STRIKE - Treating Patients With Early Axial Spondyloarthritis to Target - a 1 Year Randomized Controlled Study Taking an Intense Treatment Approach Versus Routine Treatment
Phase: PHASE4
Conditions: Axial Spondyloarthritis
Sponsor: AbbVie

Adalimumab
W15-679 Protocol Amendment 2 
EudraCT 2015-005398-18
1 
1.0
Title Page
Clinical Study Protocol W15-679
Incorporating Amendments 1 and 2
STRIKE – Treating Patients with Early Axial 
Spondyloarthritis to Target – a 1 Year Randomized 
Controlled Study Taking an Intense Treatment 
Approach Versus Routine Treatment
AbbVie
Investigational 
  Product: 
Adalimumab
Date:
 30 March 2017  
Development Phase:
4
Study Design:
This is a randomized, controlled, open-label, monocountry, 
multicenter study
EudraCT Number: 
2015-005398-18 
Investigators: 
Multicenter trial (Investigator information is on file at AbbVie)
Sponsor: 
AbbVie Deutschland GmbH & Co. KG (AbbVie)  
Mainzer Str. 81 
65189 Wiesbaden  
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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
2
1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol 
Date
Original
04-February-2016
Amendment 1
24-June-2016
Amendment 2
The purpose of this amendment is to:
Ɣ
Update Section 1.2, Synopsis
Rationale: Added change in BASMIlin to secondary objectives in Objectives and
Criteria for Evaluation subsections to align with Section 5.3.1, Table 1 – Study 
Activities; increased the number of participating study sites to allow for faster 
enrollment; and aligned the Statistical Methods subsection with the respective 
wording concerning the safety analyses in Section 8.1.6 of the protocol.
Ɣ
Update Section 5.1, Overall Study Design and Plan: Description, and Section 5.5.1,
Treatments Administered
Rationale: Provided clarification regarding NSAIDs to be used in case of escalation 
to Escalation Step 2 due to intolerance to NSAID 2.
Ɣ
Update Section 5.2.1, Inclusion Criteria
Rationale: Removed statement concerning male contraception from inclusion 
criterion 9 to align with contraception requirements outlined in Section 5.2.4.
Ɣ
Section 5.2.4, Contraception Recommendations
Rationale: Aligned Section title and Section with updates in inclusion criterion 
concerning contraception as well as corresponding Section 5.2.4 in new protocol 
template.
Ɣ
Section 5.3.1, Efficacy and Safety Measurements assessed and Flow Chart
Rationale: Updated footer l in Table 1 – Study Activities for further clarification
concerning MRI assessment in case of premature study discontinuation.
Ɣ
Section 5.3.1.1, Study Procedures

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
3
Aligned time point of 1st MRI (Screening) between Section 5.3, Table 1 - Study 
Activities and the text; provided further clarification on the IGRA test to be used for 
TB screening; updated study drug to study treatment in ‘Medical and Surgical 
History’and ‘Laboratory Analyses’ subsections for further clarification; and clarified 
that the visit schedule will continue with the first dose of study treatment subsequent to 
completion of TB screening and prophylaxis (if applicable).
Ɣ
Section 5.3.2.1, Collection of samples for analysis
Rationale: Ensured alignment of the data points recorded during central laboratory 
sample collection with the eCRF (instead of with the sample requisition form).
Ɣ
Section 5.3.3.2, Secondary Endpoints
Rationale: Added change in BASMIlin to secondary objectives to align with Section 
5.3.1, Table 1 – Study Activities.
Ɣ
Section 6.1, Medical Complaints
Rationale: Changed Section title from ‘Adverse Events’ to ‘Medical Complaints’ to
align with new protocol template.
Ɣ
Section 6.1.3, Relationship to Humira
Rationale: Updated definitions of reasonable versus no reasonable possibility to align 
with new protocol template.
Ɣ
Section 6.1.5, Adverse Event Reporting
Rationale: Updated responsible safety contact due to change in AbbVie 
Pharmacovigilance team.
Ɣ
Section 6.1.6, Pregnancy Reporting
Rationale: Updated Section to align with new protocol template.
Ɣ
Section 9.1, Independent Ethics Committee (IEC) or Institutional Review Board (IRB)
Rationale: Updated Section to align with new protocol template.
Ɣ
Section 13, Completion of the Study
Rationale: Updated Section to align with new protocol template.
Changes to the specific sections of the protocol are shown in the redline version of the 
protocol using strike through red fond for deletions and red underlined for insertions.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
4
A copy of this protocol amendment will be sent to the Institutional Review Board (IRB)/ 
Independent Ethics Committee (IEC) and the responsible Health Authority.
The changes described in this protocol amendment required IRB/IEC approval prior to
implementation.
The changes will not affect the study population.
Amendment 1
The purpose of this amendment was to:
Ɣ
Update Section 1.2, Synopsis.
Rationale: Aligned the Statistical Methods subsection with Section 8.1.6 of the 
protocol in view of the definition and collection period of treatment emergent adverse 
events.
Ɣ
Update Section 1.3, List of Abbreviations.
Rationale: Removed high sensitivity C-reactive protein (hs CRP) from the List of 
Abbreviations to reflect that C-reactive protein (CRP) will be assessed instead of hs 
CRP.
Ɣ
Update Section 5.2.2, Exclusion criteria.
Rationale: Amended the criteria upon Ethics Committee’s request, to reflect that 
vulnerable patients are not eligible to participate in the study.
Ɣ
Section 5.2.4, Contraception Recommendations.
Rationale: Corrected the threshold concerning age limits for menopause to account 
for female subjects at 55 years of age.
Ɣ
Section 5.3.1, Efficacy and Safety Measurements Assessed and Flow Chart.
Rationale: Updated Table 1 (Study Activities), Table 2 (Clinical Laboratory Tests) 
and the Section text to reflect that CRP will be assessed instead of hs CRP; updated 
the Section text to clarify that Human Leukocyte Antigen-B27 (HLA-B27) does not 
have to be performed (again) in case of a rescreen or if a result of a previously 
documented HLA-B27 test is available; aligned the Section text with Table 1 to reflect 
that MRI assessments will be performed at Screening instead of Baseline, and to 
simultaneously provide instructions on the time points of the MRI assessments at 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
5
Screening; and updated the Section text to provide more detailed clarification to 
subject numbering. 
Ɣ
Updated Section 5.4.1, Discontinuation of Individual Subjects.
Rationale: Upon Ethics Committee’s request, provided more detailed clarification on 
the reasons for premature study discontinuation of individual subjects by cross-
referencing to Section 6.1.7.
Ɣ
Updated Section 5.4.2, Discontinuation of Entire Study.
Rationale: Upon Ethics Committee’s request, provided more detailed clarification on 
the reasons for premature study termination.
Ɣ
Updated Section 5.6.3, Suitability of Subject Population.
Rationale: Corrected Section text for alignment with inclusion criterion 5 in Section 
5.2.1.
Ɣ
Updated Section 6.1.3, Relationship to Humira.
Rationale: Updated the Section text to clarify that relationship to Humira will be 
assessed for all adverse events irrespective of their seriousness.
Ɣ
Updated Section 6.1.7, Toxicity Management.
Rationale: Amended Section text with information on management of selected 
laboratory abnormalities.
Ɣ
Updated Section 8.1.6, Safety Analysis.
Rationale: Amended Section text for alignment with Section 1.2 (Synopsis).
Ɣ
Updated Appendix C, Assessment of SpondyloArthritis International Society (ASAS) 
Axial Spondyloarthritis Criteria for Classification.
Rationale: Updated Appendix C for alignment with inclusion criterion 2 in Section 
5.2.1.
Ɣ
Updated Appendix S, Berlin Magnetic Resonance Imaging (MRI) Score for the Spine 
and the Sacroiliac Joints.
Rationale: Updated Appendix S to correct the Grades in the Berlin Magnetic
Resonance Imaging (MRI) Score assessed.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
6
1.2
Synopsis
AbbVie Inc.
Protocol Number: W15-679
Name of Study Drug: Adalimumab
Phase of Development: 4
Name of Active Ingredient: Adalimumab
Date of Protocol Synopsis: 30 March 2017
Protocol Title: STRIKE – Treating Patients with Early Axial Spondyloarthritis to Target – a 1 Year 
Randomized Controlled Study Taking an Intense Treatment Approach Versus Routine Treatment
Objectives:
The Primary Objective of this study is to compare a treat-to-target (T2T) intense treatment approach 
with a routine treatment approach (Standard of Care [SOC]) in reducing disease activity at Week 32 in 
patients with axial spondyloarthritis (axSpA).
The Secondary Objectives are to compare a T2T intense treatment approach with SOC by assessing the 
following at Week 32 and Week 52:
improvement of quality of  life
x
Quality of life by the European Quality of Life – 5 Dimension Questionnaire (EQ-5D)
x
Overall functioning by Assessment of Spondyloarthritis International Society (ASAS) Health 
Index (HI)
improvement of function
x
Function – Represented by the Bath AS (Ankylosing Spondylitis) Functional Index (BASFI) 
Numerical Rating Scale (NRS) score (0 to 10)
improvement of work productivity
x
Work Productivity and Activity Impairment – Axial Spondyloarthritis (WPAI-axSpA)
reducing inflammation
x
Active inflammation as measured by magnetic resonance imaging of the sacroiliac joints and the 
spine (Berlin Magnetic Resonance Imaging [MRI] scores for the sacroiliac [SI] joints and spine)
x
C-reactive Protein 
x
Erythrocyte sedimentation rate
reducing disease activity
x
Disease activity as measured by Bath AS Disease Activity Index (BASDAI)
x
Percentage of subjects achieving 50% improvement in BASDAI (BASDAI 50 response)
x
Change from Baseline in disease activity measured by Ankylosing Spondylitis Disease Activity 
Score (ASDAS) 
x
Percentage of subjects achieving ASDAS major improvement
x
Percentage of subjects achieving ASDAS clinically important improvement 
x
Percentage of subjects in ASDAS inactive disease (ASDAS < 1.3) 
x
Percentage of subjects with low disease activity (ASDAS < 2.1)
x
3HUFHQWDJHRIVXEMHFWVZLWKPRGHUDWHGLVHDVHDFWLYLW\$6'$6WR
x
Percentage of subjects ZLWKKLJKGLVHDVHDFWLYLW\$6'$6WR
x
3HUFHQWDJHRIVXEMHFWVZLWKYHU\KLJKGLVHDVHDFWLYLW\$6'$6

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
7
Objectives (Continued):
x
Percentage of subjects achieving ASAS 20, ASAS 40, and ASAS Partial Remission
x
Change from Baseline in Physician's Global Assessment of Disease Activity
x
Change from Baseline in Patient's Global Assessment of Disease Activity
x
Change from Baseline in Patient's Global Assessment of Pain
x
Change from Baseline in Swollen Joint Count (66 joints)
x
Change from Baseline in Tender Joint Count (68 joints)
x
Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
x
Change from Baseline in the Dactylitis count (0 – 20)
x
Change from Baseline in BASMIlin
x
Anterior uveitis
Other variables to be analyzed at various time points including Week 32 and Week 52:
x
ASDAS course over time
x
BASDAI course over time
Exploratory Objectives:
x
Serum autoantibodies against cluster of differentiation 74 class II-associated invariant chain 
peptide (CD74 CLIP)
x
Reduction of disease progression (as measured by MRI of the sacroiliac joints and the spine)
Investigators: Multicenter (Investigator information is on file at AbbVie).
Study Sites: Approximately 30 sites
Study Population: Adult subjects with a diagnosis of axSpA and disease duration less than 5 years
Number of Subjects to be Enrolled: Approximately 240
Methodology:
This is a Phase 4, multicenter, randomized, open-label, parallel-group study comparing an intensified 
T2T treatment approach with SOC.
The study duration will include a 42-day Screening period, a 52-week treatment period (treatment T2T 
according to randomization or SOC), and – only for subjects who receive study drug Humira but do not 
continue on commercially available Humira after the study – a 70 day follow-up phone call.
Subjects who have signed the informed consent and who fulfill all screening criteria will be randomized 
to receive either treatment following an intensified T2T approach (T2T group) or treatment according to 
SOC (following the local practice standards) (SOC group).
T2T Group (Investigational Group):
After randomization subjects are seen at Weeks 2, 4, 6, 8 and afterwards every 4 weeks up to Week 52.  
Basic treatment will be started with a non-steroidal anti-inflammatory drug (NSAID).  Treatment should 
EHLQWHQVLILHGHVFDODWHGEHJLQQLQJDW:HHNLIWKH$6'$6LVHVFDODWLRQVWHS7UHDWPHQW
escalation is planned to be initiated at Week 4, if needed and further escalation is planned at Week 8, if 
needed (escalation step 2).  However, if not required at Week 8, treatment can be escalated at every visit 
thereafter if the ongoing treatment is not sufficiently efficacious and the escalation step 2 has not yet been 
reached.  Treatment escalation steps are as follows:

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
8
Methodology (Continued):  
T2T Group (Investigational Group) (Continued):
x
Basic treatment (NSAID 1):  Treatment will be started with any NSAID and given for 4 weeks 
at full anti-inflammatory dose.  If at Week 2 ASAS 20 response is not achieved, subjects may 
early escape to Escalation Step 1.  If the chosen NSAID cannot be continued due to intolerance, 
escalation to the next escalation step is possible at any time point.  If basic treatment is well 
tolerated and sufficiently efficacious the subject will be continued on this treatment.
x
Escalation step 1 (NSAID 2):  Treatment will be changed to a second NSAID if after 4 weeks of 
WUHDWPHQWWKHILUVW16$,'LVQRWVXIILFLHQWO\HIILFDFLRXV$6'$6DQGRUQRWWROHUDWHG
The second NSAID will be given for 4 weeks.  Early escape is possible if after 2 weeks no 
ASAS 20 response is achieved.  In this case treatment can be switched to escalation step 2 after 
2 weeks of NSAID 2.  If the chosen NSAID cannot be continued due to intolerance, escalation 
to the next escalation step is possible at any time point.  If NSAID 2 treatment is well tolerated 
and sufficiently efficacious the subject will be continued on this treatment.
x
Escalation step 2 (Combination with adalimumab):  In case of failure of NSAID 2 (ASDAS 
 2.1 after 4 weeks of NSAID 2) the treatment will be intensified by switching to the 
combination of NSAID and adalimumab 40 mg s.c. every other week (eow).  Escalation step 2 
can be initiated at Week 4 visit at the earliest if early escape is chosen during Basic Treatment 
and during NSAID 2. 
SOC Group (Reference Group):
After randomization, subjects will receive treatment according to local practice standards.  Subjects are 
seen at Weeks 12, 24, 32, and 52.  
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:
1.
Subjects must have signed written informed consent before starting any study-related assessments or 
procedures.
2.
Diagnosis of axSpA (either ankylosing spondylitis or non-radiographic axSpA) and fulfilling the 
ASAS classification criteria for axSpA.
3.
6XEMHFWVDJHG\HDUV
4.
Disease duration < 5 years.
5.
6XEMHFWVPXVWKDYHDEDVHOLQHGLVHDVHDFWLYLW\DVGHILQHGE\KDYLQJDQ$6'$6RUD%$6'$,
 4.
6.
Subjects must be either NSAID-naïve or had not been treated with the maximal recommended dose 
during the last 2 weeks prior to the Baseline Visit.
7.
Subjects must never have failed a NSAID taken at maximal recommended dose for 2 weeks or more.
Main Exclusion:
1.
Contraindications for NSAIDs or Tumor Necrosis Factor (TNF) blocker according to local labeling.
2.
If entering the study on concomitant NSAIDs, subjects taking the maximal recommended dose 
during the last 2 weeks prior to the Baseline Visit or have failed or developed intolerance to a 
NSAID taken at maximal recommended dose for 2 weeks or more at any time.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
9
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
3.
Prior exposure to any anti-TNF therapy; any biologic therapy with a potential therapeutic impact on 
SpA, or subject has been treated with any investigational drug of chemical or biologic nature within a 
minimum of 30 days or five half-lives (whichever is longer) of the drug prior to the Baseline Visit.
Investigational Product:
Adalimumab
Dose:
40 mg eow
Mode of Administration:
s.c.
Reference Therapy:
Local Standard of Care
Duration of Treatment:
Subjects will be treated for 52 weeks receiving either treatment according to the T2T intensified 
treatment scheme or SOC.  Study drug will only be administered in the T2T group.  Length of exposure 
will depend on individual necessity for intensifying treatment.  The maximal duration of treatment with 
adalimumab is up to 48 weeks.
Criteria for Evaluation:
Efficacy:
The primary efficacy endpoint is the clinical disease activity at Week 32 as measured by the percentage 
of subjects in ASDAS inactive disease (ASDAS < 1.3).
Secondary efficacy endpoints include the following at Week 32 and Week 52:
x
Quality of life by the European Quality of Life – 5 Dimension Questionnaire (EQ-5D)
x
Work Productivity and Activity Impairment – axSpA (WPAI-axSpA)
x
Overall functioning by ASAS HI
x
Disease activity as measured by BASDAI
x
Percentage of subjects achieving 50% improvement in BASDAI (BASDAI 50 response)
x
Function – Represented by the BASFI NRS score (0 to 10)
x
Change from Baseline in ASDAS 
x
Percentage of subjects achieving ASDAS major improvement
x
Percentage of subjects achieving ASDAS clinically important improvement 
x
Percentage of subjects in ASDAS inactive disease (ASDAS < 1.3) 
x
Percentage of subjects with low disease activity (ASDAS < 2.1)
x
Percentage of subjects with moderate GLVHDVHDFWLYLW\$6'$6WR
x
3HUFHQWDJHRIVXEMHFWVZLWKKLJKGLVHDVHDFWLYLW\$6'$6WR
x
3HUFHQWDJHRIVXEMHFWVZLWKYHU\KLJKGLVHDVHDFWLYLW\$6'$6
x
Percentage of subjects achieving ASAS 20, ASAS 40, and ASAS Partial Remission
x
Active inflammation as measured by magnetic resonance imaging of the sacroiliac joints and the 
spine (Berlin MRI scores for the SI joints and spine)
x
Change from Baseline in Physician's Global Assessment of Disease Activity
x
Change from Baseline in Patient's Global Assessment of Disease Activity

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
10
Criteria for Evaluation (Continued):
Efficacy (Continued):
x
Change from Baseline in Patient's Global Assessment of Pain
x
Change from Baseline in Swollen Joint Count (66 joints)
x
Change from Baseline in Tender Joint Count (68 joints)
x
Change from Baseline in the MASES 
x
Change from Baseline in the Dactylitis count (0 – 20)
x
Change from Baseline in BASMIlin
x
Anterior uveitis
Other variables to be analyzed at various time points including Week 32 and Week 52:
x
C-reactive Protein 
x
Erythrocyte sedimentation rate
x
ASDAS course over time
x
BASDAI course over time
Exploratory endpoints:
x
Serum autoantibodies against CD74 CLIP
x
Reduction of disease progression (as measure by MRI of the sacroiliac joints and the spine)
Pharmacokinetic:
N.A.
Safety:
Screening assessments will include medical history, vital signs, physical examination, and clinical 
laboratory tests.  The following safety evaluations will be performed during the study:  concomitant 
medication review, adverse event (AE) monitoring, assessments of vital signs, physical examination and 
laboratory tests.
Statistical Methods:
Efficacy:
The primary efficacy endpoint is the response rate of clinical disease activity at Week 32 as measured by 
the percentage of subjects with ASDAS inactive disease (ASDAS < 1.3) in the two treatment arms.  
Subjects with missing data at Week 32 subjects will be counted as non-responders (non-responder 
imputation).  The null hypothesis states that there is no difference in response rates between the 
intensified T2T arm and the SOC arm; the alternative hypothesis is that the response rates are different.  
The response rates will be tested using a two-VLGHG3HDUVRQ
VFKLVTXDUHWHVWZLWKĮ 7KH)LVKHU
V
H[DFWWHVWZLOOEHDSSOLHGLIRIWKHFHOOVLQWKHIUHTXHQF\WDEOHKDYHH[SHFWHGFRXQWVOHVVWKDQ
All statistical tests which will be performed for secondary endpoints are only of exploratory nature and 
no adjustment for multiple comparisons is planned.  Discrete secondary efficacy variables will be 
compared between the two treatment arms using Pearson's chi-square (or Fisher's exact test if more 
appropriate) and continuous secondary variables will be compared between the treatment arms using an 
analysis of covariance method adjusting for the corresponding baseline values.  Descriptive statistics will 
also be provided for primary and secondary variables.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
11
Statistical Methods (Continued):
Pharmacokinetic:
N.A.
Safety:
Safety analyses will be carried out using the safety population, which includes all subjects who received 
treatment for axSpA after randomization Treatment-emergent AEs and serious AEs (SAEs), which 
include pre- and post-treatment SAEs, will be summarized and reported.
Treatment-emergent AEs are defined as AEs that begin either on or after the Baseline Visit up to the end 
of the study (including for the T2T arm, up to 70 days after the last dose of the study medication, except 
for those subjects that initiate adalimumab therapy not supplied in the context of the clinical trial after the 
end of study participation).  The number and percent of subjects experiencing AEs will be tabulated by 
system organ class and Medical Dictionary for Drug Regulatory Activities (MedDRA®) preferred term.  
In addition, a summary of treatment-emergent AEs by severity and relationship to study drug will be 
presented.  Serious, severe, or life.threatening AEs and those that lead to premature study discontinuation 
will be listed and described.
Mean change in vital signs and laboratory variables at each visit as compared to Baseline will be 
summarized for all treated subjects, and compared between treatment groups using a one way Analysis of 
Variance (ANOVA).  The last evaluation on or prior to the Baseline visit will be used as baseline for all 
analyses.  For selected parameters, a listing of all subjects with any laboratory determination meeting 
Common Toxicity Criteria (CTC) of Grade 3 or higher will be provided.  Shift tables for changes from 
Baseline according to the normal range will also be provided for laboratory variables.
Sample Size:
Based on available data from previous studies it is assumed that ASDAS inactive disease could be 
reached by 40% in the T2T group versus 20% in the control group.  In total 2 × 90 evaluable subjects are 
necessary to detect with 80% power an increase in ASDAS inactive disease at Week 32 from 20% in the 
SOC arm to 40% in the intensified T2T arm, if a two sided Fisher's exact test is applied.  If the Pearson 
chi-square test instead of the Fisher's exact test can be applied (see Section 8.1.4.1), then only 
2 × 83 subjects are necessary.
Assuming that about 18% of the randomized subjects will drop out prior to Week 32 and have to be 
counted as non-responder the assumed ASDAS inactive disease rate will be diluted to 16.4% in the SOC 
arm and 32.8% in the intensified T2T arm.  The necessary sample size for this scenario (intent to treat 
[ITT] population) is 2 × 109 subjects for the chi-square test and 2 × 119 subjects for the Fisher's exact 
test.  In summary, 2 × 120 subjects should be randomized.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
12
1.3
List of Abbreviations and Definition of Terms
Abbreviations
6-MP
6-mercaptopurine
AE
Adverse event
ALT
Alanine aminotransferase
ANA
Antinuclear antibody
ANOVA
Analysis of variance
AS
Ankylosing Spondylitis
ASAS 
Assessment of Spondyloarthritis International Society
ASDAS
Ankylosing Spondylitis Disease Activity Score
AST
Aspartate aminotransferase
ATEMS
AbbVie Temperature Excursion Management System
axSpA
Axial spondyloarthritis
AZA
Azathioprine
BASDAI
Bath AS Disease Activity Index
BASFI
Bath AS Functional Index
BASMI
Bath Ankylosing Spondylitis Metrology Index
BCG
Bacillus Calmette-Guérin
BD
Behçet's disease
CD
Crohn's disease
CD74 CLIP
Cluster of differentiation 74 class II-associated invariant chain peptide
CDC
Centers for Disease Control and Prevention
CRA
Clinical Research Associate
CRP
C-reactive Protein
CS
Clinically significant
csDMARD
conventional systemic disease-modifying anti-rheumatic drug
CTC
Common toxicity criteria
CXR
Chest X-ray
DMARD
Disease-modifying anti-rheumatic drug
DNA
Deoxyribonucleic acid
ECG
Electro Cardiogram
eCRF
Electronic Case Report Form
EDC
Electronic data capture

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
13
EMA
European Medicines Agency
Eow
Every other week
EQ-5D
European Quality of Life – 5 Dimension
ESR
Erythrocyte sedimentation rate
EU
European Union
EULAR
European League Against Rheumatism
FDA
Food and Drug Administration
FSH
Follicle-stimulating hormone
GCP
Good Clinical Practice
GPRD
Global Pharmaceutical Research and Development
HBc Ab
Hepatitis B core antibody
HBs Ab
Hepatitis B surface antibody
HBs Ag
Hepatitis B surface antigen
HBV
Hepatitis B virus
HI
Health Index
HIV
Human Immunodeficiency Virus
HLA-B27
Human Leukocyte Antigen-B27
IBP
Inflammatory back pain
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IgG1
Immunoglobulin G1
IGRA
Interferon-Gamma Release Assay
IMP
Investigational Medicinal Product
IP
Investigational product
IRB
Institutional Review Board
ITT
Intent to treat
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous
JIA
Juvenile idiopathic arthritis
LSMEAN
Least square mean values
LOCF
Last observation carried forward
MASES
Maastricht AS Enthesitis Score

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
14
MedDRA
Medical Dictionary for Drug Regulatory Activities
MRI
Magnetic Resonance Imaging
MTX
Methotrexate
NCS
Not clinically significant
nr-axSpA
Non-radiographic axial spondyloarthritis
NRS
Numerical Rating Scale
NSAID
Nonsteroidal Anti-inflammatory Drug
NYHA
New York Heart Association
PA
Posterior-anterior
PCR
Polymerase chain reaction
POR
Proof of receipt
PPD
Purified Protein Derivative
PsA
Psoriatic arthritis
PTGA
Patient's Global Assessment
RA
Rheumatoid arthritis
RBC
Red blood cell
SAE
Serious adverse event
SAP
Statistical analysis plan
SC
subcutaneous
SI
Sacroiliac
SJC
Swollen Joint Count
SOC
Standard of Care
SpA
Spondyloarthritis
SSZ
Sulfasalazine
SUSAR
Suspected Unexpected Serious Adverse Reactions
T2T
Treat-to-target
TB
Tuberculosis
TJC
Tender Joint Count
TNF
Tumor Necrosis Factor
UC
Ulcerative colitis
US
United States
WBC
White blood cell
WOCBP
Women of childbearing potential
WPAI
Work Productivity and Activity Impairment

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
15
2.0
Table of Contents
1.0 
Title Page..................................................................................1 
1.1 
Protocol Amendment:  Summary of Changes ...........................................2 
1.2 
Synopsis .....................................................................................................6 
1.3 
List of Abbreviations and Definition of Terms........................................12 
2.0 
Table of Contents...................................................................15 
3.0 
Introduction ...........................................................................20 
3.1 
Axial Spondyloarthritis............................................................................20 
3.2 
Current Treatments ..................................................................................20 
3.3 
Adalimumab Overview............................................................................23 
3.4 
Safety Information ...................................................................................24 
3.5 
Considerations on the Best Outcome Parameter for a 
Treat-to-Target (T2T) Approach in axSpA..............................................24 
3.6 
Rationale for the Study ............................................................................27 
3.7 
Differences Statement..............................................................................28 
3.8 
Benefits and Risks....................................................................................28 
4.0 
Study Objective......................................................................29 
5.0 
Investigational Plan...............................................................29 
5.1 
Overall Study Design and Plan:  Description ..........................................29 
5.2 
Selection of Study Population..................................................................35 
5.2.1 
Inclusion Criteria .....................................................................................35 
5.2.2 
Exclusion Criteria ....................................................................................36 
5.2.3 
Prior and Concomitant Therapy...............................................................39 
5.2.3.1 
Prior Therapy ...........................................................................................40 
5.2.3.2 
Concomitant Therapy...............................................................................41 
5.2.3.3 
Prohibited Therapy...................................................................................42 
5.2.4 
Contraception Recommendations ............................................................43 
5.3 
Efficacy, Pharmacodynamic, and Safety Assessments/Variables ...........45 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart ................45 
5.3.1.1 
Study Procedures .....................................................................................53 
5.3.2 
Measurement of Autoantibodies Against CD74 CLIP ............................67 
5.3.2.1 
Collection of Samples for Analysis .........................................................67 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
16
5.3.2.2 
Handling/Processing of Samples for the Detection of 
Autoantibodies Against CD74 CLIP .......................................................68 
5.3.2.3 
Disposition of Samples for the Detection of Autoantibodies 
Against CD74 CLIP.................................................................................68 
5.3.3 
Efficacy Endpoints...................................................................................69 
5.3.3.1 
Primary Efficacy Endpoint ......................................................................69 
5.3.3.2 
Secondary Endpoints ...............................................................................69 
5.3.3.3 
Exploratory Endpoints .............................................................................71 
5.3.4 
Safety Variables.......................................................................................71 
5.4 
Removal of Subjects from Therapy or Assessment.................................71 
5.4.1 
Discontinuation of Individual Subjects....................................................71 
5.4.2 
Discontinuation of Entire Study...............................................................73 
5.5 
Treatments................................................................................................73 
5.5.1 
Treatments Administered.........................................................................73 
5.5.2 
Identity of Investigational Product...........................................................75 
5.5.2.1 
Packaging and Labeling...........................................................................75 
5.5.2.2 
Storage and Disposition of Study Drug ...................................................75 
5.5.3 
Method of Assigning Subjects to Treatment Groups...............................76 
5.5.4 
Selection and Timing of Dose for Each Subject......................................76 
5.5.5 
Blinding....................................................................................................77 
5.5.5.1 
Blinding of Investigational Product.........................................................77 
5.5.6 
Treatment Compliance.............................................................................77 
5.5.7 
Drug Accountability.................................................................................77 
5.6 
Discussion and Justification of Study Design..........................................78 
5.6.1 
Discussion of Study Design and Choice of Control Groups....................78 
5.6.2 
Appropriateness of Measurements...........................................................79 
5.6.3 
Suitability of Subject Population .............................................................79 
5.6.4 
Selection of Doses in the Study ...............................................................79 
6.0 
Complaints .............................................................................80 
6.1 
Medical Complaints.................................................................................80 
6.1.1 
Definition .................................................................................................81 
6.1.1.1 
Adverse Event..........................................................................................81 
6.1.1.2 
Serious Adverse Events ...........................................................................82 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
17
6.1.2 
Adverse Event Severity............................................................................83 
6.1.3 
Relationship to Humira............................................................................83 
6.1.4 
Adverse Event Collection Period.............................................................84 
6.1.5 
Adverse Event Reporting.........................................................................85 
6.1.6 
Pregnancy.................................................................................................86 
6.1.7 
Toxicity Management ..............................................................................87 
6.2 
Product Complaint ...................................................................................88 
6.2.1 
Definition .................................................................................................88 
6.2.2 
Reporting..................................................................................................89 
7.0 
Protocol Deviations................................................................89 
8.0 
Statistical Methods and Determination of Sample 
Size ..........................................................................................90 
8.1 
Statistical and Analytical Plans................................................................90 
8.1.1 
Analysis Population .................................................................................90 
8.1.2 
Statistical and Analytical Plan .................................................................91 
8.1.3 
Analysis of Demographic Data and Baseline Disease 
Characteristics..........................................................................................92 
8.1.4 
Statistical Analysis of Efficacy................................................................92 
8.1.4.1 
Analysis of Primary Efficacy Endpoint ...................................................92 
8.1.4.2 
Analysis of Secondary Efficacy Endpoints..............................................93 
8.1.4.3 
Other Exploratory Analyses.....................................................................94 
8.1.5 
Pharmacokinetic Analyses.......................................................................94 
8.1.6 
Safety Analysis ........................................................................................94 
8.1.7 
Interim Analysis.......................................................................................94 
8.2 
Determination of Sample Size .................................................................95 
8.3 
Randomization Methods ..........................................................................96 
9.0 
Ethics.......................................................................................96 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) .............................................................................................96 
9.2 
Ethical Conduct of the Study...................................................................97 
9.3 
Subject Information and Consent.............................................................97 
10.0 
Source Documents and Case Report Form 
Completion .............................................................................98 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
18
10.1 
Source Documents ...................................................................................98 
10.2 
Case Report Forms...................................................................................99 
11.0 
Data Quality Assurance ......................................................100 
12.0 
Use of Information...............................................................100 
13.0 
Completion of the Study .....................................................101 
14.0 
Investigator's Agreement....................................................102 
15.0 
Reference List ......................................................................103 
List of Tables
Table 1. 
Study Activities........................................................................................46 
Table 2. 
Clinical Laboratory Tests.........................................................................59 
Table 3. 
Identity of Investigational Products.........................................................75 
Table 4. 
Specific Toxicity Management Guidelines for Abnormal 
Laboratory Values....................................................................................88 
List of Figures
Figure 1. 
Study Design Schematic ..........................................................................31 
Figure 2. 
Adverse Event Collection ........................................................................84 
List of Appendices
Appendix A. 
Responsibilities of the Clinical Investigator..........................................109 
Appendix B. 
List of Protocol Signatories....................................................................111 
Appendix C. 
Assessment of SpondyloArthritis International Society (ASAS) 
Axial Spondyloarthritis Criteria for Classification................................112 
Appendix D. 
Features of Spondyloarthritis.................................................................113 
Appendix E. 
Ankylosing Spondylitis Disease Activity Score (ASDAS) 
Calculation .............................................................................................114 
Appendix F. 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 
Numerical Rating Scale (NRS)..............................................................115 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
19
Appendix G. 
Patient's Global Assessment of Disease Activity, Numerical 
Rating Scale (NRS)................................................................................117 
Appendix H. 
Tender and Swollen Joint Counts ..........................................................118 
Appendix I. 
Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin).......120 
Appendix J. 
Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)............122 
Appendix K. 
Bath Ankylosing Spondylitis Functional Index (BASFI), 
Numerical Rating Scale (NRS)..............................................................123 
Appendix L. 
Physician's Global Assessment of Disease Activity, Numerical 
Rating Scale (NRS)................................................................................126 
Appendix M. 
Patient's Assessment of Nocturnal Back Pain, Numerical Rating 
Scale (NRS) ...........................................................................................127 
Appendix N. 
Patient's Assessment of Total Back Pain, Numerical Rating Scale 
(NRS) .....................................................................................................128 
Appendix O. 
Patient's Global Assessment of Pain, Numerical Rating Scale 
(NRS) .....................................................................................................129 
Appendix P. 
Assessment of Spondyloarthritis International Society (ASAS) 
Health Index (HI)...................................................................................130 
Appendix Q. 
Work Productivity and Activity Impairment Questionnaire:  Axial 
Spondyloarthritis, V2.0 (Work Productivity and Activity 
Impairment [WPAI]:  Axial Spondyloarthritis).....................................133 
Appendix R. 
European Quality of Life – 5 Dimension (EQ-5D) (United States 
[US] English Version)............................................................................135 
Appendix S. 
Berlin Magnetic Resonance Imaging (MRI) Score for the Spine 
and the Sacroiliac Joints.........................................................................138 
Appendix T. 
70-Day Follow-Up Call – Sample .........................................................139 
Appendix U. 
Injection Instructions – Sample Pre-Filled Syringe...............................140 
Appendix V. 
Subject Dosing Diary Sheet (Sample) ...................................................157 
Appendix W. 
Subject NSAID Dosing Diary Sheet (Sample) ......................................160 
Appendix X. 
Nonsteroidal Anti-Inflammatory Drug (NSAID) Intake Score .............162 
Appendix Y. 
Recommended Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 
to Treat Axial Spondyloarthritis ............................................................163 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
20
3.0
Introduction
3.1
Axial Spondyloarthritis
The term axial spondyloarthritis (axSpA) covers both patients with non-radiographic 
axSpA (nr-axSpA) and radiographic axSpA (the latter also termed ankylosing spondylitis 
[AS]).  New classification criteria have been developed in 2009 by the Assessment in 
Spondylo-Arthritis international Society (ASAS) for axSpA which have already been 
applied in several treatment trials of patients with nr-axSpA or for the whole group of 
axSpA patients.1 The prevalence of axSpA has been estimated to be between 0.2 and 
1.9%, strongly dependent on the Human Leukocyte Antigen-B27 (HLA-B27) prevalence 
in a specific country.  No exact data are available on the percentage of nr-axSpA among 
axSpA patients but have been calculated to be around 50% in the first 10 years of the 
disease.2 The new classification criteria and related diagnostic algorithm make an early 
diagnosis and treatment now possible because the occurrence of structural bony damage 
(radiographic sacroiliitis), which can take years to develop, is no longer mandatory.
3.2
Current Treatments
According to the ASAS and European League Against Rheumatism (EULAR) 
recommendations, nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of 
therapy in symptomatic patients with axSpA.3 Tumor necrosis factor alpha 
71)Į-blocking agents (TNF-blockers) are recommended in active axSpA with 
predominant axial manifestations if patients are still active after starting an NSAID 
therapy or if there are contraindication for an NSAID therapy.  However, conventional 
DMARDs are not effective for the treatment the axial component of spondyloarthritis 
(SpA).  In case of peripheral arthritis and/or enthesitis local glucocorticosteroid injections 
can be considered.3 Currently NSAIDs and TNF-blockers are the only effective and 
approved drugs for the treatment of axSpA.
Recently, similar to previous 'treat to target' (T2T) recommendations for rheumatoid 
arthritis (RA),4 T2T recommendations for the whole group of SpA including patients with 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
21
axSpA and psoriatic arthritis have been developed.5 Key statements are that a major 
treatment target should be clinical remission/inactive disease of musculoskeletal 
involvement and that clinical remission/inactive disease is defined as the absence of 
clinical and laboratory evidence of significant inflammatory disease activity.  However, 
axSpA treatment targets and treatment escalation strategies have not been identified and 
validated in a prospective study.
Thus, the question arises how such an aim can be achieved in patients with axSpA.  The 
following data are currently available on a potential escalation strategy for the treatment 
of axSpA.
NSAIDs: 
NSAIDs play a crucial role in the treatment of axSpA as NSAIDs are very effective drugs 
to treat signs and symptoms of AS patients, have a dose-dependent efficacy, have the 
ability to lower elevated C-reactive protein (CRP) levels and importantly seem to have a 
disease-modifying effect as has recently been shown in prospective studies.6-8
Furthermore, in early axSpA treatment with NSAIDs a state of Ankylosing Spondylitis 
Disease Activity Score (ASDAS) inactive disease (and 35.3% ASAS partial remission) 
can be reached in about 20% of patients, and also a reduction of active inflammation as 
detected by magnetic resonance imaging (MRI).9 To facilitate and harmonize axSpA 
treatment with NSAIDs, ASAS has developed a NSAID equivalent score providing for 
each NSAID the dosage equivalent to 150 mg diclofenac together with the maximum dose 
used in axSpA.10 However, a T2T approach for NSAIDs therapy in axSpA has not been 
investigated so far.
TNF-Blocker Treatment: 
Numerous clinical trials have shown a clear efficacy of TNF-blocker treatment in axSpA.  
TNF-blockers are the treatment of choice in patients with axSpA and predominant axial 
manifestation after failure of NSAIDs in both established AS and nr-axSpA.11-13

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
22
However, it is not clear whether a combination therapy of TNF-blockers plus NSAIDs 
would be superior to TNF-blocker alone.
In a recently performed trial (INFAST), 51.4% of patients with early axSpA with a 
disease duration of < 3 years reached a status of ASDAS inactive disease during 
combination treatment with a TNF-blocker and a full dose of a NSAID (compared to 
19.6% of patients who reached ASDAS inactive disease during NSAID monotherapy, as 
mentioned above).  The corresponding figures for reaching ASAS partial remission were 
61.9% and 35.3%, respectively.9
T2T Experience in RA: 
In RA it has been shown that patients in whom treatment is intensified according to 
clearly defined treatment goals have a better outcome, both change scores and status 
scores have been proposed.14-17
The better outcome was defined here as a lower disease activity which could be reached 
during conventional systemic disease-modifying anti-rheumatic drug (csDMARD) 
therapy (without TNF-blocker) in CAMERA14 (RA patients with disease duration 
< 1 year, 2 year follow-up), TICORA15 (RA patients with disease duration < 5 years, 
18 month follow-up) or the TNF-blocker trial by Schipper et al16 (RA with disease 
duration < 1 year, 1 year follow-up) and the Dutch BeST study17,18 by 
Goekoop-Ruiterman and co-workers (RA with disease duration < 2 years, 1 year 
follow-up).  In most of these studies the primary outcome parameter was remission and/or 
low disease activity; functional status and radiographic progression after 1.5 – 2 years 
were secondary outcome parameters.  A tight control, target-oriented therapy was 
typically superior to Standard of Care (SOC).
Treat to Target Experience in Patients with Spondyloarthritis
The recently published T2T recommendations in spondyloarthritis define remission or 
low disease activity as the treatment target.5 These recommendations are largely based 
upon expert consensus, built on experience in RA patients and defined a research agenda.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
23
Recently, the TICOPA trial assessed treatment escalation with conventional DMARDs 
followed by TNF-blocker therapy in patients with psoriatic arthritis, which was superior 
to the SOC for most outcome parameters.19,20 Currently, no trials have evaluated whether 
a targeted treatment approach and combination of anti-TNF therapy with NSAIDs 
provides superior outcomes in patients with axSpA.  
3.3
Adalimumab Overview
Adalimumab (the TNF-blocker used in this study) is a recombinant human 
immunoglobulin G1 (IgG1) monoclonal antibody containing only human peptide 
sequences.  Adalimumab is produced by recombinant deoxyribonucleic acid (DNA) 
technology in a mammalian cell expression system.  It consists of 1330 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 light chain sequences.  Adalimumab binds 
with high affinity and specificity to soluble TNF-ĮEXWQRWWRO\PSKRWR[LQ-Į71)-ȕ
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF 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 (CRP and erythrocyte sedimentation rate [ESR]) and serum cytokines 
rapidly decrease.
Adalimumab was first approved for the treatment of subjects with RA in the United States 
(US) in December 2002 and in the European Union (EU) in September 2003.  In addition 
adalimumab is approved for the treatment of patients with early RA, polyarticular juvenile 
idiopathic arthritis (JIA) (4 to 17 years of age), psoriatic arthritis (PsA), AS, Crohn's 
disease (CD), Ulcerative colitis (UC), and Psoriatic arthritis (PsA) in the EU, the US, and 
many other countries worldwide.  Adalimumab is also approved for the treatment of 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
24
patients with polyarticular JIA (2 to < 4 years of age), pediatric CD, and nr-axSpA in the 
EU and several other countries, as well as intestinal Behçet's disease (BD) in Japan.  
Additional updates regarding approved indications can be found in the current edition of 
the Humira Investigational Drug Brochure.
3.4
Safety Information
Adalimumab therapy has a well-established and well described safety profile based on 
extensive postmarketing experience and continued clinical trial patient exposure since the 
first approved indication in 2002 for rheumatoid arthritis.  A detailed discussion of the 
pre-clinical toxicology, metabolism, pharmacology and safety experience with 
adalimumab can be found in the current Investigator's Brochure.  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 a Food and Drug Administration (FDA)-requested, TNF inhibitor class 
wide exploration of the rare appearance of malignancy in patients who are 30 years old or 
younger at the time of diagnosis.  The risk of malignancy in this age group has not been 
established and is difficult to study due to its rarity.  AbbVie appreciates your attention to 
the additional reporting requirements needed in this unlikely event, outlined in 
Section 6.1.5 under Adverse Event (AE) Reporting.
3.5
Considerations on the Best Outcome Parameter for a 
Treat-to-Target (T2T) Approach in axSpA
The current ASAS recommendations only give limited guidance regarding a sufficient 
response for a TNF-blocker treatment: a responder is defined as a patient who shows a 
50% improvement of the Bath AS Disease Activity Index (BASDAI) or an absolute 
change of at least 2 points after 12 weeks.21
Thus, in axSpA – in contrast to RA – only relative treatment targets (change scores) for 
TNF-blocker treatment recommendations have been proposed until now.  There are 
several potential outcome parameters in the treatment of axSpA such as patient reported 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
25
outcomes (PROs) including the BASDAI and Bath AS Functional Index (BASFI), but 
also objective parameters of inflammation such as CRP and active inflammation on MRI.
There is ongoing discussion about the role of the BASDAI for measuring disease activity 
in axSpA as it has the limitations of being only a subjective patient-reported outcome 
parameter and it shows a poor correlation with objective parameters of disease activity 
such as CRP or inflammation on MRI.21 CRP has the advantage that it is an objective 
measure of disease activity.  Furthermore, CRP has been shown to be a predictor for a 
major response during TNF-blocker treatment 22-24 and a predictor for radiographic 
progression both in the sacroiliac joints 25 and in the spine.26 Active inflammation on 
MRI can add valuable information in terms of disease activity.  However, MRI cannot be 
performed routinely on every visit (feasibility problem).
The more recently introduced ASDAS combines both patient reported outcomes and an 
objective disease parameter represented by an acute phase reactant (CRP or ESR).27
The ASDAS is a composite disease activity outcome measure which combines patient 
reported back pain, duration of morning stiffness, patient global assessment of disease 
activity, patient assessment of peripheral joint pain and swelling and an acute phase 
reactant (CRP or ESR) as an objective measure of inflammation.  As a continuous 
measure of disease activity, the ASDAS can be used to measure both relative 
improvement between 2 timepoints and also patient status at a single visit.  The ASDAS 
was first published online in July 2008, since this time the ASDAS has undergone 
additional validation 28-32 and has emerged as the measurement tool recommended by 
experts in assessing axSpA disease activity.  Furthermore, it is now recommended that the 
treatment goal should be to achieve remission (or low disease activity) in SpA patients.5
For the following reasons ASDAS is an appropriate measurement tool to determine 
inactive disease and clinical trial results for this outcome are important to provide to 
physicians who treat patients with axSpA:  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
26
The ASDAS has proven to be a highly discriminatory tool for the detection of clinically 
meaningful differences in clinical studies.33,34
The ASDAS has superior psychometric properties and is more sensitive to change as 
compared to previously existing tools used to measure disease activity in SpA.33
The ASDAS better reflects spinal inflammation, which is a hallmark of axSpA, than other 
composite measures due to inclusion of an acute phase reactant (ESR or CRP).35
ASDAS is the recommended outcome measure for a T2T paradigm36 and importantly 
ASDAS inactive disease and MRI-remission have more overlap compared to ASAS 
partial remission and MRI-remission 37 with ASDAS also demonstrating a significant 
association with radiographic progression in the spine.38
Thus, the ASDAS seems currently to be the best outcome parameter to be applied in a 
77DSSURDFKLQD[6S$$WOHDVWGLVHDVHDFWLYLW\DVPHDVXUHGE\$6'$6RIZLOOEH
used as the indicator for need to intensify treatment in this study. 
An ASDAS of < 1.3 (which represents ASDAS inactive disease) will be used as the 
primary outcome parameter.
ASDAS Data from Other Studies/Cohorts: 
Published ranges for disease activity states as defined by the ASDAS are:  < 1.3 for 
LQDFWLYHGLVHDVHWRIRUPRGHUDWHGLVHDVHDFWLYLW\WRIRUKLJK
disease activity" and > 3.5 for "very high disease activity."33 Ramiro et al showed in an 
analysis of the OASIS cohort24 that disease activity, as measured by ASDAS, is 
longitudinally associated with radiographic progression in AS.  Vastesaeger et al 
LQYHVWLJDWHGZKHWKHUXVLQJDQ$6'$6RILQVWHDGRID%$6'$,RI4.0 would be a 
better cut-off for the initiation of a TNF-blocker treatment.  He analyzed cross-sectional 
data of the Spanish Regisponser registry (n = 1161) and found that 66.4% of these patients 
KDGDQ$6'$6RIZKLOHRQO\RIWKHVDPHSDWLHQWVKDGD%$6'$,RI39

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
27
Fagerli et al in the NOR-DMARD cohort also compared whether using an ASDAS of 
 LVPRUHDFFXUDWHWKDQD%$6'$,RIIRUWKHVWDUWRID71)-blocker treatment.40
Their analysis showed that the majority of patients fulfilled both criteria, however, 16.6% 
RIWKHSDWLHQWVKDGDQ$6'$6RIDQGD%$6'$,PHDQLQJWKDWZRXOG
have been missed by the BASDAI eligibility criterion), and these patients responded 
similarly well to TNF-blocker treatment compared to a BASDAI cut-off (about 18% 
showed an ASDAS major improvement and about 50% reached ASDAS inactive 
disease).40 The ASDAS was found to be applicable also in subgroups without elevated 
CRP and without peripheral joint swelling.  At the 3-month follow-up of the 
NOR-DMARD cohort after initiation of a TNF-blocker treatment 33.6% of patients 
reached a status of ASDAS inactive disease.
In the German Spondyloarthritis Inception Cohort (GESPIC),41 which is a prospective 
observational cohort including AS patients with a disease duration of < 10 years in 
Year 6, (which was chosen here because all patients had potentially full access to 
TNF-EORFNHUWUHDWPHQWRI$6SDWLHQWVKDGDQ$6'$6$PRQJWKHVH
patients only 14.5% were on TNF-blocker treatment (unpublished data).
3.6
Rationale for the Study
So far in axSpA no clear treatment targets have been proposed, and there is a lack of 
evidence regarding the advantage of a T2T approach combining NSAID therapy with 
TNF-blockers.  Indeed, data from observational cohorts indicate that a substantial number 
of patients in routine care are not sufficiently treated with about 50% of AS patients 
KDYLQJD%$6'$,DQGDERXWRISDWLHQWVKDYLQJD%$6'$,LQWKH*(63,&
cohort.  Data from the DESIR cohort also shows that not the full anti-inflammatory dose 
of NSAID is taken as measured by the ASAS-NSAID-Score of 42% – 55%.42 To monitor 
disease activity and the effectiveness of the therapy the BASDAI is currently used in 
routine care.43

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
28
Therefore, in this study an intensified T2T treatment approach comprising clearly defined 
treatment targets and cut-offs for treatment escalation shall be investigated in comparison 
to SOC treatment.
3.7
Differences Statement
This is the first adequately powered study to evaluate the efficacy and safety of an 
intensified T2T treatment approach using clearly defined treatment targets and cut-offs for 
treatment escalation and escalating to combination treatment with a NSAID and 
adalimumab (if needed) versus routine treatment according to local SOC in subjects with 
axSpA.
3.8
Benefits and Risks
There is an unmet medical need for the treatment of axSpA.  A T2T paradigm has been 
proposed but no data are available to support this treatment approach.  In this study, a T2T 
treatment scheme escalating to combination treatment with one NSAID and adalimumab 
(if needed) is investigated.  The utility of TNF blockade with adalimumab in axSpA has 
been established in randomized controlled trials which demonstrated a safety profile 
similar to that observed in the extensive clinical and post-marketing experience of 
adalimumab in a wide range of disease states.  The safety profile of adalimumab in this 
and other approved indications is well established.  Adverse events in the categories of 
autoimmunity, demyelinating disorders, congestive heart failure, gastrointestinal 
disorders, hematologic events, hepatic events, hypersensitivity, immunosuppression, 
infections, malignancies, respiratory thoracic and mediastinal disorders, and vascular 
disorders have been observed with adalimumab therapy.  The investigator is referred to 
the current Investigator's Brochure where additional and more detailed information 
regarding potential risks and benefits of adalimumab can be found.  The potential benefit 
of the proposed study in axSpA is that it is designed to evaluate the efficacy and safety of 
an intensified T2T treatment approach to achieve and maintain remission of disease.  As 
axSpA is associated with considerable pain, reduction in health-related quality of life, and 
work impairment it would be beneficial to know if using an intensified T2T treatment 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
29
approach remission of disease may be achieved and better maintained – while at the same 
time keeping acceptable adverse events rates – as compared to when using SOC.
In a randomized controlled trial comparing tight control of early psoriatic arthritis 
(TICOPA)19,20 with standard care an increased rate of adverse events (AEs) were seen in 
the tight control arm:  eight serious AEs in the tight control arm compared to two in the 
SOC arm; altogether 622 AEs (in 97% of patients) in the tight control arm versus 249 (in 
80% of patients) with SOC.
4.0
Study Objective
The primary objective of this study is to compare a T2T intense treatment approach with a 
routine treatment approach (SOC) in reducing disease activity at Week 32 in patients with 
axSpA. 
The secondary objectives are to compare a T2T intense treatment approach with SOC by 
assessing improvement of quality of life, function and work productivity as well as 
reducing inflammation (as measured by MRI, CRP, ESR) and disease activity.  
Exploratory endpoints include investigating serum autoantibodies against CD74 CLIP and 
reduction of disease progression as measured by MRI of the sacroiliac joints and the 
spine.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This is a Phase 4, multicenter, randomized, open-label, parallel-group study comparing an 
intensified T2T treatment approach with SOC.  The study duration per subject may 
include a 42-day Screening period, a 52-week treatment period (T2T according to 
randomization or treatment SOC), and a 70 day follow-up period which will be completed 
by a phone call. 
Subjects who have signed the informed consent and who fulfill all screening criteria will 
be randomized to receive either treatment following an intensified T2T approach (T2T 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
30
group) or treatment according to SOC (following the local practice standards) (SOC 
group).
The study design schematic is presented in Figure 1.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
32
Screening Period:
Within 42 days prior to the Baseline Visit, subjects will receive a full explanation of the 
study design and study procedures, provide a written informed consent, and undergo the 
screening procedures outlined in Table 1.
Subjects who initially screen-fail for the study may be permitted to re-screen following 
re-consent.  The reason for screen failure will be captured in the appropriate Electronic 
Case Report Forms (eCRFs).  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; however, a subject should 
only be re-screened once for this study upon prior agreement with AbbVie Clinical 
Monitor.  Subjects who have screen-failed previously and do not have a reasonable 
chance of meeting the inclusion/exclusion criteria should not be re-screened.  If the 
subject had completed initial screening evaluation assessments including HLA-B27, 
Antinuclear Antibody (ANA), Magnetic Resonance Imaging (MRI) or electrocardiogram 
(ECG), these tests will not need to be repeated during re-screening provided the 
conditions noted in Section 5.3 are met and no more than 3 months (90 days) have passed 
for the ECG and no more than 42 days for the MRI.  There is no need to redraw the 
HLA-B27 or ANA if results from the initial screening are available. 
Treatment Period:
This period will begin at the Baseline Visit (Day 1) and will end at the Week 52 visit.  At 
the Baseline Visit, subjects who have signed the informed consent and meet the eligibility 
(all of the inclusion and none of the exclusion) criteria described in Section 5.2.1 and 
Section 5.2.2 will be enrolled and randomized in a 1:1 ratio to receive either intensified 
T2T treatment or SOC treatment.  Study physician and patients might be aware of the 
allocated treatment group.  However, an influence of the SOC treatment based upon 
knowledge and potential benefits/risks in the intensified T2T treatment arm is not 
expected based on experience of other T2T-Studies like TICOPA.20

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
33
T2T Group (Investigational Group):
After randomization, subjects are seen at Weeks 2, 4, 6, 8 and afterwards every 4 weeks 
up to Week 52.  
Basic treatment will be started with a NSAID.  Treatment should be intensified (escalated) 
EHJLQQLQJDW:HHNLIWKH$6'$6LVHVFDODWLRQVWHp 1).  Treatment escalation is 
planned to be initiated at Week 4 if needed and further escalation is planned at Week 8 if 
needed (escalation step 2).  However, if not required at Week 8, treatment should be 
escalated at every visit thereafter if the ongoing treatment is not sufficiently efficacious 
(ASDAS is < 2.1) and the last escalation step has not yet been reached.  Treatment 
escalation steps are as follows:
Basic Treatment (NSAID 1):  Treatment will be started with any NSAID at full 
anti-inflammatory dose (see Appendix Y).  If at Week 2 ASAS 20 response is not 
achieved, subjects may early escape to Escalation Step 1.  If the chosen NSAID cannot be 
continued due to intolerance escalation to the next Escalation Step is possible at any time 
point.  If Basic Treatment is well tolerated and ASDAS is < 2.1 the subject will be 
continued on this treatment.
Escalation Step 1 (NSAID 2):  Treatment will be changed to a second NSAID if after 
4 ZHHNVRIWUHDWPHQWWKHILUVW16$,'LVQRWVXIILFLHQWO\HIILFDFLRXV$6'$6DQGRU
not tolerated.  The second NSAID will be given for 4 weeks.  Early escape is possible if 
after 2 weeks no ASAS 20 response is achieved.  In this case treatment can be switched to 
escalation step 2 after 2 weeks of NSAID 2.  If the chosen NSAID cannot be continued 
due to intolerance, escalation to the next escalation step is possible at any time point. In
that case, adalimumab may be combined with the second or – if deemed required by the 
treating physician – the first NSAID used (provided escalation from Basic Treatment to 
Escalation Step 1 did not occur due to any safety issues related to NSAID 1 therapy). If 
NSAID 2 treatment is well tolerated and sufficiently efficacious the subject will be 
continued on this treatment.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
34
Escalation Step 2 (Combination with adalimumab):  At Week 8 in case of failure of 
16$,'$6'$6DIWHUZHHNVRI16$,'WKHWUHDtment will be intensified by 
switching to the combination of NSAID and adalimumab 40 mg s.c. every other week 
(eow).  Escalation step 2 can be initiated at Week 4 visit at the earliest if early escape is 
chosen during Basic Treatment and during NSAID 2.
Before initiating Escalation Step 2 additional screening testing for hepatitis B and 
tuberculosis (TB) is required, as described in Section 5.3.1 and Table 1.  If a subject is 
diagnosed with latent TB prophylactic treatment must be given.  The subject must not 
receive adalimumab before completing at least 1 month of prophylactic anti-TB 
chemotherapy.  If a subject is diagnosed with active hepatitis B (acute or chronic) the 
subject is not eligible to receive adalimumab and should discontinue from the study.
In case of peripheral arthritis and/or enthesitis:  intra-articular injections of 
glucocorticosteroids are permitted at any time point and will be recorded in the 
concomitant medication electronic Case Report Form (eCRF).
SOC Group (Reference Group):
After randomization, subjects will receive treatment according to local practice standards.  
NSAIDs should be used according to ASAS recommendations (see Appendix Y) in a full 
dose.  Unlike in the T2T group, the treating physician is blinded for the ASDAS 
calculated by the eCRF.  Subjects are seen at Weeks 12, 24, 32 52 or if they discontinue 
early from the study. 
T2T Group and SOC Group:
Subjects that end study participation early will have a Discontinuation Visit.  Subjects of 
the T2T group who were on treatment with study drug adalimumab during the study but 
do not continue on commercially available Humira after discontinuation from the study 
will have a follow-up phone call approximately 70 days after the last visit within the 
Treatment Period (i.e., Week 52 visit or early Discontinuation Visit) to obtain information 
on any new or ongoing AEs. 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
35
Subjects who prematurely discontinue from the study should complete the procedures 
outlined for the Discontinuation Visit in Table 1 as soon as possible and preferably prior 
to the administration of new therapies.
The study is designed to enroll approximately 240 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. 
5.2
Selection of Study Population
5.2.1
Inclusion Criteria
1.
Subjects must have signed written informed consent before starting any 
study-related assessments or procedures.
2.
Diagnosis of axSpA (either AS or nr-axSpA) (see Appendix D) and fulfilling the 
ASAS classification criteria for axSpA (see Appendix C).
3.
6XEMHFWVDJHG\Hars.
4.
Disease duration < 5 years.
5.
Subjects must be either NSAID-naïve or had not been treated with the maximal 
recommended dose during the last 2 weeks prior to Baseline (see Appendix X).
6.
Subjects must never have failed a NSAID taken at maximal recommended dose for 
2 weeks or more.
7.
Subjects must be disease-modifying anti-rheumatic drug (DMARD)-naïve except 
for methotrexate (MTX), sulfasalazine (SSZ), azathioprine (AZA), and 
6-mercaptopurine (6-MP).
8.
6XEMHFWVPXVWKDYHEDVHOLQHGLVHDVHDFWLYLW\DVGHILQHGE\KDYLQJDQ$6'$6
RUD%$6'$,
9.
If female, subject must be either postmenopausal, OR permanently surgically 
sterile OR for Women of Childbearing Potential practicing at least one protocol 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
36
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.
If the male subject is sexually active with female partner(s) of childbearing 
potential, he must agree, from Study Day 1 through 20 weeks after the last dose of 
study drug, to practice the protocol specified contraception (Section 5.2.4).
10.
Females of childbearing potential must have a negative serum pregnancy test result 
at Screening, and a negative urine pregnancy test at Baseline Visit.
Females of non-childbearing potential (either postmenopausal or permanently 
surgically sterile as defined above) at Screening do not require pregnancy testing.
11.
Subject is judged to be in good health as determined by the Principal Investigator 
based upon the results of medical history, laboratory profile, physical examination, 
and a 12-lead ECG performed at Screening.
12.
Subjects must be able and willing to self-administer SC injections or have a 
qualified person available to administer SC injections.
13.
Subjects must be able and willing to provide written informed consent and comply 
with the requirements of this study protocol.
Rationale for Inclusion Criteria
1 – 9
To select the appropriate subject population for this study
11 – 12
To increase subject compliance potential
13
In accordance with the harmonized Good Clinical Practice (GCP)
5.2.2
Exclusion Criteria
A subject will be excluded from the study if he/she meets any of the following criteria:
1.
Contraindication for NSAIDs or TNF blocker according to local labeling.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
37
2.
Subject has a medical condition precluding an MRI (e.g., magnetic activated 
implanted devices – cardiac pace-maker, insulin pump, neurostimulators, etc. and 
metallic devices or fragments in the body).
3.
Subject has active inflammatory bowel disease.
4.
Prior exposure to any anti-TNF therapy; any biologic therapy with a potential 
therapeutic impact on SpA, or subject has been treated with any investigational 
drug of chemical or biologic nature within a minimum of 30 days or five half-lives 
(whichever is longer) of the drug prior to the Baseline Visit.
5.
If entering the study on concomitant NSAIDs, subjects taking the maximal 
recommended dose during the last 2 weeks prior to the Baseline Visit or have 
failed or developed intolerance to a NSAID taken at maximal recommended dose 
for 2 weeks or more at any time (see Appendix Y).
6.
Subject on opioid analgesics or use of marijuana within 14 days prior to the 
Baseline Visit.
7.
If entering the study on concomitant oral corticosteroids, subject has not been on 
VWDEOHGRVHRISUHGQLVRQHPJSHUGD\RURUDOFRUWLFRVWHURLGHTXLYDOHQWVIRU
at least 14 days prior to the Baseline Visit.
8.
Subject has been treated with intra-articular joint injection(s) or spinal/paraspinal 
injection(s) of corticosteroids in the preceding 28 days prior to the Baseline Visit.
9.
Subject has undergone spinal surgery within 2 months prior to Baseline or subject 
has been diagnosed with a spinal condition that may interfere with study 
assessments (i.e., disc herniation, degenerative spine disease, etc.) in the opinion of 
the investigator.
10.
Subject has a history of fibromyalgia or inflammatory arthritis of a different 
etiology other than SpA (e.g., rheumatoid arthritis, systemic lupus erythematosus, 
polyarticular or systemic juvenile idiopathic arthritis).

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
38
11.
Infection(s) requiring treatment with intravenous (IV) anti-infectives within 
30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the 
Baseline Visit.
12.
Known hypersensitivity to adalimumab or its excipients as stated in the label.
13.
Known intolerance of NSAID treatment that does not allow use of at least 
two different NSAIDs at full anti-inflammatory dose (see Appendix Y).
14.
History of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease.
15.
History of invasive infection (e.g., listeriosis and histoplasmosis), human 
immunodeficiency virus (HIV).
16.
Subjects with any active viral infection that based on the investigator's clinical 
assessment, makes the subject an unsuitable candidate for the study.
17.
Hepatitis B:  Hepatitis B surface antigen (HBs Ag) positive (+) or detected 
sensitivity on the hepatitis B virus (HBV)-DNA polymerase chain reaction (PCR) 
qualitative test for hepatitis B core antibody (HBc Ab)/hepatitis B surface antibody 
(HBs Ab) positive subjects (see Section 5.3.1.1).
18.
Chronic recurring infections or active TB.
19.
History of moderate to severe congestive heart failure (New York Heart 
Association [NYHA] class III or IV), recent cerebrovascular accident and any other 
condition which would put the subject at risk by participation in the study.
20.
Evidence of dysplasia or history of malignancy (including lymphoma and 
leukemia) other than a successfully treated non-metastatic cutaneous squamous
cell, basal cell carcinoma or localized carcinoma in situ of the cervix.
21.
Positive pregnancy test at Screening or Baseline.
22.
Female subject who is pregnant, breastfeeding or is considering becoming pregnant 
during the study or for approximately 150 days after the last dose of study drug.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
39
23.
Male subject who is considering fathering a child or donating sperm during the 
study or for approximately 150 days after the last dose of study drug.
24.
Clinically significant abnormal screening laboratory results as evaluated by the 
Investigator.
25.
History of clinically significant drug or alcohol abuse in the last 12 months.
26.
Subject is considered by the Investigator, for any reason, to be an unsuitable 
candidate for the study.
27.
Any vulnerable subject (e.g., person kept in detention, or dependent from the 
Sponsor, Investigator or study site)
The Investigator should contact the AbbVie Medical Monitor identified in Section 6.1.5 if 
there are any questions regarding inclusion and exclusion criteria and subject eligibility.
Rationale for Exclusion Criteria
1 – 24, 26
To avoid medical conditions, medications or procedures that 
may compromise subject safety and the ability to make 
causality assessments relative to adalimumab
25
27
To increase subject compliance potential
In accordance with GCP and to comply with legal requirements 
5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject is receiving at the time of Screening, 
and/or receives during the study, must be recorded along with the reason for use, date(s) 
of administration including start and end dates, and dosage information including dose, 
route and frequency on the appropriate eCRF.  Treatment for axSpA will be recorded in a 
separate section of the eCRF.  NSAIDs administered to a subject for treatment of axSpA 
following the T2T intensified schedule will be recorded on the appropriate eCRF page.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
40
The AbbVie Study Designated Physician identified in Section 6.1.5 (Adverse Event 
Reporting) should be contacted if there are any questions regarding concomitant or prior 
therapies.
,QDGGLWLRQIRUVXEMHFWVDJHGZLWKDUHSRUWHGPDOLJQDQF\DGYHUVHHYHQWSULRU
exposure to, or current use of, anti-neoplastics, or other drugs which have a risk of 
malignancy as stated in their label and other relevant dosing information to estimate total 
exposure will be collected in the source documents and appropriate eCRF pages.  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 in these categories 
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.
Medication Categories:
Ɣ
corticosteroids
Ɣ
immunosuppressants
Ɣ
biologic agents
Ɣ
anti-neoplastics
Ɣ
other
5.2.3.1
Prior Therapy
All prior drug therapies for axSpA, since initial diagnosis, must be recorded on the source 
documents and on the appropriate eCRF along with the dates of first and last dose, 
maximum dosage taken, route of administration and reason for discontinuation, if known.
For each subject that is screened for the study, any other medication (including, but not 
limited to, over-the-counter medicines such as aspirin, antacids, vitamins, mineral 
supplements, and herbal preparations) taken at the time of Screening through the end of 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
41
the study must be recorded on the appropriate eCRF along with the date(s) of 
administration, reason for use, dosage, route and frequency.
5.2.3.2
Concomitant Therapy
In case of peripheral arthritis and/or enthesitis:  (intra-articular) injection of 
glucocorti-costeroids are permitted at any time point.
T2T Group
Treatment for axSpA will be recorded in a separate section of the eCRF.  NSAIDs 
administered to a subject for treatment of axSpA following the T2T intensified schedule 
should be recorded in the eCRF as "T2T-NSAID," adalimumab should be recorded as 
study drug.
Each vaccine and all medications except study drug and T2T-NSAIDs, administered to a 
subject during the study should be recorded in the eCRF as a concomitant medication.
All non-drug therapies administered to a subject during the study should be recorded in 
the eCRF as a concomitant medication.
SOC Group
All medications administered to a subject for treatment of axSpA following the local SOC 
schedule should be recorded in the eCRF as "for axSpA." 
Each vaccine and all medications except "for axSpA," administered to a subject during the 
study should be recorded in the eCRF as a concomitant medication.
All non-drug therapies administered to a subject during the study should be recorded in 
the eCRF as a concomitant medication.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
42
5.2.3.3
Prohibited Therapy
T2T Group
The following are prohibited medications during the study:
Ɣ
All biologic therapy with a potential therapeutic impact on SpA including but 
not limited to the following:
ż
Infliximab (Remicade®);
ż
Etanercept (Enbrel®);
ż
Ustekinumab (Stelara®);
ż
Natalizumab (Tysabri®);
ż
Anakinra (Kineret®);
ż
Abatacept (Orencia®);
ż
Rituximab (Rituxan®);
ż
Tocilizumab (Actemra®);
ż
Golimumab (Simponi®);
ż
Efalizumab (Raptiva®);
ż
Certolizumab (Cimzia®);
ż
Belimumab (Benlysta®);
ż
Infliximab biosimilar(s) (Remsima®, Inflectra®);
ż
Etanercept biosimilar(s);
ż
Secukinumab (Cosentyx®).
Ɣ
Live vaccines (during the study and for 70 days after the last dose of study 
drug Humira).
Ɣ
Rifampin/Pyrazinamide combination.
Ɣ
Anti-retroviral therapy.
Ɣ
All oral DMARDs other than MTX, SSZ, AZA (permitted for inflammatory 
bowel disease only), or 6-MP (permitted for inflammatory bowel disease 
only).
Ɣ
Opioid analgesics (other than tramadol or codeine) or marijuana, except as 
medical indicated for an AE.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
43
Ɣ
Any investigational drug of chemical or biologic nature.
Subjects may have to be discontinued from the study if any of the above prohibited 
medications are used during the study.
SOC Group
During the study (after randomization) no medication is explicitly prohibited by the study 
protocol.  Investigators should follow the labeling of the medications administered and 
record them as required in the eCRF.
5.2.4
Contraception Recommendations
If female, subject must be either postmenopausal defined as:
Ɣ
Age > 55 years with no menses for 12 or more months without an alternative 
medical cause.
Ɣ
Age  55 years with no menses for 12 or more months without an alternative 
medical cause AND a follicle-stimulating hormone (FSH) level > 40 IU/L.
OR
Ɣ
Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy 
or hysterectomy).
OR
Ɣ
Practicing at least one of the following methods of birth control, on Study 
Day 1 (or earlier) through at least 150 days after the last dose of study drug:
ż
Combined (estrogen and progestogen containing) hormonal contraception 
(oral, intravaginal, transdermal) associated with the inhibition of ovulation, 
initiated at least 1 month prior to Baseline Visit.
ż
Progestogen-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation, initiated at least 1 month prior to 
Baseline Visit.
ż
Bilateral tubal occlusion/ligation.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
44
ż
Bilateral tubal occlusion via hysteroscopy (i.e., Essure), provided a 
hysterosalpingogram confirms success of the procedure.
ż
Vasectomized partner(s), provided the vasectomized partner verbally 
confirms receipt of medical assessment of the surgical success and is the 
sole sexual partner of the women of childbearing potential (WOCBP) trial 
participant.
ż
Intrauterine device (IUD).
ż
Intrauterine hormone-releasing system (IUS).
ż
Progestogen-only oral hormonal contraception, where inhibition of 
ovulation is not the primary mode of action, initiated at least 1 month prior 
to Baseline Visit.
ż
Male or female condom with or without spermicide.
ż
Cap, diaphragm or sponge with spermicide.
ż
A combination of male condom with either cap, diaphragm or sponge with 
spermicide (double barrier method).
ż
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).
If a male subject is either surgically sterile (vasectomy with medical assessment 
confirming surgical success) or has a female partner who is postmenopausal or
permanently sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy), no 
contraception is required.
If a male subject is sexually active with female partner(s) of childbearing potential, he 
must agree from Baseline Visit through 20 weeks after the last dose of study drug to 
practice contraception with:
Ɣ
Condom use and female partner(s) using at least one of the contraceptive 
measures (as defined in the protocol for female study subjects of childbearing 
potential).

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
45
Ɣ
True abstinence:  Refraining from heterosexual intercourse-when this is in line 
with the preferred and usual lifestyle of the subject. (Note:  Periodic 
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] 
and withdrawal are not acceptable).
Additionally, male subject agrees not to donate sperm from Baseline Visit through 
20 weeks after the last dose of study drug.
5.3
Efficacy, Pharmacodynamic, and Safety 
Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Subjects will be allowed a visit window of ± 7 days for all study visits.
If a subject has an out of window visit, the next visit should occur as originally scheduled 
based on the date of the Baseline Visit.
In subjects of the T2T group, HBV screening, TB screening and chest X-ray (CXR) will 
be performed before Escalation Step 2 is initiated (before adalimumab is administered).  If 
a subject is diagnosed with latent TB the subject has to undergo a minimum of 1 month of 
anti-TB prophylaxis before Escalation Step 2 can be initiated.  In this case the time until 
the next visit will be counted from the start of adalimumab; e.g., if a subject starts TB 
prophylaxis at Week 8 visit and initiates Escalation Step 2 after receiving 2 months of 
prophylaxis, i.e., 16 weeks after Baseline, the next visit (nominal Week 12 visit) will be 
postponed by these 2 months (to 20 weeks after Baseline).  All subsequent visits will be 
postponed accordingly, e.g., Week 16 visit to 24 weeks after Baseline. 
Study procedures will be performed as outlined in the schematic presented in Table 1.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
46
Table 1.
Study Activities
T2T Group 
Activity
SCR 
'
BLa
(D1)
Randomized Open-Label Treatment Period
Disc. 
Visitb
70-Day 
F/U 
Call
Week(s) (from D1) (1 wk Equals 7 Days)
2
4
6
8
12
16
20
24
28
32
36
40
44
48
52
Informed Consent
x
Inclusion/Exclusion Criteria
x
xc
Medical/Surgical History
x
xc
Vital Signs/Weight/Heightd
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Anterior Uveitis
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical Exam
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
12-Lead ECG
xe
Chest X-Ray
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
TB Screening (IGRA)
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
xf
Pregnancy Test
xg
xh
x
x
Chemistry and Hematology
x
xi
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Urinalysisj
x
xi
x
x
x
x
x
x
x
x
x
x
x
x
x
x
HLA-B27
xe
Anti-dsDNA Antibodies
xe
HBV Screening
x
xk
xk
xk
xk
xk
xk
xk
xk
xk
xk
xk
xk
xk
ESR
x
xi
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
CRP
x
xi
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Antibodies against CD74 CLIP
x
x
x
x
MRI of the Spine and SI Joints
xe
x
xl

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
47
Table 1.
Study Activities (Continued)
T2T Group 
Activity
SCR 
'
BLa
(D1)
Randomized Open-Label Treatment Period
Disc. 
Visitb
70-Day 
F/U 
Call
Week(s) (from D1) (1 wk Equals 7 Days)
2
4
6
8
12
16
20
24
28
32
36
40
44
48
52
TJC/SJC
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
BASDAI
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
BASMIlin
x
x
x
x
x
x
BASFI
x
x
x
x
x
x
MASES
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Dactylitis
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physician's Global Assessment of Disease Activity
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Patient's Global Assessment of Disease Activity
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Patient's Assessment of Nocturnal Back Pain NRS
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Patient's Assessment of Total Back Pain NRS
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Patient's Global Assessment of Pain NRS
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
ASAS HI
x
x
x
x
x
x
EQ-5D
x
x
x
x
x
x
WPAI-axSpA
x
x
x
x
x
x
Prior and Concomitant Therapy Assessment
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Recording of NSAID:  substance, dose, patient 
compliance (diary)
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Recording of Study Drug:  dose and patient 
compliance (diary)
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
48
Table 1.
Study Activities (Continued)
T2T Group 
Activity
SCR 
 42 D)
BLa
(D1)
Randomized Open-Label Treatment Period
Disc. 
Visitb
70-Day 
F/U 
Call
Week(s) (from D1) (1 wk Equals 7 Days)
2
4
6
8
12
16
20
24
28
32
36
40
44
48
52
Monitor AEs
xm
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
xn
Treatment Escalation Decision
xo
xo
xo
xo
xo
xo
xo
xo
xo
xo
xo
xo
xo
xo
Enrollment/Randomization
x
Study drug administration
xp
xp
xp
xp
xp
xp
xp
xp
xp
xp
xp
xp
xp

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
49
Table 1.
Study Activities (Continued)
SOC Group 
Activity
6&5'
BLa (D1)
Randomized Open-Label Treatment Period
Disc. Visitb
Time of Visit (Weeks from D1) (1 wk Equals 7 Days)
Week 12
Week 24
Week 32
Week 52
Informed Consent
x
Inclusion/Exclusion Criteria
x
xc
Medical/Surgical History
x
xc
Vital Signs/Weight/Heightd
x
x
x
x
x
x
x
Anterior Uveitis
x
x
x
x
x
x
x
Physical Exam
x
x
x
x
x
x
x
12-Lead ECG
xe
Pregnancy Test
xg
xh
x
x
Chemistry and Hematology
x
xi
x
x
x
x
x
Urinalysisi
x
xi
x
x
x
x
x
HLA-B27
xe
Anti-dsDNA Antibodies
xe
HBV Screening
x
ESR
x
xi
x
x
x
x
x
CRP
x
xi
x
x
x
x
x
Antibodies against CD74 CLIP
x
x
x
x
MRI of the Spine and SI Joints
xe
x
xl
TJC/SJC
x
x
x
x
x
x
BASDAI
x
x
x
x
x
x
x

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
50
Table 1.
Study Activities (Continued)
SOC Group 
Activity
6&5'
BLa (D1)
Randomized Open-Label Treatment Period
Disc. Visitb
Time of Visit (Weeks from D1) (1 wk Equals 7 Days)
Week 12
Week 24
Week 32
Week 52
BASMIlin
x
x
x
x
BASFI
x
x
x
x
MASES
x
x
x
x
x
x
Dactylitis
x
x
x
x
x
x
Physician's Global Assessment of Disease Activity
x
x
x
x
x
x
Patient's Global Assessment of Disease Activity
x
x
x
x
x
x
Patient's Assessment of Nocturnal Back Pain NRS
x
x
x
x
x
x
Patient's Assessment of Total Back Pain NRS
x
x
x
x
x
x
Patient's Global Assessment of Pain NRS
x
x
x
x
x
x
ASAS HI
x
x
x
x
x
x
EQ-5D 
x
x
x
x
x
x
WPAI-axSpA
x
x
x
x
x
x
Prior and Concomitant Therapy Assessment
x
x
x
x
x
x
x
Assessment of SOC Treatment for axSpA:  Recording 
of substances, dose, frequency 
x
x
x
x
x
x
Monitor AEs
xm
x
x
x
x
x
x
Enrollment/Randomization
x
Ada = Adalimumab; BL = Baseline; D = Day; Disc. Visit = Discontinuation Visit; F/U = Follow-Up
a.
Baseline Visit is defined as Day1, the day of Enrollment and Randomization.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
51
Table 1.
Study Activities (Continued)
b.
Subjects who prematurely discontinue from the study should complete the procedures outlined for the Discontinuation Visit as soon as possible and preferably prior to the 
administration of new therapies.
c.
Medical History and Inclusion/Exclusion Criteria must be confirmed by the Investigator prior to enrollment to verify patient eligibility.
d.
Height will be measured at Screening Visit only.
e.
ECG will not be required if the subject had a previous normal ECG within 90 days of Screening, provided all protocol required documentation is available at the site and 
nothing has changed in the subject's health status since the time of the test that warrants a repeat test.  MRI of the SI joint and spine will also not be required if the subject had 
a previous test within 42 days of Screening, respectively.  There is no need to redraw the HLA-B27 or ANA once results are available.
f.
CXR and TB screening will be only performed in subjects in the T2T group for whom initiation of Escalation Step 2 is planned. CRX and TB screening must be performed 
and evaluated before adalimumab is administered.  These procedures will not be required if the subject had a previous normal CXR or negative IGRA  within 90 days of the 
planned start date of adalimumab, provided all protocol required documentation is available at the site and nothing has changed in the subject's health status since the time of 
the test that warrants a repeat test.  If the subject has a positive IGRA test, has had a past CXR consistent with prior TB exposure, the subject will be required to initiate and 
complete at least the first 1 months of the prescribed TB prophylaxis (Section 5.3.1.1). 
g.
All females of childbearing potential will have a serum pregnancy test at Screening.
h.
All females of childbearing potential will have a urine pregnancy test performed at Baseline prior to study enrollment and at study discontinuation/completion.  Any subject 
with a positive urine pregnancy test must have a negative serum test performed prior to enrollment or continuation in the study.
i.
Laboratory assessments (chemistry, hematology, ESR, CRP and urinalysis) will be repeated at Baseline if the time between Screening and Baseline is greater than 14 days, or 
if the subject's health status has changed to warrant a repeat test.
j.
Dipstick urinalysis will be completed at all required 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.
k.
Must be performed and evaluated before adalimumab is administered.  If a subject is diagnosed with active hepatitis B (acute or chronic) the subject is not eligible to receive 
adalimumab and should discontinue from the study.
l.
For subjects that are discontinued prematurely the site should attempt to reschedule the MRI within 2 weeks (14 days) of the Discontinuation Visit or – if this is not possible –
shortly thereafter.
m.
SAEs will be collected starting from time of signing informed consent; nonserious AEs will be collected starting from Baseline.  Any AE that occurs between Screening and 
Baseline should be captured as medical history.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
52
Table 1.
Study Activities (Continued)
n.
Site personnel will contact all subjects of the T2T group who were on treatment with study drug adalimumab during the study but don't continue on commercially available 
Humira after discontinuation from the study by telephone approximately 70 days after the last dose of study drug to determine the occurrence of AEs or SAEs.  Subjects that 
initiate adalimumab therapy not supplied in the context of the clinical trial after the end of study participation need not be contacted by phone as new AEs or SAEs should be 
reported through the mechanism used for all post marketing adverse experiences.
o.
ASDASESR will be calculated to determine if treatment escalation is required.  The subject will wait in the clinic until the ESR result is available, the ASDASESR results are 
calculated, and the treatment escalation decision is made.
p.
To be performed if according to the T2T escalation schedule the subject is allocated to study drug.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
53
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 AE information (discussed in Section 6.1).  All study data 
will be recorded on the appropriate eCRF pages.
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-related procedures are undertaken, or before any medications are withheld from 
the subject in order to participate in this study. 
Inclusion/Exclusion Criteria
Subjects will be screened to ensure they meet all inclusion criteria and none of the 
exclusion criteria at both Screening and Baseline Visits.
Medical and Surgical History
A complete medical and surgical history, including history of tobacco and alcohol use, 
uveitis, inflammatory bowel disease (CD, UC only), psoriasis, spinal surgery, joint 
replacement, joint surgery or arthroscopy, will be obtained from each subject during the 
Screening Visit.  An updated medical history will be obtained at the Baseline Visit prior 
to study treatment administration and updated as necessary throughout the study on the 
eCRF.
A detailed medical history with respect to TB exposure needs to be documented.  This 
information needs to include Bacillus Calmette-Guérin (BCG) vaccination, cohabitation 
with individuals who have had TB, and/or who reside or work in TB endemic locations.
An updated medical history will be obtained at the Baseline Visit prior to study treatment 
administration and updated as necessary throughout the study on the eCRF.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
54
Vital Signs/Weight/Height
Vital signs 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 the designated study visits in Table 1.  Vital signs 
should be measured before blood draws are performed and prior to receiving study 
medication.  Height without shoes will be measured at the Screening Visit only. 
Anterior Uveitis
At the Screening Visit a detailed medical history of anterior uveitis, as confirmed by an 
ophthalmologist, will be documented.  It should include the date of initial diagnosis, 
frequency of flares, including specific eye (right, left or both), within the prior 12 months, 
date of the most recent flare and treatments received in the past.
At Baseline and all subsequent visits, the investigator will document new onset of uveitis 
and/or the number of flares, including specific eye (right, left or both), since the last visit.  
The corresponding AE eCRF should also be completed.  Initial documentation of uveitis 
must be confirmed by an ophthalmologist.  Flares following initial confirmation by an 
ophthalmologist can be self-reported by the subject.
Physical Examination
A full physical exam will be performed by medically qualified personnel at the designated 
study visits in Table 1.  Physical examination findings that are related or part of each 
subject's medical history should be captured on the appropriate eCRF page.  The physical 
exam at the Baseline Visit will serve as the Baseline exam for the entire study.
A symptom-directed physical examination can be performed at any other visits if, in the 
opinion of the Investigator, it is warranted by the subject's AE status or on review of 
symptoms.  Any clinically significant physical examination findings after the Baseline 
Visit – or worsening of pre-existing findings – will be recorded as adverse events.  For 
further definition of an adverse event please refer to Section 6.1.1.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
55
12-Lead Electrocardiogram (ECG)
A resting 12-lead ECG will be performed at the Screening Visit.  A qualified physician 
will interpret, determine the clinical significance of any abnormal finding, sign, and date 
each ECG.  Any clinically significant findings will be documented in the source 
documents and later transcribed on to the appropriate eCRF.  If there is no clinically 
significant finding this needs to be confirmed in the eCRF.  Each signed original ECG 
will be monitored by the responsible Clinical Research Associate (CRA) and kept with 
subject's source documents onsite.
For subjects with a normal ECG taken within 90 days of Screening, a repeat ECG at 
Screening will not be required, provided all protocol required documentation is available 
and nothing has changed in the subject's health status since the time of the test that 
warrants a repeat test.  If there are other findings that are clinically significant, the 
Principal Investigator must contact the Study Designated Physician 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.
Chest X-Ray (CXR)
Before initiating T2T Escalation Step 2 (combination with adalimumab) subjects will 
undergo a standard CXR (Posterior-anterior [PA] and lateral views) 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 the first date of adalimumab 
administration, provided all protocol required documentation is available at the site (as 
outlined below in Section 5.3.1.1) and nothing has changed in the subject's health status 
since the time of the test that warrants a repeat test.
Subjects can have a repeat CXR at any time during the study as warranted based on the 
opinion of the Investigator.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
56
A radiologist must perform an assessment of the CXR.  The Principal Investigator will 
indicate the clinical significance of any findings and will sign and date the report.  In the 
assessment of the chest x-ray, the Principal Investigator or their physician delegate must 
indicate the presence or absence of (1) calcified granulomas, (2) pleural 
scarring/thickening, and (3) signs of active TB.
Tuberculosis (TB) Screening
Before initiating T2T Escalation Step 2 (combination with adalimumab) TB screening 
will be performed.  An Interferon-Gamma Release Assay (IGRA; QuantiFERON test or T 
SPOT TB test) must be performed locally for all subjects who are to escalate T2T 
treatment to Escalation Step 2 including those with a prior history of BCG administration.  
If a subject had a negative IGRA test within 90 days prior to the first date of adalimumab 
administration, and all protocol required documentation is available, this test does not 
need to be repeated, provided nothing has changed in the subject's medical history to 
warrant a repeat test.  
If there are sites where the accepted testing materials are not available an alternative may 
be substituted, but the method must be submitted to and approved by AbbVie prior to use 
with study subjects.
A radiologist must perform an assessment of the CXR.  The Principal Investigator will 
indicate the clinical significance of any findings and will sign and date the report.  In the 
assessment of the CXR, the Principal Investigator or their physician delegate must 
indicate the presence or absence of (1) calcified granulomas, (2) pleural 
scarring/thickening, and (3) signs of active TB.  If the CXR demonstrates changes 
suggestive of previous TB (e.g., calcified nodule, fibrotic scar, apical or basilar pleural 
thickening) or other findings that are clinically significant, the Principal Investigator must 
contact the AbbVie Medical Monitor before enrolling the subject.
If the IGRA test is positive or the subject has a CXR indicative of latent TB, the subject 
will be required to initiate and complete at least 1 months of the prescribed course of 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
57
recommended prophylaxis per German guidelines 44 (Isoniazid 5 mg/kg) prior to starting 
adalimumab. The visit schedule will continue with the 1st dose of study treatment 
subsequent to completion of TB screening and of at least 1 month of prophylaxis (if 
applicable).
Subjects with a prior history of latent TB that have a documented completion of the 
Centers for Disease Control and Prevention (CDC) recommended or local guideline 
recommended prophylaxis may be permitted to enroll.  If the subject has a prior history of 
latent TB but has not completed or received prophylaxis, prophylaxis must be initiated 
and the subject must have completed at least 1 months of the prescribed TB prophylaxis 
before enrolling into the study.
If the subject has a prior history of active TB they must have documentation of 
completion of CDC recommended or local guideline recommended treatment and 
documentation of resolution of the infection.
If the IGRA test is indeterminate, the site should repeat the test with another blood 
sample.  If the second IGRA test is also indeterminate, the subject is considered to be 
positive and should initiate TB prophylaxis.
Newly initiated prophylactic treatment should be captured on the concomitant 
medications page in the eCRF and in the source documents.  Prior therapy should be 
captured in medical history.
For any subject with clinical signs/symptoms of active TB or newly identified TB risk 
factors a CXR may be required for evaluation of active TB and the site should contact the 
AbbVie Medical Monitor for further discussion.  Subjects with confirmed active TB
should be discontinued from the study and receive standard of care treatment for TB.   
Pregnancy Tests
A serum pregnancy test will be performed at the Screening Visit on all female subjects of 
childbearing potential.  At the Baseline Visit, subjects of childbearing potential will have 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
58
a urine pregnancy test performed locally by designated study personnel.  If any urine 
pregnancy test is positive, a serum pregnancy test will be performed.  A lactating or 
pregnant female will not be eligible for participation or continuation in this study.
All women of childbearing potential will have a repeat urine pregnancy test at the final 
study visit performed locally by designated study personnel.
Females of non-childbearing potential (either postmenopausal or permanently surgically 
sterile as defined above) at Screening do not require pregnancy testing.
Laboratory Analyses
Blood and urine samples will be obtained for clinical laboratory tests.  Samples will be 
obtained at the designated study visits in Table 1.  Samples will be obtained for the 
laboratory tests listed in Table 2.
The local laboratory of the respective study site will be utilized to process and provide 
results for the clinical laboratory tests, except for autoantibodies against CD74 CLIP.  The 
local laboratory will provide instructions regarding the collection, processing and 
shipment of appropriate samples.
The laboratory results will be provided by the local laboratory to the investigative site 
where they will be reviewed, signed and dated by the Investigator and filed as source data.  
For any abnormal value outside of the reference range, the Investigator will indicate on 
the report if the result is clinically significant (CS) or not clinically significant (NCS).  All 
abnormal laboratory test results that are considered clinically significant by the 
Investigator will be followed to a satisfactory resolution.
A certified central laboratory will be utilized to process and provide results for the testing 
of autoantibodies against CD74 CLIP.  The central laboratory chosen for this study will 
provide instructions regarding the collection, processing and shipment of appropriate 
samples.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
59
The laboratory results will be provided by the central laboratory to the investigative site 
where they will be reviewed, signed and dated by the Investigator and filed as source data.  
Blood draws should be performed after questionnaires and vital sign determinations have 
been completed but prior to any study treatment administration.
Urine samples will be obtained for macroscopic urinalysis (dipstick done at the local lab).  
Macroscopic urinalyses will include specific gravity, pH, protein, glucose, ketones, blood 
and nitrites.  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.
Clinical laboratory tests will need to be repeated at the Baseline Visit only if the time 
between the Screening Visit and the Baseline Visit is greater than 14 days.
Table 2.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
Other
Hematocrit
Hemoglobin
Red Blood Cell 
(RBC) count
White Blood Cell 
(WBC) count
Neutrophils
Bands
Lymphocytes
Monocytes
Basophils
Eosinophils
Platelet count 
(estimate not 
acceptable)
Creatinine
Total bilirubin
Albumin
Aspartate aminotransferase 
(AST)
Alanine aminotransferase 
(ALT)
Glucose
Specific gravity
Ketones
pH
Protein
Glucose
Nitrite
Blood
Pregnancy test
ESR
CRP
Anti-dsDNA 
Antibodies
HLA-B27
HBsAg
HBsAb
HBcAb
Biomarkers
Autoantibodies against 
CD74 CLIP
Human Leukocyte Antigen-B27 (HLA-B27)
Testing for HLA-B27 will be performed on specimens collected during the Screening 
Visit.  The HLA-B27 can be used to fulfill the ASAS classification criteria (Appendix C).  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
60
For subjects that may need to be rescreened or where the result of a previously 
documented HLA-B27 test is available, repeat HLA-B27 testing is not required.
Anti-dsDNA Antibody
Testing for antibodies against dsDNA will be performed on specimens collected during 
the Screening Visit.  For subjects that may need to be rescreened, once results are 
available repeat testing is not required.
Hepatitis B Testing
All subjects will be tested for the presence of the HBV at Screening.  A positive result for 
the HBs Ag will be exclusionary.  Samples that are negative for HBs Ag will be tested for 
surface antibodies (HBs Ab) and core antibodies (HBc Ab Total = HBc IgG and HBc 
IgM).  Subjects with HBs Ag (-), HBs Ab (-), and HBc Ab Total (+) require PCR 
qualitative testing for HBV DNA.  Any HBV DNA PCR result that meets or exceeds 
detection sensitivity will be exclusionary. 
Subjects with a negative HBs Ag test and tests showing results in (1), (2), or (3) do not 
require HBV DNA PCR qualitative testing. 
(1) HBc Ab Total (-) and HBs Ab (-):  no evidence of prior infection 
(2) HBc Ab Total (-) and HBs Ab (+):  immunity due to HBV vaccination 
(3) HBc Ab Total (+) and HBs Ab (+):  immunity due to past infection
Subjects with HBs Ag (-), HBs Ab (-), and HBc Ab Total (+) require PCR qualitative 
testing for HBV DNA to determine if
Ɣ
Resolved HBV infection
Ɣ
False positive HBc Ab test
Ɣ
Low level chronic HBV infection
Ɣ
Resolving acute HBV infection

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
61
Hepatitis B testing (as described above) will be repeated for subjects of the T2T group 
before initiating escalation step 2.  Hepatitis B testing must be performed and evaluated 
before adalimumab is administered.  If a subject is diagnosed with active hepatitis B 
(acute or chronic) the subject is not eligible to receive adalimumab and should discontinue 
from the study.
C-Reactive Protein (CRP)
Testing for CRP will be performed on specimens collected at the designated study visits 
listed in Table 1.
If a subject has an elevated CRP which the investigator believes to be secondary to an AE 
and not due to axSpA, sites may repeat the CRP later on within the time window allowed 
for the respective visit following a discussion with the AbbVie Study Designated
Physician.  Instances where AE-related CRP elevation spans more than one study visit 
will be addressed on a case-by-case basis.
Erythrocyte Sedimentation Rate (ESR)
Testing for ESR will be performed on specimens collected at the designated study visits 
listed in Table 1.  ESR will be evaluated at the site and expressed in mm/hg (1st hour).  In 
order to enable making the decision about T2T treatment escalation at the day of the 
respective visit, ASDASESR will be calculated for the purpose of decision making. 
Antibodies Against CD74 CLIP
Samples will be obtained for biomarker testings at the designated study visits in Table 1.
Sample collection is described in more detail under Section 5.3.2.1.  The primary 
biomarker is anti-CD74 CLIP antibodies.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
62
Magnetic Resonance Imaging (MRI) of the Spine and Sacroiliac Joints
All subjects will have a MRI evaluation of the sacroiliac (SI) joints as well as the cervical, 
thoracic and lumbar regions of the spine at Screening and the last visit (at Week 52 visit 
or – in case of early discontinuation – the Discontinuation Visit).  All assessments and 
procedures to determine subject eligibility should be performed and results available, 
showing subject may be eligible for study participation, before MRI assessment is carried 
out. The Screening MRI will not be required if the subject had a previous MRI fulfilling 
the study requirements (actual MRI films must be available to the site) within 42 days of 
the Screening Visit.
Images will be sent to the central imaging vendor designated by the Sponsor.  Images will 
be scored for inflammatory lesions and chronic structural changes in the spine and the 
sacroiliac joints using the Berlin MRI score (Appendix S).  Information on the central 
imaging vendor as well as procedures for performing and shipping the MRIs are provided 
in a separate manual. 
Tender Joint Count (TJC)
An assessment of 68 joints will be done by physical examination at the designated study 
visits in Table 1, by pressure manipulation on physical exam.  Joint pain/tenderness will 
be classified as present ("1"), absent ("0"), replaced ("9"), or no assessment ("NA") 
(Appendix H).
A joint undergoing surgery or intra-articular injection with corticosteroids will not be 
evaluable ("NA") for 28 days.
Site should make every attempt to have the same qualified Investigator or designee 
conduct these assessments throughout the study for any given subject.
Swollen Joint Count (SJC)
An assessment of 66 joints will be done by physical examination at the designated study 
visits in Table 1.  The joints to be examined for swelling are the same as those examined 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
63
for tenderness, except the hip joints are excluded.  Enthesitis is not part of the swollen 
joint assessment.  Joint swelling will be classified as present ("1"), absent ("0"), replaced 
("9"), or no assessment ("NA") (Appendix H).
A joint undergoing surgery or injected intra-articularly with corticosteroids will not be 
evaluable ("NA") for 28 days.
Site should make every attempt to have the same qualified Investigator or designee 
conduct these assessments throughout the study for any given subject.
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI will be completed at the designated study visits in Table 1.  The subject will 
assess his/her disease activity using the BASDAI which consists of Numerical Rating 
Scale (NRS) used to answer 6 questions pertaining to symptoms experienced by the 
subject during the past week (Appendix F).
Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin)
The BASMIlin will be conducted at the designated study visits in Table 1 to evaluate 
spinal mobility in a subject (Appendix I).
Site should make every attempt to have the same qualified Investigator or designee 
conduct these assessments throughout the study for any given subject.
Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
The MASES evaluation will be conducted at the designated study visits in Table 1 to 
assess the presence or absence of enthesitis at 13 different sites, noting the subjects' 
responses (Appendix J).
Site should make every attempt to have the same qualified Investigator or designee 
conduct these assessments throughout the study for any given subject.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
64
Dactylitis
Evaluation for dactlyitis will be conducted at the designated study visits in Table 1 to 
assess the presence or absence of dactylitis in all 20 of the subjects' digits.
Site should make every attempt to have the same qualified Investigator or designee 
conduct these assessments throughout the study for any given subject.
Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI will be completed at the designated study visits in Table 1.  The subject will 
assess his/her ability of ten selected activities for the past week using a NRS 
(Appendix K).  This assessment should be completed prior to any other study related 
procedures being performed.
Numerical Rating Scales (NRS)
NRS will be used to assess physician's and patient's global assessment of disease activity, 
as well as the patient's global assessment of pain, patient's assessment of nocturnal back 
pain, and patient's assessment of total back pain.  The left end of the NRS (0) signifies the 
absence of symptoms and the right end (10) signifies maximum activity in terms of the 
parameters assessed:
Ɣ
Physician's global assessment of disease activity (current status)
ż
Physician's global assessment of patient's current disease activity 
(Appendix L). Site should make every attempt to have the same qualified 
Investigator or designee (physician required) conduct these assessments 
throughout the study for any given subject.
Ɣ
Patients global Assessment of Disease activity within the last week 
(Appendix G)
Ɣ
Patient's assessment of nocturnal back pain within the last week (Appendix M)
Ɣ
Patient's assessment of total back pain within the last week (Appendix N)
Ɣ
Patient's global assessment of pain within the last week (Appendix O)

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
65
Health Outcomes Questionnaires
Subjects will complete the following questionnaires:  ASAS Health Index (HI) 
(Appendix P), European Quality of Life – 5 Dimension Questionnaire (EQ-5D) 
(Appendix R), and Work Productivity and Activity Impairment Questionnaire – Specific 
Health Problem Questionnaire (WPAI-axSpA) (Appendix Q).  The ASAS HI will assess 
the overall functioning of each subject.  The EQ-5D will assess the subject's view of their 
health.  The WPAI-axSpA will assess work related issues.  These assessments should be 
completed prior to any other study related procedures being performed in the order 
outlined on Table 1.
Prior and Concomitant Therapy Assessment
Any medication that the subject is receiving at the time of Screening or receives during 
the study must be recorded on the source documents as well as the appropriate eCRF.  
Previous prescription medications or physician-administered treatments used for axSpA 
prior to study entry will be recorded.  See Section 5.2.3 for full details regarding 
documentation of prior and concomitant therapy.
Ankylosing Spondylitis Disease Activity Score (ASDAS) Calculation 
(Treat-to-Target [T2T] Group)
The ASDASESR will be calculated for each visit as outlined in Table 1 for subjects in the 
T2T group.  The ASDASESR will be calculated using the parameters listed in Appendix E
of the respective visit including the ESR measurement of the respective visit. 
The ASDASESR will be automatically calculated by the eCRF upon entry of the respective 
parameters. 
In order to enable making the decision about T2T treatment escalation on the day of the 
respective visit, ASDASESR will be calculated.  The subject will need to wait at the site for 
approximately 1 hour until the ESR result is available, the ASDASESR is calculated, and 
treatment escalation decision is made.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
66
Published ranges for disease activity states as defined by the ASDAS are:  < 1.3 for 
LQDFWLYHGLVHDVHWRIRUPRGHUDWHGLVHDVHDFWLYLW\WRIRUKLJK
disease activity" and > 3.5 for "very high disease activity."33
If a subject has an elevated ESR which the investigator believes to be secondary to an AE 
and not due to axSpA, sites may repeat the ESR later on within the time window allowed 
for the respective visit following a discussion with the AbbVie Study Designated
Physician.  Instances where AE-related ESR elevation spans more than one study visit 
will be addressed on a case-by-case basis.
Enrollment and Randomization
Subjects who meet the inclusion criteria and do not meet any of the exclusion criteria will 
be enrolled into the Randomized Open-Label Treatment Period randomized in a 1:1 ratio 
to receive either T2T treatment or SOC as outlined in Section 5.1.  Subjects will not be 
enrolled in the study if laboratory or other screening results are clinically unacceptable.
As they are enrolled into the study, subjects will be assigned unique consecutive numbers 
starting with 10001_ _, whereas, the first 2 digits represent the country, the next 3 digits 
represent the site number and the last 2 digits represent a sequential number.  Site 
numbers will be assigned sequentially.
Dispense Study Drug
Study drug will be dispensed to subjects as outlined in Table 1 and described in more 
detail under Section 5.5.
Administration of Study Drug
The first time study drug is administered this will be done under direct observation in the 
Investigator's office to ensure proper technique as described in more detail under 
Section 5.5.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
67
70-Day Follow-Up Call for Treat-to-Target (T2T) Group
Subjects of the T2T group who were on treatment with study drug adalimumab during the 
study but do not continue on commercially available Humira after completing or 
discontinuation from the study will be contacted approximately 70 days following their 
last dose of study drug to check for new, and update ongoing AEs or Serious AEs (SAEs) 
except those subjects that continue on Humira therapy after the end of study participation.  
Any new AEs/SAEs reported during the 70-day follow-up period should be submitted to 
AbbVie.  The 70-day follow-up phone call will be recorded in source document only and 
confirmation of the contact will be faxed to AbbVie (Appendix T).  Subjects that continue 
on adalimumab therapy after study end are not required to complete the 70-day follow-up
and any new AEs should be reported through the mechanism used for all post marketing 
adverse experiences. 
5.3.2
Measurement of Autoantibodies Against CD74 CLIP
5.3.2.1
Collection of Samples for Analysis
Please refer to the central laboratory manual for specific instructions regarding sample 
collection, processing, storage and shipment.
Blood samples for the detection of autoantibodies against CD74 CLIP will be obtained, 
when the blood samples are drawn according to the local standards at each center at 
Baseline, Week 32, 52, and at discontinuation visit in the case of early discontinuation per 
Section 5.3.2.  The serum sample (2 mL) for the central laboratory in Hannover, 
Germany, will be obtained and processed as described below.
The date that each blood sample is collected will be recorded in the appropriate eCRF.
Sample collection will be prior to dosing of adalimumab (if appropriate) at the study 
visits specified in Table 1.

Adalimumab
W15-679 Protocol Amendment 2 
EudraCT 2015-005398-18
68
5.3.2.2
Handling/Processing of Samples for the Detection of 
Autoantibodies Against CD74 CLIP
Within 2 hours after the blood sample was obtained, the tube will be spun down (see 
laboratory manual for detailed instructions).  The supernatant will be frozen immediately 
and stored at at least –20°C.  The serum samples will be pseudonymized using the 
subject's unique identification code and initially stored at the site where the subject was 
recruited. 
5.3.2.3
Disposition of Samples for the Detection of Autoantibodies 
Against CD74 CLIP
Shipment of pseudonymized samples to the central laboratory will be done by a courier 
service on dry ice per the central laboratory instruction manual when 20 sera have been 
collected or every 3 months, whatever is earlier.  An inventory of the samples included 
will accompany the package.
The shipment address for the samples is: 
The samples will be stored in the central lab at at least –70°C until they are used for the 
study specific analysis of the antibodies against CD74 CLIP.  Remaining rest of serum 
samples will be discarded.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
69
5.3.3
Efficacy Endpoints
5.3.3.1
Primary Efficacy Endpoint
The primary efficacy endpoint is the clinical disease activity at Week 32 as measured by 
the percentage of subjects in ASDAS inactive disease (ASDAS < 1.3).
5.3.3.2
Secondary Endpoints
Secondary endpoints include the following:
At Week 32 and Week 52
Ɣ
Quality of life by the EQ-5D Questionnaire
Ɣ
WPAI-axSpA
Ɣ
Overall functioning by ASAS HI
Ɣ
Disease activity as measured by BASDAI
Ɣ
Percentage of subjects achieving 50% improvement in BASDAI (BASDAI 50 
response)
Ɣ
Function – Represented by the BASFI NRS score (0 to 10)
Ɣ
Disease activity measured by ASDAS
Ɣ
ASDAS major improvement
Ɣ
ASDAS clinically important improvement 
Ɣ
Percentage of subjects in ASDAS inactive disease (ASDAS < 1.3)
Ɣ
Percentage of subjects with low disease activity (ASDAS < 2.1)
Ɣ
3HUFHQWDJHRIVXEMHFWVZLWKPRGHUDWHGLVHDVHDFWLYLW\$6'$6WR
Ɣ
3HUFHQWDJHRIVXEMHFWVZLWKKLJKGLVHDVHDFWLYLW\$6'$6WR
Ɣ
3HUFHQWDJHRIVXEMHFWVZLWKYHU\KLJKGLVHDVHDFWLYLW\$6'$6
Ɣ
ASAS 20, ASAS 40, and ASAS Partial Remission
ż
$6$6UHVSRQVHLPSURYHPHQWRIDQGDEVROXWHLPSURYHPHQWRI
 XQLWRQDVFDOHRIWRIURP%DVHOLQHLQRIWKHIROORZLQJ
4 domains, with no deterioration in the remaining domain (defined as a 
worsHQLQJRIDQGDQHWZRUVHQLQJRIXQLW

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
70
Ɣ
Patient's Global Assessment (PTGA) – Represented by the 
PTGA-disease activity NRS score (0 to 10)
Ɣ
Pain – Represented by the patient's assessment of total back pain NRS 
score (0 to 10)
Ɣ
Function – Represented by the BASFI NRS score (0 to 10)
Ɣ
Inflammation – Represented by the mean of the 2 morning 
stiffness-related BASDAI NRS scores (mean of items 5 and 6 of the 
BASDAI [0 to 10])
ż
$6$6UHVSRQVHLPSURYHPHQWRIDQGDEVROXWHLPSURYHPHQWRI
 2 units (on a sFDOHRIWRIURP%DVHOLQHLQRIWKHGRPDLQV
above in ASAS20 with no deterioration in the potential remaining domain 
ż
ASAS partial remission: absolute score of < 2 units for each of the 
4 domains identified above in ASAS20
Ɣ
Active inflammation as measured by magnetic resonance imaging of the 
sacroiliac joints and the spine (Berlin MRI scores for MRI of the SI joint and 
spine)
Ɣ
Physician's Global Assessment of Disease Activity
Ɣ
Patient's Global Assessment of Disease Activity
Ɣ
Patient's Global Assessment of Pain
Ɣ
Swollen Joint Count (66 joints)
Ɣ
Tender Joint Count (68 joints)
Ɣ
Change from Baseline in MASES
Ɣ
Change from Baseline in Dactylitis count (0 – 20)
Ɣ
Change from Baseline in BASMIlin
Ɣ
Anterior uveitis
Other variables to be analyzed at various time points including Week 32 and Week 52 
include:
Ɣ
C-reactive Protein 
Ɣ
Erythrocyte sedimentation rate

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
71
Ɣ
ASDAS course over time
Ɣ
BASDAI course over time
5.3.3.3
Exploratory Endpoints
Ɣ
Serum autoantibodies against CD74 CLIP
Ɣ
Reduction of disease progression (as measured by MRI of the sacroiliac joints 
and the spine)
5.3.4
Safety Variables
Screening assessments will include medical history, vital signs, physical examination, and 
clinical laboratory tests.  The following safety evaluations will be performed during the 
study:  medical history and concomitant medication review, AE monitoring, assessments 
of vital signs, physical examination and laboratory tests.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
A subject may withdraw from the study at any time.  The Investigator may discontinue 
any subject's participation prematurely for any reason, including an adverse event, safety 
concerns or failure to comply with the protocol. See section 6.1.7 for toxicity management 
criteria.
Subjects will be withdrawn from the study immediately if any of the following occurs:
Ɣ
Clinically significant abnormal laboratory result(s) or adverse event(s), as 
determined by the Investigator in consultation with the AbbVie Study 
Designated Physician.
Ɣ
The Investigator believes it is in the best interest of the subject.
Ɣ
The subject requests withdrawal from the study.
Ɣ
Inclusion and exclusion criteria violation was noticed after the subject started 
study drug, when continuation of the study drug would place the subject at risk 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
72
as determined by the AbbVie Study Designated Physician (Section 5.2 and 
Section 7.0).
Ɣ
Introduction of prohibited medications or dosages when continuation of the 
study drug would place the subject at risk as determined by the AbbVie Study 
Designated Physician.
Ɣ
Subject is non-compliant with TB prophylaxis.
Ɣ
The subject becomes pregnant while on study.
Ɣ
Subject has dysplasia of the gastrointestinal tract 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.
Ɣ
Subject is diagnosed with lupus-like syndrome, multiple sclerosis or 
demyelinating disease.
Ɣ
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 the AbbVie Study Designated Physician.
If, during the course of the study, the subject prematurely discontinues from the study, the 
procedures outlined for the Discontinuation Visit must be completed within 2 weeks of 
the last dose of study drug (if applicable), and, if possible, 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 subjects of the T2T group who were on treatment with 
study drug adalimumab during the study but do not continue on commercially available 
Humira after discontinuation from the study approximately 70 days after the end of their 
Treatment phase (i.e., their Week 52 visit) or – in case of premature discontinuation –
their Discontinuation Visit to determine the status of any ongoing AEs/SAEs or the 
occurrence of any new AEs/SAEs unless not required as outlined in Section 5.3.1.1.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
73
All attempts must be made to determine the date of the last dose of study drug and the 
primary reason for premature discontinuation.  The information will be recorded on the 
appropriate eCRF page.
For subjects that are considered lost to follow-up, reasonable attempts must be made to 
obtain information on the final status of the subject.  As a minimum, two phone calls must 
be made and one certified letter must be sent.  The attempts should be documented in the 
subject's source documents.
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 
concerns. AbbVie will terminate the trial prematurely if any new safety signal for the 
study drug is identified which indicates an unacceptable risk for patients in this trial. If 
AbbVie terminates the study for safety reasons, AbbVie will immediately notify the 
Investigator by telephone and subsequently provide written instructions for study 
termination.
5.5
Treatments
5.5.1
Treatments Administered
T2T Group
Treatment escalation steps are as follows:
Ɣ
Basic Treatment (NSAID 1):  Treatment will be started with any NSAID at 
full anti-inflammatory dose and given for 4 weeks (see Appendix Y).  Early 
escape is possible, if after 2 weeks no ASAS 20 response is achieved.  In this 
case, treatment can be switched to Escalation Step 1 at the Week 2 visit.  If the 
chosen NSAID cannot be continued due to intolerance, escalation to the next 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
74
escalation step is possible at any time point.  If Basic Treatment is well 
tolerated and ASDAS is < 2.1 the subject will be continued on this treatment.
Ɣ
Escalation Step 1 (NSAID 2):  At Week 4 (after 4 weeks of NSAID 1), if 
$6'$6LVRUWUHDWPHQWZLWK16$,'LVQRWWROHUDWHGWUHDWPHQWZLOOEH
changed to a second NSAID at full anti-inflammatory dose (see Appendix Y).  
The second NSAID will be given for 4 weeks.  Early escape is possible if after 
2 weeks (at Week 6 or Week 4 for subjects who early escaped from Basic 
Treatment) no ASAS 20 response is achieved.  In this case, treatment can be 
switched to Escalation Step 2 after 2 weeks of NSAID 2.  If the chosen NSAID 
cannot be continued due to intolerance, escalation to the next escalation step is 
possible at any time point.  In that case, adalimumab may be combined the 
second or – if deemed required by the treating physician – the first NSAID 
used (provided escalation from Basic Treatment to Escalation Step 1 did not 
occur due to any safety issues related to NSAID 1 therapy). If NSAID 2 
treatment is well tolerated and ASDAS is < 2.1, the subject will be continued 
on this treatment.
Ɣ
Escalation step 2 (Combination with adalimumab):  In case of failure of 
16$,'$6'$6DIWHUZHHNVRI16$,'WKHWUHDWPHQWZLOOEH
intensified by switching to the combination of NSAID and adalimumab 40 mg 
s.c. eow.  Escalation step 2 can be initiated at Week 4 visit at the earliest if 
early escape is chosen during basic treatment and during NSAID 2.  
Since subjects may be unfamiliar with sterile SC injection technique, qualified study site 
personnel will instruct them on proper technique and should directly observe the 
first injection of study drug to ensure proper injection technique (Appendix U).  This 
supervision will serve as a confirmation of the use of safe and appropriate drug injection 
techniques and to answer any questions related to drug administration.
SOC Group
Subjects will receive treatment according to local SOC.  For use of NSAID please see 
Appendix Y.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
75
5.5.2
Identity of Investigational Product
The individual study drug information is presented in Table 3.
Table 3.
Identity of Investigational Products
Drug
Dosage Form
Device
Formulation
Manufacturer
Adalimumab
Parenteral
Pre-filled 
syringe
40 mg/0.8 mL solution for injection 
Adalimumab/Mannitol, Citric acid 
monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, 
Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, 
Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary
to adjust pH
AbbVie
5.5.2.1
Packaging and Labeling
Investigational product (IP) will be packaged separately in 0.8 mL syringes containing 
adalimumab 40 mg/0.8 mL.  Each dosing kit carton will contain two pre-filled syringes to 
accommodate study design. 
The syringe and/or carton labels will minimally contain the information as required per 
country requirements.
All labels must remain affixed to study medication at all times, and should never be 
removed for any reason.
5.5.2.2
Storage and Disposition of Study Drug
Adalimumab 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 refrigerator temperature 
must be recorded on each business day.  Malfunctions or any temperature excursion must 
be reported to the Sponsor immediately.  Study medication should be quarantined and not 
dispensed until AbbVie Global Pharmaceutical Research and Development (GPRD) or 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
76
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 destroyed via on-site destruction (if allowed by AbbVie, local 
guidelines and a well-documented procedure is in place) or 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 Groups
All subjects will be enrolled at the Baseline Visit and centrally randomized in a 1:1 ratio 
to the two treatment arms (intensified T2T or SOC).  Centralized permuted block 
randomization will be performed.
5.5.4
Selection and Timing of Dose for Each Subject
Subjects should take study medication as outlined in Section 5.5.1.
If a subject should in the T2T group forget to administer the injection of study medication 
on their regularly scheduled dosing date, they should take the forgotten injection as soon 
as they remember the dose was missed up to the day of their next scheduled dose.  The 
subject should not administer two doses on the same day.
In the event the incorrect dose is taken or a dose is missed, the subject should be 
instructed to contact the site to determine how to proceed with dosing.  The subject must 
record all dosing information on the Subject-Dosing Diary Sheet (Appendix V).
Doses not administered (e.g., not taken before next dose is scheduled), should be recorded 
as not taken in the source.  Remaining doses should be fully returned to the study site.  
The subject should resume their regular dosing schedule based on the first dosing date at 
Baseline.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
77
5.5.5
Blinding
5.5.5.1
Blinding of Investigational Product
Neither the investigator(s) nor their study staff, or subjects will be blind to the treatment 
arm subjects are randomized to.  The investigator should not influence their SOC 
treatment based upon knowledge and potential benefits/risks in the intensified T2T 
treatment arm.
5.5.6
Treatment Compliance
The Investigator or his/her designated representatives will dispense study drug only for 
use by subjects enrolled in the study.
The subject or their qualified designee will administer all doses of study drug.  
Appropriate site staff will supervise the first administration of the study drug in-office to 
ensure proper injection technique. In order to document compliance with the treatment 
regimen, the subject will be given a subject dosing diary sheet (Appendix V) 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.  Subjects will be 
instructed to return all drug containers (even if empty) to the study site.  If the subject 
does not return the subject dosing diary 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 once the dosing 
sheet is returned before completing the applicable eCRF page.
5.5.7
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 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
78
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 on a Site 
Drug Accountability log including date received, the lot number, kit number(s), date 
dispensed, subject number, and the identification with date of the person dispensing the 
drug.
All empty IP boxes and used pre-filled syringes will be inventoried by the site.  Each 
subject will be given their own sharps disposal container to store used pre-filled syringes.  
Empty IP boxes and 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 prohibited by local law) 
until the CRA is on site to confirm the returned medication.  CRAs 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 CRA has verified drug accountability at the site, the site staff may destroy or 
initiate shipment for shipment of used pre-filled syringes.  Site staff and CRA will 
document that the used pre-filled syringes have been destroyed, using appropriate 
biohazard precautions, when appropriate.  A copy of the destruction methodology should 
be maintained at the site's facility.  At the end of the study, after drug accountability has 
been completed at the site and verified by the CRA, unused medication will be returned to 
a destruction facility by the CRA or – if approved by AbbVie and permitted according to 
local guidelines – destroyed at site (or by a third party vendor contracted by the site).
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
This clinical trial was designed to compare a T2T intensified treatment approach 
(escalating quickly with two different NSAIDs to a combination of adalimumab with 
NSAID) with SOC in reducing disease activity/achieving remission in patients with 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
79
axSpA.  Recently T2T recommendations for the whole group of SpA including patients 
with axSpA have been developed.  However, a T2T approach starting with NSAID 
treatment and escalating to combining NSAID with a TNF blocker has not yet been 
investigated. 
The duration of 52 weeks was chosen to reasonably reflect long term treatment of chronic 
disease.
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 to assess disease activity in 
subjects with axSpA.  Other than the biomarker analysis and the measurement of MRI 
progression which will be exploratory, all clinical and laboratory procedures in this study 
are standard and generally accepted.
5.6.3
Suitability of Subject Population
Males and females at least 18 years of age with axSpA who have a minimum level of 
GLVHDVHDFWLYLW\DW%DVHOLQH$6'$6&RQILQLQJWKHGXUDWLRQRIGLVHDVHWR
< 5 years and including only subjects who are TNF-alpha-blocker-naïve and either 
NSAIDs-naïve or should not have taken NSAIDs at maximal recommended dose over the 
last 2 weeks prior to Baseline minimalizes the probability to include treatment 
experienced/resistant subjects. 
5.6.4
Selection of Doses in the Study
The recommended dose of adalimumab for adults with AS and nr-axSpA is 40 mg 
administered eow.  Adalimumab is approved for the treatment of AS and nr-axSpA in the 
EU.  Adalimumab was generally well-tolerated and has demonstrated therapeutic efficacy 
compared to placebo in AS subjects in Study M03-607 (ATLAS) and Study M03-606 as 
well as in nr-axSpA subjects in Study M10-791 which were the pivotal studies used to 
support registration for these indications.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
80
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 study medication in this trial contains both:
A Biologic compound and
Device components (pre-filled syringe)
Complaints associated with any component of this study medication must be reported to 
the Sponsor (Section 6.2.2).  For adverse events, please refer to Sections 6.1 through 
6.1.6.  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 adverse 
events on a routine basis throughout the study.  The Investigator will assess and record 
any adverse event in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
adverse event to Humira, and any action(s) taken.  For serious adverse events considered 
as having "no reasonable possibility" of being associated with Humira, the Investigator 
will provide an "Other" cause of the event.  For adverse events to be considered 
intermittent, the events must be of similar nature and severity.  Adverse events, whether in 
response to a query, observed by site personnel, or reported spontaneously by the subject 
will be recorded.
All adverse events will be followed to a satisfactory conclusion.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
81
6.1.1
Definition
6.1.1.1
Adverse Event
An AE is defined as any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An adverse event 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 adverse event.  
Worsening of SpA per investigator judgment is considered an AE, however the expected 
manifestations of disease (arthritis, enthesitis, back pain, etc.) are not considered AEs.  
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  Laboratory abnormalities and changes in vital signs are considered to be adverse 
events 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 adverse events.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event 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 adverse event.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
82
6.1.1.2
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as a 
serious adverse event (SAE) within 24 hours of the site being made aware of the serious 
adverse event.
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the Investigator, would have 
resulted in immediate fatality if medical intervention had not 
been taken.  This does not include an event that would have 
been fatal if it had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to an 
outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that 
results in fetal loss.
Persistent or 
Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes 
with the activities of daily living of a study subject.  Disability 
is not intended to include experiences of relatively minor 
medical significance such as headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g., sprained 
ankle).
Important Medical 
Event Requiring 
Medical or Surgical 
Intervention to 
Prevent Serious 
Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based 
on medical judgment may jeopardize the subject and may 
require medical or surgical intervention to prevent any of the 
outcomes listed above (i.e., death of subject, life-threatening, 
hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  
Additionally, any elective or spontaneous abortion or stillbirth 
is considered an important medical event.  Examples of such 
events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
83
For serious adverse events with the outcome of death, the date and cause of death will be 
recorded on the appropriate case report form.
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.
6.1.3
Relationship to Humira
The Investigator will use the following definitions to assess the relationship of the adverse 
event to the use of Humira:
Reasonable 
Possibility
After consideration of factors including timing of the event,
biologic plausibility, clinical judgment, and potential alternative 
causes, there is sufficient evidence (information) to suggest a 
causal relationship.
No Reasonable 
Possibility
After consideration of factors including timing of the event,
biologic plausibility, clinical judgment, and potential alternative 
causes, there is insufficient evidence (information) to suggest a 
causal relationship.
For causality assessments, events assessed as having a reasonable possibility of being 
related to Humira will be considered "associated."  Events assessed as having no 
reasonable possibility of being related to Humira will be considered "not associated."  In 
addition, when the Investigator has not reported a causality or deemed it not assessable, 
AbbVie will consider the event associated.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
84
If an Investigator's opinion of no reasonable possibility of being related to Humira is 
given, an "Other" cause of event must be provided by the Investigator for the adverse 
event.
6.1.4
Adverse Event Collection Period
All adverse events reported from Baseline until 70 days following discontinuation of 
study drug administration have elapsed will be collected, whether solicited or 
spontaneously reported by the subject.  In addition, serious adverse events and 
protocol-related nonserious adverse events 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 who continue on Humira therapy eow after the end of study participation will not 
be contacted for follow-up as any new adverse events should be reported through the 
mechanism used for all post-marketing adverse experiences.  All other subjects of the T2T 
group treated with study drug will be contacted approximately 70 days following study 
drug discontinuation for an assessment of any new or ongoing AEs.  The 70-day 
follow-up call will not be required for subjects of the SOC group.  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.  All SAEs and all ongoing adverse events reported during the 70-day 
follow-up phone call must be captured in the clinical database.
Figure 2.
Adverse Event Collection

Adalimumab
W15-679 Protocol Amendment 2 
EudraCT 2015-005398-18
85
6.1.5
Adverse Event Reporting
In the event of a serious adverse event, and additionally, any nonserious event of 
malignancy in subjects 30 years of age and younger, whether related to Humira or not, the 
physician will notify the AbbVie Clinical Pharmacovigilance Team within 24 hours of the 
site being made aware of the event by entering the serious adverse event or nonserious 
event of malignancy in subjects 30 years of age and younger data into the electronic data 
capture (EDC) system.  Serious adverse events and nonserious events of malignancy in 
subjects 30 years of age and younger, that occur prior to the site having access to the EDC 
system or if the EDC system is not operable should be documented on the SAE Non-CRF 
Forms and sent (preferable by email) to Clinical Pharmacovigilance within 24 hours of 
being made aware of the adverse event.
For safety concerns, contact:
For any subject safety concerns, please contact the physician listed below:
Primary Study Designated Physician:

Adalimumab
W15-679 Protocol Amendment 2 
EudraCT 2015-005398-18
86
Should in case of subject safety concerns or medical emergencies the Study Designated 
Physician be unavailable, please call the following central back-up number 
Phone:  
The sponsor will be responsible for Suspected Unexpected Serious Adverse Reactions 
(SUSAR) reporting for the Investigational Medicinal Product (IMP) in accordance with 
Directive 2001/20/EC.  The reference document used for SUSAR reporting in the EU 
countries will be the most current version of the Investigator's Brochure. 
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 prematurely 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 for 
either mother or infant, meeting any serious criteria including elective or spontaneous 
abortion is considered a SAE and must be reported to AbbVie within 24 hours of the site 
becoming aware of the event.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
87
6.1.7
Toxicity Management
Subjects who develop a new infection while undergoing treatment with adalimumab 
should be monitored closely.  Administration of study injections should be interrupted if a 
subject develops an infection requiring IV anti-infective treatment or if an infection meets 
the definition of "serious" (see Section 6.1 for definitions).  Study medication may be 
restarted once the physician determines that the infection has been successfully treated.  
Otherwise prohibited concomitant medications may be given if medically necessary.  
Prior to use, every attempt should be made to contact the AbbVie Study Physician for 
direction on re-introduction of adalimumab therapy after prohibited medication 
administration.
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.
Management of Select Laboratory Abnormalities: For any given confirmed laboratory 
abnormality (repeat testing with a new sample), the Investigator should assess the subject, 
apply the standard of care for medical evaluation and treatment following any local 
guidelines. Specific toxicity management guidelines for abnormal laboratory values 
(confirmation by repeat testing is required) are described in Table 4.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
88
Table 4.
Specific Toxicity Management Guidelines for Abnormal 
Laboratory Values
Laboratory 
Parameter
Toxicity Management Guideline
Absolute neutrophil 
count (ANC)
x
Discontinue from study LIFRQILUPHGFHOOVȝ/E\UHSHDWWHVWLQJZLWK
new sample.
Absolute lymphocyte
counts (ALC)
x
•Discontinue from VWXG\LIFRQILUPHGFHOOVȝ/E\UHSHDWWHVWLQJZLWK
new sample.
Total white blood cell
count
x
Discontinue from study if confirmed < 10FHOOVȝ/E\UHSHDWWHVWLQJZLWK
new sample.
Platelet count
x
Discontinue from study if confirmed < 20,FHOOVȝ/E\UHSHDWWHVWLQJZLWK
new sample
AST or ALT
x
Discontinue from study if confirmed ALT or AST > 3 × ULN and total 
bilirubin > 2 × ULN (repeat testing with new samples are required for both) 
x
Discontinue from study if confirmed ALT or AST > 3 × ULN by repeat 
testing with new sample along with appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%).
x
Discontinue from study if confirmed ALT or AST > 8 × ULN by repeat 
testing with new sample.
Serum Creatinine
Discontinue study drug if confirmed > 3 × ULN by repeat testing with new 
sample.
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 components.  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.
For medical devices, a product complaint also includes all deaths of a subject using the 
device, any illness, injury, or adverse event in the proximity of the device, an adverse 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
89
event that could be a result of using the device, any event needing medical or surgical 
intervention including hospitalization while using the device and use errors.  
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be 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 (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 
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.  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 IEC/IRB regulatory authorities (as applicable), and their 
assigned CRO Clinical Monitor or the following AbbVie Clinical Monitors:

Adalimumab
W15-679 Protocol Amendment 2 
EudraCT 2015-005398-18
90
Primary Contact:
Alternate Contact:  (CPM)
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: 
Ɣ
Subject entered into the study even though she/he did not satisfy entry criteria 
Ɣ
Subject who developed withdrawal criteria during the study and was not 
withdrawn
Ɣ
Subject who received wrong treatment or incorrect dose 
Ɣ
Subject who received excluded or prohibited concomitant treatment 
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
8.1.1
Analysis Population
The primary and secondary efficacy variables will be analyzed for the intent to treat (ITT) 
population, defined as all subjects who were randomized to one of the two treatment arms.  
Subjects in the ITT population will be analyzed according to the treatment group they 
were randomized to.  In order to evaluate the impact of major protocol violations on the 
results of the trial, additional analyses of the primary efficacy variable may be conducted 
on the per-protocol population, which consists of all ITT subjects who were randomized, 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
91
have sufficient data regarding the primary efficacy endpoint (clinical disease activity at 
Week 32) and did not meet any major protocol violation.
The safety population consists of all subjects who were randomized and received 
treatment for axSpA after randomization. 
8.1.2
Statistical and Analytical Plan
Complete and specific details of the final statistical analysis will be described and fully 
documented in the Statistical Analysis Plan (SAP).  The SAP will be finalized prior to the 
database lock.  The analysis will be performed using SAS (SAS Institute Inc., Cary, NC, 
USA).
8QOHVVRWKHUZLVHVWDWHGDOOVWDWLVWLFDOWHVWVZLOOEHFRQGXFWHGDWĮ OHYHOVLGHG
Descriptive statistics data will be provided including but not limited to the number of 
observations, mean, standard deviation, median, minimum and maximum for continuous 
variables; and counts and percentages for discrete variables.
All statistical comparisons for the primary efficacy endpoint will be performed at 
Week 32 and secondary efficacy endpoints will be performed at the time points specified 
in Section 5.3.3.2, unless otherwise stated.  All statistical comparisons for the primary and 
secondary endpoints will be done at the end of the study.
The last available pre-treatment values recorded on or before Day 1 will be considered as 
the Baseline value.
In case of missing data for the primary efficacy endpoint (proportion of subjects with 
ASDAS < 1.3 at Week 32), the non-responder imputation (NRI) will be applied, 
i.e., missing value at Week 32 will be counted as non-response. 
In addition to this imputation approach, the following sensitivity analyses will be 
performed:

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
92
1.
Observed cases:  all subjects with data available at Week 32 will be analyzed 
without imputation.
2.
Last observation carried forward (LOCF) rule:  replacing the missing value by the 
last non-missing post-baseline value prior to the missing value.
The LOCF rule will be also applied to impute missing continuous efficacy data at 
post-Baseline Visits (including Week 52).  In addition, an analysis using only the 
observed or reported data will be performed as a sensitivity analysis for the continuous 
secondary efficacy endpoints. 
8.1.3
Analysis of Demographic Data and Baseline Disease 
Characteristics 
Demographic and Baseline characteristics will be summarized and compared, among 
treatment groups.  The number of observations, mean, standard deviation, median, 
quartiles, minimum and maximum will be summarized for continuous variables; and 
treatment group homogeneity will be assessed using a one-way analysis of variance 
(ANOVA) model using treatment, as the independent factor.  Discrete variables will be 
summarized via counts and percentages; and treatment group homogeneity will be 
evaluated using the appropriate chi-square method.  Duration of treatment will be 
summarized.  Medical History will be presented by count and percentage of subjects 
broken down by Body System and Diagnosis.
8.1.4
Statistical Analysis of Efficacy
8.1.4.1
Analysis of Primary Efficacy Endpoint
The primary efficacy endpoint is the response rate of clinical disease activity at Week 32 
as measured by the percentage of subjects with ASDAS inactive disease (ASDAS < 1.3) 
in the two treatment arms. 
The null hypothesis states that there is no difference in response rates between the 
intensified T2T arm and the SOC arm; the alternative hypothesis is that the response rates 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
93
are different.  The response rates will be tested using a two-sided Pearson's chi-square test 
ZLWKĮ 7KH)LVKHU
VH[DFWWHVWZLOOEHDSSOLHGLIRIWKHFHOOVLQWKH
frequency table have expected counts less than 5. 
For subjects with missing data at Week 32 regarding the primary endpoint the imputation 
rules specified in Section 8.1.2 will be applied.
The ITT analysis will be considered as primary analysis. 
8.1.4.2
Analysis of Secondary Efficacy Endpoints
The null hypothesis for each secondary efficacy endpoint is that there is no difference 
between the intensified T2T arm and the SOC arm in the ITT analysis; the alternative 
hypothesis is that there are differences between the two treatment arms.  All statistical 
tests which will be performed for secondary endpoints are only of exploratory nature and 
no adjustment for multiple comparisons is planned.
Discrete variables will be summarized using count and percentages will be compared 
between the two treatment arms using Pearson's chi-square.  The Fisher's exact test will be 
applied instead of the chi-VTXDUHWHVWLIRIWKHFHOOVLQWKHIUHTXHQF\WDEOHKDYH
expected counts less than 5.
Continuous efficacy variables will be summarized by common statistics (number of 
subjects, mean, 95% confidence interval, standard deviation, first quartile, median, 
third quartile, minimum and maximum) at Baseline, post-baseline Time points and for 
change from Baseline to the post-baseline Time points.  The changes from Baseline to 
Week 52 in continuous variables will be compared between the treatment arms using an 
analysis of covariance method adjusting for the corresponding Baseline values and 
treatment arm as independent factor.  Least square mean values (LSMEAN) for the 
difference of the mean changes between the two treatment arms and corresponding 95% 
confidence intervals will be determined.  This will be done both for the observed and 
LOCF imputed values.  All further details will be specified in the SAP.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
94
8.1.4.3
Other Exploratory Analyses
Other exploratory analyses will be specified in the SAP. 
8.1.5
Pharmacokinetic Analyses
No pharmacokinetic investigations are planned.
8.1.6
Safety Analysis
Safety analyses will be carried out using the safety population, which include all subjects 
who were randomized and received treatment for axSpA after randomization.  
Treatment-emergent AEs and serious AEs (SAEs), which include pre- and post-treatment 
SAEs, will be summarized and reported, while pre-randomization AEs will be only listed.
Treatment-emergent AEs are defined as AEs that begin either on or after the Baseline 
Visit up to end of the study.  All AEs will be coded using the Medical Dictionary for Drug 
Regulatory Activities (MedDRA®).  The number and percent of subjects experiencing 
treatment emergent AEs will be tabulated by system organ class and preferred term.  In 
addition, a summary of treatment emergent AEs by severity and relationship to study drug 
will be presented.  AEs, which are serious, severe, or life-threatening, and those which 
lead to premature study discontinuation will be listed and described in detail.
Mean change in vital signs and laboratory variables at each visit as compared to Baseline 
will be summarized for all subjects in the safety population, and compared between 
treatment groups using a one way ANOVA.  The last evaluation on or before the Baseline 
Visit will be used as baseline for all analyses.  For selected parameters, a listing of all 
subjects with any laboratory determination meeting Common Toxicity Criteria (CTC) of 
Grade 3 or higher will be provided.  Shift tables for changes from Baseline according to 
the normal range will also be provided for laboratory variables.
8.1.7
Interim Analysis 
No interim analysis is planned for this study. 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
95
8.2
Determination of Sample Size
In the relevant RA strategy trials the drop-out rates were 3.6% after 2 years in the 
STREAM study,44 6.4% after 18 months in the TICORA study15 and 32.1% after 2 years 
in the CAMERA trial.14
In the RA T2T trials remission was reached in 50% (tight control) versus 37% (usual care) 
in the CAMERA trial (DMARD trial) after 2 years,14 in 31% versus 18% after 1 year in 
another trial,17 in 65% versus 16% in the TICORA trial after 18 months of follow-up 15
and in 55% (tight control) versus 30% (usual care) after 1 year (including the possibility 
to use TNF-blockers).16
In a recently performed trial (INFAST) 51.4% of patients with early axSpA who had a 
disease duration of < 3 years and who were not yet NSAID failures reached a status of 
ASDAS inactive disease during combination treatment with a TNF-blocker and an 
NSAID compared to 19.6% of patients who reached ASDAS inactive disease during 
NSAID treatment.9 This treatment in the INFAST trial comes closest to the T2T arm in 
the study proposed here. 
Data from the NOR-DMARD register, which is a Norwegian longitudinal observational 
study, including 212 patients with mean disease duration of 9.9 years, showed that 
ASDAS inactive disease was reached by 33.6% of patients after 3 months of treatment 
with a TNF-blocker in routine care.40
In the observational GESPIC cohort (Year 6) only 12.3% of patients with potentially full 
access to TNF-blocker therapy reached a status of ASDAS inactive disease. 
Based on the above discussed available data it is assumed that ASDAS inactive disease 
could be reached by 40% in the T2T group versus 20% in the control group.  In total 
2 × 90 evaluable patients are necessary to detect with 80% power an increase in ASDAS 
inactive disease at Week 32 from 20% in the SOC arm to 40% in the intensified T2T arm, 
if a two sided Fisher's exact test is applied.  If the Pearson chi-square test instead of the 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
96
Fisher's exact test can be applied (see Section 8.1.4.1), then only 2 × 83 patients are 
necessary.
Assuming that about 18% of the randomized subjects will drop out prior to Week 32 and 
has to be counted as non-responder the assumed ASDAS inactive disease rate will be 
diluted to 16.4% in the SOC arm and 32.8% in the intensified T2T arm.  The necessary 
sample size for this scenario (ITT population) is 2 × 109 subjects for the chi-square test 
and 2 × 119 subjects for the Fisher's exact test.  In summary, 2 × 120 subjects should be 
randomized. 
8.3
Randomization Methods
Subjects who meet the eligibility criteria (see Section 5.2) will be randomized in a 
1:1 ratio to the two treatment arms (intensified T2T or SOC).  Centralized permuted block 
randomization will be performed.
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
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.
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 International Conference on 
Harmonization (ICH) GCP and all other applicable regulatory requirements.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
97
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, 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 will
be reviewed and signed and dated by the subject, the person who administered the 
informed consent, and any other signatories according to local requirements.
A copy of the informed consent form will be given to the subject and the original will be 
placed in the subject's medical record.  An entry must also be made in the subject's dated 
source documents to confirm that informed consent was obtained prior to any 
study-related procedures and that the subject received a signed copy.
Information regarding 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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
98
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 
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 or physician may be 
considered source documentation:
BASDAI
BASMIlin
BASFI
MASES
Physician's Global Assessment of Disease Activity NRS
Patient's Global Assessment of Disease Activity NRS
Patient's Assessment of Nocturnal Back Pain NRS
Patient's Assessment of Disease Severity
Patient's Global Assessment of Disease Severity NRS
Patient's Global Assessment of Pain NRS
ASAS HI
EQ-5D
WPAI-axSpA
subject Dosing Diary Sheet
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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
99
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 EDC system provided by the technology vendor Amedon GmbH, 
Willy-Brandt-Allee 31 c, 23554 Lübeck, Germany.  The documentation related to the 
validation of the EDC system and study-specific eCRFs is available through the vendor, 
Amedon, and will be archived as required.
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.  All data entered into the 
eCRF will be supported by source documentation.
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.
Patient Reported Outcomes (PRO) data are collected directly onto paper source 
worksheets by the subjects.  The completion of these forms is verified by the site staff.  
The source worksheets will be entered into the EDC system by the site staff.
Amedon 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 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
100
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.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
An Investigator's Meeting will be held with AbbVie personnel, the investigators and their 
study coordinators and the Monitors for the study.  This meeting will include a detailed 
discussion of the scientific rational, protocol, performance of study procedures, eCRF and 
Subject Diary and log completion, Imaging requirement, 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. 
The CRO 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
Please refer to the Investigator site contract for specific information related to publication 
practices.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
101
AbbVie abides by the PhRMA Principles on Conduct of Clinical Trials and 
Communication of Clinical Trial results.  AbbVie's registrations and results disclosure 
adhere to all relevant state and federal laws.
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 
site and will not be retrieved by AbbVie.
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 Investigator and AbbVie.  
The Investigator must submit, maintain, and archive any records related to the study 
according to ICH GCP and all other applicable regulatory requirements.  If the 
Investigator is not able to retain the records, he/she must notify AbbVie 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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
103
15.0
Reference List
1.
Rudwaleit M, van der Heijde D, Landewe R, et al.  The development of 
Assessment of SpondyloArthritis international Society classification criteria for 
axial spondyloarthritis (part II):  validation and final selection.  Ann Rheum Dis.  
2009;68(6):777-83.
2.
Sieper J, van der Heijde D.  Review:  nonradiographic axial spondyloarthritis:  new 
definition of an old disease?  Arthritis Rheum.  2013;65(3):543-51.
3.
Braun J, van den Berg R, Baraliakos X, et al.  2010 update of the ASAS/EULAR 
recommendations for the management of ankylosing spondylitis.  Ann Rheum Dis.  
2011;70(6):896-904.
4.
Smolen JS, Aletaha D, Bijlsma JW, et al.  Treating rheumatoid arthritis to target:  
recommendations of an international task force.  Ann Rheum Dis.  
2010;69(4):631-7.
5.
Smolen JS, Braun J, Dougados M, et al.  Treating spondyloarthritis, including 
ankylosing spondylitis and psoriatic arthritis, to target:  recommendations of an 
international task force.  Ann Rheum Dis.  2014;73(1):6-16.
6.
Song IH, Poddubnyy DA, Rudwaleit M, et al.  Benefits and risks of ankylosing 
spondylitis treatment with nonsteroidal antiinflammatory drugs.  Arthritis Rheum.  
2008;58(4):929-38.
7.
Poddubnyy D, Rudwaleit M, Haibel H, et al.  Effect of non-steroidal 
anti-inflammatory drugs on radiographic spinal progression in patients with axial 
spondyloarthritis:  results from the German Spondyloarthritis Inception Cohort.  
Ann Rheum Dis.  2012;71(10):1616-22.
8.
Kroon F, Landewe R, Dougados M, et al.  Continuous NSAID use reverts the 
effects of inflammation on radiographic progression in patients with ankylosing 
spondylitis.  Ann Rheum Dis.  2012;71(10):1623-9.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
104
9.
Sieper J, Lenaerts J, Wollenhaupt J, et al.  Efficacy and safety of infliximab plus 
naproxen versus naproxen alone in patients with early, active axial 
spondyloarthritis:  results from the double-blind, placebo-controlled INFAST 
study, part 1.  Ann Rheum Dis.  2014;73(1):101-7.
10.
Dougados M, Paternotte S, Braun J, et al.  ASAS recommendations for collecting, 
analysing and reporting NSAID intake in clinical trials/epidemiological studies in 
axial spondyloarthritis.  Ann Rheum Dis.  2011;70:249-51.
11.
Haibel H, Rudwaleit M, Listing J, et al.  Efficacy of adalimumab in the treatment 
of axial spondylarthritis without radiographically defined sacroiliitis:  results of a 
twelve-week randomized, double-blind, placebo-controlled trial followed by an 
open-label extension up to week fifty-two.  Arthritis Rheum.  2008;58(7):1981-91.
12.
Barkham N, Keen HI, Coates LC, et al.  Clinical and imaging efficacy of 
infliximab in HLA-B27-Positive patients with magnetic resonance 
imaging-determined early sacroiliitis.  Arthritis Rheum.  2009;60(4):946-54.
13.
Song IH, Hermann K, Haibel H, et al.  Effects of etanercept versus sulfasalazine in 
early axial spondyloarthritis on active inflammatory lesions as detected by 
whole-body MRI (ESTHER):  a 48-week randomised controlled trial.  Ann Rheum 
Dis.  2011;70(4):590-6.
14.
Verstappen SM, Jacobs JW, van der Veen MJ, et al.  Intensive treatment with 
methotrexate in early rheumatoid arthritis: aiming for remission.  Computer 
Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label 
strategy trial).  Ann Rheum Dis.  2007;66(11):1443-9.
15.
Grigor C, Capell H, Stirling A, et al.  Effect of a treatment strategy of tight control 
for rheumatoid arthritis (the TICORA study):  a single-blind randomised controlled 
trial.  Lancet.  2004;364(9430):263-9.
16.
Schipper LG, Vermeer M, Kuper HH, et al.  A tight control treatment strategy 
aiming for remission in early rheumatoid arthritis is more effective than usual care 
treatment in daily clinical practice:  a study of two cohorts in the Dutch 
Rheumatoid Arthritis Monitoring registry.  Ann Rheum Dis.  2012;71(6):845-50.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
105
17.
Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Kerstens PJ, et al.  DAS-driven 
therapy versus routine care in patients with recent-onset active rheumatoid arthritis.  
Ann Rheum Dis.  2010;69(1):65-9.
18.
Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al.  Clinical and
radiographic outcomes of four different treatment strategies in patients with early 
rheumatoid arthritis (the BeSt study):  a randomized, controlled trial.  Arthritis 
Rheum.  2005;52(11):3381-90.
19.
Coates LC, Moverley AR, McParland L, et al.  Results of a randomised controlled 
trial comparing tight control of early psoriatic arthritis (TICOPA) with standard 
care:  tight control improves outcome.  Arthritis Rheum.  2013;65(10): S346.
20.
Coates LC, Moverley AR, McParland L, et al.  Effect of tight control of 
inflammation in early psoriatic arthritis (TICOPA):  a UK multicentre, open-label, 
randomised controlled trial.  Lancet.  2015;386(10012):2489-98.
21.
van der Heijde D, Sieper J, Maksymowych WP, et al.  Update of the international 
ASAS recommendations for the use of anti-TNF agents in patients with axial 
spondyloarthritis.  Ann Rheum Dis.  2011;70(6):905-8.
22.
Rudwaleit M, Listing J, Brandt J, et al.  Prediction of a major clinical response 
(BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis.  
Ann Rheum Dis.  2004;63(6):665-70.
23.
Sieper J, van der Heijde D, Dougados M, et al.  Efficacy and safety of adalimumab 
in patients with non-radiographic axial spondyloarthritis: results of a randomised 
placebo-controlled trial (ABILITY-1).  Ann Rheum Dis.  2013;72(6):815-22.
24.
Rudwaleit M, Claudepierre P, Wordsworth P, et al.  Effectiveness, safety, and 
predictors of good clinical response in 1250 patients treated with adalimumab for 
active ankylosing spondylitis.  J Rheumatol.  2009;36(4):801-8.
25.
Poddubnyy D, Rudwaleit M, Haibel H, et al.  Rates and predictors of radiographic 
sacroiliitis progression over 2 years in patients with axial spondyloarthritis.  Ann 
Rheum Dis.  2011;70(8):1369-74.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
106
26.
Poddubnyy D, Haibel H, Listing J, et al.  Baseline radiographic damage, elevated 
acute-phase reactant levels, and cigarette smoking status predict spinal 
radiographic progression in early axial spondylarthritis.  Arthritis Rheum.  
2012;64(5):1388-98.
27.
Lukas C, Landewe R, Sieper J, et al.  Development of an ASAS-endorsed disease 
activity score (ASDAS) in patients with ankylosing spondylitis.  Ann Rheum Dis.  
2009;68(1):18-24.
28.
van der Heijde D, Lie E, Kvien TK, et al; Assessment of SpondyloArthritis 
international Society (ASAS).  ASDAS, a highly discriminatory ASAS-endorsed 
disease activity score in patients with ankylosing spondylitis.  Ann Rheum Dis.  
2009;68(12):1811-8.
29.
Fernández-Espartero C, de Miguel E, Loza E, et al; ESPERANZA Study Group.  
Validity of the ankylosing spondylitis disease activity score (ASDAS) in patients 
with early spondyloarthritis from the Esperanza programme.  Ann Rheum Dis.  
2014;73(7):1350-5.
30.
Godfrin-Valnet M, Prati C, Puyraveau M, et al.  Evaluation of spondylarthritis 
activity by patients and physicians:  ASDAS, BASDAI, PASS, and flares in 
200 patients.  Joint Bone Spine.  2013;80(4):393-8.
31.
van der Heijde D, Braun J, Dougados M, et al.  Sensitivity and discriminatory 
ability of the Ankylosing Spondylitis Disease Activity Score in patients treated 
with etanercept or sulphasalazine in the ASCEND trial.  Rheumatology (Oxford).  
2012;51(10):1894-905.
32.
Machado PM, Landewé RB, van der Heijde DM.  Endorsement of definitions of 
disease activity states and improvement scores for the Ankylosing Spondylitis
Disease Activity Score:  results from OMERACT 10.  J Rheumatol.  
2011;38(7):1502-6.
33.
Machado P, Landewe R, Lie E, et al.  Ankylosing Spondylitis Disease Activity 
Score (ASDAS):  defining cut-off values for disease activity states and 
improvement scores.  Ann Rheum Dis.  2011;70(1):47-53.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
107
34.
van der Heijde D, Braun J, Dougados M, et al.  Sensitivity and discriminatory 
ability of the Ankylosing Spondylitis Disease Activity Score in patients treated 
with etanercept or sulphasalazine in the ASCEND trial.  Rheumatology (Oxford).  
2012;51(10):1894-905.  Epub 2012 Jul 06.
35.
Machado P1, Landewé RB, Braun J, et al.  MRI inflammation and its relation with 
measures of clinical disease activity and different treatment responses in patients 
with ankylosing spondylitis treated with a tumour necrosis factor inhibitor.  Ann 
Rheum Dis.  2012;71(12):2002-5.
36.
Wei JC.  Treat-to-target in spondyloarthritis:  implications for clinical trial designs.  
Drugs.  2014;74(10):1091-6.
37.
Song IH, Hermann KG, Haibel H, et al.  Consistently Good clinical response in 
patients with early axial spondyloarthritis after 3 years of continuous treatment 
with etanercept:  longterm data of the ESTHER trial.  J Rheumatol.  
2014;41(10):2034-40.
38.
Ramiro S, van der Heijde D, van Tubergen A, et al.  Higher disease activity leads 
to more structural damage in the spine in ankylosing spondylitis:  12-year 
longitudinal data from the OASIS cohort.  Ann Rheum Dis.  2014;73(8):1455-61.
39.
Vastesaeger N, Cruyssen BV, Mulero J, et al.  ASDAS high disease activity versus 
BASDAI elevation in patients with ankylosing spondylitis as selection criterion for 
anti-TNF therapy.  Reumatol Clin.  2014;10(4):204-9.
40.
Fagerli KM, Lie E, van der Heijde D, et al.  Selecting patients with ankylosing 
spondylitis for TNF inhibitor therapy:  comparison of ASDAS and BASDAI 
eligibility criteria.  Rheumatology (Oxford).  2012;51(8):1479-83.
41.
Rudwaleit M, Haibel H, Baraliakos X, et al.  The early disease stage in axial 
spondylarthritis:  results from the german spondyloarthritis inception cohort.  
Arthritis Rheum.  2009;60(3):717-27.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
108
42.
Molto A, Granger B, Wendling D, et al.  Brief report:  nonsteroidal 
antiinflammatory drug-sparing effect of tumor necrosis factor inhibitors in early 
axial spondyloarthritis:  results from the DESIR cohort.  Arthritis & Rheumatology.  
2015;67(9):2363-8.
43.
Kiltz U, Sieper J, Rudwaleit M, et al.  DGRh-S3-Leitlinie Axiale Spondyloarthritis 
inklusive Morbus Bechterew und Frühformen.  Z Rheumatol.  
2014;73 (Suppl 2):23-5.
44.
Diel R, Hauer B, Loddenkemper R, et al.  Empfehlungen für das
tuberkulosescreening vor Gabe von TNF-Į-Inhibitoren bei rheumatischen 
Erkrankungen.  Pneumologie.  2009;63(6):329-34.
45.
van Eijk IC, Nielen MM, van der Horst-Bruinsma I, et al.  Aggressive therapy in 
patients with early arthritis results in similar outcome compared with conventional 
care:  the STREAM randomized trial.  Rheumatology.  2012;51(4):686-94.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
109
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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
110
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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
111
Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Provided in a separate document

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
112
Appendix C.
Assessment of SpondyloArthritis International Society (ASAS) 
Axial Spondyloarthritis Criteria for Classification
,QVXEMHFWVZLWKPRQWKVEDFNSDLQADQGDJHDWRQVHW\HDUV
Sacroiliitis on imaging*
HLA-B27
plus
or
Plus
6S$IHDWXUH#
6S$IHDWXUH#
#
SpA features
Inflammatory back pain
Arthritis
Enthesitis (heel)
Uveitis
Dactylitis
Psoriasis
Crohn's Disease/Ulcerative colitis
Good response to NSAIDs
Family history for SpA
HLA-B27
Elevated CRP
*
Sacroiliitis on imaging:  active (acute) 
inflammation on MRI highly 
suggestive of sacroiliitis associated 
with SpA, or definite radiographic 
sacroiliitis according to modified New 
York criteria
^
Almost daily back pain.
Adapted from:  Rudwaleit M, van der Heijde D, Landewé R, et al.  The development of Assessment of 
SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (part II):  validation 
and final selection.  Ann Rheum Dis.  2009;68:777-83.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
113
Appendix D.
Features of Spondyloarthritis
SpA Feature
Definition
Inflammatory back pain (IBP)
IBP according to experts:  at least 4 out of 5 parameters present:  
1.  age at onset < 40 yrs; 2.  insidious onset; 3.  improvement with 
exercise; 4.  no improvement with rest; 5.  pain at night (with
improvement upon getting up)
Arthritis
Past or present active synovitis diagnosed by a physician
Enthesitis (heel)
Heel enthesitis:  past or present spontaneous pain or tenderness at 
examination of the site of the insertion of the Achilles tendon or plantar 
fascia at the calcaneus
Uveitis
Past or present uveitis anterior, confirmed by an ophthalmologist
Dactylitis
Past or present dactylitis, diagnosed by a physician
Inflammatory bowel disease
Past or present Crohn's disease or ulcerative colitis diagnosed by a 
gastroenterologist
Psoriasis
Past or present psoriasis (skin and/or nail lesions) diagnosed by a 
physician
Good response to NSAIDs
24 – 48 hours after a full dose of a NSAID the back pain is not present 
anymore or is much better
Family history for SpA
Presence in first-degree (mother, father, sisters, brothers, children) or 
second-degree (maternal and paternal grandparents, aunts, uncles, 
nieces, and nephews) relatives of any of the following:  a) ankylosing 
spondylitis, b) psoriasis, c) acute uveitis, d) reactive arthritis, 
e) inflammatory bowel disease
Elevated CRP
C-reactive protein concentration above upper normal limit in the 
presence of back pain; after exclusion of other causes for elevated CRP 
concentration
HLA-B27
Positive testing according to standard laboratory techniques
Sacroiliitis by MRI
Active inflammatory lesions of sacroiliac joints with definite bone 
marrow edema/osteitis, suggestive of sacroiliitis associated with 
spondyloarthritis as defined by ASAS
Adapted from:  Rudwaleit M, van der Heijde D, Landewé R, et al.  The development of Assessment of 
SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (part II):  validation 
and final selection.  Ann Rheum Dis.  2009;68:777-83.
Adapted from:  Dougados M, Braun J, Burgos Vargas R, et al.  ASAS recommendations for variables to be collected in 
clinical trials/epidemiological studies of spondyloarthritis.  Ann Rheum Dis.  2012;71(6):1103-4.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
114
Appendix E.
Ankylosing Spondylitis Disease Activity Score (ASDAS) Calculation
Parameters used for the ASDAS:
1.
Patient's assessment of total back pain 
2.
Patient global assessment of disease activity 
3.
Peripheral pain/swelling (BASDAI question 3)
4.
Duration of morning stiffness (BASDAI question 6)
5.
ESR in mm/hr
Calculation of ASDAS (for reference only; the eCRF will be programmed to calculate the 
ASDAS)
ASDASESR:  0.08 × total back pain + 0.110 × patient global + 0.09 × peripheral 
SDLQVZHOOLQJîGXUDWLRQRIPRUQLQJVWLIIQHVVî¥(65
References:
Machado P, Navarro-Compan V, Landewé R, et al.  Calculating the ankylosing 
spondylitis disease activity score if the conventional c-reactive protein level is below the 
limit of detection or if high-sensitivity c-reactive protein is used: an analysis in the DESIR 
cohort.  Arthritis Rheumatol.  2015;67(2):408-13.
Lukas C, Landewé R, Sieper J, et al; Assessment of SpondyloArthritis international 
Society.  Development of an ASAS endorsed disease activity score (ASDAS) in patients 
with ankylosing spondylitis.  Ann Rheum Dis.  2009;68:18-24.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68;ii1-ii44.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
115
Appendix F.
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 
Numerical Rating Scale (NRS)
Please mark the box which represents your answer to each question relating to the past 
week (i.e., 
)
1. How would you describe the overall level of fatigue/tiredness you have experienced?
0
1
2
3
4
5
6
7
8
9
10
none
very severe
2. How would you describe the overall level of AS neck, back or hip pain you have 
had?
0
1
2
3
4
5
6
7
8
9
10
none
very severe
3. How would you describe the overall level of pain/swelling in joints other than neck, 
back or hips you have had?  
0
1
2
3
4
5
6
7
8
9
10
none
very severe
4. How would you describe the overall level of discomfort you have had from any areas 
tender to touch or pressure?
0
1
2
3
4
5
6
7
8
9
10
none
very severe

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
116
5. How would you describe the overall level of morning stiffness you have had from the 
time you wake up?
0
1
2
3
4
5
6
7
8
9
10
none
very severe
6. How long does your morning stiffness last from the time you wake up?
0
1
2
3
4
5
6
7
8
9
10
0 hr
1
hr
2 or more 
hrs
Scoring of the BASDAI:
BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5 + Item 6)
2             2
The BASDAI Score has a maximum value of 10.
References:
Garrett S, Jenkinson T, Kennedy LG, et al.  A new approach to defining disease status in 
ankylosing spondylitis:  the Bath Ankylosing Spondylitis Disease Activity Index.  J 
Rheumatol.  1994;21:2286-91.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68;ii1-ii44.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
117
Appendix G.
Patient's Global Assessment of Disease Activity, Numerical Rating 
Scale (NRS)
Please place a mark in the box below to indicate disease activity (i.e., 
)
What is your overall assessment of your disease activity during the last week?
0
1
2
3
4
5
6
7
8
9
10
none
very severe
References:
van der Heijde D, Dougados M, Davis J, et al.  Assessment in Ankylosing Spondylitis 
International Working Group/Spondylitis Association of America recommendations for 
conducting clinical trials in ankylosing spondylitis.  Arthritis Rheum.  2005;52(2):386-94.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68;ii1-ii44.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
118
Appendix H.
Tender and Swollen Joint Counts
JOINT EVALUATION
Patient Right
Patient Left
JOINT 
(Mark Correct Answer)
0 = Absent 
1 = Present
9 = Replaced 
NA = No 
Assessment
0 = Absent 
1 = Present
9 = Replaced
NA = No 
Assessment
Pain/ 
Tenderness
Swelling
Joint
Pain/ 
Tenderness
Swelling
Joint
1. Temporomandibular
0
1
0
1
9
NA
0
1
0
1
9
NA
2. Sternoclavicular
0
1
0
1
9
NA
0
1
0
1
9
NA
3. Acromio-clavicular
0
1
0
1
9
NA
0
1
0
1
9
NA
4. Shoulder
0
1
0
1
9
NA
0
1
0
1
9
NA
5. Elbow
0
1
0
1
9
NA
0
1
0
1
9
NA
6. Wrist
0
1
0
1
9
NA
0
1
0
1
9
NA
7. Metacarpophalangeal I
0
1
0
1
9
NA
0
1
0
1
9
NA
8. Metacarpophalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
9. Metacarpophalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
10. Metacarpophalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA
11. Metacarpophalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA
12. Thumb Interphalangeal
0
1
0
1
9
NA
0
1
0
1
9
NA
13. Prox. Interphalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
14. Prox. Interphalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
15. Prox. Interphalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA
16. Prox. Interphalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA
17. Distal Interphalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
18. Distal Interphalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
19. Distal Interphalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA
20. Distal Interphalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA
21. Hip
0
1
-
-
9
NA
0
1
-
-
9
NA
22. Knee
0
1
0
1
9
NA
0
1
0
1
9
NA
23. Ankle
0
1
0
1
9
NA
0
1
0
1
9
NA
24. Tarsus
0
1
0
1
9
NA
0
1
0
1
9
NA
25. Metatarsophalangeal I
0
1
0
1
9
NA
0
1
0
1
9
NA
26. Metatarsophalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
27. Metatarsophalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
28. Metatarsophalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
119
JOINT EVALUATION
Patient Right
Patient Left
JOINT 
(Mark Correct Answer)
0 = Absent 
1 = Present
9 = Replaced 
NA = No 
Assessment
0 = Absent 
1 = Present
9 = Replaced
NA = No 
Assessment
Pain/ 
Tenderness
Swelling
Joint
Pain/ 
Tenderness
Swelling
Joint
29. Metatarsophalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA
30. Great Toe/Hallux
0
1
0
1
9
NA
0
1
0
1
9
NA
31. Interphalangeal II
0
1
0
1
9
NA
0
1
0
1
9
NA
32. Interphalangeal III
0
1
0
1
9
NA
0
1
0
1
9
NA
33. Interphalangeal IV
0
1
0
1
9
NA
0
1
0
1
9
NA
34. Interphalangeal V
0
1
0
1
9
NA
0
1
0
1
9
NA

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
120
Appendix I.
Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin)
1.
Lateral lumbar flexion:  patient stands with heels and buttocks touching the wall, 
knees straight, shoulders back, hands by the side.  The patient is then asked to bend 
to the right side as far as possible without lifting the left foot/heel or flexing the 
right knee, and maintaining a straight posture, with heels, buttocks, and shoulders 
against the wall.  The distance from the third fingertip to the floor when patient 
bends to the side, is subtracted from the distance when the patient stands upright.  
The maneuver is repeated on the left side.
Left exact measurement (cm)_______   Right exact measurement (cm)_______
2.
Tragus-to-wall distance:  maintain same starting position as above.  The distance 
between tragus of the ear and wall during maximal effort to draw the head back 
without raising the chin above its usually carrying level is measured on both sides 
to the nearest 0.1 cm, using a rigid ruler.  Ensure no cervical extension, rotation, 
rolation, flexion or side flexion occurs.
Left exact measurement (cm)_______   Right exact measurement (cm)_______
3.
Lumbar flexion (modified Schober):  set marks in upright position at the level of 
the spinous process of L5 (found as the first process below the projected line across 
the back at the level of the top iliac crest) and 10 cm above the first mark.  Measure 
distraction of the marks when the patient bends forward as far as possible, keeping 
the knees straight.
Exact measurement (cm)_______
4.
Intermalleolar distance:  patient supine on the floor or a wide plinth, with the knees 
straight and the feet pointing straight up.  Patient is asked to separate legs along the 
resting surface as far as possible.  Distance between medial malleoli is measured.
Exact measurement (cm)_______
Cervical rotation:  patient supine on plinth, head in neutral position, forehead 
horizontal (if necessary head on pillow or foam block to allow this, must be

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
121
documented for future reassessments).  Gravity goniometer placed centrally on the 
forehead.  Patient rotates head as far as possible, keeping shoulders still, ensure no 
neck flexion or side flexion occurs.  Rotational angled to the right and to the left is
measured.
If you do not have a gravity goniometer: patient sits with shoulders to the wall.  
Place goniometer to the wall above the patient's head.  Patient rotates head as 
described above.  Examiner aligns goniometer branch parallel to sagittal plane of
the head.
Left exact measurement (degrees)_____Right exact measurement (degrees)_____
Adapted from:  van der Heijde D, et al.  Proposal of a linear definition of the bath 
ankylosing spondylitis metrology index (BASMI) and comparison with the 2-step and 
10-step definitions.  Ann Rheum Dis.  2008;67;489-93.  Epub 2007 Aug 29.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
122
Appendix J.
Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
1st Costochondral joint left/right
7th Costochondral joint left/right
Posterior superior iliac spine left/right
Anterior superior iliac spine left/right
Iliac crest left/right
5th Lumbar spinous process
Proximal insertion of Achilles tendon left/right
Reference:
Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al.  Assessment of enthesitis in 
ankylosing spondylitis.  Ann Rheum Dis.  2003;62:127-32.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
123
Appendix K.
Bath Ankylosing Spondylitis Functional Index (BASFI), Numerical 
Rating Scale (NRS)
Please mark the box to indicate your level of ability with each of the following activities 
during the last week.  (i.e., 
)
(An aid is a piece of equipment which helps you to perform an action or movement)
1. Putting on your socks or tights without help or aids (e.g., sock aid).
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
2. Bending forward from the waist to pick up a pen from the floor without an aid.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
3. Reaching up to a high shelf without help or aids (e.g., helping hand).
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
4. Getting up out of an armless dining room chair without using your hands or any other 
help.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
124
5. Getting up off the floor without help from lying on your back.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
6. Standing unsupported for 10 minutes without discomfort.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
7. Climbing 12 – 15 steps without using a handrail or walking aid.  One foot at each step.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
8. Looking over your shoulder without turning your body.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
9. Doing physically demanding activities (e.g., physiotherapy exercises, gardening or 
sports).
0
1
2
3
4
5
6
7
8
9
10
easy
impossible

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
125
10. Doing a full days activities, whether it be at home or at work.
0
1
2
3
4
5
6
7
8
9
10
easy
impossible
References:
Calin A, Garrett S, Whitelock H, et al.  A new approach to defining functional ability in 
ankylosing spondylitis:  the development of the Bath Ankylosing Spondylitis Functional 
Index.  J Rheumatol.  1994;21:2281-5.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68:ii1-ii44.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
126
Appendix L.
Physician's Global Assessment of Disease Activity, Numerical 
Rating Scale (NRS)
Please mark box to indicate disease activity (independent of the patient's self assessment) 
(i.e., 
)
0
1
2
3
4
5
6
7
8
9
10
None
severe
References:
van der Heijde D, Dougados M, Davis J, et al.  Assessment in Ankylosing Spondylitis 
International Working Group/Spondylitis Association of America recommendations for 
conducting clinical trials in ankylosing spondylitis.  Arthritis Rheum.  2005;52(2):386-94.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68;ii1-ii44.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
127
Appendix M.
Patient's Assessment of Nocturnal Back Pain, Numerical Rating 
Scale (NRS)
Please place a mark in the box below to indicate your answer (i.e., 
)
What is the amount of back pain at night that you experienced during the last week?
0
1
2
3
4
5
6
7
8
9
10
No 
Pain
Most 
severe pain
References:
van der Heijde D, Dougados M, Davis J, et al.  Assessment in Ankylosing Spondylitis 
International Working Group/Spondylitis Association of America recommendations for 
conducting clinical trials in ankylosing spondylitis.  Arthritis Rheum.  2005;52(2):386-94.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68;ii1-ii44.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
128
Appendix N.
Patient's Assessment of Total Back Pain, Numerical Rating Scale 
(NRS)
Please place a mark in the box below to indicate your answer (i.e., 
)
What is the amount of back pain that you experienced at any time during the last week?
0
1
2
3
4
5
6
7
8
9
10
No 
Pain
Most 
severe pain
References:
van der Heijde D, Dougados M, Davis J, et al.  Assessment in Ankylosing Spondylitis 
International Working Group/Spondylitis Association of America recommendations for 
conducting clinical trials in ankylosing spondylitis.  Arthritis Rheum.  2005;52(2):386-94.
Sieper J, Rudwaleit M, Baraliakos X, et al.  The Assessment of SpondyloArthritis 
International Society (ASAS) handbook:  a guide to assess spondyloarthritis.  Ann Rheum 
Dis.  2009;68;ii1-ii44.  

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
129
Appendix O.
Patient's Global Assessment of Pain, Numerical Rating Scale (NRS)
Please place a mark in the box below to indicate your answer (i.e., 
)
How much pain have you had because of your condition during the last week?
0
1
2
3
4
5
6
7
8
9
10
No 
Pain
pain as bad 
as it could 
be

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
130
Appendix P.
Assessment of Spondyloarthritis International Society (ASAS) 
Health Index (HI)
Please answer all statements by placing one check mark per statement to indicate which 
response best applies to you at this moment in time taking into account your rheumatic 
disease (the term "rheumatic disease" contains all forms of spondyloarthritis including 
ankylosing spondylitis) 
1.
Pain sometimes disrupts my normal activities.
܆
I agree
܆
I do not agree
2.
I find it hard to stand for long.
܆
I agree
܆
I do not agree
3.
I have problems running.
܆
I agree
܆
I do not agree
4.
I have problems using toilet facilities.
܆
I agree
܆
I do not agree
5.
I am often exhausted.
܆
I agree
܆
I do not agree
6.
I am less motivated to do anything that requires physical effort.
܆
I agree
܆
I do not agree

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
131
7.
I have lost interest in sex.
܆I agree
܆I do not agree
8.
I have difficulty operating pedals in my car.
܆I agree
܆
I do not agree
9.
I am finding it hard to make contact with people.
܆
I agree
܆
I do not agree
10.
I am not able to walk outdoors on flat ground.
܆
I agree
܆
I do not agree
11.
I find it hard to concentrate.
܆
I agree
܆
I do not agree
12.
I am restricted in traveling because of my mobility.
܆
I agree
܆
I do not agree
13.
I often get frustrated.
܆
I agree
܆
I do not agree
14.
I find it difficult to wash my hair.
܆
I agree

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
132
܆I do not agree
15.
I have experienced financial changes because of my rheumatic disease.
܆
I agree
܆
I do not agree
16.
I sleep badly at night.
܆
I agree
܆
I do not agree
17.
I cannot overcome my difficulties.
܆
I agree
܆
I do not agree
Reference:
Kiltz U, van der Heijde D, Boonen A, et al.  Development of a health index in patients 
with ankylosing spondylitis (ASAS HI):  final result of a global initiative based on the 
ICF guided by ASAS.  Ann Rheum Dis.  2015;74:830-835.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
133
Appendix Q.
Work Productivity and Activity Impairment Questionnaire:  Axial 
Spondyloarthritis, V2.0 (Work Productivity and Activity 
Impairment [WPAI]:  Axial Spondyloarthritis)
The following questions ask about the effect of your axial spondyloarthritis on your 
ability to work and perform regular activities.  Please fill in the blanks or circle a number, 
as indicated.
1.
Are you currently employed (working for pay)? ____NO
____YES
If NO, check "NO" and skip to question 6.
The next questions are about the past seven days, not including today.
2.
During the past seven days, how many hours did you miss from work because of 
problems associated with your axial spondyloarthritis? Include hours you missed 
on sick days, times you went in late, left early, etc., because of your axial 
spondyloarthritis.  Do not include time you missed to participate in this study.
______HOURS
3.
During the past seven days, how many hours did you miss from work because of 
any other reason, such as vacation, holidays, time off to participate in this study?
______HOURS
4.
During the past seven days, how many hours did you actually work?
______HOURS (If "0," skip to question 6.)
5.
During the past seven days, how much did your axial spondyloarthritis affect your 
productivity while you were working?
Think about days you were limited in the amount or kind of work you could do, days you 
accomplished less than you would like, or days you could not do your work as carefully 

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
134
as usual.  If axial spondyloarthritis affected your work only a little, choose a low number.  
Choose a high number if axial spondyloarthritis affected your work a great deal.
Consider only how much axial spondyloarthritis
affected productivity while you were working.
Axial 
Spondyloarthritis 
had no effect on 
my work
Axial 
Spondyloarthritis 
completely 
prevented me 
from working
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
6.
During the past seven days, how much did your axial spondyloarthritis affect your 
ability to do your regular daily activities, other than work at a job?
By regular activities, we mean the usual activities you do, such as work around the house, 
shopping, childcare, exercising, studying, etc.  Think about times you were limited in the 
amount or kind of activities you could do and times you accomplished less than you would 
like.  If axial spondyloarthritis affected your activities only a little, choose a low number.  
Choose a high number if axial spondyloarthritis affected your activities a great deal. 
Consider only how much axial spondyloarthritis affected your ability 
to do your regular daily activities, other than work at a job.
Axial 
Spondyloarthritis 
had no effect on 
my daily 
activities
Axial 
Spondyloarthritis 
completely 
prevented me 
from doing my 
daily activities
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
Reference:  Reilly MC, Zbrozek AS, Dukes EM.  The validity and reproducibility of a 
work productivity and activity impairment instrument.  Pharmacoeconomics.  
1993;4(5):353-65.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
135
Appendix R.
European Quality of Life – 5 Dimension (EQ-5D) (United States 
[US] English Version)
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 
܆

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
136
Anxiety/Depression
I am not anxious or depressed 
܆
I am moderately anxious or depressed 
܆
I am extremely anxious or depressed 
܆

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
137
Reference:  McDowell I, Newell C.  The EuroQol Quality of Life Scale.  Measuring 
health:  a guide to rating scales and questionnaires.  2nd ed.  1996;9:480-3.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
138
Appendix S.
Berlin Magnetic Resonance Imaging (MRI) Score for the Spine and the Sacroiliac Joints
Grade 0
Grade 1
Grade 2
Grade 3
Sacroiliac joints
Active inflammation (BMO of quadrant 
area)
Absent
Up to 33% of the 
quadrant area
33% – 66%
> 66%
Erosions (per quadrant)
Absent
Minor (one to 
two erosions)
Moderate (three to 
five single erosions
Multiple (confluent 
erosions)
Fatty bone marrow deposition per quadrant
Absent
< 33%
33-– 66%
>66%
Sclerosis (per joint)
Absent
Present
--
--
Ankylosis (per joint)
Absent
Present
--
--
Spine
Active Inflammation (BMO of VU area)
Absent
< 33% of VU area
33% – 66%
> 66%
Erosions (% of the bone surface per VU)
Absent
present
Fatty bone marrow deposition per VU
Absent
< 33%
33% – 66%
> 66%
Bone proliferation (per VU)
Absent
Syndesmophytes
without bridging
Bridging 
syndesmophytes
Transdiscal ankylosis
Activity in facet joints (right and/or left)
Absent
present
--
Activity in Proc. spinosus
Absent
present
Activity of soft tissue in posterior spinal 
sites
Absent
present
BMO = bone marrow edema; VU = vertebral unit
Reference:  Althoff CE, Sieper J, Song IH, et al.  Active inflammation and structural change in early active axial spondyloarthritis as detected by whole-body MRI.  Ann Rheum 
Dis.  2013;72:967-73.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
139
Appendix T.
70-Day Follow-Up Call – Sample
Site Name/Number:  ________
Subject Number:  ________
Please contact subjects who discontinued fromadalimumab therapy 70 days following the 
end of Treatment period (Week 52) or 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
܆
NA – subject continued adalimumab therapy after the end of their study participation.
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject 
was last seen in clinic for this study.  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.)
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:
[Name] at XXX-XXX-XXXX

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
140
Appendix U.
Injection Instructions – Sample Pre-Filled Syringe
Instruction for subjects of the T2T arm escalated to Treatment Escalation step 2.
Subject Instructions
0.8 mL dose
(Administered as a single dose-pre-filled syringe)
Protocol W15-679
Tables of Contents
Dosing Schedule
General Information & Supplies
Injection Procedures

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
141
Study Drug Dosing Schedule
Subject Number:  _____________________________________
You will require SC injections probably for the rest of the study.  From now, you will 
receive a kit each visit containing 2 syringes.
When starting SC injections (at the first visit to receive study medication for this study) 
you will administer 1 injection at the clinic to allow site staff to view your injection 
technique.   
Thereafter you will administer 1 injection at home every other week until the end of the 
study.  Note on clinic days, you must inject study drug after all study procedures are 
performed (not prior).
You will not administer study medication at your last visit.
Please return all used and unused syringes, the sharps container 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 with study medication will be labeled "Adalimumab."
Store all pre-filled syringes in your refrigerator at 2° to 8°C in the original container until 
it is used.  NOT in the freezer.  Should the syringes accidentally become frozen, call your 
study doctor's office.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
142
Protect the study medication from light.
When traveling, study medication should be stored in a cool carrier with an ice pack.
Do not use a prefilled syringe if the liquid is cloudy, discolored, or has flakes or particles 
in it.
Do not drop or crush the study medication.  The prefilled syringe is glass.
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.
Keep study medication, injection supplies, and all other medicines out of the reach of 
children.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
143
Injection Procedures (PFS)
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 prefilled syringe(s) of study drug from the refrigerator.  Do not use a 
prefilled 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
alcohol prep(s) or swab(s)
cotton ball(s) or gauze pad(s)
puncture-proof sharps container for prefilled syringe disposal
The diagram below shows what a prefilled syringe looks like.  See Figure A.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
144
Figure A. 
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 study drug comes in.
Do not use and call your study doctor if:
the seals on top and bottom of the carton are broken or missing.
the study medication labeling has an expired date.  Check the expiration date on your 
study medication carton and do not use if the date has passed.
the prefilled syringe has been frozen or left in direct sunlight.
the liquid in the prefilled syringe is cloudy, discolored or has flakes or particles in it.  
Make sure the liquid is clear and colorless.
For your protection, it is important that you follow these instructions.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
145
2. Choosing and preparing an injection site
Wash and dry your hands well
Choose an injection site:
Ɣ
on the front of your thighs or
Ɣ
your lower abdomen (belly). If you choose your abdomen, you should avoid 
the area 2 inches around your belly button (navel). See Figure B.
Figure B.
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.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
146
Do not inject into skin that is:
Ɣ
sore (tender)
Ɣ
bruised
Ɣ
red
Ɣ
hard
Ɣ
scarred or where you have stretch marks
If you have psoriasis, you should try not to inject directly into any raised, thick, red or 
scaly skin patches or lesions on your skin.
You may find it helpful to keep notes on the location of your injection sites.
Do not inject through your clothes.
Wipe the injection site with an alcohol prep (swab) using a circular motion.
Do not touch this area again before giving the injection.  Allow the skin to dry before 
injecting.  Do not fan or blow on the clean area.
3. How to prepare your study drug dose for injection with a Prefilled Syringe
Check the fluid level in the syringe:
Ɣ
Always hold the prefilled syringe by the body of the syringe. Hold the syringe 
with the covered needle pointing down. See Figure C.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
147
Figure C.
Hold the syringe at eye level.  Look closely to make sure that the amount of liquid in the 
syringe is the same or close to the 0.8 mL line for the 40 mg prefilled syringe.  See 
Figure D.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
148
Figure D.
The top of the liquid may be curved.  If the syringe does not have the correct amount of 
liquid, do not use that syringe.  Call your study doctor.
Remove the needle cover:
Ɣ
Hold the syringe in one hand. With the other hand gently remove the needle 
cover. See Figure E.
Ɣ
Throw away the needle cover.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
149
Figure E.
Do not touch the needle with your fingers or let the needle touch anything.
Turn the syringe so the needle is facing up and hold the syringe at eye level with one hand 
so you can see the air in the syringe.  Using your other hand, slowly push the plunger in to 
push the air out through the needle.  See Figure F.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
150
Figure F.
You may see a drop of liquid at the end of the needle.  This is normal.
Do not shake the syringe.
4. Injecting Study Drug
Hold the body of the prefilled syringe in one hand between the thumb and index fingers.  
Hold the syringe in your hand like a pencil.  See Figure G.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
151
Figure G.
Do not pull back on the plunger at any time.
With your other hand, gently squeeze an area of the cleaned area of skin and hold it 
firmly.  See Figure H.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
152
Figure H.
Using a quick, dart-like motion, insert the needle into the squeezed skin at about a 
45-degree angle.  See Figure I.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
153
Figure I.
After the needle is in, let go of the skin.  Pull back gently on the plunger.
If blood appears in the syringe:
It means that you have entered a blood vessel.
Do not inject study drug.
Pull the needle out of the skin while keeping the syringe at the same angle.
Press a cotton ball or gauze pad over the injection site and hold it for 10 seconds.  See 
Figure J.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
154
Figure J.
Do not use the same syringe and needle again.  Throw away the needle and syringe in 
your special sharps container.
Do not rub the injection site.  You may have slight bleeding.  This is normal.
Repeat Steps 1 through 12 with a new prefilled syringe.
If no blood appears in the syringe:
Slowly push the plunger all the way in until all of the liquid is injected and the syringe is 
empty.
Pull the needle out of the skin while keeping the syringe at the same angle.
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.  See Figure K.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
155
Do not throw the needle, or syringe, in the household trash.  Do not recycle.
Do not try to touch the needle.
Figure K.
For the safety and health of you and others, needles and used syringes must never be 
re-used.
Always keep the sharps container out of the reach of children.
The used alcohol pads, cotton balls, dose trays and packaging may be placed in your 
household trash.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
156
When you go to your study visit tape the cap or lid of the sharps container down so it does 
not come off and take it to your visit.  Do not throw the container in the household 
trash. Do not recycle.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
157
Appendix V.
Subject Dosing Diary Sheet (Sample)
To be completed for every study dose administered.  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, kit number, dose administered, 
injection location, initials of person administering study medication, 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.
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):
Subject Study Number:  _____________
Date 
day/mm/yr
Day or 
Week
Time of Study 
Drug 
Administrationa
Kit 
Numbername
Dose (mL) 
Administered
Injection 
Site 
(Abdomen 
or Thigh)
Initials of 
Person 
Administering 
Study 
Medication
Comments
31/MAY/16
EXAMPLE
09:30 hrs
123456
0.8 mL
abdomen
PG
Clinic 
injection
First 
injection
_ _:_ _  hrs
2 weeks 
after 1st
injection
_ _:_ _  hrs
4 weeks 
after 1st
injection
_ _:_ _  hrs
6 weeks 
after 1st
injection
_ _:_ _  hrs
8 weeks 
after 1st
injection
_ _:_ _  hrs

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
158
Date 
day/mm/yr
Day or 
Week
Time of Study 
Drug 
Administrationa
Kit 
Numbername
Dose (mL) 
Administered
Injection 
Site 
(Abdomen 
or Thigh)
Initials of 
Person 
Administering 
Study 
Medication
Comments
10 weeks 
after 1st
injection
_ _:_ _  hrs
12 weeks 
after 1st
injection
_ _:_ _  hrs
14 weeks 
after 1st
injection
_ _:_ _  hrs
16 weeks 
after 1st
injection
_ _:_ _  hrs
18 weeks 
after 1st
injection
_ _:_ _  hrs
20 weeks 
after 1st
injection
_ _:_ _  hrs
22 weeks 
after 1st
injection
_ _:_ _  hrs
24 weeks 
after 1st
injection
_ _:_ _  hrs
26 weeks 
after 1st
injection
_ _:_ _  hrs
28 weeks 
after 1st
injection
_ _:_ _  hrs
30 weeks 
after 1st
injection
_ _:_ _  hrs
32 weeks 
after 1st
injection
_ _:_ _  hrs
34 weeks 
after 1st
injection
_ _:_ _  hrs

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
159
Date 
day/mm/yr
Day or 
Week
Time of Study 
Drug 
Administrationa
Kit 
Numbername
Dose (mL) 
Administered
Injection 
Site 
(Abdomen 
or Thigh)
Initials of 
Person 
Administering 
Study 
Medication
Comments
36 weeks 
after 1st
injection
_ _:_ _  hrs
38 weeks 
after 1st
injection
_ _:_ _  hrs
40 weeks 
after 1st
injection
_ _:_ _  hrs
42 weeks 
after 1st
injection
_ _:_ _  hrs
44 weeks 
after 1st
injection
_ _:_ _  hrs
46 weeks 
after 1st
injection
_ _:_ _  hrs
48 weeks 
after 1st
injection
_ _:_ _  hrs
a.
Please note the time as full hours (24 hours scale) and minutes (e.g., 22:00 hrs etc.).

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
160
Appendix W.
Subject NSAID Dosing Diary Sheet (Sample)
To be completed for every medication, other than study drug, administered as defined for 
T2T-Group.  Please record the date of drug administration, dose administered, and any 
comments.
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
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
161
Subject Study Number:  _____________
Date 
day/mm/yr
NSAID name
Dose (mg) taken
Comments
31/MAY/16
Diclofenac
100 mg

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
162
Appendix X.
Nonsteroidal Anti-Inflammatory Drug (NSAID) Intake Score
When the exact number of days with NSAID intake is not known (usually when the interval of time between two visits 
exceeds 2 weeks), it is recommended to refer to the semiquantitative estimation.  In this case, a score of 7/7 is proposed 
IRUWKHDQVZHU
HYHU\GD\
IRU!GD\VZHHNIRU!WRGD\VZHHNIRU!WRGD\VZHHNIRU
 3 days/week and 0 if the patient did not take any NSAID during the period of interest.
Reference:  Dougados M, Paternotte S, Braun J et al.  ASAS recommendations for 
collecting, analyzing and reporting NSAID intake in clinical trials/epidemiological 
stusdies in axial spondyloarthritis.  Ann Rheum Dis.  2011;70:249-51.

Adalimumab
W15-679 Protocol Amendment 2
EudraCT 2015-005398-18
163
Appendix Y.
Recommended Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) to 
Treat Axial Spondyloarthritis
Reference:  Song IH, Poddubnyy DA, Rudwaleit M, et al.  Benefits and risks of 
ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs.  Ann Rheum 
Dis.  2008;58:929-38.