of the conduct of the study, making 
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
7.
Maintaining records demonstrating that an ethics committee reviewed and 
approved the initial clinical investigation and all substantial amendments.


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8.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
9.
Following the protocol and not make any changes in the research without ethics 
committee approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.


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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Global Medical Affairs
Clinical
Statistics
Regulatory Affairs
Clinical Program Development


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Appendix C.
Schedule of Activities
Activity
Period A
Period B
Period C
Unscheduled 
Study Visit
70-Day 
Call
Screening 
(Day –30 to 
Day –7)
Baseline 
(Day 1)
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
13
Wk 
14
Wk 
15
Wk 
17
Wk 
20
Wk 24 or 
Premature 
Discontinuation 
Visit
Informed Consent
X
Inclusion/Exclusion Criteria
X
Xa
Medical/Surgical History
X
Xa
Eligibility Visit with Surgeon
X
Prior and Concomitant Therapy 
Assessmentb
X
Xa
X
X
X
X
X
X
X
X
X
X
X
Alcohol Use
X
Nicotine Use
X
X
X
Physical Exam
X
X
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
X
Xc
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
Height
Xd
Waist Circumference
X
X
CXR/ECG
X
Xe
TB Screening
X
General Labs:  Chemistry and 
Haematology
Xg
Xg
X
Xf
X
X
X
Xf
Pregnancy Tests
Xh
Xi
Xi
Urinalysisj
X
X
X
X
X
X
X
X


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Activity
Period A
Period B
Period C
Unscheduled 
Study Visit
70-Day 
Call
Screening 
(Day –30 to 
Day –7)
Baseline 
(Day 1)
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
13
Wk 
14
Wk 
15
Wk 
17
Wk 
20
Wk 24 or 
Premature 
Discontinuation 
Visit
Hepatitis B Screen
X
HIVk and ANA/Anti dsDNA
X
hsCRP
X
X
X
HbA1c
X
X
X
Lipid Testing
Xf
Xf
Xf
PK Measurementsl
X
X
X
X
X
X
X
X
AAA Measurementsm
X
X
X
X
X
X
X
Monitor Adverse Eventsn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Digital Imagingo
X
X
X
X
X
X
X
X
Doppler Ultrasoundp
X
X
X
X
X
Dispense Study Drugq
X
X
Xq
X
X
X
Administer Study Drugr
X
X
X
X
X
X
X
X
X
X
Hurley Stage
X
Xt
X
X
Lesion Countss
X
X
X
X
X
X
X
X
X
X
X
DLQIw (10 items)
X
X
X
X
X
EQ-5Dw (5 items)
X
X
X
X
X
X
HSIAu,w (18 items)
X
X
X
X
X
HS-PGA-SPw (2 items)
X
X
X
X
X
X
X
X
X
HS-PGICw (1 item)
X
X
X
X
X
X
X
HSSA-7du,w (9 items)
X
X
X
X
X
X


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Activity
Period A
Period B
Period C
Unscheduled 
Study Visit
70-Day 
Call
Screening 
(Day –30 to 
Day –7)
Baseline 
(Day 1)
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
13
Wk 
14
Wk 
15
Wk 
17
Wk 
20
Wk 24 or 
Premature 
Discontinuation 
Visit
SF-12w (12 items)
X
X
X
X
TSQMv,w (14 items)
X
X
X
X
X
WPAI:SHPw (6 items)
X
X
X
X
Surgical/ICU/Hospital Days
X
X
X
X
X
X
Follow-Up Telephone Call
Xx
a.
Update inclusion/exclusion, prior and concomitant therapy, and medical history information to assure subject eligibility.
b.
Confirm ongoing antiseptic wash requirement at every visit on the concomitant medication page.
c.
A full physical exam is required at the Screening, Baseline and Week 24 or the Premature Discontinuation Visit if subject discontinues prior to Week 24.  A symptom directed 
physical examination should be performed at other visits if, in the opinion of the Study Investigator, it is warranted by the subject's AE status or on review of symptoms.
d.
Height will be measured at Baseline and Waist Circumference will be measured at Baseline and Week 12.
e.
Subjects will have a repeat ECG or CXR at Week 24 or the Premature Discontinuation Visit, only if in the opinion of the Study Investigator clinically significant AEs develop 
during the study that warrant a repeat ECG or CXR.
f.
Subject should be fasting at Baseline and Weeks 12 and 24.  Please refer to the laboratory manual for further instructions.
g.
Lab assessments will only need to be repeated at Baseline if the time between Screening and Baseline is greater than 14 days, or if the subject's health status has changed to 
warrant a repeat test.  The chemistry at Baseline should be fasting.  If the screening period is 14 days or less, and lab assessments are not repeated, then Screening labs should 
be fasting.
h.
All females of childbearing potential will have a serum pregnancy test at Screening that is performed at the central laboratory.
i.
All females of childbearing potential will have a urine sample collected at Baseline and at Week 24 or the Premature Discontinuation Visit (conducted by the site).  (If 
required by local regulatory authorities, monthly urinary pregnancy tests will be performed locally by designated study personnel.)  Any subject with a positive urine 
pregnancy test must have a negative serum test performed at the central laboratory prior to enrollment or continuation in the study.
j.
Dipstick urinalysis will be conducted by the central laboratory at required study visits.  A microscopic analysis will be performed in the event the dipstick results show 
protein, ketones or blood greater than negative, or glucose greater than normal.


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k.
If required by country regulatory authorities to confirm eligibility, subjects will be tested for antibodies to the HIV, and document that the test has been performed.  The 
testing is to be done at a local lab.  A subject will not be eligible for study participation if test results indicate a positive HIV infection.  AbbVie will not receive results from 
the testing and not be made aware of any positive results.
l.
Blood samples must be obtained prior to dosing.
m.
AAA samples are not collected as separate venipuncture; they are pipetted from the PK serum.
n.
All AEs reported from the time of study drug administration until approximately 70 days following discontinuation of study drug administration will be collected.  SAEs will 
be collected from the time the subject signed the study-specific informed consent until approximately 70 days following discontinuation of study drug administration (See 
Sections 5.3.1.1 Study Procedures – Follow-up telephone call and Section 6.1.4 Adverse Event Collection Period).
o.
A subset of subjects at pre-selected study sites will have photographs taken of their HS surgical site at Baseline, Weeks 4, 12, 13 (post-surgical), 15, 17, 20 and 24 or at the 
Premature Discontinuation Visit if the subjects discontinues prior to Week 24.
p.
A subset of subjects at pre-selected study sites will undergo Doppler Ultrasound examination Baseline, Week 4, Week 12, Week 17, and Week 24 or at the Premature 
Discontinuation Visit if the subjects discontinues prior to Week 24.  During Period A (pre-surgery) examination will be performed on all HS-affected anatomical regions.  
During Period C (post-surgery) examination will be performed on all non-surgical HS-affected anatomical regions.
q.
Study drug will be dispensed via Interactive Response Technology (IRT) at each Study Visit.  An adequate amount should be dispensed in order to ensure enough study drug 
to cover the weekly injections until the next Study Visit.  At Week 12, the Study Investigator should dispense study drug for Weeks 13 and 14, if the investigator is not the 
designated surgeon.
r.
At Study Visits the study drug will be administered by the subject with observation by qualified study personnel to ensure proper technique.
s.
The number, location, longest distance between relevant lesions, and whether the lesions are separated by normal-appearing skin will be measured.  The site is responsible for 
counting lesions that received intervention (Section 5.2.3.2) as permanently present in the lesion counts from the date of intervention.
t.
Study site must enter worst Hurley stage across all body regions into IRT.
u.
The questionnaire shall not be used for any research purposes whatsoever without express prior written permission from AbbVie.
v.
Only the treatment efficacy subscale of the TSQM will be used.
w.
It is preferred that the staff that assists patients with PRO completion should not be the same staff member that administers the injections at clinic visits.
x.
Study site personnel will contact all subjects by telephone at Weeks 6 and 10 to monitor whether any signs and symptoms of a skin or soft tissue infection are present near or 
at any HS lesion (see Section 5.1.1) and approximately 70 days after the last dose of study drug (except as described in Section 5.3.1.1 Study Procedures – Follow-up 
telephone call) to determine the status of any ongoing AEs/SAEs or the occurrence of any new AE/SAE.  


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Appendix D.
Optional Exploratory Research and Validation Studies – Schedule of Activities
Activity
Period A
Period B
Period C
Unscheduled 
Study Visit
70-Day 
Call
Screening 
(Day –30 to 
Day –7)
Baseline 
(Day 1)
Wk 
2
Wk 
4
Wk 
8
Wk 
12
Wk 
13
Wk 
14
Wk 
15
Wk 
17
Wk 
20
Wk 24 or 
Premature 
Discontinuation 
Visit
Informed Consent for Exploratory 
Research and Validation Studiesa
X
Pharmacogenetic Samplea,b
X
Epigenetic Samplea,b
X
X
X
X
X
Transcriptomic Samplea,b
X
X
X
X
X
Serum and Plasmaa,b
X
X
X
X
X
Peripheral Blood Mononuclear 
Cellsa,b
X
X
X
X
X
Microbiome Swaba,b
X
X
X
X
X
Surgical Resection Punch Biopsiesa,b
X
Skin Punch Biopsiesa,b
X
Xc
X
a.
Subjects must sign and date the separate informed consent before any of these optional exploratory research and validation studies samples may be collected (see Section 9.3).  
A subject may participate in the main study whether or not that subject volunteers to the collection of these optional samples.
b.
Blood and tissue samples must be obtained prior to dosing.
c.
Collected only from subjects who will not undergo surgery.


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Appendix E.
Lesion Counts – Sample
Lesion Countsa
Abscess
Non-Draining 
Fistula
Draining 
Fistula
Non-Inflammatory 
Nodule
Inflammatory 
Nodule
Hypertrophic 
Scar
Longest 
Distance 
(mm) 
Between 
2 Relevant 
Lesionsb
Intervening 
Normal 
Appearing 
Tissue 
(Yes or No)c
Left Axilla
Right Axilla
Left Sub/inframammary Area
Right Sub/inframammary Area
Intermammary Area
Left Buttock
Right Buttock
Left Inguino-crural Foldd
Right Inguino-crural Foldd
Perianal
Perineal
Other
Totals
a.
Lesion counts are to be recorded at every Study Visit in Period A and Period C.
b.
If only 1 lesion, record diameter of that single lesion.
c.
Are all lesions in this area clearing separated by normal appearing tissue?  Answer:  'Yes' or 'No'
d.
Includes the immediate adjacent area.


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Appendix F.
Dermatology Life Quality Index (DLQI) – Example
The aim of this questionnaire is to measure how much your skin problem has 
affected your life OVER THE LAST WEEK.  Please check K one box for each 
question.
Question
Response
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?
If "No," over the last week how much has your skin been a 
problem at work or studying?
Very much

A lot

A little

Not at all

Not relevant 
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.
©AY Finlay, GK Khan, April 1992, This must not be copied without the permission of the authors.


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Appendix G.
EuroQoL EQ-5D – Example
By placing a checkmark in one box in each group below, please indicate which statements 
best describe your own health state today.
Mobility
I have no problems in walking about

I have some problems in walking about

I am confined to bed

Self-Care
I have no problems with self-care

I have some problems washing or dressing myself

I am unable to wash or dress myself

Usual Activities (e.g., work, study, housework, family or leisure activities)
I have no problems with performing my usual activities

I have some problems with performing my usual activities

I am unable to perform my usual activities

Pain/Discomfort
I have no pain or discomfort

I have moderate pain or discomfort

I have extreme pain or discomfort

Anxiety/Depression
I am not anxious or depressed

I am moderately anxious or depressed

I am extremely anxious or depressed

©1998 EuroQol Group.  EQ-5D™ is a trade mark of the EuroQol Group.


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©1998 EuroQol Group.  EQ-5D™ is a trade mark of the EuroQol Group.


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Appendix H.
Hidradenitis Suppurativa Impact Assessment – Example
Instructions:  This questionnaire includes 18 questions about the impacts that you may 
experience associated with your Hidradenitis Suppurativa (HS).  Hidradenitis Suppurativa 
is a skin condition that affects areas with sweat glands such as the underarms, breasts, 
inner thighs, groin, and buttocks.  People often refer to their HS as boils, cysts, or lesions 
on their skin.
Please clearly mark an "x" in the box ( ) that best describes how you have been affected 
by your HS in the past 7 days.  There are no right or wrong answers to any of the 
questions.
[Example of HSIA in process of being reformatted for this protocol.]


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Appendix I.
Hidradenitis Suppurativa Patient's Global Assessment of Skin Pain 
– Example


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Appendix J.
Hidradenitis Suppurativa Patient Global Impression Change –
Example
1.
Since your last visit, how would you rate your pain due to your Hidradenitis 
Suppurativa (HS)?
 Very much worse
 Much worse
 A little worse
 No change
 A little better
 Much better
 Very much better


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Appendix K.
Hidradenitis Suppurativa Symptom Assessment – 7 Day Recall –
Example
Instructions:  This questionnaire includes nine questions about the symptoms you may 
experience associated with your Hidradenitis Suppurativa (HS).  Hidradenitis Suppurativa 
is a skin condition that affects areas with sweat glands such as the underarms, breasts, 
inner thighs, groin, and buttocks.  People often refer to their HS as boils, cysts, or lesions 
on their skin. 
Please clearly mark an "x" in the box () that best describes how severe your HS 
symptoms were over the past 7 days.  There are no right or wrong answers to any of the 
questions.
1.
Over the past 7 days, what was the worst pain you felt in the area(s) affected by 
your HS?
No pain at all
Extreme pain


0
1
2
3
4
5
6
7
8
9
10
2.
Over the past 7 days, what was the worst drainage you had in the area(s) affected 
by your HS?
No drainage at all
Extreme drainage


0
1
2
3
4
5
6
7
8
9
10
3.
Over the past 7 days, how red was your skin in the area(s) affected by your HS?
Not red at all
Extremely red


0
1
2
3
4
5
6
7
8
9
10


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4.
Over the past 7 days, how tender was your skin in the area(s) affected by your HS?
Not at all tender
Extremely tender


0
1
2
3
4
5
6
7
8
9
10
5.
Over the past 7 days, how swollen was your skin in the area(s) affected by your 
HS?
Not at all swollen
Extremely swollen


0
1
2
3
4
5
6
7
8
9
10
6.
Over the past 7 days, how hard did you skin feel in the area(s) affected by your 
HS?
Note: Please do not consider any hardness that you may have from the scars left on 
your skin from HS. 
Not at all hard
Extremely hard


0
1
2
3
4
5
6
7
8
9
10
7.
Over the past 7 days, how hot was your skin in the area(s) affected by your HS?
Not at all hot
Extremely hot


0
1
2
3
4
5
6
7
8
9
10


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8.
Over the past 7 days, how bad was the smell coming from the area(s) affected by 
your HS?
No bad smell
Extremely bad smell


0
1
2
3
4
5
6
7
8
9
10
9.
Over the past 7 days, how itchy was your skin in the area(s) affected by your HS?
Not at all itchy
Extremely itchy


0
1
2
3
4
5
6
7
8
9
10


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Appendix L.
Short Form-12 – Example
[Sample not available, licensing in process.]


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Appendix M.
Treatment Satisfaction Questionnaire for Medication – Example


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Appendix N.
Work Productivity and Activity Impairment Questionnaire:  
Specific Health Problem – Example
The following questions ask about the effect of your hidradenitis suppurativa on your 
ability to work and perform regular activities.  Please fill in the blanks or circle a number, 
as indicated.
1.
Are you currently employed (working for pay)?
______NO____YES
If NO, check "NO" and skip to question 6.
The next questions are about the past 7 days, not including today.
2.
During the past seven days, how many hours did you miss from work because of 
problems associated with your hidradenitis suppurativa?  Include hours you missed 
on sick days, times you went in late, left early, etc. because of your hidradenitis 
suppurativa.  Do not include time you missed to participate in this study.
_________
HOURS
3.
During the past seven days, how many hours did you miss from work because of 
any other reason, such as vacation, holidays, time off to participate in this study?
_________
HOURS
4.
During the past seven days, how many hours did you actually work?
_________
HOURS (If "0," write "0" and skip to question 6.)


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5.
During the past seven days, how much did hidradenitis suppurativa affect your 
productivity while you were working?
Think about days you were limited in the amount or kind of work you could do, days you 
accomplished less than you would like, or days you could not do your work as carefully as 
usual.  If hidradenitis suppurativa affected your work only a little, choose a low number.  
Choose a high number if hidradenitis suppurativa affected your work a great deal.
Hidradenitis 
suppurativa had 
no effect on my 
work
________________________________
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
Hidradenitis 
suppurativa 
completely prevented 
me from working
6.
During the past seven days, how much did hidradenitis suppurativa affect your 
ability to do your regular daily activities, other than work at a job?
By regular activities, we mean the usual activities you do, such as work around the house, 
shopping, child care, exercising, studying, etc.  Think about times you were limited in the 
amount or kind of activities you could do and times you accomplished less than you would 
like.  If hidradenitis suppurativa affected your activities only a little, choose a low 
number.  Choose a high number if hidradenitis suppurativa affected your activities a 
great deal.
Hidradenitis 
suppurativa had 
no effect on my 
daily activities
________________________________
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
Hidradenitis 
suppurativa 
completely prevented 
me from doing my 
daily activities
WPAI:SHP (US English)


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Appendix O.
Clinical Study Site Personnel – Study Drug Dispensing Table
Visit
Dose
Dispense Study Drug for 
Weeks**
Number of 
Syringes Used 
Day of Visit
Number of Kits and Syringes 
per Kit Dispensed for Between 
Visits
Baseline
160 mg
(1st loading dose)
Week 1 (D1 or split over 
D1+D2)
4
(or 2 if split on 
two days)
2 kits (4 syringes)
Week 2
80 mg
(2nd loading 
dose)
Week 2 (Day 15)
40 mg/week
2
1 kit (2 syringes)
Week 4
40 mg/week
Weeks 4, 5, 6 and 7
1
2 kits (4 syringes)
Week 8
40 mg/week
Weeks 8, 9, 10, and 11
1
2 kits (4 syringes)
Week 12
40 mg/week
Weeks 12, 13, 14 and 15
1
2 kits (4 syringes)
Week 15
40 mg/week
Weeks 16 and 17
1
1 kit (2 syringes)
Week 17
40 mg/week
Weeks 18, 19, 20 and 21
1
2 kits (4 syringes)
Week 20
40 mg/week
Weeks 22, and 23
1
2 kits (4 syringes) resulting in 
1 kit/2 PFS* left over at study's 
end which should be destroyed if 
not being used as replacement.
*
PFS = Pre-filled syringes.
**
Study Investigators will ensure that enough study drug is dispensed at each visit to cover the subject until their next 
visit.


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Appendix P.
Subject Injection Instructions – Example Pre-Filled Syringe
1.
You will not administer injections to yourself at home on clinic visit days.  You or 
your helper will be taught on a clinic visit day how to give injections 
subcutaneously (under the skin, not in the muscle) and you will be asked to show 
the study staff you or your helpers ability to self-inject in the clinic.
2.
You will administering injections at home on Day 2 of Week 0 (if directed by your 
study doctor), on the first day of Weeks 5, 6, 7, 9, 10, 11, (ask your study doctor 
about Weeks 13 and 14), and on the first day of Weeks 16, 18, 19, 21, 22 and 
23 (last dose).
3.
Check your dosing chart to make sure you are giving yourself the injection on the 
same day of the week as your last injection and check the location of the last 
injection on your home chart so you choose a different location for the current 
injection
4.
Remove your carton from the refrigerator and remove one pre-filled syringe (there 
will be two syringes in the carton).  Put the other syringe (syringe 2) back in the 
carton and place the carton back in the refrigerator. 
5.
If your pre-filled syringe accidentally becomes frozen, do not use the syringe and 
contact your study doctor.
6.
Prepare a clean area where you will not be distracted.
7.
You may self-administer your injection or have a helper, someone who has been 
approved by the study staff, do so.
8.
Check the syringe to make sure the fluid in the syringe is clear and colorless.  If 
you notice anything unusual about the pre-filled syringe, such as the liquid is 
cloudy, discolored or has flakes in it or the syringe itself doesn't look right to you, 
contact your study doctor before administering your injection.  If there is a question 
or something unusual suspected by your study doctor, you may be required to 
return the carton with the full liquid amount in the syringe to your study doctor if 
requested to do so. 


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9.
Wash your hands with soap and warm water or have your helper do the same.  
Clean medical gloves are not necessary but may be preferred by your helper.
10.
If you or your helper is ready to administer your injection, have your alcohol swab, 
sharps container (a safe place to put your used syringes) and gauze or cotton ball 
ready.  
a.
As you or your helper was taught in the clinic, you will first swab the area with 
alcohol, being careful to go from the inside out in a circular motion, trying not to 
put alcohol on the same area of your skin twice.  
b. You will pinch together about 1 inch of skin on either side of your stomach or 
your upper thighs, remove the needle cap (do not try to put the cap back on after 
your injection) and stick the needle in with the needle slightly sideways at an angle 
as shown (see the pictures below).  
c.
Pull back slightly on the plunger.  
d. If blood does not appear push the plunger until all of the liquid is gone. 
e.
If blood appears in the syringe it means the tip of the needles has entered a blood 
vessel.  Do not begin the injection of the liquid.  Pull the needle out of the skin and 
dispose of that pre-filled syringe.
f.
Repeat the step 10 to choose and clean a new injection site.  Do not use the same 
syringe; instead use a new pre-filled syringe (syringe 2).


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11.
Remove the syringe and apply pressure with a cotton ball to the injected area.
12.
Immediately put the used syringe in your sharps container.
13.
Please return all used and unused syringes and empty boxes to the clinic on your 
next visit.


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14.
If an injection is missed or something occurs where the full dose cannot be 
injected, contact your study doctor immediately for further instructions.  Please 
record any missed doses on your subject dosing sheet.
15.
Remember to complete your dosing sheet after each injection and to call the study 
doctor if you are having problems administering your study medication.
Sample Home Chart for Injections


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Appendix Q.
Subject Dosing Chart – Example


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Appendix R.
Study Site Drug Accountability (by Subject) Log – Example
Subject 
Number
Kit 
Number
Date Dose 
Administered
Total Dose 
Administered 
(mg)
Total Volume 
Administered 
(mL)
Start 
Time of 
Dose
End time 
of Dose
:
:
:
:
:
:
Administered By
(Sign and Date)
Verified By
(Sign and Date)
I attest that the subject identified by number above, or designated helper (documented in 
source document as having been trained), has demonstrated safe administration of study 
drug on Date:  ______________ Time:  _________ and the subject is approved to 
self-administer or have study drug administered by their designated (trained) helper.
________________________________________
Name of Study Investigator or Designee
________________________________________
Signature of Study Investigator Designee






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Has been changed to read:
1 North Waukegan Road
North Chicago, IL USA 60064
Office:
Mobile:
Email:
Section 8.1.4.1  Primary Analysis of Efficacy
First paragraph
Add:  new last sentence
The 95% confidence intervals of treatment difference will also be provided.
Section 8.1.4.1  Primary Analysis of Efficacy
Add:  new last paragraph
In addition, a sensitivity analysis controlling for change from baseline in body weight 
using logistic regression models, for the primary efficacy endpoint.  Analysis details will 
be specified in the SAP prior to study unblinding and prior to database lock.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Global Medical Affairs
Global Medical Affairs
Statistics
CPPM
Regulatory Affairs
Biologics 
Clinical Program Development


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Has been changed to read:
Name
Title
Functional Area
Global Medical Affairs
Clinical
Statistics
Regulatory Affairs
Clinical Program Development



SAP_000.pdf: