A Phase 2a Study to Evaluate the Safety and Efficacy of Namilumab in Subjects With Moderate-to-severely Active Axial Spondyloarthritis
Phase: PHASE2
Conditions: Axial Spondyloarthritis
Sponsor: Izana Bioscience Ltd.

 
 
 
 
 
Study Number: IZN-101 
 
 
Study Title: A Phase 2a Proof of Concept, Randomised, Double-Blind, Placebo-Controlled Study 
to Evaluate the Safety/Tolerability and Efficacy of 4 Subcutaneous Injections of Namilumab 
(150mg) Given Over 10 weeks in Subjects with Moderate-To-Severely Active Axial 
Spondyloarthritis Including Those Previously Exposed to Anti-TNF Therapy (NAMASTE 
Study) 
 
 
 
Clinical Study Protocol 
 
 
Amendment 2, FINAL 05 July 2018 
NCT03622658 

CONFIDENTIAL 
Protocol IZN-101 -Amendment 2 
Final, 05 Jul 2018 
Page I of78 
 
 
 
TITLE PAGE 
Protocol Title: A phase 2a proof of concept, randomised, double-blind, placebo-controlled study to 
evaluate the safety/tolerability and efficacy of 4 subcutaneous injections of namilumab (I 50 mg) given 
over 10 weeks in subjects with moderate-to-severely active axial spondyloaitlnitis including those 
previously exposed to anti-TNF therapy (NAMASTE study) 
Protocol Number: IZN-101 
Amendment Number: 2 
Product: Namilumab 
Short Title: Efficacy and safety of namilumab for moderate-to-severe axial spondyloaitlnitis 
Study Phase: 2a 
Sponsor Name: Izana Bioscience Limited 
Legal Registered Address: 
Orchai·d Frum, Wootton Village, Boai·s Hill 
Oxford, OXl 5HW 
United Kingdom 
Tel: +44 1865 686090 
 
Regulatory Agency Identifying Number(s): 
IND number: Not applicable 
EudraCT number: 2018-000176-15 
 
Date of Protocol: Final, 05 Jul 2018 

CONFIDENTIAL 
Protocol IZN-101 -Amendment 2 
Final, 05 Jul 2018 
Page 2 of 78 
 
 
Sponsor Signatory: 
 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Coordinating Investigator: 
 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
 
911Jully2018 
 
Date 
 
 
 
 
 
 
 
Medical Monitor name and contact information can be found in Appendix 2. 

CONFIDENTIAL 
Protocol IZN-101 -Amendment 2 
Final, 05 Jul 2018 
Page 3 of 78 
 
 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Table 1 
Document History 
 
Document 
Date 
Substantial 
Region 
Amendment 2 
05 Jul 2018 
No 
Global 
Amendment 1 
04 May 2018 
Yes 
Global 
Original Protocol 
16 Feb 2018 
- 
- 
 
Amendment 2 (05 Jul 2018) 
 
This amendment is considered to be non-substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
The protocol was amended to include a review of the safety data by a Safety Review Team, 
revise the number of Investigators and study centres from 8 to 10, and to clarify or correct 
several inconsistencies and editorial errors. 

CONFIDENTIAL 
Protocol IZN-101 -Amendment 2 
Final, 05 Jul 2018 
Page 4 of 78 
 
 
Table 2 
Description of Changes in Amendment 
Section # 
Description of Change 
Brief Rationale 
 
1.1 
 
Number of Investigators and study centres updated 
from 8 to 10. 
Revised for increase in number of 
participating Investigators and 
study centres. 
1.1 , 9.6 
Safety Review Team added to review safety data. 
Revised per input from Ethics 
Committee. 
1.2 
Screening Period in Figure 1 revised from “Up to 
28 weeks” to “Up to 28 days”. 
 
Corrected an error in the figure. 
4.2.1, 5.1/Inclusion 
criterion #9, 6.5 
 
5.1 /Inclusion criteria 
Changed “and” to “or” for stable doses of MTX, 
sulfasalazine or leflunomide. 
Revised for clarity and accuracy. 
Revised to include links to the list 
#8, 9, and 10 
Added references and links to Appendix 5. 
of excluded medications and 
treatments in the appendix. 
5.2 /Exclusion 
criterion #4 
 
 
6.5 
 
 
 
8.1 
Revised exclusion of intra-articular corticosteroids 
to during the Screening Period. 
Revised permitted use of stable non-steroidal anti- 
inflammatory drugs (NSAIDs) and COX-2 to 
within 28 days prior to randomisation and during 
the study; revised permitted use of stable oral 
corticosteroids (≤ 10 mg) to 28 days prior to 
Baseline, not Screening. 
Basis of subject’s overall assessment of the 
severity of spinal pain revised to single question 
on VAS. 
 
Revised for clarity and accuracy. 
 
 
Revised for consistency with 
Appendix 5. 
 
 
Revised to correct an error in 
number of questions. 
 
Removed to lessen the burden on 
8.2.4.2 
Lateral chest x-ray deleted. 
 
Appendix 5 
Revised excluded oral corticosteroids to within 28 
days prior to Baseline, not Screening. 
Appendix 8 
Added new appendix for protocol amendment 
history. 
Throughout 
Minor editorial and document formatting 
revisions. 
subjects as in the experts’ opinions 
this procedure is not required. 
Revised for consistency with 
inclusion/ exclusion criteria. 
Revised per protocol template to 
include previous amendments. 
 
Editorial updates and corrections. 
Title Page, page 
headers and footers, 
Protocol Amendment 
Summary, Table 1, 
Table 2, Appendix 9 
 
 
Updated amendment number, date, and changes 
made with current amendment. 
 
 
Revised to include changes 
included with current amendment. 

CONFIDENTIAL 
Protocol IZN-101 -Amendment 2 
Final, 05 Jul 2018 
Page 5 of 78 
 
 
 
TABLE OF CONTENTS 
TABLE OF TABLES .............................................................................................................. 8 
TABLE OF FIGURES ............................................................................................................ 9 
1.0 
PROTOCOL SUMMARY ....................................................................................... 10 
1.1 
Synopsis .......................................................................................................... 10 
1.2 
Study Schema ................................................................................................ 12 
1.3 
Schedule of Activities .................................................................................... 13 
2.0 
INTRODUCTION ..................................................................................................... 16 
2.1 
Study Rationale ............................................................................................. 16 
2.2 
Background ................................................................................................... 16 
2.3 
Benefit/Risk Assessment ............................................................................... 18 
3.0 
OBJECTIVES AND ENDPOINTS ......................................................................... 19 
4.0 
STUDY DESIGN ....................................................................................................... 21 
4.1 
Overall Design ............................................................................................... 21 
4.2 
Scientific Rationale for Study Design .......................................................... 21 
4.2.1 
Subject Population Studied (Defined    by    Demography, 
Disease and/or Treatment Characteristics) ....................................... 21 
4.2.2 
Justification for Design and Sample Size ......................................... 22 
4.2.3 
Justification of Control Group .......................................................... 22 
4.2.4 
Justification for Route,  Dose Regimen, Treatment Period, 
with Reference to Previous Exposure, PK/PD Profile and 
Non-clinical Safety ........................................................................... 22 
4.2.5 
Justification for Primary Endpoints .................................................. 23 
4.3 
Justification for Dose .................................................................................... 23 
4.4 
End of Study Definition ................................................................................ 23 
5.0 
STUDY POPULATION ........................................................................................... 24 
5.1 
Inclusion Criteria .......................................................................................... 24 
5.2 
Exclusion Criteria ......................................................................................... 25 
5.3 
Lifestyle Considerations ............................................................................... 27 
5.4 
Screen Failures ...............................................................................................27 
6.0 
STUDY TREATMENT ............................................................................................ 28 
6.1 
Study Treatment(s) Administered ............................................................... 28 
6.2 
Preparation/Handling/Storage/Accountability .......................................... 28 
6.2.1 
Preparation ........................................................................................ 28 
6.2.2 
Handling ........................................................................................... 28 

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6.2.3 
Storage .............................................................................................. 28 
6.3 
Measures to Minimise Bias: Randomisation and Blinding ....................... 29 
6.3.1 
Investigational Drug Assignment and Dispensing Procedures ......... 29 
6.3.2 
Randomisation Code Creation and Storage ...................................... 30 
6.3.3 
Investigational Drug Blind Maintenance .......................................... 30 
6.3.4 
Unblinding Procedure ....................................................................... 30 
6.3.5 
Accountability and Destruction of Sponsor-Supplied Drugs ........... 30 
6.4 
Study Treatment Compliance ...................................................................... 31 
6.5 
Concomitant Therapy ................................................................................... 32 
6.6 
Dose Modification ..........................................................................................32 
6.7 
Treatment after the End of the Study ......................................................... 32 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ............................................................... 33 
7.1 
Discontinuation of Study Treatment ........................................................... 33 
7.2 
Subject Discontinuation/Withdrawal from the Study ............................... 34 
7.3 
Lost to Follow-up .......................................................................................... 34 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 35 
8.1 
Efficacy Assessments .................................................................................... 35 
8.2 
Safety Assessments ........................................................................................ 37 
8.2.1 
Physical Examinations ...................................................................... 38 
8.2.2 
Vital Signs ........................................................................................ 38 
8.2.3 
Electrocardiograms ........................................................................... 38 
8.2.4 
Target-specific Safety Evaluation:   Pulmonary   Alveolar 
Proteinosis ........................................................................................ 38 
8.2.5 
Pulmonary Alveolar Proteinosis ....................................................... 39 
8.2.6 
Documentation of Concomitant Medications ................................... 40 
8.2.7 
Documentation of Concurrent Medical Conditions .......................... 40 
8.2.8 
Clinical Safety Laboratory Assessments .......................................... 40 
8.3 
Adverse Events .............................................................................................. 41 
8.3.1 
Time Period and Frequency for Collecting AE and SAE 
Information ....................................................................................... 41 
8.3.2 
Method of Detecting AEs and SAEs ................................................ 42 
8.3.3 
Follow-up of AEs and SAEs ............................................................ 42 
8.3.4 
Regulatory Reporting Requirements for SAEs ................................. 42 
8.3.5 
Pregnancy ......................................................................................... 43 
8.3.6 
Adverse Events of Special Interest ................................................... 43 
8.4 
Treatment of Overdose ..................................................................................44 
8.5 
Pharmacokinetics .......................................................................................... 44 
8.6 
Pharmacodynamics ....................................................................................... 44 
8.7 
Genetics .......................................................................................................... 44 
8.8 
Biomarkers .................................................................................................... 44 
8.8.1 
Immunogenicity Assessments .......................................................... 45 
8.9 
Medical Resource Utilisation and Health Economics ................................ 45 

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9.0 
STATISTICAL CONSIDERATIONS .................................................................... 46 
9.1 
Statistical Hypotheses ................................................................................... 46 
9.2 
Sample Size Determination .......................................................................... 49 
9.3 
Populations for Analyses .............................................................................. 51 
9.4 
Statistical Analyses ........................................................................................ 51 
9.4.1 
Efficacy Analyses ............................................................................. 51 
9.4.2 
Safety Analyses ................................................................................ 52 
9.4.3 
Other Analyses ................................................................................. 53 
9.4.4 
Missing Data ..................................................................................... 53 
9.5 
Interim Analyses ........................................................................................... 53 
9.6 
Safety Review Team ...................................................................................... 53 
10.0 
REFERENCES .......................................................................................................... 54 
11.0 
APPENDICES ........................................................................................................... 57 
Appendix 1 
Abbreviations .................................................................................. 58 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations ......... 61 
Regulatory and Ethical Considerations ........................................................... 61 
Financial Disclosure ........................................................................................ 61 
Insurance ......................................................................................................... 62 
Informed Consent Process .............................................................................. 62 
Data Protection ................................................................................................ 62 
Administrative Structure ................................................................................. 63 
Medical Monitor ............................................................................................. 63 
Dissemination of Clinical Study Data ............................................................. 64 
Data Quality Assurance .................................................................................. 64 
Source Documents .......................................................................................... 64 
Study and Study Centre Closure ..................................................................... 65 
Publication Policy ........................................................................................... 65 
Appendix 3 
Clinical Laboratory Tests .............................................................. 66 
Appendix 4 
Adverse 
Events: 
Definitions 
and 
Procedures for 
Recording, Evaluating, Follow-up, and Reporting .................................... 68 
Appendix 5 
Excluded Medications/Therapy ..................................................... 72 
Appendix 6 
Management of Respiratory Signs   and   Symptoms   in 
Relation to PAP Disease Background ......................................................... 74 
Appendix 7 
Contraception and Pregnancy Avoidance Procedure ................. 75 
Appendix 8 
Protocol Amendment History ........................................................ 77 
Appendix 9 
Signature of Investigator ................................................................ 78 

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Final, 05 Jul 2018 
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TABLE OF TABLES 
Table 1 
Document History ............................................................................................. 3 
Table 2 
Description of Changes in Amendment ............................................................ 4 
Table 3 
Schedule of Activities ..................................................................................... 13 
Table 4 
Study Objectives and Endpoints ..................................................................... 19 
Table 5 
Study Treatment Details ................................................................................. 28 
Table 6 
MRC Breathlessness Scale ............................................................................. 38 
Table 7 
Reported ASAS20   Results   for   Placebo   Treatment   Group   for 
Reference Studies ............................................................................................ 47 
Table 8 
Reported ASAS20 Results for Active Treatment Group for Reference 
Studies ............................................................................................................. 49 
Table 9 
Sample Sizes for 6:1 Randomisation, Based on the Parameter γ .................... 49 
Table 10 
Analysis Sets ................................................................................................... 51 
Table 11 
Efficacy Analyses ........................................................................................... 52 
Table 12 
Study Administrative Structure ....................................................................... 63 
Table 13 
Protocol Required Safety Laboratory Assessments ........................................ 66 
Table 14 
Description of Changes in Amendment 1 ....................................................... 77 

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TABLE OF FIGURES 
Figure 1 
Study Schema .................................................................................................. 12 
Figure 2 
Estimated ASAS20 and 95% Confidence   Intervals   for   Placebo 
Treatment Group Data .................................................................................... 47 
Figure 3 
Estimated ASAS20 and 95%   Confidence   Intervals   for   Active 
Treatment Group Data .................................................................................... 48 
Figure 4 
Distribution of Posterior Probability P(θact > θpbo) as a Function of 
Total Sample Size, Under Both Hypotheses ................................................... 50 

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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A phase 2a proof of concept, randomised, double-blind, placebo-controlled study to 
evaluate the safety/tolerability and efficacy of 4 subcutaneous injections of namilumab (150 mg) given 
over 10 weeks in subjects with moderate-to-severely active axial spondyloarthritis including those 
previously exposed to anti-TNF (tumour necrosis factor) therapy. (NAMASTE study) 
Short Title: Efficacy and safety of namilumab for moderate-to-severe axial spondyloarthritis 
Rationale: 
The purpose of this study is to assess the effect of namilumab, a granulocyte-macrophage colony- 
stimulating factor (GM-CSF) inhibitor, on the clinical response in subjects with axial spondyloarthritis 
(axSpA). Current treatment options, including non-steroidal anti-inflammatory drugs (NSAIDs), tumour 
necrosis factor inhibitors (TNFi) and interleukin (IL)-17 inhibitors, do not provide clinical response for 
many patients (see Section 2.2) and new treatment options are needed. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
• 
To assess the efficacy of namilumab 150 mg 
subcutaneous (sc), given on Weeks 0, 2, 6 and 10 
in subjects with axSpA 
• 
Proportion of subjects who achieve an ASAS20 
clinical response at Week 12 
Secondary 
• 
To assess the efficacy of namilumab 150 mg sc, 
given on Weeks 0, 2, 6 and 10 on other clinical 
responses in subjects with axSpA 
• 
Proportion of subjects who achieve ASAS40 and 
ASAS70 response at Week 12 
• 
Proportion of subjects who achieve an ASAS20 
clinical response at Week 6 
• 
Proportion of subjects who achieve ASDAS-CRP 
response at Weeks 6 and 12 
• 
To assess the safety and tolerability 
of 
namilumab 150 mg sc, given on Weeks 0, 2, 6 
and 10 in subjects with axial spondyloarthritis 
• 
Adverse events (AEs) 
• 
Serious adverse events (SAEs) 
• 
Laboratory evaluations 
• 
Vital signs 
• 
Electrocardiograms (ECGs) 
• 
Physical examinations 
• 
Assessments of pulmonary function 
o 
MRC breathlessness scale 
o 
Chest x-ray 
o 
Lung function tests 
o 
Pulse oximetry 
• 
Immunogenicity 
• 
AEs of special interest: 
o 
Pulmonary alveolar proteinosis (PAP) 
o 
Neutropaenia 
o 
Myeloid suppression 

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Exploratory 
• 
To assess the efficacy of namilumab 150 mg sc, 
given on Weeks 0, 2, 6 and 10 on radiologic 
responses in subjects with axial spondyloarthritis 
• 
To assess the effect of namilumab 150 mg sc, 
given on Weeks 0, 2, 6 and 10 on other clinical 
responses, biomarkers, immunophenotyping, and 
pain 
scores 
in 
subjects 
with 
axial 
spondyloarthritis 
• 
Proportion of subjects who show a radiological 
response on MRI at 12 weeks 
• 
Proportion of subjects who achieve ASAS20 
clinical response at Weeks 2 and 10 
• 
Proportion of subjects who achieve ASDAS-CRP 
response at Weeks 2 and 10 
• 
Joint count, tendon swelling, and enthesitis at 
Weeks 2, 6, 10, and 12 
• 
Serum 
biomarkers 
including 
CRP, 
faecal 
biomarkers including calprotectin and microbiome 
• 
Pre- and post-treatment immunophenotyping with 
CyTOF and gene expression (RNA seq) of CD4, 
CD8, CD56 and CD14 cells 
• 
Neuropathic pain score (painDETECT™) at 6 and 
12 weeks 
AE=adverse event; ASAS20/40/70=Assessment in Ankylosing Spondylitis with 20%/40%/70% improvement; 
ASDAS-CRP=Ankylosing Spondylitis Disease Activity Score C-reactive Protein; axSpA=axial spondyloarthritis; 
CyTOF=cytometry by time of flight; ECG=electrocardiogram; MRC=Medical Research Council; MRI=magnetic 
resonance imaging; PAP=pulmonary alveolar proteinosis; SAEs=serious adverse events. 
 
Overall Design: 
This is a proof-of-concept, randomised, double-blind, placebo-controlled, multi-centre study designed to 
evaluate the safety/tolerability and efficacy of 4 subcutaneous (sc) injections of namilumab 150 mg given 
over 10 weeks as therapy in subjects with moderately-to-severely active axSpA, including those with a 
history of inadequate response to or intolerance to anti-TNF therapy. The study will allow enrolment of 
up to 50% of subjects with primary non-response to prior anti-TNF treatment. 
The study will consist of a maximum 4-week Screening Period, followed by a 12-week double-blind 
treatment evaluation period, followed by a 16-week safety follow-up period, for a maximum study 
duration of approximately 32 weeks or 224 days per subject. Eligible subjects will be randomised on 
Day 1 of Week 0 and receive study treatment administered sc on Day 1 of Week 0, Week 2 (loading 
dose), Week 6 and Week 10. Subjects will return on Week 12 for an End of Treatment (EoT) visit during 
which efficacy and safety assessments will be performed. Subjects will have a follow-up visit 16 weeks 
after the EoT visit. 
Number of Investigators and Study Centres: 
Up to 10 Investigators and 10 study centres are expected to participate in this study. 
Number of Subjects: 
Approximately 70 subjects will be screened to achieve 42 subjects randomly assigned to study treatment 
(36 on active treatment and 6 on placebo) and 42 evaluable subjects for an estimated total of 36 evaluable 
subjects on the active treatment arm and 6 evaluable subjects in the placebo treatment arm. 
Treatment Groups and Duration: 
Test product, dose and mode of administration: 
Namilumab 150 mg sc administered at Weeks 0, 2, 6 and 10. 
Reference therapy, dose and mode of administration: 
Matching placebo solution sc administered at Weeks 0, 2, 6 and 10. 

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Statistical Methods: 
The primary endpoint will be ASAS20. Based on literature data, the prior for the placebo and namilumab 
groups will follow a beta distribution with mean of 0.3 and 0.6, respectively. Weighting for the priors will 
be equivalent to 20 and 5 subjects, respectively. Sample size is the smallest sample size so that P{θact 
> θpbo| Y(HA)} >0.927 with probability 0.9, assuming true response rates of 0.3 and 0.6 for the control 
and namilumab arms, respectively. For a 6:1 randomisation, 42 patients need to be randomised. 
Efficacy endpoints will be summarised by treatment group and visit. The posterior distribution of the 
primary endpoint will be computed using the conjugate priors, and the mean, standard deviation, and 5th, 
10th, 25th, 50th, 75th, 90th, and 95th percentiles of the posterior distribution will be presented. 
Safety data will be analysed using the Safety Analysis Set. Adverse events will be summarised by the 
Medical Dictionary for Regulatory Activities (MedDRA). Incidence rates of treatment-emergent AEs 
(TEAEs) will be presented by treatment group. Laboratory, ECG, and vital signs will be summarised by 
treatment group and scheduled visit. 
Safety Review Team: 
A Safety Review Team consisting of the Coordinating Investigator, the Sponsor’s Medical Expert/Chief 
Medical Officer, and an independent Safety Physician will review ongoing safety data on a monthly basis. 
The data review will be conducted for randomised subjects and will include a review of vital signs, 
laboratory assessments, ECGs, AEs (including AEs of special interest and SAEs), physical examinations, 
and assessments of pulmonary functions. The Safety Review Team will provide consolidated feedback of 
the Team’s findings to the study team. Additional details of the Safety Review will be provided 
separately. 
1.2 
Study Schema 
 
Figure 1        Study Schema 

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1.3 
Schedule of Activities 
Table 3 
Schedule of Activities 
 
Procedure 
Screening1 
(Up to 28 Days 
before Day 1) 
Treatment Period2 
EoT/ ET 
Visit 
FU Phone 
Contact3 
Follow- 
up 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
Study Week 
-4 to -1 
0 
2 
6 
10 
12 
28 
Study Day/Window 
-28 to -8 
1 
15/±2 43/±2 71/±2 85/±2 
197/±4 
Screening 
Informed consent 
X 
Inclusion and exclusion criteria 
X 
X 
Demography 
X 
Medical history 
X 
Past and current medical conditions 
X 
Safety Assessments 
Full physical examination 
X 
X 
X 
Height 
X 
Weight 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
Clinical laboratory assessments 
(haematology, chemistry including 
CRP and ESR, urinalysis) 
X 
X 
X5 
X 
X5 
X 
X5 
Serum pregnancy test6 (WOCBP only) 
X 
Urine pregnancy test6 (WOCBP only) 
X 
X 
X 
X 
X 
X 
HIV testing 
X 
Serology (Hep B and C) 
X 
QuantiFERON-TB (or equivalent test) 
X 
Lung function tests7 
X 
X 
Pulse oximetry 
X 
X 
X 
X 
X 
X 
X 
MRC breathlessness scale 
X 
X 
X 
X 
X 
X 
X 
Chest x-ray8 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 

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Procedure 
Screening1 
(Up to 28 Days 
before Day 1) 
Treatment Period2 
EoT/ ET 
Visit 
FU Phone 
Contact3 
Follow- 
up 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
Study Week 
-4 to -1 
0 
2 
6 
10 
12 
28 
Study Day/Window 
-28 to -8 
1 
15/±2 43/±2 71/±2 85/±2 
197/±4 
Efficacy Assessments 
Subject’s Global Assessment of 
Disease Status 
X 
X 
X 
X 
X 
Subject’s assessment of spinal pain 
X 
X 
X 
X 
X 
X 
BASFI 
X 
X 
X 
X 
X 
BASDAI 
X 
X 
X 
X 
X 
X 
MRI 
X9 
X10 
ASDAS-CRP assessment 
X 
X 
X 
X 
X 
Neuropathic pain score 
(painDETECT™) 
X 
X 
X 
Joint count, tendon swelling, and 
enthesitis 
X 
X 
X 
X 
X 
PK/PD Assessments11 
Blood sample saved for Total GM-CSF 
(namilumab/GM-CSF complexes), 
namilumab serum concentration, 
immunogenicity12 and immunology13 
X 
X 
X 
X 
Saliva sample for DNA (optional) 
X 
Blood sample for biomarkers and 
immunophenotyping 
X 
X 
X 
X 
Blood sample for HLA-B2714 
X 
Stool sample for calprotectin 
X 
X 
X 
X 
Stool sample for microbiome analysis 
X 
X 
X 
X 
IMP administration 
Randomisation 
X 
Subcutaneous dosing of IMP 
X 
X 
X 
X 
AE=adverse event; ANA=anti-nuclear antibody; ASDAS=Assessment of SpondyloArthritis Disease Activity Score; 
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional 
Index; CRP=C-reactive protein; ECG=electrocardiogram; EoT=End of Treatment; ESR=erythrocyte sedimentation 
rate; ET=Early Termination; FU=Follow-up; GM-CSF=granulocyte-macrophage colony-stimulating factor; 
Hep=hepatitis; HIV=human immunodeficiency virus; IMP=investigational medicinal product; MRC=Medical 
Research Council; MRI=magnetic resonance imaging; PAP=pulmonary alveolar proteinosis; 
PD=pharmacodynamic; PK=pharmacokinetic; WOCBP=women of childbearing potential. 

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1. Screening may be a maximum 4 weeks prior to baseline for some subjects (where stabilisation/wash-out of 
concomitant medication is needed) and only 1 week prior to baseline for subjects that already meet all 
inclusion/exclusion criteria). 
2. Subjects who discontinue the study prior to the EoT visit should attend the EoT/ET visit and follow the schedule 
for the FU period. 
3. One FU telephone contact will be performed between study completion and end of study visit approximately 
6 weeks after last dosing; AE and concomitant medication will be collected. 
4. In the treatment period, both pre-dosing and post-dosing (approximately 30 minutes post-dosing) vital sign 
assessments are to be performed. 
5. Blood draw for evaluation of CRP and ESR only. 
6. Pregnancy testing at Screening will be in serum; pregnancy testing at other visits will be in urine; a positive urine 
test will be confirmed with a serum pregnancy test. 
7. Lung function tests includes: FEV1, FVC and PEF. 
8. Chest x-ray within 3 months of Screening to assess for PAP. 
9. The pre-dosing MRI can be performed within 6 months before Screening. 
10. Although the post-dosing EoT MRI is scheduled to occur at the week 12 visit, the MRI may be performed 
between weeks 12 and 16 if possible for study centres with logistical issues that prevent performing the MRI at 
the week 12 visit. The EoT MRI is optional; however, the study centres are requested to perform the EoT MRI 
on all subjects to the extent possible. 
11. PK/PD sampling must be taken pre-dose (t=0). 
12. Stored sample for immunogenicity assessment for evaluation of anti-namilumab antibodies. 
13.Immunology assessment for evaluation of ANA (anti-dsDNA if ANA is positive). 
14.HLA-B27 testing will only be performed in subjects whose HLA-B27 status is unknown. 

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2.0 INTRODUCTION 
Namilumab (AMG203 or MT203) is a human immunoglobulin G1 (IgG1) monoclonal anti- 
granulocyte-macrophage colony stimulating factor (GM-CSF) antibody, with a molecular weight 
of approximately 146 kDa, which potently and specifically neutralises human and macaque GM-
CSF. 
2.1 
Study Rationale 
The purpose of this study is to assess the effect of namilumab, a GM-CSF inhibitor, on the 
clinical response in subjects with axial spondyloarthritis (axSpA). Current treatment options 
including non-steroidal anti-inflammatory drugs (NSAIDs), tumour necrosis factor inhibitors 
(TNFi) and interleukin (IL)-17 inhibitors do not provide clinical response for many patients (see 
Section 2.2) and new treatment options are needed. 
GM-CSF is thought to be a key activator of the innate arm of the immune system and as such is 
involved in the chronic stages of inflammatory and autoimmune diseases. GM-CSF acts as a pro-
inflammatory cytokine and is aberrantly overproduced in a multitude of inflammatory and 
autoimmune human diseases, including rheumatoid arthritis (RA), psoriasis and axSpA. The 
central role of GM-CSF in the immune response and evidence of its involvement in human 
inflammatory and autoimmune diseases is a major rationale for the development of an anti–GM- 
CSF antibody as novel therapy for the treatment of these diseases, including axSpA. 
2.2 
Background 
Spondyloarthropathy (SpA) refers to a group of rheumatic disorders that share common clinical 
features, extra-articular manifestations and a genetic association with the type 1 major 
histocompatibility complex HLA-B27. SpA comprises two subgroups based on primary 
localisation of symptoms: axSpA, which includes non-radiographic axSpA (nr-axSpA), 
radiographic axSpA and ankylosing spondylitis (AS), and peripheral SpA (phSpA), which 
includes psoriatic arthritis, reactive arthritis, enteropathic arthritis and undifferentiated SpA 
(Scotti 2017). 
AxSpA is characterised by a broad clinical spectrum of disease manifestations, including 
inflammatory back pain, peripheral arthritis, dactylitis, uveitis, psoriasis, inflammatory bowel 
disease and aortic insufficiency (Strand 2017). Additional symptoms such as fatigue, sleep 
problems, depression and sexual dysfunction can profoundly affect health-related quality of life 
and limit work, leisure and daily activities (Strand 2017). The prevalence of axSpA is 
approximately 1% of the general population (Raine 2014). 
Current pharmacological treatment options for patients with axSpA include local glucocorticoid 
injections, NSAIDs, TNFi and IL-17A inhibitors (Toussirot 2017). However, results from 

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clinical trials show that only 50 to 65% of subjects with axSpA who were treated with TNFi for 
24 weeks and 58 to 64% of subjects with AS who were treated with IL-17A inhibitors for 16 
weeks exhibit a low level clinical response (ASAS20) (Davis 2005; Inman 2008; Landewe 2014; 
van der Heijde 2005; van der Heijde 2006; Baeten 2015). In clinical practice, up to 45% of 
subjects with axSpA treated for 2 years with TNFi discontinue this treatment. Thus, there is a 
need for new therapies to expand the treatment options in this chronic progressive disease. 
Namilumab has been investigated by Takeda Pharmaceuticals (Takeda) as a treatment option for 
RA. Non-clinical studies have shown that namilumab has demonstrated potent and specific 
neutralising bioactivity of cynomolgus monkey and human GM-CSF. 
Safety Pharmacology: No namilumab-related acute effects on the respiratory, cardiovascular, 
and central nervous system were detected in cynomolgus monkeys in safety pharmacology 
investigations included in the 4-week toxicity study and an initial 26-week repeat-dose toxicity 
study with namilumab. Mild and transient elevations in C-reactive protein (CRP) as well as 
aspartate transaminase (AST) and alanine transaminase (ALT) were observed in some test 
animals. In an initial 26-week repeat-dose toxicity study, minimal-to-moderate foamy alveolar 
macrophage accumulation occasionally accompanied by inflammation and the presence of 
extracellular debris in the alveolar space of the lung were noted at higher doses of 
10 mg/kg/2-weeks or   more.   In   a   supplemental   toxicity   study   of   namilumab   up   to 
3 mg/kg/2-weeks, foamy alveolar macrophage accumulation was observed across all dose groups 
as well as the control group, but no inflammation or extracellular debris was observed, and the 
findings were considered to be incidental and/or spontaneous in nature and not adverse. 
Clinical Studies: Seven clinical studies have been completed with namilumab: 2 studies in 
healthy subjects; a study in Japanese and Caucasian healthy subjects; 4 studies in subjects with 
mild-to-moderate RA on treatment with methotrexate (MTX); and 1 study in subjects with 
moderate-to-severe psoriasis. The half-life (t1/2) of namilumab was 25 days following 
intravenous (i.v.) administration and 21 days following subcutaneous (sc) administration. The 
safety profile of namilumab showed the treatment was generally safe and well-tolerated. One 
serious adverse event (SAE) was reported in a healthy subject: this consisted of a 6 second, self-
limited episode of wide complex tachycardia after infusion of 3 mg/kg namilumab, which was 
recorded as a suspected unexpected serious adverse reaction (SUSAR) (serious due to a 
medically important event, unexpected and related as assessed by the Investigator), but was not 
considered life-threatening or medically serious. No other related SAEs were reported. Non- 
related SAEs included cardiac events, breast cancer and non-small cell lung cancer. No allergic 
reactions were reported. 
A detailed description of the chemistry, pharmacology, efficacy and safety of namilumab is 
provided in the current Investigator’s Brochure. 

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2.3 
Benefit/Risk Assessment 
Namilumab has not yet been administered to patients with axSpA, and therefore no benefit has 
yet been shown. 
Namilumab has been administered to healthy volunteers, subjects with psoriasis and subjects 
with RA. However, due to limited clinical experience with namilumab, all subjects should be 
closely monitored for any potential occurrence of serious events, such as severe hypersensitivity 
or lung disorders, cardiac events and hepatic toxicity. When necessary, namilumab 
administration should be discontinued and appropriate medical interventions initiated. In 
addition, appropriate prophylactic measures should also be considered in subjects thought to be 
at higher risk for these events. 
The possibility of a severe allergic reaction, including anaphylaxis, which can manifest as life- 
threatening bronchospasm or hypotension, should always be considered. A physician should be 
available on-site and supplies of epinephrine, antihistamine and corticosteroid readily accessible 
when a subject is being administered the investigational medicinal product (IMP). A subject who 
has such an allergic reaction should not receive additional IMP injections. 
Special attention should be given to respiratory symptoms arising during namilumab treatment, 
due to the theoretical risk of pulmonary alveolar proteinosis (PAP). If the symptoms are mild and 
a likely cause of the symptoms can be established, the subject can remain in the study and the 
condition treated at the discretion of the Investigator. Should the symptoms be severe, or no 
likely cause can be established, the subject should be referred to a pulmonologist for further 
evaluation that may include chest computer tomography scanning and broncho-alveolar lavage 
including cytology. 
In case of unforeseen (e.g., dental) surgery between Screening and End of Study, subjects should 
receive adequate antibiotic prophylaxis. 
Clinical evidence indicates that immunisation in subjects with immune-mediated inflammatory 
diseases does not increase clinical or laboratory parameters of disease activity (Gluck 2008). 
Live vaccines are contraindicated because of the potential risk of immune-suppression associated 
with any immunomodulators, but non-live (killed) vaccines can be used (Rahier 2010). 
Vaccination status is best checked and updated before the start of any immunomodulatory 
therapy with agents such as MTX or namilumab. 
In view of the potential for interference with response to an investigational drug, restrictions on 
vaccine use are in place for clinical studies involving namilumab. At present the effect of 
namilumab on vaccine response is not known. 
Live (live-attenuated) vaccines are not permitted within 2 weeks prior to randomisation or during 
the study treatment and safety follow-up periods. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of namilumab may be found in the Investigator’s Brochure. 

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3.0 OBJECTIVES AND ENDPOINTS 
Table 4 
Study Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• 
To assess the efficacy of namilumab 150 mg 
subcutaneous (sc), given on Weeks 0, 2, 6 and 10 
in subjects with axSpA 
• 
Proportion of subjects who achieve an ASAS20 
clinical response at Week 12 
Secondary 
• 
To assess the efficacy of namilumab 150 mg sc, 
given on Weeks 0, 2, 6 and 10 on other clinical 
responses in subjects with axSpA 
• 
Proportion of subjects who achieve ASAS40 and 
ASAS70 response at Week 12 
• 
Proportion of subjects who achieve an ASAS20 
clinical response at Week 6 
• 
Proportion of subjects who achieve ASDAS-CRP 
response at Weeks 6 and 12 
• 
To assess the safety and tolerability 
of 
namilumab 150 mg sc, given on Weeks 0, 2, 6 
and 10 in subjects with axial spondyloarthritis 
• 
AEs 
• 
SAEs 
• 
Laboratory evaluations 
• 
Vital signs 
• 
Electrocardiograms (ECGs) 
• 
Physical examinations 
• 
Assessments of pulmonary function 
o 
MRC breathlessness scale 
o 
Chest x-ray 
o 
Lung function tests 
o 
Pulse oximetry 
• 
Immunogenicity 
• 
AEs of special interest: 
o 
Pulmonary alveolar proteinosis (PAP) 
o 
Neutropaenia 
o 
Myeloid suppression 

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Objectives 
Endpoints 
Exploratory 
• 
To assess the efficacy of namilumab 150 mg sc, 
given on Weeks 0, 2, 6 and 10 on radiologic 
responses in subjects with axial spondyloarthritis 
• 
To assess the effect of namilumab 150 mg sc, 
given on Weeks 0, 2, 6 and 10 on other clinical 
responses, biomarkers, immunophenotyping, and 
pain 
scores 
in 
subjects 
with 
axial 
spondyloarthritis 
• 
Proportion of subjects who show a radiological 
response on MRI at 12 weeks 
• 
Proportion of subjects who achieve ASAS20 
clinical response at Weeks 2 and 10 
• 
Proportion of subjects who achieve ASDAS-CRP 
response at Weeks 2 and 10 
• 
Joint count, tendon swelling, and enthesitis at 
Weeks 2, 6, 10, and 12 
• 
Serum 
biomarkers 
including 
CRP, 
faecal 
biomarkers including calprotectin and microbiome 
• 
Pre- and post-treatment immunophenotyping with 
CyTOF and gene expression (RNA seq) of CD4, 
CD8, CD56 and CD14 cells 
• 
Neuropathic pain score (painDETECT™) at Week 
6 and 12 
AE=adverse event; ASAS20/40/70=Assessment in Ankylosing Spondylitis with 20%/40%/70% improvement; 
ASDAS-CRP=Ankylosing Spondylitis Disease Activity Score C-reactive Protein; axSpA=axial spondyloarthritis; 
CyTOF=cytometry by time of flight; ECG=electrocardiogram; MRC=Medical Research Council; MRI=magnetic 
resonance imaging; PAP=pulmonary alveolar proteinosis; SAEs=serious adverse events. 

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4.0 STUDY DESIGN 
4.1 
Overall Design 
This is a proof-of-concept, randomised, double-blind, placebo-controlled, multi-centre study 
designed to evaluate the safety/tolerability and efficacy of 4 sc injections of namilumab 150 mg 
given over 10 weeks as therapy in subjects with moderately-to-severely active axSpA, including 
those with a history of inadequate response to or intolerance to anti-tumour necrosis factor (TNF) 
therapy. The study will allow enrolment of up to 50% of subjects with primary non-response to 
prior anti-TNF treatment. 
The study will consist of a maximum 4-week Screening period, followed by a 12-week double- 
blind treatment evaluation period, followed by a 16-week safety follow-up period, for a 
maximum study duration of approximately 32 weeks or 224 days per subject. Eligible subjects 
will be randomised on Day 1 of Week 0 and receive study treatment administered sc on Day 1 of 
Week 0, Week 2 (loading dose), Week 6 and Week 10. Subjects will return on Week 12 for an 
End of Treatment (EoT) visit during which efficacy and safety assessments will be performed. 
Subjects will have a follow-up visit 16 weeks after the EoT visit. 
4.2 
Scientific Rationale for Study Design 
This study is designed as a phase 2a proof-of-concept study evaluation of namilumab in the 
treatment of subjects with axSpA. Subjects who have inadequately responded to or experienced 
intolerance to previous treatment with an anti-TNF agent may be included but will be limited to 
50% of the total study population; this sub-population may respond significantly to namilumab, 
providing a sensitive basis for dose selection/optimisation in advance of further (phase 3) clinical 
development. The overall study population is also considered likely to benefit from the novel 
mechanism of namilumab, which may provide a new treatment option for subjects intolerant to 
or failing previous therapies. 
The choice of 150 mg/mL namilumab for this investigation was based on the dose demonstrating 
maximal efficacy in clinical studies of rheumatoid arthritis and still within the margins of safety. 
4.2.1 
Subject Population Studied (Defined by Demography, Disease and/or Treatment 
Characteristics) 
In order to ensure that the study data will be relevant to the future use of this agent in clinical 
practice, the design is representative of clinical practice in terms of both the selected study 
populations and concomitant medications (stable doses of NSAIDs, MTX, sulfasalazine or 
leflunomide). 

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4.2.2 
Justification for Design and Sample Size 
A parallel-arm, randomised, double-blind, placebo-controlled study design is a conventional and 
well-established design to assess proof-of-concept effects of new biologics in axSpA. This study 
design follows the Committee for Proprietary Medicinal Products (CPMP)/European Medicines 
Agency (EMA) Draft Guideline (12 October 2017): “EMA Guideline on the Clinical 
Investigation of Medicinal Products for the Treatment of Axial Spondyloarthritis” 
(EMA/CPMP/EWP/4891/03 Rev. 1). 
Sample size justification is provided in Section 9.2. 
4.2.3 
Justification of Control Group 
The choice and rationale of a control group is in accordance with the CPMP/EMA Guideline 
(December 2003). Section 5.1 of the guideline recommends use of placebo controls for a limited 
duration of 3 to 6 months. The use of NSAIDs with gastric protection and low-dose 
corticosteroids, all in stable doses, is allowed to ensure a minimum background treatment 
remains in place. 
Acknowledging the general need to ensure use of a minimum period for treatment comparison 
with placebo in clinical studies, the planned investigation will be conducted over 12 weeks. 
Throughout this period discomfort for placebo-treated subjects will be minimised by the 
concomitant use of standard of care therapy: this approach will include stable dose pain-relief 
medication together which may include MTX. 
4.2.4 
Justification for Route, Dose Regimen, Treatment Period, with Reference to 
Previous Exposure, PK/PD Profile and Non-clinical Safety 
This will be the first time that namilumab is to be administered subcutaneously to subjects with 
moderate-to-severe axSpA. Non-clinical studies have not revealed any risks associated with 
multiple dosing and clinical studies in healthy volunteers and subjects with RA and psoriasis 
have shown namilumab to be safe and well tolerated (see Investigator’s Brochure). The current 
administration schedule is designed based on the simulation of pharmacokinetic (PK) results of 
the first-in-man study. With the selected schedule, the steady state serum concentration is 
expected to be reached by the second injection. The half-life of namilumab as determined from 
the first-in-man study data is 25 days and thus supports maintenance dosing with a 4-week 
interval. 
The time to onset of action of namilumab in patients with axSpA is not established; however, it 
is expected to be in a range within 12 weeks from first administration. Therefore, some clinical 
effect is expected after 12 weeks in this study. 

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4.2.5 
Justification for Primary Endpoints 
The primary endpoint, Assessment in Ankylosing Spondylitis with 20% improvement (ASAS20) 
clinical response at 12 weeks, and the secondary endpoints, ASAS40, ASAS70, Ankylosing 
Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) response, and 
improvement of CRP, are consistent with the revised EMA Draft guidance (12 October 2017) for 
studies in axSpA. 
4.3 
Justification for Dose 
The namilumab drug product is a single-dose liquid solution for sc injection containing 
20 mg/mL, 50 mg/mL, 80 mg/mL or 150 mg/mL namilumab active ingredient. From the 
NEXUS study performed in subjects with moderate-to-severe RA, it was concluded that 150 mg 
was the most effective dose of namilumab in subjects with RA, as well as being associated with a 
manageable safety profile. In addition, the chronic toxicology study in cynomolgus monkeys 
demonstrated that the 150 mg dose in humans lies within a favourable therapeutic window of 
equivalent doses in monkeys (see Section 1.1.5 in the Investigator’s Brochure). Therefore, the 
dose of 150 mg/mL was chosen for the current study in subjects with axSpA. 
Treatment-related treatment-emergent AEs (TEAEs) associated with namilumab 150 mg were 
single cases of infection, oropharyngeal pain/dental caries, headache, decreases in neutrophil 
counts/neutropenia, elevated liver function tests and decreased forced expiratory volume 
(FEV)/force vital capacity (FVC) (see Table 6.b in the Investigator’s Brochure). Based on 
haematology and clinical chemistry variables, there were no clinically significant or serious 
cases of neutropenia or abnormal liver function and there were no cases of confirmed PAP. No 
deaths or treatment-related SAEs were reported in subjects receiving namilumab 150 mg. These 
results suggest that the 150 mg dose chosen for the current study is safe and well tolerated. 
4.4 
End of Study Definition 
A subject is considered to have completed the study if he/she has completed all phases of the 
study including the last visit. 
The end of the study is defined as the date of the last visit of the last subject in the study. 

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5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Age ≥18 and ≤75 years of age. 
2. Diagnosis of axSpA by an appropriately qualified physician and classified using ASAS 
criteria ≥3 months prior to Baseline; symptoms must have started before age 45. 
3. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 and spinal pain 
score ≥40, at screening and Baseline. 
4. MRI evidence of active axSpA ≤6 (ideally ≤3) months prior to randomisation using ASAS 
criteria. 
5. A negative tuberculosis (TB) screening assessment. 
6. A female subject of childbearing potential who is sexually active with a non-sterilised male 
partner agrees to routinely use adequate contraception from signing of the informed consent 
throughout the duration of the study until the end of the safety follow up (18 weeks after last 
dose) (see Appendix 7). 
7. A male subject who is non-sterilised and sexually active with a female partner of 
childbearing potential agrees to use adequate contraception from signing of the informed 
consent throughout the duration of the study until the end of the safety follow up (18 weeks 
after last dose) (see Appendix 7). 
8. Stable NSAID use for 28 days prior to study entry (see Appendix 5). 
9. Stable use of MTX (≤25 mg/week), sulfasalazine (≤3 g/day) or leflunomide (≤20 mg/day) for 
28 days prior to study entry (see Appendix 5). 
10. Stable oral corticosteroid dose ≤10 mg for 28 days prior to study entry (see Appendix 5). 
11. Capable of giving signed informed consent as described in Appendix 2, which includes 
compliance with the requirements and restrictions listed in the informed consent form (ICF) 
and in this protocol. 
In addition, the following inclusion criteria will apply for some subjects: 
12. Inadequately responded to or experienced intolerance to previous treatment with an anti-TNF 
agent (limited to 50% of the total study population). 
Note: Criteria for inadequate response to or experienced intolerance to previous treatment 
with an anti-TNF agent are defined as: 

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• Signs and symptoms of persistently active disease despite a history  of at least  one 12-
week regimen of one of the following agents: 
 
− Infliximab: 5 mg/kg i.v. 
− Etanercept: 50 mg weekly 
− Adalimumab: 40 mg fortnightly 
− Golimumab: 50 mg monthly 
− Certolizumab pegol: 400 mg SC initially and at Weeks 2 and 4, followed by 
200 mg every 2 weeks or 400 mg every 4 weeks 
OR 
• Recurrence of symptoms during scheduled maintenance dosing following prior clinical 
benefit (discontinuation despite clinical benefit does not qualify). 
OR 
• History of intolerance of at least one TNF antagonist (including, but not limited to 
infusion-related reaction, demyelination, congestive heart failure and infection). 
5.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. A current diagnosis of axSpA with a BASDAI >4 but no evidence of inflammation on MRI. 
2. Discontinued biologic therapy such as adalimumab, etanercept, infliximab, golimumab and 
certolizumab pegol <8 weeks prior to Baseline. 
3. Previous or current use of oral corticosteroid and meets one of the following criteria: 
• Is receiving prednisone or prednisone equivalent >10 mg/day at Baseline; 
• Has discontinued use of corticosteroid within 28 days of Baseline; 
• Has not been on stable doses of corticosteroid for at least 28 days prior to Baseline; or 
• Has been taking both oral budesonide and prednisone (or equivalent) simultaneously. 
4. Received intra-articular corticosteroids during the Screening Period or i.v. corticosteroids 
within 14 days prior to Screening or during the Screening Period. 
5. Received anti-IL-17A or anti IL12/23 therapy. 
6. Received cyclosporine, tacrolimus or mycophenolate mofetil within 28 days prior to 
Baseline. 
7. Previously received stem cell transplantation. 
8. Infection(s) requiring treatment with i.v. anti-infectives within 28 days prior to the Baseline 
Visit or oral anti-infectives within 14 days prior to the Baseline Visit. 
9. Screening laboratory and other analyses show any of the following abnormal results: 

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• Bilirubin > upper limit of normal (ULN) and serum AST or ALT > 1.5 × ULN; 
• Estimated glomerular filtration rate <40 mL/min/1.73 m2; 
• Total white blood cell (WBC) count <3,000/μL; 
• Absolute neutrophil count (ANC) <1,000/μL; 
• Platelet count <100,000/μL; 
• Absolute lymphocyte count <750/μL; 
• Haemoglobin <9 g/dL. 
10. Any active or recurrent viral infection that based on the Investigator's clinical assessment 
makes the subject an unsuitable candidate for the study, including recurrent/disseminated 
herpes zoster or known history of human immunodeficiency virus (HIV). 
11. Hepatitis B (hepatitis B virus surface antigen [HBsAg] positive [+] or detected sensitivity on 
the hepatitis B virus [HBV] DNA polymerase chain reaction [PCR] qualitative test for 
hepatitis B core antibodies [HBc Ab]/hepatitis B surface antibody [HBsAb] positive subjects) 
or hepatitis C (hepatitis C virus [HCV] RNA detectable in any subject with anti-hepatitis C 
virus antibody [HCV Ab]). 
12. Any active or chronic recurring infections or untreated latent TB. 
13. History of moderate-to-severe congestive heart failure (New York Heart Association 
[NYHA] class III or IV), risk factors for coronary syndrome, hypertension, angina and 
myocardial infarction, cerebrovascular accident and any other condition within 6 months, 
which in the opinion of the Investigator, would put the subject at risk by participation in the 
study. 
14. Receipt of any live vaccine within 2 weeks prior to randomisation, or will require live 
vaccination during study participation including up to 1 month after the last dose of study 
drug. 
15. Evidence of current or prior dysplasia or history of malignancy (including of the 
gastrointestinal tract) other than a successfully treated non-metastatic cutaneous squamous 
cell or basal cell carcinoma or localised carcinoma in situ of the cervix or adenomatous polyp 
that has been completely resected. 
16. Has had any uncontrolled and/or clinically significant (per Investigator's judgement) illness, 
hospitalisation, or has had any surgical procedure requiring general anaesthesia within 
30 days prior to Screening, or has any planned surgical procedure within 6 months after 
randomisation. 
17. Known current or previous interstitial lung disease. 
18. Positive pregnancy test at Screening (serum) or Baseline (urine). 
19. Female subjects who are breastfeeding or considering becoming pregnant during the study. 
20. Considered by the Investigator, for any reason, to be an unsuitable candidate for the study. 
21. Received any investigational agent or procedure within 30 days or 5 half-lives prior to 
Baseline, whichever is longer. 

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22. History of clinically significant drug or alcohol (> 40 units per week) use in the last 
12 months. 
23. Related to or a dependent of the site staff, or a member of the site staff. 
5.3 
Lifestyle Considerations 
No restrictions with regard to lifestyle are required. 
5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently randomly assigned to study treatment/entered in the study. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure subjects to meet 
the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once after discussion with the Medical Advisor/Sponsor Medical Representative. 
Rescreened subjects should not be assigned the same subject number as for the initial screening. 
Safety assessments that are measured and do not meet the inclusion/exclusion criteria may be 
repeated once without the subject being considered a screen failure. 
Subjects who are rescreened more than 2 weeks after their first screen will have all assessments 
repeated. 

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6.0 STUDY TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo or 
medical device(s) intended to be administered to a subject according to the study protocol. 
6.1 
Study Treatment(s) Administered 
Table 5 
Study Treatment Details 
 
Study Treatment Name: 
Namilumab 
Placebo 
Dosage Formulation: 
Solution for injection 
Solution for injection 
Unit Dose Strength(s)/Dosage 
Level(s): 
 
 
Route of Administration: 
Subcutaneous 
Subcutaneous 
Dosing Instructions: 
 
 
Packaging and Labelling: 
Supplies of namilumab will be labelled 
according to local regulations. 
Supplies of placebo will be labelled 
according to local regulations 
 
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Preparation 
All IMPs are provided in sterile, single-use glass vials. 
. Each carton and vial 
will be labelled with a unique medication identification (MED ID) number and will be dispensed 
via an interactive web response system (IWRS). 
6.2.2 
Handling 
All study medications will be administered by the Investigator or designee. 
The subject will visit the clinic for dosing of 
of blinded study medication by a single 
subcutaneous injection on Days 1, 15, 43 and 71. 
6.2.3 
Storage 
The Investigator or designee must confirm that appropriate temperature conditions have been 
maintained for all clinical trial material received and that any discrepancies are reported and 
resolved before use. 
The clinical trial material must be stored according to the manufacturer’s stipulation, as specified 
on the label. 

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During shipping, vials will be protected from light and maintained between 
Each 
shipment will include a packing slip listing the contents of the shipment, and any applicable 
forms. 
All clinical trial material must be kept in an appropriate, limited-access, secure location until 
used or returned to the sponsor or designee. All study medication must be stored under the 
conditions specified on the label and remain in the original container until dispensed. A daily 
temperature log of the drug storage area must be maintained every day. 
The Investigator or designee must confirm that appropriate temperature conditions have been 
maintained for all clinical trial material received and that any discrepancies are reported and 
resolved before use. 
The Investigator is responsible for ensuring that deliveries of clinical trial material from the 
sponsor are correctly received, recorded, and handled, and stored safely and properly in 
accordance with the Code of Federal Regulations (CFR) or national and local regulations, and 
used in accordance with this protocol. 
The Sponsor must be notified immediately of any temperature excursions, shipping and handling 
or storage discrepancies. 
Drug supplies will be counted and reconciled at the site before being returned to Takeda or 
designee or being destroyed. 
6.3 
Measures to Minimise Bias: Randomisation and Blinding 
6.3.1 
Investigational Drug Assignment and Dispensing Procedures 
Study medication will be provided in a blinded fashion and dispensed in accordance with 
randomisation code. Randomisation will be performed by IWRS. Before the study is initiated, 
the log-in information and directions for the IWRS will be provided to each study site. Study 
treatment will be dispensed at the study visits as summarised in the Schedule of Activities (SoA). 
Returned study treatment must not be re-dispensed to subjects. 
The Investigator or Investigator’s designee will access the IWRS at Screening to obtain the 
subject study number. The Investigator or the Investigator’s designee will utilise the IWRS to 
randomise the subject into the study. During this contact, the Investigator or designee will 
provide the necessary subject-identifying information, including the subject number assigned at 
screening. The MED ID number of the study medication to be dispensed will then be provided 
by the IWRS. If the MED ID number is lost or damaged, the site can request a replacement from 
the IWRS. (Refer to the IWRS manual provided separately). The MED ID number will be 
entered onto the electronic case report form (eCRF). At all drug-dispensing visits, the 
Investigator or designee will again contact the IWRS to request additional investigational drug 
for a subject. 

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6.3.2 
Randomisation Code Creation and Storage 
The randomisation schedule will be created by the Sponsor or designee and stored in a secure 
area, accessible only to authorised personnel. Block sizes will be specified in the randomisation 
specifications. Randomisation will be stratified by prior use of anti-TNF agents. 
6.3.3 
Investigational Drug Blind Maintenance 
Products are not visually identical, however, to protect the blind, a clear yellow label will be 
applied to the cover of the syringe prior to the drug product being drawn from the vial. Vials and 
cartons will be supplied with a blinded label, randomisation will be unblinded and dispensation 
will be completed by an unblinded pharmacist. 
The IMP blind will be maintained using the IWRS, which can be accessed and broken by the 
Investigator or designee in an emergency for unblinding of study medication assignments to 
ensure the safety of the subject. 
6.3.4 
Unblinding Procedure 
The IMP blind shall not be broken by the Investigator unless information concerning the 
investigational drug is necessary for the medical treatment of the subject. In the event of a 
medical emergency, if possible (but not required), the medical monitor should be contacted 
before the IMP blind is broken to discuss the need for unblinding and if unblinding is required. 
For unblinding a subject, the IMP blind can be obtained and broken by the Investigator at any 
time, by accessing the IWRS. 
The Sponsor must be notified as soon as possible if the IMP blind is broken. The date, time and 
reason for the blind being broken must be recorded in the eCRF. 
If any site personnel are unblinded to a subject’s treatment, investigational drug must be stopped 
immediately and the subject must be withdrawn from the study. The Investigator or other site 
personnel should not reveal the specific treatment assignment of the unblinded subject to the 
medical monitor or other contract research organisation (CRO) or Sponsor staff. The subject 
should continue to the EoT/Early Termination (ET) Visit. 
6.3.5 
Accountability and Destruction of Sponsor-Supplied Drugs 
Drug supplies will be counted and reconciled at the site before being returned to the Sponsor or 
designee, or before being destroyed at the site (if approved by the Sponsor for destruction at the 
site). 
The Investigator or designee must ensure that the clinical trial material is used in accordance 
with the approved protocol and is dispensed only to subjects enrolled in the study. To document 
appropriate use of the clinical trial material, the Investigator must maintain records of all 

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Sponsor-supplied drug delivery to the site, site inventory, dispensation and use by each subject, 
and return to the Sponsor or designee. 
Upon receipt of the clinical trial material, the Investigator or designee must verify the contents of 
the shipments against the packing list. The verifier should ensure that the quantity is correct, and 
that the medication is received within the labelled storage conditions in good condition. If there 
are any discrepancies between the packing list versus the actual product received, the Sponsor 
must be contacted to resolve the issue. The packing list should be filed in the Investigator’s 
essential document file. 
The Investigator must maintain 100% accountability for all clinical trial material received and 
dispensed during his or her entire participation in the study. Proper drug accountability includes, 
but is not limited to: 
• Frequently verifying that actual inventory matches IWRS inventory. 
• Verifying that the IWRS is completed for the MED ID used to prepare each dose. 
• Verifying that all containers used are documented accurately in the IWRS. 
• Verifying that required IWRS fields are completed accurately. 
If any dispensing errors or discrepancies are discovered, the Sponsor must be notified 
immediately. 
The current inventory of all clinical trial material at sites will be tracked through the IWRS. 
The IWRS will include all required information as a separate entry for each subject to whom 
clinical trial material is dispensed. 
The Investigator will be notified of any expiry date extension for clinical trial material during the 
study conduct. On expiry date notification from the Sponsor or designee, the site must complete 
all instructions outlined in the notification including segregation of expired clinical trial material 
for return to the Sponsor or its designee for destruction. 
In the event of expiry date extension of supplies already at the study site, supplies may be 
relabelled with the new expiry date. In such cases, the Sponsor or its designee will prepare 
additional labels and all necessary documentation for completion of the procedure. 
6.4 
Study Treatment Compliance 
The prescribed dosage, timing and mode of administration may not be changed. Any departures 
from the intended regimen must be recorded in the eCRFs. 
All study medications will be administered by the Investigator or designee. Subject 
noncompliance is therefore not applicable. 

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If a subject misses a dose, the dose should be administered as close as possible to the missed 
scheduled dose, but there should be at least 2 weeks between doses. If a period of 2 weeks 
between doses is not possible, then the missed scheduled dose should not be administered and 
the subject dosing should resume with the next scheduled dosing. 
6.5 
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 enrolment (within 28 days 
before the time of enrolment) or receives during the study must be recorded on the eCRF along 
with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
The use of stable doses of NSAIDs/COX-2 is permitted within 28 days prior to randomisation 
and during the study; the use of stable doses of MTX, sulfasalazine or leflunamide is permitted 
from 28 days prior to Screening and during the study. 
The use of stable oral corticosteroids (≤10 mg) is permitted from 28 days prior to Baseline and 
during the study. 
A list of excluded medications/therapy is provided in Appendix 5. 
6.6 
Dose Modification 
No dose modifications are permitted in this study. 
6.7 
Treatment after the End of the Study 
The Sponsor will not provide any additional care to subjects after they leave the study because 
such care should not differ from what is normally expected for subjects with axSpA. 

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7.0 DISCONTINUATION OF STUDY TREATMENT AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Treatment 
Subjects may be discontinued from study treatment for the following reasons: 
1. Pre-treatment event or treatment-emergent AE. The subject has experienced a pre-treatment 
event or a treatment-emergent AE that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health or the subject is unwilling 
to continue because of the pre-treatment event or AE. 
• Liver Function Test Abnormalities 
• Study medication must be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests) until the subject’s laboratory profile has returned to 
normal/baseline status, if the following circumstances occur at any time during study 
medication treatment: 
− ALT or AST >8 × ULN, or 
− ALT or AST >5 × ULN and persists for more than 2 weeks, or 
− ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or 
international normalised ratio (INR) >1.5, without any anti-coagulant treatment, 
or 
− ALT or AST >3 × ULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
2. If a diagnosis of PAP is confirmed during the course of this study (see Section 8.2.4), the 
subject should be withdrawn and treatment initiated as applicable. 
3. Major protocol deviation. The discovery post-randomisation that the subject failed to meet 
protocol entry criteria or did not adhere to protocol requirements, and continued participation 
poses an unacceptable risk to the subject’s health. 
4. Lost to follow-up. The subject did not return to the clinic and attempts to contact the subject 
were unsuccessful. Attempts to contact the subject must be documented. 
5. Pregnancy. The subject is found to be pregnant. 
Subjects who discontinue study treatment will not be replaced. 
See the SoA for data to be collected at the time of treatment discontinuation and follow-up and 
for any further evaluations that need to be completed. 

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7.2 
Subject Discontinuation/Withdrawal from the Study 
A subject may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioural, compliance or 
administrative reasons. 
If the subject withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
If a subject withdraws from the study, he/she may request destruction of any samples taken and 
not tested, and the Investigator must document this in the study centre study records. 
See SoA for data to be collected at the time of study discontinuation and follow-up and for any 
further evaluations that need to be completed. 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study centre. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The study centre must attempt to contact the subject and reschedule the missed visit as 
soon as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should continue 
in the study. 
• Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the subject’s medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarised in the SoA. 
Protocol waivers or exemptions are not allowed. 
Clinically significant safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue study 
treatment. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The Investigator will maintain a screening log to record details of all 
subjects screened and to confirm eligibility or record reasons for screening failure, as applicable. 
Procedures conducted as part of the subject’s routine clinical management (e.g., blood count) and 
obtained before signing of the ICF may be utilised for screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame 
defined in the SoA. 
The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, will not exceed 250 mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
8.1 
Efficacy Assessments 
The following clinical assessments will be performed according to the SoA. 
ASAS20 Clinical Response 
An improvement of at least 20% and an absolute improvement of at least 10 units on a 0-
100 scale in at least 2 of the following domains: Subject’s Global Assessment of Disease Status, 
Subject’s Assessment of Spinal Pain, Function (BASFI), and Inflammation (last 2 questions of 
BASDAI) (Sieper 2009). ASAS40 and ASAS70 are defined as above with improvements of at 
least 40% and 70%, respectively. 
Subject’s Global Assessment of Disease Status 
The subject’s overall assessment of current disease status (e.g., during the past week and the past 
48 hours) on a 100 mm horizontal visual analogue scale (VAS). The left-hand extreme of the line 
is symptom-free and no AS symptoms and the right-hand extreme is maximum AS disease 
severity. 

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Subject’s Assessment of Spinal Pain 
The subject’s overall assessment of the severity of spinal pain is based on a single question on a 
100 mm horizontal VAS. The left-hand extreme of the line is “no pain” (symptom-free) and the 
right-hand extreme is “most severe pain” (maximum pain). 
BASDAI 
The BASDAI is a subject-administered assessment of 6 parameters specific to AS. The following 
parameters are assessed on a 100 mm horizontal VAS: fatigue, spinal pain, peripheral arthritis, 
enthesitis, intensity of morning stiffness and duration of morning stiffness. 
For questions 1-5, the left-hand extreme of the line is “none” (symptom-free) and the right-hand 
extreme is “very severe” (maximum severity). Whereas for question 6, a time-axis is used. The 
left-hand extreme of the line is “0 hours” and the right-hand extreme is “2 or more hours”. 
The BASDAI score is: [Q1 + Q2 + Q3 + Q4 + (Q5 + Q6)/2]/5 
BASFI 
The BASFI is an assessment of function in an AS subject. The subject provides their own 
assessment of 10 questions on a 100 mm horizontal VAS. The BASFI score is the mean of these 
values. 
ASDAS-CRP 
The ASDAS-CRP is a composite index to assess disease activity in AS (Lukas 2009). It 
combines 5 disease activity variables with only partial overlap, resulting in one single score with 
better validity, enhanced discriminative capacity and improved sensitivity to change as compared 
to single-item variables (Lukas 2009; van der Heijde 2009). 
The ASDAS-CRP will be calculated according to the following formula: 
0.12 x back pain + 0.06 x duration of morning stiffness + 0.11 x patient global assessment + 0.07 
x peripheral pain/swelling + 0.58 x ln (CRP +1) 
Values below the CRP threshold will be computed as half of the value of the threshold. 
For disease activity states, the following defined cut-offs will be used: ASDAS <1.3 to define 
“inactive disease”, 1.3 ≤ ASDAS <2.1 to define “moderate disease activity”, 2.1 ≤ ASDAS ≤3.5 
to define “high disease activity”, and ASDAS >3.5 to define “very high disease activity”. A 
change of ≥1.1 units represents “clinically important improvement”, and a change of ≥2.0 units 
represents major improvement. 

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Magnetic Resonance Imaging 
An MRI of the axial skeleton will be taken at the times indicated in the SoA. The MRI will be 
obtained using 1.0, 1.5 or 3.0 Tesla scanners and phase array coils. Sagittal images of the upper 
(including C2 to T10) and lower (including T8 to S1) spine will be taken. The field of view is 
34 to 38 cm. The following sequences may be used: T1 weighted turbo spin echo with a slice 
thickness of 3 mm and STIR (a sequence with intrinsic fat saturation) with a slice thickness of 
3 mm. 
MRI scans will be evaluated using Spondyloarthritis Research Consortium of Canada (SPARCC) 
MRI index for scoring inflammation of the spine. 
Details of site training, MRI acquisition and central reading methods are detailed in the 
procedure manual for MRI examinations and the Imaging Review Charter (provided separately). 
MRI scans will be sent to the Central Imaging Laboratory. Specific shipping and transmitting 
instructions are provided in the procedure manual for MRI examination. 
Immunophenotyping and Biomarker Evaluation 
Pre- and post-treatment immunophenotyping with FACS, CyTOF and cell subset specific gene 
expression analysis (RNA seq and qPCR) of CD4, CD8, CD56 and CD14 cells will be 
performed. Blood, serum and urine will be analysed for protein and other biomarkers including 
genetic markers. Stool samples will be taken for microbiome analysis. 
Neuropathic Pain Score 
The painDETECT™ score (Freynhagen 2006) will be administered on Weeks 0, 6, 12 and 28. 
Absolute score and proportion fulfilling criteria for neuropathic pain on painDETECT™ score 
will be enumerated. 
Joint Count, Tendon Swelling and Enthesitis 
A swollen and tender joint count (68 joints) and the Leeds Enthesitis score (Healy 2008) will be 
performed on Weeks 0, 2, 6, 10 and 12. 
8.2 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
Safety assessments will be performed throughout the study from signing of the consent form by 
the monitoring of AEs, physical examinations, vital signs, laboratory results (haematology, 
serum biochemistry and urinalysis), lung function tests and electrocardiograms (ECG). 
In addition, exploratory monitoring for signs of PAP will be conducted throughout the study 
using a breathlessness questionnaire (Medical Research Council [MRC] Breathlessness Scale), 

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chest x-ray, lung function testing and pulse oximetry; see Section 8.2.4 for further information 
on this aspect of safety assessment. 
8.2.1 
Physical Examinations 
A general physical examination (including height and weight, cardiovascular, respiratory, 
gastrointestinal and neurological systems) should be performed and recorded as “normal” or 
“abnormal” with specified abnormalities at the times indicated in the SoA. 
8.2.2 
Vital Signs 
Vital signs (pulse rate, systolic and diastolic blood pressure and temperature) will be taken at the 
times indicated in the SoA. The blood pressures should be taken after the subject has been seated 
for at least 5 minutes. Additional readings may be taken at the discretion of the Investigator in 
the event of an adverse reaction. 
8.2.3 
Electrocardiograms 
A single 12-lead ECG will be obtained as outlined in the SoA using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. 
8.2.4 
Target-specific Safety Evaluation: Pulmonary Alveolar Proteinosis 
8.2.4.1 
Medical Research Council (MRC) Breathlessness Scale 
The MRC Breathlessness Scale will be used to assess any dyspnoea in the subjects taking part in 
the study. The scale consists of 5 levels of perceived breathlessness based on different physical 
activity: its categories range from 1-5 as shown in Table 6 (Stenton 2008). 
Table 6 
MRC Breathlessness Scale 
 
Grade 
Degree of Breathlessness Related to Activities 
1 
Not troubled by breathlessness except on strenuous exercise 
2 
Short of breath when hurrying on the level or walking up a slight hill 
3 
Walks slower than most people on the level, stops after a mile or so, or stops after 15 
minutes walking at own pace 
4 
Stops for breath after walking about 100 yards or after a few minutes on level ground 
5 
Too breathless to leave the house, or breathless when undressing 
The MRC breathlessness scale will be used at the time points specified in the SoA and any 
clinically significant changes may trigger the withdrawal of the subject and adequate follow-up, 
at the Investigator’s discretion. 

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8.2.4.2 
Chest X-ray 
A baseline posterior-anterior (PA) chest x-ray taken no later than 3 months prior to the visit, with 
no clinically significant abnormalities consistent with PAP, should be available at screening. If 
no such x-ray is available, then subjects will be required to undergo this procedure at Baseline 
and assessment made before any study medication is administered to the subject at this clinic 
visit. Further x-rays will also be required during clinic visits at Weeks 12 and 28, respectively (as 
shown in SoA). 
8.2.4.3 
Lung Function Testing 
Spirometry for pulmonary function testing will be performed at the time points specified in the 
SoA. All measurements will be performed pre-dose and will be recorded with a handheld device 
and be transferred into the eCRF. Values will be corrected to BTPS (body temperature and 
pressure, saturated) conditions. 
The following parameters will be recorded and be transferred into the eCRF: 
FEV1: Forced Expiratory Volume in the first second 
FVC: Forced Vital Capacity (expiratory) 
PEF: Peak Expiratory Flow Rate 
The Investigator should ensure that the measurement is adequately done and that no coughing, 
inadequate technique or other incidents obscure the result. 
8.2.4.4 
Pulse Oximetry 
Pulse oximetry will be measured using standardised devices, at the time points specified in the 
SoA. 
The result on the saturation of peripheral oxygen (SpO2) will be recorded and transferred into the 
eCRF. 
8.2.5 
Pulmonary Alveolar Proteinosis 
If a subject develops any signs or symptoms consistent with PAP during the course of this study, 
adequate measures to diagnose the condition should immediately be initiated and if confirmed, 
the subject should be withdrawn and treatment initiated as applicable. Judgement on symptoms 
relating to PAP will be the responsibility of the Investigator. All PAP assessments will be 
documented in the eCRF. 

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Subjects should be referred to a pulmonologist for: 
1) 12% deterioration in FEV1 and/or FVC 
or 
2) deterioration by >5% decrease in oxygen saturation (SpO2), 
or 
3) an increase in MRC Breathlessness Scale score of 2 from baseline. 
Diagnosis tools for PAP include but are not limited to, repeated chest x-ray, high resolution 
computerised tomography (CT)-scanning, and bronchoalveolar lavage (see Appendix 6 for 
guidance on management of respiratory signs and symptoms). Data from any such assessments 
will be captured in the eCRF. 
Any incident which requires an investigation for PAP should be recorded as an AE named 
“suspected pulmonary alveolar proteinosis” and followed until a final outcome is determined. 
This includes a final determination of signs and symptoms attributed to PAP and every effort 
should be made to elucidate both the actual cause as well as the causality relation to namilumab. 
8.2.6 
Documentation of Concomitant Medications 
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by the Sponsor. At each study visit, subjects will be asked whether they have taken 
any medication other than the study medication (used from signing of informed consent through 
the end of the study), and all medication including vitamin supplements, over-the-counter 
medications, and oral herbal preparations must be recorded in the eCRF. 
8.2.7 
Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are 
present at signing of informed consent. This includes clinically significant laboratory or physical 
examination abnormalities noted at the Screening examination. The condition (i.e., diagnosis) 
should be described. 
8.2.8 
Clinical Safety Laboratory Assessments 
See Appendix 3 for the list of clinical laboratory tests to be performed and the SoA for the timing 
and frequency. 
The Investigator must review the laboratory report, document this review and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 

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laboratory findings are those that are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the subject’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 18 weeks after the last dose of study treatment should be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by the 
Investigator or Medical Monitor. 
If such values do not return to normal/baseline within a period of time judged reasonable by the 
Investigator, the aetiology should be identified and the Sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 3, must be conducted in 
accordance with the laboratory manual and the SoA. 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered clinically 
significant by the Investigator (e.g., SAE or AE or dose modification), then the results must be 
recorded in the eCRF. 
8.3 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorised representative). 
The Investigator and any designees are responsible for detecting, documenting and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
subject to discontinue the study treatment (see Section 7.0). 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be collected from the signing of the ICF until the follow-up visit at the time points 
specified in the SoA (Section 1.3). 
All AEs will be collected from the signing of the ICF until the follow-up visit at the time points 
specified in the SoA (Section 1.3). 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 4. The Investigator will submit any updated SAE data to the Sponsor within 
24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 

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related to the study treatment or study participation, the Investigator must promptly notify the 
Sponsor. 
The method of recording, evaluating and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-
leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as defined in 
Section 8.3.6), will be followed until resolution, stabilisation, the event is otherwise explained, or 
the subject is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Appendix 4. 
8.3.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC) and Investigators. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and Sponsor policy and forwarded to Investigators as necessary. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then file 
it along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to 
local requirements. 

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8.3.5 
Pregnancy 
 
Details of all pregnancies in female subjects and, if indicated, female partners of male subjects, 
will be collected after the start of study treatment until term or outcome. 
If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
Adverse Events of Special Interest 
 
Adverse events of special interest include: 
• PAP 
• Neutropaenia 
• Myeloid suppression 
Prolonged systemic neutralisation of GM-CSF bears a theoretical risk of inducing PAP. This is 
based on the fact that people with an idiopathic PAP reveal polyclonal antibodies recognising 
human GM-CSF with high avidity and specificity. PAP is a rare disease and the condition has a 
variable clinical course, from spontaneous resolution to respiratory failure, and approximately 
31% of people with autoimmune PAP are asymptomatic (Suzuki 2010). Patients with idiopathic 
PAP gradually develop symptoms because surfactant protein in the lung alveoli is insufficiently 
cleared by GM-CSF-starved macrophages. Symptoms, such as dyspnoea, become clinically 
evident late, when surfactant accumulation in the alveoli has reached a level so that oxygen 
uptake is impaired (Burmester 2012). The risk of developing PAP after single or short-term 
repeated administration of namilumab is considered very low. PAP is a slowly developing 
disorder and clinical symptoms are not expected to develop until after years of disrupted GM-
CSF signalling. In hereditary PAP caused by mutation in the GM-CSF receptor, between 1.5 to 9 
years could elapse before symptoms develop, but also among homozygote carriers of the 
mutation asymptomatic cases are described, indicating that disrupted GM-CSF signalling is not 
the only factor needed for developing PAP (Fredriksson 1978). An important observation is that 
characteristic changes on x-ray develop in advance of severe symptoms. The issue has been 
addressed in the namilumab toxicology program, with no signs of PAP to date. Clinical data on 
GM-CSF inhibition are also without signals. In the mavrilimumab phase 2 study, 149 RA 
subjects were exposed to 4 different dose levels of mavrilimumab administered every 2 weeks 
for 12 weeks and no one developed PAP (Burmester 2012). In PRIORA, 3 repeated injections of 
150 mg namilumab 2 weeks apart did not induce PAP in the first 12 dosed subjects who have 
been evaluated for AEs and of which at least 8 received namilumab. 

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8.4 
Treatment of Overdose 
An overdose is defined as a known deliberate or accidental administration of investigational 
drug, to or by a study subject, at a dose above that which is assigned to that individual subject 
according to the study protocol. 
The Sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the subject for any AE/SAE and laboratory abnormalities until namilumab 
can no longer be detected systemically (at least 125 days). 
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject. 
According to the already available results of a PK study no specific antidote is available for 
namilumab. In case of overdose, it is recommended that the appropriate supportive medical care 
is provided. In case of allergic reaction, withdrawal of study medication is advised. For treatment 
of allergic reactions, current guidelines for treatment (e.g., with corticosteroids) should be 
applied. 
8.5 
Pharmacokinetics 
PK parameters are not evaluated in this study. 
8.6 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7 
Genetics 
Optional saliva samples will be taken on Day 1 from consenting subjects for genotypic analysis. 
8.8 
Biomarkers 
Collection of samples for biomarker research is also part of this study. The following samples for 
biomarker research are required and will be collected from all subjects in this study as specified 
in the SoA: 
• Blood for immunophenotyping and gene expression analysis 
• Serum/plasma for CRP and other protein and non-protein biomarkers 
• Stool for faecal calprotectin and microbiome analysis 

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Samples will be tested for exploratory objectives to evaluate the effect of namilumab on 
biomarkers at 12 weeks. 
Samples may be stored for a maximum of 10 years (or according to local regulations) following 
the last subject’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of biomarker responses to namilumab. 
8.8.1 
Immunogenicity Assessments 
Antibodies to namilumab will be evaluated in serum samples collected from all subjects 
according to the SoA. Additionally, serum samples should also be collected at the final visit from 
subjects who discontinued study treatment or were withdrawn from the study. These samples 
will be tested by the Sponsor or Sponsor's designee. 
Serum samples will be screened for antibodies binding to namilumab and the titre of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to namilumab and/or further characterise the immunogenicity of namilumab. 
The detection and characterisation of antibodies to namilumab will be performed using a 
validated assay method by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to study treatment will also be evaluated for namilumab serum 
concentration to enable interpretation of the antibody data. Antibodies may be further 
characterised and/or evaluated for their ability to neutralise the activity of the study 
treatment(s). Samples may be stored for a maximum of 5 years (or according to local 
regulations) following the last subject’s last visit for the study at a facility selected by the 
Sponsor to enable further analysis of immune responses to namilumab. 
8.9 
Medical Resource Utilisation and Health Economics 
Medical Resource Utilisation and Health Economics parameters are not evaluated in this study. 

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9.0 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
The hypothesis to be tested is H0: πnam = πpbo, where π represents the ASAS20 rate. The 
hypothesis will be evaluated using a Bayesian analysis. 
Prior clinical data in AS were used as the basis for prior distributions. Criteria for inclusion of 
studies were that the studies involved a similar biological agent, and were double-blind and 
placebo-controlled. Week 12 was the target visit and was used in the calculations for the priors, 
but for secukinumab Week 16 was used since Week 12 data were not reported outside of the 
figures. 
Data for control groups are shown in Figure 2 and Table 7. The estimated sample-size weighted 
mean ASAS20 was 0.34. The secukinumab studies allowed for prior DMART and anti-TNF 
agents, which yielded a lower ASAS20 than the other studies. 
Data for the active groups are shown in Figure 3 and Table 8. The estimated sample-size 
weighted mean ASAS20 was 0.6. As can be seen, a fair amount of variability is shown in the 
results with a secukinumab (75 mg) group with a low ASAS20 of 0.41, and tofacitinib (5 mg 
twice daily [BID]) with an ASAS20 of 0.81. The remaining studies exhibit ASAS20 tightly 
clustered around 0.6. 
Based on these results, the prior for the control will be targeted to ASAS20 of 0.3, and the active 
ASAS20 to 0.6. 

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Figure 2 
 Estimated ASAS20 and 95% Confidence Intervals for Placebo Treatment 
Group Data 
Secu = secukinumab. 
 
Table 7 
Reported ASAS20 Results for Placebo Treatment Group for Reference 
Studies 
 
Compound 
Reference 
Week 
N 
ASAS20 
Etanercept 
Maksymowych (2015) 
12 
106 
0.37 
Golimumab 
Sieper (2012, 2016) ACR 
12 
100 
0.40 
Tofacitinib 
van der Heijde (2017) 
12 
51 
0.41 
Secukinumab (phase 2) 
NCT00809159 
12 
6 
0.17 
Secukinumab 
Baeten 2015; MEASURE 1 
16 
122 
0.29 
Secukinumab 
Baeten 2015; MEASURE 2 
16 
74 
0.28 
Pooled 
459 
0.34 

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Figure 3 
 Estimated ASAS20 and 95% Confidence Intervals for Active Treatment 
Group Data 
Secu = secukinumab (M.1 = MEASURE 1 study, M.2 = MEASURE 2 study); Tofa = tofacitinib; Goli = golimumab; 
Etan = etanercept; Certo = Certolizumab pegol. 

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Table 8 
Reported ASAS20 Results for Active Treatment Group for Reference Studies 
 
Compound 
Reference 
Dose 
Week 
N 
Value 
Certolizumab pegol 
Label 
200 mg Q2weeks 
12 
65 
0.57 
Certolizumab pegol 
Label 
400 mg Q2weeks 
12 
56 
0.64 
Etanercept 
Maksymowych (2015) 
50 mg Q1week 
12 
101 
0.52 
Golimumab 
Sieper (2012, 2016) ACR 
Gol Q4weeks 
12 
97 
0.71 
Tofacitinib 
van der Heijde (2017) 
2 mg BID 
12 
52 
0.52 
Tofacitinib 
van der Heijde (2017) 
5 mg BID 
12 
52 
0.81 
Tofacitinib 
van der Heijde (2017) 
10 mg BID 
12 
52 
0.56 
Secukinumab 
NCT00809159 
10 mg/kg 
12 
23 
0.59 
Secukinumab 
Baeten 2015; MEASURE 1 
150 mg 
16 
125 
0.61 
Secukinumab 
Baeten 2015; MEASURE 1 
75 mg 
16 
124 
0.60 
Secukinumab 
Baeten 2015; MEASURE 2 
150 mg 
16 
72 
0.61 
Secukinumab 
Baeten 2015; MEASURE 2 
75 mg 
16 
73 
0.41 
Pooled 
892 
0.60 
9.2 
Sample Size Determination 
The placebo prior = beta(p=0.3, n=20), and the prior for active is beta(p=0.6, n=5). The sample 
sizes are the smallest n such that the median Q(P{θact > θpbo| Y(HA)}, 1 − γ) > Q(P{θact > θpbo| 
Y(H0)}, γ), where Q(f, γ) represents the γ quantile from the distribution f, and Y(HA) represents 
data generated under the alternative hypothesis, and Y(H0) represents data generated under the 
null hypothesis. Sample sizes are shown in Table 9. The recommended sample size is 42 (6 on 
placebo, 36 on active). A plot of the distribution of P{θact > θpbo| Y} with both hypotheses 
overlapping as a function of the total sample size is shown in Figure 4. 
Table 9 
Sample Sizes for 6:1 Randomisation, Based on the Parameter γ 
 
γ 
N Placebo 
N Active 
N Total 
0.80 
2 
12 
14 
0.85 
4 
24 
28 
0.90 
6 
36 
42 

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Figure 4 
Distribution of Posterior Probability P(θact > θpbo) as a Function of Total 
Sample Size, Under Both Hypotheses 
Shaded areas represent the middle 80% of the distribution (between the 10th and 90th percentiles). 

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9.3 
Populations for Analyses 
For purposes of analysis, the analysis sets in Table 10 are defined. For efficacy analyses, the Full 
Analysis Set (FAS) will be the primary analysis set, and the Per Protocol (PP) Analysis Set will 
be secondary. For safety analyses, the Safety Analysis Set will be the primary analysis set. 
Table 10        Analysis Sets 
 
Analysis Set 
Description 
Entered Analysis Set 
All subjects who sign the ICF. 
Randomly Assigned to Study 
Treatment Analysis Set 
All subjects in the Entered Analysis Set who are assigned to study treatment. 
Full Analysis Set 
All subjects randomly assigned to study treatment and who take at least 1 dose 
of study treatment and have specific post-baseline assessments available. 
Per Protocol 
All subjects in the Full Analysis Set that have week 10 efficacy data. 
Completer Analysis Set 
All subjects in the Full Analysis Set who complete the study. 
Safety Analysis Set 
All subjects randomly assigned to study treatment and who take at least 1 dose 
of study treatment. Subjects will be analysed according to the treatment they 
actually received. 
9.4 
Statistical Analyses 
The Statistical Analysis Plan (SAP) will be developed and finalised before database lock and will 
describe the subject analysis sets to be included in the analyses, and procedures for accounting 
for missing, unused and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints. 
All analyses, summaries and listings will be performed using SAS® software (version 9.2 or 
higher), or R (version 3.2 or higher). 
The following descriptive statistics will be used as applicable to summarise the study data unless 
otherwise specified: 
• Continuous variables: sample size (n), mean, standard deviation (SD), median, minimum 
(min), and maximum (max). 
• Categorical variables: frequencies and percentages. 
Individual subject data will be presented in listings. 
9.4.1 
Efficacy Analyses 

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Table 11 
Efficacy Analyses 
 
Endpoint 
Statistical Analysis Methods 
Primary 
The primary endpoint ASAS20 will be assessed using a Bayesian analysis. The control arm will 
have a beta prior with parameters rate = 0.3 and ν = 20, and the namilumab arm will have a beta 
prior with rate 0.6 and ν = 5. Posterior distributions will be calculated, and parameter distributions 
shown. The mean, standard deviation, and 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of the 
posterior distribution will be presented. The posterior distribution will also be presented 
graphically. Given the observed data, the posterior probability η ≡ P(πnam > πpbo) will be calculated 
(Raineri 2014) and presented. Values of η >0.927 will provide strong evidence that namilumab 
exhibits therapeutic benefit relative to placebo control. 
Missing data will be treated as non-responders for this analysis. 
For assessment of robustness of the analysis, the analysis will be performed on Completer Analysis 
Set. 
Secondary 
Summary statistics of ASAS20, ASAS40 and other efficacy endpoints will be summarised by visit 
and treatment group. Summary statistics will be provided on both the Full and PP Analysis Sets. 
Exploratory 
Statistics used to summarise these endpoints will be described in the SAP. 
 
9.4.1.1 
Handling of Missing Data 
Non-responder imputation will be used for missing data in the FAS. Missing data will be 
excluded from analysis in the PP Analysis Set. 
Missing data will not be imputed in the Safety Analysis Set. 
9.4.2 
Safety Analyses 
All safety analyses will be performed on the Safety Analysis Set. 
TEAEs are defined as AEs that first occurred or worsened in severity after the first 
administration of study treatment and prior to 125 days after the last administration of study 
treatment. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). For each 
study treatment, numbers of TEAEs and incidence rates will be tabulated by preferred term and 
system organ class. 
TEAEs by maximum severity, TEAEs by relationship to study treatment, SAEs, TEAEs leading 
to death and TEAEs leading to discontinuation of study treatment will be tabulated for each 
treatment group. Commonly occurring TEAEs, i.e., those that occur in 5% or more of the 
subjects in either treatment group, will be summarised using descriptive statistics. 
All laboratory test results, vital signs measurements, ECG results, weight and body mass index 
(BMI) will be summarised for each treatment group using descriptive statistics at each scheduled 
visit for raw numbers and change from baseline. The incidence of treatment-emergent abnormal 
laboratory, vital sign and ECG values will also be summarised using descriptive statistics. 

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visit for raw numbers and change from baseline. The incidence of treatment-emergent abnormal 
laboratory, vital sign and ECG values will also be summarised using descriptive statistics. 
9.4.3 
Other Analyses 
Biomarker exploratory analyses will be described in the SAP. 
9.4.4 
Missing Data 
Data from subjects who withdraw from the study, including AEs and any follow-up, will be 
included in the analyses of primary and secondary outcomes. 
Missing data (including those due to early discontinuations) will be imputed by a non-responder 
imputation (NRI). The NRI will be the primary imputation method for handling the missing data. 
As a sensitivity analysis, the analysis will also be performed on completers only. 
9.5 
Interim Analyses 
No interim analysis for efficacy is planned. 
9.6 
Safety Review Team 
A Safety Review Team consisting of the Coordinating Investigator, the Sponsor’s Medical 
Expert/Chief Medical Officer, and an independent Safety Physician will review ongoing safety 
data on a monthly basis. The data review will be conducted for randomised subjects and will 
include a review of vital signs, laboratory assessments, ECGs, AEs (including AEs of special 
interest and SAEs), physical examinations, and assessments of pulmonary functions. The Safety 
Review Team will provide consolidated feedback of the Team’s findings to the study team. 
Additional details of the Safety Review will be provided separately. 

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10.0 REFERENCES 
Baeten D, Sieper J, Bruan J, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing 
spondylitis. N Engl J Med 2015;373:2534-48. 
Burmester GR, Weinblatt ME, McInnes IB, et al. Efficacy and safety of mavrilimumab in 
subjects with rheumatoid arthritis. Ann Rheum Dis. 2013 Sep 1;72(9):1445-52 Epub 2012 Dec 
12. 
Davis, JC, van der Heijde DM, Braun J, et al. Sustained durability and tolerability of etanercept 
in ankylosing spondylitis for 96 weeks. Ann Rheum Dis 2005;64:1557-62. 
Fredriksson T, Petterson U. Severe psoriasis – oral therapy with a new retinoid. Dermatologica 
1978;157:234-244. 
Freynhagen R, Baron R, Gockel U et al. PainDETECT™: a new screening questionnaire to 
identify neuropathic components in patients with back pain. Curr Med Res Opin 2006;22:1911- 
20. 
Gluck T, Muller-Ladner U. Vaccination in patients with chronic rheumatic or autoimmune 
diseases. Clin Infect Dis 2008;46(9):1459-65. 
Guideline on Comparability of Medicinal Products Containing Biotechnology – Derived Proteins 
as Active Substance Non-Clinical and Clinical Issues. EMA CPMP Guideline December 
2003;3097/02. 
Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing 
measures development of an instrument specific to arthritis. Arthritis Care and Research 
2008;59:686-91. 
Inman RD, Davis JC, Heijde D, et al. Efficacy and safety of golimumab in patients with 
ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, phase III trial. 
Arthritis Rheum 2008;58:3402-12. 
Landewe R, Braun J, Deodhar A, et al. Efficacy of certolizumab pegol on signs and symptoms of 
axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind 
randomised placebo-controlled phase 3 study. Ann Rheum Dis 2014;73:39-47. 
Lukas C, Landewe R, Sieper J, et al. Development of an ASAS-endorsed disease activity scale 
(ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18-24. 
Maksymowych WP, Dougados M, van der Heijde D, et al. Clinical and MRI responses to 
etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK 
study. Ann Rheum Dis. 2016 Jul;75(7):1328-35. Epub 2015 Aug 12. 

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Rahier JF, Moutschen M, Van Gompel A, Van Ranst M, Louis E, Segaert S, et al. Vaccinations 
in 
patients 
with 
immune-mediated 
inflammatory 
diseases. 
Rheumatology 
(Oxford) 
2010;49(10):1815-27. 
Raine C, Keat A. Axial spondyloarthritis. Medicine 2014;42:251-256. 
Raineri E, Dabad M, Heath S (2014). A Note on Exact Differences between Beta Distributions in 
Genomic (Methylation) Studies. PLoS ONE 9(5): e97349. 
Scotti N, Bascherini V, Caso F, et al. TNFα-inhibitors for ankylosing spondylitis and non- 
radiographic axial spondyloarthritis. Clinical Pharmacist, 2017, Vol 9, No 1, online. 
Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, Dougados M, 
Hermann K-G, Landewé, Maksymowych W, van der Heijde D. The Assessment of 
SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. 
Ann Rheum Dis 2009;68(SupplII):ii1-ii4. 
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 Jun;72(6):815-22. Epub 2012 Jul 7. 
Sieper J, Rudwaleit M, Lenaerts J, et al. Partial remission in ankylosing spondylitis and 
nonradiographic axial spondyloarthritis in treatment with infliximab plus naproxen or naproxen 
alone: associations between partial remission and baseline disease characteristics. Rheumatology 
2016;55:1946-53. 
Stenton C. The MRC breathlessness scale. Occup Med (Lond). 2008 May;58(3):226-7. 
Strand V, Singh JA. Patient burden of axial spondyloarthritis. J Clin Rheumatol. 2017 
Oct;23(7):383-391. 
Suzuki, et al. Pulmonary alveolar proteinosis Am J Respir Crit Care Med 2010;182(10):1292- 
304. 
Toussirot E. New treatment options and emerging drugs for axial spondyloarthritis: biological 
and targeted synthetic agents. Expert Opin Pharmacother 2017;18:275-82. 
van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients 
with ankylosing spondylitis: results of a randomised, placebo-controlled trial (ASSERT). 
Arthritis Rheum 2005;52:582-91. 
van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with 
ankylosing spondylitis: results of a multicenter, randomised, double-blind, placebo-controlled 
trial. Arthritis Rheum 2006;54:2136-46. 

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van der Heijide D, Lie E, Kvien TK, et al. ASDAS, a highly discriminatory ASAS-endorsed 
disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:1811-8. 
van der Heijde D, Deodhar A, Wei JC, et al. Tofacitinib in patients with ankylosing spondylitis: 
a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 
2017;76:1340–1347. 

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11.0 APPENDICES 

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Appendix 1 
Abbreviations 
Abbreviation 
Definition 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AS 
Ankylosing spondylitis 
ASAS(20,40,70) 
Assessment in Ankylosing Spondylitis with 20%/40%/70% 
improvement 
ASDAS-CRP 
Ankylosing Spondylitis Disease Activity Score C-reactive Protein 
AST 
Aspartate aminotransferase 
axSpA 
Axial spondyloarthritis 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
BID 
twice daily 
BMI 
body mass index 
BTPS 
body temperature and pressure, saturated 
CONSORT 
Consolidated Standards of Reporting Trials 
CPMP 
Committee for Proprietary Medicinal Products 
CRO 
contract research organisation 
CRP 
C-reactive protein 
CT 
computerised tomography 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EoT 
End-of-Treatment 
ET 
Early Termination 
FAS 
Full Analysis Set 
FU 
Follow-up 
GM-CSF 
granulocyte-macrophage colony-stimulating factor 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
Hep 
hepatitis 
HIV 
human immunodeficiency virus 

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Abbreviation 
Definition 
ICF 
informed consent 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IgG1 
immunoglobulin G1 
IL(-17) 
interleukin-17 
IMP 
investigational medicinal product 
INR 
international normalised ratio 
IRB 
Institutional Review Board 
i.v. 
intravenous 
IWRS 
interactive web response system 
max 
maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
MED ID 
medication identification 
min 
minimum 
MRC 
Medical Research Council 
MRI 
magnetic resonance imaging 
MTX 
methotrexate 
nr-axSpA 
non-radiographic axSpA 
NRI 
non-responder imputation 
NSAID 
non-steroidal anti-inflammatory drugs 
PA 
posterior, anterior 
PAP 
pulmonary alveolar proteinosis 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
phSpA 
peripheral spondyloarthritis 
PK 
pharmacokinetic 
PP 
Per Protocol 
RA 
Rheumatoid arthritis 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous 
SD 
Standard deviation 

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Abbreviation 
Definition 
SoA 
Schedule of Activities 
SpA 
spondyloarthropathy 
SpO2 
saturation of peripheral oxygen 
SUSAR 
suspected unexpected serious adverse reactions 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TNF 
tumour necrosis factor 
TNFi 
tumour necrosis factor inhibitor 
ULN 
upper limit of normal 
VAS 
visual analogue scale 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 

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Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
- 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines. 
- 
Applicable ICH Good Clinical Practice (GCP) Guidelines. 
- 
Applicable laws and regulations. 
The protocol, protocol amendments, ICF, Investigator Brochure and other relevant documents 
(e.g., adve1tisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC and regulato1y authority approval, when 
applicable, before implementation of changes made to the study design, except for changes 
necessa1y to eliminate an immediate hazard to subjects. 
The Investigator will be responsible for the following: 
- 
Providing written Slllllillaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies and procedures 
established by the IRB/IEC. 
- 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
- 
Providing oversight of the conduct of the study at the study centre and adherence 
to requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
After reading the protocol, each Investigator will sign the protocol signature page and send 
a copy of the signed page to the Sponsor or representative (Appendix 9). The study will not sta1t 
at any study centre at which the Investigator has not signed the protocol. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
info1mation as requested to allow the Sponsor to submit complete and accurate financial 
ce1tification or disclosure statements to the appropriate regulato1y authorities. Investigators are 
responsible for providing info1mation on financial interests during the course of the study and for 
1 year after completion of the study. 

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Insurance 
Sponsor will provide insurance in accordance with local guidelines and requirements as a 
minimum for the subjects in this study. The terms of the insurance will be kept in the study files. 
Informed Consent Process 
The Investigator or his/her representative will explain the nature of the study to the subject or 
his/her legally authorised representative and answer all questions regarding the study. 
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorised representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study centre. 
The medical record must include a statement that written informed consent was obtained before 
the subject was entered in the study and the date the written consent was obtained. The 
authorised person obtaining the informed consent must also sign the ICF. 
Subjects must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
A copy of the ICF(s) must be provided to the subject or the subject’s legally authorised 
representative. 
Subjects who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional exploratory research. The Investigator or authorised designee will explain to each 
subject the objectives of the exploratory research. Subjects will be told that they are free to 
refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a subject’s agreement to allow 
any remaining specimens to be used for exploratory research. Subjects who decline to participate 
in this optional research will not provide this separate signature. 
Data Protection 
Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets that 
are transferred to the Sponsor will contain the identifier only; subject names or any information 
which would make the subject identifiable will not be transferred. 
The subject must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. 

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The subject must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorised personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
Administrative Structure 
Table 12        Study Administrative Structure 
 
Function 
Responsible Organisation 
Study Operations Management 
CRO 
Medical Monitoring 
CRO 
Study Master File 
CRO 
Randomisation Code 
CRO 
Data Management 
CRO 
Clinical Supply Management 
3rd party 
Quality Assurance Auditing 
CRO 
Biostatistics 
CRO 
Medical Writing 
CRO 
Laboratory Assessments 
3rd party (local laboratories at sites) 
Electrocardiogram Collection, Review, and Analysis 
At site 
Pharmacokinetic Sample Testing 
3rd party 
CRA 
CRO 
Pharmacovigilance 
CRO 
 
Medical Monitor 
 

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Dissemination of Clinical Study Data 
The results of the study should be reported within 1 year from the end of the clinical study. 
Irrespective of the outcome, the Sponsor will submit to the European Union (EU) database a 
summary of the results of the clinical study within 1 year from the end of the clinical study. It 
shall be accompanied by a summary written in a manner that is understandable to laypersons. 
Data Quality Assurance 
All subject data relating to the study will be recorded on eCRFs unless transmitted to the Sponsor 
or designee electronically (e.g., laboratory data). The Investigator is responsible for verifying 
that data entries are accurate and correct by physically or electronically signing the eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorised study centre personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of subjects are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. 
Source Documents 
The Investigator/institution should maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the study centre’s subjects. Source data 
should be attributable, legible, contemporaneous, original, accurate and complete. Changes to 
source data should be traceable, should not obscure the original entry, and should be explained if 
necessary (e.g., via an audit trail). 
Source documents provide evidence for the existence of the subject and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s study centre. 

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Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
Study and Study Centre Closure 
The Sponsor or designee reserves the right to close the study centre or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study centres will be closed upon study 
completion. A study centre is considered closed when all required documents and study supplies 
have been collected and a study centre closure visit has been performed. 
The Investigator may initiate study centre closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study centre by the Sponsor or Investigator may include but 
are not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of subjects by the Investigator. 
• Discontinuation of further study treatment development. 
Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study centre will be set forth in the Clinical Trial Agreement. 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicentre studies only in their entirety and not as individual study centre data. In this case, a 
Coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 

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Appendix 3 
Clinical Laboratory Tests 
The tests detailed in Table 13 will be performed by the local laboratory at each Investigator site. 
Additional tests may be performed at any time during the study as determined necessary by the 
Investigator or required by local regulations. 
Table 13 
Protocol Required Safety Laboratory Assessments 
 
Laboratory 
Assessments 
Parameters 
Haematology 
Platelet Count 
RBC Indices: 
Mean corpuscular volume 
(MCV) 
Mean corpuscular haemoglobin 
(MCH) 
Mean corpuscular haemoglobin 
concentration (MCHC) 
%Reticulocytes 
White Blood Cell Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red Blood Cell 
(RBC) Count 
Haemoglobin 
Haematocrit 
Clinical Chemistrya 
Blood Urea 
Nitrogen 
Potassium 
Aspartate 
Aminotransferase 
(AST)/Serum 
Glutamic- 
Oxaloacetic 
Transaminase 
(SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
Alanine 
Aminotransferase 
(ALT)/Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
Total Protein 
Glucose 
Calcium 
Alkaline 
phosphatase 
albumin 
Chloride 
Phosphorous 
Serum Lipids 
Total cholesterol 
Triglycerides 
HDL 
LDL 
Biomarkers 
Faecal calprotectin 
C-reactive protein 
(CRP) 
HLA-B27 
Erythrocyte 
sedimentation rate 
Stool sample for 
microbiome 
analysis 
Immunophenotyping 
Immunogenicity 
Anti-namilumab 
antibodies 

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Laboratory 
Assessments 
Parameters 
Routine Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in women of non-childbearing 
potential only) 
• 
Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as needed for 
women of childbearing potential)b 
• 
Serology: Hepatitis B (hepatitis B virus surface antigen [HBsAg] positive [+] or 
detected sensitivity on the hepatitis B virus [HBV] DNA polymerase chain reaction 
[PCR] qualitative test for hepatitis B core antibodies [HBc Ab]/hepatitis B surface 
antibody [HBsAb] positive subjects) or hepatitis C (hepatitis C virus [HCV] RNA 
detectable in any subject with anti-hepatitis C virus antibody [HCV Ab]). 
• 
ANA (anti-dsDNA titres if ANA is positive) 
• 
QuantiFERON-TB test (or equivalent test) 
The results of each test must be entered into the (e)CRF. 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping or 
monitoring event are given in Section 7.1. All events of ALT ≥3 × upper limit of normal (ULN) and bilirubin 
≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN and international normalised ratio (INR) >1.5, if INR 
measured, which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis). 
b Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
Investigators must document their review of each laboratory safety report. 

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Appendix 4 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
 
Definition of AE 
 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or subject, temporally associated with the use of 
study treatment, whether or not considered related to the study treatment. 
• 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) or other safety 
assessments (e.g., ECG, radiological scans, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgement of the Investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency 
and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it may have been 
present before the start of the study. 
• 
Signs, symptoms or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms or the clinical sequelae of a suspected overdose of either study treatment or a concomitant 
medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional overdose taken 
with possible suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an AE or 
SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms and/or 
clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfil the definition of 
an AE or SAE. 
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the Investigator to be more severe than expected for 
the subject’s condition. 
• 
The disease/disorder being studied or expected progression, signs or symptoms of the disease/disorder being 
studied, unless more severe than expected for the subject’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to the procedure is 
the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience admission to a 
hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the start 
of the study that do not worsen. 

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Definition of SAE 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalisation for signs/symptoms of the disease under study, death due 
to progression of disease). 
 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a) Results in death 
b) Is life-threatening 
The term ‘life-threatening’ in the definition of “serious” refers to an event in which the subject was at risk of 
death at the time of the event. It does not refer to an event, which hypothetically might have caused death, if it 
were more severe. 
c) Requires inpatient hospitalisation or prolongation of existing hospitalisation 
In general, hospitalisation signifies that the subject has been detained (usually involving at least an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during hospitalisation are AEs. If a 
complication prolongs hospitalisation or fulfils any other serious criteria, the event is serious. When in doubt as to 
whether “hospitalisation” occurred or was necessary, the AE should be considered serious. 
Hospitalisation for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
d) Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhoea, influenza, and accidental trauma (e.g., sprained ankle) 
which may interfere with or prevent everyday life functions but do not constitute a substantial disruption. 
e) Is a congenital anomaly/birth defect 
f)   Other situations: 
• 
Medical or scientific judgement should be exercised in deciding whether SAE reporting is appropriate in 
other situations such as important medical events that may not be immediately life-threatening or result in 
death or hospitalisation but may jeopardise the subject or may require medical or surgical intervention to 
prevent 1 of the other outcomes listed in the above definition. These events should usually be considered 
serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency room or 
at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation, or 
development of drug dependency or drug abuse. 

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Recording and Follow-up of AE and/or SAE 
 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (e.g., 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF. Each event must be recorded 
separately. 
• 
It is not acceptable for the Investigator to send photocopies of the subject’s medical records to the CRO in 
lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by the CRO. In this 
case, all subject identifiers, with the exception of the subject number, will be redacted on the copies of the 
medical records before submission to the CRO. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms and/or other 
clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will be 
documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study and assign 
it to 1 of the following categories: 
• 
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with 
everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not be 
confused with a SAE. Severe is a category utilised for rating the intensity of an event; and both AEs and 
SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the pre-defined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between study treatment and each occurrence of each 
AE/SAE. The AE must be characterised as unrelated, unlikely to be related, possibly related, probably related 
or unknown (unable to judge). 
o 
“Probably related” conveys that there are facts, evidence, and/or arguments to suggest a causal 
relationship, rather than a relationship cannot be ruled out. 
o 
“Possibly related” suggests that the association of the AE with the study treatment is unknown; 
however, the AE is not reasonably supported by other conditions. 
o 
“Unlikely to be related” suggests that only a remote connection exists between the study treatment 
and the AE. Other conditions, including chronic illness, progression or expression of the disease 
state or reaction to concomitant therapy, appear to explain the reported AE. 
o 
“Unrelated” is used if there is not a reasonable possibility that the study treatment caused the AE. 
o 
All efforts should be made to classify the AE according to the above categories. The category 
“unknown” (unable to judge) may be used only if the causality is not assessable, e.g., because of 
insufficient evidence, conflicting evidence, conflicting data or poor documentation. 
• 
The Investigator will use clinical judgement to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study treatment administration will be considered and investigated. 
• 
The Investigator will also consult the Investigator’s Brochure (IB) and/or Product Information, for marketed 
products, in his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the AE/SAE 

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and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal information to 
include in the initial report to the CRO. However, it is very important that the Investigator always make an 
assessment of causality for every event before the initial transmission of the SAE data to the CRO. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and send a SAE 
follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting requirements. 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements and/or 
evaluations as medically indicated or as requested by the CRO to elucidate the nature and/or causality of the 
AE or SAE as fully as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• 
If a subject dies during participation in the study or during a recognised follow-up period, the Investigator 
will provide the CRO with a copy of any postmortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to the Sponsor within 24 hours of receipt of the 
information. 
Reporting of SAEs 
 
SAE Reporting to the Medical Monitor via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to the Medical Monitor will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the study centre will use the paper SAE 
data collection tool (see next section). 
• 
The study centre will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given study centre, the electronic data collection tool will be taken off-line 
to prevent the entry of new data or changes to existing data. 
• 
If a study centre receives a report of a new SAE from a subject or receives updated data on a previously 
reported SAE after the electronic data collection tool has been taken off-line, then the study centre can report 
this information on a paper SAE form (see next section) or to the CRO Safety Team by telephone/fax or 
email. 
• 
Contacts for SAE reporting can be found in the safety paper forms for the sites. 
SAE Reporting to the Medical Monitor via Paper CRF 
• 
The secondary (backup) mechanism for reporting an SAE to the Medical Monitor will be via a paper CRF. 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this information to the 
Medical Monitor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is acceptable with 
a copy of the SAE data collection tool sent by overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the Investigator to complete and sign the SAE 
CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in the SAE paper form and the safety management plan. 

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Appendix 5 
Excluded Medications/Therapy 
Excluded medications/therapy is listed below. The use of an excluded medication/therapy is a 
protocol violation and must be recorded in the eCRF. 
Excluded Medications and Treatments: 
 
Any treatment antagonising GM-CSF or its 
receptor 
At any time prior to the Screening visit, during the study, or for 
14 weeks after the last dose of study medication 
Not stable doses of methotrexate, 
sulfasalazine, leflunomide 
Change in dosage within 28 days prior to the Screening visit 
and/or not planned to be continued at a stable dose with the same 
formulation until at least the end of Week 12 
Hydroxychloroquine >400 mg/day or 
Chloroquine > 250mg/day 
Within 4 weeks prior to the Screening visit and at any time during 
the study 
Not stable doses of Hydroxychloroquine 
≤400 mg/day or Chloroquine ≤250 mg/day 
Within 28 days prior to the Screening visit and/or not planned to 
be continued at a stable dose with the same formulation until at 
least the end of Week 24 
Any immunomodulatory biological agents or 
kinase inhibitor (either experimental or 
approved) except for previous treatment with 
TNF inhibitors. 
At any time prior to the Screening visit and at any time during the 
study 
Any adjustment in agents to treat 
dyslipidaemia 
New treatment or dose-adjustment to on-going medication for 
dyslipidaemia, such as (but not limited to) statins, within 6 weeks 
prior to randomisation, i.e., a dose that is not stable for at least 6 
weeks prior to randomisation 
Infliximab, etanercept, adalimumab, 
golimumab or certolizumab pegol 
Within 8 weeks prior to Baseline visit and at any time during the 
study 
Anti-IL-17A or IL12/23 therapy 
At any time prior to the Screening visit and at any time during the 
study 
Stem cell transplantation 
At any time prior to the Screening visit and at any time during the 
study 
Cyclosporine, tacrolimus, or mycophenolate 
mofetil 
Within 28 days prior to Baseline 
Treatment with oral corticosteroids 
exceeding 10 mg/day prednisolone or 
equivalent, or has been taking both oral 
budesonide and prednisone (or equivalent) 
simultaneously 
Within 28 days prior to the Baseline visit and at any time during 
the study 
Not stable doses of oral corticosteroids 
≤10 mg/day prednisolone or equivalent 
Change in dosage within 28 days prior to the Screening visit 
and/or not planned to be continued at a stable dose with the same 
formulation until at least the end of Week 12 
Any treatment with intravenous 
corticosteroids 
Within 14 days prior to Screening or during the Screening period 
and at any time during the study 
Intra-articular corticosteroids 
Prohibited any time during screening and up to Week 12. A 
maximum of one injection given in a small joint (DIP or MCP) 
and clearly documented in the eCRF is allowed. 

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Changes in NSAID/COX-2 dose levels 
Within 28 days prior to randomisation, and/or not planned to be 
continued at a stable dose with the same formulation until at least 
the end of Week 12 (with appropriate gastric protection). Except 
for safety related reasons, where dose reduction may be done. 
Changes in the doses of opioid-containing 
medications 
Within 4 weeks prior to randomisation and at any time during the 
study. Except for safety related reasons where reduction may be 
done. 
Immunisation with a live or live-attenuated 
vaccine 
Within 2 weeks prior to randomisation and at any time during the 
study and for 1 month following last study drug administration 
Any investigational agent 
Within 30 days or 5 half-lives prior to Baseline 

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Appendix 6 
Management of Respiratory Signs and Symptoms in 
Relation to PAP Disease Background 
A caveat of systemically neutralising GM-CSF could be a hypothetical potential for inducing 
pulmonary alveolar proteinosis (PAP). PAP is a rare disease characterised by intra-alveolar 
accumulation of surfactant components and cellular debris with minimal interstitial inflammation 
or fibrosis. In a proportion of patients with idiopathic PAP, autoantibodies against GM-CSF have 
been detected. It seems plausible that the autoantibodies reduce GM-CSF activity, resulting in 
alveolar macrophage dysfunction and surfactant accumulation. 
Idiopathic PAP is a slowly developing disease. Clinical presentation may include dyspnoea, 
cough or shortness of breath. Changes may be visible on x-ray or computer tomography before 
clinically evident. 
Management of Respiratory Signs and Symptoms in the Study 
Subjects will be closely monitored regarding respiratory tract abnormalities in this clinical study. 
Pulse oximetry and breathlessness questionnaire will be performed at almost every visit and lung 
function will be measured as described in the protocol. Subjects should be referred to a 
pulmonologist according to the below instructions. 
Events that can be handled by the primary investigator, and noted as AEs: 
• Common cold 
• URI 
• Sinusitis 
Events where referral to a pulmonologist is required 
• Any of the above showing atypical clinical picture. 
• 12% deterioration in FEV1 and/or FVC, or 
• Deterioration by >5% decrease in oxygen saturation (SpO2), or 
• An increase in MRC Breathlessness Scale score of 2 from baseline. 
• Shortness of breath and productive cough not showing typical pneumonia picture on x- 
ray. 
Pulmonologist activities at the suspicion of PAP 
The pulmonologist will investigate the condition stepwise. 
• Reversibility of decrease in FEV1 would point to the suspicion at asthma. 
• No reversibility may point at COPD, but a need to rule out PAP may be needed. 
• Investigation to rule out/ confirm PAP may include 6 min walk test, pulse oximetry 
during effort according to ATS guidelines. If a plausible explanation to the condition is 
not established, PAP may be suspected. CT scan and DLCO may be the first step in 
evaluating this condition, possibly followed by BAL and trans-bronchial biopsy. 
• If a patient is diagnosed with asthma, COPD or pneumonia during the trial he or she can 
stay on the trial under thorough monitoring. 

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Appendix 7 
Contraception and Pregnancy Avoidance Procedure 
From signing of informed consent, throughout the duration of the study, and for 18 weeks after 
last dose of study medication, nonsterilised** male subjects who are sexually active with a 
female partner of childbearing potential* must be advised not to donate sperm during this period. 
From signing of informed consent, throughout the duration of the study, and for 18 weeks after 
last dose of study medication, female subjects of childbearing potential* who are sexually active 
with a nonsterilised male partner** must use adequate contraception. In addition, they must be 
advised not to donate ova during this period. 
 
*Females NOT of childbearing potential are defined as those who have been surgically 
sterilised (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal 
(e.g., defined as at least 1 year since last regular menses with an FSH >40 IU/L or at least 
5 years since last regular menses, confirmed before any study medication is implemented). 
**Sterilised males should be at least 1 year postvasectomy and have confirmed that they have 
obtained documentation of the absence of sperm in the ejaculate. 
 
Methods that can achieve a failure rate of less than 1% per year when used consistently and 
correctly are considered as highly effective birth control methods. Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
− Oral 
− Intravaginal 
− Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
− Oral 
− Injectable 
− Implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomised partner 
• Sexual abstinence 

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Subjects will be provided with information on acceptable methods of contraception as part of the 
subject informed consent process and will be asked to sign a consent form stating that they 
understand the requirements for avoidance of pregnancy, donation of ova and sperm during the 
course of the study. 
During the Screening period of the study, a human serum chorionic gonadotropin pregnancy test 
will be performed only for women of childbearing potential. Subjects will receive continued 
guidance with respect to the avoidance of pregnancy as part of the study procedures (SoA). 
During the course of the study, regular urine human chorionic gonadotropin (hCG) pregnancy 
tests will be performed only for women of childbearing potential and subjects will receive 
continued guidance with respect to the avoidance of pregnancy and sperm donation as part of the 
study procedures (SoA). In addition to a negative serum hCG pregnancy test at Screening, 
subjects also must have a negative urine hCG pregnancy test prior to receiving any dose of study 
medication. 

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Appendix 8 
Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Amendment 1 (04 May 2018) 
 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment 1: 
The protocol was amended to address findings from a review by the Medicines and Healthcare 
Products Regulatory Agency (MHRA), which included clarifying several safety assessment time 
periods, revising an exclusion criterion based on abnormal liver transaminases, clarifying the 
process for the investigator to unblind study treatment in the event of a medical emergency, 
clarifying documentation of pulmonary alveolar proteinosis assessments, revising pregnancy 
contraception for consistency with Clinical Trial Facilitation Group (CTFG) guidance, and 
clarifying several inconsistencies. 
Table 14 
Description of Changes in Amendment 1 
Section # 
Description of Change 
Brief Rationale 
1.3/Table 
1/Footnote 4 
1.3/Table 
1/Footnote 8 
5.2/Exclusion 
criterion #9 
 
6.2.1, 6.3.1, 
6.3.3, 6.3.4, 
6.3.5 
Time period for post-dosing vital signs 
added. 
Changed chest x-ray timing from 6 
months to 3 months. 
Exclusion based on abnormal liver 
transaminases revised. 
 
Text revised to include interactive web 
response system (IWRS) for 
maintaining treatment blind that will 
allow investigators to unblind a 
subject’s investigational medicinal 
product identity at any time in the event 
of a medical emergency. 
Time period for post-dosing vital signs clarified 
per request from MHRA. 
Revised for consistency with body of protocol. 
 
Criterion revised to exclude subjects with 
elevated transaminases who also have elevated 
bilirubin. 
Process for unblinding of subject’s investigational 
medicinal product by investigator in the event of 
a medical emergency clarified. 
8.2.5 
Documentation of pulmonary alveolar 
proteinosis assessments revised. 
 
Appendix 6 
Events where referral to a 
pulmonologist is required were updated. 
Appendix 7 
Barrier methods for pregnancy 
contraception deleted and acceptable 
contraception revised. 
Throughout 
Minor editorial and document 
formatting revisions 
Documentation of pulmonary alveolar proteinosis 
assessments revised and clarified to include all 
assessments. 
Revisions were made for consistency with 
Section 8.2.5 of the protocol body. 
Methods of pregnancy contraception revised to be 
consistent with CTFG recommendations. 
 
Editorial updates and corrections. 

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Appendix 9 
Signature of Investigator 
PROTOCOL TITLE: A phase 2a proof of concept, randomised, double-blind, placebo-controlled 
study to evaluate the safety/tolerability and efficacy of 4 subcutaneous injections of namilumab 
(150 mg) given over 10 weeks in subjects with moderate-to-severely active axial 
spondyloarthritis including those previously exposed to anti-TNF therapy. (NAMASTE study) 
PROTOCOL NO:     IZN-101 
VERSION: 
Amendment 2 
This protocol is a confidential communication of Izana Bioscience Ltd. I confirm that I have read 
this protocol, I understand it and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practices and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from the Sponsor. 
 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the 
name of the study centre in which the study will be conducted. Return the signed copy to the CRO. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
Signature of Investigator: 
  
 
 
Printed Name: 
 
  
 
 
Investigator Title: 
  
 
 
Date:    
 
 
 
 
Name/Address of Centre: