Open-Label Extension Study to Evaluate the Safety of Efgartigimod in Adult Patients With Primary Sjögren's Syndrome (pSS) Who Complete Qualifying Efgartigimod pSS Studies
Phase: PHASE2
Conditions: Primary Sjögren's Syndrome
Sponsor: argenx

Clinical Trial Protocol ARGX-113-2211 v1 
 
24 Feb 2023 
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TITLE PAGE 
Protocol Title: 
Open-Label Extension Study to Evaluate the Safety of Efgartigimod in 
Adult Patients With Primary Sjögren’s Syndrome (pSS) who 
Complete Qualifying Efgartigimod pSS Studies 
Protocol Number: 
ARGX-113-2211 
Version Number: 
1 
Compound: 
Efgartigimod (ARGX-113) 
Study Phase: 
2 
Sponsor Name: 
argenx BV 
Legal Registered  
Address: 
Industriepark Zwijnaarde 7 
9052 Zwijnaarde (Ghent) 
Belgium 
Phone: +32 9 310 34 00  
Fax: +32 9 310 34 99 
Regulatory Agency 
Identifier Number(s): 
EUDRACT: 2023-503915-14-00 
Approval Date: 
24 Feb 2023 
 
 

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Sponsor’s Medical 
Contact: 
 
Global Clinical Trial Physician 
argenx BV  
33 Arch St  
Boston, MA  
United States 
Email: 
 
Contract Research 
Organization: 
IQVIA 
24-Hour Urgent 
Medical Helpline:  
IQVIA’s Medical Emergency Contact Center can be accessed 24/7 by 
calling the relevant telephone number(s) 
IQVIA 24/7 Medical Emergency Contact Center (MECC): 
EU: +33 1 86 99 00 19 
Serious Adverse 
Event Reporting: 
Email: safety@argenx.com 
Fax: +1 833 874 7325 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The information contained in this medium is the property of argenx BV and/or its subsidiaries 
(jointly “argenx”) and is confidential and proprietary. Without prior authorization from argenx, 
information contained herein may not be used, reproduced, divulged, published, or otherwise 
disclosed to anyone. 
 
PPD
PPD

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SIGNATURE OF SPONSOR 
 
Protocol Title: 
Open-Label Extension Study to Evaluate the Safety of Efgartigimod in 
Adult Patients With Primary Sjögren’s Syndrome (pSS) who 
Complete Qualifying Efgartigimod pSS Studies 
Protocol Number: 
ARGX-113-2211 
Sponsor Signatory: 
 
 
See appended signature page 
 
 
 MD, PhD 
Chief Medical Officer 
 
Date 
 
 
 
 
PPD

Clinical Trial Protocol ARGX-113-2211 v1 
 
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SIGNATURE OF THE INVESTIGATOR 
Investigator’s Acknowledgment 
I have read the protocol for study ARGX-113-2211. 
Title: Open-Label Extension Study to Evaluate the Safety of Efgartigimod in Adult Patients 
With Primary Sjögren’s Syndrome (pSS) who Complete Qualifying Efgartigimod pSS Studies 
I have fully discussed the objective(s) of this study and the contents of this protocol with the 
sponsor’s representative. 
I understand that the information in this protocol is confidential and will not be disclosed, except 
to those directly involved in the execution or the scientific/ethical review of the study, without 
written authorization from the sponsor. It is, however, permissible to provide the information 
contained herein to a participant in order to obtain their consent to participate. 
I agree to conduct this study according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with International Council for Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use guidelines on Good Clinical Practice and with 
the applicable regulatory requirements. 
I understand that failure to comply with the requirements of the protocol can lead to the 
termination of my participation as an investigator for this study. 
I understand that the sponsor can decide to suspend or prematurely terminate the study at any 
time for whatever reason; such a decision will be communicated to me in writing. Conversely, if 
I decide to withdraw from execution of the study, I will communicate my intention immediately 
in writing to the sponsor. 
 
Investigator Name 
Institution 
Address 
(please handprint or type) 
 
 
 
 
Signature 
 
 
 
Date 
 

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TABLE OF CONTENTS 
SIGNATURE OF SPONSOR ..........................................................................................................3 
SIGNATURE OF THE INVESTIGATOR ......................................................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF TABLES ...........................................................................................................................8 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................................9 
List of Abbreviations .......................................................................................................................9 
Definitions of Terms ......................................................................................................................12 
1. 
PROTOCOL SUMMARY ..........................................................................................13 
1.1. 
Synopsis ......................................................................................................................13 
1.2. 
Schema ........................................................................................................................16 
1.3. 
Schedule of Activities .................................................................................................17 
2. 
INTRODUCTION ......................................................................................................22 
2.1. 
Study Rationale ...........................................................................................................22 
2.2. 
Background .................................................................................................................22 
2.3. 
Benefit/Risk Assessment ............................................................................................23 
2.3.1. 
Risk Assessment .........................................................................................................23 
2.3.2. 
Benefit Assessment .....................................................................................................24 
2.3.3. 
Overall Benefit-Risk Conclusion ................................................................................24 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ..................................................25 
4. 
STUDY DESIGN .......................................................................................................28 
4.1. 
Overall Design ............................................................................................................28 
4.2. 
Scientific Rationale for Study Design ........................................................................29 
4.3. 
Justification for Dose ..................................................................................................30 
4.4. 
End-of-Study Definition .............................................................................................30 
5. 
STUDY POPULATION .............................................................................................31 
5.1. 
Inclusion Criteria ........................................................................................................31 
5.2. 
Exclusion Criteria .......................................................................................................31 
5.3. 
Lifestyle Considerations .............................................................................................31 
5.4. 
Screen Failures ............................................................................................................31 
5.5. 
Criteria for Temporarily Delaying Enrollment ...........................................................31 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ........................32 

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6.1. 
Investigational Medicinal Product Administered .......................................................32 
6.2. 
Preparation, Handling, Storage, and Accountability ..................................................32 
6.3. 
Assignment to IMP .....................................................................................................33 
6.4. 
Blinding ......................................................................................................................33 
6.5. 
Study Compliance .......................................................................................................33 
6.6. 
Dose Modification ......................................................................................................33 
6.7. 
Continued Access to IMP After the End of the Study ................................................34 
6.8. 
Treatment of Overdose ...............................................................................................34 
6.9. 
Prior and Concomitant Therapy ..................................................................................34 
7. 
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................37 
7.1. 
Discontinuation of IMP ..............................................................................................37 
7.1.1. 
Permanent Discontinuation .........................................................................................37 
7.1.2. 
Temporary Discontinuation ........................................................................................37 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................37 
7.3. 
Lost to Follow-up .......................................................................................................38 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................39 
8.1. 
Administrative and Baseline Procedures ....................................................................39 
8.1.1. 
Use and Storage of Biological Samples ......................................................................39 
8.2. 
Efficacy Assessments .................................................................................................39 
8.2.1. 
CRESS ........................................................................................................................39 
8.2.2. 
ESSDAI ......................................................................................................................40 
8.2.3. 
ClinESSDAI ...............................................................................................................40 
8.2.4. 
STAR ..........................................................................................................................41 
8.2.5. 
Patient-Reported Outcomes ........................................................................................42 
8.2.6. 
Additional Efficacy Measures ....................................................................................44 
8.3. 
Safety Assessments .....................................................................................................44 
8.3.1. 
Physical Examinations ................................................................................................45 
8.3.2. 
Vital Signs ..................................................................................................................45 
8.3.3. 
Electrocardiograms .....................................................................................................45 
8.3.4. 
Protocol-Required Laboratory Tests...........................................................................45 
8.3.5. 
Pregnancy Testing ......................................................................................................45 

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8.4. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting .....................45 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................46 
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................46 
8.4.3. 
Follow-up of AEs and SAEs .......................................................................................46 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...........................................................46 
8.4.5. 
Pregnancy ...................................................................................................................47 
8.4.6. 
AESIs ..........................................................................................................................47 
8.4.7. 
AEs of Clinical Interest ..............................................................................................48 
8.5. 
Pharmacokinetics ........................................................................................................48 
8.6. 
Pharmacodynamics .....................................................................................................48 
8.7. 
Genetics ......................................................................................................................49 
8.8. 
Biomarkers ..................................................................................................................49 
8.9. 
Immunogenicity Assessments ....................................................................................49 
8.10. 
Health Economics or Medical Resource Utilization and Health Economics .............49 
9. 
STATISTICAL CONSIDERATIONS .......................................................................50 
9.1. 
Statistical Hypothesis ..................................................................................................50 
9.2. 
Analysis Sets ...............................................................................................................50 
9.3. 
Statistical Analyses .....................................................................................................50 
9.3.1. 
General Considerations ...............................................................................................50 
9.3.2. 
Primary Endpoint Analysis .........................................................................................51 
9.3.3. 
Secondary Endpoint(s) Analysis.................................................................................51 
9.3.4. 
Exploratory Endpoints Analysis .................................................................................51 
9.4. 
Interim Analysis ..........................................................................................................52 
9.5. 
Sample Size Determination ........................................................................................52 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................53 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................53 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................53 
10.1.2. 
Financial Disclosure ...................................................................................................53 
10.1.3. 
Informed Consent Process ..........................................................................................54 
10.1.4. 
Recruitment Strategy ..................................................................................................54 
10.1.5. 
Data Protection ...........................................................................................................54 

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10.1.6. 
Committees Structure .................................................................................................55 
10.1.7. 
Dissemination of Clinical Trial Data ..........................................................................55 
10.1.8. 
Data Quality Assurance ..............................................................................................55 
10.1.9. 
Source Documents ......................................................................................................56 
10.1.10. 
Study and Site Start and Closure ................................................................................56 
10.1.11. 
Publication Policy .......................................................................................................57 
10.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................58 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................59 
10.3.1. 
Definition of AE .........................................................................................................59 
10.3.2. 
Definition of SAE .......................................................................................................60 
10.3.3. 
Recording and Follow-Up of AE and/or SAE ............................................................61 
10.3.4. 
Reporting of SAEs and AESIs ....................................................................................62 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ......................................................64 
10.4.1. 
Women of Childbearing Potential Definition .............................................................64 
10.4.2. 
Contraception Guidance .............................................................................................64 
10.5. 
Appendix 5: Operational Considerations for COVID-19 Risk Mitigation .................65 
10.6. 
Appendix 6: Home Study Visits .................................................................................66 
10.7. 
Appendix 7: Efficacy Endpoint Data ..........................................................................67 
10.7.1. 
ESSDAI ......................................................................................................................67 
10.8. 
Appendix 8: ACR-EULAR Classification Criteria ....................................................71 
11. 
REFERENCES ...........................................................................................................73 
 
LIST OF TABLES 
Table 1: 
Schedule of Activities .................................................................................................17 
Table 2: 
Study ARGX-113-2211 Objectives and Endpoints ....................................................25 
Table 3: 
IMP Administered ......................................................................................................32 
Table 4: 
Prior and Concomitant Therapy ..................................................................................34 
Table 5: 
Comparison of Domain Weights of Original ESSDAI and clinESSDAI ...................41 
Table 6: 
Protocol-Required Laboratory Tests...........................................................................58 
Table 7: 
ESSDAI: Domain and Item Definitions and Weights ................................................67 
Table 8: 
ACR-EULAR Classification Criteria for Primary Sjögren’s Syndrome ....................71 

Clinical Trial Protocol ARGX-113-2211 v1 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
List of Abbreviations 
 
Abbreviation 
Expansion 
21 CFR 
Title 21 of the Code of Federal Regulations 
AChR-Ab 
anti-acetylcholine receptor antibody 
ACR 
American College of Rheumatology 
ADA 
antidrug antibody(ies) 
ADL 
activities of daily living 
AE 
adverse event 
AESI 
adverse event of special interest 
BL 
Baseline 
CIDP 
chronic inflammatory demyelinating polyneuropathy 
clinESSDAI 
clinical EULAR Sjögren’s syndrome disease activity index 
CQ 
chloroquine 
CRESS 
Composite of Relevant Endpoints for Sjögren’s Syndrome 
CRO 
contract research organization 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMARD 
disease-modifying antirheumatic drug 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EDV 
early discontinuation visit 
efgartigimod IV 
efgartigimod formulation for intravenous administration 
EMA 
European Medicines Agency  
EMG 
electromyography 
ESSDAI 
EULAR Sjögren’s syndrome disease activity index 
ESSPRI 
EULAR Sjögren’s Syndrome Patient-Reported Index 
EULAR 
European Alliance of Associations for Rheumatology 
FcRn 
neonatal crystallizable fragment receptor 
FDA 
Food and Drug Administration 

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Abbreviation 
Expansion 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
gMG 
generalized myasthenia gravis 
HRCT 
High-resolution computed tomography 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IFN 
interferon 
 
 
IgG 
immunoglobulin G 
 
 
IMP 
investigational medicinal product 
IRB 
institutional review board 
ITP 
immune thrombocytopenia 
IV 
intravenous 
IVIg 
intravenous immunoglobulin 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities  
MFI 
Multidimensional Fatigue Inventory 
NCI 
National Cancer Institute 
NCS 
Nerve conduction studies 
NSAID 
non-steroidal anti-inflammatory drug 
OLE 
open-label extension 
OSS 
ocular staining score 
PASS 
patient acceptable symptom state 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s) 
PGA 
patient global assessment  
PI 
principal investigator 
CCI
CCI
CCI
CCI

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Abbreviation 
Expansion 
PK 
pharmacokinetic(s) 
PMDA 
Pharmaceuticals and Medical Devices Agency 
pSS 
primary Sjögren’s syndrome 
PT 
preferred term 
QW 
once weekly  
Q2W 
every 2 weeks 
RF 
rheumatoid factor 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SCIg 
subcutaneous immunoglobulin 
SF-36 
36-Item Short Form Survey 
SFV 
safety follow-up visit 
SGUS 
salivary gland ultrasonography 
SoA 
schedule of activities 
SOC 
system organ class 
SS-A 
Sjögren’s syndrome–related antigen A 
SS-B 
Sjögren’s syndrome–related antigen B 
STAR 
Sjögren’s Tool for Assessing Response 
SUSAR 
suspected unexpected serious adverse reaction 
SWSF 
stimulated whole salivary flow  
TEAE 
treatment-emergent adverse event 
UWSF 
unstimulated whole salivary flow 
VAS 
visual analog scale  
WOCBP 
women of childbearing potential 
 
 
 

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Definitions of Terms 
Term 
Definition 
Nonresponder 
Participant who does not have a reduction in ClinESSDAI score of ≥3 points and/or 
a change in score that alters their disease severity category 
Responder 
Participant who has a reduction in ClinESSDAI score of ≥3 points and/or a change 
in score that reclassifies their disease from moderate severity to mild severity 
Therapeutic 
failure 
Participant who are nonresponder at week 24. This participant will discontinue study 
treatment 
 

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Objectives 
Endpoints 
• 
Proportion of participants with minimal clinically 
important improvement from baseline in ESSPRI: 
decrease of 1 point or ≥ 15% at weeks 24 and 48 
• 
Change from baseline in ESSDAI score at weeks 24 
and 48 
• 
Change from baseline in clinESSDAI score at 
weeks 24 and 48 
• 
Change from baseline in ESSPRI score at weeks 24 
and 48 
• 
To evaluate the effect of efgartigimod on 
STAR 
• 
Proportion of STAR responders (score of ≥5) at 
weeks 24 and 48 when compared to baseline 
• 
To assess the PD effect of efgartigimod 
• 
Values, changes from baseline, and percent reduction 
from baseline in total IgG levels in serum over the 
48-week treatment period 
• 
Values, changes from baseline, and percent reduction 
from baseline in autoantibodies in serum over 
the  48-week treatment period: 
− Anti-Ro/SS A 
− Anti-La/SS B 
• 
To assess the exposure to efgartigimod 
• 
Efgartigimod serum concentrations over the 48-week 
treatment period 
• 
To assess the immunogenicity of 
efgartigimod 
• 
Incidence and prevalence of ADA against 
efgartigimod over the 48-week treatment period 
ADA = antidrug antibody; AESI = adverse event of special interest; clinESSDAI = clinical EULAR Sjögren’s 
syndrome disease activity index; CRESS = Composite of Relevant Endpoints for Sjögren’s Syndrome; 
ECG = electrocardiogram; ESSDAI = EULAR Sjögren’s syndrome disease activity index; ESSPRI = EULAR 
Sjögren’s Syndrome Patient-Reported Index; IFN = interferon; IgG = immunoglobulin G; RF = rheumatoid factor; 
IV = intravenous; OSS = ocular staining score; PD = pharmacodynamic(s); PK = pharmacokinetic(s); pSS = primary 
Sjögren’s syndrome; PT = preferred term; SAE = serious adverse event; SGUS = salivary gland ultrasonography; 
SOC = system organ class; STAR = Sjögren’s Tool for Assessing Response; TEAE = treatment-emergent adverse 
event; UWSF = unstimulated whole salivary flow; VAS = visual analog scale. 
 
No estimands have been defined for this study. 
Overall Design: 
ARGX-113-2211 is a long-term, single-arm, open-label, multicenter extension study of the pSS-
qualifying efgartigimod studies designed to evaluate the long-term safety of efgartigimod in 
adult patients with pSS. Participants will be enrolled from both active and placebo arms of 
qualifying efgartigimod studies and receive efgartigimod 10 mg/kg over 48 weeks in the 
extension study without knowledge of their treatment assignment in the qualifying study. 
Eligible participants must have completed the treatment period of the qualifying study and must 
not have permanently discontinued the IMP in that study. 

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Brief Summary: 
Participants will receive efgartigimod 10 mg/kg by IV infusion either Q2W or QW. The dosing 
regimen is based on whether the participant is a responder or nonresponder. Responder status 
will be determined by clinESSDAI assessments conducted on day 1, week 16, and week 24 and 
using the baseline of the qualifying study. Participants who are not responders at week 24 will be 
evaluated by PI for therapeutic failure. If a participant is a therapeutic failure, they will 
discontinue study treatment. If a participant is not a therapeutic failure, they will continue QW 
dosing regimen, and a clinESSDAI will be conducted at weeks 32, 36, 40, and 44 until 
confirming responder status and switching to Q2W dosing regimen. The PI will continue to 
evaluate the participant for therapeutic failure. 
The study’s primary objective is to assess the long-term safety of efgartigimod in participants 
with pSS. Additional assessments will be conducted, and blood samples collected to assess the 
effectiveness of efgartigimod at treating pSS, the PD effect of efgartigimod, and the 
immunogenicity of efgartigimod. Blood samples will also be collected to monitor the 
concentration of efgartigimod in blood over time. 
Number of Participants: 
Up to approximately 30 subjects who have completed the efgartigimod pSS study 
(ARGX-113-2106) will be enrolled for in the OLE study (ARGX-113-2211). 
Note: Enrolled means the participant agrees to participate in the clinical study by completing the 
informed consent process. 
Study Arms and Duration: 
Each participant will participate in the following study periods: 
• Treatment period: 48-week treatment period in which participants will receive 
efgartigimod doses either QW or Q2W based on their responder status. Switch points (ie, 
time points when clinESSDAI is conducted to determine responder status) will occur on 
day 1, week 16, and week 24. A participant who is not a responder on week 24 and 
classified by the PI as a nontherapeutic failure will continue QW dosing regimen until 
confirming the responder status. The participant will begin Q2W dosing regimen upon 
confirmation of the responder status 
• 56-day follow-up period starting after the final IMP administration 
Data Monitoring/Other Committee: No 
 

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1.2. 
Schema 
Abbreviations: D = day; IV = intravenous; QW = once weekly; Q2W = every 2 weeks; Wk = week. 
a QW or Q2W dosing regimen depending on responder status. Responders (defined as participants with a decrease in clinESSDAI of ≥3 points from 
baseline of qualifying study or who have a change clinESSDAI score that reclassifies their disease from moderate severity to mild severity) will be switched 
from QW to Q2W dosing regimen. Nonresponders will remain on QW dosing regimen. Switch points (ie, timepoints where clinESSDAI are conducted to 
determine responder status) will occur on day 1, week 16, and week 24. If a participant is not a responder at week 24, they will be evaluated by the PI for 
therapeutic failure. If not considered a therapeutic failure, the participant will continue QW dosing regimen and will return at weeks 32, 36, 40 and 44 for a 
clinESSDAI assessment until confirming the responder status and switching to Q2W dosing regimen or PI considers the participant to be a therapeutic 
failure. For QW regimen, the final dose will be administrated at week 47. For Q2W regimen, the final dose will be administered at week 46. 
 

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BLa 
Study week 
 
 
1 
2 
3 
4 
5-7 
8 
9-
11 
12 
13-
15 
16 
17-
23 
24 
25-35 
36 
37-47 
48 
EDVb 
SFVc 
Study day (±2) 
1 
8 
15 
22 
29 
36-
50 
57 
64-
78 
85 
92-
120 
127 
134-
162 
169 
176-
246 
253 
260-
330 
337 
 
393 
BL = baseline; clinESSDAI = clinical; ESSDAI; D = day; d/c = discontinuation; ECG = electrocardiogram; EDV = early discontinuation visit; 
ESSDAI = EULAR Sjögren’s syndrome disease activity index; ESSPRI = EULAR Sjögren’s Syndrome Patient-Reported Index; EULAR = European 
Alliance of Associations for Rheumatology; ICF = informed consent form; IgG = immunoglobulin G; IMP = investigational medicinal product; 
IV = intravenous; MFI = Multidimensional Fatigue Inventory; NA = not applicable; OSS = ocular staining score; PASS = patient acceptable symptom 
state; PCR = polymerase chain reaction; PD = pharmacodynamics; PGA = patient global assessment; PK = pharmacokinetics; RF = rheumatoid factor; 
SCR = screening; SFV = safety follow-up visit; SF-36 = 36-Item Short Form Survey; SGUS = salivary gland ultrasonography; SS-A = Sjögren’s 
syndrome–related antigen A; SS-B = Sjögren’s syndrome–related antigen B; SWSF = stimulated whole salivary flow; UWSF = unstimulated whole 
salivary flow; W = week. 
a BL will coincide with the final visit of a previous qualifying study. Grayed-out assessments may be conducted as part of the previous qualifying pSS studies. 
b The EDV will be performed within 7 days after last dose administration.  
c Participants will attend a safety follow-up visit 56 ± 3 days after the final IMP administration. 
d Weight mandatory at baseline. 
e Vital signs will be measured before collecting any blood sample or administering IMP infusions. 
f On IMP administration visits, blood samples must be collected predose (preferably within 2 hours before the infusion). On other visits, a blood sample may 
be collected at any time during the visit. 
 
 
h On IMP administration visits, blood samples for PK analyses will be collected predose (preferably within 2 hours before IMP administration). On other 
visits, a blood sample may be collected at any time during the visit.  
i A PK sample will also be collected within 30 minutes after the end of IMP infusion.  
j The biological domain will remain blinded until the parent study is unblinded. 
k ClinESSDAI will only be conducted at weeks 32, 36, 40, and 44 if the participant is a nonresponder at week 24 and not considered a therapeutic failure by 
the PI. 
l The questionnaires should be performed before other study interventions and can be done one day in advance. 
CCI

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BLa 
Study week 
 
 
1 
2 
3 
4 
5-7 
8 
9-
11 
12 
13-
15 
16 
17-
23 
24 
25-35 
36 
37-47 
48 
EDVb 
SFVc 
Study day (±2) 
1 
8 
15 
22 
29 
36-
50 
57 
64-
78 
85 
92-
120 
127 
134-
162 
169 
176-
246 
253 
260-
330 
337 
 
393 
m The maximum total efgartigimod dose per efgartigimod IV infusion is 1200 mg for participants weighing ≥ 120 kg. The IMP weight-based dose will be 
recalculated if a participant’s weight has changed (increased or decreased) by more than 10% from OLE baseline (ie, weight prior to IMP infusion on day 1 of 
the ARGX-113-2211 study). 
n The IMP infusion on day 1 will occur following eligibility check, informed consent signature, and baseline assessments. 
o Responders will reduce dosing frequency from QW to Q2W dosing regimen. Nonresponders will remain on QW dosing regimen. Switch points will occur at 
baseline, week 16, and week 24. The PI will evaluate a participant who is not a responder at week 24 for therapeutic failure. If the participant is not considered 
a therapeutic failure, QW dosing regimen will be continued, and the participant will return at weeks 32, 36, 40, and 44 for a clinESSDAI assessment up to 
confirming the responder status and switching to Q2W dosing regimen or if the PI considers the participant to be a therapeutic failure. For QW regimen, the 
final dose will be administrated at week 47. For Q2W regimen, the final dose will be administered at week 46. 
p If a participant who has reduced dosing frequency to Q2W considers their condition worsening, an unscheduled visit will occur during which a clinESSDAI 
and blood sampling for PK and ADA will be conducted. The participant will revert to QW dosing regimen for the remainder of the treatment period if there 
has been an increase in clinESSDAI score of ≥ 3 points and/or a change in score that reclassifies their disease from mild severity (clinESSDAI < 5) to 
moderate severity (clinESSDAI ≥ 5). 
 

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2. 
INTRODUCTION 
Participants will be enrolled from both active and placebo arms of qualifying efgartigimod 
studies in adult patients with pSS. The protocol will be amended to add additional studies at a 
later date. 
In qualifying study ARGX-113-2106, the efficacy and safety of efgartigimod in adult patients 
with pSS was evaluated using a randomized, double-blinded, placebo-controlled study design. 
Participants were randomized to receive efgartigimod IV 10 mg/kg or matching placebo in a 2:1 
ratio. The IMP (efgartigimod or matching placebo) was administered during the treatment period 
in approximately 1-hour IV infusion QW by site or a home nurse. The final dose was 
administered at week 23. At week 24, eligible participants from ARGX-113-2106 may roll over 
into the present single-arm OLE study: ARGX-113-2211. 
2.1. 
Study Rationale 
Efgartigimod is a first-in-class antibody fragment that binds to FcRn. This binding prevents 
FcRn from recycling IgG and leads to a reduction in circulating disease-causing autoantibodies. 
Efgartigimod is being clinically developed in autoimmune diseases mediated by pathogenic IgG 
autoantibodies after approval by the United States FDA, EMA, and Japan’s PMDA for use in 
adult patients with AChR-Ab seropositive gMG. 
Efgartigimod may be a viable treatment option for individuals diagnosed with pSS because it has 
been shown to reduce IgG levels, including IgG autoantibodies, that may underlie some of the 
autoimmune disease manifestations in these participants. Therefore, the reduction of 
autoantibodies may successfully reduce disease activity and symptoms in pSS participants. 
This open-label extension study will evaluate the long-term safety of efgartigimod in participants 
with pSS who have completed the treatment period of the qualifying studies. 
2.2. 
Background 
Efgartigimod is a neonatal FcRn antagonist designed to treat autoimmune diseases mediated by 
IgG autoantibodies. pSS is a chronic, progressive autoimmune disease of unknown etiology, 
typically characterized by an autoimmune exocrinopathy. Along with symptoms of excessive 
dryness, manifestations include profound fatigue, chronic pain, extraglandular organ system 
involvement, and increased risk of lymphomas. A hallmark of pSS is B-cell hyperactivity, 
causing a vicious cycle of immune activation through cytokine production, antigen presentation, 
and autoantibody secretion, potentially causing tissue damage. Currently, no immunomodulatory 
treatment is available for pSS. 
Efgartigimod, an FcRn antagonist that can rapidly reduce IgG, including pathogenic antibodies, 
contributes to successfully treat pSS and has the potential to improve disease manifestations by 
the reduction of IgG autoantibodies in pSS. This study aims to evaluate the long-term safety of 
efgartigimod in participants with pSS who have completed the treatment period of the qualifying 
studies. 

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A detailed description of the chemistry, pharmacology, efficacy, and safety of efgartigimod is 
provided in the current IB. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of efgartigimod is provided in the current IB. 
2.3.1. 
Risk Assessment 
Overall, available data confirm that efgartigimod has been well-tolerated across studies in 
different indications and has an acceptable safety profile. 
Potential clinically 
significant risk  
Summary of data/rationale for risk 
Mitigation strategy 
Serious infection 
Efgartigimod reduces IgG levels, 
potentially hindering immune response 
and increasing the risk of infection. 
Exclude participants with 
clinically significant active 
infection not sufficiently resolved 
in the investigator's opinion 
(Section 5.2). 
Infections are considered adverse 
event of special interest (AESI; 
Section 8.4.6). Monitor for 
infections and temporarily 
interrupt IMP dosing as specified 
in Section 7.1. 
Infusion/injection-
related reactions 
All therapeutic proteins can elicit immune 
responses, potentially resulting in 
hypersensitivity, or allergic reactions such 
as rash, urticaria, angioedema, serum 
sickness, and anaphylactoid, or 
anaphylactic reactions. 
 
Monitor participants during 
administration and for 30 minutes 
thereafter for clinical signs and 
symptoms of infusion/injection-
related reactions. 
Infusion/injection-related 
reactions are considered AEs of 
clinical interest (Section 8.4.7). 
If an infusion reaction occurs, 
interrupt the infusion and 
implement appropriate supportive 
measures. Once resolved, the 
infusion can be resumed, and at a 
slower rate if necessary. 
Infusion/injection site 
reactions 
Most AEs have been mild, transient 
injection site reactions, including 
erythema, pain, bruising, pruritus, 
burning, tenderness, edema, induration, 
irritation, paresthesia, numbness, and 
rash. Moderate injection site reactions 
occurring less frequently include burning, 
erythema, pain, and numbness. Mild to 
moderate headache is commonly reported. 
Continuously monitor participants 
for injection site reactions. 
Infusion/injection site reactions 
are considered AEs of clinical 
interest (Section 8.4.7). 

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Potential clinically 
significant risk  
Summary of data/rationale for risk 
Mitigation strategy 
AE = adverse event; AESI = adverse event of special interest; IgG = immunoglobulin G; IMP = investigational 
medicinal product 
2.3.2. 
Benefit Assessment 
Efgartigimod has been investigated in nonclinical studies, phase 1 clinical pharmacology studies 
in healthy participants, and phase 2/3 clinical studies in participants with IgG-driven 
autoimmune diseases, including gMG, primary ITP, CIDP, and pemphigus. 
In clinical studies, efgartigimod effectively reduces IgG antibody levels, including pathogenic 
autoantibodies. The efficacy of efgartigimod to improve clinical outcomes in gMG and reduce 
pathogenic autoantibodies was confirmed in a pivotal phase 3 study in participants with gMG 
(ARGX-113-1704). In addition, clinical benefit was observed in phase 2 studies in primary ITP 
(ARGX-113-1603) and pemphigus (ARGX-113-1701), in which pathogenic autoantibodies 
underlie the disease pathology (refer to current efgartigimod IB). Available clinical data support 
the clinical benefit of efgartigimod for reducing pathogenic IgG autoantibodies, which may 
mitigate autoimmune dysfunction and improve symptoms, as well as the ability to function, in 
participants with pSS. 
2.3.3. 
Overall Benefit-Risk Conclusion 
The potential risks associated with efgartigimod are justified by the anticipated benefits posssibly 
afforded to participants with pSS in this study and considering the measures implemented to 
minimize risks. The favorable balance between risks and anticipated efficacy/benefit supports the 
use of efgartigimod in the clinical development for pSS. 
More detailed information about the known and expected benefits and risks of efgartigimod and 
reasonably expected AEs can be found in the current IB. 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
Study ARGX-113-2211 is a long-term, single-arm, open-label, multicenter extension of 
pSS-qualifying efgartigimod studies designed to evaluate the long-term safety of efgartigimod in 
adult patients with pSS. Participants will be enrolled from both active and placebo arms of 
qualifying efgartigimod studies and receive efgartigimod IV 10 mg/kg over 48 weeks in the 
extension study without knowledge of their treatment assigned in the qualifying study. To be 
eligible to enroll in this study, participants must have completed the treatment period of the 
qualifying study and must not have permanently discontinued the IMP in that study. 
Participants will receive efgartigimod 10 mg/kg by IV infusion either Q2W or QW. The dosing 
regimen is based on whether the participant is a responder or nonresponder on day 1. Participants 
will be considered as responders if they have a reduction in clinESSDAI score of ≥ 3 points from 
baseline (ie, the final visit of a previous qualifying study) and/or a change in score that 
reclassifies their disease from moderate severity (clinESSDAI ≥ 5) to mild severity (clinESSDAI 
< 5). Participants will be considered as nonresponders if they do not have a reduction in 
clinESSDAI score of ≥ 3 points from baseline and/or did not reach a clinESSDAI < 5. 
ClinESSDAI assessments to determine responder status using the baseline will be conducted on 
day 1 and weeks 16 and 24. Responders will receive IV infusions Q2W. Nonresponders will 
receive an infusion QW until such time that they are considered to be responders. If a participant 
is not a responder at week 24, they will be evaluated by the PI for therapeutic failure: 
• Therapeutic failure - the participant will discontinue study treatment 
• Not a therapeutic failure - the participant will continue QW dosing regimen. ClinESSDAI 
will be conducted at weeks 32, 36, 40, and 44 until confirming responder status and 
switching to Q2W dosing regimen. The PI will continue to evaluate the participant for 
therapeutic failure 
If the participant and/or investigator consider there to be a reduction in therapeutic effect once 
the patient has switched to Q2W, the participant will return for an unscheduled visit during 
which a clinESSDAI, a blood sampling for PK and ADA will be collected. 
If there has been an increase in clinESSDAI score of ≥ 3 points and/or a change in score that 
reclassifies their disease from mild severity to moderate severity the participant will revert to 
QW dosing regimen and will remain on this dose regimen for the remainder of the treatment 
period. 
IMP infusions must occur at the site for a minimum of 3 consecutive visits (for QW dosing 
regimen: baseline visit and the week 1 and 2 visits; for Q2W dosing regimen: baseline visit and 
the week 2 and 4 visits) before home infusions are allowed. If doses are missed at 1 or more of 
these visits, then dosing at subsequent visits will also be on-site. IMP administration at home will 
not commence until after 3 consecutive doses have been administered on-site. 
Participants will return for a follow-up visit approximately 56 days after the final IMP 
administration. 

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The study’s primary objective is to assess the long-term safety of efgartigimod in participants 
with pSS. The primary outcome of this study will be the incidence and severity of AEs and 
AESIs, the incidence of SAEs, changes in laboratory test results, vital signs, and ECG results. 
Additional assessments will be conducted, and blood samples will be collected to assess the 
effectiveness of efgartigimod at treating pSS, the PD effect of efgartigimod, and the 
immunogenicity of efgartigimod. Blood samples will also be collected to monitor the 
concentration of efgartigimod in blood over time. 
A minimum of 10 study site visits over the 48-week treatment period and 56-day follow-up 
period are planned (baseline, weeks 1 [for QW regimen], 2, 4, 8, 12, 16, 24, 36, 48, and the 
SFV); all other visits (except for the first 3 consecutive visits) may be conducted by home health 
care service, or telemedicine visits. 
The maximum length of time a participant can be in the study is approximately 56 weeks 
(48 weeks treatment plus 8 weeks of follow-up). 
4.2. 
Scientific Rationale for Study Design 
pSS is characterized by mononuclear inflammatory infiltrates and IgG plasma cells in salivary 
and lacrimal glands that lead to irreversible destruction of the glandular tissue and is 
accompanied by a sensation of dryness of mouth and eyes. B cells play a central role in the 
immunopathogenesis and exhibit signs of hyperactivity.1 
In addition, autoantibodies can create immune complexes that maintain and amplify the 
production of IFN alpha. This combination results in a cycle of immune activation that leads to 
tissue damage. Currently, no immunomodulatory treatment is available for pSS. In this study, we 
aim to evaluate the effect of efgartigimod, an FcRn antagonist that can rapidly reduce IgG, 
including pathogenic antibodies. Efgartigimod contributes to successfully treat pSS and has the 
potential to improve disease manifestations by the reduction of IgG autoantibodies and immune 
complexes in pSS. 
In the present OLE study (ARGX-113-2211), the long-term safety, efficacy, PD, and PK of 
efgartigimod will be evaluated in participants with pSS. 
The study includes a 48-week treatment period in which patients will receive QW or Q2W doses 
of efgartigimod 10 mg/kg by IV infusion, ie, at the same dose per body weight, and mode of 
administration as in the preceding qualifying parent studies. 
The treatment allocation (efgartigimod or placebo) from the qualifying studies will be kept 
blinded in current study. 
The primary outcome measure is the ongoing safety of efgartigimod for approximately 1 year 
after completing the qualifying study. The endpoint aims to demonstrate that efgartigimod is a 
safe long-term treatment option for pSS. The safety endpoints selected for this study are those 
considered to be standard for any clinical trial evaluating the safety of an IMP. 
The secondary endpoint is the effect of efgartigimod compared to placebo on CRESS 
(Section 8.2.1). The CRESS composite measures systemic disease activity, patient-reported 
symptoms, tear gland function, salivary gland function, and serology, developed to assess 
treatment efficacy in participants with pSS. 

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All other secondary efficacy endpoints complement the first secondary endpoint and provide 
additional information on efficacy (ESSDAI, clinESSDAI, ESSPRI, STAR [Section 8.2]), 
histology, PK, PD, and immunogenicity. The totality of data from all endpoints used in the study 
will be utilized to determine treatment response in this population. 
4.3. 
Justification for Dose 
Doses of efgartigimod 10 mg/kg either QW or Q2W will be administered. For responders a Q2W 
regimen has been selected to evaluate whether a less frequent dosing regimen can maintain 
clinical efficacy, while the QW regimen for nonresponders targets efgartigimod’s to achieve a 
near maximal total IgG reduction (PD effect), thereby maximizing the chance of a clinical 
response on the efficacy outcomes in nonresponders. 
As the hypothesis for treating pSS with efgartigimod is to reduce the pathogenic autoreactive 
IgG, the selected doses and dose regimen target a nearly maximal PD effect (ie, reduction of 
pathogenic IgGs). The chronic nature of pSS reflects the need for chronic treatment to maintain 
pathogenic IgG autoantibody suppression and symptom reduction. 
The cumulative data from a phase 1 study in healthy adult subjects; phase 2 studies in 
participants with gMG, ITP, and pemphigus; phase 3 studies in gMG; and PK/PD modeling 
results demonstrate that a 10 mg/kg efgartigimod dose administered QW through IV infusion 
achieved 60% to 70% total IgG reduction, including the reduction of pathogenic autoantibodies. 
Maximal IgG reduction was associated with clinical efficacy observed in gMG, ITP, and 
pemphigus studies. Furthermore, this dose has been safe and well-tolerated in all study 
populations and has demonstrated similar PK and PD profiles across indications. Accordingly, 
the 10 mg/kg IV dose regimen (QW or Q2W) was selected for this study. 
4.4. 
End-of-Study Definition 
The end-of-study is defined as the date of the last participant’s last visit. 
A participant will have completed the study if the SFV assessments have been completed. 
 

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5. 
STUDY POPULATION 
Prospective approvals of protocol deviations to enrollment criteria, also known as protocol 
waivers or exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants can be included in the study only if all of the following criteria apply: 
1. Is at least the legal age of consent for clinical trials when signing the ICF 
2. Is capable of providing signed informed consent, as described in Section 10.1.3, and 
complying with protocol requirements 
3. Agrees to use contraceptive measures consistent with local regulations and the following: 
a. WOCBP (defined in Section 10.4.1) must have a negative urine pregnancy test at 
baseline before receiving IMP (Section 10.4.2.1) 
4. Has completed the qualifying efgartigimod pSS studies and agrees to continue study drug 
treatment without interruption in the extension study 
5.2. 
Exclusion Criteria 
Participants will be excluded from the study if any of the following criteria apply: 
1. Clinically significant disease (including newly diagnosed malignancy or cardiovascular 
disease) or intention to have surgery during the study; or any other medical condition 
that, in the investigator’s opinion, would confound the results of the study or put the 
participant at undue risk 
2. Pregnant or intention to become pregnant during the study 
3. Any severe systemic pSS manifestation that may put the participant at undue risk based 
on the investigator’s opinion 
5.3. 
Lifestyle Considerations 
Not applicable. 
5.4. 
Screen Failures 
Eligibility to roll over must be verified at the last visit of the preceding qualifying studies. 
Participants who consent to participate in the clinical trial but fail to meet the inclusion and 
exclusion criteria before IMP administration will be considered screen failures and will be 
captured as “enrollment failures”. 
Individuals who do not meet the criteria for participation in this study (screen failures), based on 
the results from assessments in the preceding study, may not be rescreened. 
5.5. 
Criteria for Temporarily Delaying Enrollment 
Not applicable. 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Efgartigimod is the IMP in this OLE study and is manufactured according to Good 
Manufacturing Practice regulations. 
6.1. 
Investigational Medicinal Product Administered 
Table 3: 
IMP Administered 
Intervention label 
Efgartigimod IV 
Intervention name 
Efgartigimod IV 
Intervention description 
Sterile, colorless, clear concentrate solution for IV infusion. 
Efgartigimod 20 mg/mL, administered IV 
Type  
Biologic 
Dose formulation 
Infusion 
Unit dose strength(s) 
10 mg/kg QW or Q2Wa 
Route of administration 
IV infusion 
Use 
Experimental 
IMP and NIMP/AxMP 
IMP 
Sourcing 
Centrally by the sponsor/designee 
Packaging and labeling 
IMP will be provided in glass vials. Each vial will be labeled per 
country requirements 
Former name 
ARGX-113 
AxMP = auxiliary medicinal product; IMP = investigational medicinal product; IV = intravenous; 
NIMP = noninvestigational medicinal product; Q2W = every 2 weeks; QW = once weekly 
a QW or Q2W frequency dependent on responder status 
6.2. 
Preparation, Handling, Storage, and Accountability 
• The IMP will be supplied to the investigational site by the sponsors' designated IMP 
supply vendor. 
• The pharmacy manual provides detailed instructions on the preparation, handling, 
storage, accountability, and disposition of unused IMP. 
• The investigator or designee is responsible for the correct and safe storage of the 
IMP. All IMP must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area following the labeled storage conditions, with access 
limited to the investigator and authorized site staff. 
• The investigator or designee must confirm that appropriate temperature conditions 
have been maintained for all IMP received during transit. Any discrepancies are 
reported and resolved before using the IMP. 

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• Only participants enrolled in the study are permitted to receive IMP, and only 
authorized site staff or designee are allowed to supply IMP. 
• Appropriate dilutions in a 0.9% saline solution in an infusion bag will be prepared 
before administration with an IV pump. 
• IMP must be stored refrigerated (2°C to 8°C) and protected from direct sunlight in 
secondary packaging. Do not shake IMP or expose it to freezing temperatures. 
• Participants will be observed for at least 30 minutes after the end of IMP infusion for 
routine safety monitoring. 
• The pharmacy manual and home guide provide further guidance and information for 
the final disposition of unused IMP. 
• Accountability of home-administered IMP will be documented as instructed in the 
home guide. 
6.3. 
Assignment to IMP 
 
All participants will receive efgartigimod 10 mg/kg by IV infusion either Q2W or QW based on 
whether the participant is a responder or nonresponder, respectively. 
6.4. 
Blinding 
ARGX-113-2211 is an open-label study. The treatment allocation (efgartigimod or placebo) from 
the double-blind qualifying studies will be kept blinded in the current study. 
6.5. 
Study Compliance 
IMP infusions must occur at the site for a minimum of 3 consecutive visits (for QW dosing 
regimen: baseline visit and the week 1 and 2 visits; for Q2W dosing regimen: baseline visit and 
the week 2 and 4 visits) before home infusions are allowed. If doses are missed at 1 or more of 
these visits, then dosing at subsequent visits will also be on-site. IMP administration at home will 
not commence until after 3 doses have been administered on-site. 
IMP may be administered at home (by a health care professional [nurse]) for other visits. 
Participant compliance with IMP administration at home will be assessed by direct questioning 
during the site visit and documented in the source documents and relevant forms. The date and 
time of each dose administered will be recorded as well as the total dose administered at each 
visit. Deviation(s) from the prescribed dosage regimen will be recorded. 
6.6. 
Dose Modification 
The maximum total efgartigimod dose per efgartigimod infusion is 1200 mg for participants 
weighing ≥ 120 kg. The IMP weight-based dose will be recalculated if a participant’s weight has 
changed (increased or decreased) by more than 10% from OLE baseline (ie, weight prior to IMP 
infusion on day 1 of the ARGX-113-2211 study). 
Modifications to the schedule of dosing are permitted as described in Section 4.1. 

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6.7. 
Continued Access to IMP After the End of the Study 
At the end of the study, argenx cannot guarantee continued access for participants but will 
comply with all local laws and regulations. 
6.8. 
Treatment of Overdose 
Any dose of efgartigimod greater than the intended QW or Q2W amount will be considered an 
overdose. 
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator or treating physician will: 
• Evaluate the participant to determine if IMP will be interrupted 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities (as 
medically appropriate and at least until the next scheduled follow-up) 
• Record the overdose in the eCRF and the quantity of the excess dose as well as the 
duration of the overdose 
6.9. 
Prior and Concomitant Therapy 
Participants must maintain a stable regimen of medications throughout the study. Any 
medication (including over-the-counter or prescription medicines, recreational drugs, vitamins, 
and/or herbal supplements [including Chinese traditional medicine]) or other specific categories 
of interest that the participant is receiving at the time of enrollment or receives during the study 
must be recorded and include the following information: 
• Reason for use 
• Dates of administration, including start and end dates 
• Dosage information (ie, dose and frequency) 
The following medications or treatments are not permitted during the periods listed in Table 4. 
Table 4: 
Prior and Concomitant Therapy 
Medication 
Period participant is receiving IMP 
Follow-up period 
Live or live-attenuated 
vaccines 
Prohibited 
Permitted from 28 days 
after the last IMP dose 
SCIg 
Prohibited 
Permitted 
IVIg 
Prohibited 
Permitted 
Corticosteroid steroids: 
Intra-muscular or intravenous 
corticosteroids 
Prohibited 
Permitted 
Oral corticosteroids 
Stable dose up to 10 mg daily 
Permitted 

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Medication 
Period participant is receiving IMP 
Follow-up period 
Inhaled corticosteroids 
Permitted 
Permitted 
Intra-articular steroids 
Prohibited 
Permitted 
Topical steroids 
Topical (non-ophthalmic) steroids are 
permitted 
Topical ophthalmic steroids are prohibited. 
Permitted 
DMARDs 
Conventional DMARDS / 
Antimalarials 
Permitted HCQ, CQ, AZA, MTX, MMF, 
leflunomide or cyclosporin at stable dose 
Permitted 
Cyclophosphamide 
Prohibited 
Permitted 
Biologic DMARDS 
Prohibited 
Permitted 
Targeted synthetic DMARDs: 
JAK inhibitors  
Prohibited 
Permitted 
IMPs: 
IMP in another clinical trial 
Prohibited 
Permitted 
Nonbiologic IMP in another 
clinical trial 
Prohibited 
Prohibited 
Biologic IMP in another 
clinical trial 
Prohibited 
Prohibited 
Other: 
Chinese traditional medicine 
with known 
immunomodulatory action 
Prohibited 
Permitted 
Anticholinergic agents  
Permitted at stable dose 
Permitted 
Topical symptomatic 
medications for pSS  
At visits with planned efficacy 
assessments, participants will be required 
to withhold ophthalmic lubricants, 
ophthalmic lubricating ointments, hydroxyl 
cellulose ophthalmic inserts, and saliva 
substitutes before efficacy assessments are 
completed. 
Permitted 
Pharmacological topical 
ophthalmic agents (eg, 
NSAIDs, cyclosporine)  
Prohibited 
Permitted 

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Medication 
Period participant is receiving IMP 
Follow-up period 
Pilocarpine and/or any other 
pharmacological stimulant for 
salivary and lacrimal glands  
Permitted at stable dose 
Not to be taken within 24 hours of clinical 
assessments 
Permitted 
AZA = azathioprine; CQ = chloroquine; DMARD = disease-modifying antirheumatic drug; EDV = early 
discontinuation visit; HCQ = hydroxychloroquine; IMP = investigational medicinal product; IVIg = intravenous 
immunoglobulin; JAK = Janus kinase; MMF = mycophenolate mofetil; MTX = methotrexate; NSAID = 
non-steroidal anti-inflammatory drug; pSS = primary Sjögren’s syndrome; SCIg = subcutaneous immunoglobulin 

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7. 
DISCONTINUATION OF IMP AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or the entire study are described in Appendix 1 (Section 10.1). 
7.1. 
Discontinuation of IMP 
7.1.1. 
Permanent Discontinuation 
Permanent discontinuation of IMP occurs when the participant stops receiving the IMP before 
the end of the study, does not resume receiving IMP, and does not withdraw informed consent. 
The investigator will document the primary reason for early discontinuation of IMP. 
Participants who permanently discontinue IMP will complete the EDV. 
The study sites will attempt to perform the EDV within 7 days after the participant’s final IMP 
administration. The SFV will occur 56 ± 3 days after the participant’s final IMP administration. 
Additionally, the following circumstances will result in the permanent discontinuation of IMP: 
• The participant becomes pregnant or intends to become pregnant (see Section 8.3.5) 
• The investigator considers discontinuing IMP is in the participant’s best interest (the 
sponsor will be informed) 
• The participant develops an SAE or AE that contraindicates further administration of 
IMP in the investigator’s opinion or an AE of CTCAE severity grade 4 that is 
considered related to IMP by the sponsor 
• The participant develops a new or recurrent malignancy except for basal cell 
carcinoma of the skin, regardless of relationship to IMP 
• The participant receives a prohibited medication or substance (Section 6.9) 
7.1.2. 
Temporary Discontinuation 
Temporary discontinuation of IMP occurs when the participant discontinues receiving IMP 
before the end of the study and resumed once the cause for the discontinuation has been 
resolved. 
Reasons requiring temporary interruption may include an AE that meets the following criteria: 
• Any SAE considered related to IMP by the sponsor 
• Clinically significant active infection considered related to the IMP by the sponsor 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
Study withdrawal is defined as the permanent cessation of further participation in any study 
assessment before its planned completion. 
The primary reason for permanent study withdrawal will be recorded. 

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The following circumstances will result in the permanent discontinuation and withdrawal from 
the study: 
• Participant withdrawal of consent 
• Sponsor request 
If the participant also withdraws consent to participate in future research, the sponsor can retain 
and continue to use any data collected before such a withdrawal of consent. 
• Samples collected from participants who have withdrawn from the study will be used 
for the study results but not for future research. 
7.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if repeatedly failing to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be completed if a participant fails to complete a required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to continue in the 
study 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (when possible, 3 telephone 
calls, and if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts will be documented in 
the participant’s medical record 
− Participants who continue to be unreachable will be considered to have withdrawn 
from the study 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers or 
exemptions are not allowed. 
Adherence to the study design requirements, including those specified in the SoA, is required for 
study conduct. 
All baseline evaluations must be completed and reviewed to confirm that participants meet all 
eligibility criteria before first dose. 
Operational considerations due to the COVID-19 pandemic are provided in Section 10.5. 
8.1. 
Administrative and Baseline Procedures 
The baseline visit for study ARGX-113-2211 will be conducted after the participant has 
completed the qualifying study. All baseline assessments will be performed before first 
administration of efgartigimod in ARGX-113-2211, if applicable. Assessments do not need to be 
repeated if they are performed as part of the last visit of the qualifying study. 
8.1.1. 
Use and Storage of Biological Samples 
Any samples remaining after the laboratory analyses as defined in the protocol have been 
completed can be stored for up to 15 years after the end of the study, in the laboratory or 
long-term storage designated by the sponsor or research partners worldwide for future additional 
medical, academic, or scientific research to address any scientific questions related to 
efgartigimod, FcRn biology, or pSS unless prohibited by local regulations or the participant. 
As stated in Section 7.2, samples collected from participants who have withdrawn from the study 
will be used for the study results but not for future research. 
8.2. 
Efficacy Assessments 
Time points for all efficacy assessments are provided in the SoA (Section 1.3). 
Patient-reported outcome questionnaires should be administered before any other study 
assessment and may be completed up to 1 day before the visit. It is preferrable that the same 
physician assesses the clinical efficacy parameters at all visits. 
Instructions on administering these assessments are provided in the Investigator Site File. 
8.2.1. 
CRESS 
CRESS has been developed to assess treatment efficacy in participants with pSS. CRESS 
consists of the following items, with definitions of treatment response and lower disease:2 
• Systemic disease activity: As measured with clinESSDAI (Section 8.2.3) 
− Response is defined as a score of < 5 points 
• Patient-reported symptoms: As measured with ESSPRI (Section 8.2.5.1) 
− Response is defined as a decrease of ≥ 1 point or ≥ 15% from baseline 

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• Tear gland function: as measured with Schirmer’s test (Section 8.2.6.3) and OSS 
(Section 8.2.6.4) 
− If Schirmer’s test is ≤ 5 mm at baseline (abnormal), a response is defined as an 
increase of at least 5 mm from baseline OR 
− If OSS is ≥ 3 points at baseline (abnormal), a response is defined as a decrease of 
at least 2 points from baseline OR 
− If both OSS and Schirmer’s scores are normal at baseline, a response is defined as 
no change that results in an abnormal OSS or Schirmer’s score 
• Salivary gland function: As measured with UWSF (Section 8.2.6.2) and SGUS 
− UWSF: At least 25% increase in score, or if score is 0 mL/min at baseline, any 
increase from baseline OR 
− SGUS: At least 25% decrease in total Hocevar3 from baseline 
• Serology: As measured with serum IgG and RF 
− RF: Decrease of at least 25% from baseline OR 
− IgG: Reduction of at least 10% from baseline 
8.2.2. 
ESSDAI 
The ESSDAI was designed to measure disease activity in patients with pSS.5 The ESSDAI 
consists of 12 domains, 11 related to organ involvement (cutaneous, pulmonary, renal, articular, 
muscular, peripheral nervous system, central nervous system, hematological, glandular, 
constitutional, and lymphadenopathic) and 1 biological domain reflecting B-cell activity 
(Section 10.7.1). The activity levels of each domain (range: 0-3 points) are multiplied by their 
respective weights (range: 1-6 points) to obtain the total score. 
ESSDAI-related laboratory tests include the following: 
• Gammaglobulins 
• Cryoglobulins 
• C3, C4 and CH50 
The gammaglobulin and cryoglobulin results will be blinded postbaseline. 
8.2.3. 
ClinESSDAI 
ClinESSDAI derives from the ESSDAI, and its score provides an accurate evaluation of disease 
activity independent of B-cell biomarkers.6 The clinical domains in clinESSDAI have different 
weights than in ESSDAI (Table 5). 

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Table 5: 
Comparison of Domain Weights of Original ESSDAI and clinESSDAI 
Domain (activity level) 
ESSDAI 
clinESSDAI 
Constitutional (0-2) 
3 
4 
Lymphadenopathy (0-3) 
4 
4 
Glandular (0-2) 
2 
2 
Articular (0-3) 
2 
3 
Cutaneous (0-3) 
3 
3 
Pulmonary (0-3) 
5 
6 
Renal (0-3) 
5 
6 
Muscular (0-3) 
6 
7 
Peripheral nervous system (0-3) 
5 
5 
Central nervous system (0-3) 
5 
5 
Hematological (0-3) 
2 
2 
Biological (0-2) 
1 
NA 
Score total 
0-123 
0-135 
Source: Seror et al6 
clinESSDAI = clinical EULAR Sjögren’s syndrome disease activity index; ESSDAI = EULAR Sjögren’s syndrome 
disease activity index; EULAR = European Alliance of Associations for Rheumatology; NA = not applicable 
The biological domain will remain blinded until the parent study is unblinded, therefore study 
sites are only expected to report clinESSDAI in the eCRF. 
8.2.4. 
STAR 
STAR has been developed to assess the efficacy of treatments for pSS.7 
This composite measure contains 5 domains: 
• Systemic activity: 3 points 
− clinESSDAI decrease of ≥ 3 points (Section 8.2.3) 
• Patient-reported outcome: 3 points 
− ESSPRI decrease of at least 1 point or ≥ 15% (Section 8.2.5.1) 
− Symptoms of dryness, pain, and fatigue rated on 3 numeric rating scales 
• Lacrimal gland function (assessed by Schirmer’s test or OSS): 1 point 
− Schirmer’s test (Section 8.2.6.3) 
 If abnormal score at baseline: increase of ≥ 5 mm from baseline 
 If normal score at baseline: no change to abnormal 
− OSS (Section 8.2.6.4) 

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8.2.5.4. 
SF-36 
The SF-36 is a 36-item scale constructed to survey health-related quality of life on 8 domains: 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.2.5.5. 
PASS 
PASS is a patient-reported outcome measure that assesses the “value beyond which patients 
consider themselves well”.12 PASS measures participant well-being and overall feeling that 
symptoms are in remission, through a single question that is dependent on the indication. 
PASS assesses the level of symptoms at which participants with rheumatic diseases consider 
themselves well. To record the PASS, the rheumatologist will ask the participant whether they 
consider their current state to be satisfactory, considering all of the consequences of their disease. 
8.2.5.6. 
EQ-5D-5L 
EQ-5D-5L is a standardized measure of health status. It was developed by the EuroQol Group to 
provide a simple, generic measure of health status for clinical and economic appraisal. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI
CCI
CCI
CCI

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8.3.1. 
Physical Examinations 
• Brief physical examination will include weight; assessments of gastrointestinal, 
pulmonary, cardiovascular, and respiratory systems; and general appearance. 
Additionally, physical examinations will be performed to assess ESSDAI, as 
appropriate 
8.3.2. 
Vital Signs 
• Body temperature, pulse rate, respiratory rate, and blood pressure will be recorded 
before blood collection for laboratory tests and IMP administration 
• Blood pressure and pulse will be assessed with the participant rested and seated 
8.3.3. 
Electrocardiograms 
• Single 12-lead ECG(s) will be obtained using an ECG machine 
8.3.4. 
Protocol-Required Laboratory Tests 
• Blood and urine samples will be analyzed at a central laboratory for serum chemistry 
and hematology, urinalysis, and specialty laboratory parameters 
• Refer to Appendix 2 (Section 10.2) for the list of protocol-required laboratory tests to 
be performed and the SoA (Section 1.3) for the timing 
• The investigator must review the laboratory results, document this review, and record 
any clinically significant changes occurring during the study as an AE. The laboratory 
results must be retained with source documents 
• Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant unless judged by the investigator to be more severe 
than expected for the participant’s condition 
8.3.5. 
Pregnancy Testing 
• WOCBP will be tested for pregnancy. Urine tests for pregnancy will occur at the time 
points specified in the SoA (Section 1.3) 
• Pregnancy testing in WOCBP will be conducted at the end of relevant systemic 
exposure (ie, at the SFV) 
• Additional pregnancy testing could be performed, as deemed necessary by the 
investigator or required by local regulations, to establish the absence of pregnancy at 
any time during the study 
8.4. 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting 
The definitions of AEs and SAEs are provided in Appendix 3 (Section 10.3). 
AEs will be reported by the participant (or, if appropriate, by the caregiver or surrogate). 

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The investigator and qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and monitoring all reported events, 
including those reported by the participant. 
The method of recording, evaluating, and assessing the causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3 
(Section 10.3). 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs will be collected from the signing of the ICF until the SFV, as specified in the SoA 
(Section 1.3). 
All SAEs and AESIs will be recorded and reported to the sponsor or designee immediately, and 
under no circumstance it will exceed 24 hours, as indicated in Appendix 3 (Section 10.3). The 
investigator will submit any updated SAE data to the sponsor within 24 hours of being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, including death, at any 
time after a participant has been discharged from the study, and they consider the event to be 
reasonably related to IMP or study participation, the investigator must promptly notify the 
sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
nonleading verbal questioning of the participant is preferred to inquire about AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator must proactively follow each participant at 
subsequent visits/contacts. All SAEs and AESIs as defined in Section 10.3 and Section 8.4.6, 
respectively, will be followed until resolution, stabilization, the event is otherwise explained, or 
the participant is lost to follow-up (defined in Section 7.3). Further information on follow-up 
procedures is provided in Section 10.3). 
8.4.4. 
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 participants and the 
safety of IMP 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 IMP under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/IECs, and investigators 
• An investigator who receives a safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and 
file it with the IB and notify the IRB/IEC, if appropriate, according to local 
requirements 

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• The sponsor or designee will be responsible for reporting SUSARs to the relevant 
regulatory authorities and IEC/IRB, as per applicable regulatory requirements. The 
sponsor or designee will also be responsible for forwarding SUSAR reports to all 
study investigators, who will be required to report these SUSARs to their respective 
IECs/IRBs per local regulatory requirements 
8.4.5. 
Pregnancy 
• If pregnancy is reported, the investigator will record the pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
pregnancy in the female participant or the female partner of the male participant. 
Contact details are provided in Serious Adverse Event Reporting 
• The participant and pregnant female partner, if consented (Section 10.1.3), will be 
followed to determine the outcome of the pregnancy. The investigator will collect 
follow-up information on the participant/pregnant female partner and the neonate and 
forward it to the sponsor 
• While pregnancy itself is not considered an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy for medical reasons will be reported as an AE 
or SAE. Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and will be 
reported accordingly 
• Any poststudy pregnancy-related SAE considered reasonably related by the 
investigator to IMP will be reported to the sponsor as described in Section 8.4.4 
• Any female participant who becomes pregnant during the study will discontinue IMP 
8.4.6. 
AESIs 
An AESI is an event of scientific and medical concern specific to the sponsor’s product or 
program. An AESI can be serious or nonserious, related or unrelated to the IMP or study 
procedures. These events will be reported according to the same timeframe as that for SAEs 
specified in Section 8.4.1 and Section 10.3.4. 
Participants for whom an AESI has been reported may be temporarily interrupted from IMP 
treatment, as specified in Section 7.1.2. 
For this study, infections will be AESIs as discussed in Section 8.4.6.1. 
8.4.6.1. 
Infections 
Efgartigimod treatment leads to reduced IgG levels. As low IgG levels can be associated with 
increased infection risks, events in the MedDRA SOC Infections and Infestations are considered 
AESIs in this study. These events will be reported according to the timeframe specified in 
Section 8.4.1 and Section 10.3.4, with the following information provided: 
• Causal pathogen 
• Location of infection 

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• Relationship to an underlying medical condition, medical history, and concomitant 
medications 
• Reoccurrence of a previous infection 
• Any confirmatory procedure, culture, or urgent medical intervention 
8.4.7. 
AEs of Clinical Interest 
8.4.7.1. 
Infusion/Injection-Related Reactions 
All therapeutic proteins can elicit immune responses, potentially resulting in hypersensitivity or 
allergic reactions such as rash, urticaria, angioedema, serum sickness, and anaphylactoid or 
anaphylactic reactions. As with any SC or IV injection, injection- or infusion-related reactions 
can occur during or after administration. 
The efgartigimod IB provides more information on infusion/injection-related reactions. 
8.4.7.2. 
Injection Site Reaction 
An injection site reaction is any AE developing at the injection site. Localized injection site 
reactions are frequently observed in studies in which efgartigimod is comixed with PH20 and 
administered SC. The most frequently reported injection site reaction AEs are Injection site 
erythema, Injection site pain, and Injection site swelling. 
Any injection site reaction will be reported as an AE (Section 8.4). Certain types of local 
reactions could be photographed and shared with the sponsor for review and assessment. 
As a routine precaution, participants will be trained or observed closely by a trained health care 
professional for any potential injection site reaction. 
Refer to the current IB for more information on injection site reactions. 
8.5. 
Pharmacokinetics 
On IMP administration visits, blood samples for PK analysis will be collected predose 
(preferably within 2 hours before IMP administration) and post-dose (within 30 minutes after the 
end of IMP infusion) at baseline and week 16, as described in the SoA (Section 1.3). Samples 
collected after the end of infusion should be collected in the opposite arm from the arm used for 
IMP infusion. At visits where the IMP is not administered, blood samples may be collected at 
any time during that visit. 
Efgartigimod serum concentrations will be determined using a validated method. 
8.6. 
Pharmacodynamics 
Baseline and postbaseline PD blood samples will be collected predose on IMP administration 
visits (preferably within 2 hours before IMP administration) as described in the SoA 
(Section 1.3). At visits where the IMP is not administered, blood samples may be collected at 
any time during that visit. 
Total IgG concentrations will be quantified at a diagnostical laboratory. Results will not be 
reported to investigative sites or other study personnel to maintain the parent study blind. 

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Participants will also be tested for anti-Ro/SS-A and anti-La/SS-B autoantibodies at the time 
points specified in the SoA (Section 1.3), as a part of secondary PD measures. All results will be 
blinded. 
8.7. 
Genetics 
Not applicable. 
8.8. 
Biomarkers 
Blood will be collected, whereas serum will be aliquoted at the time points specified in the SoA 
(Section 1.3) to explore the relation between relevant biomarkers and clinical effects. 
8.9. 
Immunogenicity Assessments 
Blood samples will be collected at the time points indicated in the SoA (Section 1.3) to evaluate 
serum levels of ADAs against efgartigimod. 
On IMP administration visits, the blood samples will be collected predose, preferable within 
2 hours before the IMP administration. Date and time of sample collection will be recorded in 
the participant’s eCRF. On other visits, blood samples may be collected at any time during the 
visit as specified in the SoA (Section 1.3). 
Samples will be analyzed by the designated laboratory in a 3-tiered approach using validated 
immunogenicity assays.16 Initially, samples will be screened for a positive assay response 
(tier 1). Screened positive samples will then be tested in a confirmation assay (tier 2). Finally, a 
titration of the ADA response will be performed on positive tier 2 samples to characterize the 
magnitude of the antibody response (tier 3). 
8.10. 
Health Economics or Medical Resource Utilization and Health 
Economics 
Not applicable. 

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9. 
STATISTICAL CONSIDERATIONS 
The SAP will be finalized before database lock and includes a more technical and detailed 
description of the statistical analyses described in this section. 
9.1. 
Statistical Hypothesis 
No formal hypothesis will be tested in this phase 2 open-label extension study. 
9.2. 
Analysis Sets 
The following analysis sets are defined: 
Analysis set 
Description 
Full analysis set (FAS) 
All enrolled subjects in the OLE study. 
Safety set 
All FAS subjects who have been administered study treatment 
during the OLE. 
9.3. 
Statistical Analyses 
9.3.1. 
General Considerations 
• Data collected will be listed with derived variables. Descriptive statistical methods will 
be used to analyze safety and efficacy data 
• The results of this study will not be used inferentially 
• No formal sample size calculation is presented 
• Summaries will include the number of observations (n), mean, SE, 90% CI, median, 
minimum, and maximum for continuous measures 
• Summaries will include sample size, frequencies, and percentages for categorical 
variables 
• The baseline value will be the last assessment before the first administration of the study 
drug in OLE 
• All study visits will be recalculated based on actual dates. The rules for calculating the 
analysis visits will be documented in the SAP 
• Rules for imputing partial dates or missing dates will be provided in the SAP 
• Exposure to IMP will be summarized 
• TEAEs, AESIs, SAEs, and other safety parameters will be summarized 
• AEs will be classified using the latest version of the MedDRA classification system 
• AEs, AESIs, and SAEs will be listed corresponding to MedDRA SOC and PT 

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• Multiple occurrences of a single PT in a participant will be counted only once at the 
maximum severity/grade 
• AEs with missing severity or relationship to IMP will be classified as severe and  
treatment-related, respectively. All AEs will be summarized by relatedness to IMP 
• Any AEs leading to death or discontinuation of IMP will also be summarized 
• Population PK/PD analysis may be performed based on the PK and PD data and reported 
separately 
• Laboratory parameters, physical examinations, vital sign measurements, ECG data and 
PK, PD, immunogenicity, and biomarker results will be summarized descriptively 
9.3.2. 
Primary Endpoint Analysis 
Primary endpoint of long-term safety will be assessed through AEs, AESI, incidence of SAEs, 
changes in laboratory test results, vital signs, and ECG. Please refer the Section 8.3 for more 
details. Full details of the secondary analyses will be included in the SAP. 
9.3.3. 
Secondary Endpoint(s) Analysis 
The key secondary endpoints of CRESS, ESSDAI, clinESSDAI, ESSPRI, and STAR responders 
will be assessed at week 24 and week 48. 
The proportion along with an exact 90% CI of CRESS, ESSDAI, clinESSDAI, ESSPRI, and 
STAR responders will be presented at week 24 and week 48. 
Secondary endpoints of change from OLE baseline in ESSDAI, clinESSDAI, and ESSPRI scores 
will be summarized descriptively at week 24 and week 48. Observed data will also be 
summarized at OLE baseline, week 24 and week 48. 
Plots of mean changes from the OLE baseline will be presented along with their 90% confidence 
intervals at each scheduled timepoint for ESSDAI, clinESSDAI, and ESSPRI. Box and Whisker 
plots will also be presented for the change from OLE baseline for each scheduled timepoint. 
9.3.4. 
Exploratory Endpoints Analysis 
To explore the effect of efgartigimod on clinical pSS, glandular measures and  
patient-reported outcomes, serum and blood biomarkers the following analysis will be 
performed: 
• The proportion along with an exact 90% CI of adjusted CRESS (without serology item) 
will be presented at week 24 and week 48 
• Change from OLE baseline in activity of individual ESSDAI domains score, Hocevar 
score, Schirmer’s test score, OSS score, MFI score, physical component and mental 
component scores of SF-36, PGA score, individual ESSPRI score, EQ-5D-5L utilities 
score, VAS score will be summarized descriptively at week 24 and week 48. Observed 
data will also be summarized at OLE baseline, week 24 and week 48 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted according to the protocol and the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences international ethical guidelines 
− Applicable ICH GCP guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) 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 approval before implementing 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
• Protocols and any substantial amendments to the protocol will require health 
authority approval before initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator is responsible for providing the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently according to 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 site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies, and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit a complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the study and for 1 year 
after completion of the study. 

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The following information will be collected: any significant payments from the sponsor such as a 
grant to fund ongoing research, compensation in the form of equipment, retainer for ongoing 
consultation or honoraria, proprietary interest in IMP, significant equity interest in the sponsor as 
defined in 21 CFR 54 2(b) (1998). 
10.1.3. 
Informed Consent Process 
• The investigator or representative will explain the nature of the study, including risks 
and benefits to the potential participant and answer all questions before the participant 
completes the informed consent process by signing the informed consent form 
• Potential participants must be informed that their participation is voluntary. A 
statement of informed consent must be signed that meets the requirements of the 
IRB/IEC or study center, ICH guidelines, local regulations, and, where applicable, 
privacy and data protection requirements 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study if the changes to the ICF impact participant participation 
• A copy of the ICF(s) must be provided to the participant 
• A copy of the ICF(s) must be provided to the participant 
• Participants who are rescreened are required to sign a new ICF (Section 5.4) 
10.1.4. 
Recruitment Strategy 
Not applicable. 
10.1.5. 
Data Protection 
• The sponsor will assign participants a unique identifier. Any participant records or 
datasets transferred to the sponsor will contain the identifier only; participant names 
or any information that would make the participant identifiable will not be transferred 
• The participant must be informed that the sponsor, sponsor representatives, competent 
authorities, etc., can review source data containing identifiers and will use their 
personal study-related data per local data protection law. The level of disclosure must 
also be explained to the participant who will be required to give consent for their data 
to be used as described in the informed consent 
• The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties 
• Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 

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such data against accidental or unlawful loss, alteration, or unauthorized disclosure or 
access 
10.1.6. 
Committees Structure 
Not applicable. 
10.1.7. 
Dissemination of Clinical Trial Data 
The sponsor will register and disclose the results of clinical studies as required by law. 
10.1.8. 
Data Quality Assurance 
• The sponsor or designee is responsible for the data management of this study, 
including quality checking of the data 
• All participant data relating to the study will be recorded on eCRFs unless transmitted 
to the sponsor (or its designee) electronically (eg, laboratory data) or paper SAE 
forms. The investigator is responsible for verifying data entries are complete, 
accurate, and verifiable by electronically signing the eCRF 
• Guidance on completing eCRFs is provided in the eCRF completion document 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and direct access to source data documents 
• Study processes, study sites (including but not limited to site visits, central 
laboratories, vendors), the study database, and study documentation can be subject to 
quality assurance audit during the study by the sponsor or sponsor’s designee on 
behalf of the sponsor. In addition, inspections could be conducted by foreign or 
domestic regulatory bodies at their discretion. Such audits/inspections can occur 
during or after the completion of the study 
• Records and documents, including signed ICFs, on the conduct of this study must be 
retained by the investigator for 25 years after study completion unless local 
regulations or institutional policies require a more extended retention period. Without 
the sponsor's written approval, no records will be destroyed during the retention 
period. No records are allowed to be transferred to another location or party without 
the sponsor’s written notification 
• Monitoring details describing strategy and activities are described in a monitoring 
plan: 
− Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are 
being protected; and that the study is being conducted following the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements 

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10.1.9. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site 
• Data 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 
• Definition of what constitutes source data, and its origin can be found in the 
monitoring plan 
• The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF 
• The sponsor or designee will perform monitoring to confirm that data entered into the 
eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants 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 
10.1.10. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the first participant rolls over to ARGX-113-2211. 
Study/Site Termination 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
The investigator could initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator could include but are 
not limited to: 
• For study termination: 
− Discontinuation of further compound development 
• For site termination: 
− 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 or lack of recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 

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− Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator will promptly inform the participant and ensure 
appropriate therapy and/or follow-up for the participant, as necessary. 
10.1.11. 
Publication Policy 
• The results of this study can 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 multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement 
• Authorship will be determined by mutual agreement and consistent with International 
Committee of Medical Journal Editors authorship requirements 
 
 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
• The tests listed in Table 6 will be performed as described in the Laboratory Manual 
• Additional tests can be performed during the study as determined necessary by the 
investigator or required by local regulations 
• Investigators must document their review of each laboratory test result 
Table 6: 
Protocol-Required Laboratory Tests 
Laboratory Test 
Parameters 
Hematology 
RBC count 
platelet count 
hemoglobin 
hematocrit 
RBC indices: 
MCV 
MCH 
%reticulocytes 
 
WBC count with differential: 
neutrophils 
eosinophils 
lymphocytes 
basophils 
monocytes 
Serum chemistry 
ALT 
AST 
GGT 
alkaline phosphatase 
albumina 
creatinine 
potassium 
BUN 
CRP 
glucose  
sodium 
total proteina 
calcium 
bilirubin (total and direct) 
 
Routine urinalysis 
Specific gravity 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase 
Microscopic examination (if blood or protein is abnormal) 
Pregnancy testing 
Urine test at baseline and other time points (as needed for WOCBP potential, defined 
in Section 10.4.1)  
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CRP = C-reactive 
protein; GGT = gamma-glutamyl transferase; MCH = mean corpuscular hemoglobin; MCV = mean corpuscular 
volume; RBC = red blood cell; WBC = white blood cell 
a This result will be blinded baseline and up to the week 4 (day 29) visit. 
 
 

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• 
The paper SAE report form will be faxed or emailed to the sponsor’s designee (see the 
Serious Adverse Event Reporting details on page 2 of this protocol) 
 
 
 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. 
Women of Childbearing Potential Definition 
A female is considered a WOCBP unless she is either: 
a. Postmenopausal: A postmenopausal state is defined by continuous amenorrhea for at 
least 1 year without an alternative medical cause with an FSH measurement 
of > 40 IU/L. If a postmenopausal woman is using hormonal therapy, such as 
hormone replacement therapy or hormonal contraceptives, FSH levels might be 
suppressed and therefore an FSH test to confirm a postmenopausal state is not 
considered valid. In this case the postmenopausal state will need to be assessed by the 
investigator. 
b. Surgically sterilized: Women who have had a documented permanent sterilization 
procedure (eg, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) 
10.4.2. 
Contraception Guidance 
10.4.2.1. Female Contraception for Women of Childbearing Potential 
WOCBP must use one of the following contraception methods from signing the ICF until the last 
dose of IMP. 
The following Clinical Trials Facilitation and Coordination Group17 acceptable methods are 
permitted for efgartigimod studies: 
• Progestogen-only oral hormonal contraception in which inhibition of ovulation is not 
the primary mode of action 
• Male or female condom with or without spermicide 
• Cap, diaphragm, or sponge with spermicide 
10.4.2.2. Male Contraception 
There are no contraception requirements for men in this study. 
 

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10.5. 
Appendix 5: Operational Considerations for COVID-19 Risk 
Mitigation 
Participants will be tested for SARS-CoV-2 if they are symptomatic or if applicable law requires 
testing. 
During the study, the sites will implement all recommendations issued by the local government 
regarding the spread of COVID-19, including specific guidelines related to clinical research 
performed in clinical research centers. 
This appendix is intended for use only if unforeseen changes in the COVID-19 pandemic result 
in new restrictions at the site or new risks for participants or site staff from attending visits at the 
site. 
Testing for COVID-19 is not required during the study unless required by local authorities. 
However, it is recommended that participants who develop COVID-19 symptoms while 
receiving IMP be tested, with results reported for the study. 
Critical Parameters to Be Collected During the Study 
All assessments will be performed as indicated in the SoA (Section 1.3). If assessments cannot 
be performed due to the COVID-19 pandemic, the following information must be collected from 
the first visit through end-of-study: all AE and concomitant medication reporting, IMP 
administration, questionnaires, and protocol-required laboratory assessments. 
 

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10.6. 
Appendix 6: Home Study Visits 
A home nurse can travel to the participant’s home to conduct visits (or meet the participant at a 
convenient alternate location). For each home visit, the investigator or designee will confer with 
the participant via an audio or video interview to elicit AEs and concomitant medications and the 
participant's general well-being. The investigator or designee will also ensure the participant has 
completed all required efficacy assessments that can be done at home (eg, questionnaires). Any 
scheduled assessments will be conducted before the home nurse administers IMP. 
 

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10.7. 
Appendix 7: Efficacy Endpoint Data 
10.7.1. 
ESSDAI 
Table 7: 
ESSDAI: Domain and Item Definitions and Weights 
Domain [Weight] 
Activity level 
Description 
Constitutional [3] 
Exclusion of fever of 
infectious origin and 
voluntary weight loss 
No = 0 
Absence of the following symptoms 
Low = 1 
Mild or intermittent fever (37.5 to 38.5°C)/night sweats 
and/or involuntary weight loss of 5 to 10% of body 
weight 
Moderate = 2 
Severe fever (> 38.5°C)/night sweats and/or 
involuntary weight loss of > 10% of body weight 
Lymphadenopathy [4] 
Exclusion of infection 
No = 0 
Absence of the following features 
Low = 1 
Lymphadenopathy ≥ 1 cm in any nodal region 
or ≥ 2 cm in inguinal region 
Moderate = 2 
Lymphadenopathy ≥ 2 cm in any nodal region 
or ≥ 3 cm in inguinal region, and/or splenomegaly 
(clinically palpable or assessed by imaging) 
High = 3 
Current malignant B-cell proliferative disorder 
Glandular [2] 
Exclusion of stone or 
infection 
No = 0 
Absence of glandular swelling 
Low = 1 
Small glandular swelling with enlarged parotid 
(≤ 3 cm), or limited submandibular or lachrymal 
swelling 
Moderate = 2 
Major glandular swelling with enlarged parotid 
(> 3 cm), or important submandibular or lachrymal 
swelling 
Articular [2] 
Exclusion of osteoarthritis 
No = 0 
Absence of currently active articular involvement 
Low = 1 
Arthralgias in hands, wrists, ankles, and feet, 
accompanied by morning stiffness (> 30 minutes) 
Moderate = 2 
1 to 5 (of 28 total count) synovitis 
High = 3 
≥ 6 (of 28 total count) synovitis 
Cutaneous [3] 
Rate as “No activity” 
stable long-lasting features 
related to damage 
No = 0 
Absence of currently active cutaneous involvement 
Low = 1 
Erythema multiforme 
Moderate = 2 
Limited cutaneous vasculitis, including urticarial 
vasculitis, or purpura limited to feet and ankle, or 
subacute cutaneous lupus 
High = 3 
Diffuse cutaneous vasculitis, including urticarial 
vasculitis, or diffuse purpura, or ulcers related to 
vasculitis 

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Table 7: 
ESSDAI: Domain and Item Definitions and Weights (Continued) 
Domain [Weight] 
Activity level 
Description 
Pulmonary [5] 
Rate as “No activity” 
stable long-lasting features 
related to damage, or 
respiratory involvement 
not related to the disease 
(tobacco use etc) 
No = 0 
Absence of currently active pulmonary involvement 
Low = 1 
Persistent cough or bronchial involvement with no 
radiographic abnormalities on radiography; or 
radiological or HRCT evidence of interstitial lung 
disease with: no breathlessness and normal lung 
function test 
Moderate = 2 
Moderately active pulmonary involvement, such as 
interstitial lung disease shown by HRCT with shortness 
of breath on exercise (NHYA II) or abnormal lung 
function tests restricted to: 70% > DLCO ≥ 40% or 
80% > FVC ≥ 60% 
High = 3 
Highly active pulmonary involvement, such as 
interstitial lung disease shown by HRCT with shortness 
of breath at rest (NHYA III, IV) or with abnormal lung 
function tests: 70% > DLCO ≥ 40% or  
80% > FVC ≥ 60% 
Renal [5] 
Rate as “No activity” 
stable long-lasting features 
related to damage, and 
renal involvement not 
related to the disease. If 
biopsy has been 
performed, please rate 
activity based on 
histological features first 
No = 0 
Absence of currently active renal involvement with 
proteinuria < 0.5 g/day, no hematuria, no leucocyturia, 
no acidosis, or long-lasting stable proteinuria due to 
damage 
Low = 1 
Evidence of mild active renal involvement, limited to 
tubular acidosis without renal failure or glomerular 
involvement with proteinuria (between 0.5 and 
1 g/day) and without hematuria or renal failure (GFR ≥ 
60 mL/min) 
Moderate = 2 
Moderately active renal involvement, such as tubular 
acidosis with renal failure (GFR < 60 mL/min) or 
glomerular involvement with proteinuria between 
1 and 1.5 g/day and without hematuria or renal failure 
(GFR ≥ 60 mL/min) or histological evidence of 
extra-membranous glomerulonephritis or important 
interstitial lymphoid infiltrate 
High = 3 
Highly active renal involvement, such as glomerular 
involvement with proteinuria > 1.5 g/day or hematuria 
or renal failure (GFR < 60 mL/min), or histological 
evidence of proliferative glomerulonephritis or 
cryoglobulinemia related renal involvement 
Muscular [6] 
Exclusion of weakness due 
to corticosteroids 
No = 0 
Absence of currently active muscular involvement 
Low = 1 
Mild active myositis shown by abnormal EMG or 
biopsy with no weakness and creatine kinase 
(N < CK ≤ 2N) 

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Table 7: 
ESSDAI: Domain and Item Definitions and Weights (Continued) 
Domain [Weight] 
Activity level 
Description 
 
Moderate = 2 
Moderately active myositis proven by abnormal EMG 
or biopsy with weakness (maximal deficit of 4/5), or 
elevated creatine kinase (2N < CK ≤ 4N) 
High = 3 
Highly active myositis shown by abnormal EMG or 
biopsy with weakness (deficit ≤ 3/5) or elevated 
creatine kinase (> 4N) 
PNS [5] 
Rate as “No activity” 
stable long-lasting features 
related to damage or PNS 
involvement not related to 
the disease 
No = 0 
Absence of currently active PNS involvement 
Low = 1 
Mild active peripheral nervous system involvement, 
such as pure sensory axonal polyneuropathy shown by 
NCS or trigeminal (V) neuralgia 
Moderate = 2 
Moderately active PNS involvement shown by NCS, 
such as axonal sensory-motor neuropathy with 
maximal motor deficit of 4/5, pure sensory neuropathy 
with presence of cryoglobulinemic vasculitis, 
ganglionopathy with symptoms restricted to 
mild/moderate ataxia, CIDP with mild functional 
impairment (maximal motor deficit of 4/5or mild 
ataxia), or cranial nerve involvement of peripheral 
origin (except trigeminal [V] neuralgia) 
High = 3 
Highly active PNS involvement shown by NCS, such 
as axonal sensory-motor neuropathy with motor deficit 
≤ 3/5, peripheral nerve involvement due to vasculitis 
(mononeuritis multiplex, etc), severe ataxia due to 
ganglionopathy, CIDP with severe functional 
impairment: motor deficit ≤ 3/5 or severe ataxia 
CNS [5] 
Rate as “No activity” 
stable long-lasting features 
related to damage or CNS 
involvement not related to 
the disease 
No = 0 
Absence of currently active CNS involvement 
Low = 1 
Moderately active CNS features, such as cranial nerve 
involvement of central origin, optic neuritis, or 
multiple sclerosis–like syndrome with symptoms 
restricted to pure sensory impairment or proven 
cognitive impairment 
High = 3 
Highly active CNS features, such as cerebral vasculitis 
with cerebrovascular accident or transient ischemic 
attack, seizures, transverse myelitis, lymphocytic 
meningitis, multiple sclerosis–like syndrome with 
motor deficit 

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Table 7: 
ESSDAI: Domain and Item Definitions and Weights (Continued) 
Domain [Weight] 
Activity level 
Description 
Hematological [2] 
For anemia, neutropenia, 
and thrombopenia, only 
autoimmune cytopenia 
must be considered 
Exclusion of vitamin or 
iron deficiency, drug-
induced cytopenia 
No = 0 
Absence of autoimmune cytopenia 
Low = 1 
Cytopenia of autoimmune origin with neutropenia 
(1000 < neutrophils < 1500/mm3), and/or anemia 
(10 < hemoglobin < 12 g/dL), and/or thrombocytopenia 
(100 000 < platelets < 150 000/mm3); or lymphopenia 
(500 < lymphocytes < 1000/mm3) 
Moderate = 2 
Cytopenia of autoimmune origin with neutropenia 
(500 ≤ neutrophils ≤ 1000/mm3), and/or anemia 
(8 ≤ hemoglobin ≤ 10 g/dL), and/or thrombocytopenia 
(50 000 ≤ platelets ≤ 100 000/mm3); or lymphopenia 
(≤ 500/mm3) 
High = 3 
Cytopenia of autoimmune origin with neutropenia 
(neutrophils < 500/mm3) and/or anemia (hemoglobin 
< 8 g/dL) and/or thrombocytopenia (platelets 
< 50 000/mm3) 
Biological [1] 
No = 0 
Absence of any of the following biological features 
Low = 1 
Clonal component and/or hypocomplementemia (low 
C4 or C3 or CH50) and/or hypergammaglobulinemia 
or high IgG level between 16 and 20 g/L 
Moderate = 2 
Presence of cryoglobulinemia and/or 
hypergammaglobulinemia or high IgG level > 20 g/L, 
and/or recent onset hypogammaglobulinemia or recent 
decrease of IgG level (< 5 g/L) 
Source: Seror et a, 20118 
C3 = Complement component 3; C4 = Complement component 4; CH50 = Total hemolytic complement; 
CIDP = chronic inflammatory demyelinating polyneuropathy; CK = creatine kinase; CNS = central nervous system; 
DLCO = diffusing capacity of the lungs for carbon monoxide; EMG = electromyogram; ESSDAI = EULAR 
Sjögren’s syndrome disease activity index; FVC = forced vital capacity; GFR = glomerular filtration rate; 
HRCT = high-resolution computed tomography; IgG = immunoglobulin G; N = normal; NCS = nerve conduction 
studies; NHYA = New York Heart Association (classification); PNS = peripheral nervous system 

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10.8. 
Appendix 8: ACR-EULAR Classification Criteria 
The ACR-EULAR classification of pSS applies to any individual who meets the following 
inclusion and exclusion criteria and has a score of ≥ 4 when summing the weights from the items 
presented in Table 8. 
Inclusion Criteria 
Inclusion criteria apply to any patient with ≥ 1 symptom of ocular or oral dryness, defined as a 
positive response to ≥ 1 of the following questions: 
1. Have you had daily, persistent, troublesome dry eyes for more than 3 months? 
2. Do you have a recurrent sensation of sand or gravel in the eyes? 
3. Do you use tear substitutes more than 3 times a day? 
4. Have you had a daily feeling of dry mouth for more than 3 months? 
5. Do you frequently drink liquids to aid in swallowing dry food? 
OR suspicion of pSS from the ESSDAI questionnaire (with ≥ 1 positive domain item) 
Exclusion Criteria 
Prior diagnosis of any of the following conditions would exclude diagnosis of pSS and 
participation in pSS studies or therapeutic studies because of overlapping clinical features or 
interference with criteria tests: 
• AIDS 
• Active hepatitis C infection (with positive PCR) 
• Sarcoidosis 
• Amyloidosis 
• Graft-versus-host disease 
• History of head and neck radiation treatment 
• IgG4-related disease 
Table 8: 
ACR-EULAR Classification Criteria for Primary Sjögren’s Syndrome 
Item 
Weight/Score 
Labial salivary gland with focal lymphocytic sialadenitis and focus score of ≥ 1a 
3 
Anti-Ro/SS-A positive 
3 
OSS of ≥ 518 (or van Bijsterfeld score of ≥ 419) on at least 1 eye 
1 
Schirmer’s test of ≤ 5 mm/5 minutes on at least 1 eyeb 
1 
UWSF rate of ≤ 0.1 mL/min20,b 
1 
Source: Shiboski et al21 
ACR = American College of Rheumatology; EULAR = European Alliance of Associations for Rheumatology; 
OSS = ocular staining score; SS-A = Sjögren’s syndrome–related antigen A; UWSF = unstimulated whole salivary 
flow 

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a A pathologist with expertise in the diagnosis of focal lymphocytic sialadenitis and focus score count (based on 
number of foci per 4 mm2) should perform the histopathologic examination following a protocol by Daniels et al22. 
b Patients who are normally taking anticholinergic drugs should be evaluated for objective signs of salivary 
hypofunction and ocular dryness after a sufficient interval off these medications so that these components can be a 
valid measure of oral and ocular dryness. 
 
 

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