Clinical trial NCT02904902
Conditions: Hidradenitis Suppurativa
Keywords: efficacy safety adalimumab japanese participants
Sponsor: AbbVie
Start date: 2016-09-06; Completion date: 2019-05-30
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study investigates efficacy, safety and pharmacokinetics of adalimumab in Japanese subjects with moderate to severe hidradenitis suppurativa (HS).

Detailed description:
Prior to initiation of this study, global Phase 2b study and pivotal Phase III studies were completed in the Western countries and market authorization of adalimumab was approved in United States (US) and European Union (EU) for the treatment of subjects with HS. The differences between this study and global studies include sample size, study design, duration, and race.

Arms: arm 1: Open-label adalimumab 160 mg subcutaneous injection at Week 0 (Baseline), 80 mg at Week 2, and 40 mg every week starting at Week 4. After Week 52, Participants who consent to receive the 80 mg eow dose, will switch from 40 mg ew to 80 mg eow at Week 0x (80 mg eow period until the end of the study).
Interventions: intervention 1: adalimumab
Intervention descriptions: intervention 1: Subcutaneous Injection

Protocol documents:
Prot_000.pdf: 
Adalimumab
M15-573 Protocol
1
1.0
Title Page
Clinical Study Protocol M15-573
A Phase 3 Multicenter, Open-Label, Single Arm Study 
of the Safety and Efficacy of Adalimumab in 
Japanese Subjects with Moderate to Severe 
Hidradenitis Suppurativa
AbbVie Investigational  
Product:
Adalimumab
Date:
07 July 2016
Development Phase:
3
Study Design:
Non-randomized, Open-label, Single-arm
EudraCT Number:
N/A
Investigators:
Multicenter Trial (Investigator information on file at 
AbbVie)
Sponsor:
AbbVie GK,
Sponsor/Emergency
  Contact:
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
NCT02904902


Adalimumab
M15-573 Protocol
2
1.1
Synopsis
AbbVie Inc.
Protocol Number:  M15-573
Name of Study Drug:  Adalimumab
Phase of Development:  3
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  07 July 2016
Protocol Title:  A Phase 3 Multicenter, Open-Label, Single Arm Study of the Safety and Efficacy of 
Adalimumab in Japanese Subjects with Moderate to Severe Hidradenitis Suppurativa
Objective:  The primary objective of this study is to evaluate the safety and efficacy of adalimumab in 
Japanese subjects with moderate to severe hidradenitis suppurativa (HS).
Investigators:  Multicenter
Study Sites:  Approximately 10 centers.
Study Population: Male or female Japanese subjects age 18 years or older with moderate to severe HS.
Number of Subjects to be Enrolled:  Approximately 15
Methodology:  
This study is an open-label, single arm study designed to investigate the safety and efficacy of 
adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa after 12 weeks of 
treatment, and to evaluate long-term safety, efficacy and tolerability.  The study will include a 35-day 
screening period, open-label treatment period and a Day 70 follow-up phone call following their last dose 
of study drug.  The treatment period is expected for at least 99 weeks until the time of approval for HS 
indication, or withdrawal of the marketing application in Japan.
All subjects will receive open-label subcutaneous injection of adalimumab 40 mg every week (ew) 
starting at Week 4, after 160 mg at Week 0 (Baseline) and 80 mg at Week 2.
The primary efficacy endpoint is the proportion of subjects achieving Hidradenitis Suppurativa Clinical 
Response (HiSCR) at Week 12.  HiSCR is defined as at least a 50% reduction in the total abscess and 
inflammatory nodule count (AN count) with no increase in abscess count and no increase in draining 
fistula count relative to Baseline.
Study visits will occur at Weeks -4 and -2 (in the Screening period), Baseline (Week 0), Weeks 2, 4, 8, 
12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or at the Premature Discontinuation visit.  After Week 52, 
study visits will occur every 12 weeks until the study end.
Additionally, all subjects will be contacted by phone 1 week before and after the Baseline visit to ensure 
daily pain assessments are being recorded, and at Week 6 and Week 10 to monitor whether any signs or 
symptoms of infection are present at or near an HS lesion.  If any signs or symptoms are reported at the 
time of the call, an unscheduled study visit will be conducted to assess whether an infection is present.  
Adverse events will be collected throughout the study.  Subjects who decide not to continue this study 
will have a Day 70 follow-up phone call following their last dose of study drug to determine the status of 
any ongoing adverse events (AEs) or serious adverse events (SAEs), or the occurrence of any new AEs or 
SAEs.  The Day 70 follow-up phone call will not be required for any subject who initiates adalimumab 
therapy not supplied in the context of the clinical trial after the end of the study participation.


Adalimumab
M15-573 Protocol
3
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion:
!
Subjects must have a diagnosis of HS;
!
Subjects must have any HS symptom at least 6 months prior to Baseline; 
!
HS lesions must be present in at least two distinct anatomic areas, one of which must be at least 
Hurley Stage II or Hurley Stage III;
!
Subject must have stable HS for at least 2 months (60 days) prior to Screening and also at the 
Baseline visit as determined by the investigator through subject interview and review of medical 
history; 
!
Subject must have a total abscess and inflammatory nodule (AN) count of greater than or equal to 3 
at the Baseline visit;
!
Subject has a negative TB screening assessment (including a PPD test or QuantiFERON-TB Gold 
test, or equivalent) and negative chest x-ray (CXR) (posterior-anterior [PA] and lateral view) at 
Screening;
!
Subject is judged to be in good general health, as determined by the Principal Investigator based 
upon the results of a medical history, physical examination, laboratory profile, CXR and a 12 lead 
ECG performed during the Screening period and confirmed at Baseline.
Main Exclusion:  
!
Prior treatment with adalimumab or other anti-TNF therapy (e.g., infliximab or etanercept), or 
participation in an adalimumab trial;
!
Subject received antibiotic treatment for HS within 28 days prior to the Baseline visit other than 
those allowed per protocol.  Subjects on permitted  oral antibiotic treatment (doxycycline or 
minocycline only) for HS who have not been on a stable dose for at least 28 days prior to the 
Baseline visit; 
!
Subject received oral concomitant analgesics (non-opioids and opioids) for HS-related pain within 
14 days prior to the Baseline visit; 
!
If entering the study on concomitant oral analgesics for non-HS-related pain:
o
Subject on opioid analgesics within 14 days prior to Baseline visit (opioid analgesics are not 
allowed);
o
Subject not on a stable dose of non-opioid oral analgesics for at least 14 days prior to the 
Baseline visit (PRN is not considered a stable dose).
!
Subject requires, or is expected to require, opioid analgesics for any reason (excluding tramadol);
!
Subject received prescription topical therapies for the treatment of HS within 14 days prior to the 
Baseline visit;
!
Subject received systemic non-biologic therapies for HS with potential therapeutic impact for HS 
less than 28 days prior to Baseline visit (other than permitted oral antibiotics);
!
Subject has a draining fistula count of greater than 20 at the Baseline visit;
!
Infection(s) requiring treatment with intravenous (IV) anti-infectives (antibiotics, antivirals, 
antifungals) within 30 days prior to Baseline or oral anti-infectives (antibiotics, antivirals, 
antifungals) within 14 days prior to Baseline, except as required as part of an anti-TB regimen;
!
Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) that may interfere 
with assessment of HS;


Adalimumab
M15-573 Protocol
4
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Exclusion (Continued):  
!
History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease;
!
History of invasive infection (e.g., listeriosis, histoplasmosis), human immunodeficiency virus 
(HIV);
!
Subject has an active systemic viral infection or any active viral infection including Hepatitis C that 
based on the investigator's clinical assessment make the subject an unsuitable candidate for the 
study;
!
Hepatitis B:  HBsAg positive (+) or detected sensitivity on the HBV-DNA PCR qualitative test for 
HBc Ab/HBsAb positive subjects;
!
Chronic recurring infections or active TB;
!
History of moderate to severe congestive heart failure (NYHA class III or IV), recent 
cerebrovascular accident and any other condition which, in the opinion of the investigator, would put 
the subject at risk by participation in the protocol;
!
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;
!
Female subjects who is pregnant, breastfeeding or is considering becoming pregnant during the study 
and for approximately 150 days after the last dose of study drug;
!
Subject currently has an adequate response to oral antibiotic treatment for HS.
Investigational Product:
Adalimumab
Doses:
160 mg Week 0 and 80 mg Week 2 followed by 40 mg every week (ew) 
starting at Week 4.
Mode of Administration:
Subcutaneously (SC)
Duration of Treatment:  Until approval of HS indication in Japan (at least 99 weeks)
Criteria for Evaluation:
Efficacy: 
The primary efficacy endpoint is the proportion of subjects achieving HiSCR at Week 12.  The study will 
provide long-term efficacy as well.
Pharmacokinetic:
Blood samples will be collected for the measurement of serum adalimumab concentrations at Baseline
(Week 0) and Weeks 2, 4, 8, 12, 16, 20, 24, 36, and 52, or at the Premature Discontinuation visit if the 
subject discontinues prior to Week 52.  Blood samples will be collected for the measurement of anti-
adalimumab antibody (AAA) at Baseline (Week0), Weeks 4, 12, 24, 36, and 52, or at the Premature 
Discontinuation visit if the subject discontinues prior to Week 52.
Safety:
Adverse events, laboratory data and vital signs will be assessed throughout the study.


Adalimumab
M15-573 Protocol
5
Statistical Methods:
Efficacy:  
The primary analysis will be the proportion of subjects achieving HiSCR at Week 12.
Secondary endpoints include:
1.
Proportion of subjects achieving AN count of 0, 1, or 2 at Week 12;
2.
Proportion of subjects achieving at least 30% reduction and at least 1 unit reduction from Baseline in 
Patient's Global Assessment of Skin Pain (NRS30) - at worst at Week 2; among subjects with 
baseline NRS ≥ 3;
3.
Change in modified Sartorius scale from Baseline to Week 12.
The degree of erythema will be assessed in each affected anatomic region as an additional secondary 
endpoint.
Efficacy variables will be analyzed at all scheduled visits.
The primary efficacy analysis will be carried out in the FAS Population, defined as all patients who 
received at least one dose of study drug and had at least one-post-treatment efficacy assessment in this 
study.  Non-responder imputation will be used as primary approach to impute the missing values, with 
last-observation-carried-forward.  Primary efficacy variable will be summarized by baseline value, 
baseline Hurley Stage (II/III), and antibiotic use (Y/N), if appropriate.
Secondary and other efficacy variables will be summarized in the FAS Population.  
Considering quite limited number of patients with HS in Japan and feasibility of the study conduct, 
15 subjects is set for sample size of this study.  The response rates of HiSCR at Week 12 in 
Study M11-810 and M11-313 were 59 % and 42% in the adalimumab ew group, and 28% and 26% in the 
placebo group, respectively.  Assuming the threshold clinical response rate of 25% and expected clinical 
response rate of 60% in adalimumab at Week 12, a sample size of 13 subjects will have 80.1% power to 
detect the difference of 35% in the primary endpoint and using one sample Chi-square test at one-sided 
2.5% significant level.
Pharmacokinetic:
Adalimumab trough serum concentrations will be summarized at each time point using descriptive 
statistics.  The results may be incorporated into a population pharmacokinetic analysis if the data 
warrants in order to estimate parameters such as apparent clearance (CL/F) and apparent volume of 
distribution (V/F) of adalimumab.
Immunogenicity:
AAA will be evaluated for each subject and rates of AAA positive will be calculated.  As appropriate, the 
effect of AAA on adalimumab pharmacokinetics, efficacy variable(s), and treatment-emergent adverse 
events may be evaluated.


Adalimumab
M15-573 Protocol
6
Statistical Methods: (Continued):
Safety:
All adverse events (AE), serious adverse events (SAE), AEs leading to discontinuation, and pre specified 
AEs of special interest will be collected during the study and up to approximately 70 days after the last 
dose of study drug for subjects who prematurely discontinue the study.  Safety analyses will be carried 
out using the Safety Population (subjects who received at least one dose of study drug).  Pretreatment 
AEs will be summarized as well.  A treatment-emergent AE 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.  The number and percent of subjects experiencing treatment-emergent AEs will be tabulated 
using the Medical Dictionary for Drug Regulatory Activities (MedDRA®) system organ class and 
preferred term.
Summaries (including percentages and event per 100 patient-years) of SAEs, deaths, AEs leading to 
discontinuation from the study, and prespecified AEs of special interest will be provided.  Mean change 
in laboratory variables and vital sign variables at each visit will be summarized for all treated subjects.  
For selected parameters, a listing of all subjects with any laboratory determination meeting Common 
Toxicity Criteria (CTC) of Grade 2 or higher will be provided.  Shift tables for changes from Baseline 
according to the normal range will also be provided.


Adalimumab
M15-573 Protocol
7
1.2
List of Abbreviations
Abbreviations
AAA
Anti-Adalimumab Antibody
AE
Adverse Event
AESI
Adverse Event of Special Interest
AN
Abscess and inflammatory Nodule 
BCG
Bacille Calmette-Guérin
bid
Twice a day
CDA
Clinical Drug Accountability
CL/F
Apparent serum clearance
CRF
Case Report Form
CRP
C-Reactive Protein
CXR
Chest X-ray
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EMA
European Medicines Agency.  European Agency for the Evaluation of 
Medicinal Products.
eow
Every Other Week
EQ-5D
Descriptive system of health-related quality of life states consisting of 
five dimensions
EU
European Union
ew
Weekly
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
HBcAb
Hepatitis B Core Antibody
HBsAb
Hepatitis B Surface Antibody
HBsAg
Hepatitis B Surface Antigen
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus


Adalimumab
M15-573 Protocol
8
HS
Hidradenitis Suppurativa
HiSCR
Hidradenitis Suppurativa Clinical Response
HS QoL
Hidradenitis Suppurativa Quality of Life
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IP
Investigational Product
IRB
Institutional Review Board
IV
Intravenous
IRT
Interactive response technology
LOCF
Last Observation Carried Forward
LOR
Loss of Response
MedDRA
Medical Dictionary for Regulatory Activities
MI
Myocardial Infarction
NRI
Non-Responder Imputation
NRS
Numeric Rating Scale
NRS30
At least a 30% reduction and at least 1 unit reduction from Baseline in 
Patient's Global Assessment of Skin Pain
OL
Open-Label
PA
posterior-anterior
PGA
Physician's Global Assessment
pH 
Power of Hydrogen Ion Concentration
PK
Pharmacokinetic
po
Oral
PML
Progressive Multifocal Leukoencephalopathy
POR
Proof of Receipt
PPD
Purified Protein Derivative
RA
Rheumatoid Arthritis
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAS
Statistical Analysis Software
SC
Subcutaneous
TA MD
Therapeutic Area Medical Director
TEAEs
Treatment Emergent Adverse Events
TB
Tuberculosis
TNF
Tumor Necrosis Factor


Adalimumab
M15-573 Protocol
9
TSQM
Treatment Satisfaction Questionnaire - Medication
US
United States 
V/F
Apparent volume of distribution
Wk
Week


Adalimumab
M15-573 Protocol
10
1.3
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.
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.
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
Inadequate 
Response to 
Antibiotics
An adequate trial of oral antibiotic therapy is considered to be at least 90 days in 
duration.  If, after at least 90 days (≥ 90 days) of oral antibiotic therapy, any of 
the following has occurred, subject will be considered to have had inadequate 
response, or loss of response, to oral antibiotics:
!
Progression of Hurley Stage (i.e., the Hurley Stage of at least one 
affected anatomic region has progressed from I – II, II – III, or I – III);
!
Subject requires at least one intervention (e.g., incision and drainage or 
intralesional injection of corticosteroid);
!
Subject experiences pain interfering with activities of daily living, with 
unsatisfactory relief from over-the-counter analgesics (e.g., ibuprofen or 
acetaminophen);
!
Subject experiences pain requiring opioids, including tramadol;
!
Subject experiences drainage interfering with activities of daily living 
(e.g., requires multiple dressing changes and/or changes of clothes 
daily);
!
Subject experiences an increase in the number of anatomic regions 
affected by HS;
!
Subject experiences at least one new abscess or one new draining fistula.
!
Sites are encouraged to contact AbbVie TA MD to confirm if the 
definition of inadequate response or loss of response has been met.


Adalimumab
M15-573 Protocol
11
Inflammatory 
nodules
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.
Intolerance to 
Antibiotics
A subject is defined as intolerant to oral antibiotic when oral antibiotic therapy 
has been discontinued by a physician as a result of a significant adverse reaction 
to oral antibiotic administration.
A reaction will be considered significant if the adverse reaction is at least 
moderately severe (i.e., the adverse event causes the subject discomfort and 
interrupts the subject's usual activities or function).  Examples of significant 
adverse reactions include, but are not limited to:
!
nausea resulting in decreased oral intake;
!
macular or papular eruption or erythema associated with pruritus or 
other associated symptoms;
!
dizziness/disequilibrium/lightheadedness/vertigo interfering with 
function;
!
allergic reaction manifesting as rash, flushing, urticaria, dyspnea, or 
drug fever ≥ 38°C;
!
diarrhea manifesting as an increase in stool frequency of at least 4 stools 
per day over Baseline.
Sites are encouraged to contact AbbVie TA MD to confirm if the definition of 
intolerance has been met.
Loss of Response 
(LOR)
An AN count that is greater than the average of AN counts at Baseline and Week 
12.  It is a loss of at least 50% of the improvement (reduction) in the AN count 
achieved from baseline to Week 12.
Calculation:  AN > ½ * (Baseline AN count + Week 12 AN count)
Baseline AN Count
Week 12 AN Count
Average of AN Counts
Minimum Count to 
Meet LOR
10
1
½ * (10 + 1) = 5.5
6
10
4
½ * (10 + 4) = 7
8
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 
nodules
Non-tender or minimally tender, non-erythematous nodules.
Protocol Allowed 
Intervention
A protocol-allowed intervention is defined as incision and drainage, or injection 
of intralesional triamcinolone acetonide suspension (at a dose of 50 mg/5 mL, up 
to 0.5 mL).
Worsening or 
Absence of 
An AN count that has been ≥ Baseline AN count at two consecutive visits 
occurring ≥ 14 days apart.


Adalimumab
M15-573 Protocol
12
Improvement
2.0
Table of Contents
1.0
Title Page..................................................................................1
1.1
Synopsis .....................................................................................................2
1.2
List of Abbreviations .................................................................................7
1.3
Definition of Terms..................................................................................10
2.0
Table of Contents...................................................................12
3.0
Introduction ...........................................................................16
3.1
Differences Statement..............................................................................16
3.2
Hidradenitis Suppurativa .........................................................................16
3.3
Current Treatments ..................................................................................17
3.4
Adalimumab Overview............................................................................18
3.5
Benefits and Risks....................................................................................22
4.0
Study Objective......................................................................24
5.0
Investigational Plan...............................................................24
5.1
Overall Study Design and Plan:  Description ..........................................24
5.2
Selection of Study Population..................................................................27
5.2.1
Inclusion Criteria .....................................................................................27
5.2.2
Exclusion Criteria ....................................................................................29
5.2.3
Prior and Concomitant Therapy...............................................................32
5.2.3.1
Prior Therapy ...........................................................................................33
5.2.3.2
Concomitant Therapy...............................................................................33
5.2.3.3
Prohibited Therapy...................................................................................38
5.2.4
Contraception Recommendations ............................................................39
5.3
Efficacy, Pharmacokinetic, and Safety Assessments/Variables ..............40
5.3.1
Safety and Efficacy Measurements Assessed and Flow Chart ................40
5.3.1.1
Study Procedures .....................................................................................45
5.3.2
Drug Concentration Measurements .........................................................60
5.3.2.1
Collection of Samples for Analysis .........................................................60
5.3.2.2
Handling/Processing of Samples .............................................................61
5.3.2.3
Disposition of Samples ............................................................................61
5.3.2.4
Measurement Methods.............................................................................61


Adalimumab
M15-573 Protocol
13
5.3.3
Efficacy Variables....................................................................................61
5.3.3.1
Primary Variable......................................................................................61
5.3.3.2
Secondary Efficacy Variables..................................................................62
5.3.4
Safety Variables .......................................................................................64
5.3.5
Pharmacokinetic Variables ......................................................................64
5.4
Removal of Subjects from Therapy or Assessment .................................65
5.4.1
Discontinuation of Individual Subjects....................................................65
5.4.2
Discontinuation of Entire Study...............................................................66
5.5
Treatments................................................................................................67
5.5.1
Treatments Administered.........................................................................67
5.5.2
Identity of Investigational Product...........................................................67
5.5.2.1
Packaging and Labeling...........................................................................68
5.5.2.2
Storage and Disposition of Study Drugs..................................................68
5.5.3
Method of Assigning Subjects to Treatment Group ................................69
5.5.4
Selection and Timing of Dose for Each Subject ......................................69
5.5.5
Treatment Compliance.............................................................................70
5.5.6
Drug Accountability.................................................................................71
5.6
Discussion and Justification of Study Design..........................................72
5.6.1
Discussion of Study Design and Choice of Control Groups....................72
5.6.2
Appropriateness of Measurements...........................................................72
5.6.3
Suitability of Subject Population .............................................................73
5.6.4
Selection of Doses in the Study ...............................................................73
6.0
Complaints .............................................................................74
6.1
Medical Complaints.................................................................................74
6.1.1
Definitions................................................................................................75
6.1.1.1
Adverse Event..........................................................................................75
6.1.1.2
Serious Adverse Events ...........................................................................75
6.1.2
Adverse Event Severity............................................................................77
6.1.3
Relationship to Study Drug......................................................................77
6.1.4
Adverse Event Collection Period.............................................................78
6.1.5
Adverse Event Reporting.........................................................................79
6.1.6
Pregnancy.................................................................................................81
6.1.7
Toxicity Management ..............................................................................81


Adalimumab
M15-573 Protocol
14
6.2
Product Complaint ...................................................................................82
6.2.1
Definition .................................................................................................82
6.2.2
Reporting..................................................................................................82
7.0
Protocol Deviations................................................................83
8.0
Statistical Methods and Determination of Sample 
Size ..........................................................................................84
8.1
Statistical and Analytical Plans................................................................84
8.1.1
Analysis Populations................................................................................84
8.1.2
Planned Methods of Statistical Analysis..................................................84
8.1.3
Demographics and Baseline Characteristics............................................85
8.1.4
Statistical Analyses of Efficacy ...............................................................85
8.1.4.1
Primary Analysis of Efficacy...................................................................86
8.1.4.2
Secondary Analysis of Efficacy...............................................................86
8.1.5
Statistical Analysis of Safety ...................................................................87
8.1.6
Interim Analysis.......................................................................................88
8.2
Determination of Sample Size .................................................................88
8.3
Study Drug Allocation Methods ..............................................................88
8.4
Pharmacokinetic Analysis........................................................................88
9.0
Ethics.......................................................................................89
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) .............................................................................................89
9.2
Ethical Conduct of the Study ...................................................................90
9.3
Subject Information and Consent.............................................................90
9.3.1
Informed Consent Form and Explanatory Material.................................91
9.3.2
Revision of the Consent Form and Explanatory Material .......................91
10.0
Source Documents and Case Report Form 
Completion .............................................................................91
10.1
Source Documents ...................................................................................91
10.2
Case Report Forms...................................................................................93
11.0
Data Quality Assurance........................................................94
12.0
Use of Information.................................................................95
12.1
Use of Information...................................................................................95
12.2
Publication ...............................................................................................96


Adalimumab
M15-573 Protocol
15
13.0
Completion of the Study .......................................................96
14.0
Investigator's Agreement......................................................98
15.0
Reference List ........................................................................99
List of Tables
Table 1.
Study Activities........................................................................................41
Table 2. 
Clinical Laboratory Tests.........................................................................52
Table 3. 
Identity of Investigational Product...........................................................68
List of Figures
Figure 1. 
Study Schematic.......................................................................................27
Figure 2. 
Criteria for HBV DNA PCR Qualitative Testing ....................................53
Figure 3. 
Adverse Event Collection ........................................................................78
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator ..........................................101
Appendix B.
List of Protocol Signatories....................................................................103
Appendix C.
Latest TB Risk Assessment Form Example...........................................104
Appendix D.
Dermatology Life Quality Index (DLQI) – Example ............................105
Appendix E.
EuroQoL (EQ-5D questionnaire) – Example ........................................107
Appendix F.
Patient's Global Assessment of Skin Pain – NRS – Example................109
Appendix G.
Daily Subject Analgesic (Pain) Use Diary – Example ..........................110
Appendix H.
Hidradenitis Suppurativa Quality of Life – Example ............................111
Appendix I.
Treatment Satisfaction Questionnaire for Medication – Example.........112
Appendix J.
Lesion Counts – Example ......................................................................116
Appendix K.
Degree of Erythema – Example.............................................................117
Appendix L.
Day 70 Follow-Up Call – Example........................................................118
Appendix M.
Injection Instructions – Example Pre-Filled Syringe.............................119
Appendix N.
Subject Dosing Sheet – Adalimumab Example.....................................128
Appendix O.
Infection Subject Information Card – Example.....................................132


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3.0
Introduction
3.1
Differences Statement
Study M15-573 is a Phase 3 clinical study to evaluate the safety and efficacy of 
adalimumab in the treatment of Japanese subjects with moderate to severe hidradenitis 
suppurativa (HS).  Prior to initiation of this trial, global Phase IIb study (Study M10-467) 
and pivotal Phase III studies (Studies M11-810 and M11-313) were completed in the 
Western countries and market authorization of adalimumab was approved in US and EU 
for the treatment of subjects with HS.  The differences between Study M15-573 and 
global studies include sample size, study design, duration, and race.
3.2
Hidradenitis Suppurativa
HS is a painful, chronic, skin disease characterized by recurrent inflamed nodules and 
abscesses, which may rupture to form fistulas and subsequent scarring.  The most 
commonly involved anatomic locations are the inguino-crural and axillary folds, with 
sub-mammary folds (in women) and the perineal area less commonly involved in the 
Western countries.
Hidradenitis Suppurativa has a severely negative effect on patients' quality of life.1  It 
typically presents with painful, deep-seated nodules, which either resolve spontaneously, 
persist as non-tender nodules, or progress to form abscesses.  Abscesses typically rupture 
and release purulent drainage.  Abscesses and nodules may heal with scarring and the 
formation of fistulas or sinus tracts.  Thus, many patients with HS develop permanent 
sequelae of past inflammation that are only remediable through surgical excision of the 
involved skin areas.  The physical and psycho-social morbidity associated with en bloc 
excision of scarred axillary, inguinal, or groin skin is substantial.  Rare complications of 
HS include fistula formation into urethra, bladder, rectum, or peritoneum, lymphedema of 
the limbs or scrotal elephantiasis, and squamous cell carcinomas of the skin originating 
from HS lesions.


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M15-573 Protocol
17
Hidradenitis Suppurativa affects approximately 1% of the general population in the 
Western countries.2,3  Disease onset is typically after puberty.  Disease prevalence 
decreases from 1.5% in those < 25 years of age to 0.5% in those older than 55 years of 
age.  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.4
The histopathologic characteristics of HS include a dense inflammatory cell infiltrate of 
neutrophils, lymphocytes, and histiocytes.5  Tumor necrosis factor-alpha (TNF-α), which 
induces pro-inflammatory cytokines and activates neutrophils and lymphocytes, may have 
a pathogenic role.
In Japan, HS is approximately two times more prevalent in men than in women, and the 
most commonly involved anatomic locations are buttocks, axillae, and groin.  These 
differences in anatomic area of skin lesion and gender between Japan and the Western 
countries may represent the different phenotypes of a single disease, as it is reported that 
HS has 3 phenotypes depending on the anatomic areas involved.6  Indeed, the 
histopathological characteristics of HS lesions in Japanese were follicular occlusion 
followed by neutrophil infiltration into the follicles and were similar to those observed in 
Western patients.7  The patient number is quite limited as reported in the questionnaire 
survey in 2014; 100 cases in 44 hospitals authorized by Japan Dermatology Association.8
3.3
Current Treatments
There were no formal treatment guidelines for this condition overseas at the time of study 
initiation for clinical development in HS in 2010.  Current treatments are still driven 
primarily by expert opinion and isolated case reports or series.  Prior to Phase 2 
Study M10-467, the only placebo controlled trial of HS demonstrated modest efficacy 
with the use of topical clindamycin.9  Treatment of HS depends on the extent and activity 
of disease.4  The recommendation by experts for mild or limited forms of the disease 
consists of topical clindamycin, short courses of systemic antibiotics, or intralesional 
steroids.  Successful use of oral retinoids, anti–androgens, or immunosuppressants for 
recalcitrant cases has been described in case reports and series, but no controlled studies 


Adalimumab
M15-573 Protocol
18
have been conducted with these agents.  In more advanced cases, a multifaceted approach 
may be adopted, where surgical therapy is used to remove the chronic components of HS 
which are not expected to respond to medical therapy (e.g., scarring, fistulas, and sinus 
tracts), and long-term systemic medical therapy is used to treat the acute or sub-chronic 
manifestations of HS (e.g., abscesses and inflammatory nodules).
Oral retinoids for treatment of HS appear to offer limited therapeutic benefit, but one 
small case series reported that the response of HS to isotretinoin is more successful in the 
milder cases.10  Other treatments for HS include:  1) Systemic combination therapy with 
clindamycin and rifampicin, 2) Radical excision, 3) Intralesional triamcinolone (which 
can add to a significant systemic exposure), 4) Systemic cyclosporine, 5) Anti-androgen 
treatment in women (which is teratogenic), and 6) systemic dapsone.11
Case reports and series have shown that inhibitors of TNF-α are effective in treating 
HS.12-14  Based on these observations, the investigation of adalimumab, a fully human 
anti-TNF monoclonal antibody, for the treatment of moderate to severe HS was 
considered warranted.  AbbVie Inc. conducted Phase 2 and Phase 3 studies in patients 
with moderate to severe HS and had approval of HS indication in 2015.  Then 
adalimumab was listed on the EU guideline as the first biologic agent.
In Japan, the treatment options for HS are basically the same as those in the Western 
countries; oral or topical antibiotics and surgery of total removal of skin lesion or incision 
for drainage of abscess.
3.4
Adalimumab Overview
Adalimumab is a recombinant human immunoglobulin (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, and human IgG1 heavy chain and kappa 


Adalimumab
M15-573 Protocol
19
light chain sequences.  Adalimumab binds with high affinity and specificity to soluble 
TNF-α but not to lymphotoxin-α (TNF-β).  TNF is a naturally occurring cytokine that is 
involved in normal inflammatory and immune responses.  Elevated levels of TNF are 
thought to play an important role in pathologic inflammation.  Adalimumab binds 
specifically to TNF and neutralizes the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.  Adalimumab also modulates 
biological responses that are induced or regulated by TNF.  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.
The role of elevated levels of TNF in pathologic autoimmune disorders and immune-
mediated disorders has led to the study and approval of anti-TNF agents in diseases such 
as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), 
ankylosing spondylitis (AS), Crohn's disease and psoriasis (Ps).  Elevated TNF levels in 
the synovial fluid of RA, including JIA, PsA, and AS patients, play an important role in 
both the pathologic inflammation and the joint destruction that are hallmarks of these 
diseases.  In plaque Ps, treatment with adalimumab may reduce the epidermal thickness 
and infiltration of inflammatory cells.  The relationship between these pharmacodynamic 
activities and the mechanism(s) by which adalimumab exerts its clinical effects is 
unknown.
Adalimumab also modulates biological responses that are induced or regulated by TNF, 
including changes in the levels of adhesion molecules responsible for leukocyte migration 
(ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1 to 2 × 10–10M).
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 Psoriasis, Psoriatic Arthritis, 
Ankylosing Spondylitis, Crohn's Disease, Juvenile Idiopathic Arthritis, and Ulcerative 
Colitis.  In 2015, adalimumab was approved for the indication of Hidradenitis Suppurativa 
with the following clinical data.  


Adalimumab
M15-573 Protocol
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A 52-week Phase 2 dose-ranging study (Study M10-467) was conducted to evaluate the 
short- and long-term clinical efficacy and safety of adalimumab in subjects with moderate 
to severe HS.  The first portion of the study was a 16-week, randomized, double-blinded, 
placebo-controlled phase in which subjects were randomized to adalimumab 40 mg ew 
(weekly starting at Week 4, after 160 mg at Week 0 and 80 mg at Week 2), or to 
adalimumab 40 mg eow (every other week starting at Week 1, after 80 mg at Week 0), or 
to placebo.  The primary endpoint was the proportion of subjects achieving an HS-
Physician's Global Assessment (PGA) of clear (0), minimal (1), or mild (2), with a 
reduction from Baseline of at least 2 grades at Week 16.  
The proportion of subjects who achieved a clinical response was significantly higher in 
the ew arm compared with subjects in the placebo arm at Week 12 and Week 16.  The 
second portion of the study was a 36-week open-label phase in which all subjects received 
adalimumab 40 mg eow and were eligible to dose escalate to ew dosing if response was 
sub-optimal.  A decline in response rate was seen following decreasing from ew to eow 
dosing, and dose escalation to ew dosing resulted in improved efficacy.
A Phase 3 Study M11-313 was a 36-week multicenter study designed to evaluate the 
safety and efficacy of adalimumab in subjects with moderate to severe HS.  The study 
included a 30 day screening period, an initial 12-week double-blind placebo-controlled 
treatment period (Period A), and a subsequent 24-week double-blind placebo-controlled 
treatment period (Period B).  Subjects were randomized 1:1 at Baseline (Week 0) to either 
adalimumab 40 mg ew (starting at Week 4 through Week 11, after 160 mg at Week 0 and 
80 mg at Week 2), or matching placebo for 12 weeks.  The randomization was stratified 
by Hurley Stage (II versus III).  The primary efficacy variable was the proportion of 
subjects achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12.  
After Week 12, subjects who had been randomized to adalimumab during Period A were 
re-randomized 1:1:1 to 1 of 3 groups:  adalimumab 40 mg ew, adalimumab 40 mg eow, or 
placebo from Week 12 to Week 35.  The re-randomization was stratified by Week 12 
response (HiSCR responder versus non responder) and by Baseline Hurley Stage 
(II versus III). 


Adalimumab
M15-573 Protocol
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A total of 307 subjects were randomized in this study.  In Period A, a statistically 
significantly higher percentage of subjects in the adalimumab ew group achieved HiSCR 
at Week 12 (primary efficacy endpoint) compared with subjects in the placebo group 
(41.8% [64/153] versus 26.0% [40/154]; P = 0.003).  Furthermore, a greater proportion of 
subjects in the adalimumab group achieved HiSCR at each visit in Period A compared 
with subjects in the placebo group (P ≤ 0.05 at all visits).  Efficacy assessments from 
subjects who were randomized to adalimumab ew in Period A and re-randomized to 
Period B as HiSCR responders showed generally better treatment outcomes among those 
continuing adalimumab ew treatment (ew/ew group) compared with subjects who reduced 
dosing frequency to eow or to placebo groups through 36 weeks.  Overall, the safety 
profile of adalimumab treatment observed in this study was consistent with the experience 
in other adalimumab clinical trials.
Another Phase 3 Study M11-810 was a 36-week multicenter study designed to evaluate 
the safety and efficacy of adalimumab in subjects with moderate to severe HS.  The study 
design and procedures were almost identical to those for Study M11-313.  The main 
differences between the studies are 1) treatment in Period B for the subjects who were 
allocated to placebo in Period A and 2) permission of use of antibiotics and its related 
study procedures.  The randomization was stratified by Hurley Stage (II versus III) and 
concomitant antibiotic use (defined as baseline use of antibiotics to be used concomitantly 
during the study; Yes versus No).  The primary efficacy variable was the proportion of 
subjects achieving HiSCR at Week 12, the same as in Study M11-313.  
A total of 326 subjects were randomized in this study.  In Period A, a statistically 
significantly higher proportion of subjects randomized to adalimumab ew achieved 
HiSCR at Week 12 (primary efficacy endpoint), as compared to subjects randomized to 
placebo (58.9% [96/163] versus 27.6% [45/163], respectively).  Consistent treatment 
effects were observed for subjects in each Hurley Stage and in each baseline antibiotic use 
strata.  Furthermore, a greater proportion of subjects in the adalimumab group achieved 
HiSCR than subjects in the placebo group at each visit during Period A (P < 0.001 at all 
visits).  Results of the secondary endpoints support the primary efficacy endpoint results.


Adalimumab
M15-573 Protocol
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Efficacy assessments from subjects who were randomized to adalimumab ew in Period A 
and re-randomized to adalimumab ew (ew/ew group) in Period B showed generally better 
treatment outcomes than subjects who reduced dosing frequency to eow (ew/eow group) 
or who were re-randomized to placebo (ew/placebo) for both HiSCR responders and 
HiSCR nonresponders.  Overall, the safety profile of adalimumab treatment observed in 
this study was consistent with that expected for the study population of moderate to severe 
HS.
3.5
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.  The safety and efficacy of 
adalimumab in HS has been demonstrated in the Phase 3 pivotal Studies M11-810 and 
M11-313.  At Week 12 of the double blind period,  the proportion of subjects who 
achieved HiSCR at Week 12 were 50.6% and 26.8% in adalimumab and placebo 
(P < 0.001) in the integrated analysis, respectively, which demonstrated statistically 
significant superiority of efficacy to placebo.  The necessity of ew dosing was also 
confirmed to maintain the efficacy in both studies.  The safety profile of adalimumab in 
HS does not appear different from that previously observed with adalimumab in the other 
indications.
Regarding safety data from the initial DB period of Phase 2 Study M10-467 
(first 16 weeks) and Period A of Phase 3 Studies M11-810 and M11-313 (first 12 weeks), 
the percentages of subjects reporting AEs were comparable between the placebo (63.7%) 
and total adalimumab (eow and ew) groups (58.2%) during the placebo-controlled period 
of the Phase 2 and 3 studies.  Similar percentages of subjects in the placebo and total 
adalimumab groups reported AEs that were considered by the investigator to be possibly 
or probably related to study drug (27.0% and 29.1%, respectively) and severe AEs (6.6% 
and 5.7%, respectively).


Adalimumab
M15-573 Protocol
23
The most frequently reported TEAEs for the adalimumab total and placebo groups in the 
placebo-controlled period were headache, hidradenitis, and nasopharyngitis.  The 
percentage of subjects who reported headache was higher in the adalimumab total group 
than in the placebo group (11.9% versus 10.4%).  The percentages of subjects who 
reported hidradenitis and nasopharyngitis were lower in the adalimumab total group than 
in the placebo group (7.6% versus 12.8% for hidradenitis and 7.4% versus 8.7% for 
nasopharyngitis).
The most frequently reported TEAEs in the adalimumab ew/ew and ew/placebo groups in 
the maintenance period were headache, nasopharyngitis, hidradenitis, and upper 
respiratory tract infection.  The most frequently reported TEAEs in the adalimumab 
ew/eow group were hidradenitis, upper respiratory tract infection, headache, and pyrexia.  
The percentage of subjects who reported hidradenitis was significantly lower in the 
adalimumab ew/ew group, as compared to the adalimumab ew/eow and ew/placebo 
groups (P = 0.007 and P = 0.002, respectively).
The potential benefit of the proposed study in HS is that it is designed to demonstrate 
whether adalimumab therapy is associated with a reduction in the extent of inflammation 
in Japanese patients with moderate to severe HS, manifested as a specific reduction in the 
number of inflammatory nodules and abscesses.  As these inflammatory lesions are 
associated with considerable pain and impairment in quality of life, a reduction in the 
number of such lesions could directly benefit patients.  Subjects with a draining fistula 
count of greater than 20 at the Baseline visit are excluded from enrolling in the study to 
exclude the most severe forms of the disease that may place subjects at a higher risk.
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 an FDA-requested, TNF inhibitor class wide exploration of the 
rare appearance of malignancy in patients 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.  


Adalimumab
M15-573 Protocol
24
Given that (a) the abscesses and inflammatory nodules of HS cause pain and malodor, and 
may culminate in scar formation; (b) there are no approved medical therapies for the 
abscesses and inflammatory nodules of HS; and (c) surgical therapies are associated with 
significant post-operative morbidity, there is a significant unmet medical need for 
therapies to treat this condition.  Based on the current treatment options and unmet 
medical need, AbbVie considers that adalimumab will provide safe and effective therapy 
also for Japanese patients with moderate to severe HS and is thus conducting Phase 3 
clinical trial for this indication in Japan.
4.0
Study Objective
The primary objective of this study is to investigate the safety and efficacy of adalimumab 
in Japanese subjects with moderate to severe HS after 12 weeks of treatment.  A 
secondary objective is to evaluate long-term safety, efficacy and tolerability by 
continuous weekly dosing from Week 12.  The pharmacokinetics and immunogenicity of 
adalimumab following subcutaneous (SC) injection will also be assessed.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
The study is a Phase 3, multicenter, open-label, single arm study of adalimumab, and 
designed to enroll 15 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.
The study duration will include a 35-day Screening Period, open-label treatment period, 
and a Day 70 follow-up phone call approximately 70 days after the last dose of study drug 
administration.  The treatment period is expected for at least 99 weeks until the time of 
approval for HS indication, or withdrawal of the marketing application in Japan.  A 
subject's participation in this study is expected up to 38 months.  


Adalimumab
M15-573 Protocol
25
The duration of the screening period will be a maximum of 35 days during which time all 
of the inclusion and exclusion criteria will be evaluated.  Subjects may enroll into the 
study after all screening procedures are complete, at least 7 days of pain diaries are 
completed, and results are known and verified for eligibility at Baseline. 
All subjects will receive open-label subcutaneous injection of adalimumab 40 mg every 
week (ew) starting at Week 4, after 160 mg at Week 0 (Baseline) and 80 mg at Week 2.  
Subjects will have to return to the site once (Week –2) in the Screening period after the 
date of the Screening visit (Week –4).  Study visits for clinical and safety assessment will 
occur at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, 
Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, and Week 52 or at the 
Premature Discontinuation visit.  After Week 52, study visits should be every 12 weeks 
until the study end.  
The primary efficacy endpoint is the proportion of subjects achieving Hidradenitis 
Suppurativa Clinical Response (HiSCR) at Week 12.  HiSCR is defined as at least a 50% 
reduction in the total abscess and inflammatory nodule count (AN count) with no increase 
in abscess count and no increase in draining fistula count relative to Baseline.  Safety and 
efficacy measurements will be performed throughout the study as described in 
Section 5.3.1.
Blood samples will be collected for clinical laboratory test, adalimumab serum 
concentrations and anti-adalimumab antibody (AAA) levels, as indicated in Table 1.  
Photography of skin lesions will also be performed in subjects who consent in pre-
selected sites.
Additionally, all subjects will be contacted by phone 1 week before and after the Baseline 
visit to ensure daily pain assessments are being recorded, and 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 are reported at the time of the call, an unscheduled study visit 
will be conducted to assess whether an infection is present.  Each subject will also be 


Adalimumab
M15-573 Protocol
26
given an information card (Appendix O) describing signs and symptoms of infections 
with instructions to contact the site immediately if any such signs or symptoms develop at 
or near an HS lesion.
The visit window will be + or –3 days for the Week –4, Week –2,Week 2 and Week 4 
visits, and + or –7 days for all study visits from Week 8 until the study end.  Subjects will 
be brought back to their original visit schedule (calculated from Baseline) if they are out 
of the visit window.  Baseline is defined as the date of first administration of study drug
(Day 1).  The phone calls at Weeks 1, 6 and 10 should be completed as close to the 
scheduled date as possible, but minimally prior to the next study visit.
No study drug will be administered or injected at the final visit.
Subjects may discontinue treatment at any time during study participation.  Subjects who 
prematurely discontinue the study, will have a Premature Discontinuation visit.  All 
subjects will have a follow-up phone call approximately 70 days after the last 
administration of study drug to determine the status of any ongoing AEs or SAEs, or the 
occurrence of any new AEs or SAEs.  The 70-day follow-up phone call will not be 
required for any subject who initiates adalimumab therapy not supplied in the context of 
the clinical trial after the end of study participation.
Subjects who 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 the assessment of an electrocardiogram (ECG) and a 
complete TB screen (PPD/QuantiFERON-TB Gold test or T-SPOT [or equivalent] and 
CXR), these tests will not be required to be repeated for the re screening visit provided the 
conditions noted in Section 5.3.1.1 are met and no more than 90 days have passed.  Sites 
are encouraged to contact AbbVie TA MD to confirm if subjects should or should not be 
re screened.


Adalimumab
M15-573 Protocol
27
A schematic of the study design is presented in Figure 1.
Figure 1. 
Study Schematic
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 have none of the exclusion criteria specified in Section 5.2.2.
5.2.1
Inclusion Criteria
1.
Male and female subjects ≥ 18 years of age at the Screening visit;
2.
Subjects must have a diagnosis of HS;
3.
Subjects must have any HS symptom at least 6 months prior to Baseline;
4.
HS lesions must be present in at least two distinct anatomic areas (e.g., left and 
right axilla; or left axilla and left inguino-crural fold), one of which must be Hurley 
Stage II or Hurley Stage III;
5.
Subject must have stable HS for at least 2 months (60 days) prior to Screening and 
also at the Baseline visit as determined by the investigator through subject 
interview and review of the medical history;
6.
Subject must have a total abscess and inflammatory nodule (AN) count of greater 
than or equal to 3 at the Baseline visit;


Adalimumab
M15-573 Protocol
28
7.
If female, subject must be either postmenopausal, OR permanently surgically 
sterile, OR for Women of Childbearing Potential practicing at least one protocol 
specified method of birth control (Section 5.2.4), starting at Study Day 1 through at 
least 150 days after the last dose of study drug;
8.
Females of childbearing potential must have a negative serum pregnancy test result 
at Screening, and negative urine pregnancy test prior to starting of study drug (at 
Study 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 has a negative tuberculosis (TB) Screening Assessment (including a PPD 
test or QuantiFERON-TB Gold test, or equivalent) 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 3 weeks of anti-
TB therapy, or have documented completion of a course of anti TB therapy, prior 
to Baseline (Section 5.3.1.1);
10.
Subject is judged to be in good general health, as determined by the Principal 
Investigator based upon the results of a medical history, physical examination, 
laboratory profile, CXR and a 12-lead ECG performed during the Screening period 
and confirmed at Baseline;
11.
Subject must be able and willing to self-administer subcutaneous (SC) injections or 
have a qualified person(s) who can reliably administer SC injections;
12.
Subjects must voluntarily sign and date an informed consent, approved by an 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to 
the initiation of any screening or study-specific procedures, and be able to comply 
with the requirements of this study protocol.  If the subject is < 20 years old, a 
subject's parent or legal guardian must be willing to give written informed consent.


Adalimumab
M15-573 Protocol
29
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 – 11
For the safety of the study subjects
12
In accordance with harmonized GCP
5.2.2
Exclusion Criteria
1.
Prior treatment with adalimumab or other anti-TNF therapy (e.g., infliximab, 
etanercept), or participation in an adalimumab trial;
2.
Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) 
that may interfere with assessment of hidradenitis suppurativa;
3.
Subject received antibiotic treatment for HS within 28 days prior to the Baseline 
visit other than those allowed per protocol.  Subjects on permitted oral antibiotic 
treatment (doxycycline or minocycline only) for HS who have not been on a stable 
dose for at least 28 days prior to the Baseline visit (see Section 5.2.3 for permitted 
medications);
4.
Subject received prescription topical therapies for the treatment of HS within 
14 days prior to the Baseline visit;
5.
Subject received systemic non-biologic therapies with potential therapeutic impact 
for HS less than 28 days prior to Baseline visit (other than permitted oral 
antibiotics – see Section 5.2.3);
6.
Subject received oral concomitant analgesics (non-opioids and opioids) for HS-
related pain within 14 days prior to the Baseline visit;
7.
If entering the study on concomitant oral analgesics for non-HS-related pain:


Adalimumab
M15-573 Protocol
30
●
Subject on opioid analgesics within 14 days prior to Baseline visit (opioid 
analgesics are not allowed);
●
Subject not on a stable dose of non-opioid oral analgesics for at least 14 days 
prior to the Baseline visit (PRN is not considered a stable dose).
8.
Subject requires or is expected to require, opioid analgesics for any reason 
(excluding tramadol);
9.
Subject has a draining fistula count of greater than 20 at the Baseline visit;
10.
Subject has been treated with any investigational drug of chemical or biologic 
nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the 
drug prior to the Baseline visit or is currently enrolled in another clinical study;
11.
Prior exposure to biologics that have a potential or known association with PML 
(i.e., natalizumab [Tysabri®], rituximab [Rituxan®], or efalizumab [Raptiva®]);
12.
Infection(s) requiring treatment with intravenous (IV) anti-infectives (antibiotics, 
antivirals, antifungals) within 30 days prior to Baseline or oral anti-infectives 
(antibiotics, antivirals, antifungals) within 14 days prior to Baseline, except as 
required as part of an anti-TB regimen;
13.
History of moderate to severe congestive heart failure (New York Health 
Association [NYHA] class III or IV), recent cerebrovascular accident and any other 
condition which, in the opinion of the investigator would put the subject at risk by 
participation in the study;
14.
History of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease;
15.
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 including 
Hepatitis C that based on the investigator's clinical assessment makes the subject an 
unsuitable candidate for the study;


Adalimumab
M15-573 Protocol
31
17.
Hepatitis B:  HBsAg positive (+) or detected sensitivity on the HBV-DNA PCR 
qualitative test for HBcAb/HBsAb positive subjects (Section 5.3.1.1);
18.
Chronic recurring infections or active TB;
19.
Known hypersensitivity to adalimumab or its excipients as stated in Section 5.5.2, 
Table 3.
20.
Positive pregnancy test at Screening or Baseline;
21.
Female subjects who is pregnant, breastfeeding or is considering becoming 
pregnant during the study and for approximately 150 days after the last dose of 
study drug;
22.
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;
23.
History of clinically significant drug or alcohol abuse in the last 12 months;
24.
Clinically significant abnormal screening laboratory results as evaluated by the 
investigator;
25.
Subject is considered by the investigator for any reason, to be an unsuitable 
candidate for the study and not able to comply with the study protocol.
26.
Subject currently has an adequate response to oral antibiotic treatment for HS.
Rationale for the Exclusion Criteria
1, 26
To avoid bias for the evaluation of safety and efficacy
2
To avoid enrollment of subjects who have concomitant skin disease 
that may interfere with HS assessment
3–8, 10
To avoid bias for the evaluation of safety and efficacy by concomitant 
use of other medications
9
Excludes the most severe forms of the disease that may place subjects 
at a higher risk


Adalimumab
M15-573 Protocol
32
11, 15 – 19, 
23 – 25
To ensure safety of the subjects throughout the study.
12, 22
To avoid a possibility of an infectious disease or a malignant tumor 
progression when administering an anti-TNF drug
13
To avoid a possibility of heart failure process 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
20, 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, but not limited to, over-the-counter or prescription 
medicines such as aspirin, antacids, vitamins, mineral supplements and/or herbal 
supplements) that the subject is receiving at the time of screening/enrollment, or receives 
during the study, must be recorded in the source and on the appropriate electronic case 
report form (eCRF), along with the reason for use, date(s) of administration including start 
and end dates, and dosage information including dose, route and frequency.
Prophylaxis treatment for TB (e.g., isoniazid) will be recorded.  Even if a subject 
prematurely discontinues this study, the treatment should be continued for a certain period 
considering the best interest of the subject at the discretion of the Investigator.  Any 
vaccine (except for live vaccine) administered during the study will be recorded in the 
eCRF as a concomitant medication.
The AbbVie TA MD identified in Section 6.1.5 should be contacted if there are any 
questions regarding prior, concomitant and/or prohibited therapy(ies).
In addition for patient's age ≤ 30 with a reported malignancy adverse event, prior 
exposure to, or current use of antineoplastics or other drugs which have a risk of 
malignancy as stated in their label and other relevant dosing information to estimate total 


Adalimumab
M15-573 Protocol
33
exposure will be collected in the source documents and appropriate eCRF pages.  At the 
time of the reported malignancy adverse event, sites 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.
5.2.3.1
Prior Therapy
Any treatments for HS since initial diagnosis (as determined through medical history 
records or through subject interview) prior to study entry will be recorded in the source 
and on the eCRF, along with the reason for discontinuation.  A detailed history of prior 
antibiotic use for HS, response and reason for discontinuation will be collected.
For subjects previously treated with biologics other than anti-TNF therapy, the duration of 
therapy, maximum dose, reason for use and reason(s) for termination of treatment with 
these products should be documented.
5.2.3.2
Concomitant Therapy
Antiseptic Therapy
Use of any antiseptic washes for HS lesion is not allowed, except for the treatment of 
wound after lesion intervention (incision and drainage), described below.  
Wound Care
Concomitant use of wound care dressings on HS wounds is allowed, and options are 
alginates, hydrocolloids, hydrogels, polyurethane film, polyurethane foam, hydrofiber and 
hydropolymer.


Adalimumab
M15-573 Protocol
34
Antibiotic Therapy
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 
4 consecutive weeks (28 days) prior to Baseline (See Exclusion Criterion 3).  The dosing 
regimen must remain stable throughout study participation.  Antibiotics taken on an "as 
needed" (PRN) basis are not considered a stable dose.
Permitted oral concomitant antibiotics include:
●
Oral:
○
doxycycline (at a dose of up to 100 mg po bid);
○
minocycline (at a dose of up to 100 mg po bid).
If another Baseline oral concomitant antibiotic for HS is medically necessitated, AbbVie 
TA MD must be contacted for approval.
Subjects taking permitted oral concomitant antibiotics for HS at Baseline (doxycycline or 
minocycline at a dose of up to 100 mg po bid, or other oral concomitant antibiotic 
previously approved by AbbVie TA MD) may continue their dose; however, starting, 
stopping or changing the dose is not allowed, with the following exceptions:
●
If a subject develops an intolerance to the oral antibiotic, the antibiotic may be 
discontinued (see definition of Intolerance in Section 1.2).
●
If at any time after Week 52, a subject achieves HiSCR, and the physician and 
subject mutually decide that the risk/benefit of continuing oral antibiotic is 
unfavorable, then the oral antibiotic dose may be reduced.  Subject is not 
obligated to reduce the dose; rather, he/she has the option to reduce the dose.  
If at any time after dose reduction the subject experiences a loss of HiSCR 
response, subject may resume his/her previous antibiotic dose.  This 
decrease/increase in dose is permitted one time only without prior contact with 
AbbVie TA MD.  AbbVie TA MD should be contacted if additional dose 
adjustments are needed.


Adalimumab
M15-573 Protocol
35
●
If a subject is receiving an oral antibiotic dose less than the maximal permitted 
dose (e.g., doxycycline at a dose of up to 100 mg po bid or minocycline at a 
dose of up to 100 mg po bid) and if, at any time after Week 52, a subject does 
not achieve HiSCR response and the physician and subject mutually decide 
that the risk/benefit of increasing the oral antibiotic is favorable, then the 
subject may increase the dose up to the maximal permitted dose.  Subject is 
not obligated to increase the dose; rather, he/she has the option to increase the 
dose.  This increase in dose is permitted one time only.  No decrease in dose is 
subsequently permitted, unless the subject develops an intolerance to the oral 
antibiotic, in which case he/she may either resume his/her previous dose, or 
discontinue the oral antibiotic.
See Section 6.1.7 for additional discussion on the use of concomitant medications if 
medically necessitated.
Analgesic Therapy
Most subjects will be required to washout of all analgesics for 14 days prior to Baseline.  
This includes analgesics for HS-related pain and other pain (non-HS-related).  However, 
if a subject is on a stable dose of a non-opioid analgesic (PRN is not considered stable) for 
a non-HS medical condition (e.g., osteoarthritis), the subject may continue the analgesic, 
provided the dose is stable for 14 days prior to Baseline and is anticipated to remain stable 
throughout study participation.
If a subject's pain (HS-related or non-HS-related) worsens after Baseline, they may 
initiate analgesic therapy at any time as follows:
For HS-related pain, permitted analgesics are limited to:
●
ibuprofen (at a dose of up to 200 mg po TID) not to exceed 600 mg/day; 
AND/OR
●
acetaminophen (at a dose of 300 – 1000 mg po every 4 to 6 hours) not to 
exceed 4000 mg/day; AND/OR


Adalimumab
M15-573 Protocol
36
●
If HS-related pain is uncontrolled with ibuprofen or acetaminophen at the 
above dosing regimens after the Baseline visit, subjects can be prescribed 
tramadol (at a dose of up to 100 mg po every 4 hours), not to exceed 
400 mg/day
Dose adjustments of ibuprofen, acetaminophen, or tramadol, and use of these analgesics 
on an "as needed" (PRN) basis for HS-related pain up to the maximum permitted dose and 
frequency, are allowed during the study.
From Screening through Week 12, subjects will complete a daily diary of their analgesic 
use (Appendix G) using paper or an electronic diary.  After Week 12 and subsequent 
designated visits including Premature Discontinuation visit, subjects will be required to 
report if they took any analgesics within 24 hours of their in-office visit at the time of 
Patient Global Assessment of Skin Pain.  All analgesics and dose adjustments will be 
captured in the source and on the appropriate eCRF.
For non-HS-related pain:
●
Opioid analgesics are prohibited 
●
All other analgesics (including tramadol) are allowed at the recommended or 
prescribed dose
See Section 6.1.7 for additional discussion on the use of concomitant medications if 
medically necessitated.
Lesion Intervention
In the event that an acutely painful lesion occurs that requires an immediate intervention, 
the Investigator will have the option to perform protocol-allowed interventions.
Only two types of interventions are allowed:  injection with intralesional triamcinolone 
acetonide suspension (at a concentration of 50 mg/5 mL and up to 0.5 mL, or equivalent) 
and incision and drainage.


Adalimumab
M15-573 Protocol
37
New systemic and topical therapies following incision and drainage (including antibiotics) 
are prohibited, except antiseptic wash limited for the wound intervened.  Concomitant use 
of wound care dressings is allowed, however options are limited to shown in 
Section 5.2.3.2.  Subjects should continue using any ongoing oral therapies (including 
antibiotics, with the constraints as described in Section 5.2.3.2) 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 
captured in the source and on the appropriate eCRF.
A total of two protocol-allowed interventions are permissible until Week 12.  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 
(i.e., two types of intervention) at the same visit.  If a subject requires more than two 
interventions within the first 12 weeks, then they must be discontinued from the study.
After Week 12 until the study end, 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 period, then he or she must be discontinued from the study.
All study visit evaluations must occur before any interventions are performed.  Any lesion 
that undergoes an intervention will be documented in the source.  The site will be required 
to count any lesion that undergoes an intervention as permanently present from the date of 
the intervention, and must account for it in the source and on the appropriate eCRF.
HS Surgery
In the event a subject undergoes a surgical procedure for medically irreversible stigmata 
of chronic HS (i.e., non-draining fistula, sinus tract, or hypertrophic scarring) after 


Adalimumab
M15-573 Protocol
38
Week 52, the procedure and other surgery detail must be collected on the appropriate 
eCRF.
As with lesion interventions, the site will be required to count any lesion that undergoes 
an HS surgical procedure as permanently present from the date of the procedure and must 
account for it in the source and on the appropriate eCRF.
Study Drug
Study drug administration will be documented in a separate section of the eCRF.
5.2.3.3
Prohibited Therapy
The following treatments are prohibited for all subjects during the study:
●
Phototherapy (PUVA and/or UVB)
●
All biologic therapy with a potential therapeutic impact on the disease being 
studied, including but not limited to the following:
○
Abatacept (Orencia®)
○
Anakinra (Kineret®)
○
Natalizumab (Tysabri®)
○
Ustekinumab (Stelara®)
○
Etanercept (Enbrel®)
○
Infliximab (Remicade®)
○
Rituximab (Rituxan®)
○
Tocilizumab (Actemra®)
○
Efalizumab (Raptiva®)
○
Golimumab (Simponi®)
○
Certolizumab (Cimzia®)
○
Belimumab (Benlysta®)
○
Secukinumab (Cosentyx®)
○
Ixekizumab (Taltz®)


Adalimumab
M15-573 Protocol
39
○
Brodalumab 
○
Vedolizumab
●
Any investigational agents
●
Any other systemic drug therapies for HS, including but not limited to 
antibiotics (except as specified in Section 5.2.3.2), methotrexate (MTX), 
cyclosporine, retinoids, fumaric acid esters, and JAK inhibitors
●
Live vaccines (during the study and for 70 days after the last dose of study 
drug)
●
Oral or injectable corticosteroids (except as allowed per Section 5.2.3.2)
●
Oral analgesics for HS not listed in Section 5.2.3.2
●
Oral opioid analgesics
●
New prescription topical therapies for HS
●
Over-the-counter topical antiseptic washes, creams, soaps, ointments, gels and 
liquids containing antibacterial agents to treat HS
●
Surgical or laser intervention for an HS lesion except as outlined in 
Section 5.2.3.2
The investigator should contact AbbVie TA MD identified in Section 1.0 if there are any 
questions regarding concomitant or prior therapy.
5.2.4
Contraception Recommendations
A woman who is postmenopausal or permanently surgically sterile (bilateral 
oophorectomy, bilateral salpingectomy or hysterectomy) is not considered to be a woman 
of childbearing potential and is not required to follow contraception recommendations.
Postmenopausal is defined as:
●
Age > 55 years with no menses for 12 or more months without an alternative 
medical cause; or
●
Age < 55 years with no menses for 12 or more months without an alternative 
medical cause AND an FSH level > 40 IU/L.


Adalimumab
M15-573 Protocol
40
A woman who does not meet the definition of postmenopausal or permanently surgically 
sterile is considered a woman of childbearing potential and is required to practice at least 
one of the following highly effective method of birth control, on Study Day 1 (or earlier) 
through at least 150 days after the last dose of study drug.
●
Combined (estrogen and progestogen containing) oral hormonal contraception 
associated with the inhibition of ovulation, initiated at least 1 month prior to 
Study Day 1.
●
Progestogen-only oral hormonal contraception associated with inhibition of 
ovulation, initiated at least 1 month prior to Study Day 1.
●
Bilateral tubal ligation.
●
Vasectomized partner(s), provided the vasectomized partner has received 
medical assessment of the surgical success and is the sole sexual partner of the 
WOCBP trial participant.
●
Intrauterine device (IUD).
●
Intrauterine hormone-releasing system (IUS).
●
True abstinence:  Refraining from heterosexual intercourse when this is in line 
with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., 
calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal 
are not acceptable)
Condom with or without spermicide OR cap, diaphragm or sponge with spermicide 
should be used in addition to one of the birth control methods listed above excluding true 
abstinence.
5.3
Efficacy, Pharmacokinetic, and Safety 
Assessments/Variables
Study procedures will be performed at the designated study visits listed in Table 1.
5.3.1
Safety and Efficacy Measurements Assessed and Flow 
Chart


Adalimumab
M15-573 Protocol
41
Table 1.
Study Activities
Activity
Screening
(Day –35 
to Day –1)
Baseline
(Day 1)
Wk 
2
Wk
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28 
32
Wk 
36
Wk 
40 
44 
48
Wk 
52
Every 
12 Weeks 
After 
Wk 52
Final or 
Premature 
Discontinuation 
Visit
Unscheduled 
Study Visit
70-Day 
Call
Informed Consent
X
Inclusion/Exclusion 
Criteria
X
Xa
Prior and Concomitant 
Therapy Assessmentb
X
Xa
X
X
X
X
X
X
X
X
X
X
X
X
X
Medical/Surgical 
History
X
Xa
Alcohol Use
X
Nicotine Use
X
X
X
Physical Exam
X
X
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
X
Xc
X
X
Chest X-ray/ ECG
X
X
Xd
TB Screening
X
X
Vital Signs
Xe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Tests
Xf
Xg
Xg
Xg
Xg
Xg
Xg
Xg
Xg
General Labs: 
Chemistry and 
Hematologyh
X
Xh
X
X
X
X
X
X
X
Urinalysisi
X
Xh
X
X
X
X
X
X
X
CRP
X
X
X
HIV
X


Adalimumab
M15-573 Protocol
42
Table 1. 
Study Activities (Continued)
Activity
Screening
(Day –35 
to Day –1)
Baseline
(Day 1)
Wk 
2
Wk
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28 
32
Wk 
36
Wk 
40 
44 
48
Wk 
52
Every 
12 Weeks 
After 
Wk 52
Final or 
Premature 
Discontinuation 
Visit
Unscheduled 
Study Visit
70-Day 
Call
Hepatitis B/C Screen
X
HbA1c
X
X
X
PK Measurementsj
X
X
X
X
X
X
X
X
X
X
X
AAA Measurementsj
X
X
X
X
X
X
X
ANA/dsDNAk
X
DLQI
X
X
X
X
X
X
X
EQ-5D
X
X
X
X
PGA of Skin pain
Xl
Xl
Xl
Xl
Xl
Xl
X
X
X
X
X
Paper Diary
X
X
X
X
X
X
HS QOL
X
X
X
X
X
X
X
X
X
TSQM
X
X
X
X
X
X
Lesion Countsm
Wk –4 Wk –2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xn
Xn
Hurley Stage 
Xn
Xn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Degree of Erythemao
Xn
Xn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Follow-up Phone Call
Xp
Xp
Xq
Xq
Xr
Photographys
X
X
X
X
X
X
Adverse Eventst
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X


Adalimumab
M15-573 Protocol
43
Table 1. 
Study Activities (Continued)
a.
Update inclusion/exclusion, prior and concomitant therapy, and medical history information to assure subject eligibility.
b.
From Screening through Week 12, subjects will complete a daily diary of their analgesic use using paper diary.  After Week 12 and subsequent designated visits including 
Premature Discontinuation visit, subjects will be required to report if they took any analgesics within 24 hours of their in-office visit at the time of Patient Global Assessment 
of Skin Pain.  Note:  Subject may not be allocated to the study drug if pain diaries are not completed for 7 days (at minimum) prior to the Baseline visit.
c.
A full physical exam is required at the Screening, Baseline, Week 52 and Final visit or Premature Discontinuation visit.  A symptom-directed physical examination should be 
performed at other visits if, in the opinion of the investigator, it is warranted by the subject's AE status or on review of symptoms.
d.
Subjects will have a repeat ECG and CXR at Week 52.  Repeat ECG or CXR at Final visit or at Premature Discontinuation visit only if in the opinion of the investigator, 
clinically significant AEs develop during the study that warrant a repeat.
e.
Height will be measured at Screening only.
f.
All females of childbearing potential will have a serum pregnancy test at Screening that is performed at the central laboratory.
g.
All females of childbearing potential will have a urine sample collected at Baseline  and at the designated study visits.  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. Urine pregnancy test at the Baseline will be performed also at 
site to confirm negative result on site. If the result at site is positive, treatment with study drug should not be started until theserum pregnancy test at the central laboratory is 
confirmed negative.
h.
Refer to the laboratory manual for further instructions.
i.
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 or in the case of abnormal macroscopic results.
j.
Blood samples must be obtained prior to dosing.  Blood samples will be collected at the Premature Discontinuation visit if the subject discontinues prior to Week 52.  
k.
ANA/Anti dsDNA is required at the Screening visit.  However, if a subject develops signs and symptoms of lupus, an ANA/Anti-dsDNA test may be repeated based on the 
investigator's clinical judgment. 
l.
From Screening through Week 12, subjects will complete a daily diary of their skin pain.  See Section 5.3.1.1.  No in-office assessment of skin pain will be completed at the 
Week 12 visit.  At the designated study visit after Week 12 until Final visit or Premature Discontinuation visit, subjects will complete skin pain assessments in the office 
based on a recall period of the last 24 hours.  Note:  Subject may not be allocated to the study drug if pain diaries are notcompleted for 7 days (at minimum) prior to the 
Baseline visit.
m.
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 the intervention.


Adalimumab
M15-573 Protocol
44
Table 1. 
Study Activities (Continued)
n.
After IC, evaluation of Lesion Counts, Hurley Stage and Degree of Erythema should be performed twice in the Screening period by site visit.  Time point will be Week –4 
(Day –28) and Week -2 (Day -14). 
o.
At every visit, for each affected anatomic region, the investigator will assess the overall degree of erythema using a four-point ordinal scale ranging between 0 and 3.
p.
Sites are encouraged to contact Subjects 1 week prior to the Baseline visit to confirm compliance with daily pain collection.  Subjects will be contacted 1 week following the 
Baseline visit to ensure daily pain assessments are being recorded.
q.
Subjects will be contacted 2 weeks following the Week 4 and 8 visits (i.e., Week 6 and Week 10) to obtain information on any signs of an infection at or near an HS lesion.
r.
Site personnel will contact all subjects by phone approximately 70 days after the last dose of study drug to determine the status of any ongoing AEs/SAEs or the occurrence of 
any new AE/SAEs.  The 70-day follow-up phone call will not be required for any subject who initiates adalimumab therapy not supplied in the context of the clinical trial 
after the end of study participation.
s.
Subjects at pre-selected sites will have photographs taken at Baseline, Week 4, Week 12, Week 24, Week 52 and Final visit or at the Premature Discontinuation visit.
t.
All AEs reported from the time of study drug administration until approximately 70 days following discontinuation of study drug administration will be collected.  SAEs and 
protocol-related AEs will be collected from the time the subject signed the study-specific informed consent until approximately 70 days following discontinuation of study 
drug administration.


Adalimumab
M15-573 Protocol
45
5.3.1.1
Study Procedures
The study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of prior and concomitant medication information 
(Section 5.2.3), drug concentration measurements (Section 5.3.2) and the collection of AE 
information (Section 6.1).  All study data will be recorded in source documents and on the 
appropriate eCRFs. 
Informed Consent
An Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approved, 
study-specific informed consent 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 order to participate in this study.  Written consent will be required for each 
subject in order to take photography of the skin lesion.  Subjects can withdraw informed 
consent at any time.
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, Alcohol and Nicotine Use
A complete medical history (which includes HS-related and non-HS-related medical and 
surgical history), including history of alcohol and tobacco (nicotine) use, will be obtained 
from each subject during the Screening visit.  Tabacco use will be checked also at 
Week 12 and Final/PD visit.  The medical history should also include a detailed history of 


Adalimumab
M15-573 Protocol
46
prior therapies used to treat HS, including antibiotics.  The prior doses and reasons for 
discontinuation of antibiotic therapy will be recorded.  Medical history will be reviewed 
and updated at the Baseline visit to ensure that 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.
Physical Examination
A full physical exam will be performed at the designated study visits listed in Table 1.  
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.
A symptom-directed physical examination should be performed at all other visits, if 
warranted.  Abnormalities noted after the Baseline visit will be evaluated and documented 
by the investigator as to whether they are AEs.
Chest X-ray (CXR)
All subjects will undergo a standard CXR (posterior-anterior [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 chest x-ray 
within 90 days of Screening, provided all protocol required documentation is available at 
the site (as outlined below).
Subjects can have a repeat CXR at any time during the study as warranted based on the 
opinion of the investigator.
In the assessment of the CXR, a radiologist or internist must specifically note the presence 
or absence of 1) calcified granulomas, 2) pleural scarring/thickening, and 3) signs of 
active TB.  The Principal Investigator will indicate the clinical significance of any 
findings and will sign and date the report.  


Adalimumab
M15-573 Protocol
47
Subject will have a repeat CXR at Final visit or at the Premature Discontinuation visit, 
only if in the opinion of the investigator, clinically significant AEs develop during the 
study that warrant a repeat exam.  If subject successfully continues at Week 52, CXR will 
be performed.
Electrocardiogram (ECG)
A resting 12-lead ECG will be performed at the designated study visits listed in Table 1.  
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 using the following conventions as appropriate:  Normal, Abnormal –
not clinically significant, Abnormal – clinically significant, or Unable to evaluate.  Each 
signed original ECG will be monitored by the responsible Monitor and kept with subject's 
source documents onsite.
Subject will have a repeat ECG at Final visit or at the Premature Discontinuation visit, 
only if in the opinion of the investigator, clinically significant AEs develop during the 
study that warrant a repeat exam.  If subject successfully continues at Week 52, ECG 
testing will be performed. 
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 Principal Investigator must 
contact AbbVie TA MD before enrolling the subject.
Subjects can have a repeat ECG at any time during the study as warranted based on the 
opinion of the investigator.
TB Screening/TB Prophylaxis
The TB screening tests are diagnostic test results to be interpreted in the context of the 
subject's epidemiology, history, exam findings, etc., and it is the responsibility of the 
Investigator to determine if a subject has previous, active, or latent TB.


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At Screening, all subjects will be assessed for evidence of increased risk for TB by a risk 
assessment form (Appendix C) and tested for TB infection by an Interferon-Gamma 
Release Assay (IGRA; QuantiFERON®-TB Gold, T-spot, or equivalent).  The PPD skin 
test should be utilized only when an IGRA is not possible for any reason.  The site staff 
will complete the TB risk assessment form and enter the data into an appropriate eCRF.  
The assessment for TB risk and TB test will be repeated at Week 52. 
●
QuantiFERON®-TB Gold Test will be analyzed by the central laboratory 
(QuantiFERON® test is preferred over PPD skin test). 
●
If the QuantiFERON®-TB Gold Test is NOT possible: the PPD skin test (also 
known as a TB skin test) will be performed according to standard clinical 
practice.  The TB skin test should be read by a licensed healthcare professional 
between 48 and 72 hours after administration.  A subject who does not return 
within 72 hours will need to be rescheduled for another skin test.  The reaction 
will be measured in millimeters (mm) of induration and induration ≥ 5 mm is 
considered a positive reaction.  The absence of induration will be recorded as 
"0 mm" not "negative."  Subjects who have had an ulcerating reaction to the 
TB skin test in the past should not be re-exposed and should not be tested by a 
PPD skin test.
If a subject had a negative QuantiFERON®-TB Gold (and/or PPD) test (or IGRA 
equivalent such as T-SPOT TB test) within 90 days prior to Screening and source 
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.  The results of the TB 
test(s) will be retained at the site as the original source documentation. 
In the event both a PPD test and a QuantiFERON®-TB Gold test (or equivalent) are 
performed, the result of the QuantiFERON®-TB Gold test will supersede the result of the 
PPD test unless otherwise required by local guidelines.  If the QuantiFERON®-TB Gold 
test is indeterminate, the site should repeat the test with another blood sample and/or 
perform a PPD test.  If the second QuantiFERON®-TB Gold test is also indeterminate, the 
subject is considered to be positive.


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Subjects with a negative QuantiFERON®-TB Gold test (and/or negative PPD TB skin 
test) and chest x-ray (CXR) not suggestive of active TB or prior TB exposure may be 
enrolled.
If the subject has evidence of latent TB infection (QuantiFERON®-TB Gold test and/or 
the PPD test positive) and has a CXR not suggestive of active TB, prophylactic treatment 
must be initiated at least 3 weeks prior to administration of study drug per local guideline 
in Japan.  The prophylaxis needs to be completed, however, the full course of prophylaxis 
does not need to be completed prior to the first dose of study drug.  
Subjects with a prior history of latent TB that have documented completion of a full 
course of anti-TB therapy within 1 year prior to first study drug administration will be 
allowed to enter the study provided nothing has changed in the subject's medical history to 
warrant repeat treatment.
Subjects with documented completion of a full course of anti-TB therapy greater than 
1 year prior to first study drug administration may be allowed to enter the study only after 
consultation with the AbbVie TA MD.
Newly initiated prophylactic treatment should be captured in the eCRF and in the source 
documents.  Prior therapy should be captured in the eCRF.
Vital Signs
Vital sign determinations of systolic and diastolic blood pressure, pulse (counted for at 
least 30 seconds after 5 minutes in sitting position), respiratory rate, body weight, and 
body temperature will be obtained at each visit.  Blood pressure and pulse should be 
performed before blood draws are performed.  Height will be measured at the Screening 
visit only.
Pregnancy Tests
A serum pregnancy test will be performed at the Screening visit on all female subjects of 
childbearing potential by the central laboratory.  At the Baseline visit and at the 


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designated study visits listed in Table 1, all female subjects of childbearing potential will 
have a urine pregnancy test by the central laboratory.  
Urine pregnancy test at the Baseline will be performed also at the site to confirm negative 
result on site prior to start of study drug.  If the result is positive, treatment with study 
drug must not be started until the serum pregnancy test at the central laboratory is 
confirmed negative.
If any urine pregnancy test is positive, a serum pregnancy test will be analyzed by the 
central laboratory.  At each visit, the study staff should review the pregnancy avoidance 
recommendations with each subject of childbearing potential.
A pregnant or breastfeeding female will not be eligible for participation or continuation in 
this study.  
Females of non-child bearing potential (either postmenopausal or permanently surgically 
sterile, defined as in Section 5.2.4) at Screening do not require pregnancy testing.
Clinical Laboratory Tests
Samples will be obtained for the laboratory tests listed in Table 2 at the designated study 
visits listed in Table 1.  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 investigator will be 
followed to a satisfactory resolution.
Instructions regarding the collection, processing and shipping of these samples will be 
provided by the central laboratory chosen for this study.


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Urinalysis
Urine samples will be obtained for urinalysis as noted in Table 1.  For samples with 
abnormal macroscopic results, or in the event the dipstick results show protein, ketones or 
blood greater than negative or glucose greater than normal, or in the case or abnormal 
macroscopic results, a microscopic test will be performed.
C-reactive Protein (CRP) Testing
Testing for CRP will be performed on specimens collected at the designated study visits 
listed in Table 1.
Human Immunodeficiency Virus (HIV) Testing
Subjects with a known history of HIV infection are excluded from study participation.  
Subjects will be tested for antibodies to the Human Immunodeficiency Virus (HIV) at 
Screening, and document that the test has been performed.  The testing is to be done at the 
Central 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.


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Table 2. 
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
Red Blood Cell (RBC) count
White Blood Cell (WBC) count
Neutrophils
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
Blood
Glucose
Microscopic analysisa
Other
Pregnancy Test
QuantiFERON-TB Gold
CRP
HIV
Hepatitis B Screening
Hepatitis C Screening
HbA1c
Antinuclear Antibody (ANA)/Anti-dsDNA (if positive for ANA)
Pharmacokinetic
AAA
Serum HCG
Urine HCG
a.
A microscopic analysis will be performed by the central laboratory, in the event the dipstick results show protein, 
ketones or blood greater than negative or glucose greater than normal, or in the case of abnormal macroscopic 
results.
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 (HBsAg) will be exclusionary.  Samples 
negative for HBsAg will be tested for surface antibodies (HBsAb) and core antibodies 


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(HBcAb).  If test results are positive for HBcAb or HBsAb, then HBV DNA PCR will be 
performed and any result that meets or exceeds detection sensitivity will be exclusionary.
●
A negative test result for HBc Ab and HBs Ab does not require HBV DNA 
PCR qualitative testing and the subject may be enrolled (Figure 2, Scenario A).  
For a subject who has had a HBV vaccination (should document in the medical 
history), a positive test result for HBs Ab is expected and the subject may be 
enrolled.
●
A positive test result for HBc Ab or HBs Ab requires HBV DNA PCR testing 
(automatic reflex testing) (Figure 2, Scenarios B, C and D).
○
A positive result for HBV DNA or a result that exceeds detection 
sensitivity will be exclusionary.
○
A subject with a negative result for HBV DNA may be enrolled.
Figure 2. 
Criteria for HBV DNA PCR Qualitative Testing
Hepatitis C Screening
All subjects will be tested for the presence of the Hepatitis C Virus (HCV) at Screening.  
A positive result for the hepatitis C will be exclusionary.


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HbA1c
All subjects will be tested for HbA1c at the designated study visits listed in Table 1.
PK and AAA Measurement
See Section 5.3.2.
Antinuclear Antibody (ANA)/Anti-dsDNA Testing
Study personnel will collect a sample for antinuclear (ANA) and reflex double stranded 
DNA antibody testing at the Screening visit.  A repeat ANA/Anti-ds-DNA would be 
warranted if a subject has clinical signs and symptoms suggestive of lupus.  The Anti ds-
DNA antibody testing will be performed in case of positive ANA result.
All samples will be sent to the central laboratory for processing.
Dermatology Life Quality Index (DLQI)
Subjects will complete a DLQI questionnaire (Appendix D) at the designated study visits 
listed in Table 1.  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 
'the last week.'  Decreased scores indicate improved health-related quality of life.
The subject should complete the questionnaire before site personnel perform any clinic 
assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.
EuroQoL (EQ-5D)
Subjects will complete the EQ-5D questionnaire (Appendix E) at the designated study 
visits listed in Table 1.  The EQ-5D is a simple generic measure that asks respondents 


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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 site personnel perform any clinic 
assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.
Patient Global Assessment of Skin Pain (Numeric Rating Scale)
The Patient Global Assessment of Skin Pain (Appendix F) will be completed on a daily 
diary by subjects from Screening through Week 12.  If pain diaries are not completed for 
at least the seven consecutive days just prior to the Baseline visit, the subject may not be 
qualified.
The Patient Global Assessment of Skin Pain will be used to assess the worst skin pain and 
the average skin pain due to HS.  Ratings for the two items will range from 0 (no skin 
pain) to 10 (skin pain as bad as you can imagine).  For the daily assessments being 
completed from Screening to Week 12, subjects should be instructed to complete the 
assessment before they go to bed, and respond to the items based on a recall period of the 
"last 24 hours."  
No in-office assessment of skin pain will be completed at the Week 12 visit.  At the 
designated study visit after Week 12 until Final visit or Premature Discontinuation visit 
listed in Table 1, subjects will complete skin pain assessments in the office based on a 
recall period of the last 24 hours.  For these in-office assessments, the subject should 
complete the assessment before site personnel perform any clinic assessments and before 
any interaction with the site personnel has occurred to avoid biasing the subject's response.
Patient's Diary
Sites should adhere to the following schedule when dispensing of paper diaries and 
collecting daily pain assessments by completing them;


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●
Screening visit:  Dispense Booklet and instruct subject on completion of daily 
pain assessments beginning at bedtime the day of the Screening visit through 
bedtime, the day prior to the Baseline visit;
●
Baseline visit:  Collect assessments that were completed beginning at bedtime 
the day of the Screening visit through bedtime, the day prior to the Baseline 
visit. Dispense Booklet and instruct subject on completion of daily pain 
assessments beginning at bedtime the day of the Baseline visit through 
bedtime, the day prior to Week 2 visit;
●
Week 2 visit:  Collect assessments that were completed beginning at bedtime 
the day of the Baseline visit through bedtime, the day prior to Week 2.  
Instruct subject continuously on completion of daily pain assessments 
beginning at bedtime the day of the Week 2 visit through bedtime, the day 
prior to Week 4 visit;
●
Week 4 visit:  Collect assessments that were completed beginning at bedtime 
the day of the Week 2 visit through bedtime, the day prior to Week 4.  
Dispense Booklet and instruct subject on completion of daily pain assessments 
beginning at bedtime the day of the Week 4 visit through bedtime, the day 
prior to Week 8 visit;
●
Week 8 visit:  Collect assessments that were completed beginning at bedtime 
the day of the Week 4 visit through bedtime, the day prior to Week 8.  
Dispense Booklet and instruct subject on completion of daily pain assessments 
beginning at bedtime the day of the Week 8 visit through bedtime, the day 
prior to Week 12 visit; 
●
Week 12 visit:  Collect assessments that were completed beginning at bedtime 
the day of the Week 8 visit through bedtime, the day prior to Week 12.  
Subjects should bring the paper diary to each visit.  Data collected using the paper diary 
will be entered by the site into the EDC system and will be available for viewing by site 
personnel.  Subjects will use paper diaries to complete pain assessments and document 
analgesic use, and site personnel have been appropriately trained.  
See Section 10.0 for a description of source documents and case report form completion.


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Analgesic Use
From Screening through Week 12, subjects will complete a daily diary of their analgesic 
use (Appendix G) using paper diary.  At the subsequent designated visits including 
Premature Discontinuation visit after Week 12, subjects will be required to report if they 
took any analgesics within 24 hours of their in-office visit at the time of Patient Global 
Assessment of Skin Pain.  All analgesics and dose adjustments will be captured in the 
source and on the appropriate eCRF.
HS Quality of Life (HS QOL)
Subjects will complete the HS QoL questionnaire (Appendix H) at the designated study 
visits listed in Table 1.  The HS QoL item will be used to assess the quality of life with 
HS.  Ratings for the items will range from 0 (worst possible) to 10 (best possible).  The 
subject should complete the questionnaire before site personnel perform any clinic 
assessments and before any interaction with the site personnel has occurred to avoid 
biasing the subject's response.
Treatment Satisfaction Questionnaire – Medication (TSQM)
Subjects will complete the TSQM questionnaire (Appendix I) at the designated study 
visits listed in Table 1.  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 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.
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 (right/left axilla, 


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right/left inframammary, intermammary, right/left buttock, right/left inguino-crural fold, 
perianal, perineal, other) will be recorded at the designated study visits listed in Figure 1
(Appendix J).
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.
The site should make every attempt to have the same investigator conduct these 
assessments throughout the study for each subject.
Hurley Stage
See Section 1.3 for definition.  The investigator will determine the Hurley Stage in each 
affected anatomical region at the designated study visits listed in Table 1.  If more than 
one stage is present in a region, the worst stage in each region should be entered.
The site should make every attempt to have the same investigator conduct these 
assessments throughout the study for each subject.
Degree of Erythema
At the designated study visits listed in Table 1, for each anatomic region affected by HS, 
the investigator will assess the overall degree of erythema (Appendix K) affecting this 
region on a four-point ordinal scale, ranging between 0 (no redness), 1 (faint but 
discernible pink coloration), 2 (moderate red coloration), or 3 (very red or bright red 
coloration).
Follow-up Calls
One Week Prior to the Baseline Visit
Sites are encouraged to contact Subjects 1 week prior to the Baseline visit to confirm 
compliance with daily pain collection.  The phone call will be recorded in source 
document.


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One Week Following the Baseline Visit
Subjects will be contacted 1 week following the Baseline visit to ensure daily pain 
assessments are being recorded.  The phone call will be recorded in source document.
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.  The phone calls will be recorded in source document.  
Subjects with signs or symptoms of an infection will be brought into the study site for an 
unscheduled visit to be evaluated.  Study procedures for an unscheduled visit will be 
performed as outlined in Table 1.
70 Days Following the Last Dose of Study Drug
Subjects will be contacted approximately 70 days following the last dose of study drug to 
determine the status of any ongoing AEs or SAEs, or the occurrence of any new AEs or 
SAEs.  The Day 70 follow-up phone call will be recorded in source document only and 
confirmation of the contact will be submitted to AbbVie (Appendix L).  Any updates to 
ongoing AEs/SAEs, or new AEs/SAEs, should be submitted on the eCRF.  Information on 
any ongoing or new AEs/SAEs will be included in the database for the study.  
Photography
Subjects at prospectively selected sites will be asked to have photographs taken of their 
disease response during the study.  Subjects who consent will have photographs taken at 
the designated study visits listed in Table 1.  Photographs will be taken by procedures 
standardized by each site in the daily clinical practice.  Sites will submit the digital images 
to AbbVie. 
Adverse Events
See Section 6.1.


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Dispense Study Drug
Study drug will be dispensed to subjects, who perform self-injection or receive the 
subcutaneous injection of study drug by a qualified person at the designated study visits 
listed in Table 1.
5.3.2
Drug Concentration Measurements
Blood samples for adalimumab and Anti-Adalimumab Antibody (AAA) assays will be 
collected by venipuncture at the designated study visits listed in Table 1.
5.3.2.1
Collection of Samples for Analysis
Blood samples for pharmacokinetic (PK) adalimumab analysis will be collected by 
venipuncture into appropriately labeled 6-mL evacuated serum collection tubes without 
gel separator at the required visits.  All samples will be obtained prior to study drug 
administration at the designated study visits listed in Table 1 (Baseline, Weeks 2, 4, 8, 12, 
16, 20, 24, 36, and 52, or at the Premature Discontinuation visit if the subject discontinues 
prior to Week 52).
Blood samples for AAA will be collected by venipuncture into appropriately labeled 6 mL 
evacuated serum collection tubes without gel separator at the required visits.  All samples 
will be obtained prior to dosing at the designated study visits listed in Table 1 (Baseline, 
Weeks 4, 12, 24, 36, and 52, or at the Premature Discontinuation visit if the subject 
discontinues prior to Week 52).
The date and time that each blood sample is collected will be recorded to the nearest 
minutes in the source document and on the appropriate eCRF.
Collection of Samples for Adalimumab Analysis
A maximum of 10 samples are planned to be collected per subject for PK adalimumab 
analysis.  The total number of PK adalimumab samples planned will not exceed 


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150 (10 samples × 15 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 6 samples are planned to be collected per subject for AAA analysis.  The 
total number of AAA samples planned will not exceed 90 (6 samples × 15 subjects) for 
the entire study.  Sample calculations are based on the maximum number of subjects.
5.3.2.2
Handling/Processing of Samples
Sufficient blood will be collected to provide approximately 2 mL serum from each 
sample.  Allow the blood to clot for 30 minutes at room temperature before centrifugation.  
Additional detailed instructions for the handling and processing of samples will be 
provided from the central laboratory.
5.3.2.3
Disposition of Samples
The frozen serum samples will be packed in dry ice (pellet form) sufficient to last 3 days 
during transport.  Samples will be shipped by central laboratory pursuant to instructions 
from the sponsor.  An inventory of the samples will be included in the package for 
shipment.
5.3.2.4
Measurement Methods
Serum concentrations of adalimumab and AAA will be determined using a validated 
assay methodology (Ligand Binding Assay, LBA) under the supervision of the Drug 
Analysis Department at AbbVie.
5.3.3
Efficacy Variables
5.3.3.1
Primary Variable
The primary efficacy endpoint is the proportion of subjects achieving HiSCR at Week 12.  
HiSCR is defined as at least a 50% reduction in the total abscess and inflammatory nodule 


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count (AN count) with no increase in abscess count and no increase in draining fistula 
count relative to Baseline.
5.3.3.2
Secondary Efficacy Variables
The following secondary efficacy variables will be analyzed:
1.
Proportion of subjects achieving AN count of 0, 1, or 2 at Week 12
2.
Proportion of subjects achieving at least 30% reduction and at least 1 unit reduction 
from Baseline in Patient's Global Assessment of Skin Pain (NRS30) – at worst at 
Week 2 among subjects with baseline NRS ≥ 3
3.
Change in modified Sartorius scale from Baseline to Week 12
Other efficacy variables will be analyzed at each scheduled visit, including the primary or 
secondary variables for visits other than Week 2 or 12.
●
Proportion of subject achieving HiSCR
●
Proportion of subjects achieving AN count of 0, 1, or 2
●
Proportion of subjects achieving NRS30 – at worst, among subjects with 
baseline Patient's Global Assessment of Skin Pain (NRS) ≥ 3
●
Proportion of subjects achieving NRS30 – on average, among subjects with 
baseline Patient's Global Assessment of Skin Pain (NRS) ≥ 3
●
Change in modified Sartorius scale from Baseline
●
Proportion of subjects achieving complete elimination of abscesses at each 
visit, among subjects who have any abscess at Baseline
●
Percentage change from Baseline in number of abscesses, among subjects who 
have at least one abscess at Baseline
●
Change from Baseline in number of abscesses
●
Proportion of subjects achieving complete elimination of draining fistulas at 
each visit, among subjects who have any draining fistulas at Baseline
●
Percentage change from Baseline in number of draining fistulas, among 
subjects who have at least one draining fistula at Baseline


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●
Change from Baseline in number of draining fistulas
●
Percentage change from Baseline in number of inflammatory nodules, among 
subjects who have at least one inflammatory nodule at Baseline
●
Proportion of subjects achieving complete elimination of inflammatory 
nodules at each visit, among subjects who have any inflammatory nodules at 
Baseline
●
Change from Baseline in number of inflammatory nodules
●
Number of interventions until Week 12
●
Proportion of subjects with DLQI = 0
●
Proportion of subjects with DLQI = 0 or 1
●
Change from Baseline in DLQI
●
Percentage change from Baseline in Patient's Global Assessment of Skin Pain 
(NRS) – at worst, among subjects who have baseline NRS ≥ 3
●
Percentage change from Baseline in Patient's Global Assessment of Skin Pain 
(NRS) – on average, among subjects who have baseline NRS ≥ 3
●
Change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – at 
worst
●
Change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – on 
average
●
Proportion of subjects achieving AN50 (at least 50% reduction in the AN 
count relative to Baseline)
●
Proportion of subjects achieving AN75 (at least 75% reduction in the AN 
count relative to Baseline)
●
Proportion of subjects achieving AN100 (100% reduction in the AN count 
relative to Baseline)
●
Absolute and percentage change from Baseline in AN count
●
Proportion of subjects achieving erythema score of 1 or 0 in all affected 
anatomic regions among subjects who have erythema score of 2 or more in at 
least one anatomic region at Baseline
●
Proportion of subjects who experience worsening by at least one Hurley Stage 
in at least 1 affected anatomic region


Adalimumab
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●
Proportion of subjects who experience improvement by at least one Hurley 
Stage in at least 1 affected anatomic region
●
Change from baseline in TSQM
●
Change from baseline in EQ-5D index
●
Change from baseline in EQ-5D VAS
●
Proportion of subjects who experience flare, defined as an at least 25% 
increase in AN counts with a minimum increase of 2 relative to Baseline
●
Number of days on flare, calculated from the day when flare is observed to the 
day prior to the observation that flare is no long present.  Of note, there could 
be multiple periods that flares are observed, in which case, the total days from 
the multiple periods will be used
●
Proportion of subjects who experience at least 25% increase in abscess counts 
with a minimum increase of 2 relative to Baseline
●
Proportion of subjects who experience at least 25% increase in inflammatory 
nodule counts with a minimum increase of 2 relative to Baseline
●
Proportion of subjects who experience at least 25% increase in draining fistula 
counts with a minimum increase of 2 relative to Baseline
●
Change from Baseline in CRP
●
Percentage change from Baseline in CRP
●
Time to the second incidence of the two-consecutive visits with AN count ≥ 
Baseline AN count
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 Table 1 and as 
described in Section 6.0 and Table 2.
5.3.5
Pharmacokinetic Variables
Adalimumab trough serum concentrations will be summarized at each time point using 
descriptive statistics.


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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 investigator may discontinue 
any subject's participation for any reason, including an adverse event, safety concerns or 
failure to comply with the protocol.
Subjects will be withdrawn from the study immediately if any one of the following 
occurs:
●
Clinically significant abnormal laboratory result(s) or adverse event(s), as 
determined by the investigator in consultation with AbbVie TA MD.
●
The investigator believes it is in the best interest of the subject.
●
The subject requests withdrawal from the study.
●
Inclusion and exclusion criteria violation is noted after the subject started study 
drug, when continuation of the study drug would place the subject at risk as 
determined by AbbVie TA-MD (Section 5.2 and Section 7.0).
●
Introduction of prohibited medications or dosages when continuation of the 
study drug would place the subject at risk as determined by AbbVie TA MD.
●
Subject is non-compliant with TB prophylaxis.
●
The subject becomes pregnant while on study medication.
●
Subject has known dysplasia of the gastrointestinal tract (a colonoscopy is not 
required to enter the study) or a malignancy, except for localized non 
melanoma skin cancer.  Discontinuation for carcinoma in-situ of the cervix is 
at the discretion of the investigator.
●
Subject is diagnosed with lupus-like syndrome, multiple sclerosis or 
demyelinating disease.
●
Subject is significantly non-compliant with study procedures which would put 
the subject at risk for continued participation in the trial, as determined by the 
investigator, in consultation with AbbVie TA MD.
●
Subject requires or receives more than 2 interventions until Week 12.


Adalimumab
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●
Subject requires or receives more than 2 interventions on the same lesion or 2 
of the same type of intervention on the same lesion within a 4-week period 
after Week 12.
If, during the course of study drug administration, the subject prematurely discontinues 
study drug use, the procedures 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 investigator feels are 
necessary to treat the subject's condition.  Following discontinuation of the study drug, the 
subject will be treated in accordance with the investigator's best clinical judgment.
A final phone call will be made to the subject approximately 70 days after the last dose of 
study drug to determine the status of any ongoing AEs/SAEs or the occurrence of any new 
AEs/SAEs.  The Day 70 follow-up phone call will not be required for any subject who 
initiates adalimumab therapy not supplied in the context of the clinical trial after the end 
of study participation.
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 in the 
source and on the appropriate eCRF page.
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 phone 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 investigator may also terminate the study at his/her 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 


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concerns.  If AbbVie terminates the study for safety reasons, AbbVie will immediately 
notify the investigator by phone 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 site.  Possible reasons for termination of the study include, but are not 
limited to:
●
Safety concerns based on reported data
●
Unsatisfactory enrollment with respect to quantity or quality
●
Inaccurate or incomplete data collection
●
Falsification of records
●
Failure to adhere to the protocol
5.5
Treatments
5.5.1
Treatments Administered
All treatments administered will be assigned by the interactive response technology (IRT).  
All subjects will receive 4 injections at Week 0 (160 mg), 2 injections at Week 2 (80 mg) 
and 1 injection weekly from Week 4 (40 mg) until the study end.
Study drug will be provided as a sterile, preservative-free solution for SC administration 
solution in 1 mL pre-filled syringes containing adalimumab 40 mg/0.4 mL.  Study drug 
will be administered subcutaneously using sterile technique by the research staff or 
qualified designee (health care professional, or patient him/herself or family member 
following proper training) at the study site or at home.
5.5.2
Identity of Investigational Product
The individual study drug information is presented in Table 3.


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Table 3. 
Identity of Investigational Product
Study Drug
Formulation
Manufacturer
Adalimumab
40 mg/0.4 mL pre-filled syringes
Adalimumab/Mannitol, Polysorbate 80, Water for injection,
AbbVie
Study drug is not blinded in this study.  As per country regulations, investigational 
product (IP) will be labeled with the following information:
●
Sponsor's name and address
●
Study protocol number
●
Study drug name
●
Storage conditions
●
Manufacturing number
●
Display of "for clinical trial"
Each site will be responsible for tracking the lot numbers and expiration dates for all non-
investigational medicinal products that are dispensed.
5.5.2.1
Packaging and Labeling
Investigational product will be provided in a 0.4 mL pre-filled syringe containing 
adalimumab 40 mg/0.4 mL and will be packaged in two pre-filled syringes per carton.  
Each adalimumab kit carton and syringe will be labeled and have a unique kit ID on the 
carton.  The labels for the adalimumab syringe, kit carton will minimally contain the 
required country information.
Each label must remain affixed to the dosing unit.
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 medication drug must not be frozen at any time.  A storage 
temperature log is to be maintained to document proper storage conditions.  The 


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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.  
Study medication should be quarantined and not dispensed until AbbVie GPRD or 
AbbVie Temperature Excursion Management System (ATEMS) deems the medication 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.
Investigational 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 Group
Before the site is initiated, the instructions for 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.  
5.5.4
Selection and Timing of Dose for Each Subject
Subjects should take study medication as outlined in Section 5.5.1.
At Baseline, after all assessments have been completed, subjects will receive four 
injections of study drug (40 mg each) as detailed in Section 5.5.1.  Appropriate site 
personnel will train and then supervise the subject or designee administering at least 
one injection of the study drug at the Baseline visit to ensure proper understanding of 
injection technique, if the subject wants to perform self-injection of the study drug 
(Appendix M).  Subject or designee will subsequently dose and be witnessed by site staff 
during their study visits to ensure continued proper technique.  When study drug is 
administered in the office, subjects should remain at the site for approximately 15 to 30 
minutes after injection for observation.


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For home administration of injections, 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 forgets to administer the injection of study medication at their regularly 
scheduled dosing date, they should take the forgotten injection as soon as she/he 
remembers the dose was missed up to the day of their next scheduled dose.  The subject 
should not administer two doses on the same day, except at Week 2.
In the event the incorrect dose is taken, the entire volume of study medication is not 
injected, or a dose is missed, the subject should contact the site to determine how to 
proceed with dosing.  The subject must record all dosing information on the subject-
dosing sheet.
Doses not administered (e.g., not taken before next dose is scheduled) should be recorded 
in the source documentation as not taken.  The unused dose should be returned full to the 
study site, and the subject should administer the next regularly scheduled dose.  The 
subject should then resume their regular dosing schedule based on the first dosing date at 
Baseline (Week 0).
5.5.5
Treatment Compliance
The investigator or his/her designated and qualified representatives will dispense study 
drug only for use by 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 their qualified designee will administer all doses of study drug when not at the 
site.  Appropriate site staff will supervise the subject's administration of the study drug at 
required in-office study visits to ensure proper injection technique.  In order to document 
compliance with the treatment regimen, the subject will be given a dosing sheet 
(Appendix N) to record all injection dates and times.  Compliance information will be 
documented on the appropriate eCRF.  Subjects will be counseled on missed doses of 
medication.


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If the subject does not return the dosing sheet, IP boxes and sharp containers (when 
applicable), the site 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 subjects are consistently not returning the dosing sheet, not providing accurate dosing 
information, or consistently missing doses and/or are deemed non-compliant with no 
explanation, the situation will be discussed with AbbVie TA MD and the subject may be 
discontinued from the study.
5.5.6
Drug Accountability
The 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 the 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 Note or similar document will be kept in the site files as a 
record of what was received.
In addition, an accurate running inventory of study drug will be kept by the 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, kit number(s), date 
dispensed, subject number, and the identification with date of the person dispensing the 
drug.
For Subjects Dosing at Home (Self-Injection)
Each subject will be given his/her own sharps disposal container to store used pre-filled 
syringes.  Empty IP boxes and returned Sharps containers should be returned by the 
subject at each visit for accountability and compliance purposes and new containers 
issued as necessary.  Empty Boxes and returned Sharps containers will be retained (unless 


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prohibited by local law or site regulation) until the Monitor is on site to confirm the 
returned medication.  Monitors and site staff will complete study medication 
accountability via study medication logs, source documents, subject dosing sheets, empty 
IP boxes and by visually inspecting the syringes in the Sharps container whenever 
possible.  Used Sharps containers should never be opened.  Once the Monitor has verified 
drug accountability at the site, the site staff and Monitor will document that the used 
pre-filled syringes have been destroyed, using appropriate biohazard precautions, when 
appropriate.  If the destruction of the used study drug is not feasible at the site, the site 
staff or Monitor will send them to the destruction facilities designated by AbbVie.  A 
copy of the destruction methodology should be maintained at the site's facility or kept by 
AbbVie.  Unused medication will be returned by the Monitor after drug accountability has 
been completed at the site.
Non-investigational medicinal products (standard of care) must be obtained commercially 
by each site.
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 was chosen to evaluate adalimumab in subjects with 
moderate to severe HS.  The first 12-week period (Weeks 0 to 12) is to provide clinical 
data demonstrating the safety and efficacy of adalimumab 160 mg at Week 0 and 80 mg at 
Week 2 and 40 mg weekly starting at Week 4 for treatment of HS.  The subsequent period 
(after Weeks 12 until the study end) is to provide information on long-term safety and 
maintenance of efficacy for subjects on adalimumab weekly dosing.  This is a single arm 
study and no control group is set.
5.6.2
Appropriateness of Measurements
Standard statistical, clinical and laboratory procedures will be utilized in this study.  
Efficacy measurements in this study have been selected or designed to assess disease 


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activity in subjects with chronic HS.  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 (abscess and 
inflammatory nodule count of greater than or equal to 3) who meet all inclusion criteria 
and who do not meet any of the exclusion criteria are eligible for this study.  The 
population being studied represents normal clinical practice with a broad spectrum of 
subjects with a high medical need due to great physical disability and discomfort.  This 
ensures the activity of adalimumab can be evaluated across a distribution of disease 
severity in the study.
5.6.4
Selection of Doses in the Study
In the global Phase 3 Studies M11-810 and M11-313, used dosing regimen (40 mg 
weekly starting at Week 4, after 160 mg at Week 0 and 80 mg at Week 2) was 
demonstrated the statistical superiority of efficacy compared to placebo.  Assessment of 
the comparative safety and efficacy of ew dosing and eow dosing confirmed that ew 
dosing provides a better benefit risk balance in the treatment of HS, based on the better 
efficacy with ew dosing and on the fact that the AE profile for ew dosing, eow dosing, and 
placebo in the Phase 3 studies were similar over the next 24 week placebo controlled 
period.  
The amount of safety data to be generated, along with the existing safety data generated in 
the existing other indications (Western patients with HS, Japanese patients with UC and 
CD for the initial high dose at Baseline and Week 2, and dose escalation to 80 mg eow in 
Japanese patients with RA, AS and Ps for the maintenance dose, where PK of 40 mg ew is 
comparable to that of 80 mg eow), supports the proposed indication with the proposed 
dose regimen.


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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 investigational product in this trial contains both
●
Biologic compound and
●
Device components (pre-filled syringe)
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For AEs, please refer to Section 6.1.  For product 
complaints, please refer to Section 6.2.
6.1
Medical Complaints
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The 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 SAEs considered as having "no reasonable possibility" of being 
associated with study drug, the Investigator will provide other cause(s) of the event.  For 
AEs to be considered intermittent, the events must be of similar nature and severity.  AEs, 
whether in response to a query, observed by site personnel, or reported spontaneously by 
the subject will be recorded.
All AEs will be followed to a satisfactory conclusion.


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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 (investigational) product, 
whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from 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 AE should be reported as a new AE.  Laboratory abnormalities and 
changes in vital signs are considered to be AEs only if they result in discontinuation from 
the study, necessitate therapeutic medical intervention, (meets protocol specific criteria 
[see Section 6.1.7 regarding toxicity management]) and/or if the investigator considers 
them to be AEs.
An elective surgery/procedure scheduled to occur during the study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE.
6.1.1.2
Serious Adverse Events
If an AE meets any of the following criteria, it is to be reported to AbbVie as an SAE 
within 24 hours of the site being made aware of the SAE.


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Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would 
have resulted in immediate fatality if medical intervention 
had not been taken.  This does not include an event that 
would have been fatal if it had occurred in a more severe 
form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to 
an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss.
Persistent or 
Significant 
Disability/Incapacity
An event that results in a condition that substantially 
interferes with the activities of daily living of a study 
subject.  Disability is not intended to include experiences of 
relatively minor medical significance such as headache, 
nausea, vomiting, diarrhea, influenza, and accidental 
trauma (e.g., sprained ankle).
Important Medical 
Event Requiring 
Medical or Surgical 
Intervention to Prevent 
Serious Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but 
based on medical judgment may jeopardize the subject and 
may require medical or surgical intervention to prevent any 
of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, 
congenital anomaly, or persistent or significant 
disability/incapacity).  Additionally, any elective or 
spontaneous abortion or still birth 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.


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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.
Severe
The adverse event causes considerable interference with the 
subject's usual activities and may be incapacitating or
life–threatening.
The CTCAE v4.0 – JCOG (Japanese translation JCOG version on 09 April 2013) can be 
used as a reference as appropriate.
6.1.3
Relationship to Study Drug
The Investigator will use the following definitions to assess the relationship of the AE 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 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 SAE.


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6.1.4
Adverse Event Collection Period
All AEs reported from the time of study drug administration until approximately 70 days 
following discontinuation of study drug administration have elapsed, as well as the 
medication for AEs/SAEs, 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.
Subjects will be contacted approximately 70 days following study drug discontinuation 
for an assessment of any new or ongoing AEs/SAEs (Appendix L) as discussed in 
protocol Section 5.3.1.1, except for those subjects who initiate adalimumab therapy 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 call and any new AEs should 
be reported through the mechanism used for all post-marketing adverse experiences. 
All SAEs or Adverse Events of Special Interest, as defined by AbbVie, reported during 
the 70 day follow-up phone call must be captured in the clinical database. 
Adverse event information will be collected as shown in Figure 3.
Figure 3. 
Adverse Event Collection
SAEs and 
Protocol-related 
Nonserious AEs
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported
Consent
Signed
Study Drug
Start
Study Drug 
Stopped
70 days After Study 
Drug Stopped




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Secondary Contact (Regional Medical Monitor):
In emergency situations involving study subjects when the primary Therapeutic Area 
Medical Director (TA-MD) is not available by phone, please contact the 24-hour AbbVie 
Medical Escalation Hotline where your call will be re-directed to a designated backup 
AbbVie TA MD:
Phone:  
The Principal Investigator will provide documentation of all SAEs to the Director of the 
investigative site and the Sponsor.


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6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the 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 site becoming aware of the event.
6.1.7
Toxicity Management
Subjects who develop a new infection while undergoing treatment with study drug should 
be monitored closely.  Administration of study injections should be interrupted if a subject 
develops an infection requiring IV anti-infective treatment or if an infection meets the 
definition of "serious" (refer to Section 6.1.1.2 for definitions).  Study medication may be 
restarted once the Investigator determines that the infection has been successfully treated.  
Otherwise prohibited concomitant medications may be given if medically necessitated.  
Specifically, if a patient develops an intercurrent infection, then topical and/or oral 
antibiotic usage is permitted.  If a patient experiences an intercurrent illness associated 
with pain for which oral analgesia is required, then otherwise-prohibited oral analgesics 
are permitted.  Topical and/or oral antibiotic usage and oral analgesia are not permitted for 
worsening of HS (except as specified in Section 5.2.3.2).  Prior to use, every attempt 
should be made to contact the AbbVie TA-MD for direction on re introduction of study 
drug after prohibited medication administration.


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If the subject must undergo elective surgery, the study injections must be interrupted 
2 weeks prior to the surgery.  If the subject must undergo emergency surgery, the study 
injections must be interrupted at the time of the surgery.  The injectable study medication 
can recommence at least 2 weeks after surgery once the physician has examined the 
surgical site and determined that it has healed and there is no sign of infection.
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 medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device not working properly or packaging issues.
Any information available to help in the determination of causality to the events outlined 
directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product and/or device 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 with the alleged complaint 
condition (prefilled syringe).  In instances where a return is requested, every effort should 
be made by the Investigator to return the product within 30 days.  If returns cannot be 


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accommodated within 30 days, the site will need to provide justification and an estimated 
date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol unless when 
necessary to eliminate an immediate hazard to study subjects.  The principal investigator 
is responsible for complying with all protocol requirements, and applicable global and 
local laws regarding protocol deviations.  If a protocol deviation occurs (or is identified) 
after a subject has been enrolled, the principal investigator is responsible for notifying 
Independent Ethics Committee (IEC)/Independent Review Board (IRB) regulatory 
authorities (as applicable), and the following AbbVie Clinical Monitor(s):
Primary Contact:
Alternate Contact:
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.  
For the purposes of this protocol, reportable deviations are defined as:
●
Subject entered into the study even though she/he did not satisfy entry criteria


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●
Subject who developed withdrawal criteria during the study and was not 
withdrawn
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded or prohibited concomitant treatment
The Investigator will record all protocol deviations in the appropriate medical records at 
site.
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 in Japanese subjects with moderate to severe HS after 12 weeks of treatment, 
and to evaluate long-term safety and efficacy for continuous weekly dosing from 
Week 12.  Complete, specific details of the statistical analysis will be described and fully 
documented in the Statistical Analysis Plan (SAP).  The SAP will be finalized by first 
interim analysis.
8.1.1
Analysis Populations
The Full Analysis Set (FAS) Population includes all subjects who complied with GCP and 
received at least one dose of study drug and had at least one-post-treatment efficacy 
assessment.  FAS is the primary population for the efficacy analysis.
The Safety Population is defined as all subjects who receive at least one dose of study 
drug in the study, and will be used for safety analysis.
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, minimum, median, and 
maximum for continuous variables; and counts and percentages for discrete variables.


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The analysis will be performed using SAS® (SAS Institute Inc., Cary, NC, USA).
8.1.3
Demographics and Baseline Characteristics
Demographics and Baseline characteristics of the study subjects will be summarized using 
descriptive statistics.  
8.1.4
Statistical Analyses of Efficacy
The efficacy analysis will be conducted in the FAS Population.  
Visit windows and the data handling convention for summarizing efficacy results will be 
defined in the Statistical Analysis Plan.
Missing data will be imputed using the following methods for the efficacy analyses in the 
FAS Populations:
●
Non-Responder Imputation (NRI):  the NRI analysis will categorize any 
subject who has missing value at a specific visit as non-responder for that visit.  
The NRI will be the primary approach in the analysis of categorical variables.  
●
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 analysis of continuous variable, and the 
secondary approach in the analysis of categorical variables.
●
As-observed:  The As-observed analysis 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 
analysis will be the secondary approach in the analysis of continuous variables.
Lesions that received intervention will be counted as permanently present from the date of 
the intervention.


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8.1.4.1
Primary Analysis of Efficacy
The primary analysis is to describe the proportion of subjects achieving HiSCR at 
Week 12.  The number and percentage of subjects achieving HiSCR will be calculated.
The primary analysis will be carried out in the FAS Population.  Non responder 
imputation will be used as primary approach for missing values.
8.1.4.2
Secondary Analysis of Efficacy
Secondary analyses of efficacy will be carried out in the FAS Population
For the analysis of Patient's Global Assessment of Skin Pain (NRS), daily assessment will 
be evaluated and weekly average will be used.  For analysis, subjects who received 
analgesics other than ibuprofen or acetaminophen (e.g., Tramadol) for skin pain will be 
counted as non-responder for categorical variables, and have their last pain assessment 
before the start of the analgesic carried forward for continuous variables, from the start 
day of the analgesics until fourteen (14) days after the stop of analgesic use.  Concomitant 
medication for treatment of HS or pain will be reviewed; confounding medications (those 
considered as having potential effect on the pain assessments) and the time periods 
affected by such medications will be determined.  Subjects will be counted as non-
responder for categorical variables, and have their last pain assessment before the start of 
the confounding medications carried forward for continuous variables for these periods.  
Additional analyses may be performed for the primary efficacy variable.  Results from 
any additional analyses may be used as supplemental information for the study report.
Subgroup Analysis of Efficacy
To evaluate the consistency of the efficacy in the primary efficacy variable over 
demographic and other baseline characteristics, summaries and analyses will be 
performed for the following subgroups:
1.
Baseline Hurley Stage (II/III)


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2.
Concomitant use of oral antibiotics (yes/no)
3.
Age group (< 40, 40–64, ≥ 65, if less than 10% of subjects in the ≥ 65 group, that 
group will be combined with 40–64 group.)
4.
Sex (male, female)
5.
Duration of HS (< median, ≥ median)
6.
Weight (< median, ≥ median)
7.
Body Mass Index (BMI)  category:  normal (< 25), over weight (25 – < 30), obese 
(30 – < 40), Morbid obesity (≥ 40)
8.
Current smoking status (yes/no)
9.
Baseline CRP level (< median, ≥ median)
10.
Baseline AN count (≤ 5, 6 – 10, 11+)
11.
Baseline AN count (< median, ≥ median)
8.1.5
Statistical Analysis of Safety
All AEs, SAEs, and AEs leading to discontinuation will be collected during the study and 
up to approximately 70 days after the last dose of the study drug.  Safety analyses will be 
carried out using the Safety Population.  SAEs and protocol-related AEs will be 
summarized as well.  A treatment-emergent AE 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.  The number and percent of subjects experiencing treatment 
emergent AEs will be tabulated using the Medical Dictionary for Drug Regulatory 
Activities (MedDRA®) system organ class and preferred term.  Summaries (including 
percentages and event per 100 patient-year) of SAEs, deaths, AEs leading to 
discontinuation from the study, and AEs of Special Interest according to the most updated 
Humira Risk Management Plan will be provided as well.  Mean change in laboratory 
variables and vital sign variables will be summarized at each visit.  The last evaluation 
prior to the first dose of study drug will be used as Baseline for all analyses.  For selected 


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parameters, a listing of all subjects with any laboratory determination meeting Common 
Toxicity Criteria (CTC) of Grade 2 or higher will be provided.  Shift tables for changes 
from Baseline according to the normal range will also be provided.
8.1.6
Interim Analysis
Interim analysis is planned at Week 24 and repeated at appropriate time after Week 52.
8.2
Determination of Sample Size
This study is designed to enroll approximately 15 subjects due to quite limited number of 
patients with HS in Japan, considering the feasibility of the study conduct.  But study 
result will provide adequate information to characterize the safety profile of adalimumab.  
In the global placebo-controlled studies (Studies M11-810 and M11-313), the response 
rates of HiSCR at Week 12 were 59% and 42% in the adalimumab ew group, and 28% 
and 26% in the placebo group, respectively.  Assuming the threshold response rate at 
Week 12 of 25% (response rate with no medication) and the expected clinical response 
rate of 60%, a sample size of 13 subjects will have 80.1% power to detect the difference 
of 35% in the primary endpoint and using one sample Chi-square test at one-sided 2.5% 
significant level.
8.3
Study Drug Allocation Methods
An IRT will be used to allocate study drug to subjects.  Detailed instructions for using the 
IRT will be provided to the site personnel.
Subjects who are eligible based on inclusion and exclusion criteria and have had all pre 
enrollment procedures performed will be allocate to the study drug.  
8.4
Pharmacokinetic Analysis
Adalimumab trough serum concentrations will be summarized 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 


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maximum as appropriate.  Individual subject concentrations versus time plots and mean 
concentration versus time plots will be provided.  Data listings 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.
The results may be incorporated into a population pharmacokinetic analysis if the data 
warrants in order to estimate parameters such as apparent clearance (CL/F) and apparent 
volume of distribution (V/F) of adalimumab.
As for the immunogenicity, serum AAA concentrations will be listed.  A subject will be 
considered to be AAA+ when the subject has at least one AAA concentration greater than 
20 ng/mL (confirmed with confirmatory assay) and the sample will be collected within 
30 days after an adalimumab dose.  The number and percentage of subjects who 
developed AAA will be determined.  As appropriate, the effect of AAA on adalimumab 
pharmacokinetics, efficacy variable(s), and treatment-emergent adverse events may be 
evaluated.
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, 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 the study 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.


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Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  The investigator will be required to submit, 
maintain and archive study essential documents according to 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 
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 
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 
Harmonization (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 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,  
including the acceptability of photography of skin lesion, will be reviewed and signed and 
dated by the subject, the person who administered the informed consent.  If the subject is 
< 20 years old, a subject's parent or legal guardian must be explained and willing to give 
written informed consent.  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.


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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.
9.3.1
Informed Consent Form and Explanatory Material
The Principal Investigator will prepare the consent form and explanatory material required 
to obtain subject's consent to participate in the study with the cooperation of the sponsor 
and will revise these documents as required.  The prepared or revised consent forms and 
explanatory material will be submitted to the sponsor.  Approval of the IRB will be 
obtained prior to use in the study.
9.3.2
Revision of the Consent Form and Explanatory Material
When important new information related to the subject's consent becomes available, the 
Principal Investigator will revise the consent form and explanatory material based on the 
information without delay and will obtain the approval of the IRB prior to use in the 
study.  The Investigator will provide the information without delay to each subject already 
participating in the study, and will confirm the intention of each subject to continue in the 
study or not.  The Investigator will also provide further explanation using the revised 
consent form and explanatory material and will obtain written consent from each subject 
of their own free will to continue participating in the study.  If the subject is < 20 years 
old, a subject's parent or legal guardian must be explained and willing to give written 
informed consent.
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 


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media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The following assessments that will be completed by the subject on paper will be 
considered source documentation:
●
DLQI
●
EQ-5D
●
Patient's Global Assessment of Skin Pain (NRS)
●
HS QoL
●
TSQM
Once collected, these outcome assessment sheets will be entered by the Site into the EDC 
system and will be available for viewing by site personnel.
The following contents recorded in eCRF may also be used as source, and will require an 
Investigator's approval on the eCRF as verification of the accuracy of the information:
●
Route of drug administration
●
Diagnostics, time course, severity, frequency and relationship to study drug, 
alternative etiology, medication for recovery, and seriousness for either SAEs 
or Nonserious AEs
●
Investigator's comments
●
Reason for Premature discontinuation for subject
●
Reason why the physician or nurse performed injection of study drug, after 
self-injection started (if applicable)
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.


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10.2
Case Report Forms
Case report forms (CRF) 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 electronic data capture (EDC) system called Rave® provided by the 
technology vendor Medidata Solutions Incorporated, NY, USA.  The EDC system and the 
study-specific electronic case report forms (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 eCRFs will be conducted 
by AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system, except for subject-
completed questionnaires, which will be completed on paper by the subject then 
transcribed into the EDC system by site personnel.  All data entered into the eCRF will be 
supported by source documentation except as noted in Section 10.1.
The investigator or an authorized member of the investigator's staff 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 
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 
Principal Investigator will review the eCRFs for completeness and accuracy and provide 
his or 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 
investigator sites at the end of the site's participation in the study.  Data from the EDC 


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system will be archived on appropriate data media (CD-ROM, etc.) and provided to the 
investigator at that time as a durable record of the site's eCRF data.  It will be possible for 
the investigator to make paper printouts from that media.  The following assessments will 
be completed by subjects on paper:
●
DLQI
●
EQ-5D
●
Patient's Global Assessment of Skin Pain (NRS)
●
HS QoL
●
TSQM
Site staff will verify completion of these forms.  All questionnaires must be legible and 
completed in indelible ballpoint ink.  Any necessary corrections are to be made by 
drawing a single line through the incorrect entry and writing in the revision, the date of 
the correction, the reason for the correction, and the initials of the study subject who is 
making the correction.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.
11.0
Data Quality Assurance
Computer logic and manual checks will be run to identify items such as inconsistent study 
dates.  Any necessary corrections will be made to the eCRF by the Site.
An Investigator's Meeting and/or Start-up Meeting at the site will be held with AbbVie 
personnel, the investigators and their study coordinators and the Monitors for the study.  
This meeting will include a detailed discussion of the protocol, performance of study 
procedures, eCRF and Subject Diary and log completion, and specimen collection 
methods.  In addition to or instead of the Investigator's Meeting, the study personnel at 
each site may be trained on the study procedures by a Monitor at a study initiation visit 
and will be given an eCRF completion guideline for reference.


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The Monitors will monitor each site throughout the study.  Source document review will 
be performed against entries in the eCRF database and a quality assurance check will be 
performed to ensure that the investigator is complying with the protocol and regulations.
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 may be disclosed as deemed necessary by AbbVie to other 
clinical investigators, other pharmaceutical companies, to the FDA and to other 
governmental agencies.  To allow for the use of the information derived from this clinical 
study and to ensure complete and thorough analysis, the 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 investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 


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site.  When a copy is provided to AbbVie, the site should carefully consider that it never 
include any subject identifying information by obscuring subject's name with a heavy 
black marker until the relevant information can no longer be seen.  
12.2
Publication
Core publication(s) will be authored by Principal Investigator(s) specified by AbbVie who 
contribute significantly to the implementation and conduct of the study and non-site 
personnel who contribute substantially to the design, interpretation or analysis of the 
study (e.g., AbbVie personnel or 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 investigators who provided significant input into study 
design, implementation, conduct and interpretation, in addition to AbbVie scientific 
personnel responsible for study conduct.
A named 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 
publication committee).  The named author approach will need sanction of the publication 
committee.
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 Director of the Site and 
the sponsor.  Continuation of this study beyond this date must be mutually agreed upon in 
writing by both the Director of the Site and the sponsor.  The investigator will provide a 
final report to the Director of the Site following conclusion of the study, and the Director 
of the Site will inform the summary of the report to IRB and the sponsor.


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The Director of the Site must retain any records related to the study according to local 
requirements.  If the Director of the Site is not able to retain the records, he/she must 
notify the sponsor to arrange alternative archiving options.
AbbVie will select the signatory investigator from the 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, investigational drug and study protocol.  
The signatory investigator for the study will review and sign the final study report in 
accordance with the European Medicines Agency (EMA) 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 Investigator's Brochure for adalimumab.
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 3 Multicenter, Open-Label, Single Arm  Study of the Safety 
and Efficacy of Adalimumab in Japanese Subjects with Moderate to 
Severe Hidradenitis Suppurativa
Protocol Date:
07 July 2016
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)


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15.0
Reference List
1.
von der Werth JM, Jemec GB.  Morbidity in patients with hidradenitis suppurativa.  
Br J Dermatol.  2001;144(4):809-13.
2.
Revuz JE, Canoui-Poitrine F, Wolkenstein P, et al.  Prevalence and factors 
associated with hidradenitis suppurativa:  results from two case-control studies.  J 
Am Acad Dermatol.  2008:59(4):596-601.
3.
Naldi L.  Epidemiology.  In:  Hidradenitis Suppurativa.  Chapter 8.  Jemec GB, 
Revuz J, Leyden J, editors.  Springer-Verlag, c.  2006.
4.
Jemec GB.  Treatment.  In:  Hidradenitis Suppurativa.  Chapter 25.  Jemec GB, 
Revuz J, Leyden J, editors.  Springer-Verlag, c.  2006.
5.
Layton A.  Pathology of Hidradenitis Suppurativa.  Chapter 4.  In:  Hidradenitis 
Suppurativa.  Jemec GB, Revuz J, Leyden J, editors.  Springer-Verlag, c.  2006.
6.
Canoui-Poitrine F, Le Thuaut A, Revuz JE, et al.  Identification of three 
hidradenitis suppurativa phenotypes:  latent class analysis of a cross-sectional 
study.  J. Invest Dermatol.  2013;133(6):1506-11.
7.
Kurokawa I.  Pathogenesis and Clinical Practice of Hidradenitis Suppurativa.  
Hihu-to-Rinsho.  2006;48(8):977-85.
8.
Kurokawa I, Hayashi N, Japan Acne Research Society.  Questionnaire surveillance 
of hidradenitis suppurativa in Japan.  J Dermatol.  2015;42(7):747-9.
9.
Clemmensen OJ.  Topical treatment of hidradenitis suppurativa with clindamycin.  
Int J Dermatol.  1983;22(5):325-8.
10.
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.
11.
Jemec GB.  Treatment of Skin Disease, 3rd ed.  Lebwohl MG et al, editors.  
Saunders; 2010.  Chapter 97.
12.
Adams DR, Gordon KB, Devenyi AG, et al.  Severe hidradenitis suppurativa 
treated with infliximab infusion.  Arch Dermatol.  2003;139(12):1540-2.


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13.
Moul DK, Korman NJ.  Severe Hidradenitis Suppurativa treated with Adalimumab.  
Arch Dermatol.  2006;142(9):1110-2.
14.
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.


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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 
amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
5.
Reading the information in the Investigator's Brochure/safety material provided, 
including the instructions for use and the potential risks and side effects of the 
investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making 
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and 
approved the initial clinical investigation and all amendments.


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9.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
10.
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
Clinical
Clinical
Statistics
Clinical
Clinical Pharmacology & Pharmacometrics
Bioanalysis
Clinical, Author
Clinical


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Appendix C.
Latest TB Risk Assessment Form Example
1.
Have you or an immediate family member or other close contact ever been 
diagnosed or treated for tuberculosis?
2.
Have you lived in or had prolonged travels to countries in the following regions:
●
Sub-Saharan Africa
●
India
●
China
●
Mexico
●
Southeast Asia or Micronesia
●
The former Soviet Union
3.
Have you lived or worked in a prison, homeless shelter, immigration center, or 
nursing home?
4.
Have you, or an immediate family member, had any of the following problems for 
the past 3 weeks or longer:
●
Chronic Cough
●
Production of Sputum
●
Blood-Streaked Sputum
●
Unexplained Weight Loss
●
Fever
●
Fatigue/Tiredness
●
Night Sweats
●
Shortness of Breath
From:  http://www.mayoclinic.com/health/tuberculosis/DS00372/DSECTION=risk-factors
http://www.in.gov/fssa/files/Tuberculosis_Questionnaire.pdf


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Appendix D.
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 √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?
yes
no
____________
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 E.
EuroQoL (EQ-5D questionnaire) – 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 F.
Patient's Global Assessment of Skin Pain – NRS – Example


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Appendix G.
Daily Subject Analgesic (Pain) Use Diary – Example
Please answer the questions below before you go to bed.  Provide your response based on 
the past 24 hours.
Did you take any pain medication in the past 24 hours?   Yes  No
If YES:
Fill in the chart with the information about the pain medication you took.  If "Other" write 
in the name of the pain medication you took.
Pain Medication
Type of Pain 
Medication 
Taken
(CHECK BOX)
Was the Pain 
Medication for 
HS?
Dose and Unit
(example:  
325 mg)
Number of Pills 
Taken
(example:  
2 pills)
Ibuprofen
 Yes  No
Acetaminophen
 Yes  No
Tramadol
 Yes  No
Other Pain 
Medication:
 Yes  No
Other Pain 
Medication:
 Yes  No
Other Pain 
Medication:
 Yes  No


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Appendix H.
Hidradenitis Suppurativa Quality of Life – Example
Overall, how 
would you rate 
your quality of 
life with 
Hidradenitis 
Suppurativa 
(HS)
Worst Possible                                                                                           Best Possible
                                                                                                                                   
0
1
2
3
4
5
6
7
8
9
10


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Appendix I.
Treatment Satisfaction Questionnaire for Medication – Example


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Appendix J.
Lesion Counts – Example
Note: Lesions that received intervention (Section 5.2.3.2) will be counted as permanently present from the date of the intervention and must be accounted for on the appropriate 
eCRF.  For a definition of terms, see Section 1.3
Lesion Counts    
(to be assessed at every 
visit)
Hurley Stage
Abscess
Non-Draining 
Fistula
Draining 
Fistula
Non-
Inflammatory 
Nodule
Inflammatory 
Nodule
Hypertrophic 
Scar
Longest 
distance (mm) 
between 2 
relevant 
lesions (If only 1 
lesion, measure 
diameter of 
lesion)
Are all lesions 
clearly 
separated by 
normal-
appearing 
skin? (yes/no)
Left Axilla
Right Axilla
Left Sub/Inframammary Area
Right Sub/Inframammary Area
Intermammary Area
Left Buttock
Right Buttock
Left Inguino-crural Fold
Right Inguino-crural Fold
Perianal
Perineal
Other
Totals
Worst Hurley


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Appendix K.
Degree of Erythema – Example
At every visit, for each anatomic region affected by HS, the investigator will assess the 
overall degree of erythema using a four-point ordinal scale ranging between 0 and 3.
Region (to be assessed at every visit)
Degree of Erythema
Left Axilla
Right Axilla
Left Sub/Inframammary Area
Right Sub/Inframammary Area
Intermammary Area
Left Buttock
Right Buttock
Left Inguino-crural Fold
Right Inguino-crural Fold
Perianal
Perineal
Other
0 = no redness
1 = faint but discernible pink coloration
2 = moderate red coloration
3 = very red or bright red coloration


Adalimumab
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Appendix L.
Day 70 Follow-Up Call – Example
Subject Number: ________
Please contact Subjects 70 days after study drug discontinuation.
______________________________________________________________________________________
Date of Call: ____________
☐Lost to Follow-up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt.)
☐No Events Reported
☐Adverse Events/ Serious Adverse Events Reported
List any new Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject 
was last seen in the clinic for this study.  Please also update the status of any ongoing AEs and/or SAEs.  If 
needed, provide AE/SAE details on the AE worksheet attached.  (Please report all SAEs to AbbVie within 
24 hours of being made aware of the event.)  Any medications taken as a result of the events should be 
entered on the eCRF.
If events are listed above, your Monitor will review and retrieve the appropriate eCRF pages during 
their next visit.
Please fax all completed forms to:
To Be Determined


Adalimumab
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Appendix M.
Injection Instructions – Example Pre-Filled Syringe
Subject Instructions
0.4 mL dose (40 mg)
(Administered as a single dose-pre-filled syringe)
Protocol M15-573
Tables of Contents
Dosing Schedule
General Information & Supplies
Injection Procedures


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Study Drug Dosing Schedule
Subject Number ________________
You will require subcutaneous (SC) injections throughout the study.
You will receive the following number of injections during this study:
●
Baseline visit (the first visit to receive study medication for this study) you 
will receive 4 injections at the clinic.  You will not be given any kits to take 
home.  The kit for Week 2 dosing will be dispensed at the Week 2 visit.
●
You will return for your Week 2 visit, at which time one kit will be dispensed 
(2 syringes total).  At the Week 2 visit, you will have a sample of blood drawn 
for PK, then the kit will be used to administer both injections in the office.  
You will not be given any kits to take home.  The kit for Week 4 dosing will 
be dispensed at the Week 4 visit.
●
You will return for your Week 4 visit, at which time two kits will be dispensed 
(4 syringes total).  At the Week 4 visit, you will have a sample of blood drawn 
for PK/AAA, then one of the kits will be used to administer 1 injection in the 
office.  You will take home the kits for your Week 5 (one injection), 6 (one 
injection) and 7 (one injection) doses, if you have qualified to conduct self-
injection of study drug after you signed for the IC.
●
You will return for your Week 8 visit, at which time two kits will be dispensed 
(4 syringes total).  At the Week 8 visit, you will have a sample of blood drawn 
for PK, then one of the kits will be used to administer 1 injection in the office.  
You will take home the kits for your Week 9 (one injection), 10 (one injection) 
and 11 (one injection) doses. 
●
You will return for your Week 12 visit, at which time two kits will be 
dispensed.  At the Week 12 visit, you will have a sample of blood drawn for 
PK/AAA, then you may take your Week 12 (1 injection) dose in the office.  
You will take home the kits for your Week 13 (one injection), 14 (one 
injection) and 15 (one injection) doses.
●
You will return for your Week 16 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 16 visit, you will have a sample of 


Adalimumab
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121
blood drawn for PK, then one of the kits will be used to administer 1 injection 
in the office.  You will take home the kits for your Week 17 (one injection), 18 
(one injection) and 19 (one injection) doses.
●
You will return for your Week 20 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 20 visit, you will have a sample of 
blood drawn for PK, then one of the kits will be used to administer 1 injection 
in the office.  You will take home the kits for your Week 21 (one injection), 22 
(one injection) and 23 (one injection) doses.
●
You will return for your Week 24 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 24 visit, you will have a sample of 
blood drawn for PK/AAA, then one of the kits will be used to administer 1 
injection in the office.  You will take home the kits for your Week 25 (one 
injection), 26 (one injection) and 27 (one injection) doses.  
●
You will return for your Week 28 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 28 visit, one of the kits will be used 
to administer 1 injection in the office.  You will take home the kits for your 
Week 29 (one injection), 30 (one injection) and 31 (one injection) doses.  
●
You will return for your Week 32 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 32 visit, one of the kits will be used 
to administer 1 injection in the office.  You will take home the kits for your 
Week 33 (one injection), 34 (one injection) and 35 (one injection) doses.  
●
You will return for your Week 36 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 36 visit, you will have a sample of 
blood drawn for PK/AAA, then one of the kits will be used to administer 1 
injection in the office.  You will take home the kits for your Week 37 (one 
injection), 38 (one injection) and 39 (one injection) doses.  
●
You will return for your Week 40 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 40 visit, one of the kits will be used 
to administer 1 injection in the office.  You will take home the kits for your 
Week 41 (one injection), 42 (one injection) and 43 (one injection) doses.  
●
You will return for your Week 44 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 44 visit, one of the kits will be used 


Adalimumab
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to administer 1 injection in the office.  You will take home the kits for your 
Week 45 (one injection), 46 (one injection) and 47 (one injection) doses.  
●
You will return for your Week 48 visit, at which time two kits will be 
dispensed (4 syringes total).  At the Week 48 visit, one of the kits will be used 
to administer 1 injection in the office.  You will take home the kits for your 
Week 49 (one injection), 50 (one injection) and 51 (one injection) doses.  
●
You will return for your Week 52 visit, at which time six kits will be dispensed 
(12 syringes total).  At the Week 52 visit, you will have a sample of blood 
drawn for PK/AAA, then one of the kits will be used to administer 1 injection 
in the office.  You will take home the kits for your Week 53 (one injection), 54 
(one injection), 55 (one injection), Week 56 (one injection), 57 (one injection), 
58 (one injection), Week 59 (one injection), Week 60 (one injection), 61 (one 
injection), Week 62 (one injection), and 63 (one injection) doses.
●
The above every 12-week visit will be repeated until the study end or the time 
you want to withdraw the study participation. 
Please return all used and unused syringes and empty boxes to the clinic on your next visit.  
Used syringes should be placed in the special sharps container provided.  All unused 
syringes should be returned in the original box.
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject dosing sheet.
Remember to complete your dosing sheet after each injection and to call the doctor's 
office if you are having problems administering your study medication.
General Information
●
Pre-filled syringes will be labeled "Adalimumab" versus Placebo.
●
Store all adalimumab pre-filled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study
doctor's office.


Adalimumab
M15-573 Protocol
123
●
Study medication should be taken at about the same time of day, on the same 
day of the week as directed by your study doctor.
●
USE A NEW SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE.
●
Save all study medications.  Pre-filled syringes (used and unused) & empty 
boxes must be returned to the study center at each visit.  Used syringes will 
be disposed of in a sharps container provided to you.
●
Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are unable 
to reach your doctor or if you experience life-threatening symptoms call, 
______________________ or proceed to your nearest emergency room.


Adalimumab
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124
Injection Procedures (Pre-filled Syringe)
1. Setting up for an injection
●
Find a clean flat surface.
●
Do not use if the seals on the carton are broken or missing.  Contact your study 
doctor's office if the seals are broken.
●
Take one kit with the pre-filled syringe(s) of adalimumab from the refrigerator.  
Do not use a pre-filled syringe that has been frozen or if it has been left in 
direct sunlight.
●
Return any unused syringe(s) to the refrigerator.
●
You will need the following items for each dose:
○
study medication in pre-filled syringe(s)
○
alcohol prep(s)
○
cotton ball or gauze pad(s)
If you do not have all of the items you need to give yourself an injection, call your study 
physician.  Use only the items provided in the box your adalimumab comes in.
●
Make sure the liquid in the pre-filled syringe is clear and colorless.  Do not use 
a pre-filled syringe if the liquid is cloudy or discolored or has flakes or 
particles in it.
●
Have a special sharps (puncture proof) container nearby for disposing of used 
needles and syringes.
For your protection, it is important that you follow these instructions.


Adalimumab
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125
2.
Choosing and preparing an injection site
●
Wash your hands well.
●
Choose a site on the front of your thighs or your stomach area (abdomen).  If 
you choose your abdomen, you should avoid the area 2 inches around your 
belly button (navel).
●
Choose a different site each time you give yourself an injection.  Each new 
injection should be given at least one inch from a site you used before.  Never 
inject into areas where the skin is tender, bruised, red or hard or where you 
have scars or stretch marks.
●
If you have psoriasis, you should try not to inject directly into any raised, thick, 
red or scaly skin patches or lesions.
●
You may find it helpful to keep notes on the location of your injection sites.
●
Wipe the site where adalimumab is to be injected with an alcohol prep (swab), 
using a circular motion.  Do not touch this area again until you are ready to 
inject.
3.
How to prepare your adalimumab dose for injection with a Pre-filled Syringe
●
Hold the syringe upright with the needle facing down.  Check to make sure 
that the amount of liquid in the syringe is the same or close to the 0.4 mL line 
for the 40 mg pre-filled syringe.  The top of the liquid may be curved.  If the 


Adalimumab
M15-573 Protocol
126
syringe does not have the correct amount of liquid, do not use that syringe.  
Call your study doctor.
●
Remove the needle cover taking care not to touch the needle with your fingers 
or allow it to touch any surface.
●
Turn the syringe so the needle is facing up and slowly push the plunger in to 
push the air in the syringe out through the needle.  If a small drop of liquid 
comes out of the needle that is okay.
●
Do not shake the syringe.
4. Injecting Adalimumab
●
With your other hand, gently squeeze an area of the cleaned area of skin and 
hold it firmly.
●
You will inject into this raised area of skin.  Hold the syringe like a pencil at 
about a 45° angle (see picture) to the skin.
●
With a quick, short, "dart-like" motion, push the needle into the skin.
●
After the needle is in, let go of the skin.  Pull back slightly on the plunger.  If 
blood appears in the syringe it means that you have entered a blood vessel.  Do 
not inject adalimumab.  Pull the needle out of the skin and repeat the steps to 
choose and clean a new injection site.  Do not use the same syringe.  Dispose 
of it in your special sharps container.  If no blood appears, slowly push the 
plunger all the way in until all of the adalimumab is injected.
●
When the syringe is empty, remove the needle from the skin keeping it at the 
same angle it was when it was pushed into the skin.


Adalimumab
M15-573 Protocol
127
●
Press a cotton ball or gauze pad over the injection site and hold it for 10 
seconds.  Do not rub the injection site.  You may have slight bleeding.  This is 
normal.
●
Dispose of the syringe right away into your special sharps container.


Adalimumab
M15-573 Protocol
128
Appendix N.
Subject Dosing Sheet – Adalimumab Example
To be completed for every study dose taken at home.  Study medication should be taken at 
about the same time of day, on the same day of the week as directed by your study doctor.  
Please record the date, time of study drug administration, if the full dose was administered, 
your initials, and any comments.  Instructions on proper study medication administration 
will be provided by your study doctor and should be followed for every injection.  Call 
the doctor's clinic if you are having problems administering your study medication.
For rows that are italicized and shaded, do not record the information.  These represent 
study visits for which injections will occur at the clinic.  The study personnel will record 
this information at the time of your study visit.
Please bring your Sheet with you to each clinic visit.
If you have any questions or concerns at any time, please call the study coordinator or 
physician at the following number(s):








Adalimumab
M15-573 Protocol
132
Appendix O.
Infection Subject Information Card – Example
It is possible that you may be at increased risk for an infection at or near your HS area.  If 
you develop any of the following signs or symptoms, you should contact your study 
doctor (number noted below) immediately for an additional examination.
Possible Signs of an Infection:
●
Fever
●
Chills
●
Unusual warmth at or near an HS area
●
Unusual redness at or near an HS area
●
Unusual swelling at or near an HS area
●
Unusual pain at or near an HS area
●
Unusual amounts of pus at or near an HS area
Call your study Dr. at (XXX) XXX–XXXX
If you notice any of the above symptoms for further evaluation.



SAP_001.pdf: 
Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
1 
1.0
Title Page
Statistical Analysis Plan
Study M15-573
A Phase 3 Multicenter, Open-Label, Single Arm Study 
of the Safety and Efficacy of Adalimumab in 
Japanese Subjects with Moderate to Severe 
Hidradenitis Suppurativa
Date: 07 NOV 2017 
NCT02904902


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
2
2.0
Table of Contents
1.0 
Title Page..................................................................................1 
2.0 
Table of Contents.....................................................................2 
3.0 
Introduction .............................................................................8 
4.0 
Study Objectives, Design and Procedures.............................8 
4.1 
Objectives ..................................................................................................8 
4.2 
Design Diagram .........................................................................................8 
4.3 
Sample Size..............................................................................................14 
4.4 
Interim Analysis.......................................................................................14 
5.0 
Analysis Populations .............................................................14 
5.1 
Definition for Analysis Populations.........................................................14 
5.2 
Variables Used for Stratification of Randomization................................15 
6.0 
Analysis Conventions ............................................................15 
7.0 
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications ..............29 
7.1 
Demographic and Baseline Characteristics .............................................29 
7.2 
Medical History .......................................................................................32 
7.3 
Prior and Concomitant Therapy...............................................................32 
8.0 
Patient Disposition.................................................................33 
9.0 
Study Drug Exposure and Compliance...............................33 
9.1 
Study Drug Exposure...............................................................................34 
9.2 
Compliance ..............................................................................................34 
9.3 
Study Drug Dose......................................................................................34 
10.0 
Efficacy Analysis....................................................................35 
10.1 
General Considerations............................................................................35 
10.2 
Primary Efficacy Analysis .......................................................................35 
10.3 
Secondary Efficacy Analyses...................................................................35 
10.4 
Handling of Multiplicity ..........................................................................43 
10.5 
Efficacy Subgroup Analysis ....................................................................43 
11.0 
Safety Analysis.......................................................................44 
11.1 
General Considerations............................................................................44 
11.2 
Analysis of Adverse Events.....................................................................44 


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3
11.2.1 
Treatment-Emergent Adverse Events ......................................................44 
11.2.2 
Listing of Adverse Events........................................................................50 
11.2.3 
Safety Subgroup Analysis........................................................................50 
11.3 
Analysis of Laboratory Data....................................................................50 
11.3.1 
Variables and Criteria Defining Abnormality..........................................50 
11.3.2 
Statistical Methods...................................................................................52 
11.4 
Analysis of Vital Signs and Weight.........................................................56 
11.4.1 
Variables and Criteria Defining Abnormality..........................................56 
11.4.2 
Statistical Methods...................................................................................56 
11.5 
Analysis of ECG Parameters....................................................................56 
11.6 
Analysis of Potentially Clinically Significant ECG Values ....................57 
12.0 
Summary of Changes ............................................................57 
13.0 
Appendices .............................................................................57 
List of Tables
Table 1. 
Study Activities:.......................................................................................10 
Table 2. 
Visit Windows for Analysis of Efficacy Variables (Lesion Count, 
Hurley Stage, Degree of Erythema).........................................................20 
Table 3. 
Visit Windows for Analysis of Vital Signs..............................................21 
Table 4. 
Visit Windows for Analysis of Efficacy Variables (PGA of skin 
pain) .........................................................................................................22 
Table 5. 
Visit Windows for Analysis of HbA1c and CRP.....................................22 
Table 6. 
Visit Windows for Analysis of Efficacy Variables (HS QOL)................23 
Table 7. 
Visit Windows for Analysis of Efficacy Variables (DLQI) ....................23 
Table 8. 
Visit Windows for Analysis of Efficacy Variables (EQ-5D) ..................24 
Table 9. 
Visit Windows for Analysis of Efficacy Variables (TSQM)...................24 
Table 10. 
Visit Windows for Analysis of General Laboratory Parameters .............24 
Table 11. 
Visit Windows for Summary of Study Drug Injections...........................26 
Table 12. 
Summary of Efficacy Variables and Statistical Analyses........................41 
Table 13. 
Clinical Laboratory Tests.........................................................................51 
Table 14. 
Potentially Clinically Significant Laboratory Findings ...........................54 
Table 15. 
Criteria for Potentially Clinically Significant Vital Sign Findings..........56


Adalimumab
M15-573 – Statistical Analysis Plan
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List of Figures
Figure 1. 
Study Schematic.........................................................................................9 
List of Appendices
Appendix A.
Calculation of the Modified Sartorius Scale............................................57
Appendix B.
Minimally Clinically Important Difference (MCID) 
Determination in Dermatology ................................................................58


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M15-573 – Statistical Analysis Plan
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List of Abbreviations
AAA
Anti-Adalimumab Antibody
AE
Adverse Event
AESI
Adverse Event of Special Interest
AN
Abscess and inflammatory Nodule 
BCG
Bacille Calmette-Guérin
bid
Twice a day
CDA
Clinical Drug Accountability
CL/F
Apparent serum clearance
CRF
Case Report Form
CRP
C-Reactive Protein
CXR
Chest X-ray
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EMA
European Medicines Agency.  European Agency for the Evaluation of 
Medicinal Products.
eow
Every Other Week
EQ-5D
Descriptive system of health-related quality of life states consisting of 
five dimensions
EU
European Union
ew
Weekly
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
HBcAb
Hepatitis B Core Antibody
HBsAb
Hepatitis B Surface Antibody
HBsAg
Hepatitis B Surface Antigen
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
HS
Hidradenitis Suppurativa
HiSCR
Hidradenitis Suppurativa Clinical Response


Adalimumab
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6
HS QoL
Hidradenitis Suppurativa Quality of Life
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IP
Investigational Product
IRB
Institutional Review Board
IV
Intravenous
IRT
Interactive response technology
LOCF
Last Observation Carried Forward
LOR
Loss of Response
MedDRA
Medical Dictionary for Regulatory Activities
MI
Myocardial Infarction
NRI
Non-Responder Imputation
NRS
Numeric Rating Scale
NRS30
At least a 30% reduction and at least 1 unit reduction from Baseline in 
Patient's Global Assessment of Skin Pain
OL
Open-Label
PA
posterior-anterior
PGA
Physician's Global Assessment
pH 
Power of Hydrogen Ion Concentration
PK
Pharmacokinetic
po
Oral
PML
Progressive Multifocal Leukoencephalopathy
POR
Proof of Receipt
PPD
Purified Protein Derivative
RA
Rheumatoid Arthritis
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAS
Statistical Analysis Software
SC
Subcutaneous
TA MD
Therapeutic Area Medical Director
TEAEs
Treatment Emergent Adverse Events
TB
Tuberculosis
TNF
Tumor Necrosis Factor
TSQM
Treatment Satisfaction Questionnaire - Medication
US
United States 


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
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V/F
Apparent volume of distribution
Wk
Week


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
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3.0
Introduction
This statistical analysis plan (SAP) describes the statistical analysis to be completed by 
the AbbVie Global Statistics Department for adalimumab study Protocol M15-573 dated 
07 July 2016.  It provides details to further elaborate statistical methods as outlined in the 
protocol and describes analysis conventions to guide the statistical programming work.
This is the first version of SAP for Protocol M15-573.
Unless noted otherwise, all analyses will be performed using SAS (SAS Institute Inc.,
Cary, NC, USA) under the UNIX operating system or in the PC environment.
4.0
Study Objectives, Design and Procedures
4.1
Objectives
The primary objective of this study is to investigate the safety and efficacy of adalimumab 
in Japanese subjects with moderate to severe hidradenitis suppurativa (HS) after 12 weeks 
of treatment. A secondary objective is to evaluate the long-term safety, efficacy and 
tolerability by continuous weekly dosing from Week 12. The pharmacokinetics and 
immunogenicity of adalimumab following subcutaneous (SC) injection will also be 
assessed in the study and analyzed in a separate report.
4.2
Design Diagram
This study is an open-label, single arm study designed to investigate the safety and 
efficacy of adalimumab in Japanese patients with moderate to severe hidradenitis 
suppurativa after 12 weeks of treatment, and to evaluate long-term safety, efficacy and 
tolerability. The study will include a 35-day screening period, open-label treatment period 
and a 70-day follow-up phone call following their last dose of study drug. The treatment 
period is expected for at least 99 weeks until the time of approval for HS indication, or 
withdrawal of the marketing application in Japan. A subject's participation in this study is 
expected up to 38 months. All subjects will receive open-label subcutaneous injection of 


Adalimumab
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9
adalimumab 40 mg every week (ew) starting at Week 4, after 160 mg at Week 0 
(Baseline) and 80 mg at Week 2.
The primary efficacy endpoint is the proportion of subjects achieving Hidradenitis 
Suppurativa Clinical Response (HiSCR) at Week 12. HiSCR is defined as at least a 50% 
reduction in the total abscess and inflammatory nodule count (AN count) with no increase 
in abscess count and no increase in draining fistula count relative to Baseline.
Study visits will occur at Weeks -4 and -2 (in the Screening period), Baseline (Week 0), 
Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or at the Premature 
Discontinuation visit.  After Week 52, study visits will occur every 12 weeks until the 
study end.
Additionally, all subjects will be contacted by phone 1 week before and after the Baseline 
visit to ensure daily pain assessments are being recorded, and at Week 6 and Week 10 to 
monitor whether any signs or symptoms of infection are present at or near an HS lesion.  
If any signs or symptoms are reported at the time of the call, an unscheduled study visit 
will be conducted to assess whether an infection is present.  
Adverse events will be collected throughout the study. Subjects who decide not to 
continue this study will have a 70-day follow-up phone call following their last dose of 
study drug to determine the status of any ongoing adverse events (AEs) or serious adverse 
events (SAEs), or the occurrence of any new AEs or SAEs.  The 70-day follow-up phone 
call will not be required for any subject who initiates adalimumab therapy not supplied in 
the context of the clinical trial after the end of the study participation.
Figure 1.
Study Schematic
g
y


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Table 1.
Study Activities:
Activity
Screening
(Day –35 
to Day –1)
Baseline
(Day 1)
Wk 
2
Wk
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
32
Wk 
36
Wk 
40
44
48
Wk 
52
Every 
12 Weeks 
After 
Wk 52
Final or 
Premature 
Discontinuation 
Visit
Unscheduled 
Study Visit
70-Day 
Call
Informed Consent
X
Inclusion/Exclusion 
Criteria
X
Xa
Prior and Concomitant 
Therapy Assessmentb
X
Xa
X
X
X
X
X
X
X
X
X
X
X
X
X
Medical/Surgical 
History
X
Xa
Alcohol Use
X
Nicotine Use
X
X
X
Physical Exam
X
X
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
Xc
X
Xc
X
X
Chest X-ray/ ECG
X
X
Xd
TB Screening
X
X
Vital Signs
Xe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Tests
Xf
Xg
Xg
Xg
Xg
Xg
Xg
Xg
Xg
General Labs: 
Chemistry and 
Hematologyh
X
Xh
X
X
X
X
X
X
X
Urinalysisi
X
Xh
X
X
X
X
X
X
X
CRP
X
X
X
HIV
X


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Table 1.
Study Activities: (Continued)
Activity
Screening
(Day –35 
to Day –1)
Baseline
(Day 1)
Wk 
2
Wk
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
32
Wk 
36
Wk 
40
44
48
Wk 
52
Every 
12 Weeks 
After 
Wk 52
Final or 
Premature 
Discontinuation 
Visit
Unscheduled 
Study Visit
70-Day 
Call
Hepatitis B/C Screen
X
HbA1c
X
X
X
PK Measurementsj
X
X
X
X
X
X
X
X
X
X
X
AAA Measurementsj
X
X
X
X
X
X
X
ANA/dsDNAk
X
DLQI
X
X
X
X
X
X
X
EQ-5D
X
X
X
X
PGA of Skin pain
Xl
Xl
Xl
Xl
Xl
Xl
X
X
X
X
X
Paper Diary
X
X
X
X
X
X
HS QOL
X
X
X
X
X
X
X
X
X
TSQM
X
X
X
X
X
X
Lesion Countsm
Wk –4 Wk –2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xn
Xn
Hurley Stage 
Xn
Xn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Degree of Erythemao
Xn
Xn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Follow-up Phone Call
Xp
Xp
Xq
Xq
Xr
Photographys
X
X
X
X
X
X
Adverse Eventst
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense Study Drug
X
X
X
X
X
X
X
X
X
X
X
X
X


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Table 1.
Study Activities: (Continued)
Footnote for Table 1;
a.
Update inclusion/exclusion, prior and concomitant therapy, and medical history information to assure subject eligibility.
b.
From Screening through Week 12, subjects will complete a daily diary of their analgesic use using paper diary.  After Week 12 and subsequent designated visits including 
Premature Discontinuation visit, subjects will be required to report if they took any analgesics within 24 hours of their in-office visit at the time of Patient Global Assessment 
of Skin Pain.  Note:  Subject may not be allocated to the study drug if pain diaries are not completed for 7 days (at minimum) prior to the Baseline visit.
c.
A full physical exam is required at the Screening, Baseline, Week 52 and Final visit or Premature Discontinuation visit.  A symptom-directed physical examination should be 
performed at other visits if, in the opinion of the investigator, it is warranted by the subject's AE status or on review of symptoms.
d.
Subjects will have a repeat ECG and CXR at Week 52.  Repeat ECG or CXR at Final visit or at Premature Discontinuation visit only if in the opinion of the investigator, 
clinically significant AEs develop during the study that warrant a repeat.
e.
Height will be measured at Screening only.
f.
All females of childbearing potential will have a serum pregnancy test at Screening that is performed at the central laboratory.
g.
All females of childbearing potential will have a urine sample collected at Baseline  and at the designated study visits.  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. Urine pregnancy test at the Baseline will be performed also at 
site to confirm negative result on site. If the result at site is positive, treatment with study drug should not be started until the serum pregnancy test at the central laboratory is 
confirmed negative.
h.
Refer to the laboratory manual for further instructions.
i.
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 or in the case of abnormal macroscopic results.
j.
Blood samples must be obtained prior to dosing.  Blood samples will be collected at the Premature Discontinuation visit if the subject discontinues prior to Week 52.  
k.
ANA/Anti dsDNA is required at the Screening visit.  However, if a subject develops signs and symptoms of lupus, an ANA/Anti-dsDNA test may be repeated based on the 
investigator's clinical judgment. 
l.
From Screening through Week 12, subjects will complete a daily diary of their skin pain.  See Protocol section 5.3.1.1.  No in-office assessment of skin pain will be 
completed at the Week 12 visit.  At the designated study visit after Week 12 until Final visit or Premature Discontinuation visit, subjects will complete skin pain assessments 
in the office based on a recall period of the last 24 hours.  Note:  Subject may not be allocated to the study drug if pain diaries are not completed for 7 days (at minimum) prior 
to the Baseline visit.


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Table 1.
Study Activities: (Continued)
m.
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 (Protocol section 5.2.3.2) as permanently present in the lesion counts from the date of the intervention.
n.
After IC, evaluation of Lesion Counts, Hurley Stage and Degree of Erythema should be performed twice in the Screening period by site visit.  Time point will be Week –4
(Day –28) and Week -2 (Day -14). 
o.
At every visit, for each affected anatomic region, the investigator will assess the overall degree of erythema using a four-point ordinal scale ranging between 0 and 3.
p.
Sites are encouraged to contact Subjects 1 week prior to the Baseline visit to confirm compliance with daily pain collection.  Subjects will be contacted 1 week following the 
Baseline visit to ensure daily pain assessments are being recorded.
q.
Subjects will be contacted 2 weeks following the Week 4 and 8 visits (i.e., Week 6 and Week 10) to obtain information on any signs of an infection at or near an HS lesion.
r.
Site personnel will contact all subjects by phone approximately 70 days after the last dose of study drug to determine the status of any ongoing AEs/SAEs or the occurrence of
any new AE/SAEs.  The 70-day follow-up phone call will not be required for any subject who initiates adalimumab therapy not supplied in the context of the clinical trial 
after the end of study participation.
s.
Subjects at pre-selected sites will have photographs taken at Baseline, Week 4, Week 12, Week 24, Week 52 and Final visit or at the Premature Discontinuation visit.
t.
All AEs reported from the time of study drug administration until approximately 70 days following discontinuation of study drug administration will be collected.  SAEs and 
protocol-related AEs will be collected from the time the subject signed the study-specific informed consent until approximately 70 days following discontinuation of study 
drug administration.


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14
4.3
Sample Size
This study is designed to enroll approximately 15 subjects due to quite limited number of 
patients with HS in Japan, considering the feasibility of the study conduct.  But study 
result will provide adequate information to characterize the safety profile of adalimumab.  
In the global placebo-controlled studies (Studies M11-810 and M11-313), the response 
rates of HiSCR at Week 12 were 59% and 42% in the adalimumab ew group, and 28% 
and 26% in the placebo group, respectively.  Assuming the threshold response rate at 
Week 12 of 25% (response rate with no medication) and the expected clinical response 
rate of 60%, a sample size of 13 subjects will have 80.1% power to detect the difference 
of 35% in the primary endpoint and using one sample Chi-square test at one-sided 2.5% 
significant level.
4.4
Interim Analysis
Interim analysis is planned at Week 24 and repeated at appropriate time after Week 52.
Measurements on or before the study drug dosing date at planned interim analysis time 
point (Week 24 or appropriate time after Week 52) will be included in the analysis. For 
subjects who do not take study drug at planned interim analysis time point, the last non-
missing measurement collected on or before the date of the vital signs measurement will 
be used.
5.0
Analysis Populations
5.1
Definition for Analysis Populations
Full Analysis Set:
Full Analysis Set (FAS) population includes all subjects who complied with GCP and 
received at least one dose of study drug and had at least one post-treatment efficacy 
assessment. FAS is the primary population for the efficacy analysis.  


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15
Safety Dataset:
Safety Population is defined as all subjects who receive at least one dose of study drug in 
the study, and will be used for safety analysis.
5.2
Variables Used for Stratification of Randomization
Not applicable.
6.0
Analysis Conventions
Unless otherwise specified, the efficacy and safety continues variables will be 
summarized using the descriptive statistics (including mean, standard deviation, median, 
minimum and maximum), and for qualitative variables, the number (n) and percentage 
(%) of subjects with non-missing data per category will be the default summary 
presentation.
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.
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.
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


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
16
Inadequate 
Response to 
Antibiotics
An adequate trial of oral antibiotic therapy is considered to be at least 90 days in 
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the following has occurred, subject will be considered to have had inadequate 
response, or loss of response, to oral antibiotics:
x
Progression of Hurley Stage (i.e., the Hurley Stage of at least one 
affected anatomic region has progressed from I – II, II – III, or I – III);
x
Subject requires at least one intervention (e.g., incision and drainage or 
intralesional injection of corticosteroid);
x
Subject experiences pain interfering with activities of daily living, with 
unsatisfactory relief from over-the-counter analgesics (e.g., ibuprofen or 
acetaminophen);
x
Subject experiences pain requiring opioids, including tramadol;
x
Subject experiences drainage interfering with activities of daily living 
(e.g., requires multiple dressing changes and/or changes of clothes 
daily);
x
Subject experiences an increase in the number of anatomic regions 
affected by HS;
x
Subject experiences at least one new abscess or one new draining fistula.
x
Sites are encouraged to contact AbbVie TA MD to confirm if the 
definition of inadequate response or loss of response has been met.
Inflammatory 
nodules
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.
Intolerance to 
Antibiotics
A subject is defined as intolerant to oral antibiotic when oral antibiotic therapy 
has been discontinued by a physician as a result of a significant adverse reaction 
to oral antibiotic administration.
A reaction will be considered significant if the adverse reaction is at least 
moderately severe (i.e., the adverse event causes the subject discomfort and 
interrupts the subject's usual activities or function).  Examples of significant 
adverse reactions include, but are not limited to:
x
nausea resulting in decreased oral intake;
x
macular or papular eruption or erythema associated with pruritus or 
other associated symptoms;
x
dizziness/disequilibrium/lightheadedness/vertigo interfering with 
function;
x
allergic reaction manifesting as rash, flushing, urticaria, dyspnea, or 
drug fHYHU&
x
diarrhea manifesting as an increase in stool frequency of at least 4 stools 
per day over Baseline.
Sites are encouraged to contact AbbVie TA MD to confirm if the definition of 
intolerance has been met.


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
17
Loss of Response 
(LOR)
An AN count that is greater than the average of AN counts at Baseline and Week 
12.  It is a loss of at least 50% of the improvement (reduction) in the AN count 
achieved from baseline to Week 12.
Calculation:  AN > ½ * (Baseline AN count + Week 12 AN count)
Baseline AN Count
Week 12 AN Count
Average of AN Counts
Minimum Count to 
Meet LOR
10
1
½ * (10 + 1) = 5.5
6
10
4
½ * (10 + 4) = 7
8
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 
nodules
Non-tender or minimally tender, non-erythematous nodules.
Protocol Allowed 
Intervention
A protocol-allowed intervention is defined as incision and drainage, or injection 
of intralesional triamcinolone acetonide suspension (at a dose of 50 mg/5 mL, up 
to 0.5 mL).
Worsening or 
Absence of 
Improvement
(WOAI)
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Definition of Baseline
The last non-missing measurement collected on or before the day of the first dose of study 
drug injection will be used as Baseline for summary of demographics and disease 
characteristics, the safety analysis and all the efficacy analysis, with the following 
exception.
For Patient's Global Assessment of Skin Pain (Numerical Rating Scale, Skin Pain NRS), 
the average of the last 7 assessments BEFORE the date of first dose of study drug 
injection will be used as Baseline. If there are only 4 to 6 daily assessments available, the 
average of the available assessments will be used. If there are 3 or less assessments 
available, the subject's Baseline will be considered as missing.


Adalimumab
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Definition of Final Observation Value
Final observation for safety analyses is defined as the last non-missing observation 
collected on or prior to the cut-off date.
¾
For subjects who did not discontinue the study before the interim cut-off date, final 
observation is defined as the last non-missing observation collected after the first dose 
of study drug and on the dose of study drug at Week 24 or Week 52.
¾
For subjects who discontinued the study before cut-off date, final observation is 
defined as the last non-missing observation collected after the first dose of study drug 
and within 70 days after the last dose. 
Definition of Rx Days (Days Relative to the First Dose of Study Drug)
Rx Days are calculated for each time point of interest and it provides a quantitative 
measure of days between the event and the first dose date. That is, the Rx Day is 
calculated as the event date minus the date of first dose of study drug plus 1. The Rx Day 
will be a negative value when the time point of interest is prior to the date of first dose of 
study drug, and the Rx Day will be a positive value when the time point of interest is after 
the first dose date. By this calculation algorithm the first dose day is Rx Day 1, while the 
day prior to the date of first dose is defined as Rx Day –1 (there is no Rx Day 0). Rx days 
are used to map actual study visits to the protocol specified study visits.
Definition of Analysis Windows
Since subjects do not always adhere to the study visit schedule, the following rules will be
applied to assign actual visits to protocol-specified visits including early termination visits.
For each study visit mentioned in the protocol, a nominal or target day will be selected to
represent the corresponding visit along with a window around the target day. Windows
will be selected in a non-overlapping fashion so that a date collected on the CRF does not
correspond to multiple visit windows. Moreover, windows will not discard any post
baseline measurement recorded on the CRF. If a subject had two or more actual visits in
one visit window, the visit closest to the target will be used as the study visit for that


Adalimumab
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19
window. If two visits are equal distance to the nominal day, then the later visit will be 
used in analysis. If more than one assessment is included on the same day, then the worst 
assessment on that day will be used in analyses.
For the visit-wise analysis of Skin Pain NRS through Week 12, the weekly averages of 
pain will be summarized for the two items (Pain at-worst and Pain on-average) separately. 
The weekly average score will be calculated based on the 7 available daily scores from the 
days within each visit window that are closest to the nominal day. If there are 4 to 6 
assessments in the visit window, the average of the available assessments will be used. If 
more than one assessment is included on the same day, the worst assessment on that day 
will be chosen as the daily score. If there are more than 7 daily scores available and the 
7th and 8th observations (ranked based on distance from the nominal day) are equidistant 
to the nominal day, the one after the nominal day will be used to calculate the weekly 
score. For any visit with less than 4 diary entries within the visit window, the weekly 
average will be recorded as missing. Of note, Skin Pain NRS is not to be collected on the 
day of Week 12 visit; if collected, the data point will not be used in the Week 12 summary
because it will be unclear if the assessment is before or after the Week 12 dose.
Rolling weekly average Skin Pain NRS (both pain at-worst and pain on-average) will be 
analyzed daily from Day 7 through the minimum of Day 98 and the day prior to week 12 
drug injection. The rolling weekly average score is calculated as follows. Let Pm-6, Pm-5,…,
Pm-1, Pm be the daily pain scores from day m – 6 to day m (Pi, m – 6 i m, will be set as 
0 if the pain score on day i is missing for the following calculation purpose) and Nm be the 
number of days with non-missing pain scores from day m – 6 to day m, then the rolling 
weekly average for day m is:
If there are less than 4 daily entries available (Nm < 4), then the rolling weekly average of 
day m will be counted as missing. If more than one assessment is included on the same 
day, the worst assessment on that day will be chosen as the daily score.
m
m
m
i
i
N
P
¦

 
6


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
20
Table 2.
Visit Windows for Analysis of Efficacy Variables (Lesion Count,
Hurley Stage, Degree of Erythema)
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Week -4
-
-35 - -22
Week -2
-
-21 - -1
Baseline
1
1
Week 2
15
2 – 22
Week 4
29
23 – 43
Week 8
57
44 – 71
Week 12
85
72 – 99
Week 16
113
100 – 127
Week 20
141
128 – 155
Week 24
169
156 – 183
Week 28
197
184 – 211
Week 32
225
212 – 239
Week 36
253
240 – 267
Week 40
281
268 – 295 
Week 44
309
296 – 323
Week 48
337
324 – 351
Week 52
365
352 – 407
Week K$
K*7 + 1
K*7-40 – K*7+43
$: Every 12 weeks thereafter


Adalimumab
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Version 1.0 – 07 NOV 2017
21
Table 3.
Visit Windows for Analysis of Vital Signs
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 2
15
2 – 22
Week 4
29
23 – 43
Week 8
57
44 – 71
Week 12
85
72 – 99
Week 16
113
100 – 127
Week 20
141
128 – 155
Week 24
169
156 – 183
Week 28
197
184 – 211
Week 32
225
212 – 239
Week 36
253
240 – 267
Week 40
281
268 – 295 
Week 44
309
296 – 323
Week 48
337
324 – 351
Week 52
365
352 – 407
Week K$
K*7 + 1
K*7-40 – K*7+43
$: Every 12 weeks thereafter


Adalimumab
M15-573 – Statistical Analysis Plan
Version 1.0 – 07 NOV 2017
22
Table 4.
Visit Windows for Analysis of Efficacy Variables (PGA of skin 
pain)
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
-1
-1
Week 2
14
1 – 21
Week 4
28
22 – 42
Week 8
56
43 – 70
Week 12
84
71 – 126
Week 24
169
127 – 211
Week 36
253
212 – 309
Week 52
365
310 – 407
Week K$
K*7 + 1
K*7-40 – K*7+43
$: Every 12 weeks thereafter
Table 5.
Visit Windows for Analysis of HbA1c and CRP
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 12
85
2 – Final or Premature Discontinuation 
after Week 12 - 1
Final or Premature 
Discontinuation after Week 12


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23
Table 6.
Visit Windows for Analysis of Efficacy Variables (HS QOL)
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 2
15
2 – 22
Week 4
29
23 – 43
Week 8
57
44 – 71
Week 12
85
72 – 127
Week 24
169
128 – 211
Week 36
253
212 – 309
Week 52
365
310 – Final or Premature 
Discontinuation after Week 52 - 1
Final or Premature 
Discontinuation after Week 52
Table 7.
Visit Windows for Analysis of Efficacy Variables (DLQI)
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 4
29
2 – 57
Week 12
85
58 – 127
Week 24
169
128 – 211
Week 36
253
212 – 309
Week 52
365
310 – Final or Premature 
Discontinuation after Week 52 - 1
Final or Premature 
Discontinuation after Week 52


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24
Table 8.
Visit Windows for Analysis of Efficacy Variables (EQ-5D)
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 12
85
2 – 225
Week 52
365
226 – Final or Premature 
Discontinuation after Week 52 - 1
Final or Premature 
Discontinuation after Week 52
Table 9.
Visit Windows for Analysis of Efficacy Variables (TSQM)
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 12
85
2 – 127
Week 24
169
128 – 211
Week 36
253
212 – 309
Week 52
365
310 – Final or Premature 
Discontinuation after Week 52 - 1
Final or Premature 
Discontinuation after Week 52
Table 10.
Visit Windows for Analysis of General Laboratory Parameters
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Baseline
1

Week 4
29
2 – 57
Week 12
85
58 – 127
Week 24
169
128 – 211
Week 36
253
212 – 309
Week 52
365
309 – 407
Week K$
K*7 + 1
K*7-40 – K*7+43
$: Every 12 weeks thereafter


Adalimumab
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25
Analysis time windows for study drug injections are constructed using the following 
algorithm:
z
Determine the nominal Rx day for each scheduled injection (e.g., Week 0
[first dose of adalimumab] equals Rx Day 1. Week 1 [1 week after first dose 
of adalimumab] equals Rx Day 8).
z
Determine the window around a specific nominal Rx day by adding or
subtracting half of the interval between adjacent scheduled injections (e.g., the 
number of days between Week 0 and Week 1 is 7). The threshold between 
adjacent scheduled injections is determined by splitting the interval evenly 
between the injections (e.g., the split between Week 0 and Week 1 would be 
between Rx Days 4 and 5).
The following time window specified will be used for the summary of study drug 
injections.


Adalimumab
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Table 11.
Visit Windows for Summary of Study Drug Injections
Scheduled Week
Nominal Day
Time Window (Rx Day Range)
Week 0 (Baseline)
1
1
Week 2
15
2 – 22
Week 4
29
23 – 32
Week 5
36
33 – 39
Week 6
43
40 – 46
Week 7
50
47 – 53
Week 8
57
54 – 60
Week 9
64
61 – 67
Week 10
71
68 – 74
Week 11
78
75 – 81
Week 12
85
82 – 88
Week 13
92
89 – 95
Week 14
99
96 – 102
Week 15
106
103 – 109
Week 16
113
110 – 116
Week 17
120
117 – 123
Week 18
127
124 – 130
Week 19
134
131 – 137
Week 20
141
138 – 144
Week 21
148
145 – 151
Week 22
155
152 – 158
Week 23
162
159 – 165
Week 24
169
166 – 172
Week K$
K*7 + 1
K*7-2 – K*7+4
$: Every weeks thereafter


Adalimumab
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27
Baseline Value is Missing
Subjects will be excluded from analysis which is based on change or percent change from 
baseline if baseline evaluation is missing.
When no baseline value is available (i.e. missing baseline) for a subject, percent change
from baseline cannot be calculated and therefore percent change values will be set to
missing.
When the baseline value is 0, the percent change from baseline will be calculated based
on the post-baseline value using the following general rules:
¾
If the post-baseline value is missing, then the percent change will be missing.
¾
If the post-baseline value is 0, then the percent change will be set to 0.
¾
If the post-baseline value is non-missing and not 0, then the percent change will be set 
to missing.
Definition of Missing Data Imputation
The following imputation methods will be used to impute missing values in the efficacy 
analyses. In general, missing Baseline and safety data will not be imputed. In addition, an 
observed case analysis will be performed.
z
Non-Responder Imputation (NRI)
The NRI analysis will categorize any subject who has missing value at a specific visit 
as non-responder for that visit. The NRI will be the primary approach in the analysis 
of categorical variables.
z
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. 


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LOCF will be the primary approach in the analysis of continuous variable, and the 
secondary approach in the analysis of categorical variables.
z As-observed:
The As-observed analysis 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 analysis will be the secondary 
approach in the analysis of continuous variables.
Lesions that received intervention will be counted as permanently present from the date of
the intervention.
z Imputation of Missing Dates
For baseline, efficacy and safety parameters, if the day and/or month are missing, the 
following conventions will be used to impute the missing dates:
¾
01 for missing start day
¾
End of month for missing end day
¾
January 1st for missing start month
¾
December 31st for missing end month
In case of missing or partially missing dosing dates, the dates will not be imputed.
In case of missing or partially missing adverse event start and stop dates, the dates will 
be imputed by comparing to the first dosing date so that the corresponding adverse 
events will be made treatment-emergent, whenever possible.
Rounding of Numeric Results
Rounding will be performed only for presentation of results. No rounding will be
performed before or during analyses/calculations. The ROUND function of SAS will be
used to round results for presentation. The mean and median will be rounded for
presentation to 1 decimal more than the data were entered into the database. 
For example, mean systolic blood pressure will be presented to one decimal place (125.2 


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mmHg) when it is recorded to integer level in the database (110 mmHg). The standard 
deviation will be rounded to 2 decimal places more than the data were entered into the
database (e.g., 25.31 mmHg for systolic blood pressure). The minimum and maximum 
values will be presented as entered into the database.
For the calculation of HiSCR, the percent change in AN count will be rounded to
3 decimal places using usual rounding rules (e.g., –19.9955% = – 19.996%). Then the
rounded result will be used to compare with –50% to determine the HiSCR (responder
versus non-responder).
Percentages will be rounded for presentation to one decimal place; e.g., the proportion
0.1244 will be reported in percent as 12.4.
7.0
Demographics, Baseline Characteristics, Medical 
History, and Previous/Concomitant Medications
7.1
Demographic and Baseline Characteristics
All demographic and baseline variables will be described with summary statistics.
Categorical data will be summarized using the frequency and percentage; continuous data 
will be summarized using the mean, standard deviation, first quartile (Q1), median,
third quartile (Q3), minimum, and maximum. The number of non-missing values will
also be summarized.
All summaries will be presented for the analysis populations defined in Section 5.1.
No statistical test will be performed.
The following demographic and baseline values will be summarized.
Continuous variables:
ە Age (years) defined as the number of years from birth to the first study visit
ە Body Weight (kg)
ە Height (cm)
ە Body mass Index (kg/m2)


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ە Blood Pressure (systolic/diastolic) (mmHg)
ە Pulse (bpm)
ە Respiratory Rate (bpm)
ە Body Temperature (°C)
ە Duration of Hidradenitis Suppurativa (HS) [year]
ە Modified Sartorius scale
ە AN count, nodule (non-inflammatory, inflammatory), abscess, fistula (non-
draining, draining) count, and hypertrophic scar count – among all subjects and 
among subjects with non-zero count
ە Number of anatomic regions affected
ە Dermatology Life Quality Index (DLQI) [0-30]
ە Numeric Rating Scale (NRS) for Patient's Global Assessment of Skin Pain (at
worst and on-average)
ە Treatment Satisfaction Questionnaire – Medication (TSQM)
ە C-Reactive Protein
ە HbA1c
ە Cigarette use
ە HSQoL
ە EQ-5D Index
ە EQ-5D VAS
Categorical variables:
ە Sex (male/female)
ە Race (White, Black or African American, Asian, American Indian or Alaska 
Native, Native Hawaiian or Other Pacific Islander, Other)
ە Ethnicity (Japanese, Chinese, Korean, Taiwanese, Other)
ە Age categories (< 40, 40–LIOHVVWKDQRIVXEMHFWVLQWKHJURXS
that group will be combined with 40–64 group.)


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ە Body Weight categories (< Median,  Median)
ە Body Mass Index (BMI) category: normal (< 25), over weight (25 – < 30), obese 
(30 – 0RUELGREHVLW\
ە Family history of HS (yes, no)
ە Screen failure (status [yes, no], experience SAE during screening [yes, no])
ە Current smoking status (yes/no)
ە Duration of Hidradenitis Suppurativa (HS) (< Median,  Median)
ە Tobacco use (Current, Former, Never, Unknown)
ە Alcohol use (Current, Former, Never, Unknown)
ە Hurley Stage (the worst level across all anatomic regions)
ە Prior HS surgery history (yes, no)
ە Time from prior HS surgery to the first dose of study drug (< Median,  Median)
ە CRP level (< Median,  Median)
ە $1FRXQW– 10, 11+)
ە AN count (< Median,  Median)
ە Degree of Erythema by anatomic region and for the worst among all anatomic
regions
ە Concomitant use of oral antibiotics (yes/no)
ە ECG assessment at screening visit (normal, abnormal-not clinically significant,
abnormal-clinically significant)
ە Chest x-ray (finding [normal, abnormal], Calcified granulomas [absent,
present], pleural scarring [absent, present], pleural thickening [absent, present])
ە Tuberculin PPD skin test result QHJDWLYH>PP@SRVLWLYH>PP@
ە QuantiFERON-TB Gold test result (negative, indeterminate, positive)
ە TB Prophylaxis (enrolled [yes, no], [INH, Other TB Prophylaxis])
ە TB history (high risk of TB [yes, no], former BCG immunization [yes, no,
unknown])


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ە Hepatitis B surface antigen (HBsAg [positive, negative])
ە Hepatitis B core antibody Total (HBcAb, Total [positive, negative])
ە Hepatitis B surface antibody (HBsAb [positive, negative, indeterminate])
ە HBV DNA PCR (positive, negative) among subjects with positive HBcAb or 
HBsAb
ە HbA1c (< 7%%)
ە Antinuclear antibody (ANA) (positive, negative)
ە Anti-double stranded DNA (dsDNA) (positive, negative)
ە Lesion Counts by anatomic region
The duration of HS will be calculated relative to the date of the screening visit
(i.e., duration = [date of first study visit – date of onset] + 1). Duration of HS will be
expressed in years, by dividing the result in days by 365.25, and then rounding to the
nearest tenth.
7.2
Medical History
For the FAS population, the medical history data will be summarized and presented using 
body systems and conditions/diagnoses as captured on the eCRF. The body systems will 
be presented in alphabetical order and the conditions/diagnoses will be presented in 
alphabetical order within each body system. The number and percentage of subjects with 
a particular condition/diagnosis will be summarized. Subjects reporting more than one 
condition/diagnosis within a body system will be counted only once for that body system.
7.3
Prior and Concomitant Therapy
Prior and concomitant therapy using drug generic name coded using World Health 
Organization (WHO) dictionary will be summarized by the generic name with counts and
percentages. 
A prior medication is defined as any medication taken prior to the first dose of the 


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analysis period of each analysis population. A concomitant medication is defined as any 
medication that started prior to the first dose of the analysis period and continued to be 
taken after the first dose of the analysis period or any medication that started after the first 
dose of the analysis period, but not after the last dose of the analysis period. The number 
and percentage of subjects who had taken medications will be summarized by generic 
drug name for both prior and concomitant medications.
Prior HS treatment received and discontinued (including reason for discontinuation) prior
to screening will be summarized as well.
Prior HS related surgery will be summarized. Subjects with prior HS related surgery will
be identified per medical review prior to database lock.
8.0
Patient Disposition
Subject disposition will be present for subjects in the safety analysis set using the 
following information
z
Number of subjects in each analysis population
z
Number of screening failure
z
Subjects who completed the study
z
Subjects who prematurely discontinued study drug
In addition, the reasons for premature discontinuation (primary reason and all reasons)
will be summarized with frequencies and percentages. Subjects with multiple reasons for
premature discontinuation will be counted once in the calculation of the number and
percentage of total discontinuations ("Premature Discontinuation").
9.0
Study Drug Exposure and Compliance 
For the Safety Analysis Set population, study drug exposure will be summarized through
the study as follows:


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9.1
Study Drug Exposure
The duration (days) of exposure to study drug will be summarized using the number of 
subjects treated, mean, standard deviation, median, minimum, and maximum. It will also 
be summarized in weekly intervals with frequencies and percentages for the number of
subjects receiving study drug doses in each interval. In addition cumulative exposure of
adalimumab (including total patient years) will be summarized.
Duration of exposure is defined the number of days since first dose of study drug through 
the last dose date plus 14 days. For interim analysis mentioned in Section 4.4, the Week 
24/appropriate time after Week 52 dosing date will be used instead of last dose plus 14 
days only for ongoing subjects. For subjects who missed the Week 24/appropriate time 
after Week 52 study drug injection but continued after the Week 24/appropriate time after 
Week 52, the study drug exposure = (date of the first available study drug injection after 
the Week 24/appropriate time after Week 52 - date of first study drug injection).
9.2
Compliance
Compliance (%) is defined as the number of injections received divided by the number of 
injections planned during the subject's participation in the study (rounded to 0.1%). In 
addition, at each scheduled time point (i.e., Week 0, Week 2, every week from Week 4), 
the number of injections received will be summarized with frequencies and percentages.
Compliance will be summarized by descriptive statistics, including the mean, standard
deviation, Q1, median, Q3, minimum, and maximum.
When computing compliance at each scheduled time point, the denominator for each 
week will include all subjects in each analysis population who have not prematurely 
discontinued prior to the scheduled study drug injection.
9.3
Study Drug Dose
160 mg starting at Baseline (Week 0) and 80 mg Week 2 followed by 40 mg every week 
(ew) starting at Week 4.


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10.0
Efficacy Analysis
This section provides the details of the efficacy analysis for the study.
10.1
General Considerations
This study is an open-label study without any comparator. No formal statistical test will 
be conducted, and descriptive statistics will be provided. These include the number of 
observations, mean, standard deviation, minimum, median, and maximum for continuous 
variables; discrete variables will be summarized by counts and percentages with 95% 
confidence intervals.
All efficacy analyses and subgroup analyses will be performed on the FAS populations.
10.2
Primary Efficacy Analysis
The primary efficacy endpoint is the proportion of subjects achieving HiSCR at Week 12.  
HiSCR is defined as at least a 50% reduction in the total abscess and inflammatory nodule 
count (AN count) with no increase in abscess count and no increase in draining fistula 
count relative to Baseline.
Imputation Method Used for the Primary Efficacy Analysis
Missing data will be imputed using the non-responder imputation (NRI) approach. For 
details on missing data imputation methods, refer to Section 6. Sensitivity analyses will be 
performed for the primary efficacy variable by using LOCF and modified NRI.
Modified NRI (mNRI): counting all subjects with any add-on antibiotics (any antibiotics 
other than the Baseline concomitant ones) or with dose increase on Baseline concomitant 
antibiotics prior to Week 12, regardless the reason for use, as non-responders.
10.3
Secondary Efficacy Analyses 
Discrete variables will be summarized by counts and percentages, and continuous 
variables will be summarized by descriptive statistics on the items below at each visit.


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The subjects who have missing data for any reason such as early terminated subjects will 
be included into analysis using NRI for discrete variables or LOCF for continuous 
variables.
For the analysis of Patient's Global Assessment of Skin Pain (NRS), daily assessment will
be evaluated and weekly average will be used. For analysis, subjects who received
analgesics other than ibuprofen or acetaminophen (e.g., Tramadol) or received ibuprofen 
or acetaminophen that exceeds the maximum allowed dose (to be determined prior to 
database lock), for skin pain, or have undergone intervention will be counted as non-
responder for categorical variables, and have their last pain assessment before the start 
date of the analgesic or date of the intervention carried forward for continuous variables, 
from the start day of the analgesics or the day of the intervention until fourteen (14) days 
after the stop of analgesic use or the day of the intervention. LOCF and As-Observed 
analysis will be the sensitivity analyses for categorical variables and for continuous 
variables, respectively.
Concomitant medication for treatment of HS or pain will be reviewed; confounding 
medications (those considered as having potential effect on the pain assessments) and the 
time periods affected by such medications will be determined. Subjects will be counted as 
non-responder for categorical variables, and have their last pain assessment before the 
start of the confounding medications carried forward for continuous variables for these 
periods.
Do not take the following exclusionary medication:
¾
Using any antibiotics for the treatment of HS (except the protocol allowed 
baseline concomitant antibiotics)
¾
Protocol allowed baseline concomitant antibiotics that are not a stable dose 
¾
Using Methotrexate (MTX), cyclosporin, corticosteroids, and retinoids for any 
reason, or other medication for treatment of their HS 


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The following secondary efficacy variables will be analyzed:
z
Proportion of subjects achieving AN count of 0, 1, or 2 at Week 12
z
Proportion of subjects achieving at least 30% reduction and at least 1 unit reduction 
from Baseline in Patient's Global Assessment of Skin Pain (NRS30) – at worst at 
:HHNDPRQJVXEMHFWVZLWKEDVHOLQH156
z
Change in modified Sartorius scale from Baseline to Week 12 including screening 
period (Week -4, Week -2)
Other efficacy variables will be analyzed at each scheduled visit, including the primary or 
secondary variables for visits other than Week 2 or 12.
z
Proportion of subject achieving HiSCR
z
Proportion of subject achieving HiSCR (first screening date as baseline)
z
Proportion of subjects achieving AN count of 0, 1, or 2
z
Proportion of subjects achieving NRS30 – at worst, among subjects with baseline 
3DWLHQW
V*OREDO$VVHVVPHQWRI6NLQ3DLQ156
z
Proportion of subjects achieving NRS30 – on average, among subjects with baseline 
3DWLHQW
V*OREDO$VVHVVPHQWRI6NLQ3DLQ156
z
Change in modified Sartorius scale from Baseline including screening period (Week -
4, Week -2)
z
Proportion of subjects achieving complete elimination of abscesses at each visit, 
among subjects who have any abscess at Baseline
z
Percentage change from Baseline in number of abscesses, among subjects who have 
at least one abscess at Baseline
z
Change from Baseline in number of abscesses
z
Proportion of subjects achieving complete elimination of draining fistulas at each visit, 
among subjects who have any draining fistulas at Baseline
z
Percentage change from Baseline in number of draining fistulas, among subjects who 
have at least one draining fistula at Baseline
z
Change from Baseline in number of draining fistulas


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z
Percentage change from Baseline in number of inflammatory nodules, among subjects 
who have at least one inflammatory nodule at Baseline
z
Proportion of subjects achieving complete elimination of inflammatory nodules at 
each visit, among subjects who have any inflammatory nodules at Baseline
z
Change from Baseline in number of inflammatory nodules
z
Number of interventions until Week 12
z
Proportion of subjects with DLQI = 0
z
Proportion of subjects with DLQI = 0 or 1
z
Change from Baseline in DLQI
z
Percentage change from Baseline in Patient's Global Assessment of Skin Pain (NRS) 
– DWZRUVWDPRQJVXEMHFWVZKRKDYHEDVHOLQH156
z
Percentage change from Baseline in Patient's Global Assessment of Skin Pain (NRS) 
– on aveUDJHDPRQJVXEMHFWVZKRKDYHEDVHOLQH156
z
Change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – at worst
z
Change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – on
average
z
Proportion of subjects achieving AN50 (at least 50% reduction in the AN count 
relative to Baseline)
z
Proportion of subjects achieving AN75 (at least 75% reduction in the AN count 
relative to Baseline)
z
Proportion of subjects achieving AN100 (100% reduction in the AN count relative to 
Baseline)
z
Absolute and percentage change from Baseline in AN count including screening 
period (Week -4, Week -2)
z
Proportion of subjects achieving erythema score of 1 or 0 in all affected anatomic 
regions among subjects who have erythema score of 2 or more in at least one 
anatomic region at Baseline
z
Proportion of subjects who experience worsening by at least one Hurley Stage in at 
least 1 affected anatomic region


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z
Proportion of subjects who experience improvement by at least one Hurley Stage in at 
least 1 affected anatomic region
z
Change from baseline in TSQM
z
Change from baseline in EQ-5D index
z
Change from baseline in EQ-5D VAS
z
Change from baseline in HSQoL
z
Proportion of subjects who experience flare, defined as an at least 25% increase in 
AN counts with a minimum increase of 2 relative to Baseline
z
Number of days on flare, calculated from the day when flare is observed to the day 
prior to the observation that flare is no long present.  Of note, there could be multiple 
periods that flares are observed, in which case, the total days from the multiple 
periods will be used
z
Proportion of subjects who experience at least 25% increase in abscess counts with a 
minimum increase of 2 relative to Baseline
z
Proportion of subjects who experience at least 25% increase in inflammatory nodule 
counts with a minimum increase of 2 relative to Baseline
z
Proportion of subjects who experience at least 25% increase in draining fistula counts 
with a minimum increase of 2 relative to Baseline
z
Change from Baseline in CRP
z
Percentage change from Baseline in CRP
z
Time to the second incidence of the two-FRQVHFXWLYHYLVLWVZLWK$1FRXQW%DVHOLQH
AN count (will be calculated from the date of the Week 12 to the second incidence of 
the two consecutive visits that lead to WOAI)
z
Time to LOR (will be calculated from the date of the Week 12 to the first visits that 
lead to LOR)
Minimal clinically important difference (MCID) for all patient reported outcomes are 
defined in Appendix B.
Additional Secondary Efficacy Variables
z
Cumulative density plot of percent change from Baseline in AN count at Week 12


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z
Plot of proportion of subjects achieving HiSCR by visit
z
Proportion of subjects achieving MCID in DLQI 
z
Proportion of subjects achieving MCIDs in TSQM 
z
Proportion of subjects achieving MCID in HSQoL 
z
Proportion of subjects achieving MCID in EQ-5D index
z
Proportion of subjects achieving MCID in EQ-5D VAS
z
Proportion of subjects achieving NRS30 – at worst based on rolling weekly average, 
among subjects with %DVHOLQH6NLQ3DLQ156
z
Proportion of subjects achieving NRS30 – on average based on rolling weekly 
DYHUDJHDPRQJVXEMHFWVZLWK%DVHOLQH6NLQ3DLQ156
z
Change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – at worst 
EDVHGRQUROOLQJZHHNO\DYHUDJHDPRQJVXEMHFWVZLWK%DVHOLQH6NLQ3DLQ156
z
Change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – on
average based on rolling weekly average, among subjects with Baseline Skin Pain 
156
z
Percent change from Baseline in Patient's Global Assessment of Skin Pain (NRS) – at 
worst, based on rolling weekly average, among subjects with Baseline Skin Pain NRS 

z
Percent change from Baseline in Patient's Global Assessment of Skin Pain (NRS) –
on average, based on rolling weekly average, among subjects with Baseline Skin Pain 
156


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Table 12.
Summary of Efficacy Variables and Statistical Analyses
Efficacy Variables
Derivation
Categorical Efficacy Variables (Proportion of Responders at Each Visit)
1.
HiSCR response
xResponder: percent reduction from baseline in
$1DQG absolute change in abscess count
DQGDEVROXWHFKDQJHLQGUDLQLQJILVWXODVFRXQW

xNon-responder: otherwise
2.
AN012
xResponder: total number of abscess counts and
inflammatory nodule counts < 3
xNon-responder: otherwise
3.
NRS30 – at worst. At least 30% 
reduction
and 1 unit absolute reduction in 
Patient's Global Assessment of Skin 
Pain – at worst
x$PRQJVXEMHFWVZLWKEDVHOLQHYDOXH
Responder: percent reduction from baseline
DQGDEVROXWHUHGXFWLRQIURPEDVHOLQH
xNon-responder: otherwise
4.
NRS30 – on average. At least 30%
reduction and 1 unit absolute 
reduction in
Patient's Global Assessment of Skin 
Pain
x$PRQJVXEMHFWVZLWKEDVHOLQHYDOXH
Responder: percent reduction from baseline
DQGDEVROXWHUHGXFWLRQ IURPEDVHOLQH
xNon-responder: otherwise
5.
Modified Sartorius Score
The derivation of modified Sartorius Score will be
provided in the SAP.
6.
Complete elimination of abscesses
$PRQJVXEMHFWVZLWKEDVHOLQHYDOXH
xResponder: abscesses count = 0
xNon-responder: otherwise
7.
Complete elimination of draining 
fistulas
$PRQJVXEMHFWVZLWKEDVHOLQHYDOXH
xResponder: draining fistulas count = 0
xNon-responder: otherwise
8.
Complete elimination of inflammatory
nodules
Among subjects with EDVHOLQHYDOXH
xResponder: inflammatory nodule count = 0
xNon-responder: otherwise


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Table 12.
Summary of Efficacy Variables and Statistical Analyses (Continued)
Efficacy Variables
Derivation
Categorical Efficacy Variables (Proportion of Responders at Each Visit) (Continued)
9.
DLQI0
xResponder: DLQI = 0
xNon-responder: otherwise
10.
DLQI01
xResponder: DLQI = 0 or 1
xNon-responder: otherwise
11.
AN50
x5HVSRQGHUSHUFHQWUHGXFWLRQIURP%DVHOLQH
xNon-responder: otherwise
12.
AN75
x5HVSRQGHUSHUFHQWUHGXFWLRQIURP%DVHOLQH
xNon-responder: otherwise
13.
AN100
xResponder: abscesses count = 0 and inflammatory 
nodule count = 0
xNon-responder: otherwise
14.
Erythema01
$PRQJVXEMHFWVZKRKDYHHU\WKHPDVFRUHLQDW
least one anatomic region at Baseline
xResponder: erythema score = 1 or 0 in all 
anatomic regions
xNon-responder: otherwise
15.
Worsening in Hurley Stage
xExperiencing worsening: the minimum increase from 
baseline in Hurley Stage among all anatomic regions > 0
xNot experiencing worsening: otherwise
16.
Improvement in Hurley Stage
xResponder: the minimum reduction from baseline in 
Hurley Stage among all anatomic regions > 0
xNon-responder: otherwise


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Table 12.
Summary of Efficacy Variables and Statistical Analyses (Continued)
Efficacy Variables
Derivation
Categorical Efficacy Variables (Proportion of Responders at Each Visit) (Continued)
17.
Abscess count

18.
Draining fistula count

19.
Inflammatory nodule count
20.
AN count
21.
Patient's Global Assessment of Skin 
Pain – at worst
$PRQJVXEMHFWVZLWKEDVHOLQHYDOXH
22.
Patient's Global Assessment of Skin 
Pain – on average
$PRQJVXEMHFWVZLWKEDVHOLQHYDOXH
23.
DLQI
The derivation of DLQI will be provided in the SAP.
24.
TSQM
Total score is calculated by summing the scores from all 
13 items.
10.4
Handling of Multiplicity
No adjustment for multiplicity will be done.
10.5
Efficacy Subgroup Analysis
To evaluate the consistency of the efficacy in the primary efficacy variable over
demographic and other baseline characteristics, summaries and analyses will be
performed for the following subgroups:
z
Baseline Hurley Stage (II/III)
z
Concomitant use of oral antibiotics (yes/no)
z
Age group (< 40, 40–LIOHVVWKDQRIVXEMHFWVLQWKHJURXSWKDW
group will be combined with 40–64 group.)
z
Sex (male, female)


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z
'XUDWLRQRI+6PHGLDQPHGLDQ
z
:HLJKWPHGLDQPHGLDQ
z
Body Mass Index (BMI)  category:  normal (< 25), over weight (25 – < 30), obese 
(30 – 0RUELGREHVLW\ 40)
z
Current smoking status (yes/no)
z
%DVHOLQH&53OHYHOPHGLDQPHGLDQ
z
%DVHOLQH$1FRXQW– 10, 11+)
z
%DVHOLQH$1FRXQWPHGLDQPHGLDQ
11.0
Safety Analysis
11.1
General Considerations
Unless otherwise specified, all safety analysis will be performed on the Safety dataset. 
Missing safety data will not be imputed.
11.2
Analysis of Adverse Events
11.2.1
Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAE) are defined as any event with an onset or
worsening date that is after the first dose of study drug and with an onset date no more
than 70 days after the last dose of study drug. Events where the onset date is the same as
the study drug start date are assumed to be treatment emergent, unless the study 
drug start time and the adverse event start time are collected and the adverse event start 
time is prior to the study drug start time. If an incomplete onset date is collected for an 
adverse event, the event will be assumed to be treatment emergent unless there is other 
evidence that confirms that the event is not treatment emergent (e.g., the event end date is 
prior to the study drug start date).


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For the interim analysis, treatment-emergent adverse events are defined as below:
¾
For subjects who did not discontinue the study before the interim cut-off date, 
treatment-emergent adverse events are defined as the events collected after the first 
dose of study drug and on or prior the dose of study drug at Week 24 or Week 52.
¾
For subjects who discontinued the study before cut-off date, treatment-emergent 
adverse events are defined as the events collected after the first dose of study drug 
and within 70 days following the last dose of study drug and before the cut-off date. 
If the discontinued subject's adverse event onset date is within 70 days following the 
last dose of study drug but after the cut-off date will be excluded from interim 
analysis. 
Treatment-emergent adverse events will be summarized and presented using the Medical 
Dictionary for Regulatory Activities (MedDRA®) system organ classes (SOCs) and 
preferred terms (PTs) according to the version of the MedDRA coding dictionary used for 
the study at the time of database lock. The actual version of the MedDRA coding 
dictionary used will be noted in the clinical study report. The system organ classes will be 
presented in alphabetical order and the preferred terms will be presented in alphabetical 
order within each system organ class.
The number and percentage of subjects experiencing treatment-emergent adverse events 
will be summarized for the following adverse event categories and by Week 12 HiSCR 
status.
Adverse Event Overview
z
Any treatment-emergent adverse event
z
Any treatment-emergent adverse event that was rated as reasonable possibility to
study drug by the investigator (Reasonable Possibility)
z
Any treatment-emergent severe adverse event
z
Any treatment-emergent serious adverse event
z
Any treatment-emergent adverse event leading to discontinuation of study drug


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z
Any treatment-emergent serious adverse event that was rated as reasonable possibility 
to study drug by the investigator (Reasonable Possibility)
z
Any treatment-emergent adverse event leading to death
z
Any treatment-emergent adverse event of special interest
z
Any Deaths
Adverse Events by SOC and PT
The number and percentage of subjects experiencing adverse events will be tabulated 
according to the primary MedDRA system organ class (SOC) and preferred term (PT).  
Subjects reporting more than one adverse event for a given MedDRA PT will be counted 
only once for that term (most severe incident for the severity tables and most related 
incident for the relationship tables). Subjects reporting more than one type of adverse 
event within a MedDRA SOC will be counted only once for that SOC. Subjects reporting 
more than one type of adverse event will be counted only once in the overall total.
The following AEs will be summarized using the conventions described above:
z
Any treatment-emergent adverse event
z
Any treatment-emergent adverse event that was rated as reasonable possibility to
study drug by the investigator (Reasonable Possibility)
z
Any treatment-emergent adverse event by maximum severity
z
Any treatment-emergent adverse event by maximum relationship to study drug
z
Any treatment-emergent serious adverse event
z
Any treatment-emergent adverse event leading to discontinuation of study drug
z
Any treatment-emergent serious adverse event that was rated as reasonable possibility 
to study drug by the investigator (Reasonable Possibility)
z
Any treatment-emergent adverse event leading to death
z
Any treatment-emergent adverse event of special interest


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Adverse Events by Maximum Severity
Adverse events will also be summarized by maximum severity. If a subject has an adverse 
event with unknown severity, then the subject will be counted in the severity category of 
"unknown," even if the subject has another occurrence of the same adverse event with a 
severity present. The only exception is if the subject has another occurrence of the same 
adverse event with the most extreme severity – "Severe." In this case, the subject will be 
counted under the "Severe" category.
Adverse Events by Maximum Relationship
Adverse events will also be summarized by maximum relationship to study, as assessed 
by the investigator. If a subject has an adverse event with unknown relationship, then the 
subject will be counted in the relationship category of "unknown," even if the subject has 
another occurrence of the same adverse event with a relationship present. The only 
exception is if the subject has another occurrence of the same adverse event with a 
relationship assessment of "Reasonable Possibility." In this case, the subject will be 
counted under the "Reasonable Possibility" category, respectively.
Adverse Event Rates per 100 Patient Years of Study Drug Exposure
Incidence rates per 100 patient years of exposure to study drug will be presented for 
adverse event overviews and for adverse events by SOC and PT.
The treatment-emergent adverse event rate per 100 patient years of exposure will be 
calculated overall, for each primary SOC, and each PT. For this calculation, 1 year will be 
considered to be 365.25 days. The numerator of the overall rate, the SOC rate, or the PT 
rate, will be the total number of treatment-emergent adverse events reported overall, for 
the SOC, or for the PT, respectively; i.e., a subject can be counted more than once overall, 
for a SOC, and for a PT. The denominator of the rates will be the total number of days 
exposed to study drug summed across all treated subjects divided by 365.25, and rounded 
to 1 decimal place. The adverse event rate per 100 subject-years of exposure will be 


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calculated as [(numerator/denominator)]*100. The number of adverse events reported 
(numerator), the total number of years of study drug exposure (denominator), and the 
adverse event rate per 100 subject-years will be presented overall, for each SOC, and for 
each PT.
Adverse Events of Special Interest (AESI)
The list of AEs of Special Interest will be based on the most updated final version of
Humira Product Safety Statistical Analysis Plan, which is consistent to the most updated 
Humira Risk Management Plan. 
The current list of AEs of special interest for treatment with adalimumab is:
z
Any Infections AE
z
Any Serious Infection AE
z
Any Legionella Infection AE
z
Any Diverticulitis AE
z
Any Opportunistic Infection (Excluding Oral Candidiasis and TB) AE
z
Any Oral Candidiasis AE
z
Any Tuberculosis AE
z
Any Active Tuberculosis AE
z
Any Latent Tuberculosis AE
z
Any Parasitic Infection AE
z
Any Reactivation of Hepatitis B AE
z
Any Progressive Multifocal Leukoencephalopathy (PML) AE
z
Any Malignancy AE
z
Any Lymphoma AE
z
Any Hepatosplenic T-Cell Lymphoma (HSTCL) AE
z
Any Non-Melanoma Skin Cancer (NMSC) AE
z
Any Melanoma AE
z
Any Leukemia AE
z
Any Other Malignant (Excluding NMSC, Melanoma, Lymphoma, HSTCL,
and Leukemia) AE


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z
Any Allergic Reaction (Including Angioedema/Anaphylaxis) AE
z
Any Lupus-Like Reactions and Systemic Lupus Erythematosus AE
z
Any Vasculitis AE
z
Any Cutaneous Vasculitis AE
z
Any Non-Cutaneous Vasculitis AE
z
Any Sarcoidosis AE
z
Any Autoimmune Hepatitis AE
z
Any Myocardial Infarction Related AE
z
Any Cerebrovascular Accident Related AE
z
Any Congestive Heart Failure Related AE
z
Any Pulmonary Embolism Related AE
z
Any Interstitial Lung Disease AE
z
Any Intestinal Perforation AE
z
Any Pancreatitis AE
z
Any Stevens-Johnson Syndrome AE
z
Any Erythema Multiforme Related AE
z
Any Worsening/New Onset of Psoriasis AE
z
Any Demyelinating Disorder AE
z
Any Amyotrophic Lateral Sclerosis AE
z
Any Reversible Posterior Leukoencephalopathy Syndrome (RPLS) AE
z
Any Hematologic Disorders (Including Pancytopenia) AE
z
Any Liver Failure and Other Liver Event AE
z
Any Humira Administration Related Medication Errors AE
z
Any Injection Site Reaction AE
z
Any AE Leading to Death
z
Any AE Leading to Discontinuation of Study Drug.
z
Any Deaths
Additional AEs may be considered for tabulation/summary based on recommendations
from Clinical and Safety as deemed appropriate.


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11.2.2
Listing of Adverse Events
The following additional summaries of adverse events will be prepared.
z
Listing of treatment-emergent adverse events
z
Listing of subject numbers associated with each PT for treatment-emergent adverse 
events
z
Listing of treatment-emergent serious adverse events
z
Listing of pre-treatment serious adverse events
z
Listing of treatment-emergent adverse events that led to discontinuation of study drug
z
Listing of treatment-emergent fatal adverse events.
z
Listing of deaths
z
Listing of treatment-emergent adverse events of special interest
11.2.3
Safety Subgroup Analysis
The AE overview and AE by SOC and PT will also be analyzed with respect to the 
following Baseline characteristics. The subgroups are:
z
Current smoking status at Baseline (yes, no)
z
HbA1c  7%)
z
%0,
z
Prior HS surgery history (yes, no)
11.3
Analysis of Laboratory Data
All summaries will be conducted for the safety analysis populations and Laboratory test 
variables will use standard units.
11.3.1
Variables and Criteria Defining Abnormality
Laboratory test variables are specified in Table 13.
Note: For urinalysis, only specific gravity, pH will be summarized.


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Table 13.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
Red Blood Cell (RBC) count
White Blood Cell (WBC) 
count
Neutrophils
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
Blood
Glucose
Microscopic analysisa
Other
Pregnancy Test
QuantiFERON-TB Gold
CRP
HIV
Hepatitis B Screening
Hepatitis C Screening
HbA1c
Antinuclear Antibody (ANA)/Anti-dsDNA (if positive for ANA)
Pharmacokinetic
AAA
Serum HCG
Urine HCG
a.
A microscopic analysis will be performed by the central laboratory, in the event the dipstick results show protein, 
ketones or blood greater than negative or glucose greater than normal, or in the case of abnormal macroscopic 
results.
Potentially Clinically Significant Laboratory Values
Potentially Clinically Significant Laboratory Findings (Common Toxicity Criteria CTC
Grades 2 or higher) will be assessed.


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11.3.2
Statistical Methods
Analysis of Quantitative Laboratory Parameters (Hematology, Chemistry and
Urinalysis)
Changes from baseline to each scheduled visit and to the final value in continuous
laboratory parameters will be summarized with the mean, standard deviation, median,
minimum value and maximum value.
The baseline and visit/final value means will also be presented for subjects who have both
the baseline and visit/final values.
Shift Tables
Shift tables for changes from baseline according to the normal range will be provided for
each hematology, clinical chemistry and urinalysis (specific gravity and pH only)
parameter. Shifts from baseline to the following endpoints will be considered: minimum
value, maximum value and final value. Categories of "low or normal" and "high or
normal" will be included at baseline in addition to the categories of "low," "normal,"
"high" and "missing."
Potentially Clinically Significant Laboratory Values
Frequencies and percentages of subjects with post baseline lab values that are Grade 2 or
above, and separately for Grade 3 or above, according to the CTC toxicity criteria will be
summarized. A separate listing will be provided that presents all of the subjects and values 
that are CTC toxicity Grade 2 or above. For each of these subjects, the whole course of 
the respective parameter will be listed.
Liver Function Tests
Additional summaries will be presented for liver function tests including serum glutamic-
pyruvic transaminase (SGPT/ALT), serum glutamic-oxaloacetic transaminase 
(SGOT/AST), alkaline phosphatase (ALP), and total bilirubin. 
Each laboratory value will be categorized as follows:


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z
< 1.5 × ULN
z
î8/1 – < 3.0 × ULN
z
.0 × ULN – < 5.0 × ULN
z
.0 × ULN – < 8.0 × ULN
z
.0 × ULN
where ULN is the upper normal limit.
Shift tables of baseline to the maximum (relative to the normal range, i.e., the largest
multiple relative to the upper limit of normal) values, and from baseline to final value will
be presented using these five categories. A listing of potentially clinically significant liver
function laboratory values will be provided. The listing will include all subjects who met
any of the following four criteria:
z
$/7× ULN, or
z
$67× ULN, or
z
$ONDOLQHSKRVSKDWDVH× ULN, or
z
7RWDOELOLUXELQ× ULN


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Table 14.
Potentially Clinically Significant Laboratory Findings
Laboratory Parameter
CTC Grade 1
CTC Grade 2
CTC Grade 3
CTC Grade 4
Hemoglobin – Low (G/L)
< LLN – 100
< 100 – 80
< 80
–
Hemoglobin – High (G/L)
CH > 0.0 – 20
CH > 20 – 40
CH > 40
–
Platelet count (× 109/L)
< LLN – 75
< 75 – 50
< 50 – 25
< 25
WBC (× 109/L)
< LLN – 3.0
< 3.0 – 2.0
< 2.0 – 1.0
< 1.0
Neutrophils (× 109/L)
< LLN – 1.5
< 1.5 – 1.0
< 1.0 – 0.5
< 0.5
Lymphocytes (× 109/L)
< LLN – 0.8
< 0.8 – 0.5
< 0.5 – 0.2
< 0.2
ALT
> ULN - 3.0 × ULN
> 3.0 - 5.0 × ULN
> 5.0 - 20.0 × ULN
> 20.0 × ULN
AST
> ULN - 3.0 × ULN
> 3.0 - 5.0 × ULN
> 5.0 - 20.0 × ULN
> 20.0 × ULN
Alkaline phosphatase
> ULN - 2.5 x ULN
> 2.5 - 5.0 x ULN
> 5.0 - 20.0 x ULN
> 20.0 x ULN
Ȗ-GTP
> ULN – 2.5 × ULN
> 2.5 – 5.0 × ULN
> 5.0 – 20.0 × ULN
> 20.0 × ULN
Total bilirubin
> ULN - 1.5 × ULN
> 1.5 - 3.0 × ULN
> 3.0 - 10.0 × ULN
> 10.0 × ULN
Albumin (G/L)
< LLN – 30
< 30 – 20
< 20
–
CPK
> ULN – 2.5 × ULN
> 2.5 × ULN – 5.0 × ULN
> 5.0 × ULN – 10.0 × ULN
> 10.0 × ULN
Creatinine*
> ULN – 1.5 × ULN;
or > 1 - 1.5 × BL
> 1.5 – 3.0 × ULN
or > 1.5 – 3.0 × BL
> 3.0 – 6.0 × ULN
or > 3.0 × BL
> 6.0 × ULN
Uric Acid (MCMOL/L)
> ULN – 590
–
–
> 590
Calcium – Low (MMOL/L)
< LLN – 2.0
< 2.0 – 1.75
< 1.75 – 1.5
< 1.5
Calcium – High (MMOL/L)
> ULN – 2.9
> 2.9 – 3.1
> 3.1 – 3.4
> 3.4
Sodium – Low (MMOL/L)
< LLN – 130
–
< 130 – 120
< 120


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Table 14.
Potentially Clinically Significant Laboratory Findings (Continued)
Laboratory Parameter
CTC Grade 1
CTC Grade 2
CTC Grade 3
CTC Grade 4
Sodium – High (MMOL/L)
> ULN – 150
> 150 – 155
> 155 – 160
> 160
Potassium – Low (MMOL/L)
< LLN – 3.0
–
< 3.0 – 2.5
< 2.5
Potassium – High (MMOL/L)
> ULN – 5.5
> 5.5 – 6.0
> 6.0 – 7.0
> 7.0
Inorganic Phosphorus 
(MMOL/L)
< LLN – 0.8
< 0.8 – 0.6
< 0.6 – 0.3
< 0.3
Magnesium - Low (MMOL/L)
< LLN – 0.5
< 0.5 – 0.4
< 0.4 – 0.3
< 0.3
Magnesium - High (MMOL/L)
> ULN – 1.23
–
> 1.23 – 3.30
> 3.30
Glucose – Low (MMOL/L)
< LLN – 3.0
< 3.0 – 2.2
< 2.2 – 1.7
< 1.7
Glucose – High (MMOL/L)
> ULN – 8.9
> 8.9 – 13.9
> 13.9 – 27.8
> 27.8
Cholesterol (MMOL/L)
> ULN – 7.75
> 7.75 – 10.34
> 10.34 – 12.92
> 12.92
Triglycerides (MMOL/L)
1.71 – 3.42
> 3.42 – 5.7
> 5.7 – 11.4
> 11.4
CH = change in ULN or change in baseline, if baseline > ULN; ULN = upper limit of normal range; LLN = lower limit of normal range; BL = baseline;
* = identify by ULN if baseline is normal else use BL if baseline is abnormal;


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11.4
Analysis of Vital Signs and Weight
11.4.1
Variables and Criteria Defining Abnormality
Vital sign variables are sitting systolic blood pressure, sitting diastolic blood pressure, 
sitting pulse, respiratory rate, body temperature and weight. The following table presents 
the Criteria for Potentially Clinically Significant Vital Sign Findings.
The following vital signs are measured at the designated study visits in Table1.
Table 15.
Criteria for Potentially Clinically Significant Vital Sign Findings
Vital Sign
Category
Criteria for Potential Clinically Significant Vital Signs
Systolic blood pressure
Low
9DOXHPP+JDQGRUGHFUHDVHPP+JIURP%DVHOLQH
High
9DOXH0 mmHg and/or LQFUHDVHPP+JIURP%DVHOLQH
Diastolic blood pressure
Low
9DOXHPP+JDQGRUGHFUHDVHPP+JIURP%DVHOLQH
High
9DOXHPP+JDQGRULQFUHDVHPP+JIURP%DVHOLQH
Pulse
Low
9DOXHESPDQGRUGHFUHDVHESPIURP%DVHOLQH
High
9DOXHESPDQGRULQFUHDVHESPIURP%DVHOLQH
11.4.2
Statistical Methods
Mean changes from Baseline to post-baseline visits will be summarized with the baseline 
mean, visit mean, change from baseline mean, standard deviation, median, minimum 
value and maximum value. The number and percentage of subjects meeting the criteria for 
potentially clinically significant vital sign values will be summarized.
Vital sign results satisfying the criteria for potentially clinically significant vital sign 
findings will be identified in a listing. For each of these subjects, the whole course of the 
respective parameter will be listed.
11.5
Analysis of ECG Parameters
ECG results will be listed in the data listings.


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11.6
Analysis of Potentially Clinically Significant ECG Values
Not applicable.
12.0
Summary of Changes
None.
13.0
Appendices
Appendix A.Calculation of the Modified Sartorius Scale
Reference: Revus J, Hidradenitis Suppurativa. JEADV. 23, pp985-998, 2009


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Appendix B. Minimally Clinically Important Difference (MCID) Determination in Dermatology
Overall Suggestion: Instruments included in each of the clinical trials are documented below with published MCIDs where available. 
The current suggestion is to include these MCIDs in the statistical analysis plans but to also include the ½ standard deviation criteria 
for each domain and each instrument. This criteria is a well-accepted and published norm in outcomes studies when clinically 
meaningful criteria have not been established. This will allow for the evaluation of each endpoint on a similar measure across
instruments.
PRO 
NAME
MCID
Reference
Link to Reference 
DLQI
'HFUHDVHRISRLQWVwill 
be considered a responder 
Shikiar R, Willian MK, Okun MM,
et al. The validity and responsiveness of 
three quality of life measures in the
assessment of psoriasis patients: results of a 
phase II study. Health Qual Life Outcomes. 
2006;4:71. 
Strand V, Fiorentino D, Hu C, et al. 
Improvements in patient-reported
outcomes with apremilast, an oral 
phosphodiesterase 4 inhibitor, in the 
treatment of moderate to severe
psoriasis: results from a phase IIb
randomized, controlled study. Health 
Qual Life Outcomes. 2013;11:82.
http://www ncbi nlm nih.gov/pmc/articles/PMC1615869/
http://www hqlo.com/content/11/1/82


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PRO 
NAME
MCID
Reference
Link to Reference 
TSQM
ò6' increase from Baseline to 
be considered a responder
Atkinson, Mark J., PhD; Hass, Steven L., 
PhD "Effectiveness" scale of the Treatment 
Satisfaction Questionnaire for Medication 
(TSQM): the mean scale score for the 
"Effectiveness" items on the TSQM 
(version II).
http://www.qualitymeasures.ahrq.gov/content.aspx?id=26
828
HS QoL
ò6'LQFUHDVHIURP
Baseline to be considered
a responder
EQ-5D- 
Index Score
An increase of SRLQWV will 
be considered a responder
Shikiar R, Willian MK, Okun MM, et al. 
The validity and responsiveness of three 
quality of life measures in the assessment of 
psoriasis patients: results of a phase II 
study. Health Qual Life Outcomes. 
2006;4:71.
http://www ncbi nlm nih.gov/pmc/articles/PMC1615869/
http://www ncbi nlm nih.gov/pmc/articles/PMC1615869/t
able/T8/
EQ-5D- 
VAS
$QLQFUHDVHRIZLOO be 
considered a responder
See above
SD = standard deviation calculated based on Baseline values.